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 series of investigations suggest a specific role for BCAA in the regulation of respiration. In vitro incubation studies have shown that BCAAs improve the recovery of muscle force after fatigue. Further investigations revealed that leucine plays a key role in this action and acts in a manner not dependent on its use as an energy substrate. In humans, solutions enriched with BCAA have decreased PCO2 and stimulated the ventilatory response to hypercapnia, thereby corresponding to an enhanced ventilatory sensitivity with the administration of BCAA. The mechanisms for these actions are unknown. The most viable hypothesis is based on the ability of BCAA to decrease the synthesis of serotonin due to altered transport of AAs, including tryptophan, to the brain. Clinical studies have suggested a potency of BCAA in the treatment of respiratory dysfunction of preterm infants, as well as of patients with sleep apnea related to various disease states. The clinical applications of BCAA-enriched mixtures in respiratory diseases are still experimental, and many controversies exist concerning the validity of BCAA in clinical practice. Most TPN regimens contain BCAA approximating the average intake of BCAA in the Western diet. The question therefore remains whether additional BCAA supplementation is useful to achieve the suggested metabolic and pharmacological effects. Meticulous future studies are needed to establish the therapeutic value of BCAA in the treatment of various respiratory functions.
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PMID:Branched-chain amino acids and respiration. 142 77

Sonography revealed multiple echo-poor lesions in the liver of a 51-year-old man with nonspecific symptoms (fatigue, drop in performance, pressure sensation in the upper abdomen), increased blood sedimentation rate (68/110 mm) and evidence of cholestasis (gamma-GT 126 U/l, alkaline phosphatase 444 U/l, leucine-aminopeptidase 64 U/l). Under the diagnosis of liver metastases the primary tumour was looked for. These investigations and a fine-needle biopsy having proved unsuccessful, laparoscopy was performed. The biopsies so obtained showed whitish yellow, tight elastic structures indicating gummas of the liver in tertiary syphilis. Treponema-specific IgM antibodies in serum characterized active syphilis requiring treatment. Administration of antibiotics (penicillin 1 mega U daily i.m.; because of allergy replaced after four days by erythromycin 2 g daily for six weeks) resulted in complete normalization of all biochemical findings and, some time later, regression of the gummas. The patient has now been symptom-free for three years. This case illustrates the need even to-day of including syphilis in the differential diagnosis of unclear space-occupying lesions of the liver.
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PMID:[Tertiary syphilis with liver gummata]. 182 7

Recombinant human interleukin 2 (rIL-2) was administered by s.c. injection daily, 5 days/week to patients with metastatic renal cell carcinoma in an escalating dose regimen. Fifteen patients were entered in this study and are evaluable for toxicity with one patient not evaluable for response because of lack of measurable disease. The patient population had a median age of 63 years with initial performance status (Southwest Oncology Group criteria) of 0 in one patient, 1 in eight patients, and 2 in six patients. The starting dose was 5 x 10(5) Cetus units/m2/day with dose escalation to 1 x 10(6), 2 x 10(6), 4 x 10(6), and 5 x 10(6) Cetus units/m2/day scheduled at 2-week intervals if no significant toxicity or response was noted. Six patients were treated with drug doses of 2 x 10(6) Cetus units/m2/day or higher with a maximum daily dose achieved of 2 x 10(6) units/m2 in two patients, 4 x 10(6) units/m2 in two patients, and 5 x 10(6) units/m2 in two patients. Fatigue with decrease in performance status and elevations in serum creatinine were the most common reasons for limiting the dose or removing a patient from the study. Only one minor anti-tumor response was seen. Subcutaneously administered rIL-2 was able to alter immunological parameters. In two of the three patients tested, development of lymphokine-activated killer cell activity in vivo was seen, and statistically significant enhancement of natural killer cell activity compared to values from a concurrently run normal control was demonstrated. With treatment, there was a trend toward increased numbers of circulating total lymphocytes, OKT 8+, OKT 11+, Leu 7+, and Leu 11a+ cells and decreased numbers of circulating OKT 3+ and OKT 4+ cells. However, for the heterogeneous group of six patients monitored, results were not statistically significant compared to pretreatment values. The levels of rIL-2-specific antibodies were followed in the sera of 10 patients. Six of the 10 developed rIL-2-specific IgG during treatment with five of the six patients also developing neutralizing activity. Recombinant human interleukin 2 given by the s.c. route in the doses and schedule used in this trial can safely be given as an outpatient regimen with manageable toxicity. It may result in enhanced immune function in some patients but also results in a high incidence of antibody formation.
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PMID:Subcutaneous recombinant interleukin 2 in a dose escalating regimen in patients with metastatic renal cell adenocarcinoma. 220 37

Twenty-three patients with low natural killer syndrome (LNKS), 7 males and 16 females, are reported here. These LNKS patients had an age range from 14 to 77 years, with a median of 36.5 years. LNKS is a newly proposed category of immune disorders, being characteristically diagnosed by lowered NK cell activity against K562 target cells as a definite laboratory abnormality, in association with general clinical symptoms of remittent fever and uncomfortable fatigue, persisting without explanation for more than 6 months. Other immune parameters, such as the DNA synthesis of peripheral blood mononuclear cells (PBMCs) in either the presence or absence of mitogens, the T4+/T8+ ratio and the number of Leu-11+ PBMCs, were usually within the normal range. Also, routine laboratory tests did not detect any abnormal findings. The LNKS patients responded well to the administration of an immunopotentiator called 'lentinan', a glucan extracted from the Japanese mushroom Lentinus edodes, despite no responses to conventional fever treatments such as the administration of antipyretics or antibiotics. All LNKS patients observed were universally free of antibodies in their sera to human T-lymphotropic retroviruses I and III, and lymphadenopathy was infrequent, indicating that the LNKS is a syndrome independent of acquired immunodeficiency syndrome (AIDS) or AIDS-related complex. Antibodies to other known viruses tested such as Epstein-Barr or measles virus, or cytomegalovirus were also negative or not significantly elevated in the sera before the initiation of lentinan administration. If a virus is the cause of LNKS, it may be a new, unknown virus or an unknown substrain of known viruses. None of the LNKS patients has died of this syndrome.
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PMID:Low natural killer syndrome: clinical and immunologic features. 244 2

In this paper is reported a case of acute biphenotypic leukemia who was treated by chemotherapy and pursued its effect by two color flow cytometry. A 33-year-old male patient was admitted due to fever and general fatigue and diagnosed as acute leukemia by hematological findings. Surface markers were investigated to find positive reaction of Leu 12 (CD19), J 5 (CD10), My 7 (CD13) and My 9 (CD33), in which Leu 12 and My 9 were simultaneously expressed on the same blast cells by two color flow cytometry. He was treated with daunorubicin, enocitabine, mercaptopurine, vincristine, and prednisolone to obtain partial remission. Then, he was administered L-asparaginase, doxorubicin, vincristine and prednisolone to reach complete remission. The effect of chemotherapy was investigated by not only bone marrow puncture, but also by two color flow cytometry. From the findings in this case, the two flow cytometry was proved to be a useful tool for not only diagnosis of acute mixed leukemia, aut also the judgement of the effect of treatment.
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PMID:[Acute biphenotypic leukemia followed by two color flow cytometry]. 259 47

The uremic syndrome is multifactorial, and affects most tissues and organs. Disturbances in protein and amino acid metabolism may play important roles, especially in chronic uremia, either directly or by production of toxic metabolites, with resultant negative nitrogen (N) balance, muscle wasting, reduced protein synthesis, and characteristically abnormal intracellular free amino acid concentrations. There are also grossly abnormal amino acid levels in the plasma of uremic patients, e.g., increases in conjugated amino acids, high levels of several nonessential and low levels of essential amino acids. The ratios of tyrosine/phenylalanine and of valine/glycine are decreased. The low tryptophan levels may contribute to encephalopathy as a result of an imbalance in neurotransmitter synthesis. Citrulline is found in excess; the explanation is unresolved. There are elevated concentrations of the sulfur-containing amino acids: cystine, taurine, cystathionine, and homocysteine. Excess of the latter is implicated in the atherogenesis of renal failure. Disturbed metabolism and interorgan exchange of amino acids in the uremic state explains some of the abnormalities in tissue and plasma concentrations of individual amino acids. Enzymatic defects are involved in the disturbed metabolism of branched chain amino acids (BCAA), with possible antagonism among them, which impairs growth and amino acid utilization. Carbohydrate intolerance, associated with insensitivity of peripheral tissues to insulin and hyperinsulinemia, elicits decreased plasma BCAA. Protein synthesis rates in normal and pathological conditions are more closely related to the intracellular amino acid pool than to plasma amino acid levels. Concentrations of individual amino acids in the plasma pool are poor indicators of their intracellular concentrations. Muscle contains the largest pool of protein and free amino acids in the body. In chronic renal failure patients, the intracellular concentrations of valine, threonine, lysine, and carnosine are low. With low protein diets and in hemodialysis, serine, tyrosine, and taurine often are also low. The low taurine may be related to fatigue and to uremic cardiomyopathies. The commonly used amino acid supplements generally fail to correct the intracellular amino acid deficits. A "New Formula" has been developed to correct these intracellular amino acid abnormalities, and to supplement a low protein diet. It provides more valine than leucine, increased tyrosine and threonine, and less histidine, leucine, isoleucine, lysine, methionine, and phenylalanine than in formulas customarily used for patients with chronic renal failure. It is uncertain whether other ap
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PMID:Amino acid metabolism in uremia. 267 58

Based on a preclinical study demonstrating the synergistic antitumor effect of recombinant interleukin 2 (rIL-2) and beta-interferon (IFN-beta) on mouse tumors and previous results of a phase I study of rIL-2, a phase I study of combination therapy with human rIL-2 and IFN-beta was conducted in 26 patients with advanced malignancy. Patients were given rIL-2 by 24-h continuous i.v. infusion and IFN-beta by 2-h i.v. infusion for 5 days each week for 4 weeks. The common side-effects were fever, malaise, chills, appetite loss, and diarrhea. Leukocytosis and eosinophilia were observed in 56% and 69% of the patients, respectively. Transient leukopenia and thrombocytopenia were also observed in some patients. Dose-limiting manifestations were intolerable fatigue and liver dysfunction, and it was concluded that the maximum tolerated doses of rIL-2 combined with IFN-beta were 1.1 x 10(6) U/m2/day for rIL-2 and 6.0 x 10(6) IU/m2/day for IFN-beta. No patients achieved complete and partial response to therapy in this study. One patient with pulmonary metastasis from pharyngeal cancer showed a minor response. Natural killer (NK) and lymphokine-activated killer (LAK) activities increased during the 5 days of treatment and decreased during the 2-day intermission. The percentage of IL-2 receptor-positive cells increased markedly until Day 12, and gradually decreased thereafter. The percentage of OKT 4-positive cells and the OKT 4/OKT 8 ratio increased. In contrast, the percentage of Leu 7- or Leu 11-positive cells decreased over the 4-week treatment. A phase II study of this combination therapy is ongoing against head and neck cancer, and renal cell carcinoma.
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PMID:Phase I study of combination therapy with interleukin 2 and beta-interferon in patients with advanced malignancy. 278 85

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

Patients with liver disease have increased plasma concentrations of the endogenous opioid peptides methionine enkephalin and leucine enkephalin. As an initial investigation to determine whether opioid peptides contribute to any of the clinical manifestations of hepatic disease nalmefene, a specific opioid antagonist devoid of agonist activity, was given to 11 patients with cirrhosis. They all experienced a severe opioid withdrawal reaction on starting the drug. In the nine patients with primary biliary cirrhosis pruritus was greatly alleviated, fatigue seemed to improve, and plasma bilirubin concentration, which had been rising, showed a modest fall in all except one patient. These results indicate that blocking opioid receptors has an effect on some of the metabolic abnormalities of liver disease.
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PMID:Opioid peptides and primary biliary cirrhosis. 314 46

Denervated (1-10 days) rat epitrochlearis muscles were isolated, and basal and insulin-stimulated protein and glucose metabolism were studied. Although basal rates of glycolysis and glucose transport were increased in 1-10-day-denervated muscles, basal glycogen-synthesis rates were unaltered and glycogen concentrations were decreased. Basal rates of protein degradation and synthesis were increased in 1-10-day-denervated muscles. The increase in degradation was greater than that in synthesis, resulting in muscle atrophy. Increased rates of proteolysis and glycolysis were accompanied by elevated release rates of leucine, alanine, glutamate, pyruvate and lactate from 3-10-day-denervated muscles. ATP and phosphocreatine were decreased in 3-10-day-denervated muscles. Insulin resistance of glycogen synthesis occurred in 1-10-day denervated muscles. Insulin-stimulated glycolysis and glucose transport were inhibited by day 3 of denervation, and recovered by day 10. Inhibition of insulin-stimulated protein synthesis was observed only in 3-day-denervated muscles, whereas regulation by insulin of net proteolysis was unaffected in 1-10-day-denervated muscles. Thus the results demonstrate enhanced glycolysis, proteolysis and protein synthesis, and decreased energy stores, in denervated muscle. They further suggest a defect in insulin's action on protein synthesis in denervated muscles as well as on glucose metabolism. However, the lack of concurrent changes in all insulin-sensitive pathways and the absence of insulin-resistance for proteolysis suggest multiple and specific cellular defects in insulin's action in denervated muscle.
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PMID:Resistance of protein and glucose metabolism to insulin in denervated rat muscle. 319 84


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