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)

30 patients with HIV infection were enrolled to evaluate the clinical efficacy and toxicity of zidovudine (AZT), 0.5 g/day p.o. (Group A) vs. AZT 0.5 g/day p.o. plus intravenous immunoglobulins (IVIG), 0.4 g/kg of body weight for three consecutive days, followed by one treatment of 0.6 g/kg of body weight every fourth week (Group B), over a period of one year. The study was open and randomized. The treatment groups were compared using the following study variables: 1) type of infections, recurrences and severity; 2) change in CD4+ T and CD8+ T cell count; 3) change in platelet count; 4) change in TNF alpha serum levels; 5) the probability of not developing an opportunistic infection over a period of 12 months. Patients from Group B developed less pathological events in comparison to Group A. No significative differences were evident with regard to values of T cell subsets obtained before and after treatment in each group and between the two groups. On the contrary, in 12 out of 15 patients from Group B there was a significant increase in platelet count. In both groups there was a significant decrease of mean serum levels of TNF alpha when a comparison was made between time 12 vs. time 6. However, when data were expressed as single values, in three subjects from Group B TNF alpha was still detectable by time 12 vs. 9 individuals in Group A. The cumulative probabilities of developing an opportunistic infection over the 12 months of treatment in the Group A subjects were significantly higher than in the Group B subjects (p less than 0.01). Adverse effects--nausea and gastric pain--were reported for 3 individuals (20%) from Group A and 4 patients (26%) from Group B. In conclusion, patients treated with AZT are especially likely to benefit from IVIG prophylaxis.
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PMID:Clinical and immunologic effects of combination therapy with intravenous immunoglobulins and AZT in HIV-infected patients. 194 58

Based on a phase I study in 1986, 22 patients have been entered in a phase II study of high-dose human tumor necrosis factor (rH-TNF) since May 1987. Of these patients, 18 are evaluable at present, 2 are still under investigation, and 2 have dropped out. All had advanced stages of cancer (9 soft-tissue sarcomas, 3 melanomas, 5 hypernephromas) and inclusion in the study was ethically acceptable (informed consent). The daily dose of rH-TNF was 15 x 10(5) units/m2, escalated to 21 x 10(5) units/m2 (683-956 micrograms/m2 every week; range 1-6 cycles). Additional prophylactic ketoprofen administration was carried out. Of the 18 evaluable patients, 4 responded with no change (2/4, clinical improvement) and 14 showed progressive disease. The main toxicities observed were hypotension (decrease in systolic blood pressure, 21-60 Torr), leukocytosis, increases in ALAT/ASAT (WHO grade 0-4), fever (WHO grade 1-2), chills (mild to moderate), neurotoxicity (WHO grade 0-2), and nausea/vomiting (WHO grade 0-3).
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PMID:Phase II clinical trial of high-dose recombinant human tumor necrosis factor. 279 Nov 93

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

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

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

The use of alpha interferon (alpha IFN) and, more recently, of the purine analogues deoxycoformycin (dCF) and 2-chlorodeoxyadenosine (2-CdA) has dramatically improved the prognosis of patients affected by hairy cell leukemia (HCL). DCF has been shown to induce an higher and more durable response rate than IFN, with only moderate myelosuppression and relatively few side effects. In this paper, we report our experience with dCF in a series of 38 HCL patients who had progression of their disease after IFN therapy. Serum interleukin-1 beta (IL-1 beta), soluble interleukin-2 receptors (sIl-2R) and Tumor Necrosis Factor alpha (TNF alpha) levels were also evaluated before, both during and after treatment in order to monitor clinical response. Two schedules of treatment were employed: 23 patients were treated with the EORTC protocol and the following 15 with the NCI regimen. The overall response rate was 94.7%; no significant differences in response rates were observed between the two schedules. In respect to toxicity, we recorded nausea and in two cases a cutaneous rash. Four patients experienced localized herpes zoster and one had a fungal pneumonia. Median overall survival after therapy is 38.5 months, 55 percent of patients enrolled in the EORTC schedule and 77% of those who received the NCI program are currently in CCR at 3 years. Serum IL-1 beta and sIL-2R levels significantly decreased after treatment, while no significant changes in serum TNF alpha levels were observed. In our study, dCF was confirmed as an effective agent in HCL, inducing an high response rate with only moderate side effects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Deoxycoformycin induces long-lasting remissions in hairy cell leukemia: clinical and biological results of two different regimens. 782 42

The use of OKT3 as an immunosuppressive agent is accompanied by increased cytokine production and constellation of side effects collectively termed cytokine release syndrome (CRS). Pentoxifylline (PTF) inhibits synthesis of some cytokines, and has been shown to attenuate CRS when administered before OKT3. In this double-blinded, placebo-controlled study, 46 renal allograft recipients were randomized to receive either PTF (800 mg q 8 hr for at least 24 h) p.o. or placebo, along with methylprednisolone (7 mg/kg), diphenhydramine, and acetaminophen, prior to beginning OKT3 as therapy for acute rejection. Patients were observed, and symptoms scored semiquantitatively. Despite the presence of therapeutic PTF levels (721 +/- 726 ng/ml), the frequency and severity of side effects (fever, chills, headache, neurocortical symptoms, dyspnea, nausea, vomiting, diarrhea) did not differ between treatment groups. Likewise PTF did not affect renal function or immunologic response to OKT3, with similar graft and patient survival in both groups. Plasma levels of TNF alpha, IFN gamma, IL-6, and IL-8 increased as predicted following OKT3 administration, without significant differences between PTF and placebo groups. In this controlled, multicenter trial, pretreatment with oral PTF was ineffective in attenuating OKT3-related CRS in renal allograft recipients.
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PMID:Pentoxifylline does not prevent the cytokine-induced first dose reaction following OKT3--a randomized, double-blind placebo-controlled study. 861 Mar 83

rHuTNF was locally applied to 26 patients with diverse advanced tumours and malignant pleural effusions following maximum possible drainage of their pleural cavities. 46 instillations (an average of 1.8 per patient) with doses between 0.10 mg and 0.50 mg were carried out. The total doses ranged from 0.15 mg to 1.01 mg per patient. 41% of the instillations resulted in flu-like symptoms, 35% fever/chill, 24% fatigue/malaise, 11% nausea/vomiting and 11% chest pain. All toxicities were fully reversible and could be treated successfully. There was no apparent relation between dose and side-effects. Of those patients treated primarily with TNF, 87% did not suffer from any recurrent effusion within 4 weeks after treatment. In patients who had already been treated employing other methods, this figure was 86%. Complete drainage of the pleural cavity was not absolutely necessary before application of TNF. Intrapleural instillation of TNF appears to be an effective method for achieving pleurodesis with relatively few side-effects and can be successful even after other methods have failed. It is a method which can also be applied to patients who have a poor general state of health.
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PMID:Recombinant tumour necrosis factor in the local therapy of malignant pleural effusion. 913 93

Pentoxifylline (POF) may suppress overproduction of tumor necrosis factor alpha (TNF alpha), which is thought to contribute to complications of human falciparum malaria. However, POF is believed to improve impaired capillary blood flow, which can be impaired in falciparum malaria. To test whether POF affects TNF alpha serum levels or other variables in this disease, we administered POF (20 mg/kg/day intravenously in 150 ml of saline for five days) randomized versus placebo (150 ml of saline without POF) in addition to standard antimalarial therapy. After recruitment of 51 patients with Plasmodium falciparum malaria, those receiving POF had more nausea and abdominal discomfort than the placebo group, as expected. Eleven of 27 patients receiving POF and three of 24 patients receiving placebo requested termination of the study medication (P < 0.05). Pentoxifylline did not change the decrease of TNF alpha levels or affect the clinical course in a significant way. Since POF failed to improve the clinical situation or to impact numerous laboratory parameters (including TNF alpha, thrombin-antithrombin III, thrombomodulin, and human neutrophil elastase), the study was terminated earlier than planned. While this study does not specifically address cerebral complications of malaria, the results suggest that POF is not useful as a routine adjunct to the standard therapy of falciparum malaria.
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PMID:Supportive pentoxifylline in falciparum malaria: no effect on tumor necrosis factor alpha levels or clinical outcome: a prospective, randomized, placebo-controlled study. 915 47

Tumor necrosis factor alpha (TNF-alpha) may be involved in the pathogenesis of metabolic and endocrine changes in HIV infection. Pentoxifylline (PTX) is able to suppress the production of TNF-alpha in vitro. The effect of two dosages of intravenously administered PTX on clinical symptoms and ex vivo LPS-stimulated TNF-alpha production was evaluated in six clinically stable AIDS patients in a saline-controlled study. PTX in a dosage of 1.5 mg/min was tolerated without side effects. PTX in a dosage of 2.1 mg/min resulted in intolerable nausea and necessitated termination of infusion after 30 min. The average plasma concentration of PTX after infusion of 1.5 mg/min for 6 hr was 510+/-56 ng/ml, which is considerably below the concentrations that have been reported to suppress TNF-alpha production in vitro. No effect of PTX infusion (1.5 mg/min) on LPS-stimulated TNF production ex vivo was found. Our conclusion is that the maximally tolerated i.v. dosage of PTX in AIDS patients is 1.5 mg/min. LPS-stimulated ex vivo TNF-alpha production, at the LPS concentrations tested, was not inhibited by the plasma concentration of PTX that could be achieved at this dosage.
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PMID:The maximal tolerable intravenous dosage of pentoxifylline in AIDS patients does not inhibit lipopolysaccharide-stimulated tumor necrosis factor alpha production. 951 90


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