Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A phase I trial of 5-fluorouracil (FUra) and leucovorin (LV) given with and without dipyridamole (DP) by concurrent 120-h continuous infusion was performed in 27 patients with advanced solid malignancies, 8 of whom had previously received FUra. The LV and DP doses were fixed at 500 mg/m2 daily and 7.7 mg/kg daily, respectively, whereas the FUra dose was escalated. Level 3 (450 mg/m2 FUra daily) represented the maximum tolerated dose for both FUra/LV+DP and FUra/LV. Dose-limiting stomatitis (greater than or equal to grade 3 or grade 2 occurring during the infusion) was encountered in 75% of the first courses given at level 4 (600 mg/m2 daily). Stomatitis was observed in 44/78 (56%) courses. Diarrhea was infrequent and mild. DP infusions were complicated by mild to moderate headache, which was controlled with narcotic analgesics, and mild to moderate nausea/vomiting. FUra-related toxicity was not enhanced by DP administration. Limited pharmacokinetic sampling at levels 3 and 4 revealed mean steady-state FUra concentrations of around 1.0 microM with infusions of FUra/LV+DP. Among three paired courses given with and without DP, no statistically significant difference was found in the total body clearance of FUra (P = 0.44). One partial response was seen in a patient with metastatic gastric carcinoma. For phase II trials, we recommend that concurrent 120-h continuous infusions of FUra (450 mg/m2 daily) and LV (500 mg/m2 daily) be given with and without DP (7.7 mg/kg daily) every 21 days.
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PMID:A phase I trial of 5-fluorouracil, leucovorin, and dipyridamole given by concurrent 120-h continuous infusions. 164 98

Thirteen patients with advanced head and neck cancer were entered into a phase II study of fludarabine phosphate. Fludarabine phosphate was given by continuous infusion for 5 days, at a starting dose of 20 mg/m2 per day for patients previously treated with one regimen and 25 mg/m2 per day for previously untreated patients; therapy was repeated every 3-4 weeks. Of the 13 patients, 3 had undergone one prior regimen and 10 patients were previously untreated by chemotherapy. No responses were observed. Myelosuppression was the most common toxicity observed. Four patients developed mild nausea, vomiting and seven developed bleeding stomatitis that resolved in one week. In addition, four patients developed headaches which resolved spontaneously. No renal, hepatic, or neurotoxicity was observed. Our study demonstrates that in previously treated and untreated patients, fludarabine phosphate given on this schedule has little activity in patients with advanced head and neck cancer.
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PMID:Phase II trial of fludarabine phosphate (F-Ara-AMP) in patients with advanced head and neck cancer. 169 46

A 71-year-old man was admitted to the Wake Forest University/Baptist Hospital Medical Center on February 1, 1989, with pharyngitis and a cutaneous eruption that began that day. The past history was significant for a diagnosis of chronic lymphocytic leukemia (CLL) made in 1984, and for longstanding hypertension, severe coronary artery disease, and prostatic hypertrophy. The patient had required no therapy for his CLL until August, 1988, when he developed hemolytic anemia and was treated with oral chlorambucil, 4 mg/day, and a tapering course of prednisone. By December, 1988, the prednisone therapy had been discontinued, but the patient required hospital admission for pneumococcal pneumonia, which responded well to intravenous antibiotic therapy. One day prior to the current admission the patient complained of persistent fevers, sore throat, productive cough, and headache. He noted a new cutaneous eruption on the day of admission in February, 1989. The past history was positive for occasional herpes stomatitis. The patient did not know if he had previously been infected with varicella. Skin examination revealed multiple (greater than 20), single, and grouped vesicles in a generalized distribution involving the bilateral trunk, head, neck, arms, and legs. The heaviest involvement was on the right posterior auricular area and on the neck. A Tzanck preparation obtained from an early lesion was positive for multinucleated giant cells. Viral culture was negative at 24 hours and at 1 week. A skin biopsy of an early vesicular lesion was performed and revealed intraepidermal vesicles with acantholysis and giant cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Granuloma annulare and disseminated herpes zoster. 145 73

On the basis of a literature review and eight cases of our own, we analyzed 37 cases of Mycoplasma pneumoniae (MP) infection and Stevens-Johnson syndrome (SJS). Our clinical and laboratory findings do not differ from those reported in the literature for MP infection with no exanthem or for SJS of various etiologies. Eighty percent of the children presented with symptoms of upper respiratory tract infection (URTI) (cough, fever, sore throat, malaise, headache), with a mean of 10 days (range 1 to 30) before skin rash broke out. Skin manifestations occurred in 94.2% of the patients after 3 to 21 days (mean 10.3 days) of fever. The exanthem, composed predominantly of maculopapular and vesicular, was distributed chiefly on the trunk and extremities and lasted less than 14 days in 87.8% of the patients. Stomatitis was observed in 91.6% of the patients and conjunctivitis in 50%. No consistent pattern seems to emerge by which one could predict the existence of MP infection causing SJS. The complications of SJS associated with MP seem less frequent (2.7%) and much less severe than in cases where SJS arises from other reported causes. Because coincidence cannot be excluded from the assessments of the degree and rate of improvement for the few patients treated with corticosteroid, from the low frequency of complications, and from the mortality rate of zero in this series of patients, the use of corticosteroids for SJS associated with MP infection is questionable.
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PMID:Mycoplasma pneumoniae infections and Stevens-Johnson syndrome. Report of eight cases and review of the literature. 189 14

Tiazofurin, an investigational antimetabolite, is undergoing clinical evaluation in leukemia. We analyzed the data base of 198 patients entered in Phase I trials to characterize the incidence and severity of toxicities associated with tiazofurin according to dose and schedule. Severe myelosuppression occurred infrequently, and was not dose-dependent. A five day bolus schedule had a higher incidence of severe or life-threatening neutropenia than other schedules. Tiazofurin produced lymphopenia which was not dose-dependent in the range of 23-36% decrease from baseline, and the effect on lymphocyte count was generally greater than the decline in neutrophil count. Non-hematologic toxicity of a moderate or worse severity (greater than or equal to grade 2) included nausea and vomiting (18% of all courses), serum transaminase elevations (SGOT, 16%; SGPT, 9%), rash (9%), stomatitis (3%), conjunctivitis (3%), headache (10%), other signs of central nervous system toxicity (8%), and cardiac toxicity, primarily pleuropericarditis (4%). Dose-related cutaneous toxicity, headache, and nausea and vomiting were evident in the five day bolus schedule, and myalgia was more frequently reported at higher doses on the single dose schedule. The five day continuous infusion (CI) schedule had a higher incidence of neurotoxicity, cardiac toxicity, SGPT elevations and ocular toxicity than the daily for five days bolus schedule, but none of these differences attained statistical significance. Although the peak plasma concentrations of tiazofurin achieved with the five day bolus schedule were 3-fold higher than the steady-state plasma levels seen with an equal dose given by CI, the area under the concentration-time curve (AUC) was approximately 1.6-fold higher with CI. These observations suggest that both high peak plasma concentrations (above 400 microM) and prolonged exposure to plasma levels exceeding 50 microM may result in a higher incidence of serious non-hematologic toxicity.
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PMID:Clinical toxicity associated with tiazofurin. 220 Jul 59

A phase I trial of 2-beta-D-ribofuranosylthiazole-4-carboxamide (NCS 286193, tiazofurin) was conducted using a 5-day i.v. bolus schedule, every 21 days. Thirty one patients with advanced cancer were entered on the trial. A total of 106 cycles were administered with doses ranging from 550 to 2750 mg/m2. Concomitant administration of Allopurinol was necessary to prevent hyperuricemia. Tiazofurin was difficult to evaluate and many side effects were variable and sporadic. The dose limiting toxicities were nonhematologic consisting particularly of myalgias, headaches and general malaise. Other toxicities included nausea, vomiting, stomatitis, lethargy, sleeping difficulty, sinus bradycardia, skin rash, desquamation of the palms and soles, photophobias and burning of the eyes. Hematologic toxicity was mild and not dose related though it led to a neutropenic septic death in one patient at 2750 mg/m2. Anemia was documented in 60% of cycles. Biochemical abnormalities consisted of mild hyperglycemia, hyperuricemia and elevated skeletal creatinine phosphokinase levels which did not correlate with the incidence or degree of myalgias. Though some patients were able to tolerate higher doses, the recommended dose for phase 2 study is 1650 mg/m2. Further studies will be required to achieve a better understanding of this interesting drug.
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PMID:Phase I study of tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide, NSC 286193). 238 15

For the purpose of evaluation of clinical efficacy, safety and usefulness on Salmonella enteritis, T-3262 (Tosufloxacin tosilate), a newly developed pyridone-carboxylic acid derivative, was administered to a total of 103 patients and carriers. In addition, in vitro antibacterial activity of T-3262 was determined against the clinical isolates, and compared with those of nalidixic acid (NA), pipemidic acid (PPA), enoxacin (ENX), norfloxacin (NFLX) and ofloxacin (OFLX). And when T-3262 was administered to the patients of acute infectious enteritis, fecal drug concentration and their correlation to the changes in the fecal microflora were investigated. The daily dose of 450 mg T-3262 was administered orally three times after meal for 7 days. A total of 63 cases were evaluated (one case of mixed infection caused by Shigella flexneri and Salmonella sp. was included). The clinical efficacy was good in all the enteritis (N = 6). As the bacteriological effect, 60 out of 61 were eradicated, and eradication rate was 98.4%. Adverse effects were observed in four of 102 cases (3.9%), consisting of one with skin rash, one with nausea, headache and stomatitis and two with soft stools. Deteriorations in laboratory findings were seen in 5 of 23 cases (17.4%), consisting of one with elevated GOT, two with elevated GOT and GPT, one with elevated BUN and one with increased eosinophiles count, although they were all slight in degree. MICs of T-3262 which inhibited 90% of the isolates of Salmonella spp. was 0.05 microgram/ml, which was the lowest among the quinolone derivatives tested. The values of the fecal drug concentration of 7 cases of acute infectious enteritis, to which T-3262 administered, were higher than that of MIC90 and recovery rates of T-3262 were distributed from 2.85 to 46.3%. The degrees of changes of the drug concentrations were dependent on individual cases, and did not show the same trend. In addition, changes in the fecal microflora with in 24 hrs after T-3262 administration did not show the same trend.
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PMID:[Clinical trial of T-3262 (Tosufloxacin tosilate) on Salmonella enteritis, and fecal drug concentration and change in the fecal microflora in the acute diarrheal patients. Japan Research Committee of T-3262, Research Group for Acute Infectious Enteritis]. 269 43

Recombinant interleukin-2 (rIL-2) (NSC# 600664; Hoffmann-La Roche, Inc., Nutley, NJ) was studied in a phase I clinical trial in 33 patients with advanced, measureable cancer of the colon or malignant melanoma, Eastern Cooperative Oncology Group (ECOG) performance status O-1, and no prior chemotherapy or radiotherapy. The goal of the study was to identify a dose and schedule of IL-2 to generate maximal immune modulation with tolerable toxicity. Such a regimen might allow the addition of other treatment modalities and/or prolonged treatment duration in later trials. Each patient received IL-2 as a continuous 24-hour infusion once weekly for 4 weeks and then twice weekly for 4 weeks. Five treatment groups received from 10(3) U/m2 to 3 x 10(7) U/m2 per 24-hour infusion. The maximal tolerated dose was 3 x 10(7) U/m2/d twice weekly. Patients treated twice weekly at 1 x 10(7) and 3 x 10(7) U/m2/d had immune modulation in terms of lymphocytosis, eosinophilia, increased natural killer (NK) activity, and elevated numbers of peripheral blood mononuclear cells expressing CD16, OKT10/Leu-17, and Leu-19 surface markers. Endogenous generation of peripheral blood lymphokine-activated killer (LAK) activity was demonstrated by lysis of NK-resistant Daudi targets, in patients treated at 3 x 10(7) U/m2/d. Biochemical and hematological abnormalities were moderate and reversible. Clinical toxicity included hypotension, myalgia, arthralgia, stomatitis, fever, fatigue, nausea, headache, chills, diarrhea, and oliguria at high doses. Cardiovascular toxicity was tolerable for most patients and reversed after IL-2 was stopped. Two of six melanoma patients at 3 x 10(7) U/m2/d achieved partial responses by the end of the eighth week. This IL-2 schedule appears to produce potentially clinically useful immune enhancement with tolerable toxicity.
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PMID:A phase I clinical trial of recombinant interleukin-2 by periodic 24-hour intravenous infusions. 278 32

Twenty-six patients with severe rheumatoid arthritis who had completed a randomized crossover trial of methotrexate elected to continue to receive the drug in a long-term prospective study. At 36 months, 16 patients remained in the study. Over this period of time, significant improvement was noted in the number of painful and swollen joints, physician and patient global assessments, erythrocyte sedimentation rate, and prednisone dose. Adverse reactions occurred in 16 patients (62%), including nausea, alopecia, headache, stomatitis, herpes zoster, and diarrhea. Mild leukopenia (3 patients), thrombocytopenia (3 patients), and elevated transaminase levels (8 patients) resolved with temporary drug discontinuation. No patient withdrew due to drug toxicity. Liver biopsy specimens in 17 patients after 24 months of treatment showed no evidence of fibrosis or cirrhosis. A significant increase in the percentage of T3 and T4 blood cells and increases in lymphocyte proliferation to concanavalin A and purified protein derivative of tuberculin were found after 2 years of therapy. Our findings indicate that methotrexate has remained effective over 36 months of therapy, with acceptable toxicity levels and no evidence of systemic immunosuppression.
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PMID:Long-term prospective trial of low-dose methotrexate in rheumatoid arthritis. 291 60

The efficacy and acceptability of low dose weekly methotrexate therapy in rheumatoid arthritis was reviewed in 587 patients in open and randomized trials. Gastrointestinal toxicity was reported most frequently. Bone marrow suppression, stomatitis, alopecia, headaches, and fever also occurred. A review of these adverse reactions, as well as of the effects of this drug on the reproductive, renal, and pulmonary systems, is discussed.
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PMID:Toxicity of low dose methotrexate in rheumatoid arthritis. 391 75


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