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)

Chronic fatigue syndrome (CFS) is a newly-recognized clinical entity characterized by chronic, debilitating fatigue lasting longer than six months. Common associated findings are chronic and recurrent fever, pharyngitis, myalgias, adenopathy, arthralgias, difficulties in cognition and disorders of mood. In the majority of patients, the illness starts suddenly with an acute, 'flu-like' illness. The following abnormalities are seen with some frequency although none are seen in all patients: lymphocytosis, atypical lymphocytosis, monocytosis, elevation of hepatocellular enzymes, low levels of antinuclear antibodies, low levels of immune complexes. Clinical and serologic studies suggest an association of CFS with all of the human herpesviruses, particularly Epstein-Barr virus (EBV) and the recently-discovered human B-lymphotropic virus (HBLV) or human herpesvirus-6; neither EBV nor HBLV has yet been shown to play a causal role in the illness.
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PMID:Chronic fatigue syndromes: relationship to chronic viral infections. 284 19

This report describes a patient who developed a malignant proliferation of granular lymphocytes following Epstein-Barr virus (EBV) infection. For many months, his illness resembled prolonged infectious mononucleosis with persistent fatigue, fever, leukocytosis, and serologic evidence of recent primary EBV infection. After approximately 1 year, however, he developed progressive granular lymphocytosis and extensive lymphocytic infiltration of the bone marrow and liver. Tests for EBV DNA in pre- and postmortem tissue samples using a sensitive DNA hybridization technique were negative. Southern blot analysis of DNA prepared from blood mononuclear cells demonstrated clonal T-cell antigen receptor gene rearrangement. Despite increased numbers of circulating lymphocytes with the morphology and surface phenotype of normal donor natural killer (NK) cells, the patient's NK activity was consistently depressed in a standard in vitro assay. However, in vitro incubation with interleukin-2 (IL-2), but not with alpha- or gamma-interferon, increased the NK activity of the patient's lymphocytes. Intravenous recombinant IL-2 treatment transiently increased the patient's blood NK activity and was associated with seroconversion to EBV nuclear antigens but failed to affect the progression of his disease. Our findings indicate that clonal granular lymphocytic proliferation may develop after EBV infection and confirm the utility of DNA hybridization analysis in distinguishing monoclonal from benign immunoreactive lymphoproliferation. Furthermore, our results suggest that certain functionally inert neoplastic granular lymphocytes acquire NK activity when exposed to IL-2.
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PMID:Malignant granular lymphoproliferation after Epstein-Barr virus infection: partial immunologic reconstitution with interleukin-2. 303 37

Eleven patients received four consecutive weekly cycles of human recombinant interleukin 2 (IL-2) by continuous infusion for 4 days/week. Two dose levels were tested, 1 and 3 X 10(6) units/m2/day. Toxicities experienced by most patients included fever, rigors, fatigue, anemia, eosinophilia, and liver function abnormalities. All side effects from treatment reversed and no severe or life-threatening problems occurred. A marked lymphocytosis was seen following the 4 weeks of therapy. Fresh lymphocytes obtained during this lymphocytosis mediated enhanced destruction in vitro of a natural killer cell-resistant tumor cell line (Daudi). The increase in the absolute number of circulating lymphocytes and their enhanced ability to mediate direct lysis of Daudi targets resulted in a greater than 100-fold mean increase in cytotoxic potential by the end of IL-2 treatment. One patient, with renal carcinoma, who was treated at 3 X 10(6) units/m2/day experienced a sustained measurable response with greater than 50% regression of pulmonary and hepatic metastases. Five patients were retreated with a second course of IL-2, lasting 4 weeks. This therapy was well tolerated in four of these five patients, with similar immunological changes occurring. No further antitumor responses were seen in these patients. Thus, a relatively well tolerated immunotherapy regimen using IL-2 can induce dramatic increases in lymphocyte number and augment their in vitro antitumor reactivity.
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PMID:Clinical and immunological effects of recombinant interleukin 2 given by repetitive weekly cycles to patients with cancer. 325 45

Long-term subcutaneous (s.c.) administration of recombinant Interleukin-2 (rIL-2) was evaluated in 18 patients with advanced malignancy who received escalating doses of rIL-2 (1.0-9.8 X 10(6) U/m2) s.c. five times per week for a median of 38 days (range 5-228 days). Prior to the s.c. phase of the study, 24 patients received low doses (50 or 350 mg/m2) of cyclophosphamide (CPM) i.v. on day 1 followed by 10 doses (days 5-9 and 12-16) of rIL-2 (1 X 10(6) U/m2) given by 6 h i.v. infusion. There were no major antitumor effects. Toxicity was not clearly dose-related, with pain and induration at s.c. injection sites, fatigue, malaise, and palpitations most often observed. Pretreatment baseline ranges (PBR), which are 95% prediction intervals that reflect both intra- and interpatient variability, were calculated for nine hematologic and immunologic variables derived from 21 of the 24 patients. While pretreatment with CPM had no significant effect on these variables during the i.v. phase of the study as compared to a prior study using an identical rIL-2 i.v. infusion schedule, prolonged administration of s.c. rIL-2 was associated with (a) enhancement of natural killer (NK) cytotoxicity against K562 in 13 of 21 patients (p less than 0.00001), (b) increases in cytotoxicity against K562 (15 patients) and against Daudi (9 patients) in the presence of 10 U/ml of rIL-2 (p = 0.007), (c) increases in the proliferative response in vitro to OKT3 and rIL-2 in 12 patients (p less than 0.00001), (d) lymphocytosis with increase in percentage of Tac (13 patients, p less than 0.00001), T8 (11 patients, p = 0.0005), and T9 (8 patients, p = 0.021) expression, and (e) eosinophilia. While initial rises in some of these variables occurred during the i.v. phase of the study, maximum increases for all variables except T9 positivity occurred during prolonged s.c. therapy. Nine of 10 patients studied while on therapy greater than 50 days had anti-rIL-2 antibodies in an enzyme-linked immunosorbent assay; in only one case was the antibody neutralizing. This study demonstrates that significant enhancement of cytotoxicity against both NK-sensitive and -resistant targets and improvements in T-cell mitogenic response occur with long-term administration of rIL-2. Further evaluation of long-term administration of tolerable doses of rIL-2 is warranted.
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PMID:Phase I trial of recombinant interleukin-2 and cyclophosphamide: augmentation of cellular immunity and T-cell mitogenic response with long-term administration of rIL-2. 326 71

The activity of 38 calves aged 15-30 days of the Simenthal breed and of crosses with Ireshire was studied before and after transportaton at a distance of 38-100 km. It was established that transportation causes fatigue, thirst and a weight reduction of 4.3 kg, due to loss of liquid in the calf's organism. Caughing, soft faeces, even diarrhea, 1.5 degrees C higher rectal temperature, and 3.0 degrees C lower skin temperature, were recorded. the MacClure--Oldridge test proved twice as fast. As a result of hemoconcentration hemoglobin and hematocrite were higher. Eosinopaenia and neutrophylia with a nuclear deviation to the left similar to the reaction of experimentally induced lipopolysaccharide fever were established. On the 72d hour lymphocytosis and an enhanced lymhocytal index were observed. Transportation led to 15-18% higher number of phagocyted neutrophyls, 30-35% higher Wright number and nearly two times higher total blood phagocytal ability. Seventy two hours after two times higher total blood phagocytal ability. Seventy two hours after transportation the total blood phagocytal ability was reduced 15%. Another effect of calf transportation was the reduced total immunological reactivity, scored by the skin test of Yoffe.
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PMID:[Reactivity changes in calves during transportation]. 741 35

The safety, tolerance, and clinical effects of combined therapy with recombinant interferon-alpha (IFN-alpha) and interleukin-2 (rIL-2) administered subcutaneously for 2 courses of 4 weeks each, with 4 weeks interval between courses, given as outpatient therapy have been assessed in 10 patients with Philadelphia chromosome (Ph1)-positive chronic myelogenous leukemia (CML). All patients were previously treated with conventional chemotherapy and 3 failed to respond to IFN-alpha administered prior to our study. Median duration of disease from diagnosis was 36 months. Seven patients were in first chronic phase and the other 3 were in blast crisis, second chronic phase, and relapse post-bone marrow transplantation (BMT), respectively. Hematological response (median follow-up 16 months) was observed in 9 patients, with a decline in number of white blood cells and platelets. Elimination of Ph1 was observed in the patient who relapsed post-BMT with complete elimination bcr/abl RNA by polymerase chain reaction. Rebound lymphocytosis and eosinophilia were observed in most of the patients. Toxicity was acceptable. The main adverse effects were fever, chills, fatigue, anorexia, nausea, and vomiting. The side effects were reversible and no interruption of treatment was required. There was no treatment-related hospitalization or deaths. These data suggest that simultaneous subcutaneous IFN-alpha and rIL-2 home therapy is feasible, reasonably well tolerated, and potentially beneficial in CML patients. These observations may have important implications for the treatment of minimal residual disease following allogeneic and autologous marrow transplantation.
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PMID:Treatment of chronic myelogenous leukemia with recombinant human interleukin-2 and interferon-alpha 2a. 792 12

In the immunocompromised patients and during foetal life an acute infection due to the cytomegalovirus (CMV) causes great morbidity. In adults without predisposing factors the acute infection with CMV is rarely symptomatic, but can also provoke fever, fatigue, headache and anorexia for weeks. The peripheral blood smear shows big atypical lymphocytes within a relative lymphocytosis. The suspicion of the CMV infection is confirmed by the serological evidence of IgM anti-CMV antibodies. There is no etiological treatment, the evolution is spontaneously favorable most of the time. Establishing the diagnosis is reassuring for the patient and for the physician and avoids unnecessary analyses and treatments. We describe a series of 11 adults without predisposing factors who contracted an acute cytomegalovirus infection.
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PMID:[Clinical presentation of primary cytomegalovirus infection in a non-immunodepressed adult]. 869 75

A benign, transient proliferation of atypical lymphocytes and a monoclonal rearrangement of the T-cell receptor beta (TRB) locus was found in a 60-year-old woman who presented with low-grade fever, anorexia and fatigue. A marked and transient atypical lymphocytosis (white blood cell count 90.5 x 10(9)/l) with CD8 surface antigen improved without specific treatment. Although tests for IgM antibodies to hepatitis A, varicella zoster, Epstein-Barr virus (EBV), and cytomegalovirus (CMV) were all negative, a monoclonal gene rearrangement of TRB locus was observed in the DNA of the proliferated atypical lymphocytes by Southern blotting. The clonal rearrangement and the atypical lymphocytes disappeared after 14 d, and the patient has remained well for 7 years. These results suggest that monoclonal proliferation of CD8 lymphocytes can occur based on a non-neoplastic aetiology.
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PMID:Transient appearance of CD3+CD8+ T lymphocytes with monoclonal gene rearrangement of T-cell receptor beta locus. 948 37

Lower extremity symptoms are caused by lesions at any level of the neuraxis, from cortex to muscle. HIV affects virtually every level of the nervous system, either directly or indirectly. The presence of pathology at multiple levels and by multiple processes further complicates the bedside diagnosis of a patient with AIDS and neurologic symptoms. Many neuropathies and other conditions that affect the lower extremities can be identified with careful history and physical examination, confirmed with limited testing, and can be treated successfully. Distal symmetric polyneuropathy is the most common lower extremity disorder, but it must be distinguished from similar-appearing neuropathies caused by medications, B12 deficiency, or vasculitis. Diffuse infiltrative lymphocytosis syndrome also causes a painful peripheral neuropathy that must be distinguished from distal symmetric polyneuropathy. Inflammatory demyelinating polyneuropathies are characterized by muscle weakness. They occur in early, asymptomatic HIV infection and respond to plasmapheresis or steroids. Mononeuropathies in patients with CD4 counts more than 200 often resolve on their own. Multiple mononeuropathies, which occur in patients with CD4 counts less than 50, are often associated with cytomegalovirus infection and may follow a rapidly progressive course unless treated promptly and aggressively. Progressive polyradiculopathy occurs late in the course of AIDS, is often caused by cytomegalovirus, is rapidly progressive, and generally is fatal unless recognized and treated promptly. Muscle weakness, myalgia, and fatigue are common in HIV and have multiple causes. Lower extremity spasticity may be caused by treatable etiologies such as spinal cord abscess, tumor, disc compression, B12 deficiency, or ischemia. Gait disturbances are common but nonspecific and may be caused by treatable neurologic disorders at any level of the neuraxis.
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PMID:Neurologic problems of the lower extremity associated with HIV and AIDS. 957 54

A Phase I dose escalation trial of i.v. administered recombinant human interleukin 12 (rhIL-12) was performed to determine its toxicity, maximum tolerated dose (MTD), pharmacokinetics, and biological and potential antineoplastic effects. Cohorts of four to six patients with advanced cancer, Karnofsky performance >/=70%, and normal organ function received escalating doses (3-1000 ng/kg/day) of rhIL-12 (Genetics Institute, Inc.) by bolus i.v. injection once as an inpatient and then, after a 2-week rest period, once daily for five days every 3 weeks as an outpatient. Therapy was withheld for grade 3 toxicity (grade 4 hyperbilirubinemia or neutropenia), and dose escalation was halted if three of six patients experienced a dose-limiting toxicity (DLT). After establishment of the MTD, eight more patients were enrolled to further assess the safety, pharmacokinetics, and immunobiology of this dose. Forty patients were enrolled, including 20 with renal cancer, 12 with melanoma, and 5 with colon cancer; 25 patients had received prior systemic therapy. Common toxicities included fever/chills, fatigue, nausea, vomiting, and headache. Fever was first observed at the 3 ng/kg dose level, typically occurred 8-12 h after rhIL-12 administration, and was incompletely suppressed with nonsteroidal anti-inflammatory drugs. Routine laboratory changes included anemia, neutropenia, lymphopenia, hyperglycemia, thrombocytopenia, and hypoalbuminemia. DLTs included oral stomatitis and liver function test abnormalities, predominantly elevated transaminases, which occurred in three of four patients at the 1000 ng/kg dose level. The 500 ng/kg dose level was determined to be the MTD. This dose, administered by this schedule, was associated with asymptomatic hepatic function test abnormalities in three patients and an onstudy death due to Clostridia perfringens septicemia but was otherwise well tolerated by the 14 patients treated in the dose escalation and safety phases. The T1/2 elimination of rhIL-12 was calculated to be 5.3-9.6 h. Biological effects included dose-dependent increases in circulating IFN-gamma, which exhibited attenuation with subsequent cycles. Serum neopterin rose in a reproducible fashion regardless of dose or cycle. Tumor necrosis factor alpha was not detected by ELISA. One of 40 patients developed a low titer antibody to rhIL-12. Lymphopenia was observed at all dose levels, with recovery occurring within several days of completing treatment without rebound lymphocytosis. There was one partial response (renal cell cancer) and one transient complete response (melanoma), both in previously untreated patients. Four additional patients received all proposed treatment without disease progression. rhIL-12 administered according to this schedule is biologically and clinically active at doses tolerable by most patients in an outpatient setting. Nonetheless, additional Phase I studies examining different schedules and the mechanisms of the specific DLTs are indicated before proceeding to Phase II testing.
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PMID:Phase I evaluation of intravenous recombinant human interleukin 12 in patients with advanced malignancies. 981 99


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