Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Brucellosis has always been an unusual disease in children and, concomitant with the control of the disease in domestic animals, reports have become sparse. The pediatrician, therefore, may not be aware of the protean clinical manifestations of childhood brucellosis. In 1973, nine cases occurred during a three-month period in El Paso, Texas. All cases were marked by spiking fevers and lethargy of four days to four weeks in duration. Tender hepatomegaly or splenomegaly was striking in seven patients. Other characteristics included epistaxis, arthralgia, myalgia, and weight loss. Leukopenia and leukemoid reaction were found in five patients. All of the patients tested had elevated liver enzymes. Febrile agglutinins were invaluable in screening for an early clue to diagnosis. When Brucella abortus antigen agglutinated serum from patients with a positive screen in dilutions greater than 1:320, a presumptive diagnosis of brucellosis was made. Brucella was isolated from the blood or bone marrow in seven patients and the time of incubation proved crucial for successful recovery. Bacterial blood cultures are usually discarded at ten days of age, as were cultures from the only two patients from whom the organism was not recovered. All of the cultures incubated for 12 to 15 days grew B. melitensis, an unusual causative species in the United States. However, several patients admitted eating cheese from the State of Chihuahua, Mexico, made from unpasteurized goat's milk, the presumed source of the infection. Within one to three days, all patients responded dramatically to antibiotics; tetracycline was given orally for 21 days and streptomycin intramuscularly for 14 days. Pediatricians caring for patients in areas where consumption of unpasteurized milk products is likely would do well to consider brucellosis in a child with obscure fever or toxic hepatosplenomegaly.
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PMID:Brucellosis in childhood. 80 83

The effect of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) was assessed in 17 patients with small cell lung cancer. GM-CSF was initially given alone by subcutaneous injection for 10 days at 50-500 micrograms/m2 per day. There was a significant rise in neutrophils and eosinophils and to a lesser extent in monocytes at all dose levels. During the next phase, patients received chemotherapy (etoposide, ifosfamide and doxorubicin), and GM-CSF was given on alternate cycles, the patients acting as their own controls, so that the amelioration of chemotherapy could be assessed. Despite partial abrogation of the neutropenia associated with chemotherapy (P = 0.04), GM-CSF failed to reduce the frequency of febrile episodes in association with neutropenia, with six episodes occurring on GM-CSF and seven while patients were not receiving GM-CSF after a total of 66 cycles of chemotherapy. After GM-CSF, there was a reduction in polymorph phagocytic ability and chemotaxis in 6/12 and 9/11 patients, respectively. Timed blood counts after GM-CSF administration showed that peak leucocytosis occurred at 8-12 h and fell to two-thirds of this level at 24 h. Toxicity consisting of lethargy, myalgia and bone pain occurred at all dose levels but was manageable. 2 patients had thromboembolism. This study failed to demonstrate a reduction in the infection risk associated with moderately intensive chemotherapy for small cell lung cancer despite the partial abrogation of neutropenia.
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PMID:Infection risk in patients with small cell lung cancer receiving intensive chemotherapy and recombinant human granulocyte-macrophage colony-stimulating factor. 131 26

This phase I study investigated flavone acetic acid (FAA) given as a 12-h intravenous infusion every 3 weeks in the absence of urinary alkalinisation. Cohorts of three patients were treated at doses of 7, 10 and 13 g/m2. One subject had colon cancer; 5, renal cancer; and 3, lung cancer. The Eastern Cooperative Oncology Group (ECOG) performance status was 0 in four patients, 1 in two subjects and 2 in three cases. The maximum tolerated dose was 13 g/m2. The dose-limiting toxicities were WHO grade 3 hypotension and grade 3 diarrhoea. Other toxicities included lethargy and dizziness, nausea, temperature fluctuation, myalgia and dry mouth, but no significant myelosuppression was encountered. One patient receiving 10 g/m2 for renal cancer showed a partial response that lasted for 3 months and included the resolution of pulmonary and cutaneous metastases. The pharmacokinetics showed large interpatient variability. At 12-16 h post-infusion, the plasma elimination profile entered a plateau phase, with frequent increases in concentration suggesting enterohepatic recycling. Neither peak FAA levels nor AUC values were dose-dependent at the doses studied. Peak plasma levels were 101-402 micrograms/ml and AUC (0-48 h) values were 75-470 mg ml-1 min. Plasma protein binding varied with total concentration. Two metabolites were detected in the plasma, and both also underwent apparent enterohepatic recycling. Repeat dosing resulted in decreases of up to 48% in peak levels and AUC values for FAA in three of six patients. Of the total FAA dose, 39%-77% was excreted in the urine as FAA or metabolites within 2 days. The dose recommended for further phase II studies is 10 g/m2.
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PMID:A phase I and pharmacokinetic study of 12-h infusion of flavone acetic acid. 155 Nov 73

In the present investigation, 20 patients with ET were treated with recombinant interferon alfa-2c (IFN) for up to 4 years. Initially, IFN was administered subcutaneously at a dosage of 6-45 MU/week. The dosage was adjusted according to individual tolerance and response. The median dose during induction was 20 MU/week, 10 MU/week during the remaining first year, 6 MU/week during the second year and 2 MU/week thereafter. 13 patients (65%) achieved complete remission (platelet count less than 440/nl), four patients (20%) had partial remission (greater than 440/nl but a reduction by more than 50% of the initial count). The median platelet count remained steady throughout the 4-year period of treatment, in spite of extreme dose reductions. After withdrawal of IFN, however, platelet counts again increased. The white blood cells showed a marked decrease similar to that of platelet counts, whereas the haemoglobin level remained fairly stable. In the bone marrow, a significant decrease in megakaryocyte density and size could be observed. Concurrently with the improvement of haematological parameters, clinical symptoms improved, but reappeared after withdrawal of IFN. During induction, fever, bone and/or muscle pain, fatigue, lethargy and psychological symptoms were the most prominent side-effects in the majority of patients. In three patients these symptoms led to discontinuation of the treatment. With repeated dose reductions, excellent long-term tolerance was achieved, and during late maintenance treatment the only observed side-effect was an induction of thyroid autoimmunity in three patients. IFN is an effective, well-tolerated alternative in the long-term treatment of symptomatic ET. However, since withdrawal of IFN leads to recurrence of thrombocytosis, continued treatment is to be recommended.
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PMID:Interferon in essential thrombocythaemia. 193 8

A young, previously healthy woman presented with increasing muscle pain, lower limb swelling, fatigue and eosinophilia. She had consumed L-tryptophan tablets (one to two at night) over the preceding five months for management of her insomnia. Her condition slowly deteriorated and she developed generalised oedema and severe lethargy. A white blood cell count was 21.3 x 10(9)/L with 43% eosinophils (Normal range: 4.0-11.0 x 10(9)/L with 1-6% eosinophils. A biopsy specimen of the deep fascia and gastrocnemius muscle demonstrated fasciitis and myositis. The patient failed to recover after cessation of L-tryptophan use but her condition improved rapidly without significant sequelae after systemic treatment with corticosteroids.
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PMID:Eosinophilia-myalgia syndrome associated with L-tryptophan use. 199 19

In the course of a prospective immunoepidemiological study of homosexual men in Sydney, seroconversion to the AIDS-associated retrovirus (ARV) was observed in 12 subjects. Review of the clinical files defined an acute infectious-mononucleosis-like illness in 11 subjects. The illness was of sudden onset, lasted from 3 to 14 days, and was associated with fevers, sweats, malaise, lethargy, anorexia, nausea, myalgia, arthralgia, headaches, sore throat, diarrhoea, generalised lymphadenopathy, a macular erythematous truncal eruption, and thrombocytopenia. In 1 subject an incubation period of 6 days after presumed exposure to ARV was determined and in 3 subjects seroconversion took place 19, 32, and 56 days after onset. Comparison of T-cell subsets before and after the acute illness showed inversion of T4:T8 ratio in 8 subjects, due to increased numbers of circulating T8+ cells. These findings support the notion of an acute clinical, immunological, and serological response to infection with ARV which should be considered in the differential diagnosis of mononucleosis-like syndromes in groups at high risk for the development of AIDS.
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PMID:Acute AIDS retrovirus infection. Definition of a clinical illness associated with seroconversion. 285 99

Twenty previously treated patients with advanced bone sarcomas received thrice weekly im 50 X 10(6) IU/m2 doses of human alfa-interferon (interferon alfa-2a, recombinant; Roche). Seventeen patients had metastatic osteosarcomas and one each had fibrosarcoma, mesenchymal chondrosarcoma, and malignant fibrous histiocytoma. Two patients with osteosarcoma and the one with malignant fibrous histiocytoma experienced objective partial tumor regression for 1, 3, and 2 months, respectively. Fever, anorexia, myalgia, fatigue, lethargy, and moderate myelosuppression were observed commonly, and some patients developed mild nausea, vomiting, and diarrhea. No patient withdrew because of toxicity and no dose reductions were necessary except adjustments for changes in body surface area secondary to weight loss.
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PMID:Phase II study of recombinant alfa-2a interferon in patients with advanced bone sarcomas. 303 15

Eighteen patients with solid tumours were treated with human recombinant interferon-gamma at escalating dose levels starting at 1 X 10(6) units/m2 per infusion and rising through 3 X 10(6), 6 X 10(6), 9 X 10(6) and 22 X 10(6) to a maximum of 110 X 10(6) units/m2 per infusion. The IV infusions were given three times a week over a 4-week period. Side effects were seen in all patients, but were mild except at the highest dose. Acute dose-related effects included pyrexia, tiredness, thirst, chills and rigors. Chronic dose-related effects included anorexia, lethargy, weakness, disorientation, a trace of proteinuria and minimal rises in liver enzymes. In addition, effects were observed which were not related to dose. These included headache, nausea and vomiting, backache, myalgia, flatulence and a mild, transient reduction in neutrophils and erythrocytes. At the highest dose level dose-limiting toxicity was observed, consisting in severe tiredness and anorexia, hypotension, disorientation and changes on the electrocardiograph. Overall, toxicity was similar to that seen with preparations of interferon-alpha, except that no tolerance to the effects of interferon-gamma was noted. We observed less hepatic and haematological toxicity, but also recorded flatulence, handcramps and electrocardiograph changes, which have not been reported with interferon-alpha. When given according to this regimen, doses of 22 X 10(6) units/m2 per infusion of recombinant interferon-gamma were generally well tolerated by the patients.
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PMID:A toxicity study of recombinant interferon-gamma given by intravenous infusion to patients with advanced cancer. 309 8

24 patients with advanced, histologically proven cancer were treated with difluoromethylornithine 2.25 g/m2 orally every 6 h for the first 7 days of each 4-week treatment cycle. These patients also received daily i.m. doses of recombinant human alpha 2a-interferon (IFN) on Days 3 through 7 of each cycle. IFN doses of 3, 6, 12, 24, 36, and 48 X 10(6) units/m2 have been studied utilizing three patients at each daily dose level. Three additional patients have been observed at each of the two highest doses for better toxicity definition. This combination produced slight transient declines in leukocyte and platelet counts and transient rises in serum aspartate aminotransferase; however, these changes were no more pronounced at the higher IFN doses than at daily doses of 6 X 10(6) units/m2. Mild nausea and vomiting occurred in most patients and mild diarrhea also was common at all IFN dose levels. Chills, fever, myalgia, lethargy and fatigue, and anorexia were also observed at all IFN doses; however, lethargy and fatigue (lassitude) seemed to be the major factor which limited patient tolerance of IFN to 48 X 10(6) units/m2 daily. No ototoxicity was identified clinically or audiometrically and no life-threatening toxicity has occurred. Initial Phase II studies in melanoma are currently in progress.
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PMID:Phase I study of difluoromethylornithine in combination with recombinant alpha 2a-interferon. 314 Oct 46

The clinical symptoms and signs were assessed in 20 consecutive patients developing infection with the human immunodeficiency virus (HIV). All were male homosexuals and all presented with a glandular-fever-like illness. Changes in laboratory values were compared with findings in 40 HIV negative male homosexual controls. In the 10 patients for whom date of exposure to the virus could be established the incubation period was 11-28 days (median 14). One or two days after the sudden onset of fever patients developed sore throat, lymphadenopathy, rash, lethargy, coated tongue, tonsillar hypertrophy, dry cough, headache, myalgia, conjunctivitis, vomiting, night sweats, nausea, diarrhoea, and palatal enanthema. Twelve patients had painful, shallow ulcers in the mouth or on the genitals or anus or as manifested by oesophageal symptoms; these ulcers may have been the site of entry of the virus. During the first week after the onset of symptoms mild leucopenia, thrombocytopenia, and increased numbers of banded neutrophils were detected (p less than 0.0005). The mean duration of acute illness was 12.7 days (range 5-44). All patients remained healthy during a mean follow up period of 2.5 years. Heightened awareness of the typical clinical picture in patients developing primary HIV infection will alert the physician at an early stage and so aid prompt diagnosis and help contain the epidemic spread of AIDS.
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PMID:Clinical picture of primary HIV infection presenting as a glandular-fever-like illness. 314 67


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