Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recombinant human interleukin 3 (rhIL-3) has been suggested to be a useful agent for the treatment of chemotherapy-induced thrombocytopenia. For evaluation of this possibility, rhIL-3 was given subcutaneously for 10 days to patients with small-cell lung cancer (SCLC). Chemotherapy consisted of carboplatin (CBDCA) given at 400 mg/m2 to previously untreated patients or at 350 mg/m2 to previously treated patients on day 1 and etoposide (VP-16) given at 100 mg/m2 on days 1-3 every 4 weeks. If the platelet count nadir was < 75,000/microliters in the control cycle of chemotherapy, patients were randomly assigned for the next cycle to rhIL-3 given at 5 or 10 micrograms/kg per day on days 4-13. A total of 41 patients (32 previously untreated patients and 9 previously treated patients) were enrolled in the study. The platelet count nadir in the cycles including rhIL-3 was significantly higher at both dose levels (P < 0.01) than in the control cycle. The duration of thrombocytopenia (< 75,000/microliters) and the mean time from the 1st day of chemotherapy to thrombocyte recovery (> 100,000/microliters) in the rhIL-3 cycle were significantly shorter than those in the control cycle (P < 0.01). The neutrophil count nadir and the duration of neutropenia (<1,000/microliters) were also significantly improved in the rhIL-3 cycle (P < 0.05). The major side effects were fever (80.5%), headache (24.3%), and fatigue (14.6%). All side effects were tolerable and of less than grade II. There was no difference in the efficacy of the two dose levels, but the 5-micrograms/kg dose appeared to be better tolerated than the 10-micrograms/ kg dose. We conclude that rhIL-3 administration following chemotherapy consisting of CBDCA and VP-16 reduces the incidence and severity of chemotherapy-induced thrombocytopenia and neutropenia with an acceptable adverse-events profile.
 ...
PMID:Phase II study of recombinant human interleukin 3 administration following carboplatin and etoposide chemotherapy in small-cell lung cancer patients. SDZ ILE 964 (IL-3) Study. 876 25

Intravenous immune globulin (IVIg) is advocated as a safe treatment for immune-mediated neurologic disease. We reviewed the medical records of 88 patients who were given IVIg for a neurologic illness. Major complications in four patients (4.5%) included congestive heart failure in a patient with polymyositis, hypotension after a recent myocardial infarction, deep venous thrombosis in a bed-bound patient, and acute renal failure with diabetic nephropathy. Other adverse effects included vasomotor symptoms 26, headache 23, rash 5, leukopenia 4, fever 3, neutropenia 1, proteinuria (1.9 g/day) 1, viral syndrome 1, dyspnea 1, and pruritus 1. Fifty-two patients (59%) had some adverse effect of IVIg infusion, most commonly vasomotor symptoms, headaches, fever, or shortness of breath in 40 (45%), which improved with reduced infusion rate or symptomatic medications. Five (6%) had asymptomatic laboratory abnormalities and seven (8%) had other minor adverse effects. Adverse effects led to discontinuation of therapy in 16% and permanent termination of therapy in 10% of patients. There was no mortality or long-term morbidity. Although adverse effects were frequent, serious complications were rare except in patients with heart disease, renal insufficiency, and bed-bound state.
 ...
PMID:Complications of intravenous immune globulin treatment in neurologic disease. 930 72

We tested paclitaxel (Taxol) and low dose hydroxyurea as second line therapy in 30 patients with non-small cell lung cancer since both drugs are active against non-small cell lung cancer in other settings, and since hydroxyurea may reverse chemotherapy resistance by disrupting double minute chromosomes. Hydroxyurea 500 mg was given orally each Monday, Wednesday, Friday starting 1 week before paclitaxel, and continuing until removal from study. Paclitaxel 135 mg/m2 was given i.v. over > or = 1 h every 3 weeks with dexamethasone, diphenhydramine, and ranitidine. Patients could have paclitaxel doses escalated to 175 mg/m2 in course 2 and to 200 mg/m2 in course 3, where tolerated. Sixteen males and 14 females were treated. All patients had previously received a single cisplatin-based chemotherapy regimen and 23 had previously received radiotherapy. Twelve patients had adenocarcinomas, six had squamous cell carcinomas, and 12 had large cell carcinomas. Eight patients had Stage IIIb cancers and 22 had Stage IV. Paclitaxel doses were 135 mg/m2 in 56 courses, 175 mg/m2 in 24, and 200 mg/m2 in 15. Treatment was well tolerated. Median granulocyte nadirs were 2.5 (x 10(9)/l) for paclitaxel 135 mg/m2, 1.8 for 175 mg/m2, and 1.3 for 200 mg/m2. No patient developed febrile neutropenia, and none required a dose reduction. Two patients had reversible anaphylaxis. Other toxicities were quite tolerable. They included fatigue, myalgias, dizziness, paresthesias, diarrhea, alopecia, mucositis, flushing, headache, swollen red hands, and anxiety. One patient had a partial remission and 15 had stable disease (including six with minor responses). Median survival was 20 (95% CI, 12-34) weeks, with 19% of patients remaining alive at 1 year from initiation of treatment. This is a well-tolerated regimen with modest activity as second line chemotherapy for patients with non-small cell lung cancer previously treated with cisplatin regimens. Higher doses would be feasible and other strategies are now being explored.
 ...
PMID:Paclitaxel plus hydroxyurea as second line therapy for non-small cell lung cancer. 886 29

The clinical trial development programme of mirtazapine (Org 3770), performed in Europe and the United States, demonstrated an outstanding safety profile of this compound. The evaluation of the safety was based on data from all patients who took at least one dose of study medication during studies comparing mirtazapine with placebo, amitriptyline or other active comparators. A general indication of mirtazapine's safety is the significantly lower percentage of patients (65%) who complained of any adverse clinical experiences compared with the placebo- (76%) or amitriptyline-treated group (87%). Moreover, drop-out rates due to adverse clinical experiences were significantly lower than in the amitriptyline-treatment group. Mirtazapine has virtually no anticholinergic, adrenergic or typical selective serotonin reuptake inhibitor (SSRI) side effects. The only significantly higher incidences versus placebo were seen in the adverse clinical effects of drowsiness (23% versus 14%), excessive sedation (19% versus 5%), dry mouth (25% versus 16%), increased appetite (11% versus 2%) and weight increase (10% versus 1%). These complaints were typically mild and transient in nature, and decreased over time despite increased doses of mirtazapine. In contrast, significantly higher incidences of headache (5% versus 10%) and weight decrease (2% versus 6%), symptoms commonly seen in depressed patients, were recorded in the placebo-treated patients. Also, typical SSRI adverse events, such as nausea, vomiting, diarrhoea and insomnia, and symptoms of sexual dysfunction were registered less frequently in mirtazapine-treated patients than in the placebo-treated patients. Approximately 10% of the mirtazapine-treated patients in the clinical trial programme were older than 65 years. The pattern of adverse clinical experiences seen in this group of patients is fully in line with that seen in the overall patient population. The analysis of vital sign indices, i.e. blood pressure and heart rate, showed that no changes occurred with mirtazapine treatment; this pattern was fully comparable to that seen with placebo. Furthermore, very low incidences of clinically relevant changes in laboratory indices, such as the liver enzymes alanine aminotransferase and aspartate aminotransferase or neutropenia, were recorded in each treatment group. Mirtazapine has a very low seizure-inducing potential: only one case was recorded in a patient with a history of seizures during previous treatment with clomipramine. The low seizure-inducing potential combined with a lack of cardiotoxic properties allows safety in an overdose of mirtazapine, even in elderly patients. The only symptom seen in the patients taking an overdose of mirtazapine alone or in combination with other drugs was excessive but transient somnolence, which resolved spontaneously within a few hours. In conclusion, the new antidepressant mirtazapine offers clinicians a unique combination of strong efficacy and good safety.
 ...
PMID:Safety of mirtazapine: a review. 893 8

Bropirimine (U-54461S), an oral interferon (IFN) inducer that has also a direct antiproliferative activity, is a novel antitumor agent. To investigate the safety and pharmacokinetics of bropirimine tablets and to measure IFN concentrations in patients with cancer, Phase I studies were conducted. In single dose study (0.25 to 3g) and multiple-dose study with one-day dosing (1 or 2g, every one or two hours, three times a day), bropirimine treatment was well tolerated by the patients with cancer. In multiple-dose study with consecutive days dosing (1 or 2g, every 2 hours, three times a day for 3 or 5 consecutive days), a regimen with a dose of 1g orally administered every two hours, three times a day for three consecutive days was considered to be tolerable to cancer patients. Adverse drug reactions frequently observed were generalized malaise, fever, nausea/vomiting, anorexia, headache/dull headache, and tachycardia. Abnormalities in laboratory tests frequently observed were leukemia, neutropenia, thrombocytopenia, and elevation in GOT/GPT. IFN was not induced in any patients in the single dose study. It was, however, induced in 3 of 16 cases (18.8%) in the one-day dosing study and in 6 of 7 cases (85.7%) in the consecutive days dosing study. As to clinical antitumor efficacy, a decrease in size of the tumor lesions and improvement in subjective/objective symptoms were noted in two cases in the one-day dosing study. With these findings, the regimen with the dose of 1g orally administered every two hours, three times a day for three consecutive days with a four-day drug-free interval per week was recommended for early phase II studies.
 ...
PMID:[Bropirimine (U-54461S) phase I clinical studies]. 897 2

Infections of the nervous system remain a significant source of morbidity and mortality in patients with cancer. This paper reviews the main pathogens and emphasizes some of the principles of diagnosis and management of nervous system infections in cancer patients. Due to immunosuppression, diagnosis is more difficult in this group, secondary to the multitude of potential pathogens, and often by their atypical presentations. Fever or headache are often the only symptoms. Clinical history and general examination should guide appropriate studies such as neuroimaging. CSF analysis, cultures, and brain biopsy. Diagnostic evaluation should be pursued rapidly and aggressively since specific treatments can often reduce morbidity and mortality. Bacterial infections are generally due to break-down of the natural barriers and neutropenia. In neutropenia, Pseudomonas aeruginosa, and Enterobacteriae are the most frequent etiology. If all causes of immunodepression are included, Listeria monocytogenes meningitis is the main bacterial infection encountered. Fungal infections have emerged as a major cause of death among cancer patients. The prognosis of cryptococcosis and histoplasmosis meningitis are markedly improved with new antifungal therapy. Aspergillosis and Mucormycosis, which may cause cerebral abcesses and secondary vascular complications, are almost always fatal. The incidence of meningo-cerebral Candidiasis is often underestimated. Similar to Histoplasmosis, it is frequently disseminated. Viral infections are mainly seen in patients with T-lymphocyte defects. Herpes-simplex virus and Varicella-Zoster virus encephalitis should quicky lead to intravenous treatment with Acyclovir. As in AIDS patients, cerebral toxoplasmosis is the most frequent parasitic infection and appropriate therapy greatly reduces morbidity. It should be emphasized that multitude pathogens are often seen in cancer patients. Despite development of new therapeutic agents, central nervous system infections should still be considered life-threatening. Therefore, antibacterial, antifungal, and antiviral prophylaxis should be the rule for all cancer patients.
 ...
PMID:[Central nervous system infections in patients with malignant diseases]. 903 51

To determine the characteristics of clinical illness accompanying Plasmodium falciparum infection induced by controlled exposure to infected mosquitoes, records of 118 volunteers participating in studies conducted between 1985 and 1992 were reviewed. One hundred fourteen volunteers (97%) reported at least one symptom attributable to malaria, with fatigue, myalgias or arthralgias, headache, and chills most commonly reported. The median duration of symptoms was 3 days. Fever was recorded in 61% of volunteers; 4 volunteers had temperatures >40 degrees C. Neutropenia and thrombocytopenia were present in 9% and 12% of volunteers, respectively. Despite counts as low as 658/microL (neutrophils) or 73,000/microL (platelets), no secondary infectious or hemorrhagic complications occurred. In all cases, volunteers recovered completely and laboratory values returned to baseline after specific antimalarial therapy. Recrudescence did not occur in any volunteer. In this model, mosquito inoculation of P. falciparum is a reliable, safe, and well-tolerated method of experimental challenge.
 ...
PMID:Clinical manifestations of Plasmodium falciparum malaria experimentally induced by mosquito challenge. 960 76

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.
 ...
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

Zidovudine is approved for administration in doses given every 4 hours. Less frequent dosing has been used in many clinical trials, but the toxicity and efficacy of such regimens have not been formally compared with the approved regimen. In this multicenter, randomized, double-blind, controlled trial, the safety, tolerance and efficacy of 600 mg of zidovudine given daily in two or six divided doses were compared. Three hundred and twenty patients with a CD4 lymphocyte count < 250 cells/mm3 (mean, 104 cells/mm3) or a prior AIDS-defining illness were treated with zidovudine 100 mg every 4 hours (regimen A) or 300 mg every 12 hours (regimen B). Eighty-eight patients (56%) and 94 patients (58%), assigned to regimens A and B, respectively, completed the planned 48 weeks of treatment. Serious anemia (hemoglobin < or = 7.5 g/dl) occurred in 13% and 7% of patients treated with regimens A and B, respectively (difference, 6%, 95% confidence interval [CI], 2, 12%; p = .13). The mean duration of treatment and the frequency of neutropenia and symptomatic complaints including nausea and headache were similar in the two treatment groups. The number of patients experiencing a new opportunistic infection (18% versus 20% for regimens A and B, respectively), and the number of deaths (five in each group) did not differ significantly between groups. The effect of treatment on CD4 lymphocyte counts and HIV p24 antigenemia also was similar for both regimens. Zidovudine given at the more convenient dose of 300 mg twice daily has similar safety, and tolerance and appears to have similar efficacy to the currently approved regimen. Use of this regimen should help simplify the treatment of HIV disease.
 ...
PMID:A comparative trial of zidovudine administered every four versus every twelve hours for the treatment of advanced HIV disease. 929 87

A syndrome involving periodic fever, pharyngitis, adenitis and aphthous stomatitis is described in 8 children. Attacks are characterized by abrupt onset of fever and, in addition to the above symptoms, by malaise, headache and abdominal pain. Mild leukocytosis and elevation of the erythrocyte sedimentation rate are found in the laboratory. Patients exhibit normal growth and development and are otherwise healthy. PFAPA is clinically benign, with no long-term sequelae. Recognition and diagnosis of the syndrome eliminate the need for intensive work-up. The cause remains unknown. No evidence linking bacterial, viral, or fungal pathogens to this syndrome has been found. No patient has exhibited atypical lymphocytosis or neutropenia, and all patients had normal levels of immunoglobulin. All had received antibiotics early in the course of their illness but without effect. Cimetidine has been discussed in the literature as a possible treatment, but the results are controversial.
 ...
PMID:[PFAPA syndrome: periodic fever, adenitis, pharyngitis and aphthous stomatitis]. 933 38


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>