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)

Neocarzinostatin (NCZ), an acidic polypeptide antibiotic, was given to 47 patients with cancer and leukemia, and tolerance to two schedules, a single dose given as a 2 hour infusion and a continuous infusion over 5 days was investigated. Immediate reactions, including fever, chills, rigor, hypertension and mental confusion, were dose-limiting for the 2 hour infusion schedule, occurring at 3000 U/m2 and higher. Continuous administration for 5 days eliminated the immediate reactions and then hematological toxicity--often prolonged leukopenia and thrombocytopenia--became dose-limiting. Other toxicities of NCZ at both dose schedules included anemia, fever and chills, anorexia, nausea and vomiting, hepatic dysfunction, azotemia, hypophosphatemia, aminoaciduria, stomatitis, phlebitis and/or cellulitis at the venous infusion site and pruritus. Patients with solid tumors who had received little or no prior chemotherapy and had good bone marrow reserve tolerated up to 6000 U/m2/24 hours X 5 days. One patient with previously treated acute myelocytic leukemia was induced into a good partial remission lasting 10 weeks.
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PMID:Phase I study with neocarzinostatin: tolerance to two hour infusion and continuous infusion. 15 43

A clinical trial of the oral form of VP 16-213 (NSC-141540), a semisynthetic podophyllotoxin, was undertaken. In 20 patients, treatment was started at 200 mg/day p.o. for 5 days; courses were repeated after a rest period of 16 days. Five patients were treated at the same dose, repeated with only 9-day rest periods. Subsequently, 65 patients were given 300-400 mg/day for 5 days, with rest periods of 9 days between courses. The side effects encountered included anorexia, nausea and vomiting, stomatitis, diarrhea, leukopenia, thrombocytopenia, alopecia, and pruritus. Substernal discomfort with or without palpitations was reported by 18 patients; no explanation for this symptom could be found. No complete remissions (CR) were observed. Parital remissions (PR) and improvement (IMP) were seen as follows: small cell carcinoma, lung (10 patients)--2 PR, 3 IMP; adenocarcinoma, lung (4 patients)--1 PR; alveolar cell carcinoma, lung (1 patient)--1 IMP; mesothelioma (4 patients)--1 IMP; ovarian cancer (12 patients)--3 PR, 3 IMP; breast cancer (20 patients)--4 IMP; colon cancer (8 patients)--2 IMP; bladder cancer (4 patients)--2 IMP; histiocytic lymphoma (7 patients)--2 PR, 3 IMP; chronic myeloid leukemia (1 patient)--1 IMP.
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PMID:A clinical trial of the oral form of 4'-demethyl-epipodophyllotoxin-beta-D ethylidene glucoside (NSC 141540) VP 16-213. 16 75

After some general preliminary remarks concerning aetiopathogenetic hypoteses and therapeutic possibilities for Wilson's disease, the Authors report the data obtained from a long-term study carried out on a family of nine brothers. These subjects were all affected with Wilson's syndrome and kept under a D-penicillamine treatment. The addition of 4-5 oral adminstrations a day of 30 mg SAMe resulted in highly significant favourable modifications of all the laboratory data considered to test liver function. The progressive worsening of the same data observed after 60, 90 and 120 days from SAMe withdrawal, seems to prove the actual activity of this molecule on liver function. During SAMe therapy no clinical and laboratory side-effects (macular and papular eruption, pruritus, neutropenia, thrombocytopenia, etc.) were observed while they were detectable in some patients treated with D-penicillamine alone.
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PMID:[On the therapeutic combination of S-adenosylmethionine with D-penicillamine in Wilson's disease]. 114 93

We report the findings in 21 Belgian patients (12 males and 9 females, median age 61 years) with LGLPD. Symptoms at presentation included infection (n = 9), weight loss (n = 5), asthenia (n = 9), pruritus (n = 2) and arthralgia (n = 7). Four patients were asymptomatic. The main clinical findings were hepatomegaly (n = 5), splenomegaly (n = 8), lymph node enlargement (n = 3) and arthritis (n = 5). All patients had an increased LGL count associated with anemia (n = 12), neutropenia (n = 17), often less than 0.5.10(9)/L (n = 10) and thrombocytopenia (n = 6). Three patterns of lymphocyte surface markers were observed: CD3+CD4-8+ (14 patients), CD3+CD4-8+ (5 patients) and CD3+CD4+8- (1 patient). An abnormal karyotype was found in 2 patients. T-cell receptor gene was rearranged in all cases tested (9/9).
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PMID:Large granular lymphocyte proliferative disease: 21 Belgian cases and review of the literature. 131 80

We report here the long-term toleration of treatment with a highly purified human leukocyte alpha-interferon (Interferon Alfanative) in patients with midgut carcinoid tumours with liver metastases. During an 18-month period, 13 consecutive patients with this diagnosis commenced treatment with a-interferon. Five patients died during the first 2 years of treatment due to tumour progression, and in 2 patients the treatment with a-interferon had to be stopped due to severe adverse effects (mainly joint pain and tiredness). Hence, 6 patients tolerated the treatment for a long-term period (greater than 2 years), and in these patients the treatment has continued for more than 3 years; in 3 of them for more than 4 years. In these 6 patients, adverse effects of mild or moderate degree have been observed in 2 patients: itching and hair loss in one and joint pain and hair loss in another. Except for a significant reduction in the blood number of WBC and thrombocytes (although in no patient did leukocytopenia or thrombocytopenia develop) and the development of hypothyroidism in one patient, no biochemical tests have shown significant changes during the long-term treatment. In these 6 patients, objective tumour regression has been observed in 2 patients, stable disease in 3 patients and progression in 1 patient. We conclude that, of the patients initiated on treatment with a-interferon for midgut carcinoids with liver metastases, only approximately 50% are still on the treatment after 2 years. These patients, on the other hand, may continue for a longer period of time with a low degree of adverse effects.
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PMID:Tolerance to long-term treatment of malignant midgut carcinoid with a highly purified human leukocyte alpha-interferon. 162 46

Forty-three patients with disseminated refractory malignancies each received an individually specified combination of either Adriamycin (n = 24) or mitomycin-C (n = 19) conjugated to a cocktail of murine monoclonal antibodies (mAb). Cancers were typed with both immunohistochemistry and flow cytometry using a panel of antibodies. Cocktails of up to six antibodies were selected based on total binding of greater than 80% of the malignant cells in the biopsy specimen. These mAb cocktails were then drug conjugated, safety tested, and administered intravenously. The Adriamycin immunoconjugates were well tolerated in 22/24 patients, with 17/24 having significant side effects. Fever, chills, pruritus, and skin rash were by far the most common transitory reactions. All were well controlled with premedication. A total of up to 1 g Adriamycin and 5 g mAb were administered to each patient. The limiting factor appeared to be a variable dissociation of active Adriamycin from the antibody that unpredictably caused hemopoietic depression. Similar findings were noted among 19 patients treated with mitomycin-C conjugates. Thrombocytopenia at a 60-mg dose of mitomycin-C in this schedule was dose limiting. Serological evidence suggested that the development of an immunoglobulin M antibody specific against the mouse mAb had the specificity and sensitivity to predict clinical reactions. These antibodies were quantitatively less in mitomycin-C-treated patients. Selected patients were retreated. One patient with chronic lymphocytic leukemia was treated on three occasions with 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. Drug-induced colitis was seen at higher doses with some binding of these conjugates to normal colon epithelium. This study demonstrated the feasibility of preparing individually specified drug immunoconjugate cocktails for patients with refractory malignancies. Cocktail formulation and antibody delivery to the tumor in vivo was accomplished. There was limited antigenic drift among various biopsies within the same patient over time. The major technical hurdle continues to be the selection of effective drug conjugation methods to optimally bind drugs to mAbs for targeted cancer therapy.
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PMID:Custom-tailored drug immunoconjugates in cancer therapy. 176 66

The clinical and immune modulatory effects of interleukin-2 (IL-2) and interferon (INF) alfa-2a were examined in a phase II study in patients with metastatic renal cell carcinoma (six patients) and melanoma (eight patients). Treatment consisted in IL-2 3 MU/m2 continuous infusion days 1-4 and INF alfa-2a 6 MU/m2 subcutaneously day 1 and 4, both given on alternate weeks. Tumour response was assessed after four cycles of treatment or earlier, if necessary. Patients with stable disease or response were to be continued for another nine cycles or up to disease progression. The 14 patients received a total of 60 cycles of treatment. Major toxicities (WHO Grade III/IV) were fever, capillary leak syndrome with hypotension, nausea and vomiting, erythema with pruritus, leuco- and thrombopenia and sepsis with staphylococcus aureus. Five of 14 patients (36%) developed a self limiting autoimmune thyroiditis with HLA-DR expression on thyrocytes. Long term treatment toxicity was moderate with an average weight loss of 5% and an average fall in Karnofsky index of 10% compared to baseline. No responses were seen in renal cell carcinoma, two patients with melanoma had a partial and two a minor response with a duration of 1-7 months. Serial measurements of immune modulatory parameters showed a functional response to treatment with an increase of NK- and LAK-activity during the first two cycles, followed by a plateau and decrease during the third and fourth cycles. These findings were paralleled by a successive decline in treatment induced INF gamma response. These findings suggest, that alternative weekly treatment with IL-2 and INF alfa-2a results in an exhaustion of lytic capacity of NK- and LAK-cells and an attenuation of secondary cytokine release.
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PMID:Clinical and immune modulatory effects of alternative weekly interleukin-2 and interferon alfa-2a in patients with advanced renal cell carcinoma and melanoma. 199 8

A woman with a history of polyarthralgias appeared to develop systemic lupus erythematosus and lymphoma simultaneously. The diagnosis of the concurrent lymphoma was made on biopsy of a left axillary lymph node. Generalized lymphadenopathy, splenomegaly and pruritus had given rise to suspicion of an underlying lymphoma. The lymphoma responded well to chemotherapy. Her condition was further complicated by an arterial occlusion involving the right 2nd toe which was eventually amputated, transient ischemic attacks (amaurosis fugax), livedo reticularis and thrombocytopenia which were accompanied by elevations of IgM anticardiolipin antibodies and a biological false test for syphilis. The lupus anticoagulant test was not performed as she was given anticoagulation therapy.
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PMID:Systemic lupus erythematosus and lymphoma: association with antiphospholipid syndrome. 202 23

Twenty-six patients with metastatic cancer were entered into a phase I trial of concurrent recombinant interleukin-2 (IL-2) and recombinant interferon-gamma (IFN-gamma). IL-2 was administered as a continuous intravenous infusion for 5 days. IFN-gamma was administered by a daily intramuscular (IM) injection during the 5 days of IL-2 administration. Treatment was repeated twice after 9-day rest periods. After a 2-week rest, patients without evidence of tumor progression were retreated. Natural killer (NK)- and lymphokine-activated killer (LAK)-cell activity were assayed in each patient before treatment, on day 1, and on day 5 of each cycle. Constitutional symptoms occurred in most patients but were not dose-limiting. Other toxicities included hypotension responsive to fluids, transient elevations in liver function tests, erythema/pruritus, eosinophilia, and transient leukopenia/thrombocytopenia. The maximum-tolerated dose (MTD) of the combination was 1 x 10(6) U/m2/d of IL-2 combined with 0.50 mg/m2/d of IFN-gamma. The dose-limiting toxicity was pulmonary manifesting as rales and shortness of breath. The dose of the combination that resulted in the optimal generation of in vivo LAK-cell activity was a dose of at least 0.25 mg/m2/d of IFN-gamma combined with 1 x 10(6) U/m2/d of IL-2. Objective clinical responses were seen in five of 26 patients. These included a partial response of 2 months duration in a patient with non-Hodgkin's lymphoma (NHL), mixed responses in a patient with NHL and two patients with renal cell carcinoma (RCC), and an ongoing assessable response in a patient with bone metastases from RCC. The recommended dose for phase II trials of this combination is 0.50 mg/m2 of IFN-gamma and 1 x 10(6) U of IL-2.
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PMID:A phase I trial of recombinant interleukin-2 combined with recombinant interferon-gamma in patients with cancer. 211 71

One hundred and forty patients with classic or definite rheumatoid polyarthritis were treated with N2 mercapto-propionly-glycine: thiopronine (Acadione) at an average dose of 1 g per day over a mean duration of 11.7 months + 10.7 months. The retrospective study of these cases, followed between 1980 and 1988 by the same medical team, permits to evaluate the long-term tolerance of the product. Adverse reaction, always subsiding were observed in 55 p. cent of the patients, requiring discontinuation of the treatment in 40 p. cent of the cases. These side effects occur in 3/4 of the cases, during the first 6 months of the treatment. The intolerance mainly affect skin and mucosae: 46 cases (32.8 p. cent) resulting in 32 instances (22.8 p. cent) discontinuation of the treatment because of stomatitis, pruritus, various types of erythema, pemphigus (1 case). Fourteen patients presented a renal failure (10 p. cent) requiring in 8 instances (5.7 p. cent) discontinuation of the thiopronine because of nephrotic syndrome (3 case) and proteinuria (5 cases). Haematological disorders were observed in 13 instances (9.2 p. cent), justifying, in 10 instances (7.1 p. cent) discontinuation of the treatment because of thrombopenia or leucothrombopenia. The other side effects observed are the following: digestive disorders 15 cases (10.7 p. cent) requiring discontinuation of the treatment in 3 instances (2.1 p. cent), agueusia in 6 instances (4.2 p. cent) requiring discontinuation of the treatment in one case; miscellaneous disorders 13.5 p. cent for which the responsibility of thiopronine is not precisely established (especially hepatic cholostasis, muscle disorders), requiring discontinuation the the treatment in 1.4 p. cent of the cases.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Long-term tolerability of tiopronin (Acadione) in the treatment of rheumatoid arthritis. Apropos of 140 personal cases]. 213 12


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