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)

A phase I study of VP was undertaken using the methods of a single (40 cases; range of dose levels 30-540 mg/m2) and 5-day (41 cases; range of dose levels 40-140 mg/m2/day) intravenous administration. The dose-limiting toxicity of VP was moderate to severe leukopenia. MTD was estimated to be 540 mg/m2 for a single and 140 mg/m2/day for 5-day administration. The median days to WBC nadir from the start of therapy and to recovery from reaching the nadir were 10 and 10.5 for single, and 15 and 7 for 5-day administration, respectively. Thrombocytopenia was less frequent and less pronounced than leukopenia. Mild gastrointestinal disturbances and alopecia were frequently observed. Transient hepatic dysfunction, fever, headache, fatigue, dyspnea, hypotension, and pain along the vein were also encountered in a small number of patients. There were no cases with renal, neurologic or cardiac toxicity. Objective tumor regression was seen in one case each of IBL(CR), bladder cancer, non-Hodgkin's lymphoma and ATL (PR). The post-infusion plasma decay of VP in 4 cases given 80-120 mg/m2 by a single administration was biphasic with t1/2 alpha ranging from 0.13 to 0.39 h and t1/2 beta ranging from 3.33 to 4.85 h. No accumulation of VP was found in plasma after five repeated daily doses. Doses of 360-480 mg/m2 by single and 80-100 mg/m2/day by 5-day administration repeated every 3 to 4 weeks can therefore be recommended for phase II studies in good-risk patients.
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PMID:[A phase I study of VP-16-213 (VP, etoposide) by single and 5-day intravenous administration]. 394 9

A single rising dose tolerance trial of rDNA interferon-alpha 2 (IFN-alpha 2) was conducted in eight patients with the diagnoses of non-Hodgkin's lymphoma (NHL), multiple myeloma, and chronic lymphocytic leukemia (CLL). Patients received a total of six i.m. doses at weekly intervals as follows: 1, 3, 10, 30, 60, and 100 x 10(6) IU. Patients were monitored at each dose level for serum IFN activity, anti-IFN antibodies, immunomodulation, clinical toxicity, and response. All patients exhibited clinical toxicity, including fever, chills, fatigue, headache, anorexia, mild-to-moderate leukopenia, nausea, and vomiting. Toxicity was dose-related, with significant side effects occurring in all patients at levels of 10 x 10(6) IU and above and some evidence of tachyphylaxis at higher doses. All side effects, including leukopenia and thrombocytopenia, were of short duration and were resolved within 3-5 days. Fevers, rigors, myalgias, and fatigue were partially alleviated by premedication with acetaminophen or hydrocortisone. Pharmacokinetic data indicated mean peak serum IFN titers greater than 90 at a dose of 10 x 10(6) IU and greater than or equal to 200 at doses greater than or equal to 30 x 10(6) IU 8 h after injection. No anti-IFN antibodies were detected. However, the serum levels achieved at higher doses were not linear, possibly indicating in vivo degradation. Total T cells, B cells, monocytes, and T subsets monitored by flow cytometry with monoclonal antibodies remained essentially constant throughout the trial. Although some patients demonstrated minor augmentations of antibody-dependent cellular cytotoxicity (ADCC) and natural killing (NK) activity at the lowest IFN-alpha 2 doses, the majority of patients demonstrated decreases in NK activity after higher IFN doses. No correlation between immunomodulation and clinical response to IFN was observed. At higher dose levels, the predominant immunomodulatory effect of IFN-alpha 2 was suppression of NK, ADCC, and blastogenic responses to T-cell mitogens and recall antigens. B-cell functional deficits as well as radioresistant T-helper and radiosensitive T-suppressor function assessed in a pokeweed mitogen-driven immunoglobulin secretion assay appeared unaffected by IFN administration. One myeloma patient showed progression and was discontinued after 60 x 10(6) IU. There were four patients (3 NHL, 1 myeloma) who achieved partial remission (greater than or equal to 50% tumor reduction) and three (1 CLL, 2 NHL) who showed objective tumor responses of less than 50%. These data suggest that rDNA IFN-alpha 2 is well-tolerated and may have significant antitumor activity against lymphoproliferative malignancies. Clin
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PMID:Immunomodulation by recombinant interferon-alpha 2 in a phase I trial in patients with lymphoproliferative malignancies. 660 23

Eighty-one patients with a variety of refractory disseminated malignant neoplasms have been treated in the first multiple fixed-dose phase I trial of recombinant leukocyte A interferon (IFL-rA). Each patient received IFL-rA by intramuscular injection, three times weekly for 28 days. Dosages were escalated in different patients from 1 to 136 x 10(6) units per injection. The toxic reactions seen with IFL-rA resembled those of nonrecombinant leukocyte interferon and included fever, chills, fatigue, anorexia, myalgia, headache, occasional nausea and vomiting, and dose-dependent reversible leukopenia and hepatic transaminase elevations. The pharmacokinetics of IFL-rA were also comparable with nonrecombinant leukocyte interferon. Objective evidence of antitumor activity was seen in non-Hodgkin's lymphoma, chronic lymphocytic leukemia, Hodgkin's disease, breast cancer, and melanoma, indicating that IFL-rA, the first genetically engineered biological response modifier available for testing in cancer patients, is biologically active in vivo.
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PMID:A multiple-dose phase I trial of recombinant leukocyte A interferon in cancer patients. 675 47

Meningeal involvement occurred in eight (22%) of 36 adult patients with AIDS-related systemic non-Hodgkin's lymphoma, seen over a 10-year period. Clinical symptoms consisted of cranial nerve palsies, radicular involvement, headache or diffuse encephalopathy. CSF examination established the diagnosis in all cases. Systemic disease had been diagnosed seven to 33 weeks before lymphomatous meningitis in six patients, whereas in the remaining two patients diagnoses of systemic and meningeal disease were made simultaneously. All patients had intermediate or high grade lymphomas and widespread disease. In contrast to non-AIDS related lymphomas, bone marrow involvement at initial staging cannot be used to select patients for prophylactic treatment, as seven of our eight patients had no initial bone marrow involvement. In this retrospective review, prognosis of lymphomatous meningitis was extremely poor, with a mean survival of only five weeks. Survival of patients with systemic lymphoma who eventually developed lymphomatous meningitis was 4.0 months compared with 7.2 months for those who did not. Lymphomatous meningitis appears to have the worst outcome of all AIDS-related neurological complications, regardless of treatment.
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PMID:Lymphomatous meningitis in AIDS-related systemic non-Hodgkin's lymphoma: a report of eight cases. 812 96

The objective of this phase-I study was to establish the maximum tolerable dose of recombinant human interleukin-3 (rhIL-3) after salvage chemotherapy in patients with malignant lymphoma. Twenty-one patients with relapsed Hodgkin's disease or intermediate/high-grade non-Hodgkin's lymphoma received rhIL-3 after the second cycle of DHAP chemotherapy (cisplatin, cytosine-arabinoside, dexamethasone). Cycles 1 and 3 were given without rhIL-3. The rhIL-3 was administered as a continuous intravenous infusion for 10 days starting 48 h after chemotherapy in cycle 2. Five different dose levels of rhIL-3 (0.25, 1.0, 2.5, 5.0, and 10.0 micrograms/kg/day) were sequentially tested. At the three lowest dose levels one double-blinded placebo was included for every four patients per dose level. Low-grade fever occurred in 15/21 patients, unrelated to the dose of rhIL-3. Nausea and vomiting (grade 1-2) occurred in seven patients. Headache was dose related, with 3/4 patients at a dose of 10 micrograms/kg/day experiencing troublesome grade-2 headache precluding further dose escalation. Facial flushing developed in 3/8 patients at the highest dose levels of rhIL-3. There was a significant increase in eosinophil count during rhIL-3 (p = 0.03 cycle 2 vs cycle 1 and p = 0.002 cycle 2 vs cycle 3) without accompanying clinical signs of symptoms. No increase in basophil count was observed. There were no increased plasma levels of interleukin-6 or macrophage colony-stimulating factor (M-CSF) during rhIL-3. We conclude that rhIL-3 can be safely administered as a continuous intravenous infusion for 10 days after DHAP chemotherapy. Dose-limiting side effects, especially headache, occur at a dose of 10 micrograms/kg/day.
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PMID:The tolerability of continuous intravenous infusion of interleukin-3 after DHAP chemotherapy in patients with relapsed malignant lymphoma. A phase-I study. 821 38

A 7-year-old boy presented with headache, vomiting, fever, epileptic seizure, and a left hemiparesis. Computed tomography revealed low-density areas in the left frontal lobe and right occipital lobe. Incisional biopsy of the right occipital lesion showed a diffuse and laminar destruction accompanied by microglial reaction in the cortex. An encephalitis of unknown etiology was suspected without data on viral titers in the serum and cerebrospinal fluid. Two months later right hemiparesis and ataxia appeared that were alleviated by prednisolone. Thereafter, similar symptoms repeatedly appeared, but disappeared after treatment with prednisolone. Approximately 5 years later, hemiparesis recurred: computed tomography revealed an 8 x 5 cm mass in the right lobe. A brain biopsy revealed non-Hodgkin's lymphoma of diffuse large, predominantly non-cleaved cell type of B-cell nature. The patient died 1 week after the surgery. The first biopsy specimen (taken at 7 years of age) did not contain Epstein-Barr virus genomes even when examined by polymerase chain reaction. The polymerase chain reaction and in situ hybridization techniques on the second biopsy specimens (taken at 12 years of age) revealed the Epstein-Barr virus sequences in the nuclei of diffuse large cell lymphoma. These findings suggested that the Epstein-Barr virus infection occurring between the first and second biopsies played an etiologic role in the pathogenesis of the brain lymphoma.
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PMID:Primary lymphoma of the brain developing in a boy after a 5-year history of encephalitis: polymerase chain reaction and in situ hybridization analyses for Epstein-Barr virus. 839 12

A 61-year-old man with multiple subcutaneous, ileocecal and neurologic manifestations was reported. Histological examination of subcutaneous and ileocecal mass showed non-Hodgkin's lymphoma (diffuse medium cell type [LSG classification]), B-cell type. Headache, somnolence and incontinence of urine were considered owing to the CNS involvement by lymphoma cells. The cranial CT findings showed diffuse spread involving the lateral and third ventricle and hypothalamus with adjacent edema. Then he was treated by VEMP regimen and repeated intrathecal MTX injections. The neurologic remission with improvement of cranial CT findings was obtained and he has been free of the disease for 15 years.
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PMID:[Long-term survivor (15 years) following central nervous system involvement in B-cell lymphoma]. 896 Jun 70

The purpose of this study was to, assess the efficacy of glycosylated recombinant human granulocyte colony-stimulating factor (lenograstim) in the prevention of neutropenia and infection in patients receiving dose-intensive chemotherapy for non-Hodgkin's lymphoma (NHL). A second objective was to determine clinical predicators of delay to cytotoxic chemotherapy administration. One hundred-sixty two patients with intermediate- or high-grade NHL and at least one poor prognostic factor received a total of 4 cycles of the LNH-84-regimen every 2 weeks, with an open randomization to treatment with anthracyclines. Patients were randomized to receive subcutaneous lenograstim 5 micrograms/kg/day (n = 82) or placebo (n = 80) from day 6 to day 13 of each cycle. The incidence of severe neutropenia (absolute neutrophil count (ANC) < 0.5 x 10(9)/L) was reduced in the lenograstim group compared with placebo (52% vs 75%). A significant reduction (p < 0.001) in the median duration of ANC < 0.5 x 10(9)/L was also observed in patients treated with lenograstim during each cycle of chemotherapy (0-1 day vs 2-4 days in placebo recipients). Fever occurred in 66 patients in each treatment group. Thirty-four percent of placebo recipients had documented infections during ANC < 1.0 x 10(9)/L compared with 18.5% of lenograstim-treated patients (p < 0.05). Infections of > or = 2 severity were significantly less frequent (p = 0.001) among lenograstim recipients compared with placebo (25 vs 49). The most common adverse events among lenograstim recipients were headache, mild bone pain and injection site reactions. Although lenograstim significantly increased (p = 0.0001) relative dose intensity compared with placebo (93% vs 80%), no difference in CR rate (67% vs 71%) or 3-year survival (63% vs 55%) was observed. The results of this study suggest that patients treated with a chemotherapy regimen that induces severe neutropenia can benefit from treatment with lenograstim. Furthermore, lenograstim permits treatment to be delivered at full dose intensity at 2 week intervals, even in patients with bone marrow involvement, and may permit further dose escalation of the chemotherapeutic regimen used.
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PMID:Placebo-controlled phase III study of lenograstim (glycosylated recombinant human granulocyte colony-stimulating factor) in aggressive non-Hodgkin's lymphoma: factors influencing chemotherapy administration. Groupe d'Etude des Lymphomes de l'Adulte. 916 39

We present a case of primary B-cell, large-cell, lymphoma of the skull vault in a 50-year-old HIV-positive male, who presented with a history of unilateral headache and a swelling on the scalp. Primary non-Hodgkin's lymphoma of the skull is rare, with only ten such cases in adults previously described. We suggest that this is the second reported case in an HIV-positive individual.
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PMID:Primary non-Hodgkin's lymphoma of the cranial vault. 926 57

A 64-year-old patient with herpetic keratouveitis was hospitalized because of fatigue, fever, headache and confusion. Three days before admittance keratouveitis was diagnosed. He reported a recent onset of aversion against meat consumption and weight loss of 11 kg over the last 4 months. Clinical investigation revealed a slightly confused patient with conjunctivitis and reduced vision of the left eye. Laboratory tests showed anemia, hyponatremia, and increased carcinoembryonic antigen (CEA). In the cerebrospinal fluid examination protein concentration was increased, glucose concentration was decreased. CT-scan of the brain revealed multiple, hyperintense, circular lesions. Biopsy showed lymphoplasmacellular infiltration with increased number of glial and oligodendroglial cells with central necrosis. Despite therapy with tuberculostatic and antiviral drugs and corticosteroids the condition of the patient progressively deteriorated. The patient died 42 days after admission. Autopsy revealed a high grade B-cell non-Hodgkin's lymphoma of the jejunum. Septic shock was the cause of death with the lymphoma of the jejunum as a possible nidus of infection. The multiple brain lesions with central necrosis were probably caused by thromboembolization or by a previous viral meningoencephalitis.
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PMID:[Headache, painful eyes, fever and weight loss]. 1052 60


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