Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Moxonidine is an imidazoline receptor modulator, specific for the I1-imidazoline receptor. The stimulation of imidazoline receptors represents a new mode of antihypertensive action to inhibit peripheral alpha-adrenergic tone by a central mechanism. Acute hemodynamic studies reveal moxonidine produces an acute fall of blood pressure and systemic vascular resistance. Heart rate, cardiac output, stroke volume, and pulmonary artery pressures are not affected. Left ventricular end-systolic and diastolic volumes are reduced. Ejection fraction is not significantly affected but 6-month studies showed a regression of left ventricular hypertrophy. After oral administration the maximum concentration of moxonidine is reached in about 1 hour, and elimination half-life is 2.5 hours, prolonged by renal insufficiency. The antihypertensive effect lasts longer than would be expected from the half-life. Open studies with moxonidine have revealed falls between 20 and 29 mmHg systolic, and between 10 and 19 mmHg diastolic blood pressure. In the largest study, over 12 months in 141 patients, most patients were controlled by 0.2 mg daily (58%) or 0.2 mg b.i.d. (38%). Moxonidine has been compared with representatives from each important class of antihypertensive drugs. In a crossover trial of clonidine in 20 patients, blood pressure control was similar, but the incidence of tiredness and dry mouth was less on moxonidine, as was the total number of patients experiencing side effects, 85% versus 30% (p < 0.01). In a larger parallel group study of moxonidine (n = 122) and clonidine (n = 30), blood pressure control was similar, but the overall incidence of side effects was less on moxonidine. In comparative studies of moxonidine with atenolol, ACE inhibitors, dihydropyridine calcium antagonists, hydrochlorothiazide, and alpha 1 blockade, the blood pressure control with representatives of these various classes of drugs was similar to moxonidine.
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PMID:Clinical experience with moxonidine. 806 79

Amantadine has found use primarily as an antiviral agent and in the symptomatic treatment of parkinsonism. However, the use of amantadine for the subjective alleviation of fatigue in multiple sclerosis and in the treatment of agitated aggressive behavior in the traumatic brain injured patient has also been described. Side effects of amantadine are primarily related to the central nervous system and include hallucinations, confusion, and nightmares. Toxic manifestations include acute psychosis, coma, cardiovascular toxicity, and death. Amantadine toxicity is a particular problem in patients with renal insufficiency because 90% of an oral dose is excreted unchanged in the urine. We present a case of amantadine-induced coma in a patient with multiple sclerosis and end-stage renal disease. Moreover, this degree of amantadine toxicity was profoundly apparent at a drug level usually not associated with such a severe presentation.
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PMID:Amantadine-induced coma. 821 67

Valsartan competitively and selectively inhibits the actions of angiotensin II at the AT1 receptor subtype which is responsible for most of the known effects of angiotensin II. In clinical trials in patients with mild to moderate essential hypertension valsartan was as effective as losartan, lisinopril, enalapril, amlodipine and hydrochlorothiazide. Addition of the latter reduced blood pressure in patients who did not respond sufficiently to valsartan monotherapy. Preliminary data also suggest valsartan may be effective in patients with severe essential hypertension. The drug was as effective as lisinopril as treatment for mild to moderate essential hypertension in patients with renal insufficiency and did not worsen renal function. Headache, dizziness and fatigue were the most common adverse events in placebo-controlled studies; the incidence of these adverse events was not significantly different between placebo and valsartan recipients. Compared with ACE inhibitors, valsartan was associated with a significantly lower incidence of dry cough. Thus, valsartan is an effective treatment for mild to moderate essential hypertension and may be particularly useful in patients who experience persistent cough during ACE inhibitor therapy.
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PMID:Valsartan. A review of its pharmacology and therapeutic use in essential hypertension. 925 84

Here, we report a 35-year-old man with non-fulminant acute non A, non B, non C hepatitis which developed into acute renal failure. The patient was admitted to hospital with the chief complaints of general fatigue, nausea and a high-grade fever of 40 degrees C. Laboratory examination revealed severe liver dysfunction and renal insufficiency on admission: his serum glutamic oxaloacetic transaminase was 3.203 IU/ml, serum glutamic pyruvic transaminase was 3.825 IU/ml, lactic dehydrogenase was 2.840 IU/ml, blood urea nitrogen was 65 mg/dl, and creatinine was 7.6 mg/dl. Hemodialysis was conducted during the initial 19-day period after admission because anuria was manifested on admission. On the 36th day after onset, renal functions returned to normal and the patient was negative for IgM-HA antibody. HBs antigen, IgM-HBC antibody, HCV antibody, cytomegalovirus antibody, and Epstein-Barr virus antibody. However, liver biopsy for histological examination on the 44th day after onset revealed no specific findings except the healing stage of acute hepatitis. Renal biopsy on the 49th day showed the healing stage of acute tubular necrosis without any glomerular change. It has been infrequently reported that acute renal failure develops following a non-fulminant acute state without hepatitis A, B or C virus infection. It is necessary to take acute renal failure into account in the clinical course of non-fulminant non A, non B, non C hepatitis.
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PMID:[Acute renal failure in non-fulminant acute hepatitis without hepatitis A, B or C virus infection]. 951 78

Previous data suggested interaction of cisplatin with interferon (IFN) in non-small cell lung cancer and a possible effect of IFN in maintaining remission in small cell lung cancer (SCLC). This study was designed to further examine the effect of IFN in the treatment of extensive disease (ED) SCLC. Forty previously untreated patients with performance status (PS) of 0-2 (Zubrod scale) were treated with etoposide (100 mg/m2 for 3 days), cisplatin (25 mg/m2 for 3 days) (EP), and recombinant IFN-alpha2a (rIFN-alpha2a) (5 x 10(6) U/m2 for 3 days) for six cycles (induction), followed by rIFN-alpha2a (5 x 10(6) U/m2) thrice weekly and megestrol acetate (40 mg q.i.d.) as maintenance therapy for 6 months or until progressive disease or intolerable toxicity was documented. Patients were 25 men (62%) and 15 women (38%), median age 58 (28-76), median Zubrod performance status 1 (0-2). Major sites of metastasis include liver (55%), bone (42%), bone marrow (25%), and adrenal gland (18%). Of 40 eligible patients accrued to this trial, 35 were evaluable for response, and 37 were evaluable for toxicity. There were 3 complete and 28 partial responses, for an overall response rate of 89%. With 39 of 40 patients followed until death, median survival (Kaplan-Meier) is estimated at 46 weeks (95% CI range 35-55). Twenty patients completed six cycles of induction, and 16 received maintenance therapy, median 2 cycles (range 1-3). Major toxicity during induction included grade 4 granulocytopenia in 24%, grade 2-3 nausea or vomiting or both in 41%, grade 2 fatigue in 24%, grade 2 anorexia in 22%, and grade 2-3 renal insufficiency in 9% of 175 total courses of chemotherapy administered. Toxicity during the maintenance phase was notable for grade 2-3 fatigue in 43%, grade 2-3 anorexia in 24%, grade 2-3 weight loss in 10%, and grade 3-4 anemia in 17% of 30 courses. There were no treatment-related deaths. The addition of rIFN-alpha2a to EP in induction chemotherapy of ED SCLC, followed by rIFN-alpha2a and megestrol acetate maintenance therapy, was reasonably well tolerated. The complete and overall response rates and duration of remission and survival appear to be similar to those generally obtained with EP alone in similar patients.
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PMID:Phase II trial of recombinant IFN-alpha2a with etoposide/cisplatin induction and interferon/megestrol acetate maintenance in extensive small cell lung cancer. 956 26

Multiple myeloma is characterized by the presence of bone pain, weakness, and fatigue. Ninety-eight percent of patients have an M-protein in the serum or urine at the time of diagnosis. Skeletal roentgenograms are abnormal in nearly 80%. Renal insufficiency (creatinine > or = 2 mg/dL) is present in one-fourth. The major causes of renal insufficiency are "myeloma kidney" and hypercalcemia. The diagnosis of multiple myeloma depends upon the presence of more than 10% plasma cells or a plasmacytoma plus an M-protein in the serum or urine or lytic bone lesions. Multiple myeloma must be differentiated from monoclonal gammopathy of undetermined significance and smoldering multiple myeloma. The plasma cell labeling index and the presence of circulating plasma cells in the peripheral blood are helpful in the differential diagnosis. Plasma cell leukemia, osteosclerotic myeloma (POEMS syndrome), and plasmacytomas are discussed. The heavy-chain diseases consist of alpha, gamma, and mu heavy-chain disease. The fibrils of primary amyloidosis consist of kappa or lambda monoclonal light chains. Weakness, fatigue, and weight loss are the most frequent symptoms. Macroglossia occurs in 10%. An M-protein is found in the serum or urine in 90%. The presence of nephrotic syndrome, renal insufficiency, congestive heart failure, orthostatic hypotension, or sensorimotor peripheral neuropathy, and an M-protein in the serum or urine suggest the possibility of primary amyloidosis. The diagnosis depends upon the demonstration of amyloid in tissues. The subcutaneous fat aspirate is positive in 80% while the bone marrow is positive in 55%. If these tissues are negative, one should obtain tissue from an involved organ.
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PMID:Clinical aspects of multiple myeloma and related disorders including amyloidosis. 1019 81

Farnesyl protein transferase (FT), an enzyme that catalyzes the first step in the posttranslational modification of ras and a number of other polypeptides, has emerged as an important target for the development of anticancer agents. SCH66336 is one of the first FT inhibitors to undergo clinical testing. We report a Phase I trial to assess the maximum tolerated dose, toxicities, and biological effectiveness of SCH66336 in inhibiting FT in vivo. Twenty patients with solid tumors received 92 courses of escalating SCH66336 doses given orally twice a day (b.i.d.) for 7 days out of every 3 weeks. Gastrointestinal toxicity (nausea, vomiting, and diarrhea) and fatigue were dose-limiting at 400 mg of SCH66336 b.i.d. Moderate reversible renal insufficiency, secondary to dehydration from gastrointestinal toxicity, was also seen. Inhibition of prelamin A farnesylation in buccal mucosa cells of patients treated with SCH66336 was demonstrated, confirming that SCH66336 inhibits protein farnesylation in vivo. One partial response was observed in a patient with previously treated metastatic non-small cell lung cancer, who remained on study for 14 months. This study not only establishes the dose for future testing on this schedule (350 mg b.i.d.) but also provides the first evidence of successful inhibition of FT in the clinical setting and the first hint of clinical activity for this class of agents.
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PMID:A Phase I trial of the farnesyl transferase inhibitor SCH66336: evidence for biological and clinical activity. 1076 74

A 57-year-old woman had been diagnosed as systemic sclerosis (SSc) with Raynaud's phenomenon, acrosclerosis and polyarthritis since 1995. She admitted to our hospital in July 1996 because of general fatigue, hemosputa and progressive renal insufficiency. On admission, the blood pressure was normal and laboratory findings showed elevation of the serum creatinin level and a high titer of the myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) (> 1000 EU). The renal biopsy revealed crescentic glomerulonephritis. Both renal insufficiency and high titers of MPO-ANCA improved remarkably after methylpredonisolone pulse therapy. This case was suggestive of elucidating the pathogenesis of SSc and MPO-ANCA related glomerulonephritis.
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PMID:[A case of myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) related glomerulonephritis associated with systemic sclerosis treated by steroid pulse therapy: a case report]. 1121 62

Cisplatin-based chemotherapy improves survival in appropriately selected patients with stage IV non-small cell lung cancer (NSCLC). However, cisplatin-based regimens have well-known dose-related toxicities, particularly renal insufficiency and neurotoxicity. On the basis of prior preclinical and phase I studies, we initiated a phase II study of SPI-77 (STEALTH) Liposomal Cisplatin) in patients with stage IIIB and IV NSCLC who failed previous treatment with platinum. Disease in all subjects had progressed during therapy, failed to respond, or progressed within 3 months after discontinuing the platinum-based chemotherapy. Between January and June 1999, 13 patients were enrolled at our institution. Patient characteristics included: seven women, six men; median age, 61 years; median Karnofsky performance status, 80%; median number of prior chemotherapy regimens, two (range, 1-3). All patients had adequate hepatic and renal function. SPI-77 was administered at a dose of 260 mg/m(2) IV every 3 weeks. A median of two cycles (range 1-6) were given; the total number of cycles was 35. Among the 12 patients evaluable for response, two had (17%) stable disease and ten (83%) had progressive disease. The median survival was 24.3 weeks, and the median follow-up was 43.9 weeks. Toxicity could be evaluated in all subjects. Moderate anemia (46% of cycles, <or=grade 2; 3% of cycles, >or=grade 3) with minimal granulocytopenia and thrombocytopenia (26% of cycles grade 1; 0% of cycles, >or=grade 2) were the most notable manifestations of myelosuppression. Grade 3 nonhematological toxicities included dyspnea (8%), fatigue (8%), and pain (8%). There were no grade 4 toxicities. These data suggest that this liposomal cisplatin formulation does not have appreciable activity in this population of patients with NSCLC who had received prior platinum-based chemotherapy. The lack of encouraging results from SPI-77 use in other phase I and II studies resulted in early closure of this trial by the manufacturer.
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PMID:A phase II study of STEALTH cisplatin (SPI-77) in patients with advanced non-small cell lung cancer. 1171 40

This presentation represents consensus recommendations on prognostic markers and criteria to initiate therapy in patients with Waldenstrom's macroglobulinemia (WM), which were prepared in conjunction with the Second International Workshop held in Athens, Greece during September 2002. The panel recommended that initiation of therapy should not be based on the IgM level per se since this may not correlate with the clinical manifestations of WM. The consensus panel agreed that initiation of therapy was appropriate for patients with constitutional symptoms such as recurrent fever, night sweats, fatigue due to anemia, or weight loss. The presence of progressive, symptomatic lymphadenopathy or splenomegaly provide additional reasons to begin therapy. The presence of anemia with a hemoglobin value of <or= 10 g/dL or a platelet count < 100 x 10(9)/L due to marrow infiltration also justifies treatment. Certain complications such as hyperviscosity syndrome, symptomatic sensorimotor peripheral neuropathy, systemic amyloidosis, renal insufficiency, or symptomatic cryoglobulinemia may also be indications for therapy. Recommendations for follow-up of watch-and-wait patients are that those with monoclonal gammopathy of undetermined significance (MGUS) should have serum protein electrophoresis repeated each year. Patients with asymptomatic (smoldering) macroglobulinemia should be evaluated every 6 months. Regarding prognostic markers, hemoglobin and beta(2)-microglobulin levels at diagnosis are important prognostic markers in WM: they influence the timing of treatment and survival. Age is a consistently important prognostic factor for survival. However, the panel felt that current data are inadequate to support the use of any prognostic marker to select the timing and type of therapy, and called for studies on the application of prognostic markers in WM.
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PMID:Prognostic markers and criteria to initiate therapy in Waldenstrom's macroglobulinemia: consensus panel recommendations from the Second International Workshop on Waldenstrom's Macroglobulinemia. 1272 Jan 19


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