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)

Survival of media-suspended porcine erythrocytes exposed to various hydrodynamic environments was investigated with and without such shear protectant additives as bovine serum albumin, dextran and the non-ionic surfactant Pluronic F68. Erythrocytes provided a model cell population with cells of a uniform size, metabolic state and shear tolerance. Because the cells were non-growing, any shear adaptation effects were avoided. Cell lysis was followed by microscopic counts or release of haemoglobin. The cells were susceptible to agitation damage in unaerated shake flasks agitated at 100 rpm or greater. Relative to additives-free operation, the presence of 0.1% (w/v) dextran or albumin prolonged cell survival, but Pluronic F68 actually enhanced cell lysis in flasks agitated at 100 rpm. The protective effect of the additives depended on the hydrodynamic conditions. The protective effect of albumin was demonstrated also in aerated conditions in a split-cylinder airlift bioreactor (aspect ratio of 8.8; riser-to-downcomer cross-sectional area ratio of 1.0; specific power input of 0.34 W m-3). Comparison of the cell lysis characteristics in the airlift device and the best case performance of the shake flask showed longer survival in the flask (100 rpm); however, the length of survival in the reactor (approx. 70 h) was sufficient for practical purposes. In all cases, the cell lysis pattern conformed initially to zero-order dependence in cell concentration, becoming first-order after varying degrees of exposure to hydrodynamic forces. Fatigue failure of cells was inferred.
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PMID:Effects of the hydrodynamic environment and shear protectants on survival of erythrocytes in suspension. 857 20

Anemia is often associated with neoplastic disorders. Blood transfusions are used to alleviate the discomfort of anemic cancer patients. Of 246 terminally ill cancer patients admitted to our palliative care unit from October 1991 to December 1993 (128 women and 118 men), 31 patients (12.6%) (17 men and 14 women; age, 69.5 +/- 12 years) received on average 2.8 units of packed red blood cells (PRBCs) (range, 2-7 units/patient) in 35 separate admissions. PRBCs were transfused in the presence of low hemoglobin (Hb) levels ( < or = 8 g/dL) and/or severe fatigue or dyspnea. Pre-transfusion performance status, cognitive function, dyspnea, and fatigue at rest (evaluated by a four-point scale), complete blood count, serum albumin, and C-reactive protein were determined. The day after transfusion, subjective well-being was recorded as "yes/no" improvement in comparison with the pre-transfusion day. Improved subjective well-being after blood transfusion was reported in 51.4%, without significant relationship to pre-transfusion Hb levels or performance status. The influence of blood transfusion on subjective well-being was not related to the severity of dyspnea or fatigue. Twenty-one patients (60%), including seven with subjective improvement, died during the same hospitalization, a median of 49 days after transfusion. Pre-transfusion Hb level did not differ significantly in patients who benefited and did not benefit from transfusion, whereas time before death was significantly (P < 0.001) shorter in patients who did not benefit. In the discharged patients (40%), the median interval between transfusion and discharge was 13 days and the frequency of subjective improvement in well-being was 78.6%. Our data suggest that two main areas should be investigated, namely the relation between low Hb levels and symptoms and signs in terminally ill cancer patients, and the correct timing for effective blood transfusion. A combination of criteria is needed for effective transfusion; they must include not only Hb levels but also type and severity of anemic symptoms and signs. Furthermore, the identification of reliable prognostic indicators for survival would be useful.
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PMID:Use of red blood cell transfusions in terminally ill cancer patients admitted to a palliative care unit. 920 50

In this study perceived well-being and functioning in 28 uraemic patients (14 women and 14 men, mean age 54 years) were measured in the predialysis stage during conservative renal therapy and 3-9 months after having started maintenance dialysis treatment. The patients had participated in a patient education programme in the predialysis stage. Disease-specific symptoms, perceived health (Health Index), functional (SIP) and emotional (STAI) status were analysed. The results showed that there were no significant differences in the patients' correction of uraemia, frequency of symptoms or anxiety prior to and after having started dialysis. After having started dialysis treatment, fatigue, lack of energy and functional disability in work increased while disability in recreation and pastime decreased. Standard bicarbonate correlated significantly to the symptoms of leg cramps and itching. Serum albumin correlated significantly to eating dysfunction in the SIP. There was a large variation within the group with regard to their self-rated disturbances. Some patients reported a relatively intact quality of life, some reported a moderate influence, and some a severe decrease in quality of life irrespective of whether they were in the predialysis state or on maintenance haemodialysis or CAPD. In conclusion, dialysis treatment resulted in increased fatigue and lack of energy, while disease-specific symptoms, functional disability and anxiety did not increase during the first months on dialysis. The symptoms of itching and leg cramps correlated significantly with level of metabolic acidosis, and eating disability correlated with serum albumin levels, indicating that biochemical variables should be combined with patient assessment of health and well-being in order to optimize treatment and care. Moreover, the wide range of scores in all the research variables indicates that assessment of quality of life can be helpful in allocating support to those patients in need of it.
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PMID:Well-being and functional ability in uraemic patients before and after having started dialysis treatment. 934 57

Menetrier's disease (MD) or polyadenomes en nappe is a form of hypertrophic gastropathy occurring primarily in middle-aged males. Patients generally present clinically with dyspepsia and, on occasion, with hypoproteinemic edema and anemia. The latter feature, when combined with the radiographic appearance of the stomach in MD, can lend to confusion with carcinoma and malignant lymphoma. To illustrate this diagnostic problem, a case is reported of a 41-year-old female who initially presented to her family physician with symptoms of easy fatigue and dyspnea on exertion and signs of pallor and ankle edema. Pertinent laboratory findings included a hemoglobin of 2.8 g/dL, hematocrit of 10.3 percent, mean corpuscular volume of 63.4 mu 3, a serum albumin of 2.7 g/dL, and heme positive stools. Endoscopic examination revealed a circumferential polypoid mass involving the cardia and fundus of the stomach with relative sparing of the antrum. A CT scan of the abdomen and pelvis showed a large mass in the stomach which the radiologists and gastroenterologists believed probably represented a lymphoma or gastric carcinoma. A total gastrectomy specimen exhibited features of MD. Routine bright-field microscopy and immunohistochemical reactivity for transforming growth factor-alpha confirmed the diagnosis of MD. Moreover, ulceration of the tips of some of the hypertrophied gastric folds provided an explantation for the iron deficiency anemia. Awareness that MD may present with anemia will help in the differential diagnosis with lymphoma and carcinoma.
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PMID:Menetrier's disease presenting with iron deficiency anemia. 951 79

GI1147211 is a 7-substituted 10,11-ethylenedioxy-20(S)-camptothecin analogue that inhibits the nuclear enzyme topoisomerase I. In this Phase I and pharmacological study, 24 patients with advanced solid malignancies received a total of 72 courses of GI147211 as a 30-min infusion daily for 5 consecutive days, at doses ranging from 0.3 to 1.75 mg/m2/day. Severe neutropenia precluded dose escalation above 1.5 mg/m2/day in minimally pretreated patients, and both severe neutropenia and thrombocytopenia were dose limiting in heavily pretreated patients at doses above 1.0 mg/m2/day. These doses are, therefore, recommended for subsequent Phase II evaluations of GI147211 in patients with comparable prior therapy. Nonhematological toxicities, including nausea, vomiting, fatigue, and anorexia, were mild to moderate. The disposition of GI147211 in blood was described by a linear three-compartment model, with renal elimination accounting for only 11% of drug distribution. No relationship was observed between the pharmacological exposure to GI147211 and effects on neutrophils; however, patients who developed dose-limiting myelosuppression did experience greater exposure to both the lactone and total forms of the drug. The hydrolysis kinetics of GI147211 revealed not only a shift of the drug to the inactive carboxylate form in human serum albumin but also stabilization of the lactone in erythrocytes, perhaps accounting for the observed lactone:total area under the concentration-time curve ratio of 0.27. These results indicate that GI147211 exhibits predictable toxicities and that further studies are warranted to determine the distinct role of this compound among currently available camptothecin analogues.
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PMID:Phase I and pharmacokinetic study of GI147211, a water-soluble camptothecin analogue, administered for five consecutive days every three weeks. 953 26

Four women aged 30, 29, 52 and 43 years presented with what appeared to be subacute thyroiditis (De Quervain's thyroiditis). This disease is characterized by fatigue, a painful thyroid gland and thyrotoxic manifestations. The diagnosis is further based on a high erythrocyte sedimentation rate and low tracer uptake during thyroid scintigraphy. Only the first patient showed a typical course. In the second and third ones the painful thyroid was associated with nodular enlargement. Fine needle aspiration cytology was at first consistent with subacute thyroiditis but a repeated aspiration showed papillary carcinoma in the second and anaplastic carcinoma in the third patient. In the fourth one, subacute thyroiditis was accompanied by normochromic anaemia, a low serum albumin concentration and liver function disorders. She made a full recovery without treatment. Thyroid malignancies can mimic subacute thyroiditis. Persistent nodular enlargement of the thyroid is suspicious and requires careful investigation.
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PMID:[A painful inflammation of the thyroid]. 976 25

BACKGROUND: In an elderly population of surgical patients, poor mobility, poor diet and chronic disease contribute to a significant risk of malnutrition. Malnutrition is associated with muscle weakness, fatigue, poor wound healing and immunological dysfunction. The aim of the study was to establish the prevalence of malnutrition in vascular surgical patients and to compare postoperative infection rates in well nourished and malnourished patients. METHODS: A nutritional assessment was performed on 71 patients (49 men; median age 65 (range 26-85) years) attending preassessment for vascular surgical procedures. Nutritional status was measured using validated indicators of malnutrition: estimated weight changes over 3 months; body mass index; mid-arm muscle circumference (MAMC) calculated using triceps skin fold thickness (TSF) and mid-arm circumference (MAC) (MAMC = MAC - (3.14 x TSF)); and serum albumin concentration. Fifty-nine patients were followed after vascular surgery. The incidence of postoperative infections was related to preoperative nutritional status. RESULTS: Nineteen patients (27 per cent) had normal values for all nutritional indicators examined. The remaining 52 patients (73 per cent) had one (37), two (12), three (two) or four (one) nutritional indicators within the range for malnutrition. Among the 59 patients who underwent surgery there were five chest infections, seven wound infections, one urinary tract infection and one infected central line in 13 patients following six femorodistal bypasses, four abdominal aortic aneurysm repairs and three miscellaneous arterial procedures. The incidence of septic complications was zero in 14 patients with normal nutritional indicators and 41 per cent (13 of 32) in patients with indicators of malnutrition (P < 0.05, Fisher's exact test). CONCLUSION: Malnutrition is prevalent among vascular patients and may contribute to postoperative morbidity. Malnourished patients should be identified and referred to the dietician at the earliest opportunity to minimize the morbid effects of undernutrition.
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PMID:Vascular surgical society of great britain and ireland: contribution of malnutrition to postoperative morbidity in vascular surgical patients 1036 Dec 8

Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease that predominantly affects middle-aged women; fatigue and pruritus are the most common symptoms at presentation. Liver function tests are consistent with cholestasis and reveal an elevation of serum alkaline phosphatase and gamma-glutamyl transpeptidase with or without elevation of aminotransferase levels. Histologically, PBC is characterized by the destruction of the intrahepatic small bile ducts and subsequently fibrosis. The serological hallmark of the disease is the presence of antimitochondrial antibodies, which are found in 95% of patients with PBC. The antimitochondrial antibodies are directed against the 2-oxo-acid dehydrogenase complexes located on the inner membrane of the mitochondria. PBC generally slowly progresses, even over decades, and may lead to liver failure. In symptomatic patients, advanced age, elevated serum bilirubin levels, decreased serum albumin levels, and cirrhosis each correlate with shortened survival. Immunosuppressive and anti-inflammatory drugs have been used in the treatment of PBC based on the presumed autoimmune pathogenesis, but satisfactory agents leading to complete reversal or cure of the disease are not available. At present ursodeoxycholic acid appears to be the only effective therapy in preventing or delaying the need for liver transplantation and improving survival. However, a number of patients receiving ursodeoxycholic acid still develop progressive disease and require transplantation; transplantation is the only effective therapy at the end stage of the disease.
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PMID:Primary biliary cirrhosis: from induction to destruction. 1135 23

Chronic obstructive pulmonary disease (COPD) is a leading cause of death, and constitutes a major medical and an increasing economic problem for acute and long term care. A low level of irreversible airway obstruction when in stable condition, hypercapnia, hypoxia, the presence of comorbid heart disease, right ventricular failure, and low serum albumin are the main factors related to risk of exacerbations. Bronchial infections, bronchospasm, left ventricular failure, pneumonia, pneumothorax and thromboembolism are described as the most frequent relapsing causes of COPD. During exacerbation, the inflammatory process, the ventilation/perfusion (V'A/Q') mismatching, an increased airflow resistance and dynamic hyperinflation (PEEPidyn) expose the respiratory muscles to the risk of fatigue, eventually leading to ventilatory pump failure and rising hypercapnia. Prevention of exacerbations and subsequent hospitalisations may be obtained with careful rehabilitation programs, a strict drug protocol, long term oxygen therapy and sometimes using home noninvasive mechanical ventilation (NMV). During exacerbation proper management of infection and lung mechanics derangement has to be adopted using an accurate assessment of severity and standardized treatment protocols. Patient history and examination and functional tests are beneficial to decide how and where to treat these patients. Mechanical ventilation (possibly noninvasive) may be required to reverse the acute episode. The aims of all these procedures remain: i) to prolong length and quality of life; ii) to save costs. Both hospital and post-discharge mortality of exacerbated COPD remain high while quality of life appears to be poor. Future studies will elucidate the relation between number and severity of exacerbations and prognosis.
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PMID:Exacerbations of COPD: predictive factors, treatment and outcome. 1149 3

The cytotoxicity of hydroquinone (HQ) and several of its metabolites was studied using freshly isolated proximal tubular (PT) kidney cells from rats. Incubations were conducted for periods of up to 4 h at 37 degrees C, with cytotoxicity measured either as increased leakage of lactate dehydrogenase or as a decreased energy status, as determined by decreased ratios of adenosine triphosphate (ATP) to adenosine diphosphate (ADP). Incubation atmospheres consisted of either 95% O(2)/5% CO(2), to promote cell viability in vitro, or 5% O(2)/5% CO(2)/90% N(2). Preliminary studies with bovine serum albumin (BSA) added to the incubation media indicated a lack of toxicity for HQ or its metabolites. For the tests discussed in this report, incubations were performed without the addition of BSA. Under 95% O(2) atmospheres, PT cells from male Fischer F344 rats were significantly more sensitive to HQ than those from male Sprague-Dawley (SD) rats, with decreases in ATP to ADP ratios seen as early as 0.5 h at a concentration of 0.5 mM. When incubations were performed under a 5% O(2) atmosphere, 2-(cysteine-S-yl)hydroquinone (Cys-HQ) and HQ toxicities were observed later (3-4 h) in the incubation period, occurred at higher concentrations, were similar in magnitude for the two strains, and were greater for Cys-HQ than for HQ. These results show that variations in oxygen tension can dramatically influence the toxicity of HQ and its metabolites. The specific compounds tested that were cytotoxic at a physiologically relevant oxygen tension (5%) were (in decreasing order of potency): Cys-HQ > 2-(glutathion-S-yl)hydroquinone > HQ. These results support an association of toxicity with metabolism through the glutathione pathway, with ultimate toxicity associated with the cysteinyl conjugate. Biochemical characteristics of PT cells from these two strains suggest a significantly greater capacity of cells from the SD rat to respond to oxidative stress.
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PMID:The effect of oxygen tension on the cytotoxicity of hydroquinone and selected hydroquinone metabolites to isolated rat renal proximal tubular cells. 1508 69


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