Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033774 (pruritus)
 14,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) has been used in two clinical studies at the Christie Hospital in Manchester, United Kingdom. Short daily "bolus" injections (over 30 min) were associated with serious toxicity which included bone pain, pruritus and pericarditis. In contrast, continuous infusions did not cause any toxicity and produced significantly higher increments of the peripheral neutrophil counts. rhGM-CSF reduced the period of life-threatening neutropenia following high-dose i.v. melphalan (120 mg/m2). Also, rhGM-CSF shortened the duration of thrombocytopenia induced by this chemotherapy to less time than has been seen historically in conjunction with autologous bone marrow rescue.
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PMID:Clinical studies with recombinant human granulocyte-macrophage colony-stimulating factor. 218 43

Forty-three patients with disseminated refractory malignancies each received an individually-specified combination of either Adriamycin (24 patients) or mitomycin-C (19 patients) conjugated murine monoclonal antibodies. Tumors were typed using a panel of antibodies with both immunohistochemistry and flow cytometry. Cocktails of up to six antibodies were selected based on binding greater than 80% of the malignant cells in the biopsy specimen. These monoclonal antibody cocktails were drug conjugated and administered intravenously. Seventeen out of twenty-four patients had reactions to the administration of Adriamycin immunoconjugates, but these were tolerable in all but two patients. Fever, chills, pruritus and skin rash were by far the most common transitory reactions. All were well controlled with premedication. In several patients it was demonstrated that there was limited antigenic drift among various biopsies within the same patient over time. Up to 1 gram of Adriamycin and up to 5 grams of monoclonal antibody were administered. The limiting factor appeared to be a variable dissociation of active Adriamycin from the antibody which unpredictably caused hemopoietic depression. Similar findings were noted in 19 patients with mitomycin-C conjugates. Thrombocytopenia at a 60mg dose of mitomycin-C in this schedule was dose limiting. Preliminary serological evidence suggests that the development of an IgM antibody which is specific against the mouse monoclonal antibody has the specificity and sensitivity to predict clinical reactions. These antibodies were quantitatively less in mitomycin-C patients. Selected patients were re-treated. One patient with chronic lymphocytic leukemia had re-treatment on three occasions and demonstrated regression of peripheral lymph nodes. Two patients with breast carcinoma had definite improvement in ulcerating skin lesions and two patients with tongue carcinoma had shrinkage of their lesions. No responses were seen with mitomycin-C conjugates but binding was noted to tumors and colon with likely drug induced colitis seen after colon binding. This study demonstrates the feasibility and illustrates technical considerations in preparing drug immunoconjugate cocktails for patients with refractory malignancies. Cocktail formulation and antibody delivery was accomplished. The major technical hurdle appears to be the selection of effective conjugation methods that can be used to optimally bind drugs to monoclonal antibodies for targeted cancer therapy.
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PMID:Individually specified drug immunoconjugates in cancer treatment. 250 30

Black widow spider (Latrodectus mactans) envenomation is found throughout both the temperate and tropical latitudes, and is one of the leading causes of death from arthropod envenomations worldwide. The venom is highly neurotoxic, affecting the presynaptic motor endplate to allow massive noradrenaline (norepinephrine) and acetylcholine release into synapses causing excessive stimulation and fatigue of the motor end plate and muscle. Clinically, patients develop a bite site lesion and pain, abdominal pain and tenderness, and lower extremity pain and weakness within minutes to hours of envenomation. Symptoms progress over several hours, then subside over 2 to 3 days. The recommended treatment of 'common' envenomation is calcium gluconate 10% intravenously, titrated to relief of symptoms; antivenin, although effective, may cause hypersensitivity and serum sickness reactions, and should be restricted to life-threatening envenomations only. Brown recluse spider (Loxosceles reclusa) envenomations are seen in the Americas and in Europe, and are endemic to the south and central United States. The venom contains at least 8 enzymes, consisting of various lysins (facilitating venom spread) and sphingomyelinase D, which causes cell membrane injury and lysis, thrombosis, local ischaemia, and chemotaxis. Local envenomations begin as pain and itching that progresses to vesiculation with violaceous necrosis and surrounding erythema, and ultimately ulcer formation. Systemic envenomations may be life threatening, and present with fever, constitutional symptoms, petechial eruptions, thrombocytopenia, and haemolysis with haemoglobinuric renal failure. Treatment of local envenomations is conservative (local wound care, cryotherapy, elevation, tetanus prophylaxis, and close follow-up); systemic envenomation requires supportive care and treatment of arising complications, corticosteroids to stabilise red blood cell membranes, and support of renal function. Dapsone 100mg daily has emerged as a promising therapeutic agent in both animal studies and clinical trials. Over 650 species of scorpions are known to cause envenomation (mostly in children under 10 years); they are endemic mostly in arid and tropical areas. Different venoms and clinical presentations are seen across the different species. Most commonly, an inflammatory local reaction occurs with envenomation, which is treated with wound debridement and cleaning, tetanus prophylaxis, and antihistamines. Occasionally the venom is allergenic, and the resultant allergic reaction is treated in a standard fashion.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Acute arthropod envenomation. Incidence, clinical features and management. 266 28

High-dose interleukin-2 (IL-2) with or without lymphokine-activated killer (LAK) cells has been reported to have activity in certain solid tumors, but toxicity has usually required hospitalization for administration. The purpose of this trial was to determine the antineoplastic effect and toxicity of IL-2 administered at a lower dose in an outpatient setting. Eligibility criteria included measurable disease, Karnofsky performance greater than or equal to 70%, age greater than 18 years, and adequate bone marrow, renal, and hepatic function. The median age of 35 patients was 56 years (range, 20 to 75). Diagnoses included malignant lymphoma (ML), (nine patients), chronic lymphocytic leukemia (CLL) (eight), melanoma (eight), colorectal cancer (six), renal cancer (two), and breast cancer (two). The initial 18 patients were treated with 1 mg/m2 (3 x 10(6) U/m2 intravenous [IV] bolus) for five days every other week for a total of 4 treatment weeks (8 weeks total). The subsequent 17 patients were treated with 0.5 mg/m2 (1.5 x 10(6) U/m2). All patients were evaluable for toxicity, and 26 for tumor response. Toxicities included fatigue (71%), nausea (69%), hypotension (54%), fever (51%), chills (40%), weight gain (37%), pruritus or rash (31%), dyspnea (14%), azotemia (6%), confusion (6%), thrombocytopenia (6%), and myocardial infarction (3%). Four patients died from apparently unrelated causes within the first 2 weeks of treatment. Treatment was discontinued before the completion of 8 weeks of treatment because of progressive disease (12 patients), severe hypotension (three), azotemia (one), myocardial infarction (one), early death (four), and miscellaneous causes (two). IL-2 at 1 mg/m2 IV for five days is associated with moderate toxicity, but a dose of 0.5 mg/m2 is tolerable for outpatient administration. Three partial responses (PR) and one minor response (MR) lasting 1 to 17+ months have been observed in 12 patients with ML and CLL evaluable for response. One additional MR was observed in a patient with melanoma. IL-2 deserves further study in patients with ML and CLL.
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PMID:Phase II trial of outpatient interleukin-2 in malignant lymphoma, chronic lymphocytic leukemia, and selected solid tumors. 278 39

We conducted a phase II trial of deoxycoformycin (pentostatin [DCF]) in chronic lymphocytic leukemia (CLL). Eligibility criteria included age greater than 18 years, Cancer and Leukemia Group B (CALGB) performance status 0 to 2, lymphocyte count greater than or equal to 15,000 cells/microL, international stage B or C disease (multiple lymph nodes involved and/or hemoglobin [Hgb] less than 11 g and/or platelets less than 100,000/microL) and no more than one prior treatment regimen. DCF dose was 4 mg/m2 intravenously (IV) weekly for 3 weeks and then every 2 weeks. There were 39 eligible patients (35 men and four women; median age, 63 years; median time from diagnosis to study entry, 3 years). Of these 39 patients, 31% were stage B and 33% had no prior treatment. Median laboratory values at entry were Hgb 10.5 g, WBC 96,100/microL, and platelets 93,500/microL. Nodal involvement was present in 90%, splenomegaly in 81%, and hepatomegaly in 47%. Patients received a median of nine DCF injections, with a range of four to 26. Three patients were not evaluable for response. Overall, 3% achieved a complete response (CR), 23% a partial response (PR), 28% showed clinical improvement (CI), and 38% had stable disease (SD). Associated toxicities (grade 2 or worse) observed were infections (52%), worsening of thrombocytopenia (26%) or anemia (33%), nausea and vomiting (31%), rash or pruritus (20%), and stomatitis (8%). We conclude that DCF is an active agent in CLL with acceptable toxicity.
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PMID:Pentostatin in chronic lymphocytic leukemia: a phase II trial of Cancer and Leukemia group B. 278 91

In order to evaluate the efficacy of dexamethasone (dex) in reducing the toxicity of therapy with lymphokine-activated killer (LAK) cells and interleukin-2 (IL-2), we treated six patients receiving this form of immunotherapy with intravenous (IV) dex, 4 mg every six hours. Compared with a control group of 27 patients not receiving dex with their immunotherapy, these corticosteroid-treated patients were able to tolerate the administration of more IL-2, yet experienced significantly less toxicity. Dyspnea, confusion, fever, mean peak serum creatinine, and bilirubin levels during treatment were significantly reduced in corticosteroid-treated patients, with a corresponding decrease in pruritus in this group as well. Overall weight gain was not different between groups, although a curtailment of weight gain temporally related to dex treatment was seen in some patients. Hematologic side effects, including anemia, eosinophilia, and thrombocytopenia, were not reduced by dex. These results suggest that dex can inhibit at least some of the toxic side effects of LAK cell and IL-2 therapy. Because of the concern that the therapeutic effect may also be abrogated, future studies combining corticosteroids with this form of immunotherapy should be undertaken with caution.
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PMID:Reduction of toxicity of interleukin-2 and lymphokine-activated killer cells in humans by the administration of corticosteroids. 349 32

Twenty-six adult patients were entered in a phase I trial of carboplatin, a new cisplatin derivative with reduced potential for nephrotoxicity. All patients had solid tumors and the median World Health Organization performance score was 2 (0-3). Twelve patients had not received prior chemotherapy. The drug was administered as a 15-minute IV infusion, without pre- or posthydration, at daily doses of 40-125 mg/m2 for five consecutive days. Antiemetics were given only if needed. Thrombocytopenia and neutropenia were dose related and dose limiting. One patient died from septic shock at the highest dose level. Nonhemolytic anemia was also encountered. Nausea and vomiting were experienced by most patients but gastrointestinal intolerance was severe in only two patients. One patient had hypercreatininemia, which was minor and rapidly reversible. Other toxic effects consisted of negligible fatigue, paresthesia, pruritus, local pain, stomatitis, headache, and alopecia. Although none of the patients achieved a partial or complete response, antitumor effect was strongly suggested in two patients with thyroid and cervix cancer, respectively. Carboplatin is an attractive candidate for phase II trials. In good-risk patients, such trials could be initiated at a daily dose of 100 mg/m2 for five consecutive days every five to six weeks.
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PMID:Phase I study of carboplatin given on a five-day intravenous schedule. 636 28

Two hundred six patients were entered into a prospective controlled, double-blind, multicenter trial comparing azathioprine (AZA) 1.25-1.5 mg/kg/day with D-penicillamine (DP) 10-12 mg/kg/day. One hundred thirty-four patients completed 24 weeks of therapy. Improvement in nearly all efficacy variables was seen in both groups. Patients taking DP demonstrated a greater rise in hemoglobin concentration and greater fall in erythrocyte sedimentation rate than patients receiving AZA; these were the only efficacy variables with a significant difference between the treatment groups. Fewer withdrawals for adverse reactions occurred among the patients receiving AZA, but the difference was not significant. Patients receiving AZA were withdrawn from the drug mainly for abnormal liver function test results, nausea and gastrointestinal upset, and leukopenia. The main reasons for withdrawal of patients receiving DP were nausea, rash and pruritus, thrombocytopenia, dysgeusia, and proteinuria.
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PMID:Azathioprine versus D-penicillamine in rheumatoid arthritis patients who have been treated unsuccessfully with gold. 637 8

Auranofin is the first orally active gold compound for the treatment of rheumatoid arthritis. Like other chrysotherapeutic agents, its exact mechanism of action is unknown, but it probably acts via immunological mechanisms and alteration of lysosomal enzyme activity. Although long term clinical experience with auranofin is limited, its efficacy appears to approach that of sodium aurothiomalate. Further comparative studies with aurothioglucose, hydroxychloroquine and D-penicillamine are required before definitive statements can be made regarding the relative efficacy of auranofin and these agents. While patients have demonstrated clinical remission of rheumatoid arthritis in response to auranofin therapy, radiological studies have been inconclusive regarding its effect on the occurrence or progression of erosive lesions. Auranofin is relatively well tolerated in most patients, but diarrhoea, skin rash, and pruritus are sometimes troublesome, and thrombocytopenia and proteinuria are potentially serious side effects which may occur during therapy. Whereas mucocutaneous side effects are more frequent with injectable gold compounds, gastrointestinal reactions are the most common adverse effect seen with auranofin. The frequency of side effects has been similar with auranofin and sodium aurothiomalate, but they are generally less severe with auranofin. While some of the side effects are controlled by a reduction in dosage, temporary or permanent withdrawal of auranofin may be necessary. Auranofin is clearly a useful addition to the limited list of agents with disease-modifying potential presently available for the treatment of rheumatoid arthritis. It will doubtless generate much interest as its final place in therapy becomes better defined through additional well-designed studies and wider clinical experience.
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PMID:Auranofin. A preliminary review of its pharmacological properties and therapeutic use in rheumatoid arthritis. 642 23

Oral gold(Auranofin; SKF) 6 mg/d has been used in an open study in 31 patients with active rheumatoid disease, 19 of whom have been on continuous treatment for 1 year. Four of these patients were considered to be in remission and 9 had a good clinical response to treatment. Four showed only minimal improvement and 2 did not improve at all. There were, however, no changes in the biochemical parameters of inflammation, e.g. haemoglobin concentration, erythrocyte sedimentation rate, platelet count and rheumatoid factor, or in renal and hepatic function. Of the 31 patients, 9 (29%) have discontinued treatment but only 3 (9.7%) because of side-effects. Minor side-effects have been fairly common, occurring in 19 patients (61%), and included skin rashes and pruritus, diarrhoea and loose stools, nausea, stomatitis and thrombocytopenia or leucopenia. Oral gold would seem to be a safer, less potent form of chrysotherapy than parenteral gold.
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PMID:An oral gold formulation in rheumatoid arthritis. A 12-month follow-up report. 681 Apr 77


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