Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The neurotoxicity of local administration of nitrosoureas in malignant gliomas was investigated clinicopathologically. Twenty patients were entered into this study: 13 were treated with 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) and 7 with methyl 6-[3-(2-chloroethyl-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside (MCNU). On the average, a single dose of 20 mg of ACNU was administered 15 times, for a total dose of 295 mg in each case, while a single dose of 11 mg of MCNU was given 2 times, for a total dose of 24 mg. These nitrosoureas provoked greater toxicity when the administration dose was larger or the indwelling multiperforated Silastic basket was in direct continuity with the ventricle or the basal cistern. Usually ACNU was well tolerated, whereas MCNU induced marked brain edema. Side effects consisted of headache, nuchal stiffness, vomiting, motor weakness, and cranial nerve palsy for ACNU, and headache, vomiting, abnormal respiration, and arrhythmia for MCNU. Pathological changes were represented by capsule formation, spongy degeneration and reactive gliosis of adjacent white matter, occlusion of neighboring arteries, and demyelination of cranial nerves in the patients treated with ACNU, while they were represented by focal brain necrosis in two patients treated with MCNU. The differences in neurotoxity of ACNU and MCNU conceivably derive from the different blood-brain delivery of these drugs.
 ...
PMID:Neurotoxicity of local administration of two nitrosoureas in malignant gliomas. 235 97

The pharmacological properties of MCNU, methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside, were investigated in laboratory animals. MCNU had no effects on the central nervous, respiratory or the cardiovascular systems, but dilation of isolated auricular vessel was seen. No local anesthetic activity was demonstrated. Treatment with MCNU had practically no influence on the contraction of the isolated phrenic nerve-diaphragm, ileum, vas deferens or uterus. Furthermore, no effects on the passage of charcoal meal, size of the pupil and the contraction of nictitating membrane were observed. MCNU caused a reduction of leucocyte counts, suppression of immune responses, local irritation, suppression of blood coagulating activity and slight inhibition of gastric secretion. No definite effects were observed on blood glucose level or renal and liver functions. MCNU had no antiinflammatory and diuretic activities and did not cause hemolysis. Vomiting and diarrhea were observed by the administration of MCNU. In conclusion, the major pharmacological effects of MCNU are reduction of leukocyte counts, local irritation and immuno-suppression. The reduction of leukocyte counts induced by MCNU was more significant than that by chlorozotocin, but less than that by CCNU. Other effects may be considered somewhat weak or almost the same extent compared with these agents.
 ...
PMID:[Pharmacological studies on MCNU: a new antitumor agent]. 322

A phase II study of the oral agent methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside (MCNU tablet) for myeloproliferative disorders was performed. Fifty-two patients were treated with MCNU tablets and 43 patients were evaluated for clinical effects and 45 for adverse effects. The standard regimen was as follows; oral administration of 50mg (one tablet)/body/day every 4-6 days was considered as one course, and this was repeated at 6-8-week intervals if possible, with certain modifications according to dosage, period of administration and dose interval wherever necessary. Of 16 patients with chronic myelogenous leukemia (CML) in the chronic phase, 13 achieved complete remission (CR), and 3 achieved partial remission (PR). The overall response ratio was 100%. Rapid reduction of leucocytes was detected within two weeks. One patient with CML in blast crisis achieved PR (100%). Of 15 patients with polycythemia vera, 13 showed an excellent effect (87%), and 1 a moderate effect (6.7%), the overall response ratio being 93%. In essential thrombocythemia, an excellent effect (70%) was obtained in 7 of 10 patients. One patient with myelofibrosis showed an excellent effect (100%). Nausea & vomiting (33%) and anorexia (13%) were major adverse effects, but these symptoms were observed only transiently. Liver dysfunction was also seen in 8.9% of patients, but no patient showed severe manifestations. Our study supports the contention that MCNU tablet is a useful agent against myeloproliferative disorders.
 ...
PMID:[Phase II study of a new nitrosourea derivative, MCNU, in tablet form. Takai Blood Cancer Study Group]. 356 4

Sixty-seven patients with hematological malignancies and 4 with cancers were evaluated in this study. Standard administration of MCNU was instituted intravenously using 50-100 mg/m2 every 2 or 4 weeks, whereas some cases were treated with a higher dose therapy. Of 10 patients with chronic myelogenous leukemia, 7 achieved complete remission (CR), and 1 achieved partial remission (PR). A good response was also obtained in 9 of 10 patients with polycythemia vera and in all 4 patients with essential thrombocythemia. MCNU was less effective in malignant lymphoma (ML) and multiple myeloma (MM) than in myeloproliferative disorders. Two of 15 patients with ML and one of 21 patients with MM achieved CR, and two with ML and three MM achieved PR. Three patients with lung cancer and 1 with gastric cancer showed no response to MCNU. Delayed anemia, leukocytopenia and thrombocytopenia were observed in 38.7% of patients, and these were regarded as major side effects of MCNU. Nausea, vomiting, anorexia and elevated transaminase were also found in about 24% of patients, but only transiently. Our study indicates that MCNU is useful for chemotherapy of hematological malignancies, especially of myeloproliferative disorders. Therefore, further studies on combination chemotherapy with MCNU should be developed.
 ...
PMID:[Phase II study of methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside (MCNU)]. 385 48

A phase II study on MCNU (Methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside) was performed in 33 patients with advanced or recurrent gastrointestinal cancer under the cooperation of eight institutions in Hiroshima Prefecture. MCNU was given by means of intravenous drip infusion and the 33 cases were divided into three groups according to the method of administration; (A) 50mg/m2 every 1 or 2 weeks, (B) 70mg/m2 every 2 weeks or (C) 90mg/m2 every 6-8 weeks. Among 28 evaluable cases, 1 complete response (CR) and 1 partial response (PR) were observed and these two cases were gastric cancer patients. Platelet nadir occurred at the 3rd or fifth week after MCNU administration, but the leukocyte count was not so decreased. Subjective side effects were nausea, general fatigue and vomiting, but these were observed to be only mild.
 ...
PMID:[Phase II study on MCNU in patients with advanced or recurrent gastrointestinal cancer]. 403 10

Experimental studies with orally administered MCNU, a water-soluble nitrosourea, yielded the following results. MCNU produced a significant increase in life span, and 60-day survivors were observed by various schedules in L1210 leukemia. The therapeutic ratios of MCNU were almost similar to those of CCNU. With Lewis lung carcinoma and Ehrlich ascites carcinoma implanted into the stomach wall, its antitumor activity by oral administration was slightly more effective than by intravenous route. In Beagle dogs, hematologic toxicity and gastrointestinal toxicity (vomiting, diarrhea) were noted by oral administration, similar to intravenous administration, but its toxicity was mild. The maximum blood level of MCNU was noted at 30 minutes after oral administration in Beagle dogs. The half life (23.7 min) by oral administration was similar to that by intravenous route. From these results, the oral administration of MCNU deserves the consideration as a form of treatment now given other MCNU routes.
 ...
PMID:[Experimental studies on oral administration of nitrosourea anti-tumor agent, MCNU]. 623 61

The incidence of SIADH (the syndrome of inappropriate antidiuretic hormone secretion) was analyzed retrospectively in 43 children who received marrow-ablative chemotherapy before autografts with peripheral blood stem cells for lymphoid malignancies. SIADH was documented in three children (ages 3, 13, and 13 years) who received chemotherapy, which included high-dose methyl 6-[3-(chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside (MCNU) and cyclophosphamide, under a concomitant overhydration protocol. SIADH was manifested as frequent vomiting in two patients and as generalized seizure in one. Hyponatremia (< 125 mEq/L), hypo-osmolality (< 260 mOsm/kgH2O), and continued urinary excretion of sodium (> 30 mEq/L) were used to diagnose SIADH in these three patients. All signs and symptoms subsided within 24 hours either by fluid restriction alone (n = 1) or by supportive care including anticonvulsant and D-mannitol, or hyperhydration with saline plus 5% glucose and diuretic. None of the patients died. Careful monitoring of the serum sodium level, as well as the osmolality of plasma and urine, should be incorporated into the patient management protocol for this type of high-dose chemotherapy.
 ...
PMID:Syndrome of inappropriate antidiuretic hormone secretion (SIADH) in children undergoing high-dose chemotherapy and autologous peripheral blood stem cell transplantation. 757 88

From January 1988 until December 1990, 99 previously untreated patients with multiple myeloma (MM) were enrolled in a randomized prospective study comparing two combination chemotherapies with and without MCNU as induction therapy for MM; 49 patients with vindesine, melphalan and prednisolone (VMP therapy) versus 50 patients with MCNU, vindesine, melphalan and prednisolone (MCNU-VMP therapy). Seventy-two evaluable patients (34 patients in the VMP group, 38 in the MCNU-VMP group) were analyzed. The response rate was slightly higher with MCNU-VMP than with VMP (81.6% vs. 64.7%). In 43 responders (21 patients in the VMP group and 22 in the MCNU-VMP group) who were treated with the same regimen as the induction therapy to maintain remission, the remission duration was significantly longer in patients treated with MCNU-VMP than in those treated with VMP (median > 10.1 vs. 8.0 months, P = 0.018), particularly in patients with PS 3-4. The remission duration in the MCNU-VMP group was also slightly longer in the patients with stage III disease and who were older than 65 years. The median survival time showed no significant difference between the VMP group (20.3 months) and the MCNU-VMP group (> 15 months). Leukopenia, thrombocytopenia and nausea/vomiting were found to be somewhat severe in the MCNU-VMP group. In summary, MCNU-VMP therapy is effective as induction therapy for MM.
 ...
PMID:Combination chemotherapy with MCNU, vindesine, melphalan, and prednisolone (MCNU-VMP therapy) in induction therapy for multiple myeloma. Japan Myeloma Study Group. 801 4

This is the first report of successful treatment of recurrent retinoblastoma with vitreous seeding by a combination of ranimustine (MCNU) and carboplatin. The patient was diagnosed with bilateral retinoblastoma at 3 years of age. Although he received photocoagulation and radiotherapy for the left eye after enucleation of the right eye, a recurrent tumor associated with vitreous seeding developed 6 years later. The child underwent chemotherapy with cyclophosphamide and nimustine hydrochloride (ACNU), and a transient decrease of tumor cells in the vitreous was seen. We then changed the chemotherapy regimen to MCNU (70 mg/m2/ day for 1 day) and carboplatin (400 mg/m2/day for 2 days). After five courses of this chemotherapy, the tumor in the vitreous completely disappeared. No recurrence has been observed for > 4 years. Side effects, including myelosuppression, general fatigue, and vomiting, were observed during the course of chemotherapy, but they were ameliorated with supportive therapy. Neither nephro- nor ototoxicity was observed. The patient has useful vision. These results warrant further study of this novel drug combination in patients with recurrent, or even primary, retinoblastoma.
 ...
PMID:Successful treatment with ranimustine and carboplatin for recurrent intraocular retinoblastoma with vitreous seeding. 893 71