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)

A phase I trial of Roussel-Uclaf recombinant human interleukin 2 (IL 2) was performed on 31 cancer bearing patients of the Institut Gustave-Roussy, Villejuif, and the Institut Curie, Paris. This study allowed to define a schedule for administration of IL 2 in continuous infusion over 5 day cycles. This schedule is manageable in patients without major visceral failure. It is reproducibly feasible in conventional medical oncology units, without specialized intensive care facilities. Toxicities, although numerous, are acceptable for IL 2 doses below 24,000,000 IU/m2/day. There is a close relationship between secondary effect severity and IL 2 doses received. Main toxicities were: fever with chills, fatigue and general discomfort in 23 patients, nauseas and vomiting in 12, diarrhea in 10 and cutaneous rashes with erythema and dermal vascularitis in 13. One peculiar feature of this study was the minimal occurrence of manifestation related to leaky capillary syndrome prominant in other studies. Oliguria, functional renal failure and edema were observed in only 4 patients with functionally unique kidney. Five patients had severe anemia, 2 grade III thrombocytopenia, 1 grade IV hepatic cytolysis, 4 severe confusion episodes and 2 hypothyroidism with anti-thyroid microsome auto-antibodies. All these toxicities were reversible after withdrawal of IL 2 treatment. During this phase I trial, 3 therapeutic objective responses were observed, all 3 occurring in patients with metastatic melanoma treated with IL 2 doses equal to, or above 16,000,00 IU/m2/d. Recombinant IL 2 Roussel-Uclaf thus can be administered through a simple, manageable and efficient regimen.
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PMID:[Phase I trial of a recombinant human interleukin 2. Results in patients with disseminated solid tumors]. 182 63

Twenty-five assessable patients with metastatic melanoma have been entered in a multicenter phase II study of two induction cycles of human recombinant interleukin-2(IL2), 18 x 10(6) IU/m2/d continuous intravenous (IV) infusion on days 1 to 5 and days 12 to 17. Dacarbazine (DTIC), 850 mg/m2 IV bolus was given on day 26. The cycle was repeated at 5 weeks. Maintenance therapy was scheduled 3 weeks after the completion of induction treatment, consisting of IL2, 18 x 10(6) IU/m2/d for 5 days alternating with DTIC, 850 mg/m2 IV every 3 weeks, for a total of 18 weeks. Six patients responded (24%); two complete and four partial. Stable disease was seen in five patients. None of the six patients with more than two sites of metastases responded. Maximum response was observed in the first 3 months of treatment. Progression-free periods of 6 months and longer were seen in the two complete responders (8 and 17+ months), in two of the four partial responders (7 and 12+ months), and in three of the five patients with stable disease (9+, 15, and 17+ months). Toxicity included fever, skin rash, fatigue, anorexia, and diarrhea in most patients. Two patients had a weight gain of more than 10%. Eight patients needed intensive care for the observation and treatment of a myocardial injury (one patient), ventricular tachycardia (one), hypotension and oliguria (four), and sepsis (two). Sequential treatment with IL2 and DTIC appears to be effective but not clearly better than could be expected of IL2 alone.
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PMID:Sequential administration of recombinant human interleukin-2 and dacarbazine in metastatic melanoma: a multicenter phase II study. 187 25

To document the clinical presentation of malignant accelerated hypertension in Nigerians, 56 patients were studied between 1987 and 1989 (30 months). Age range was 16 to 55 years with 59% in the range of 30-49 years; 47 were male. Mean systolic and diastolic blood pressures were 217 mmHg and 146 mmHg, respectively. Thirty patients had grade III and 26 grade IV hypertensive retinopathy. Mean body mass index was only 22.4 in the 21 patients who had no evidence of fluid retention. Seventy-five percent of patients had no awareness of hypertension. Essential hypertension accounted for 66%, chronic renal disease 32% and renal artery stenosis 2% of cases. The most common clinical features were headaches (80%), fatigue (68%), oliguria (52%), heart failure (46%), weight loss (41%), and poor vision (21%). Multiple symptoms were common and 24 patients had both renal and cardiac failure. Laboratory features included microscopic haematuria (100%) and proteinuria (100%). In 37 patients with essential hypertension, renal failure was a complication in 60%. Microangiopathic haemolytic anaemia was present in 23 patients. In addition to eight deaths from renal failure in the acute stage, 23 of these patients required long-term dialysis. Thus, malignant accelerated hypertension was associated with high morbidity, especially renal failure; it primarily afflicted patients in their prime years. Known survival at one year was 37.5%, but some patients were lost to follow-up.
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PMID:The clinical presentation of malignant hypertension in Nigerians. 195 31

Altitude sickness is a clinical syndrome that occurs with abrupt ascents to altitudes of 3000 metres and above. Symptoms include headache, malaise, fatigue, dizziness, anorexia, nausea and vomiting, and oliguria. At higher altitudes more severe illness resulting from pulmonary oedema or cerebral oedema can occur.
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PMID:Altitude sickness. 232 86

Preclinical data suggest synergy of interleukin-2 (IL-2) combined with alpha-interferon (IFN). In addition, toxicities of IL-2 may be decreased by intermittent continuous infusion. The purpose of this trial was to determine the maximum tolerated dose (MTD) of recombinant IL-2 combined with alpha-IFN in patients with renal cancer, colon cancer, melanoma, and malignant B-cell disease. IL-2 was given by continuous i.v. infusion at an initial dose of 5 X 10(5) units (U)/m2/d for 4 days plus IFN at 6 X 10(6) U/m2/d intramuscularly days 1 and 4 weekly for 4 weeks. Patients who achieved a response or stable disease received an additional 4 weeks of therapy. IL-2 doses were increased to 1, 2, 3, 5, and 7 X 10(6) U/m2/d with three to eight patients at each dose level, at each of the two participating institutions. The dose of IFN was 6 X 10(6) U/m2 days 1 and 4 for all but five patients whose IFN dose was doubled to 12 X 10(6) U/m2/d. Forty-three patients were entered on this study with 34 completing at least 4 weeks of therapy. Six patients were taken off study because of Grades III or IV pulmonary, neurologic, or cardiac toxicity; one for progressive disease; one for CNS metastases, and one for personal reasons. All of the toxicities were reversible. Chills and fever were universal, especially on days 1 and 4. Mild and moderate nausea, vomiting, diarrhea, anorexia, malaise, and cutaneous erythema were present in most patients. Fluid retention and occasional pleural effusions were observed at the higher IL-2 doses but were not dose-limiting. Significant hypotension associated with oliguria was seen, and these patients were treated with vasopressors and colloids. None of the patients required ICU admission. Thirty-four patients were evaluable for response. There were 4/18 (22%) renal cell patients who experienced a partial response. No responses were seen in patients with melanoma, lymphoma, or colorectal cancer. The combined debilitating symptoms of fatigue, diarrhea, hypotension, fluid retention, and anorexia defined the MTD as 5 X 10(6) U/m2/d of IL-2 and 6 X 10(6) U/m2 of alpha-IFN.
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PMID:A phase I study of recombinant human interleukin-2 and alpha-interferon-2a in patients with renal cell cancer, colorectal cancer, and malignant melanoma. 238 96

Recombinant interleukin-2 (rIL-2) (NSC# 600664; Hoffmann-La Roche, Inc., Nutley, NJ) was studied in a phase I clinical trial in 33 patients with advanced, measureable cancer of the colon or malignant melanoma, Eastern Cooperative Oncology Group (ECOG) performance status O-1, and no prior chemotherapy or radiotherapy. The goal of the study was to identify a dose and schedule of IL-2 to generate maximal immune modulation with tolerable toxicity. Such a regimen might allow the addition of other treatment modalities and/or prolonged treatment duration in later trials. Each patient received IL-2 as a continuous 24-hour infusion once weekly for 4 weeks and then twice weekly for 4 weeks. Five treatment groups received from 10(3) U/m2 to 3 x 10(7) U/m2 per 24-hour infusion. The maximal tolerated dose was 3 x 10(7) U/m2/d twice weekly. Patients treated twice weekly at 1 x 10(7) and 3 x 10(7) U/m2/d had immune modulation in terms of lymphocytosis, eosinophilia, increased natural killer (NK) activity, and elevated numbers of peripheral blood mononuclear cells expressing CD16, OKT10/Leu-17, and Leu-19 surface markers. Endogenous generation of peripheral blood lymphokine-activated killer (LAK) activity was demonstrated by lysis of NK-resistant Daudi targets, in patients treated at 3 x 10(7) U/m2/d. Biochemical and hematological abnormalities were moderate and reversible. Clinical toxicity included hypotension, myalgia, arthralgia, stomatitis, fever, fatigue, nausea, headache, chills, diarrhea, and oliguria at high doses. Cardiovascular toxicity was tolerable for most patients and reversed after IL-2 was stopped. Two of six melanoma patients at 3 x 10(7) U/m2/d achieved partial responses by the end of the eighth week. This IL-2 schedule appears to produce potentially clinically useful immune enhancement with tolerable toxicity.
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PMID:A phase I clinical trial of recombinant interleukin-2 by periodic 24-hour intravenous infusions. 278 32

The Orellanus syndrome is a rare nephrotoxic disease caused by several fungi of the genus Cortinarius. For a long time the sole report of this syndrome was a mass intoxication in Poland. About 32 cases of Orellanus syndrome caused by Cortinarius orellanus, speciocissimus and splendens have been described in recent years. A few other species are also suspected of being nephrotoxic. The syndrome is characterized by a delayed latency period of 2 days to 3 weeks, and a chronic evolution involving fatigue, anorexia, headache, thirst, pains in the lumbar region and renal insufficiency with oliguria and anuria, and the clinical picture by reversible or irreversible interstitial nephritis. In this report the clinical and mycological features are summarized.
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PMID:[Orellanus syndrome: mushroom poisoning with kidney insufficiency]. 713 47

Simvastatin belongs to a class of lipid-lowering drugs which completely inhibit 3-hydroxy-3-methylglutaryl co-enzyme A (HMG CoA) reductase. The commonest adverse effects of therapy with simvastatin HMG CoA reductase inhibitors are gastro-intestinal disturbance, myositis and myopathy. Rhabdomyolysis leading to renal failure has been reported, but it appears to be very rare, except in patients also receiving cyclosporin, nicotinic acid or gemfibrozil. Here we report the case of an elderly lady who was known to have chronic renal failure, but who developed rhabdomyolysis following simvastatin therapy. Her symptoms of muscle pain, fatigue, myoglobulinuria, oliguria and pulmonary oedema appeared 48 h after the first dose of simvastatin. Simvastatin was immediately stopped, and the patient was dialysed for 1 week. Her renal function improved and came back. We suggest that extreme care should be exercised in prescribing this drug, particularly for the elderly with renal impairment.
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PMID:Simvastatin-induced rhabdomyolysis in a patient with chronic renal failure. 1127 41

A 43-year-old man, with a history of central diabetes insipidus diagnosed 3 years previously, complained about reduced libido. An MRI scan showed a suprasellar lesion just below the supraoptic recess of the third ventricle. A stereotactically guided biopsy revealed fibrous glia, but no other specific tissue and no inflammatory cells. Two months later the patient presented with fatigue and muscular weakness. Tertiary adrenal failure and hypothyroidism were diagnosed by endocrine function tests and therapy with levothyroxine and hydrocortisone was started. Another 2 months later the patient was admitted with giddiness, nausea, peripheral oedema and oliguria. Radiological imaging and an open transperitoneal kidney exploration showed severe fibrosis around both ureters. Histological examination confirmed the diagnosis of idiopathic retroperitoneal fibrosis. Presumably the suprasellar tumour was the first manifestation of retroperitoneal fibrosis. Once the diagnosis 'idiopathic retroperitoneal fibrosis' is confirmed, fibrotic manifestations and complications involving extra-retroperitoneal tissues including the endocrine system, should be sought.
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PMID:Panhypopituitarism associated with severe retroperitoneal fibrosis. 1120 44

A Japanese girl aged 13 years with myeloperoxidase anti-neutrophil cytoplasmic antibodies(MPO-ANCA)-associated glomerulonephritis(GN) progressed to end-stage renal failure after 7 years' clinical observation. She had been suffering from recurrent disease flare associated with serum MPO-ANCA elevation(i.e. 153 EU/ml, 208 EU/ml and 358 EU/ml, maximum at each of the episodes, normal < 10 EU/ml). Each flare was treated successfully with prednisolone combined with cyclophosphamide and azathioprine. However, her renal function gradually deteriorated, and peritoneal dialysis(PD) was initiated 7 years after the onset of the disease. During the clinical course, no extrarenal manifestations were observed. Due to subsidence of the serum MPO-ANCA titer(10 EU/ml) after starting PD, prednisolone and azathioprine were tapered thereafter. Her daily urine volume was preserved at approximately 600 ml at that time. She suddenly developed fatigue with severe anemia, oliguria and hypertension 4 months after discontinuation of immunosuppressive therapy. The serum titer of MPO-ANCA increased to 100 EU/ml. These clinical observation suggests that disease flare may occur in selected patients with MPO-ANCA-associated GN, who develop end-stage renal failure requiring PD. Although recurrent flare associated with an increased serological activity in a proportion of patients with lupus nephritis who have received dialysis has been reported to date, to our knowledge, a similar clinical observation in the MPO-ANCA-associated GN has not been reported. Selected patients with the disease should be followed with close observation after undergoing dialysis.
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PMID:[A case of ANCA-associated glomerulonephritis without extrarenal symptoms with disease flare after starting dialysis]. 1221 82


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