Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nineteen patients with advanced cancer for which there was no effective standard therapy or whose disease was refractory to standard therapy were treated with recombinant tumor necrosis factor (rTNF). The rTNF was administered subcutaneously for 5 consecutive days every other week for 3 treatment weeks. The doses administered ranged from 5 micrograms/m2/day to 150 micrograms/m2/day. There was no intrapatient dose escalation. Systemic side effects of chills, fever, hypotension, nausea, vomiting, and headache were mild and self-limiting. At the maximum tolerated dose of 150 micrograms/m2/day, five of seven patients experienced moderate to severe thrombocytopenia. Mild rapid declines in total leukocyte count occurred within 60-90 min of administration of the drug, followed by a rise in the total leukocyte count by 120 min. When the total daily dose was administered in a single subcutaneous site, skin ulceration and necrosis occurred at the 100 micrograms/m2/day dose. By giving the total daily dose in two subcutaneous sites, the maximum tolerated dose increased to 150 micrograms/m2/day, and there was no further skin ulceration or necrosis. Skin necrosis occurred in the abdomen and thigh but not on the upper extremity at the 100 micrograms/m2/day dose given in a single site. There was no other significant organ toxicity. No rTNF was detectable in the serum even at the highest doses. No antibodies to TNF developed in any of the patients. The recommended dose of rTNF for Phase II trials given for 5 days subcutaneously is 150 micrograms/m2/day divided into two or more sites.
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PMID:A phase I trial of subcutaneously administered recombination tumor necrosis factor to patients with advanced malignancy. 279 95

Twenty-seven patients with metastatic cancer were treated with a daily continuous intravenous (IV) infusion of recombinant human interleukin-2 (rhIL-2) along with daily intramuscular recombinant interferon-alpha-2a (rIFN-alpha-2a) 4 days per week for 4 weeks with repeated treatment after 2 to 4 weeks of rest. The maximum-tolerated dose (MTD) was 3 million U/m2/d of rhIL-2 with 5 to 10 million U/m2/d of rIFN-alpha-2a. The dose-limiting toxicities are moderate hypotension requiring low doses of pressors and chronic fatigue associated with decreased performance status. Other common side effects included fever, chills, fluid retention, nausea/vomiting, erythrodermia, weight loss, elevated liver transminase levels, anemia, thrombocytopenia, and CNS toxic effects. There were seven objective responses among 25 evaluable patients. Four major responses (one complete response and three partial responses) were observed among 10 patients with melanoma treated with the MTD level. These data suggest that for cancer patients, concomitant rhIL-2 and rIFN-alpha-2a therapy is tolerable and has manageable side effects. Further phase II studies will be needed to define the antitumor activity of this combination.
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PMID:Concomitant administration of recombinant human interleukin-2 and recombinant interferon alpha-2A in cancer patients: a phase I study. 280 85

2 cases of thromboembolism in young women with no risk factors except use of triphasic oral contraceptives are reported. A 21-year old White woman, Gravida I Para I, presented to the emergency room with a painful, blue, mottled right lower leg after pain in the hip and buttock for 1 week. She had taken a triphasic oral contraceptive containing 35 mcg ethinyl estradiol and 0.5, 0.75, 1 mg norethindrone for 1 month, and had no other related history. Doppler and venogram tests showed thrombosis of the ileal, femoral, popliteal and infrapopliteal veins. She was treated with heparin, streptokinase, and urokinase without success and recovered after ileal, femoral and popliteal thrombectomy. The 2nd case was a 30-year-old Gravida III Para I Black woman who had taken a pill containing 50 mcg ethinyl estradiol and 500 mcg norgestrel for 13 years and had recently switched to the triphasic pill described above. She had dull midepigastric pain, nausea, vomiting, diarrhea and chills, for 1 week. Physical exam was negative except for abdominal tenderness and a heart murmur. Abdominal ultrasound revealed portal venous thrombosis extending to the splenic and superior mesenteric veins. She was treated with transhepatic urokinase without effect and celiotomy was performed. She was discharged with an occluded right branch of the portal vein. These cases point out the fact that the estrogen dose in triphasic pills is not lower than that in low dose combined oral contraceptives.
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PMID:Idiopathic thromboembolism associated with triphasic oral contraceptives. 281 53

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

An explosive outbreak of gastrointestinal illness occurred among students and employees at a small college in Florida in November 1980. Common symptoms were diarrhea, nausea, weakness, abdominal cramps, chills, vomiting, and low-grade fever. Cases of illness were identified in 40% of 628 students and 15% of 162 employees who responded to a survey. Among students, there was a sevenfold excess risk associated with eating one or more meals at the campus cafeteria November 3-5 (p much less than 0.001). Tossed salad from one meal was strongly associated with illness (p less than 0.0001). Fecal contamination of the salad was documented, although the source of contamination was not identified. Person-to-person spread could not be demonstrated. Seroconversion to Norwalk antigen occurred in significantly more cases (5/6) than noncases (1/6) (p = 0.04).
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PMID:Norwalk virus gastroenteritis. An outbreak associated with a cafeteria at a college. 299 Jan 97

A Phase I study of rHu-TNF (PT-050) was conducted in patients with various malignant tumors refractory to conventional therapy. rHu-TNF was administered by 30-min intravenous (i.v.) infusion or intratumor (i.t.) injection. The starting dose of 1 X 10(5) U/body was increased to 5 X 10(6) U/body in the i.v. group and to 2 X 10(6) U/body in the i.t. group. rHu-TNF was evaluated in 41 patients among the enrolled 43 patients of the i.v. group, and in 9 out of 10 in the i.t. group. In the i.v. group, fever (68.3%), chills (75.6%), hypotension (46.3%), general fatigue (34.1%), nausea/vomiting (22.0%/22.0%), pain in the extremities (17.1%), etc. were observed as adverse reactions (ADRs), and elevation of GOT/GPT (46.3%/43.9%), elevation of ALP(26.8%)and decrease in platelets (12.2%), etc. were observed as abnormal laboratory findings. Among these, hypotension was recognized as the dose-limiting factor and the maximum tolerated dose was considered to be 1 X 10(6) U/body. Plasma levels of rHu-TNF after 30-min i.v. administration were dose-related, and decreased with half-lives of 0.5-2.4 hours. In the i.t. group, ADRs occurred with a lower incidence than in the i.v. group except for fever, chills and general fatigue. Plasma levels after i.t. administration were all within the assay limit. Evident tissue necrosis was observed in the region where rHu-TNF was administered in the i.t. group.
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PMID:[A phase I study of recombinant human tumor necrosis factor (rHu-TNF: PT-050). The PT-050 Study Group]. 302 81

Recombinant human interleukin-2 (rIL-2) was administered to 34 patients with advanced malignancy. Three schedules of rIL-2 administration employed were as follows: (A) 2-hr iv infusion of 6.7 X 10(5) U/m2/day (A1, 6 cases) or 2.2 X 10(6) U/m2/day (A2, 8 cases) for five consecutive days; (B) 24-hr continuous iv infusion of 3.3 X 10(5) U/m2/day (B1, 3 cases), 6.7 X 10(5) U/m2/day (B2, 7 cases) or 1.1 X 10(6) U/m2/day (B3, 5 cases) for 28 consecutive days; and (C) 24-hr continuous iv infusion of 6.7 X 10(5) U/m2/day (C, 5 cases) for 5 consecutive days per week for four weeks. The common side effects were fever (79%), eosinophilia (61%), malaise (56%), erythema or rash (50%), chills (38%) and nausea or vomiting (35%), with the dose-limiting toxicities being hypotension in group A, and renal dysfunction with fluid retention in groups B and C. In the case of 2-hr iv infusion, rIL-2 was rapidly cleared from the plasma, with a half life of about 30 min, while in the case of 24-hr continuous infusion, more than 1 U/ml serum IL-2 activity was maintained for 14 days in group B3. Natural killer (NK) and lymphokine-activated killer (LAK) activities were augmented by rIL-2 administration in patients of groups A, B3 and C. In eight patients of group B, NK and LAK activities transiently decreased after rIL-2 administration, and recovered by day 3. The percentage of IL-2 receptor and Leu HLA-DR positive cells reached the peak level on day 7 in group B. In patients of group C, the percentage of Leu HLA-DR positive cells as well as NK and LAK activities increased upon rIL-2 administration and decreased during an intermission of two days. However, the percentage of rIL-2 receptor positive cells increased during the intermission of rIL-2. The most effective schedule of rIL-2 administration was considered to be the schedule of group C on the basis of this study.
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PMID:Three schedules of recombinant human interleukin-2 in the treatment of malignancy: side effects and immunologic effects in relation to serum level. 312 1

Three placebo-controlled double-blind and crossover trials were carried out to analyze the effects of oral yohimbine (YOH) 0.8 mg/kg on mood and performance in 16 healthy students. Subjective assessments (visual analogue scales, side-effects on questionnaire) and objective measurements (digit symbols, flicker fusion, tapping, heterophoria) were done at baseline, and post treatment. YOH shifted the healthy subjects' mood towards feeling panicked, elevated systolic blood pressure and plasma prolactin concentrations, reduced digit symbol substitution, and induced drowsiness and passiveness. Caffeine (CAF) 10 mg/kg raised plasma cortisol and rendered the subjects slightly panicked. Muzziness, clumsiness, tremor, chills and nausea were common after both YOH and CAF. Diazepam (DZ) 0.3 mg/kg given at 60 min antagonized some effects of CAF but failed to antagonize YOH. Clonidine (CLO) 100 micrograms counteracted YOH effects on blood pressure but less the subjective and hormonal effects. CLO 200 micrograms partly antagonized the pressor, sedative but not the hormonal responses of YOH. DZ counteracted YOH effects on plasma cortisol on panic but not on other subjective measures or plasma prolactin. Since CLO did not abolish YOH-induced prolactin increase, it is suggested that these effects of YOH are mediated not only via adrenergic alpha 2-receptors; other mechanisms made important contributions.
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PMID:Anxiogenic effect of yohimbine in healthy subjects: comparison with caffeine and antagonism by clonidine and diazepam. 315 10

Twelve children ages 3-15 years with relapsed acute lymphocyte leukemia (ALL) were treated over 25 days by intravenous or intramuscular administration of interferon-alpha n1 (IFN-alpha n1). Single doses ranged from 2.5 to 15 MU/m2, total doses from 60 to 200 MU/m2. Serum pharmacokinetics were determined following administration of two different doses. Calculation of area under serum concentration curve (AUC) values showed increased AUC with increased dose. Mean AUC (h x U/ml) ranged from 735 to 3986 at doses of 2.5 and 15 MU/m2, respectively, when given intramuscularly. AUC for i.v. and i.m. administration were similar. Side effects reported most commonly were fever and chills in 11 of 12 patients, nausea/vomiting in 7, mild lethargy in 3, and injection site pain in 4 of 9 treated i.m. Reversible hepatotoxicity occurred in the 3 patients receiving the highest doses, 10 then 15 MU/m2. Three patients had clinically significant bleeding associated with mildly increased coagulation studies and an additional three patients had increased coagulation parameters without bleeding. Four patients were considered to have stable disease; one treated at the highest dose level had clearance of peripheral blasts but remained in bone marrow relapse. IFN-alpha n1 as used in this study produced detectable blood levels with associated side effects. A Phase II intramuscular trial is recommended.
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PMID:Interferon-alpha n1 in children with recurrent acute lymphocytic leukemia: a phase I study of pharmacokinetics and tolerance. 316 26

A phase I study of recombinant human tumor necrosis factor (rHu-TNF:PT-050) given by intravenous infusion over 30 min or by intratumoral administration was performed in 53 patients with various types of malignant tumors. The dose of rHu-TNF was started with 0.1 x 10(6) U/body for both intravenous infusion and intratumoral administration and increased to 5 x 10(6) U/body for intravenous infusion and 2 x 10(6) U/body for intratumoral administration. The side effects of rHu-TNF given by intravenous infusion included fever, shaking chills, hypotension, general malaise, nausea, and vomiting, and clinical laboratory tests showed elevations of GOT, GPT, and ALP, etc. Among these, only hypotension was dose-related and was considered to be a dose-limiting factor. The maximum tolerable dose estimated was 1 x 10(6) U/body. The plasma concentration of rHu-TNF after completion of a 30-min infusion was dose-dependent, and the elimination half-life was 0.5-2.4 hr. When the rHu-TNF was administered intratumorally, the frequency of side effects was low compared with intravenous infusion.
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PMID:Phase I study of recombinant human tumor necrosis factor (rHu-TNF:PT-050). 318 Jan 46


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