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)

Cefotaxime has been used to treat serious bacterial infections in children since 1982. With the predominant use of cephalosporins in pediatrics, reports of adverse effects of certain compounds have increased. A retrospective review is presented of 2,243 cases of children receiving therapy with cefotaxime in order to evaluate the safety profile and efficacy of cefotaxime in the treatment of serious infections in hospitalized children. Overall, 57 (2.5%) children experienced adverse reactions. These included local reactions in 6 (0.3%), rash in 28 (1.2%), diarrhea in 15 (0.97%), vomiting in 10 (0.7%), abdominal pain in 1 (0.1%), headache in 3 (0.4%), and drug fever in 1 (0.1%). No cases of hemolytic anemia, bleeding, or hyperbilirubinemia were found. Efficacy of treatment for different disease categories ranged from 90.5% to 100%. The percentage of children in any treatment group with a particular laboratory abnormality following initiation of cefotaxime therapy ranged from 0% to 2.6%, and rates of superinfection with bacteria or Candida were 0.4% to 1.7%. Cefotaxime has the distinct advantage of high rates of efficacy and low rates of complications and superinfection among children hospitalized for serious infections.
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PMID:Safety profile and efficacy of cefotaxime for the treatment of hospitalized children. 152 Jul 74

A phase I trial of intramuscularly administered recombinant human tumor necrosis factor (rTNF) was conducted in 19 adult patients with advanced solid tumors. The agent was administered daily for up to five consecutive days every other week for two to four courses. Doses of rTNF ranged from 5 to 200 micrograms/m2/d. Dose-limiting toxicities were encountered at doses greater than 100 micrograms/m2/d. Toxicities included tenderness, erythema and induration at the site of injection, fatigue, fever, chills, headache, anorexia, nausea, vomiting, and diarrhea. Moderate to marked reductions in WBC and platelet counts were observed regularly at the highest dose levels, but none were clinically significant. Hepatic enzyme elevation was seen frequently, and two patients developed hyperbilirubinemia. Only one of seven patients treated with doses greater than 100 micrograms/m2/d completed the planned course of therapy. Even at the highest dose levels, serum concentrations of rTNF could only rarely be detected in the serum. No therapeutic responses were observed. The maximal tolerated dose (MTD) of rTNF in this trial was 150 micrograms/m2/d, administered for two courses.
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PMID:Phase I trial of intramuscularly administered tumor necrosis factor in patients with advanced cancer. 291 29

Twelve patients were treated in a Phase I trial of purified human interleukin-2 (IL-2) derived from the JURKAT cell line (E.I. duPont Corp., Glenolden, PA, U.S.A.). The serum half-life, toxicity, and in vivo immunologic effects of IL-2 were studied in patients with cancer unresponsive to standard therapy and in patients with acquired immunodeficiency syndrome (AIDS). Patients received 0.25, 2.5, or 25 micrograms/kg IL-2 by bolus or 24-h continuous infusion on a weekly basis for 4 weeks. The serum half-life of JURKAT IL-2 in humans was approximately 6 min. At higher doses of IL-2 a second component of clearance with a half-life of 30-120 min was found. Acute toxicity was minimal and consisted of headache (6 of 12), nausea (4 of 12), malaise (6 of 12), and fever and chills (8 of 12). No evidence of pulmonary, hematologic, or renal toxicity or any evidence of autoimmune phenomena was detected. A transient hyperbilirubinemia was seen in two patients receiving 2 mg purified IL-2. No demonstrable effect on tumors or chronic immunodeficiency (AIDS) was seen. No consistent chronic immunologic effects (natural killer or lymphokine-activated killer activity, mitogen responsiveness, total lymphocyte counts, or change in the proportion of various mononuclear cell phenotypes as defined by monoclonal antibody) were seen on a week-to-week basis during or following therapy. Acute changes in lymphokine responsiveness, the ability to generate lymphokine-activated killers, and an increase in macrophages in the mononuclear population were noted following administration of 1-2 mg IL-2.
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PMID:Systemic administration of interleukin-2 in humans. 633 35

To evaluate the safety of cryopreserved and thawed peripheral blood stem cell (PBSC) autografts in children with active cancer, a toxicity assessment was made of 54 PBSC transfusions to 52 children (aged 1-16 years; median, 9 years). Patients were conditioned with high-dose chemotherapy without total body irradiation. The volume of PBSCs transfused varied from 46 to 500 mL (219.6 +/- 118.4 mL, mean +/- SD), with a mean of 0.91 g per kg of dimethyl sulfoxide. Insignificant and transient toxicities included hemoglobinuria in 40 patients (74%), headache in 38 (70%), nausea in 37 (69%), and vomiting in 25 patients (46%). Significant shock developed in 8 patients (15%), but they recovered quickly, whether they had supportive therapy or not. Vomiting and hyperbilirubinemia were the only toxicities that showed a correlation with the amount of PBSCs transfused. The data suggest that transient toxicity associated with PBSC autografts is rather common in children, and close observation of patients for possible serious morbidity is required.
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PMID:Toxicities associated with cryopreserved and thawed peripheral blood stem cell autografts in children with active cancer. 810 99

Thirty five patients with imported malaria were hospitalised in a period of 1980-93 in Department of Infectious Diseases of Pomeranian Medical School, Szczecin, Poland. The diagnosis of malaria was established on a base of clinical feature, the presence of Plasmodium in peripharal blood smears and, in some cases, on positive serological tests. Thirty two patients were Polish citizens, and three persons were foreigners. Malaria was caused mostly by invasion of Plasmodium falciparum (62.8), then P. vivax (31, 4), in 1 case--P. ovale and 1 case--mixed invasion occurred (P. falciparum and P. vivax). The majority of cases caused by P. falciparum were imported from Central Africa. Invasions of P. vivax were brought from North Africa, India and Middle East. Malaria in Polish patients was connected with occupational exposure and lack of proper antimalarial prophylaxis was obvious. A clinical course of disease was serious, with one mortal case. Fever, headache, abdominal pain, weakness, jaundice, insomnia were main complaints. Anemia, leucopenia, thrombocytopenia, hyperbilirubinemia, hypertransaminasemia and high serum concentration of urea were observed. A level of parasitemia in peripheral blood varied from minimal to very high (22.5%) in cases of P. falciparum invasions. In treatment chloroquine, fansidar, quinine, primaquine, halfan were used.
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PMID:[Observation of patients with malaria hospitalized during the years 1980-1993 in the Clinic of Infectious Diseases in Szczecin]. 886 94

The goal of our study was to determine the epidemiological and clinical features of imported malaria seen at our military hospital in Hawaii. We reviewed the records of malaria cases seen from January 1, 1979, to December 31, 1995, and compared our results with published reviews from civilian hospitals in North America. Seventy-nine patients were diagnosed with malaria by blood smears. All acquired malaria abroad, mostly in southeast Asia. Sixty-seven percent of cases were vivax malaria, 22% were falciparum malaria, and 11% were caused by undetermined species. Common symptoms were fever (100%), alternate day fever (41%), rigors (91%), headache (59%), nausea (41%), fatigue (39%), dark urine (32%), and vomiting (31%). Ninety-one percent had fever during hospitalization, but 39% were afebrile on admission. Splenomegaly was detected in 49% of cases. The white blood cell count was normal in 65%, low in 31%, and elevated in 4% of cases. Other laboratory findings were anemia (58%), thrombocytopenia (74%), and mild hyperbilirubinemia (64%). Military physicians initially considered the diagnosis of malaria in only 54% of patients. The epidemiological features of our patients differ from those described in the civilian hospitals. Most of our patients were nonimmune, U.S.-born, military personnel infected in southeast Asia, whereas patients described in reviews from U.S. civilian hospitals were usually foreign-born civilians who were infected in Africa or India. The clinical features of malaria, and the problems of initial misdiagnosis in our patients, were similar to those reported from civilian hospitals. Military physicians, like their civilian colleagues, need more training and experience in malaria.
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PMID:A review of 79 patients with malaria seen at a military hospital in Hawaii from 1979 to 1995. 950 98

A Phase I dose escalation trial of i.v. administered recombinant human interleukin 12 (rhIL-12) was performed to determine its toxicity, maximum tolerated dose (MTD), pharmacokinetics, and biological and potential antineoplastic effects. Cohorts of four to six patients with advanced cancer, Karnofsky performance >/=70%, and normal organ function received escalating doses (3-1000 ng/kg/day) of rhIL-12 (Genetics Institute, Inc.) by bolus i.v. injection once as an inpatient and then, after a 2-week rest period, once daily for five days every 3 weeks as an outpatient. Therapy was withheld for grade 3 toxicity (grade 4 hyperbilirubinemia or neutropenia), and dose escalation was halted if three of six patients experienced a dose-limiting toxicity (DLT). After establishment of the MTD, eight more patients were enrolled to further assess the safety, pharmacokinetics, and immunobiology of this dose. Forty patients were enrolled, including 20 with renal cancer, 12 with melanoma, and 5 with colon cancer; 25 patients had received prior systemic therapy. Common toxicities included fever/chills, fatigue, nausea, vomiting, and headache. Fever was first observed at the 3 ng/kg dose level, typically occurred 8-12 h after rhIL-12 administration, and was incompletely suppressed with nonsteroidal anti-inflammatory drugs. Routine laboratory changes included anemia, neutropenia, lymphopenia, hyperglycemia, thrombocytopenia, and hypoalbuminemia. DLTs included oral stomatitis and liver function test abnormalities, predominantly elevated transaminases, which occurred in three of four patients at the 1000 ng/kg dose level. The 500 ng/kg dose level was determined to be the MTD. This dose, administered by this schedule, was associated with asymptomatic hepatic function test abnormalities in three patients and an onstudy death due to Clostridia perfringens septicemia but was otherwise well tolerated by the 14 patients treated in the dose escalation and safety phases. The T1/2 elimination of rhIL-12 was calculated to be 5.3-9.6 h. Biological effects included dose-dependent increases in circulating IFN-gamma, which exhibited attenuation with subsequent cycles. Serum neopterin rose in a reproducible fashion regardless of dose or cycle. Tumor necrosis factor alpha was not detected by ELISA. One of 40 patients developed a low titer antibody to rhIL-12. Lymphopenia was observed at all dose levels, with recovery occurring within several days of completing treatment without rebound lymphocytosis. There was one partial response (renal cell cancer) and one transient complete response (melanoma), both in previously untreated patients. Four additional patients received all proposed treatment without disease progression. rhIL-12 administered according to this schedule is biologically and clinically active at doses tolerable by most patients in an outpatient setting. Nonetheless, additional Phase I studies examining different schedules and the mechanisms of the specific DLTs are indicated before proceeding to Phase II testing.
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PMID:Phase I evaluation of intravenous recombinant human interleukin 12 in patients with advanced malignancies. 981 99

LGD1069 [Targretin; 4-[1-(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2-naphtalenyl) propenyl] benzoic acid] is a novel synthetic retinoid X receptor-selective retinoid that has been recently identified. The goals of this study were to determine the safety, toxicity, pharmacokinetics (PKs), and metabolic profile of LGD1069 in advanced cancer patients. Sixty patients received oral LGD1069 at doses ranging from 5-1000 mg/m2/day with PK sampling performed on days 1 and 15. No dose-limiting toxicities (DLTs) were observed up to the 500 mg/m2/day dose level. DLT observed at and above 650 mg/m2/day included skin desquamation, hyperbilirubinemia, transaminase elevation, leukopenia, and diarrhea. Asymptomatic, dose-related alterations in lipid and thyroid metabolism were also observed. DLTs frequently observed with retinoic acid receptor-selective retinoids and pan agonists, including headache, mucocutaneous toxicity, and hypercalcemia, were not dose-limiting with LGD1069. Day 1 LGD1069 Cmax and area under the curve values increased dose-proportionately up to 800 mg/m2/day. Repeat-dose (day 15) area under the curve values varied between 25 and 105% of day 1 values. Although no objective tumor responses were observed, tumor progression may have been substantially arrested or delayed in non-small cell lung cancer (5 of 16) and in head and neck cancer (1 of 5), as well as other tumor types. At the higher dose levels, the molar concentration of LGD1069 was up to 10-fold higher than observed with other retinoids, yet toxicity was minimal. LGD1069 is an retinoid X receptor-selective retinoid agonist with a more favorable PK and toxicity profile than previously studied retinoids and merits further investigation as a chemopreventive and anticancer agent. On the basis of this Phase I trial, the recommended Phase II dose is 500 mg/m2/day.
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PMID:A Phase I study of LGD1069 in adults with advanced cancer. 1043 65

Although retinoids show promise for prevention of second primary upper aerodigestive tract tumors, the optimum retinoid, dose, and schedule are unknown. All-trans retinoic acid (ATRA) has greater affinity for retinoic acid receptors and may be more active than other retinoids but has a shorter plasma half life and may up-regulate its own metabolism. We defined the maximum long-term tolerable dose, dosing frequency, pharmacokinetics, and toxicity of ATRA in patients with treated squamous cell carcinoma of the head and neck (SCCHN). Twenty-one patients were randomized to 45, 90, or 150 mg/m2 ATRA either once daily, or as divided doses every 8 h, for 1 year. Pharmacokinetics were assessed periodically. Fourteen men and seven women with previous SCCHN of initial stage I-IV were treated. Grade > or =3 toxicities (reversible) included headache and hypertriglyceridemia in 5 and 6 patients each, mucositis in 2 patients, and hyperbilirubinemia, elevated alkaline phosphatase, colitis, lipasemia, xerostomia, eczema, and arthritis in 1 patient each. The 150-mg/m2 dose was not tolerable. Doses were reduced for grade > or =3 toxicity in seven of eight patients at 90 mg/m2 daily. Three of nine patients at 45 mg/m2/day required dose reduction, two at the once-daily dose. Day 1 ATRA area under the plasma concentration versus time curve (AUC) increased with dose, and after 1-2 months of continued dosing, the AUC declined in 7 of 13 patients (54%) studied. ATRA AUC did not correlate with toxicity severity or frequency. Fifteen mg/m2/day every 8 h is a tolerable dose for 1 year in patients with treated SCCHN. ATRA pharmacokinetics did not correlate with toxicity.
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PMID:Phase I trial of all-trans retinoic acid in patients with treated head and neck squamous carcinoma. 1074 6

Our purpose in this study was to determine the efficacy and toxicity of losoxantrone (DuP-941), an anthrapyrazole, in patients with metastatic hormone-refractory prostate cancer. Patients with metastatic prostate cancer progressing on androgen ablation therapy without demonstrable antiandrogen withdrawal response were treated with losoxantrone 50 mg/m2 i.v. bolus every 21 days. All of the patients had elevated serum prostate-specific antigen (PSA) before study entry and had no prior chemotherapy. Forty-three assessable patients were entered. The median age was 70.6 years (range, 53.9-85.9), median Karnofsky performance scale (KPS), 70% (50-90%), and the median serum PSA, 173 microg/liter (12.5-11,140). The median number of courses was 4 (1-9). Five patients (25%) had a partial response as defined by >50% decline in the serum PSA. Two of nine patients with measurable disease had partial responses and three had minor responses. Thirty percent of patients had improvement in KPS and 37% had an improvement in symptoms with decrease in pain and/or decrease in analgesic requirement. Nonhematological grade 3 and 4 toxicities were one each of grade 3 headache, grade 4 hypocalcemia, grade 3 hyperbilirubinemia, and grade 3 dyspnea. Twenty-six patients (60%) had grade 3 or 4 absolute neutropenia. In conclusion, losoxantrone demonstrated a partial biochemical response rate of 25%, response in measurable disease sites in 22%, and improvement in clinical symptoms in one-third of patients. In this study, PSA increase was not necessarily associated with lack of palliative response.
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PMID:A multicenter phase II trial of losoxantrone (DuP-941) in hormone-refractory metastatic prostate cancer. 1077 59


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