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)

10-Edam (10-ethyl-10-deaza-aminopterin), an antifolate derivative, was administered to 14 chemotherapy-naive patients with advanced colorectal carcinoma. The drug was given weekly by intravenous route at an initial dose of 80 mg/m2, with escalation or attenuation according to tolerance. Mucositis was dose limiting and occurred in 11 of 14 patients (78.6%). Removal from the study was required in one patient due to progressive pulmonary fibrosis that was histologically identical to methotrexate-induced lung damage. Toxicity was otherwise mild to moderate and included diarrhea, constipation, abdominal discomfort, anorexia, nausea/vomiting, rash, and fatigue. There were no responses to 10-Edam in this study, 95% confidence interval (0-0.23). Stable disease was achieved in four patients; the remaining 10 patients demonstrated progression within 9 weeks of initiating systemic therapy. 10-Edam employed at this dosage and schedule was not effective as a treatment against advanced colorectal carcinoma.
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PMID:Phase II trial of 10-Edam in patients with advanced colorectal carcinoma. 230 19

The results of a serosurvey of Oklahomans for the presence of antibody to Ehrlichia canis is reported. Paired serum specimens, from patients lacking the serologic criteria for diagnosis of Rocky Mountain spotted fever (RMSF), were tested. A four-fold increase in E. canis-IFA antibody was found in 16/144 (11 percent) of these paired serum samples. Patients with serologic evidence of E. canis infection had a mean age of 34 years, 69 percent were male, and 63 percent lived in a town less than 10,000 population. Signs and symptoms included: fever 94 percent, headache 94 percent, fatigue 94 percent, anorexia 81 percent, nausea 60 percent, and rash 44 percent. When compared to control patients, whose sera were submitted for RMSF testing but did not meet serologic criteria for RMSF or E. canis, case-patients were more likely to have had leukopenia (OR = 4.9, 95 percent Cl = 1.2, 19.0) and tick exposure (OR = 9.5, 95 percent Cl = 1.4, 62.7). The results suggest E. canis, or a closely related agent, is a cause of human illness. Ticks are probable vector.
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PMID:Epidemiologic and clinical characteristics of persons with serologic evidence of E. canis infection. 231 66

Rickettsial infections of a spotted fever group have recently been experience in Japan. Although there have been 50 cases reported by this time, they were exclusively distributed in the areas along the Pacific coast. We report in this paper the first case of spotted fever group rickettsiosis in Shimane prefecture, an area faced to the Japan Sea. A 57 year-old man with high fever, general fatigue and rash was admitted to the hospital of Shimane Medical University at the end of September 1987, who had been treated with cefaclor for a few days without effect before his visit to the University Hospital. Physical examination revealed erythematous eruption, eschar on the left side of the abdomen, and generalized lymphadenopathy. Hepatosplenomegaly was not detected. Laboratory studies showed normal leukocyte counts with relative lymphopenia, high ESR and increased CRP. Transaminase levels were slightly elevated. Paul-Bunnel and Weil-Felix tests resulted in negative. Specific immunofluorescence tests demonstrated that IgG and IgM antibodies of acute-phase serum to Rickettsia japonica, a spotted fever group rickettsia isolated from patients in Japan, were not detected, while both IgG and IgM antibody titers of convalescent-phase serum increased to 1:320. Convalescent-phase serum reacted at significantly lower titers with R.typhi as well as other pathogenic spotted fever group rickettsiae. The patient was treated with ofloxacin for six days and then with combination of ofloxacin and minocycline. It should be noted that clinical symptoms such as high fever and general fatigue disappeared during a single therapy with ofloxacin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[A case report of spotted fever group rickettsiosis first encountered in Shimane Prefecture, Japan]. 233 50

A double-blind controlled, randomized, parallel, multicenter 12-week study was conducted to compare the antihypertensive efficacy of lisinopril with that of metoprolol in treatment of moderate to severe hypertension. Initially, 118 patients were recruited on lisinopril and 61 on metoprolol; and for the purpose of efficacy analysis at week 8, 115 patients on lisinopril and 60 on metoprolol were included. The doses of lisinopril or metoprolol were 40-80 mg/day and 100-200 mg/day, respectively. At week 4, the pretreatment diastolic blood pressure of 111 mm Hg was decreased to 97 mm Hg (p less than 0.01) with lisinopril: metoprolol decreased the diastolic blood pressure from 110 to 99 mm Hg (p less than 0.01). Similar decreases were noted at week 8; however, the drop in blood pressure with lisinopril was not significantly different from that with metoprolol. Systolic blood pressure also demonstrated a decrease of about 18 mm Hg with lisinopril and 12 mm Hg with metoprolol (p less than 0.01). This larger decrease in systolic blood pressure with lisinopril was statistically significant at week 4 (p less than 0.05). These decreases in systolic blood pressures were maintained at week 8, again with statistical significance (p less than 0.01). Of the 118 lisinopril-treated patients, four were discontinued from lisinopril therapy because of headache, dizziness, rash, flushing, or lymphadenopathy. Four patients out of 61 (9.8%) were discontinued from metoprolol therapy because of fatigue, somnolence, asthenia, weight gain, flatulence, tremor, or bronchospasm. In conclusion, lisinopril 40-80 mg once daily is as effective as metoprolol 100-200 mg once daily in reducing diastolic blood pressure in patients with moderate to severe hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evaluation of antihypertensive efficacy of lisinopril compared to metoprolol in moderate to severe hypertension. 244 53

The safety and tolerability of lisinopril were assessed in 1,476 patients [1,165 hypertensives and 311 patients with congestive heart failure (CHF)] and 211 normal volunteers. The duration of lisinopril therapy ranged from 1 day to 16 months, with a mean duration of 105 days. In the hypertensive population, the most frequent clinical adverse experiences on lisinopril alone were headache, dizziness, cough, and diarrhea. Not all of these adverse experiences were thought to be drug related. Five percent of patients were discontinued because of adverse clinical experiences; cough and dizziness were the most common reasons for discontinuation. Two of 1,165 (0.17%) hypertensive patients treated with lisinopril died, compared to 0.41% of hypertensive patients on other therapies. Neither case was considered to be drug related. In patients with CHF, the most frequent clinical adverse experiences were dizziness, diarrhea, hypotension, fatigue, headache, and rash. Not all of these adverse experiences were thought to be drug related. The percent of CHF patients discontinuing because of an adverse clinical experience was 7.4%; the most frequent causes for discontinuation were hypotension, dizziness, or renal impairment. Twelve deaths occurred in 311 CHF patients treated with lisinopril (3.9%) compared to 4/104 (3.8%) of CHF patients treated with placebo and 2/65 (3.1%) treated with captopril. Hypotension, orthostatic effects, or dizziness following the initial lisinopril dose occurred infrequently in patients treated with lisinopril. In hypertensive patients with normal renal function, including those treated previously or concomitantly with diuretic therapy, a first-dose hypotensive episode was reported in six of 955, or 0.6%. The incidence was higher (6.7%) in hypertensive patients with impaired renal function.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The safety and tolerability of lisinopril in clinical trials. 244 61

Based on the synergy of sequential methotrexate (MTX) and 5-fluorouracil (5-FU) in vitro and in vivo and the superior antitumor activity of trimetrexate (TMTX) compared with MTX in preclinical models, we carried out a phase I trial of TMTX and 5-FU (fixed dose, 400 mg/m2 per day), both given as 10-min i.v. infusions daily x 5 days, every 28 days. The TMTX dose was escalated from 3.0 to 14.0 mg/m2 per day. In all, 92 evaluable courses were given to 34 patients, half of whom were heavily pretreated with radiation or cytotoxics. Myelosuppression and mucositis were the dose-limiting toxicities but were not different in heavily or minimally pretreated patients; there were five episodes of moderate to severe mucositis. Rash, fatigue, and diarrhea were mild toxicities. Plasma TMTX elimination was biexponential, with a mean t.1/2 alpha of 0.23 h and a t.1/2 beta of 16.7 h. The area under the plasma TMTX concentration versus time curve increased linearly with dose, suggesting first-order elimination. Total plasma TMTX clearance (mean +/- SD) was 14.3 +/- 5.9 ml/min per m2. Renal clearance accounted for approximately 7% of total clearance, indicating biotransformation as the major route of elimination. TMTX was highly protein-bound (97%). Thus, TMTX can be given with 5-FU (400 mg/m2) on a daily x 5-day bolus schedule at the 12 mg/m2 per day dose level, which was the recommended dose of TMTX as a single agent for phase II studies using the 5-day bolus schedule.
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PMID:Phase I clinical and pharmacologic trial of trimetrexate in combination with 5-fluorouracil. 252 77

A mononucleosis-like illness is frequently recognized retrospectively as the first manifestation of infection with human immunodeficiency virus-type 1 (HIV-1). This acute but transient retroviral syndrome may include symptoms such as malaise, fever, sweats, myalgia, arthralgia, maculopapular rash, diarrhea, and lymphocytic meningitis. We observed two intravenous drug users who developed a severe, febrile illness with subsequent oral thrush (one also had biopsy-proven esophageal candidiasis). Both patients had weight loss, arthralgia, myalgia, and fatigue. These symptoms occurred two weeks after needle-sharing and persisted for 7 weeks in one patient and 10 weeks in the other. Both patients had serologic evidence for both acute HIV-1 and cytomegalovirus infection. Cytomegalovirus enhances HIV-1 replication in vitro, presumably by stimulating HIV-1 gene expression. Thus, the observed syndrome suggests that this viral interaction may be clinically significant because it appears to cause severe additional morbidity, which is not typical for primary infection with HIV-1. After 6 months of follow-up, one patient is completely asymptomatic but shows markedly reduced CD4+ lymphocytes. The other patient developed persistent lymphadenopathy after the acute illness, but is feeling well 21 months after infection.
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PMID:Co-infection with human immunodeficiency virus-type 1 (HIV-1) and cytomegalovirus in two intravenous drug users. 215 58

The safety and tolerability of lisinopril (1.25-160 mg daily) were assessed in 3,270 patients (2,688 hypertensives and 582 patients with congestive heart failure (CHF] and 280 healthy subjects. The duration of therapy ranged from a single dose to 43 months; 438 patients received lisinopril for at least 12 months (mean 20 months). In the hypertensive population, the most frequent adverse events reported were headache, dizziness, cough, nausea, diarrhoea and fatigue, although not all of these events were thought to be related to lisinopril; 6.1% discontinued lisinopril due to adverse clinical events, most commonly cough and nausea. Twelve hypertensive patients died (0.45%), but most of these were not receiving lisinopril at the time of death and none was considered to be drug-related. In CHF patients, the most frequently reported adverse events were dizziness, dyspnoea, diarrhoea, hypotension and fatigue. Again, not all of these reports were considered to be drug-related. Therapy was withdrawn in 9.6% of patients--hypotension, dizziness, diarrhoea and rash being the most frequent reasons. Fifty-three CHF patients died (9.1%) and in three cases death was considered to be related to lisinopril therapy. Hypotension, orthostatic effects or dizziness following the initial dose of lisinopril occurred infrequently (in 1.3% of the hypertensive group, including those receiving hydrochlorothiazide, and in 4.8% of CHF patients). Changes in laboratory parameters were generally minor and seldom resulted in discontinuation of therapy. Long-term treatment of hypertension and CHF with lisinopril for at least 3 years confirms that the drug is well tolerated. Overall, the side-effect profile is very similar to that of other ACE inhibitors with regard to class-specific effects. However, taste disturbance was rarely observed.
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PMID:Clinical experience with lisinopril. Observations on safety and tolerability. 255 Jun 41

Since the introduction of fenofibrate to European clinical practice in 1975, some 6.5 million patient-years of experience in the treatment of hyperlipidemia have been accumulated. A review of results of clinical trials shows fenofibrate to have a broad spectrum of lipid-lowering activity, reducing the total cholesterol level by 20-25% in type IIa patients and triglycerides by 40-60% in type IIb and IV patients. High levels of low-density lipoprotein cholesterol are reduced and, where low at baseline, high-density lipoprotein levels are increased. An associated activity is a 10-28% reduction in serum uric acid levels. Adverse reactions in the mostly open clinical trials ranged from 2-15%; mild gastrointestinal problems dominated, and occurred with much the same frequency in the placebo-treated groups of controlled trials. There are also reports of fatigue, headache, loss of libido, dizziness, and insomnia. Some excess of skin rash emerged as the only statistically significant unwanted clinical effect in one placebo-controlled trial. Biochemically, there are occasional fluctuations in serum transaminase values, while gamma-glucuronyl transferase and alkaline phosphatase are often decreased, all without apparent clinical significance. Lithogenicity of the bile is often increased above pretreatment levels, but there is no evidence from trials or postmarketing surveillance that the use of fenofibrate is associated with an increase of gallstone formation.
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PMID:Review of European clinical experience with fenofibrate. 265 20

Toxic shock syndrome (TSS), is an acute illness with four major criteria: involvement of multiple organ systems, fever greater than 38.9 degrees C, hypotension or shock and rash with subsequent desquamation. TSS was first reported by Todd et al. in 1978, and is a rare complication of staphylococcal infection. Although it at first was thought to be a childhood disease and an illness of menstruating women using intravaginal tampons, it has now been described as a complication of minor surgery, burns and minimal skin infections (Reingold et al., 1982; Jacobson et al., 1983). More than 2800 cases have been reported at the Centers for Disease Control (CDC) in Atlanta (Reingold, 1985). Jacobson and Kasworm (1986) estimate the incidence after nasal surgery to be 16.5 per 100.000, which in fact is higher than the incidence in women of menstrual age using intravaginal tampons. TSS usually occurs within 24-48 hours after surgery, often starting with nausea and vomiting. Although the syndrome can be lethal or can have troublesome sequelae, as prolonged weakness fatigue and neuropsychological disturbances, complete recovery is often the case.
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PMID:Toxic shock syndrome after nasal surgery: is prevention possible? A case report and review of the literature. 267 75


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