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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This multi-center trial was carried out to assess the therapeutic potential of recombinant tumor necrosis factor (rTNF) as the first form of systemic therapy for advanced carcinomas of gastric and pancreatic origin. To be eligible patients were required to have no overt sign of coagulopathy and hepatic function studies with enzymes less than two times beyond the normal range. Twenty nine patients with gastric cancer and 26 with pancreatic cancer were entered from various institutions in the Southwest Oncology Group with 27 and 22, respectively, meeting eligibility criteria. Drug treatment consisted of rTNF (Genentech) given at a dose of 150 micrograms intravenously for five consecutive days every 3 weeks; 50% dose reduction was made for acute intolerance such as hypotension or severe fever and chills. Although eight patients with gastric cancer and five patients with pancreatic cancer received four or more courses of treatment, no objective antitumor responses were recorded. As in other trials common toxicities of rTNF included nausea and vomiting, chills and fever, hypotension, headache, myalgias, fatigue and malaise. However, in this trial, other toxicities became prominent: four episodes of symptomatic disseminated intravascular clotting occurred among patients with pancreatic cancer. Eleven with this disease and five with gastric cancer manifested laboratory findings of abnormal amounts of fibrin split products, and/or hypofibrinogenemia, and/or thrombocytopenia after treatment began. Other laboratory abnormalities that were commonly encountered included hyperglycemia, hypertriglyceridemia, anemia, neutropenia and an elevation in liver enzymes. We conclude that rTNF does not demonstrate antitumor efficacy against adenocarcinomas of the stomach and the pancreas.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:High incidence of coagualopathy in phase II studies of recombinant tumor necrosis factor in advanced pancreatic and gastric cancers. 152

Congenital malformations are the leading cause of the increased perinatal mortality in the infants of insulin-dependent diabetic mothers. The mechanisms(s) of diabetic teratologic development has yet to be defined. Hyperglycemia is known to depress aerobic metabolism in many organisms and cell lines. Reid hypothesized that exposure to hyperglycemia could result in decreased mitochondrial biogenesis in embryonic cells. Should these cells suddenly be changed to an environment of lower glucose concentration, decreased energy capabilities would exist until sufficient numbers of mitochondria could be regenerated. Such cells may not be capable of meeting temporal-spatial requirements, thereby resulting in structural abnormalities. In our study the explanted rat embryo model demonstrated that in the head-fold region hyperglycemia produced morphologic alterations of mitochondria but no difference in the number of mitochondria per cell. Specifically, embryos cultured in euglycemia demonstrated orthodox mitochondrial configuration, whereas those cultured in hyperglycemia had mitochondria in a condensed configuration. These findings were reversible. A modification of Reid's original hypothesis may provide an explanation for the mechanism of diabetic teratologic development.
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PMID:Effects of hyperglycemia on mitochondrial morphology in the region of the anterior neuropore in the explanted rat embryo model: evidence for a modified Reid hypothesis as a mechanism for diabetic teratogenesis. 175 Apr 57

Squash is a moderate- to high-intensity intermittent exercise. Players are active 50 to 70% of the playing time. 80% of the time, the ball is in play 10 seconds or less. The rest intervals fit a normal distribution with an average duration of 8 seconds. Heart rate increases rapidly in the first minutes of play and remains stable at approximately 160 beats/min for the whole match no matter what levels the players are. The energy expenditure for medium-skilled players is approximately 2850 kJ/h and over 3000 kJ/h for A grade players. The thermal and metabolic response to squash is similar to that of moderate intensity running. Hyperglycaemia, elevated free fatty acids and growth hormone levels, and low serum insulin values are the common metabolic changes. Blood lactate levels are understandably low due to the very short work to rest pattern of play. Injuries are not frequent in squash but they can occur. Serious eye injuries have been documented and as a result protective equipment is highly recommended. To reduce the possibility of sudden death on the court or after the game, older players that present some risk factors for cardiovascular disease should be warned against smoking after the game and informed of the serious implications of the development of chest pain, or undue tiredness before, during or after squash.
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PMID:Applied physiology of squash. 219 98

The diabetic hypersomolar state is defined by a serum glucose greater than 600 mg/dl and a serum osmolarity greater than 320 m Osm/L. Ketoacidosis or lactic acidosis may co-exist with DHS in the same patient. The incidence of this acute complication of diabetes is high enough (17.5 cases per 100,000 person-years) for primary care physicians to encounter a case every year or two. Predisposing factors include older age, female sex, nursing home residence, and infection. A substantial proportion of cases occur in patients with no prior history of diabetes. Common presenting signs include fatigue or weakness, polydipsia, polyuria, nausea, and alteration of consciousness. The mainstay of therapy is intravenous fluid replacement with close monitoring of glucose and electrolytes in a hospital setting. Current mortality figures are high, at 10% to 20%, and the chance of survival is adversely affected by older age, higher osmolarity, and the presence of an associated severe illness. Prevention includes screening for diabetes, educating diabetic patients and their care givers about the symptoms of hyperglycemia, prompt treatment of any infection in a diabetic person, avoidance of drugs that increase carbohydrate intolerance in diabetic people, and encouraging compliance with treatment of diabetes.
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PMID:The diabetic hyperosmolar state. 222 47

From 1969-1985, 106 people contracted tetanus in Finland. The outcome of the disease was good in 78 cases (returned to work), poor in 27 (12 died, 5 institutionalized and 10 retired) and unknown in 1. Poor outcome was the result of a disease requiring respirator treatment. Other clinical factors significantly correlated with poor outcome were blood pressure lability, hyperglycemia, hyperthermia, tachycardia and anticoagulation therapy. Forty people who were representative of the whole series with regard to sex, age and severity of disease attended a follow-up study on average 7 years and 4 months later. Forty age- and sex-matched controls had the same examinations, and compared with them, the 40 patients still had significantly more muscle fatigue and cramps, nervousness, decreased mental capacity and difficulties in balance, speech and memory. They also had more clinical findings, such as peripheral paresis, muscular atrophy, decreased or absent tendon reflexes and decreased mental capacity than the controls.
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PMID:Outcome and neurological sequelae of patients after tetanus. 261 76

We studied the effect of spontaneous long-term (9-10 months) diabetes on the heart of Chinese hamsters (CHAD strain) to elucidate the relationship between diabetes mellitus and cardiomyopathy. The diabetic hamsters, aged approximately 11 months, showed body weight loss, hyperglycemia (mean fasting plasma glucose 402 mg/dl), hypoinsulinemia, hyperlipidemia and ketonemia. The diabetic hamsters showed reduced activities of cytoplasmic glycolytic key enzymes; hexokinase, pyruvate kinase and phosphofructokinase, increases in cardiac glycogen and glucose-6-phosphate contents and a 40% decrease in cardiac ATP content, indicating decreased energy production. An accumulation of myocardial triglyceride and cholesterol was found in the diabetic hamsters. In addition, the cardiac norepinephrine content was increased in the diabetic hamsters, suggesting the presence of autonomic nervous disorder. Increased heart weight and thickening of the septum and both ventricular walls were found in the diabetic hamsters. Light-microscopic analysis revealed that 42.9% of the diabetic hamsters had myocardial degeneration without any vascular lesion of extramural large and intramural small vessels, whereas the non-diabetic controls had no myocardial or vascular lesions. These data suggest that the diabetic Chinese hamsters had cardiomyopathy, which is possibly caused by extravascular factors such as metabolic or autonomic nervous disorder although conclusive evidence is lacking.
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PMID:Metabolic and morphological changes of the heart in Chinese hamsters (CHAD strain) with spontaneous long-term diabetes. 366 31

Effectiveness of recombinant DNA (rDNA) human interferon alpha 2 (IFN alpha 2) in advanced breast cancer was evaluated in 14 patients who had received prior endocrine and/or cytotoxic therapy. After randomization, 7 patients received IFN alpha 2 two million IU m-2 day-1, s.c., 3 times a week (schedule 1) and 7 patients received 50 million IU m-2 day-1, i.v., for 5 consecutive days, every 3 weeks (schedule 2). Treatment duration was 4-21 weeks in schedule 1 and 6-24 weeks (2-8 courses) in schedule 2. Regressions were not achieved with either schedule. Treatment was associated with significant toxicity and was more severe in schedule 2. Dose limiting toxicities were leukopenia, elevation of liver enzymes, hyperglycemia and fatigue. Serum IFN activity was low or undetectable in patients on schedule 1 and high in patients on schedule 2. At 24 h, serum IFN activity was detectable in only 1/6 patients on schedule 1 as compared to 3/7 patients on schedule 2. IFN neutralizing factors were detected in the serum of only 1 patient prior to treatment but none were detected in any of the patients during or after discontinuation of treatment (4-24 weeks). IFN alpha 2 increased the expression of both HLA class 1 antigens and beta 2 microglobulin in peripheral blood lymphocytes in vivo. This effect was dose related.
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PMID:Recombinant DNA human interferon alpha 2 in advanced breast cancer: a phase 2 trial. 391 78

The present study evaluates the energy and skeletal muscle metabolism in malnourished patients, with and without cancer, in response to nutrition. The energy balance was positive in all patients receiving nutritional support. This led to an increase in body weight and body potassium levels. Glucose turnover increased in all patients. In patients with cancer, elevated glucose turnover reflected increased utilization of glucose preferentially for synthetic pathways rather than for oxidation. Protein synthesis and RNA content in skeletal muscles increased during nutrition. Nutritional support improved energy balance and protein synthesis capacity in skeletal muscles in patients with cancer to the same extent as in malnourished patients without cancer. Malignant cachexia seems to be a consequence of a relative lack of energy and not of impaired energy utilization in host tissues, at least early in the disease.
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PMID:Energy and tissue metabolism in patients with cancer during nutritional support. 681 8

A 58-year-old woman was admitted to our hospital for impaired consciousness, hyperglycemia and bitemporal hemianopsia. She was diagnosed as having NIDDM one year ago and was treated with diet and glibenclamide (1.25 mg/day) for 6 months. However, she stopped her medical treatment one month ago and then polydipsia and general fatigue were manifested. She was admitted to a hospital five days ago at which time hyperglycemia (405 mg/dl) and anemia (Hb8.0g/dl) were detected. She was transferred to our hospital for control of blood glucose and further examination of bitemporal hemianopsia. She showed typical acromegalic features including enlargement of the nose, lips and tongue, increased heel pad and acral growth. Conscious disturbance was cured by the infusion of saline and the administration of insulin. Endoscopy revealed an active gastric ulcer (A1). Endocrine data disclosed increased GH levels in plasma and urine, whereas plasma IGF-1 levels were low. Plasma GH paradoxically increased following the administration of TRH. A water deprivation test showed an impaired increase in urinary osmolarity, indicating partial central diabetes insipidus (DI). MRI with Gd-contrast revealed a macroadenoma which progressed toward suprasella. She was diagnosed as having acromegaly, partial DI and probable hyperosmolar hyperglycemic nonketotic diabetic pre-coma. Polyuria (5-101/day) due to partial DI was controlled by the administration of DDAVP (10 micrograms/day). The constant subcutaneous administration of octreotide (240 micrograms/day) resulted in normal plasma GH levels and a marked shrinkage of the pituitary tumor. The pituitary tumor was finally removed by the transsphenoidal approach following treatment with octreotide for 4 months. HE staining of the pituitary tumor showed atrophic and acidophilic cells surrounded by hyaloid connective tissue. After the surgery, plasma GH levels were normalized and complications were cured. In conclusion, this is a very rare case of acromegaly associated with diabetic pre-coma and partial DI, and effectively treated with constant subcutaneous infusion of octreotide.
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PMID:[Effective treatment with constant subcutaneous infusion of octreotide in a patient with acromegaly associated with diabetic pre-coma and diabetes insipidus]. 785 21

The Southwest Oncology Group (SWOG) studied the response rate and toxicity of merbarone (1,000 mg/m2 IV continuous infusion days 1-5, q 21 days) in patients with advanced metastatic renal cell carcinoma. Among 36 eligible patients, there was one partial response for a response rate of 3% (95% C.I. 0.1-15%). There were no mixed responses. There were no treatment related deaths or adverse drug reactions. Significant anemia, diarrhea, and hypercalcemia were observed. Mild to moderate degrees of malaise/fatigue/lethargy, dizziness/vertigo, hyperglycemia, creatinine increase, nausea, vomiting, weight loss, pedal edema, dyspnea, and granulocytopenia were noted. Merbarone does not have significant activity as a single agent in advanced renal cell carcinoma.
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PMID:Phase II evaluation of merbarone in renal cell carcinoma. 786 Feb 33


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