Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recombinant human interleukin 2 (rIL-2) was administered by s.c. injection daily, 5 days/week to patients with metastatic renal cell carcinoma in an escalating dose regimen. Fifteen patients were entered in this study and are evaluable for toxicity with one patient not evaluable for response because of lack of measurable disease. The patient population had a median age of 63 years with initial performance status (Southwest Oncology Group criteria) of 0 in one patient, 1 in eight patients, and 2 in six patients. The starting dose was 5 x 10(5) Cetus units/m2/day with dose escalation to 1 x 10(6), 2 x 10(6), 4 x 10(6), and 5 x 10(6) Cetus units/m2/day scheduled at 2-week intervals if no significant toxicity or response was noted. Six patients were treated with drug doses of 2 x 10(6) Cetus units/m2/day or higher with a maximum daily dose achieved of 2 x 10(6) units/m2 in two patients, 4 x 10(6) units/m2 in two patients, and 5 x 10(6) units/m2 in two patients. Fatigue with decrease in performance status and elevations in serum creatinine were the most common reasons for limiting the dose or removing a patient from the study. Only one minor anti-tumor response was seen. Subcutaneously administered rIL-2 was able to alter immunological parameters. In two of the three patients tested, development of lymphokine-activated killer cell activity in vivo was seen, and statistically significant enhancement of natural killer cell activity compared to values from a concurrently run normal control was demonstrated. With treatment, there was a trend toward increased numbers of circulating total lymphocytes, OKT 8+, OKT 11+, Leu 7+, and Leu 11a+ cells and decreased numbers of circulating OKT 3+ and OKT 4+ cells. However, for the heterogeneous group of six patients monitored, results were not statistically significant compared to pretreatment values. The levels of rIL-2-specific antibodies were followed in the sera of 10 patients. Six of the 10 developed rIL-2-specific IgG during treatment with five of the six patients also developing neutralizing activity. Recombinant human interleukin 2 given by the s.c. route in the doses and schedule used in this trial can safely be given as an outpatient regimen with manageable toxicity. It may result in enhanced immune function in some patients but also results in a high incidence of antibody formation.
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PMID:Subcutaneous recombinant interleukin 2 in a dose escalating regimen in patients with metastatic renal cell adenocarcinoma. 220 37

Interferon-beta-serine (IFN-beta-ser) is a muteine, recombinant IFN that is tolerated at a dose fivefold to 10-fold higher than IFN-alfa and interacts with the same cell membrane receptor as IFN-alfa. We hypothesized that at high doses IFN-beta-ser might induce a higher response rate than IFN-alfa in metastatic renal cell carcinoma. We undertook a phase II trial of IFN-beta-ser in patients with metastatic renal cell carcinoma. Patients were treated three times each week by a 2-hour intravenous infusion. Doses were escalated weekly (.25 to 5.5 mg, 1 mg = 180,000,000 U) until the maximum-tolerated treatment dose (MTTD) was determined. The MTTD is defined as one dose level less than that which caused grade 3 toxicity and was subsequently administered three times weekly for at least 4 weeks. Twenty-nine patients were entered, and 25 were assessable for response and toxicity. The performance status was 0-1 in all patients and only one patient received previous chemotherapy. The MTTD dose was 2.5 mg (range, 0.5 to 5.5 mg per treatment), although in 10 patients, doses were later deescalated because of cumulative toxicity. Initial dose-limiting toxicity and cumulative toxicity were fatigue, malaise, and fever in most patients. Hepatic transaminitis, neutropenia, and elevation of serum creatinine were also observed but were not dose-limiting. There was one complete response (CR) and four partial responses (PRs). All responses but one occurred in pulmonary metastases. The median time to response was 26 days (range, 17 to 102 days). These data demonstrate that IFN-beta-ser given in high doses exhibits significant antitumor activity in renal cell carcinoma; however, the objective response rate is 20%. This is no higher than previous IFN studies; therefore, we reject the hypothesis than IFN-beta-ser at high doses may induce a greater response rate than IFN-alfa. However, we did observe more responses than were seen in a similar trial undertaken with lower dose IFN-beta serine in renal cell carcinoma.
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PMID:Phase II trial of interferon-beta-serine in metastatic renal cell carcinoma. 233 72

A phase I trial and pharmacokinetic study of 5-aza-2'-deoxycytidine (5-aza-dCyd) were conducted in 21 patients with advanced solid tumors. The drug was given as three 1-h infusions, separated by intervals of 7 h. Treatment was repeated every 3-6 weeks. Forty-six cycles of 5-aza-dCyd were administered at 7 dose levels ranging from 25 to 100 mg/m2 in three infusions. The dose-limiting toxicity was myelosuppression, with a delayed white blood cell nadir, occurring at Day 22. Other toxicities included a mild, reversible elevation of serum creatinine in three patients, minimal nausea and vomiting in six patients, and transient fatigue in three patients. In this study one partial response in a patient with an undifferentiated carcinoma of the ethmoid sinus was observed. Plasma and urinary concentrations of 5-aza-dCyd were measured using a bioassay based on growth inhibition of L1210 leukemia cells in vitro. For 75 and 100 mg/m2 given as 1-h infusions, mean peak plasma concentrations of 0.93 and 2.01 microM, respectively, were attained. In seven of nine courses at doses of 25-60 mg/m2, plasma 5-aza-dCyd concentration was less than 0.01 microM. In one case at 30 mg/m2 and another at 60 mg/m2, peak plasma drug concentrations were determined to be 0.244 and 0.409 microM, respectively. Following cessation of the infusion rapid disappearance of drug from plasma was observed with a t1/2 alpha and t1/2 beta of 7 and 35 min, respectively. High clearance values and a total urinary excretion of less than 1% of the administered dose suggest that 5-aza-dCyd is eliminated rapidly and largely by metabolic processes. For the present schedule studied, a dose of 75 mg/m2 in three infusions, every 5 weeks, is recommended for phase II trials in solid tumors.
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PMID:Phase I and pharmacokinetic study of 5-aza-2'-deoxycytidine (NSC 127716) in cancer patients. 242 59

A randomized, parallel, double-blind study was performed with lisinopril, a long-acting angiotensin-converting enzyme inhibitor, versus captopril, a shorter-acting angiotensin-converting enzyme inhibitor, in the treatment of congestive heart failure. All patients were in New York Heart Association class II, III or IV and had remained symptomatic despite therapy with digoxin and diuretics. After a 4 to 14 day placebo baseline period, patients were randomized to receive either lisinopril, 5 mg orally once per day (n = 94), or captopril, 12.5 mg orally three times per day (n = 95), in addition to continuation of digoxin and diuretics. The dose of study drug could be doubled at 4 week intervals for a total of 12 weeks of double-blind therapy. The maximal dose was 20 mg once per day of lisinopril or 50 mg three times per day of captopril. The addition of either lisinopril or captopril to a regimen of diuretics or digoxin, or both, caused an increase in exercise duration as assessed on a motorized treadmill. When protocol violators were excluded, patients receiving lisinopril had a statistically greater increase in exercise duration than that of patients receiving captopril. In patients with renal impairment (serum creatinine greater than 1.6 mg/dl at baseline), lisinopril was superior to captopril in improving exercise duration. Lisinopril, but not captopril, increased left ventricular ejection fraction in patients with moderately to severely (less than 35%) decreased function (p less than 0.05). Improvement in functional capacity and quality of life, as assessed by the Yale Scale dyspnea/fatigue index, was significantly greater for the lisinopril group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Short- and long-acting angiotensin-converting enzyme inhibitors: a randomized trial of lisinopril versus captopril in the treatment of congestive heart failure. The Multicenter Lisinopril-Captopril Congestive Heart Failure Study Group. 215 58

The present study was conducted to estimate the effects of the physical load of instructors during ice skating camp. The subjects were 9 instructors aged from 20 to 24. To discover measures to relieve the physical load, we measured 1) urinary excretion of catecholamine (noradrenaline; NA, adrenaline; A), 17-OHCS, creatinine and nitrogen; N each day, 2) subjective symptoms of fatigue three time a day (morning, after skating, and at night), 3) nutrient intakes, 4) performed a time study and 5) measured the heart rate during skating instruction. The main results obtained were as follows: 1) The mean heart rate during skating instruction was 98.4-113.1 beats/min. 2) Urinary excretions of NA, A, and 17-OHCS were observed to have increased gradually during skating camp. The values of NA, A and 17-OHCS in the skating camp period were significantly higher than those of daily life. Subjective symptoms of fatigue were also increased gradually. The construction of symptom clusters was of the I-dominant type (I greater than III greater than II) at each point. 3) Intakes of energy, carbohydrate, protein and fat during the skating camp period were higher in comparison with those of daily life. 4) Urinary-N and creatinine levels during the skating camp period showed no changes. N-intake/urinary-N of the skating camp period tended to be higher than that of daily life. 5) In the time study, mean energy consumption was 3300-3400 kcal/day. The mean time of skating instruction was 218-227 min. The sleeping time was observed to have decreased gradually.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[A study on the effects of the physical load of instructors during ice skating camp]. 263 76

Copper refinery workers exposed to selenium were studied before, during, and after a shutdown period. Urine selenium levels were 83 +/- 30 mumol/mol creatinine and 69 +/- 27 mumol/mol creatinine when measured on two occasions during exposure compared with 56 +/- 17 mumol/mol creatinine when the workers had been free of exposure for 10 wk during a shutdown. The refinery workers reported more nose and eye irritation, indigestion, stomach pain, and fatigue than controls. "Garlic-like" breath odor was reported to be personally and socially offensive by many of the workers. Reporting of symptoms, pulmonary function indices, and laboratory test results did not change with exposure except for hemoglobin level, which rose during the shutdown. Hemoglobin levels were found to be inversely correlated with the urine selenium level, and there was a positive correlation noted for the interactive effect of urine selenium and urine arsenic levels on hemoglobin.
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PMID:Health status of copper refinery workers with specific reference to selenium exposure. 268 43

Twenty-four evaluable patients with metastatic melanoma have been entered in a multicentre Phase II study of two induction cycles of human recombinant interleukin-2 (rIL-2) 18 x 10(6) IU/m2/day continuous i.v. bolus on days 1-5 and days 12-17. Dacarbazine (DTIC) 850 mg/m2 i.v. bolus was given on day 26. The cycle was repeated at five weeks. Maintenance therapy was scheduled three weeks after the completion of the induction treatment, consisting of rIL-2 18 x 10(6) IU/m2/day for five days alternating with DTIC 850 mg/m2 i.v., every three weeks, for a total of 18 weeks. Median age was 44 years (range 23-80), and Karnofsky index was 100 (range 80-100). One patient had received prior chemotherapy with hydroxyurea and one patient had prior radiotherapy. Six patients responded (25%): two had complete responses (CR) and four had partial responses (PR). Stable disease (SD) was seen in five patients. Responses occurred in the following sites: liver 2/9 (22%), lung 3/14 (21%), skin 2/11 (18%), and lymph nodes 3/12 (25%). Duration of CR was 11+ and 13 months. PRs lasted 2, 5, 7, and 11+ months. Of note, time to progression in patients with SD was similar to that of responders: 4, 4, 11+, 11+, and 14+ months. Toxicity included fever, skin rash, fatigue, anorexia, and diarrhoea in most patients. Two patients had a weight gain of more than 10%. Hypotension requiring vasoactive agents or interruption of rIL-2 occurred in four patients, creatinine elevations WHO grade 1-2 in seven patients, and bilirubin elevations WHO grade 1-3 in six patients. One patient developed transient ventricular tachycardia. It appears that rIL-2 and DTIC in this schedule is feasible and effective, but not clearly superior to rIL-2 alone.
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PMID:Sequential administration of recombinant human interleukin-2 and dacarbazine in metastatic melanoma. A multicentre phase II study. 269 78

The effectiveness of enalapril 10-40 mg/day as first choice treatment of mild (90-104 mmHg, n = 37), moderate (105-114 mmHg, n = 21), or severe (115-130 mmHg excluding accelerated hypertension, n = 16) essential hypertension was studied in an open multicentre trial. Enalapril alone controlled the hypertension (diastolic blood pressure 90 mmHg or less) in 25 patients (34%). Of these, 20 had mild and 5 had moderate hypertension. The remaining patients required either enalapril plus hydrochlorothiazide 12.5 or 25 mg/day (n = 30), or a third drug of the physician's choice (n = 9). A relationship was present between baseline blood pressure and the number of drugs required to achieve blood pressure control. Plasma creatinine increased beyond the limits of laboratory error in 3 patients, and from 100-108 mumol/l (p less than 0.05) on enalapril alone in a subgroup of patients who ultimately required a diuretic. Enalapril was well tolerated; 60 (73%) had no drug related side effects during active treatment. Tiredness (n = 5), headache (n = 4), dizziness (n = 4) and palpitations (n = 3) were the most frequent side effects. Cough was a feature in 3 patients and 1 patient had a rash. This study suggests that enalapril is an effective and well tolerated anti-hypertensive agent in mild, moderate or severe hypertension, but that caution may be required in patients with impaired renal function.
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PMID:Enalapril as first choice treatment of mild, moderate and severe essential hypertension: results of an open multicentre clinical trial. New Zealand Hypertension Study Group. 283 97

A 60-year-old woman who for many years had been taking salicylate-containing tablets for headaches, was admitted to hospital, in a somnolent state, because of increasing weakness, tiredness, memory and speech disorders, and tinnitus. Laboratory tests revealed a decompensated metabolic acidosis (pH 7.25), renal insufficiency (creatinine 2.3 mg/dl) and a decreased Quick value (63%). Whole-blood acetylsalicylic acid concentration was markedly elevated to 330 micrograms/ml. After treatment of the acidosis with bicarbonate and forced diuresis she at first regained consciousness, but clouding of consciousness again occurred eight hours later progressing to coma with unequal pupils and seizure potentials in the electroencephalogram. Status epilepticus without motor component was diagnosed, perhaps the result of a dysequilibrium of acid-base balance between blood and cerebrospinal fluid. The signs and symptoms were quickly reversed under treatment with clonazepam.
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PMID:[Cerebral complications in chronic acetylsalicylic acid poisoning]. 291 58

Cilazapril (CIL), a new angiotensin-converting enzyme inhibitor, was evaluated for 16 weeks in 29 patients with mild to moderate essential hypertension (diastolic pressure 95 mm Hg to 115 mm Hg). Twenty-four patients (83%) normalized their blood pressure (BP) (diastolic pressure less than 90 mm Hg), 11 with low-dose CIL, six with high-dose CIL, one with high-dose CIL plus low-dose thiazide, and six with high-dose CIL and high-dose thiazide. Three withdrew because of side effects (fatigue, bloating, and polyuria). Statistically significant reductions in sitting and standing systolic and diastolic pressures occurred at 8 and 16 weeks on CIL. There was no change in standing or sitting heart rate, white blood cell count, creatinine clearance, urine protein levels. This is the first long-term data on this new converting enzyme inhibitor in human beings.
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PMID:Efficacy and safety of cilazapril, a new angiotensin-converting enzyme inhibitor. 297 Aug 56


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