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)

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

We conducted a double-blind, placebo-controlled trial of oral azidothymidine (AZT) in 282 patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex. Although significant clinical benefit was documented (N Engl J Med 1987; 317:185-91), serious adverse reactions, particularly bone marrow suppression, were observed. Nausea, myalgia, insomnia, and severe headaches were reported more frequently by recipients of AZT; macrocytosis developed within weeks in most of the AZT group. Anemia with hemoglobin levels below 7.5 g per deciliter developed in 24 percent of AZT recipients and 4 percent of placebo recipients (P less than 0.001). Twenty-one percent of AZT recipients and 4 percent of placebo recipients required multiple red-cell transfusions (P less than 0.001). Neutropenia (less than 500 cells per cubic millimeter) occurred in 16 percent of AZT recipients, as compared with 2 percent of placebo recipients (P less than 0.001). Subjects who entered the study with low CD4 lymphocyte counts, low serum vitamin B12 levels, anemia, or low neutrophil counts were more likely to have hematologic toxic effects. Concurrent use of acetaminophen was also associated with a higher frequency of hematologic toxicity. Although a subset of patients tolerated AZT for an extended period with few toxic effects, the drug should be administered with caution because of its toxicity and the limited experience with it to date.
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PMID:The toxicity of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial. 329 90

This review summarizes adverse reactions probably or possibly attributable to oral ciprofloxacin therapy in worldwide clinical experience involving over 6500 patients. In Europe and Japan the overall incidence of adverse reactions amongst patients receiving ciprofloxacin is reported to be 3.0% and 6.5%, respectively. An increased incidence (13.4%) has been reported from the U.S.A., possibly relating to the use of higher dosages. Very few reactions have necessitated withdrawal of treatment. The most common adverse effects involve the gastro-intestinal system (2-8% of patients treated) and usually comprise nausea, vomiting, diarrhoea and abdominal discomfort. CNS effects are seen in 1-4% of patients but are usually minor dizziness or mild headache only. Hypersensitivity reactions, most commonly skin rashes or pruritus, affect about 1% of patients. There is little evidence of significant haematological or biochemical toxicity, other than a few reports of transient neutropenia and the finding, in a minority of clinical studies, of equally transient, usually trivial and invariably reversible elevations of serum aminotransferases. Serious, ciprofloxacin-related toxicity has been observed in only three patients: one who developed pseudomembranous colitis, another who developed interstitial nephritis and a third who had a grand-mal convulsion during concomitant administration of theophylline. Ciprofloxacin appears to have an excellent safety profile.
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PMID:Ciprofloxacin: an overview of adverse experiences. 354 45

A syndrome of periodic fever that resembles human cyclic neutropenia in its clinical presentation has been identified in 12 children observed at two major referral centers. Attacks characterized by abrupt onset of fever, malaise, chills, aphthous stomatitis, pharyngitis, headache, and tender cervical adenopathy occur at 4- to 6-week intervals over periods of years. These episodes of illness resolve spontaneously in 4 to 5 days. Mild leukocytosis and elevation of the erythrocyte sedimentation rate during attacks are the only laboratory abnormalities. Affected children grow normally, are not unusually susceptible to infection, and exhibit no long-term sequelae. Attacks may be aborted by short courses of prednisone but do not respond to nonsteroidal anti-inflammatory agents. This syndrome is sporadic and appears to be much more common than cyclic neutropenia.
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PMID:Syndrome of periodic fever, pharyngitis, and aphthous stomatitis. 379 85

Nine patients with chronic type B hepatitis were entered into a preliminary study of recombinant, human alpha-interferon therapy. Patients received one to four courses of interferon, each consisting of a fixed dose of 18, 36, 50, 68, or 100 million units given three times a week for 2 wk. Side effects including fever, chills, fatigue, myalgias, headache, and neutropenia were common and especially severe with higher doses. Serum hepatitis B virus DNA polymerase activity fell during therapy to 15%-30% of the pretreatment levels irrespective of interferon dose, but rose to the initial level by 10 days after the course ended. During follow-up, 2 patients had a sustained clinical remission in which hepatitis B virus DNA, DNA polymerase, and hepatitis B e antigen disappeared from serum and amino-transferase activities fell to normal. One patient became hepatitis B surface antigen negative. We conclude that higher doses (50 and 68 million units) of interferon have greater side effects than lower doses (18 and 36 million units), without having any greater antiviral efficacy. Further studies should be directed at therapy with lower doses given over longer periods.
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PMID:Pilot study of recombinant human alpha-interferon for chronic type B hepatitis. 394 Feb 41

Twenty-six adult patients were entered in a phase I trial of carboplatin, a new cisplatin derivative with reduced potential for nephrotoxicity. All patients had solid tumors and the median World Health Organization performance score was 2 (0-3). Twelve patients had not received prior chemotherapy. The drug was administered as a 15-minute IV infusion, without pre- or posthydration, at daily doses of 40-125 mg/m2 for five consecutive days. Antiemetics were given only if needed. Thrombocytopenia and neutropenia were dose related and dose limiting. One patient died from septic shock at the highest dose level. Nonhemolytic anemia was also encountered. Nausea and vomiting were experienced by most patients but gastrointestinal intolerance was severe in only two patients. One patient had hypercreatininemia, which was minor and rapidly reversible. Other toxic effects consisted of negligible fatigue, paresthesia, pruritus, local pain, stomatitis, headache, and alopecia. Although none of the patients achieved a partial or complete response, antitumor effect was strongly suggested in two patients with thyroid and cervix cancer, respectively. Carboplatin is an attractive candidate for phase II trials. In good-risk patients, such trials could be initiated at a daily dose of 100 mg/m2 for five consecutive days every five to six weeks.
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PMID:Phase I study of carboplatin given on a five-day intravenous schedule. 636 28

Since their initial description in 1957, the interferons (IFNs) have been increasingly used to treat a wide array of diseases. Acute adverse effects, i.e. 'flu-like' syndromes, hypo- or hypertension, tachycardia, headache, myalgias and gastrointestinal disorders, occur within the first hour or day after starting treatment. They are seldom treatment-limiting and are easily manageable. Sub-acute and chronic effects develop after several days, usually within 2 and 4 weeks of therapy. The most typical is neurological toxicity, including fatigue/asthenia, and behavioural and cognitive changes. Such symptoms may seriously impair quality of life and result in treatment discontinuation. Seizures have seldom been described. Other infrequent central nervous system adverse effects include vertigo, cramp and oculomotor nerve paralysis. Distal paraesthesias and peripheral neuropathy have been reported. IFN-associated autoimmunity is quite rare but a matter of concern. Biological or clinical manifestations usually require several months to become apparent. Autoantibodies have been shown to develop in most patients but have been inconsistently associated with clinical symptoms of systemic lupus erythematosus, rheumatoid-like arthritis and thyroiditis. Both hypo- and hyperthyroidism have been described but are usually reversible. Other infrequent autoimmune reactions include diabetes, pemphigus and worsening of multiple sclerosis. Although several patients present with a pre-existing autoimmune disorder, no predisposing factor has been clearly established. While hypotension and tachycardia are the most frequent acute cardiovascular complications, a few additional cases of cardiac arrhythmias and myocardial ischaemia have been reported after a short course or several weeks of treatment. These latter complications do not appear to be dose-dependent or age-related. Isolated cases of congestive heart failure have also been described. Mild proteinuria has been observed in 15 to 25% of patients, but acute renal toxicity is uncommon. A transient rise in serum aminotransferase levels is frequently noted during the first stage of therapy, especially in patients receiving the highest dosages. Direct hepatotoxicity is extremely rare. Autoimmune hepatitis, which is ill-diagnosed as chronic viral hepatitis, and de novo induction of autoimmune hepatitis, account for the majority of liver diseases. Haematotoxicity is relatively common but mild to moderate, and develops gradually during the first weeks of treatment. Neutropenia is the most common haematological toxicity, but is usually not dose-limiting and resolves rapidly upon drug discontinuation. Myelosuppression, autoimmune and immune allergic haemolytic anaemias and thrombocytopenias have seldom been described. Cutaneous adverse effects comprised nonspecific erythema and hair loss and, less frequently, vasculitis, local ulcerations at the site of injection and exacerbation of psoriasis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical toxicity of the interferons. 751 63

Dengue fever is a viral disease, transmitted to man via mosquito bites. It is endemic in tropical regions (10 million infected annually) and is characterized by high fever, headache, myalgia, lethargy, vomiting, rash and neutropenia. The upward trend in the number of young Israelis visiting tropical countries increases the number of those potentially exposed to this disease. We present 4 Israelis who returned with dengue fever from Thailand.
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PMID:[Dengue fever]. 755 5

Colony-stimulating factors (CSFs) are glycoprotein growth factors that influence the proliferation and differentiation of hematopoietic progenitor cells. Among CFSs granulocyte colony-stimulating factor (G-CSF) is thought to be major stimulator of production of human neutrophilic granulocyte. G-CSF have recently moved from the basic research to the clinical use and have been suggested to have important roles in cancer management. Today two kinds of recombinant G-CSF which have similar specific activity are commercially available, one is derived from ovarian cells of Chinese hamster and the other from E. coli. (Variant type of E. coli is now in trial.) Difference of these two is whether carbohydrate chain primarily seen in molecule of natural form is contained or not. In this report recombinant product of G-CSF for the clinical use is introduced. Preclinical study with recombinant G-CSF have suggested that it would stimulate granulocyte production in cancer patients with myelosuppression due to chemotherapy. Thus, after evaluation of toxicities and possible efficacy recombinant G-CSF has been introduced into phase II trial for the prevention of chemotherapy-induced neutropenia in various cancers. In this setting 2 micrograms/kg of subcutaneous administration for 14 days after aggressive chemotherapy was suggested to be optimal and to be acceptable for toxicities including bone pain or headache. In conclusion recombinant G-CSF is thought to be very useful drug for reduction of nadir of cancer chemotherapy-induced neutropenia and shortening of period of neutropenia.
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PMID:[Recombinant human granulocyte colony-stimulating factor (G-CSF)]. 768 Aug 49

Retinoids have anti-tumor activity in several malignant and premalignant conditions. Since Kaposi's sarcoma is regulated by steroid hormones both in vivo and in vitro, we hypothesized that retinoids may have anti-tumor effects in AIDS-related Kaposi's sarcoma. Thus, 27 patients with mucocutaneous, non-visceral AIDS-related Kaposi's sarcoma were treated with all-trans retinoic acid (tRA). Poor tolerance was observed at the initial starting dose of 150 mg/m2, and thus subsequent patients were treated using a weekly dose escalation, starting with 45 mg/m2 (given daily, in subdivided doses), to the target dose of 150 mg/m2 (given daily in three subdivided doses). Nearly half (46%) of the patients had extensive mucocutaneous disease with over 25 lesions. No patient had received prior cytotoxic chemotherapy. Ten patients had CD4 lymphocytes of 200/mm3 or greater (strata I); and 17 had under 200/mm3 CD4 lymphocytes (strata II). The median of the average daily tRA dose administered was 150 mg (90 mg/m2; there was no significant difference in the dose tolerance between the two strata). Adverse effects consisted of transient mild to moderate headaches in 65% of patients, mild to moderate skin dryness and cheilitis in 61%, and nausea and vomiting in 31%. Hematologic toxicities included hypertriglyceridemia in 62%, anemia in 23%, and neutropenia in 23%. Partial response to therapy was observed in 4/24 (17%) evaluable patients, occurring after 12, 20, 24, and 28 weeks of therapy, and lasting 4-24 weeks. Three responders had baseline CD4 lymphocyte counts < 200/mm3. Three additional patients experienced reduction in measured indicator lesions of greater than 25% but less than 50%, and seven patients experienced disease stabilization of 16 weeks or greater. In evaluable patients, the median time to disease progression was 22 weeks and the overall median survival in all patients was 27.3 months. No significant changes in CD4 lymphocyte counts, p24 antigen, and beta 2 microglobulin were observed over time. However, a statistically significant increase was observed in soluble IL-2 receptor levels while on tRA (p = 0.037). We conclude that tRA has activity in patients with mucocutaneous AIDS-related Kaposi's sarcoma with acceptable toxicity. tRA has immunological effects without upregulation of HIV parameters. Additional studies in combinations or with more active retinoids are warranted.
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PMID:All-trans retinoic acid for the treatment of AIDS-related Kaposi's sarcoma: results of a pilot phase II study. 780 21


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