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)

This retrospective study from two hospitals is about a hundred patients who have been operated upon a spontaneous cerebral hematoma. By a spontaneous cerebral hematoma we mean a hematoma without a proven tumor, without aneurysm, without arteriovenous malformation, without preceding trauma, without aortical phlebitis and without pathology of the vessel-wall. In this study patients with coagulopathy, arterial hypertension and artherosclerosis are included. In order to comply with these conditions an angiography will have to take place pre-operatively as well as postoperatively. Moreover histological examination of the wall of the hematoma will have to be done. The etiology of the spontaneous cerebral hematoma is not clear in most cases. The indication to operate, the way of operating and the moment in which the operation takes place, vary strongly in medical literature. We operate when there is an aggravation of the clinical picture, persisting severe headache and neurological paresis which does not improve. As a rule we abide for one week before operating, if the clinical picture allows this. After the operation unconscious patients may recover and a hemiparesis may improve. The best way of diagnosing a cerebral hematoma is computerised tomography.
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PMID:[The spontaneous cerebral hematoma (author's transl)]. 744 12

Amonafide (AMF), NSC 308847 is an investigational anticancer drug acting as a DNA intercalating agent. This paper presents results of a phase II clinical study of AMF in disseminated malignant melanoma. Twenty patients, eleven males and nine females, with biopsy proven malignant melanoma, performance status 0-2; median age 59 (range 29-74), and no previous chemotherapy, were treated with AMF 300 mg/m2/day by 60 min i.v. infusion for five days repeated every three weeks. Fifteen patients had lung (9 patients) and/or liver (8 patients) involvement. None had known brain metastasis at entry. All 20 patients were evaluated for response and toxicity. Six patients had stable disease and fourteen had increasing disease. With 0/20 responses, the upper 95% confidence limit for the response rate was 14%. The median survival time was 5.7 months. Hematologic toxicity was dose limiting with the incidence of leucopenia 45% and thrombocytopenia 20%. The nonhematologic toxicities included nausea and vomiting (60%), alopecia (20%), headaches (15%), diarrhea (10%), and phlebitis (10%). We conclude that AMF administered at this dose and schedule is not active in the treatment of patients with malignant melanoma, previously untreated with chemotherapy.
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PMID:Evaluation of amonafide in disseminated malignant melanoma. A Southwest Oncology Group study. 826 36

The effect of the rate of infusion of disodium aminohydroxypropylidene bisphosphonate (APD; CGP 23339A), an inhibitor of bone resorption, on urinary excretion of this agent was studied in a randomized open-label study in 20 cancer patients. Ten patients received 60 mg of APD over 4 h, and the remaining 10 patients received the same dose over 24 h. Urine collected during specified intervals for 72 h after the start of the infusion was analyzed by high-performance liquid chromatography for unchanged APD. Mild and transient adverse experiences were observed in 12 (60%) patients; the most common were headache, fever, and phlebitis at the infusion site. No clinically significant laboratory abnormalities were observed, and none of the experiences were serious enough to require discontinuation of treatment. Cumulative urinary excretion of APD was a linear function of time, increasing rapidly after both the 4- and 24-h infusions were started. The mean (+/- standard deviation) cumulative urinary excretion of APD was 51.1 +/- 13.0% of the dose in the 20 patients, 55.0 +/- 15.0% in the 10 patients given the 4-h infusion, and 47.2 +/- 9.9% in the 10 patients receiving the 24-h infusion. Thus, the rate of infusion of the 60-mg dose did not influence retention of APD at 72 h after the start of therapy. Similarly, the presence or absence of bone metastases did not influence cumulative urinary excretion or the retention of APD.
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PMID:Urinary excretion of aminohydroxypropylidene bisphosphonate in cancer patients after single intravenous infusions. 833 45

The safety profile of isepamicin has been assessed from a series of phase II and III clinical trials. A total of 1243 patients were randomised to treatment with isepamicin, mainly administered once daily at a dose of 15 mg/kg or 8 mg/kg depending on the severity of infection. A small proportion of patients were randomised to isepamicin at a dosage of either 7.5 mg/kg twice daily or 4 mg/kg twice daily. In the majority of studies, isepamicin was compared with a standard twice-daily dosing regimen of 7.5 mg/kg amikacin = (n - 552). The clinical studies included patients with a variety of bacterial infections, including lower respiratory tract, urinary tract, intra-abdominal and skin and skin structure infections. The study aminoglycosides were co-administered with other antimicrobial agents in line with normal clinical practice depending on the site, nature and severity of infection. Most patients received isepamicin or amikacin as a 30-minute intravenous infusion and a small proportion of patients with less severe infections received intramuscular injections. The mean duration of treatment was nine days for both the isepamicin and amikacin treatment groups, and was similar for patients with both severe and less severe infections. Overall, the proportion of patients reporting any adverse event was comparable between the isepamicin (13%) and amikacin (11%) groups. No individual adverse event was reported in more than 2% of patients, the most commonly reported events being phlebitis, rash, headache and renal compromise. The frequency of adverse events was not influenced by treatment duration, age or gender. Treatment-related adverse events which were considered severe or life-threatening were reported in 1.8% of patients receiving isepamicin and 2.0% of patients receiving amikacin. Two per cent of patients in each treatment group discontinued the study because of adverse events and 2% of patients in each treatment group died during treating. Four per cent of patients in each treatment group died within 30 days after the end of treatment. Changes in laboratory tests were similar in both treatment groups; few changes were considered by the investigators to be treatment-related. Increases in serum creatinine indicative of possible renal compromise occurred in 4.6% of isepamicin and 5.1% of amikacin patients. The occurrence of ototoxicity as measured by standard frequency pure tone audiometry was low. In summary, isepamicin is a sell-tolerated aminoglycoside with a safety similar to that of amikacin.
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PMID:An overview of the safety of isepamicin in adults. 862 16

Systemic lupus erythematosus (SLE) patients, especially those with antiphospholipid antibodies, have a high incidence of arterial and venous thrombotic manifestations. However, renovascular hypertension (RVH) has been rarely reported in these patients. We describe here a 49-year-old female with antiphospholipid antibodies, complicated with RVH and presenting with sudden onset of severe hypertension, headache and nausea. She had experienced phlebitis and arterial thrombosis of the right leg. At the age of 38 years, she was diagnosed as SLE and steroid therapy was started, but she had poor drug compliance and irregularly visited our clinic. On admission, hypertension was recognized and abdominal bruit was audible on physical examination. Serological findings were compatible with SLE. She was also found to have IgG anti-cardiolipin antibody and lupus anticoagulant. Peripheral plasma renin activity (PRA) was elevated, and captopril test showed hyper-response of PRA with lowering of blood pressure. Renal echography and scintigram showed a small and poorly perfused right kidney. Selective angiography demonstrated a severe stenosis of the right renal artery at origin. A stenosis at the origin of both the superior mesenteric artery (SMA) and celiac trunk was also detected. Percutaneous transluminal angioplasty was performed, achieving successful dilatation of the right renal artery and SMA, whereas the attempt to insert the catheter into the celiac trunk was unsuccessful. After this procedure, abdominal bruit has not been audible. Following the initiation of steroid pulse therapy combined with heparin and dipyridamole, her blood pressure was gradually depressed and the test for lupus anticoagulant became negative. Therefore, RVH of this patient is thought to be associated with antiphospholipid antibodies.
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PMID:[Renovascular hypertension associated with antiphospholipid antibodies in a woman with systemic lupus erythematosus]. 891 95

A Phase Ib trial of bryostatin 1, a macrocyclic lactone and protein kinase C (PKC) activator, was conducted in patients with refractory nonhematological malignancies with the primary goal of determining whether down-regulation of peripheral blood mononuclear cell (PBMNC) PKC activity could be achieved in vivo in humans. Patients (four patients/cohort) received bryostatin 1 (25 microg/m2) as a 1-h infusion weekly three times every 4 weeks, but to study the schedule dependence of pharmacokinetics and pharmacodynamics, the first dose was administered according to one of three schedules: (a) a 1-h infusion; (b) a 24-h infusion; or (c) a split course (12.5 microg/m2 as a 30-min infusion) on days 1 and 4. Conventional toxicities (grades I-III) included myalgias, fever, anemia, fatigue, phlebitis, and headache; in addition, two patients in cohort 3 experienced transient elevations in liver function tests, although these patients had preexisting liver metastases. No objective clinical responses were encountered. Effects on PBMNC PKC activity were heterogeneous. Several patients in cohorts 1 and 2 experienced significant declines in activity (approximately 50%) that were sustained in some cases for periods of > or = 72 h. Comparison of 72-h with baseline values for all three patient cohorts combined revealed a trend toward PKC down-regulation (P = 0.06; signed rank test). For each schedule, plasma bryostatin 1 levels were below the level of detection of a platelet aggregation-based bioassay (3-4 nm). Bryostatin 1 administration failed to produce consistent alterations in lymphocyte immunophenotypic profiles, interleukin 2-induced proliferation, or cytotoxicity, although two of three samples from patients in cohort 3 did show significant posttreatment increases in proliferation. Moreover, in some patients, bryostatin 1 treatment increased lymphokine-activated killer cell activity. These findings indicate that bryostatin 1 doses of 25 microg/m2 can induce in vivo PBMNC PKC down-regulation in at least a subset of patients and raise the possibility that higher bryostatin 1 doses may be more effective in achieving this effect.
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PMID:Phase Ib trial of bryostatin 1 in patients with refractory malignancies. 953 28

Didemnin B (NSC-325319), a new depsipeptide isolated from a Caribbean tunicate, has been evaluated in a clinical phase I study. The drug was administered in a schedule of a 4 weekly intravenous injection in a six-weeks cycle. Fifty-three patients received 71 evaluable cycles in an escalated dose ranging from 0.4 mg/m2/week to 2.5 mg/m2/week. No hematological toxicity was demonstrated at any dose level. Without prophylactic antiemetics nausea and vomiting was dose limiting at 1.2 mg/m2/week. Due to the use of Cremophor EL as a solvent, hypersensitivity reactions occurred in 9 patients. These reactions occurred following prior exposure to the drug and were commonly seen at the 3rd dose. They were not dose related but became more frequent at 1.5 mg/m2/week necessitating prophylactic treatment with H and H2 receptor blocking agents. Non-hematological toxicities included mild diarrhea, mucositis, anorexia, headaches, and local phlebitis. The dose- limiting toxicity was generalized weakness which became severe and disabling in 3 of 6 patients treated at 2.5 mg/m2/week. No objective responses were documented in 39 patients with evaluable disease. The recommended dose for phase II studies was 2.3 mg/m2/week x 4 in a 6-weeks cycle given with prophylactic antiemetics and H1 and H2 receptor blocking agents.
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PMID:Phase I clinical study of didemnin B. A National Cancer Institute of Canada Clinical Trials Group study. 974 May 44

GI147211 is a novel, totally synthetic camptothecin with promising preclinical and early clinical activity. This study was designed to determine the maximum tolerated dose of Gl147211 as a 72-h infusion and to describe its pharmacokinetics and pharmacodynamics on this schedule. In a single-arm, rising-dose study in patients with advanced cancer, eight cohorts of three or more patients received 72-h infusions of Gl147211 at doses ranging from 0.25 to 2.5 mg m(-2) day(-1). Forty-four patients received a total of 124 cycles. All patients had refractory tumours and 40 had received prior chemotherapy and/or radiotherapy. Whole-blood Gl147211 lactone, total blood and total concentrations were measured during and over the 12 h following the infusion. Myelosuppression was observed at all dose levels. Neutropenia was dose limiting at 2.0 mg m(-2) day(-1) in minimally pretreated patients, while both neutropenia and thrombocytopenia were limiting at 1.5 mg m(-2) day(-1) in those more heavily pretreated. Phlebitis occurred with infusions through peripheral veins early in this study, necessitating the use of central venous access. Other toxicities included mild nausea and vomiting, fatigue, headache, central venous catheter infections and alopecia. Three partial and two minor responses lasting 8-34+ weeks were noted in patients with ovarian, colon and breast carcinomas and hepatoma. Mean steady-state concentrations of Gl147211 increased with dose over a range of 0.25-1.24 ng ml(-1). The mean terminal elimination half-life was 7.5 h, and the clearance averaged 1074 ml min(-1) m(-2) over the doses studied. The mean fractional excretion of unchanged drug in urine was 0.114. Gl147211 lactone exposure correlated with haematological toxicity. The recommended phase II doses for this regimen are 1.75 mg m(-2) day(-1) and 1.2 mg m(-2) day(-1) for minimally pretreated and heavily pretreated patients respectively. At these doses, steady-state Gl147211 concentrations within the range of those effective in vitro were achieved. Extensive phase II evaluation of this compound and further phase I trials evaluating more prolonged infusions are ongoing.
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PMID:A phase I clinical and pharmacokinetic study of the new topoisomerase inhibitor GI147211 given as a 72-h continuous infusion. 982 74

This multicentre, randomised, double-blind study compared oral zolmitriptan 2.5 mg with a combination of oral acetylsalicylic acid 900 mg and metoclopramide 10 mg as acute anti-migraine therapy for 3 migraine attacks. In total, 666 patients took at least one dose of study medication (326 took zolmitriptan and 340 took acetylsalicylic acid plus metoclopramide). The percentage of patients with a 2-hour headache response after the first dose for all 3 attacks (the primary end point) was 33.4% with zolmitriptan and 32.9% with acetylsalicylic acid plus metoclopramide [odds ratio 1.06, 95% confidence interval (CI) 0.77-1.47; p = 0.7228]. For the majority of secondary end points, the two treatments demonstrated comparable efficacy. However, post hoc analysis showed that significantly more patients receiving zolmitriptan were free of pain 2 h after the first dose in all 3 attacks compared with patients receiving acetylsalicylic acid plus metoclopramide (10.7 vs. 5.3%; odds ratio 2.19, 95% CI 1.23-4.03; p = 0.0095). In addition, post hoc analysis showed that the overall 2-hour pain-free response rate was consistently higher with zolmitriptan (34.6%) than with acetylsalicylic acid plus metoclopramide (27.9%) (odds ratio 1.40, 95% CI 1.09-1.78; p = 0.007). Both treatments reduced migraine-associated nausea, vomiting, phonophobia and photophobia. There were no important inter-group differences with respect to the onset of meaningful migraine relief, the frequency of headache recurrence, the usage or efficacy of a second dose of medication or the use of escape medication. However, at the last attack, the proportion of patients who expressed overall satisfaction with the treatment was significantly higher in the zolmitriptan group, i.e. 83.7%, versus 75.0% with acetylsalicylic acid plus metoclopramide (p = 0.0346). Both agents were well tolerated. Adverse events were reported by 40.8% (133/326) of zolmitriptan-treated patients and 29.1% (99/340) of those treated with acetylsalicylic acid plus metoclopramide. The incidence of withdrawals due to adverse events was very low with both zolmitriptan (0.9%) and the combination regimen (1.5%); the latter percentage included 1 patient who withdrew from the study due to phlebitis, which was classified as a serious adverse event. This study showed that zolmitriptan is effective and well tolerated for the acute treatment of moderate to severe migraine. Zolmitriptan was at least as effective as acetylsalicylic acid plus metoclopramide in achieving a 2-hour headache response, but significantly more effective than the combination therapy for other end points, including the 2-hour pain-free response.
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PMID:Zolmitriptan versus a combination of acetylsalicylic acid and metoclopramide in the acute oral treatment of migraine: a double-blind, randomised, three-attack study. 1184 97

SU5416 is a small molecule antiangiogenic agent that inhibits vascular endothelial growth factor (VEGF) stimulation of the KDR tyrosine kinase receptor. In this Phase I dose escalation trial, a weekly dose schedule of SU5416 was tested whereby an initial 5-day loading dose was followed by weekly maintenance infusions. The start dose was 20 mg/m(2) for the loading dose followed by 65 mg/m(2) for the weekly infusions. Dose escalations occurred at 33% until a final dose of 65 mg/m(2) (loading dose) and 190 mg/m(2) (weekly infusion) was obtained. Twenty-two patients were treated at five dose levels; tumor types included gastrointestinal (8), breast (3), lung (4), sarcoma (2), and other (5). The most common serious drug-related toxicity was headache, often associated with nausea and vomiting. Grade 1 and 2 toxicities included headache, nausea, vomiting, asthenia, pain at the infusion site, phlebitis, change in voice, and fevers. Of 19 evaluable patients, 4 obtained clinical benefit as defined by tumor regression (1) or disease stabilization for at least 12 weeks (3). Pharmacokinetic data revealed that the weekly infusion schedule prevented the reported 50-60% induction in SU5416 clearance observed with either daily or twice weekly dosing. Higher baseline levels of urine VEGF were observed in the 4 patients who gained clinical benefit, suggesting this may be a useful marker for predicting response to anti-VEGF therapies. Our results suggest that a weekly schedule of SU5416 shows signs of biological activity and is well tolerated at doses up to 145 mg/m(2).
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PMID:Results of a Phase I dose-escalating study of the antiangiogenic agent, SU5416, in patients with advanced malignancies. 1223 19


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