Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
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The dose of interleukin 2 (IL-2) which can be administered to cancer patients is limited largely by a capillary leak syndrome. Pentoxifylline (PTX) is a methylxanthine which reduces IL-2 toxicity in animals. Ciprofloxacin (Cipro) modifies the metabolism of methylxanthines and, when coadministered with PTX, increases levels of PTX and certain of its metabolites. We conducted a phase Ib trial in patients receiving IL-2 and lymphokine-activated killer cell (LAK) cell therapy for metastatic renal cell carcinoma to identify the maximum tolerated dose of PTX which could be coadministered with Cipro in this setting. Eighteen patients received IL-2 (Roche) by continuous infusion at 6 x 10(6) units/m2/day on days 1-5 and underwent leukapheresis on days 7-9. LAK cells were infused on days 12-14. IL-2 was administered at 2 x 10(6) units/m2/day on days 10-20. Cohorts of patients received PTX at 2.5 (n = 3), 3.1 (n = 6), 3.9 (n = 6), and 4.9 (n = 3) mg/kg by 30 min i.v. infusion every 4 h on days 0-5 and 10-20 and Cipro (500 mg p.o. every 12 h) on days 1-5 and 10-20. Toxicity was compared with that observed in 33 historical control patients who received 37 cycles of an identical regimen of IL-2/LAK without PTX/Cipro. PTX at 2.5-3.9 mg/kg and Cipro were well tolerated. The maximum tolerated dose of PTX was 3.9 mg/kg. Dose-limiting emesis (n = 1) and atrial fibrillation (n = 2) occurred at 4.9 mg/kg and were reversible. Two complete, one partial and one minor, responses were observed. Patients treated with 3.9 mg/kg PTX received 95.0% of the planned dose of IL-2 as compared to 72.8% in the control patients (P < 0.025), primarily due to a lower incidence of azotemia and metabolic acidosis in PTX/Cipro recipients than had been seen in the historical control patients. The results of this study demonstrate that PTX/Cipro can be administered to patients receiving IL-2/LAK without apparent loss of therapeutic efficacy. Moreover, PTX/Cipro recipients exhibited less toxicity than historical controls. Therefore, treatment with PTX/Cipro may allow delivery of higher doses of IL-2, which might induce more responses in IL-2-responsive tumors and regression of tumors unresponsive to conventional doses of IL-2.
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PMID:Phase Ib trial of pentoxifylline and ciprofloxacin in patients treated with interleukin-2 and lymphokine-activated killer cell therapy for metastatic renal cell carcinoma. 801 63

The systemic toxicity of doxorubicin, 30 mg/m2 body surface area (BSA) every 21 days to a cumulative dose of 300 mg/m2, was evaluated in six cats. Appetite, body weight, and the presence of vomiting and/or diarrhea were monitored throughout the study. Renal function was monitored by measuring serum blood urea nitrogen (BUN) and creatinine concentrations, urine specific gravity, and creatinine clearance before each treatment. Electrocardiograms and echocardiograms were also done before each treatment. The cats were killed 3 weeks after the last treatment, and complete necropsies were performed. Partial or complete anorexia occurred in all cats with significant weight loss occurring after a cumulative doxorubicin dose of 150 mg/m2 BSA. Mild vomiting and diarrhea that required no treatment also occurred sporadically in all cats. Echocardiographic changes consistent with doxorubicin-induced cardiomyopathy occurred in four cats after cumulative doses of 170 to 240 mg/m2 BSA. Clinical heart disease and electrocardiographic changes were not observed. Subsequent histological examination revealed myocyte vacuolization and myocytolysis in all six hearts. Renal dysfunction, characterized by increasing azotemia with progressively more dilute urine, was detected in two cats. Mean creatinine clearance values also decreased significantly throughout the study. At necropsy, all cats had histological evidence of renal disease.
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PMID:Systemic toxicity associated with doxorubicin administration in cats. 826 50

To study acute organophosphorus (OP) poisoning cases, 190 OP-intoxicated cases admitted to Civil Hospital, Ahmedabad, were investigated in depth. The group consisted of subjects ranging from 11 to 60 years of age, with the maximum number of cases in the age group 21-30 years and a male-to-female ratio of 2.1:1. Most of the subjects (71.61%) were partially educated, 24.2% of the cases were illiterate, and only 4.2% of the cases were highly educated. Socioeconomically, 21.1% of the subjects were of low economic status, 52.6% were low middle class, 16.8% were upper middle class, and only 9.5% were upper class. With regard to marital status of the subjects, 98 cases were married and 92 were unmarried. About 67.4% of the cases had the intention of committing suicide, 16.8% of the cases were the result of occupational exposure, and 15.8% of the cases were from accidental poisoning. Social and domestic problems (37.5%), marital friction (15.6%), financial stress (15.6%), love affairs (14.1%), job problems (10.9%), chronic illness (4.7%), and failure in examination (1.6%) were observed as the precipitating factors. Muscarinic manifestations such as vomiting (96.8%), nausea (82.1%), miosis (64.2%), excessive salivation (61.1%), and blurred vision (54.7%) and CNS manifestations such as giddiness (93.7%), headache (84.2%), disturbances of consciousness (44.2%), and typical pungent odor from mouth and clothes (77.9%) were the main presenting symptoms. Cardiac manifestations such as sinus tachycardia (25.3%), sinus bradycardia (6.3%), and depression of ST segments with T-wave inversion (6.3%) were observed electrocardiographically, with hypertension (10.5%) and muscular twitching in some (2.1%) cases. Biochemical changes such as albuminuria (12.6%) and azotemia (18.9%) with inhibition of acetylcholinesterase enzyme activity in blood were recorded in 78.9% of the cases. About 89.5% of the cases recovered completely, 4.2% of the cases absconded after partial recovery, and 6.3% of the cases died. The mortality rate (6.3%) depended on various factors such as the organophosphorus compound consumed, the amount ingested, the time interval for hospitalization, and the general health of the patient. Chances of recovery were higher when the patient was hospitalized at the earliest indication.
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PMID:A clinical, biochemical, neurobehavioral, and sociopsychological study of 190 patients admitted to hospital as a result of acute organophosphorus poisoning. 832 67

Three cases of acute pancreatitis following transurethral resection of the prostate are reported. The incidence is rare. A review of perioperative data failed to disclose any unique factor except in 1 patient who had an underlying biliary tract disease. Hyperamylasemia or hyperlipaemia in association with abdominal pain and vomiting was noted in all patients to establish the diagnosis. Computed tomography also confirmed the existence of acute pancreatitis. One patient died of respiratory and renal failure. However, early diagnosis and prompt treatment are essential to reduce high mortality. In conclusion, acute pancreatitis should be considered as one of the differential diagnoses in the presence of abdominal pain with vomiting, azotemia or oliguria after transurethral resection of the prostate.
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PMID:Acute pancreatitis following transurethral resection of prostate. 850

Apomorphine, a potent dopamine agonist with mixed D1 and D2 properties, has long been recognized to have antiparkinsonian effect. Its oral administration is limited by both its hepatic first pass metabolism and adverse side effects (nausea, vomiting, azotemia). It is now widely used by subcutaneous route for the treatment of severe "off" periods seen with levodopa treatment. However, the use of penjects can be difficult in some patients with severe tremor or akineto-rigid symptoms during "off" periods. Our group has recently investigated the effect of sublingual administration of apomorphine in patients suffering from Parkinson's disease. Sublingual apomorphine was shown to reduce extrapyramidal symptoms. The main characteristics of the pharmacodynamic effects of sublingual apomorphine in parkinsonians and the relationship between pharmacodynamic and pharmacokinetic effects are discussed. Sublingual apomorphine has the advantage of being easier to administer than subcutaneous injection. For the moment, the long-term use of sublingual apomorphine is limited by two major problems: first, time for dissolution and switch "on" (which is longer than after subcutaneous route) and secondly, the occurrence of local side effects (stomatitis). Further clinical studies using either more efficient (tablets with faster dissolution) and better tolerated sublingual formulations or other dopamine agonists should be carried on before recommending this approach in the treatment of Parkinson's disease.
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PMID:Sublingual apomorphine: a new pharmacological approach in Parkinson's disease? 874 21

Tetracyclines have been used as in vivo indicators of new bone formation because they form complexes with mineral at bone-forming surfaces. Four of 12 dogs in a bone-labeling study developed clinical signs of renal disease (vomiting, diarrhea, dehydration, and azotemia) within 1 to 2 days of receiving oxytetracycline at a bone-labeling dose of 25 mg/kg of body weight, once daily for 2 consecutive days. To delineate the relationship between oxytetracycline administration and renal damage, six dogs were given the bone-labeling dose intravenously and were subsequently evaluated by determination of clinical signs, serum biochemical analysis, urinalysis, and histologic examination (experiment 1). Drug administration was modified in the five dogs remaining in the bone-labeling orthopedic study. These dogs received the oxytetracycline dose as a slow intravenous infusion diluted with 250 ml of lactated Ringer's solution (experiment 2). All six dogs of experiment 1 developed persistent isosthenuria within 2 days of receiving the bone-labeling dose of oxytetracycline. Clinical illness (three of six dogs) was associated with azotemia, creatinemia, and hyperphosphatemia. All dogs had multifocal, mild to moderate flattening of renal tubular epithelium, characteristic of nephrosis. None of the dogs of experiment 2 developed any clinical indications of renal disease, and the only biochemical abnormality was isosthenuria in two of the five dogs. Thus the development of clinical signs and biochemical abnormalities associated with the intravenous administration of oxytetracycline was obviated by the slow administration of a dilution of the calculated bone-labeling dose of the antibiotic.
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PMID:Oxytetracycline-induced nephrotoxicosis in dogs after intravenous administration for experimental bone labeling. 890 81

The authors report a case of post-traumatic rhabdomyolysis in a victim of a car accident who, after having being initially examined at an emergency ward, was sent home having been requested to return for a control visit a few days later. The patient did not attend the control visit on the appointed day but returned to the same emergency ward eight days after the accident suffering from vomiting, general malaise and violent pain in the left forearm that appeared swollen. Anamnesis revealed a severe condition of rhabdomyolysis with dehydration, pale red urine and general signs of marked renal insufficiency. Tests showed marked myoglobinemia and myoglobinuria, very high CPK, azotemia, creatinemia, transaminase and high diastasemia. Given the disappearance of peripheral pulse and the severe neurovascular impairment of the left forearm caused by edematous compression, it was decided to proceed to surgical decompression using extensive longitudinal fasciotomy under supraclavicular anesthesia. After surgery peripheral pulse returned to normal, as was confirmed by Doppler. After adequate hydration while renal insufficiency lasted, hemodialysis was commenced immediately and repeated during the following days. Given that all the tests had improved and results were virtually within the norm, the patient was transferred to the medical ward after eight days for continuation of therapy. It is important to underline the importance of possible signs, such as oleguria, dark urine, swelling and edemas of the limbs, in injured patients. If renal insufficiency occurs, it is important to commence early hemodialysis. On day 23 the patient was again transferred to the intensive care ward because he presented epigastric pain and vomiting. CAT showed acute pancreatitis which resolved leading to full recovery after 20 days.
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PMID:[Traumatic rhabdomyolysis. A clinical case]. 901 71

Butyrates have been studied as cancer differentiation agents in vitro and as a treatment for hemoglobinopathies. Tributyrin, a triglyceride with butyrate molecules esterified at the 1, 2, and 3 positions, induces differentiation and/or growth inhibition of a number of cell lines in vitro. When given p.o. to rodents, tributyrin produces substantial plasma butyrate concentrations. We treated 13 patients with escalating doses of tributyrin from 50 to 400 mg/kg/day. Doses were administered p.o. after an overnight fast, once daily for 3 weeks, followed by a 1-week rest. Intrapatient dose escalation occurred after two courses without toxicity greater than grade 2. The time course of butyrate in plasma was assessed on days 1 and 15 and after any dose escalation. Grade 3 toxicities consisted of nausea, vomiting, and myalgia. Grades 1 and 2 toxicities included diarrhea, headache, abdominal cramping, nausea, anemia, constipation, azotemia, lightheadedness, fatigue, rash, alopecia, odor, dysphoria, and clumsiness. There was no consistent increase in hemoglobin F with tributyrin treatment. Peak plasma butyrate concentrations occurred between 0.25 and 3 h after dose, increased with dose, and ranged from 0 to 0.45 mM. Peak concentrations did not increase in three patients who had dose escalation. Butyrate pharmacokinetics were not different on days 1 and 15. Because peak plasma concentrations near those effective in vitro (0.5-1 mM) were achieved, but butyrate disappeared from plasma by 5 h after dose, we are now pursuing dose escalation with dosing three times daily, beginning at a dose of 450 mg/kg/day.
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PMID:Phase I study of the orally administered butyrate prodrug, tributyrin, in patients with solid tumors. 953 30

A 42-year-old man came to our emergency room hyperthermic (oral temperature, 42.4 degrees C), diaphoretic, and delirious. Other findings included labile blood pressure, sinus tachycardia (heart rate, 138/min), tachypnea (respiratory rate 34/min), muscle rigidity, and incontinence. Two days earlier, he had gone to a local clinic with complaints of abdominal pain, nausea, and vomiting. Promethazine was prescribed, and this was the patient's only medication on admission. Laboratory studies showed leukocytosis, hypernatremia, metabolic acidosis, elevated creatinine phosphokinase level, elevated transaminase levels, azotemia, hyperkalemia, hyperphosphatemia, hypocalcemia, and myoglobulinuria. The clinical and laboratory findings were characteristic of the neuroleptic malignant syndrome, with promethazine as the offending agent.
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PMID:Neuroleptic malignant syndrome due to promethazine. 1054 78

Membranoproliferative glomerulonephropathy was diagnosed in 5 of 7 adult Beagles from the same litter. Dogs were raised in more than 1 area of the United States. One died without evidence of renal disease when it was 3 years old. At 8 years of age, 2 dogs developed signs of uremia, including polyuria, polydipsia, and infrequent episodes of anorexia and vomiting. Serum biochemical variables and urine specific gravity values were consistent with renal azotemia. Both dogs had proteinuria. Although healthy, 3 of the 4 remaining Beagles had proteinuria. Of these 3, only 1 was azotemic. Membranoproliferative glomerulonephritis was diagnosed on the basis of results of histologic examination of renal biopsy specimens from 4 of the dogs. Electron microscopy performed on 3 of the renal biopsy specimens revealed identical lesions, consisting of an extremely thickened glomerular basement membrane with multilaminar splitting. Immunoglobulin or amyloid deposits were not detected. On the basis of similar clinicopathologic abnormalities, common genetic background, and identical histopathologic and electron microscopic findings, familial renal disease was diagnosed. Additional studies involving other related Beagles are needed to identify the hereditary nature of membranoproliferative glomerulonephropathy in Beagles.
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PMID:Familial glomerulonephropathy in a litter of beagles. 1063 17


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