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

Acute and 1-month toxicity studies with SCH 31846, a nonsulfhydryl anti-hypertensive agent which acts by inhibiting angiotensin-converting enzyme, were initiated to evaluate its toxicity. The oral LD50s in mice and rats were approximately 1.8 and 2.5 g/kg, respectively, while the iv LD50 was approximately 450 mg/kg in mice and 150 mg/kg in rats. Signs of acute toxicity in rats and mice included salivation, hypoactivity, ataxia, prostration, and convulsions. In a 1-month dog study at oral doses of 25, 75, or 150 mg/kg, there was a dose-related increase in emesis between 1 and 2 hr after dosing. Absorption studies showed peak blood concentrations occurring in dogs between 0.3 and 1 hr after dosing. No other noteworthy antemortem changes were observed. In a 1-month rat study at oral doses of 30, 180, or 600 mg/kg, the hematocrit and hemoglobin values of the 600 mg/kg-dosed female rats were slightly but significantly (p less than 0.05) decreased and the blood urea nitrogen was slightly but significantly (p less than 0.05) increased in all SCH 31846-dosed male rats and the 600 mg/kg-dosed female rats. Absorption studies in male rats at doses of 30, 180, and 600 mg/kg indicate that SCH 31846 is well absorbed in rats. The 150 mg/kg-dosed dogs and the 180- and 600 mg/kg-dosed rats had a slight increase in the number of renin-containing granules in the renal juxtaglomerular cells. No other compound-related microscopic changes were observed. These data are similar to data reported for Captopril and suggest that in the dog and rat the toxicity of ACE inhibitors is not dependent upon the presence or absence of a sulfhydryl group.
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PMID:Acute and subchronic toxicity of a nonsulfhydryl angiotensin-converting enzyme inhibitor. 300 64

The patient was a 63-year-old female, who was admitted to the National Nagoya Hospital with complaints of left cervical and bilateral axillary lymphadenopathy on 12 May, 1987. Since May 1985, with the diagnosis of non-Hodgkin lymphoma, she had been successfully treated with combination chemotherapy (VEPA) and radiotherapy at another hospital. Left axillary lymphode biopsy revealed a diagnosis of non-Hodgkin lymphoma, diffuse large cell type. Then, she was given intravenous administration of carboplatin (400 mg/body) on 26 May, 1987. After a single course of this regimen, the lymphnode swelling subsided, and she achieved complete remission on 6 June. Thereafter, she was placed on the maintenance chemotherapy of carboplatin (400 mg/body) every 5 weeks. Through the whole course of this patient, the serum levels of blood urea nitrogen and creatinine were normal, and she did not notice nausea, vomiting and peripheral neuropathy. To our knowledge, this is the first report of complete response by the administration of carboplatin for non-Hodgkin lymphoma.
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PMID:[A case of non-Hodgkin lymphoma with complete remission achieved by carboplatin]. 304 95

Benzoate and phenylacetate improve prognosis in inherited urea cycle enzyme deficiencies by increasing waste nitrogen excretion as amino acid acylation products. We studied metabolic changes caused by these substances and their pharmacokinetics in a biochemically different urea cycle disorder, lysinuric protein intolerance (LPI), under strictly standardized induction of hyperammonemia. Five patients with LPI received an intravenous infusion of 6.6 mmol/kg L-alanine alone and separately with 2.0 mmol/kg of benzoate or phenylacetate in 90 min. Blood for ammonia, serum urea and creatinine, plasma benzoate, hippurate, phenylacetate, phenylacetylglutamine, and amino acids was obtained at 0, 120, 180, and 270 min. Urine was collected in four consecutive 6-h periods. Alanine caused hyperammonemia: maximum increase 107, 28-411 microM (geometric mean, 95% confidence interval); ammonia increments were nearly identical after alanine + benzoate (60, 17-213 microM) and alanine + phenylacetate (79, 13-467 microM) (NS). Mean plasma benzoate was 6.0 mM when extrapolated to the end of alanine + benzoate infusions; phenylacetate was 4.9 mM at the end of alanine + phenylacetate. Transient toxicity (dizziness, nausea, vomiting) occurred in four patients at the end of combined infusions, and we suggest upper therapeutic plasma concentrations of 4.5 mM for benzoate and 3.5 mM for phenylacetate. Benzoate and phenylacetate then decreased following first-order kinetics with t1/2S of 273 and 254 min, respectively. Maximal plasma hippurate (0.24, 0.14-0.40 mM) was lower than maximal phenylacetylglutamine (0.48, 0.22-1.06 mM, p = 0.008).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Waste nitrogen excretion via amino acid acylation: benzoate and phenylacetate in lysinuric protein intolerance. 309 49

Acute toxicity of cefodizime sodium (THR-221) was examined in mice of both sexes, rats of both sexes (including 5-day-old young), and male dogs. The LD50 values of THR-221 (mg/kg) were as follows: (1) mice: intravenous, 7200 for males and 5000 for females; intraperitoneal, 10500 for males and 11000 for females; subcutaneous, 17500 for males and 16500 for females; and oral, 28000 for males and 29000 for females. (2) rats (adult): intravenous, 7000 for males and 8200 for females; intraperitoneal, 9500 for males and 8800 for females; subcutaneous, 17000 for males and 15500 for females; oral, more than 20000 for both sexes; and intramuscular, more than 3200 for both sexes. (3) 5-day-old rats: subcutaneous, 5278 for males and 5314 for females. (4) male dogs: intravenous, more than 5000. Major changes in general conditions observed in mice and rats were decreased spontaneous activity, lying prone, respiratory changes, staggering gait, clonic or clonic-tonic convulsions, and cyanosis, and in the animals dosed orally, diarrhea or salivation was also noted. The changes in 5-day-old rats were respiratory changes, agony, loss of reflex to an external stimulus, and congestion at the injection site, and those in dogs were vomiting, dryness of the nose, and soft or mucous stools. Autopsies on the mice and rats which died revealed hemorrhage on the brain surface. In addition, the following were seen: intraperitoneal retention of fluid and dark red spots on the abdominal wall (i.p.), subcutaneous retention of fluid or jellylike material and hemorrhage at the injection site (s.c.), and retention of fluid and dark red spots on the mucosa in the digestive tract (mice p.o.). In 5-day-old rats which died, the subcutaneous tissue at the injection site showed hemorrhage macroscopically and inflammatory changes microscopically. Hematological and blood chemical tests performed in dogs showed an increase in white blood cells and changes suggesting anemia, increases in GOT, LDH and ALP activities, and slight changes in urea nitrogen and inorganic phosphorus. In one animal given a low dose of 2500 mg/kg, an increase in GPT activity was also seen. However, these changes were all transient. Microscopic findings in dogs were slight inflammatory changes in the subcutaneous tissue around the injection site.
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PMID:[Acute toxicity study of cefodizime sodium]. 317 86

A seventy-two-year-old man with hypertensive cerebral hemorrhage acutely developed severe headache, nausea, vomiting, agitation, and disorientation with abrupt rise in blood pressure on the sixth day after the onset. At that time, there were no remarkable changes in focal neurologic deficits, and repeated brain CT scans revealed a small hematoma located in the right basal ganglia without further enlargement or herniation. Blood chemistry and arterial gas analysis were within the normal ranges except for a slight rise in blood urea nitrogen. Similar episodes occurred three times within two days, and each time the cerebral symptoms disappeared in accordance with lowering of blood pressure by antihypertensive therapy. Complication of hypertensive encephalopathy was strongly suggested. The authors discuss the pathophysiology of this encephalopathy in relation to cerebral hemorrhage.
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PMID:Transient encephalopathy related to rapidly and markedly elevated blood pressure in acute stage of hypertensive cerebral hemorrhage--relationship to hypertensive encephalopathy--a case report. 317 64

Forty-one dogs with a variety of histopathologically diagnosed, measurable tumors were treated with cisplatin (cis-diamminedichloroplatinum, Platinol, Bristol Laboratories, Syracuse, NY 13221-4755) as a single agent at a dosage of 60 mg/m2 given intravenously at 3-week intervals. In an attempt to avoid renal toxicity of cisplatin, saline diuresis was induced and maintained for 4 hours before and 2 hours following cisplatin administration. The dogs received one to ten doses of cisplatin. To determine response to therapy and to monitor toxicity of the drug, the dogs were evaluated with physical examinations including tumor measurements, radiography, complete blood counts, platelet counts, urinalyses, serum urea nitrogen concentrations, and serum creatinine concentrations. An overall response rate of 19% was observed. Complete remission occurred in one of 11 dogs with squamous cell carcinomas and one of one dog with a mediastinal undifferentiated carcinoma. Partial remissions were documented in one of 11 dogs with squamous cell carcinomas, two of three dogs with metastatic osteosarcomas, one of three dogs with nasal adenocarcinomas, and one of one dog with a thyroid adenocarcinoma. Toxic side effects were primarily gastrointestinal in nature, with vomiting occurring 1-6 hours after cisplatin administration in 27 of 41 dogs. Severe anorexia occurred in three dogs, and hemorrhagic diarrhea was observed in one dog. One dog developed grand mal seizures and died 3 hours following therapy. Granulocytopenia was documented in six dogs, and thrombocytopenia was observed in four dogs. One dog showed an increase in serum urea nitrogen and creatinine concentrations, but this patient had known pre-existing renal disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cisplatin therapy in 41 dogs with malignant tumors. 322 54

A toxicology study of cis-diamminedichloroplatinum (II) (CDDP), aqua(1,1-bis-(aminomethyl)cyclohexane)sulfatoplatinum(II) (TNO-6), diammine(1,1-cyclobutanedicarboxylato)platinum(II) (CBDCA), cis-dichloro-trans-dihydroxo-cis-bis(isopropylamine)platinum-(IV) (CHIP) and ethylenediaminemalonatoplatinum(II) (JM-40) was carried out in dogs. The main purpose of the study was to compare the results with those obtained earlier in mice and rats and with the toxicology data in humans. Each platinum compound was tested in three dogs. Each dog received three intravenous bolus injections at intervals of 3 weeks. The compounds were administered in dosages of 1.2, 1.0, 12, 10 (or 6) and 10 mg/kg, respectively. Toxic death occurred for two dogs (both on day 54) from haematotoxicity (10 mg/kg CHIP) and renal toxicity (TNO-6), respectively. Serum urea nitrogen and creatinine concentrations were variable after TNO-6 and remained within normal values after treatment with the other compounds. Severe proteinuria was observed in all three dogs treated with TNO-6. Values returned to normal within 16 days. JM-40 did not cause significant proteinuria. CDDP, CBDCA and CHIP caused short-lasting and slight proteinuria. CHIP caused a severe reduction in the number of leukocytes and platelets, while the other drugs caused acceptable reductions. Except after the high dose CHIP regimen, haematotoxicity was of a transient nature. Vomiting in order of severity occurred after TNO-6, CHIP, CDDP and JM-40, while CBDCA did not cause any vomiting. The dogs were sacrificed 6 weeks after the last drug dose. Organs were fixed for histopathology to complete and support clinical-toxicological parameters. On the basis of the results from the single-dose study in dogs and those obtained earlier in mice and rats it can be concluded that the gain from the use of the dog as a prognosticator for organ toxicity in man was disappointing and limited to the prediction of vomiting.
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PMID:Preclinical toxicology of platinum analogues in dogs. 330 82

Ciprofloxacin is a new quinolone antimicrobial agent with activity against a broad spectrum of gram-negative and gram-positive organisms, including Pseudomonas aeruginosa and methicillin-resistant strains of staphylococci. The efficacy and safety results of 80 clinical studies of the oral form of ciprofloxacin are reported. Drug safety was assessed in 2236 courses in 2203 adult patients treated primarily in the United States. Data from 1676 courses were suitable for analysis of drug efficacy. The unit dose for most patients ranged from 250 mg to 750 mg (median, 500 mg), usually given every 12 hours. The duration of treatment ranged from 3 to 231 days (median, 10 days). Predominant among 1722 infections were those of the urinary tract (43%), skin structures (29%), and respiratory tract (19%); the remainder were bone and joint infections (5%), bacteremias (2%), and intra-abdominal (1%), gastrointestinal (1%), and pelvic infections (less than 1%). Signs and symptoms of infection resolved in 79% of all cases; a further 15% improved, and 5% failed to improve. Pathogens were eradicated in 89% of urinary tract infections and persisted in 5%; 80% of patients still had sterile urine at the 3-to 6-week follow-up. In 81% of nonurinary tract infections, pathogens were eradicated; they persisted in 11%, and superinfection occurred in less than 5%. After treatment, 89% of the 2253 causative organisms were eradicated and 2% were reduced to clinically insignificant counts; 8% persisted. Of 411 isolates of P. aeruginosa, 77% were eradicated, as were 97% of 421 Escherichia coli and 80% of 248 Staphylococcus aureus isolates. Also eradicated were 95% of 166 Klebsiella, 96% of 139 Proteus mirabilis, 100% of 20 other Proteus, 94% of 123 Enterobacter, 100% of 68 Haemophilus influenzae, 96% of 49 Citrobacter, 89% of 45 Serratia, 95% of 41 Streptococcus pneumoniae, 91% of 43 Salmonella, 100% of 38 Morganella morganii, and 100% of 35 Providencia isolates. Adverse reactions were judged probably or possibly drug-related in 14.8% of courses; drug treatment had to be stopped prematurely in 3.5%. The most frequent reactions were gastrointestinal complaints (chiefly nausea, diarrhea, and vomiting), metabolic disorders (elevated SGOT, SGPT, serum creatinine, or blood urea nitrogen), and nervous system effects (dizziness, light-headedness, restlessness, tremor, and headache). Crystalluria, judged to be related to ciprofloxacin, occurred in two patients.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:A survey of clinical experience with ciprofloxacin, a new quinolone antimicrobial. 336 Sep 68

The substitution of chlorambucil for nitrogen mustard and vinblastine for vincristine has been suggested to be an equally effective and well-tolerated variation of the MOPP regimen (mechlorethamine, vincristine, procarbazine, and prednisone). We treated 76 patients with advanced (i.e., Stage III, IV, or II with bulky mediastinal mass) or recurrent Hodgkin's disease with chlorambucil 6 mg/m2, procarbazine 100 mg/m2, and prednisone 40 mg p.o. daily, all on days 1-14; plus vinblastine 6 mg/m2 i.v. on day 1 and 8 of each 28-day cycle (ChlVPP). There was no maximum dose of the myelosuppressive agents. Patients who had not previously been irradiated received from 2,300 to 4,100 cGY to sites of previously bulky diseases after completing 6 cycles of ChlVPP. ChlVPP was easy to administer (i.e., 87% of patients without previous chemotherapy received greater than or equal to 80% of the planned doses of myelosuppressive drugs) and was generally well tolerated, with only occasional vomiting from procarbazine and phlebitis from vinblastine. In patients without previous chemotherapy, 49 (76%) achieved a complete remission (CR) and 7 (11%) a stable partial remission (i.e., residual, stable radiographic abnormality). With a maximum follow-up of 4 years, only one CR has relapsed for an actuarial CR durability of 97%. ChlVPP with consolidative radiation therapy to sites of bulky disease is effective in advanced Hodgkin's disease and, compared with most other available regimens, is extremely well tolerated.
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PMID:ChlVPP--an effective and well-tolerated alternative to MOPP therapy for Hodgkin's disease. 340 20

The pathology of malignant hypertension in dogs induced either purposely or inadvertently by the Goldblatt procedure has not been previously reported. Malignant hypertension was experimentally produced in beagle dogs by a modified Goldblatt procedure; in a single surgical procedure, one kidney was removed and the blood flow to the remaining kidney was reduced by 50%. A sudden onset of severe clinical signs developed within one to three weeks after surgery. The dogs were markedly depressed or in shock, were vomiting, and had either bloody feces or bloody diarrhea. Hematologic changes compatible with a diagnosis of microangiopathic hemolytic anemia consisted of hemolysis, thrombocytopenia, and the presence of burr cells and schistocytes. Some dogs had neutrophilia and slight to moderate increases in blood urea nitrogen and creatinine. At necropsy, there were gross hemorrhages in the heart, brain, urinary bladder, and gastrointestinal tract. Histologic findings consisted of multifocal parenchymal hemorrhage, fibrinoid necrosis of arterioles, medial smooth muscle hyperplasia, adventitial fibroplasia and mononuclear cell infiltrates, and microthrombi. The vascular clamp most likely protected the kidney from the systemic hypertension since the remaining kidney was largely not remarkable by light or electron microscopy. The dog appears to be a good model to study the pathology of malignant hypertension and microangiopathic hemolytic anemia.
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PMID:Experimentally induced malignant hypertension in beagle dogs. 376 16


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