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)

Twenty-three patients with disseminated refractory malignancies each received a tailored combination of adriamycin-conjugated murine monoclonal antibodies. Tumors were typed using a panel of antibodies. Cocktails of up to six antibodies were selected based on binding greater than 80% of the malignant cells as tested by immunoperoxidase and flow cytometry. These monoclonal antibodies were then conjugated to Adriamycin and administered intravenously. Seventeen of 23 patients had reactions to the administration of 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 there was limited antigenic drift among various biopsies within the same patient over time. This observation confirms the necessity for the use of a cocktail of antibodies if one wishes to cover all tumor cells. Preliminary serologic 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. 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. In the course of the study free Adriamycin released from the monoclonal antibodies was discovered to be a limiting factor in the amount of antibody that could be administered. Up to 1 g of Adriamycin and up to 5 g of monoclonal antibody were administered. The limiting factor appeared to be a variable dissociation of active Adriamycin from the antibody that unpredictably caused hemopoietic depression. This study demonstrates the feasibility and reviews technical considerations in preparing immunoconjugate cocktails for patients with refractory malignancies. The major technical hurdle appears to be the selection of an effective conjugation method that can be used to optimally bind Adriamycin to monoclonal antibodies for targeted cancer therapy.
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PMID:Adriamycin custom-tailored immunoconjugates in the treatment of human malignancies. 326 48

Data about adverse events can be particularly useful when assessing newly marketed drugs. However, spontaneous reporting of adverse events does not generally provide sufficient or highly accurate data on incidence and prevalence. In order to provide the most complete and accurate data, a postmarketing surveillance program (PMSP) for auranofin (AF) oral gold therapy for rheumatoid arthritis (RA) was conducted in the Federal Republic of Germany (FRG) from December 1982 through December 1985. The objectives of the program were to observe a large population treated with AF for more than a year; to compare the safety profile of AF with experience from clinical trials; and to register rare or previously unknown adverse events. The program included 2,777 patients with RA from 928 test centers. Disease duration was less than 2 years in 29%. 2-5 in 23.2%, 5-10 in 32.5%, and more than 10 in 13.3% (no data for 2%); disease was mild or moderate in 67.4% and severe in 29.9% (no data for 2.7%). Auranofin was given 6 mg/day as either two 3-mg tablets at breakfast or 1 tablet at breakfast and 1 at the evening meal. Laboratory studies and efficacy, as indicated by increase in grip strength and decrease in number of tender and swollen joints, were monitored regularly. A total of 1,595 patients completed 1 year of treatment with AF. Withdrawals included 12.9% for adverse events, 4.2% for insufficient therapeutic effect, and 33.1% for a variety of administrative or technical reasons. The most common adverse event was alteration in stool pattern, which occurred in 22.5% of patients, compared with 46.6% in worldwide AF clinical trials. Other gastrointestinal symptoms occurred in 17.4%, compared with 22.4% worldwide. The occurrence of most adverse events in the PMSP was much less than in worldwide studies, for example: skin rash 7.3% vs. 24.2% worldwide, pruritus 4.2% vs. 16.6%, proteinuria 1.0% vs. 5.0%, and leukopenia 0.7% vs. 1.9%. These discrepancies may be explained by the method of monitoring employed in the postmarketing study, which favored the reporting of only clinically relevant adverse events. The pattern of occurrence of adverse events was similar to that seen during other AF trials, indicating that any intolerance to AF occurs primarily within the first 6 months of treatment. However, hematologic or nephrologic adverse events appear to be independent of time on therapy, with a constant monthly prevalence of about 0.1-0.2%.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Postmarketing experience with auranofin in the Federal Republic of Germany. 329 83

In a double-blind parallel group comparison of efficacy and safety, 19 patients with peri-arthritis of the shoulder received 200 mg fentiazac twice daily and 19 received 50 mg diclofenac sodium twice daily, with both drugs given orally for 3 weeks. In both groups, observers' verbal rating scales of pain severity at rest and on movement showed decreases that were significant by week 1. Both groups also had significant improvement in abduction, external rotation, retroversion and anteversion. At week 1, the patients reported improvement, on a verbal rating scale, of global effectiveness, but there were no subsequent changes. There were no statistically significant differences between the treatments in any of these variables. Five (26%) fentiazac-treated patients and four (21%) diclofenac sodium-treated patients reported adverse effects, mostly gastro-intestinal. One case of rash in each group and one case of pruritus in a diclofenac sodium-treated patient were severe enough for the patients to be withdrawn from therapy. There were no clinically significant changes in laboratory values. It was concluded that fentiazac (400 mg/day) and diclofenac sodium (100 mg/day) were equally effective within 1 week in decreasing pain severity and improving shoulder mobility.
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PMID:The efficacy and safety of fentiazac and diclofenac sodium in peri-arthritis of the shoulder: a multi-centre, double-blind comparison. 332 16

One hundred sixty patients were entered in two multicenter protocols to receive 400 to 2,000 mg of ketoconazole once daily for nonmeningeal or meningeal coccidiodomycosis. For 24 h after administration of all doses, mean concentrations in serum exceeded MICs for Coccidioides immitis (trough concentrations, greater than 1 microgram/ml). Mean peak concentrations occurred 4 to 6 h after administration, ranging from 7 to 17 micrograms/ml for doses of 400 to 2,000 mg. Incremental increases in peak concentrations in serum were greatest at doses of less than or equal to 1,200 mg. To investigate whether long-term therapy altered concentrations in serum, serial data were studied by several methods. The results suggested a trend to increased levels in serum with prolonged therapy, but were not statistically significant. All 168 cerebrospinal fluid (CSF) samples from meningitis patients contained less than or equal to 2.9 micrograms/ml, and only 6 contained greater than 1 microgram/ml. There was no apparent relation between dose, time after dose, site of CSF sampling, or concurrent inflammation and CSF ketoconazole concentration. Neither concentration in serum, toxicity, nor outcome correlated with dose, calculated in milligrams per kilogram at the fixed doses (400-mg increments) under study. Likewise, at the various doses, concentration in serum did not correlate with outcome or toxicity, suggesting that individual drug disposition was not an important factor in outcome or toxicity. Toxicity was reversible, and principal side effects were nausea and vomiting (50%), gynecomastia (21%), decreased libido (13%), alopecia (8%), elevated liver function tests (5%), pruritus (5%), and rash (4%). Gastrointestinal and endocrinologic toxicity were dose related and increased at doses greater than 800 mg. The cumulative percent toxicity requiring discontinuation of drug was 6, 17, 23, and 56% at 400-, 800-, 1,200-, and 1,600-mg doses. Doses of >400 mg are thus markedly more toxic, and efficacy data for nonmeningeal disease have not demonstrated that they are more efficacious.
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PMID:Pharmacology and toxicity of high-dose ketoconazole. 332 25

We describe seven patients, four female and three male, who developed intense pruritus on sun-exposed skin without visible change. The clinical features resembled those of polymorphic light eruption (PLE) without rash. Four patients also occasionally developed typical PLE upon sun exposure, but sun-induced pruritus alone occurred most frequently. No patient was taking any drug therapy. One patient developed similar pruritus following solar simulated irradiation, and one following PUVA therapy. All other laboratory investigations were negative. Treatment with low dose UVB phototherapy or PUVA therapy was effective. The condition, which we have called polymorphic light eruption sine eruptione (PLESE), appears to be a variant of PLE not previously reported.
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PMID:Polymorphic light eruption sine eruption. 334 78

Cytologic scrapings of skin vesicles from an eight-day-old newborn who had a generalized maculopapular, vesicular and pustular rash contained mycelia and ovoid spores of fungal organisms. The cytodiagnosis of cutaneous candidiasis was confirmed by the study of a direct smear and a skin biopsy. The candidiasis was congenital; the 15-year-old mother had had vulvar pruritus prior to delivery. Since the variable clinical picture of this disease must be differentiated from those of other types of congenital dermatitis, an early cytologic study of skin scrapings may prove useful for its rapid diagnosis and treatment.
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PMID:Congenital cutaneous candidiasis diagnosed in cytologic scrapings. 340 Mar 87

Dermatoses of pregnancy are relatively rare. The terminology becomes increasingly confusing, as only few of these skin eruptions are proved entities. Apart from pruritus gravidarum and herpes gestationis (pemphigoid gestationis), the symptoms of dermatoses of pregnancy should be classified according to polymorphic exanthema, which are characterized by urticarial lesions, or according to prurigo gravidarum, predominantly characterized by excoriated papules.
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PMID:[Pregnancy dermatoses]. 342

The safety of ciprofloxacin, given via 30- and 60-min intravenous infusions at a dose of 300 mg every 12 h for 4 days, was studied in 12 healthy subjects (6 females, 6 males). Local effects of the drug were assessed by frequent examination at the infusion site while systemic safety was determined by haematological and biochemical tests and by careful microscopic examination of the urine for drug crystals and by electroencephalographic studies performed in all subjects before and after dosing. At the site of infusion erythema, itching and a burning sensation developed 10-15 min after onset of infusion in some subjects. These symptoms were slight and did not necessitate termination of the infusions. The rash disappeared in some instances during the infusion and in others within minutes after the end of infusion. The changes usually disappeared, even during the infusion. The incidence of the adverse reactions was not related to the duration of the infusion (30 or 60 min), but was less (frequency and extent) when the anticubital vein was used for infusion rather than when smaller more peripheral veins were employed. Thrombophlebitis occurred after 1 of 96 administrations, and was followed by a return to normal. The electroencephalograms remained normal in all instances. One subject experienced mild nausea of a few hours duration. Only 1 volunteer showed crystalluria; the two such specimens from this subject had the most alkaline pH of all urine samples collected in this study. The probability of crystalluria upon intravenous administration appears not to be higher than after oral administration of ciprofloxacin.
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PMID:Tolerance of ciprofloxacin at injection site, systemic safety and effect on electroencephalogram. 342 12

Imipenem-cilastatin was evaluated for efficacy and toxicity as an antistaphylococcal agent in 23 patients; 11 of these patients were infected with methicillin-resistant Staphylococcus aureus (MRSA), and 12 were infected with methicillin-susceptible S. aureus (MSSA). There were 15 soft tissue, 5 endovascular, and 3 skeletal infections and a total of nine patients with bacteremia. As determined by in vitro susceptibility testing, the MICs for 90% of the MRSA and MSSA isolates tested were 6.25 and 0.39 micrograms/ml, respectively. Two MRSA isolates were resistant to a concentration of greater than 16 micrograms/ml. When 11 MRSA isolates and 7 MSSA isolates were incubated for 48 h the MICs for 90% of the isolates increased to greater than 50 micrograms/ml for the MRSA isolates and 6.25 micrograms/ml for the MSSA isolates. Three S. aureus isolates emerged resistant. Ten of 11 (91%) MRSA infections and 11 of 12 (92%) MSSA infections were clinically cured. Adverse reactions occurred in 25% of the imipenemcilastatin-treated patients. These reactions included gastrointestinal intolerance (7% of the patients), rash or pruritus (6%), eosinophilia (6%), thrombocytosis (4%), and a positive, direct Coomb test without hemolysis (3%). One of the two patients for whom therapy was discontinued because of gastrointestinal intolerance had antibiotic-associated colitis. Imipenem appears to be an effective antistaphylococcal agent against both MRSA and MSSA infections.
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PMID:Imipenem-cilastatin in the treatment of methicillin-sensitive and methicillin-resistant Staphylococcus aureus infections. 346 May 21

Although leukaemic infiltration of the skin commonly occurs in acute monoblastic leukaemia, the association with chronic myelomonocytic leukaemia (CMML) has only been described recently. We confirm the association and report histologically proven monocytic infiltration of the skin in four patients with CMML. This did not herald a more aggressive phase of the disease as previously suggested. Treatment of the rash with low dose cytarabine or etoposide was effective but razoxane produced no benefit. Superficial radiotherapy was useful to control pruritus in one patient.
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PMID:Monocytic skin infiltration in chronic myelomonocytic leukaemia. 346 Jul 29


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