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)

Recombinant gamma interferon (r-GIFN) demonstrates in vitro and in vivo characteristics that contrast with those of alpha and beta interferons. It has relatively weak antiviral properties, yet relatively potent immunomodulatory effects. A phase I trial was performed with r-GIFN (specific activity 2.6 X 10(6) IU/mg protein), administered as a continuous intravenous (IV) infusion over 24 hours for five days (Cl X 5) and repeated every 28 days. This schedule was chosen based on the short half-life of r-GIFN in animal systems and the in vitro augmentation of biologic effects with continuous exposure to interferons. Twenty-one patients with refractory solid tumors received 46 evaluable courses of therapy. The dose-limiting toxicities included fever, flu-like symptoms, cardiovascular toxicity, and neurotoxicity. The cardiovascular toxicity included hypotension and one episode of cardiac ischemia with chest pain. Neurotoxicity consisted of lethargy and confusion. These toxicities were reversible, and although dose-limiting, occurred sporadically throughout all dosage levels. Mild to moderately severe non-dose-limiting toxicities included nausea and vomiting, leukopenia, and liver function abnormalities. Other infrequent toxicities included hypocalcemia, diarrhea, constipation, and alopecia. The maximally tolerated dose of r-GIFN on this schedule is 0.5 X 10(6) IU/m2/d. Partial responses were seen in one patient with metastatic melanoma and in one patient with renal cell carcinoma. Toxicity and antitumor activity were seen at doses where interferon serum levels could not be detected by radioimmunoassay. In addition, the toxicity and antitumor activity seen were at much lower doses than previously described for shorter infusion schedules of other recombinant gamma interferon preparations. Differences in biologic activity of interferon preparations and/or differences in scheduling may account for this variability. Although this study defines a recommended phase II dose of r-GIFN based on the maximally tolerated dose, the optimal therapeutic index may exist at a lower dosage level.
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PMID:A phase I clinical trial of recombinant DNA gamma interferon. 310 84

Clinicians and nurses should obtain a history of antecedent illness occurring within 2 weeks of the onset of vomiting. Ninety percent of school-age children will give a history of an antecedent illness (varicella or influenza-like respiratory illness) within 1 week of the onset of vomiting. The vomiting of Reye's syndrome is usually persistent, lasting for 24 to 96 hours before the onset of serious brain signs. We believe that any child with the history of flu or chickenpox within 1 week of the onset of vomiting, which lasts for more than 12 hours, and is unusually severe or is associated with lethargy, should have an SGPT (alanine aminotransferase). This laboratory measure is clearly elevated in most cases of Reye's syndrome.
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PMID:Management of Reye's syndrome: need for early diagnosis and intravenous treatment of stage I non-comatose cases. 402 67

Mice intravenously injected with concentrated infectious influenza B/Lee/40 virus (LD50 = 6400 hemagglutinin units) developed lethargy, seizures, coma, and death 1 to 3 days later. The cerebrospinal fluid cell count was normal. Serum glutamic oxaloacetic transaminase levels increased 19-fold and plasma ammonia levels elevated 2.6-fold over control values. Serum bilirubin levels remained normal. Microvesicular fatty metamorphosis developed in the liver, whereas the brain showed mild cerebral edema without inflammatory changes. Viral propagation did not occur in liver or brain, but viral hemagglutinin, neuraminidase, and probably nucleoprotein antigens were produced in hepatocytes. Many of the clinical, biochemical, and pathologic features of the mouse illness are similar to those seen in Reye's syndrome.
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PMID:Experimental influenza B virus toxicity in mice. A possible model for Reye's syndrome. 629 39

Clinical and laboratory data of 12 previously healthy infants under 3 months of age hospitalized for suspected sepsis and subsequently diagnosed as suffering from influenza A viral infection were obtained prospectively during two epidemics of influenza A/Bangkok/H3N2 epidemics. The onset of the illness was generally acute, and the infants presented with high fever, lethargy often alternating with irritability, anorexia and signs of upper respiratory tract infection. History of contact with at least one person with signs and symptoms consistent with viral disease was present in all infants. White blood cell counts were within normal limits. Only one child had pneumonia and all had normal cerebrospinal fluid findings. Viral diagnosis was made by immunofluorescent testing of nasopharyngeal specimens within several hours of admission in 7 of the 9 infants tested and was isolated within 5 days from admission in 6 of 10 infants. Increasing awareness of the possible viral etiology of acute fever along with a greater availability of rapid viral diagnosis should result in better management of these young infants.
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PMID:Influenza A virus infection imitating bacterial sepsis in early infancy. 637 55

Ten women with advanced locally recurrent breast cancer who had failed to respond to radiation and hormonal and cytotoxic agents were given up to 12 weeks of recombinant leucocyte interferon 20 X 10(6) U/m2 daily or 50 X 10(6) U/m2 three times a week. Within one hour of administration influenza-like symptoms began, which one week later were superseded by lethargy, anorexia, and nausea, with a consequent loss of weight in most patients. Other side effects included profound somnolence, confusion, paraesthesia, and (in one patient) signs of an upper motor neurone lesion in the legs. All these effects together with increased slow wave activity in electroencephalograms from all patients during treatment disappeared when interferon was withdrawn and did not recur on reintroducing the drug at a lower dosage. Studies are continuing to determine the mechanisms of these effects.
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PMID:Neurological effects of recombinant human interferon. 640 63

This study was designed to evaluate the clinical tolerance to multiple IM injections of rDNA-produced human alpha-2 interferon (IFN) (Schering-Plough 30500) in patients with solid tumours. IFN was administered in escalating IM doses in separate groups of patients daily for 14 days and then twice weekly for a further 10 weeks. The dosage levels were 1, 3, 10, and 30 million U/injection. Subjective toxicity could be divided into two types, acute and chronic. The acute reactions took the form of an influenza-like syndrome consisting in chills, rigors, headache, tremor, nausea, vomiting, and myalgia. These symptoms were dose-related but tachyphylaxis developed with continued dosing. The chronic toxicity consisted of malaise, lethargy, fatigue, anorexia, and confusion. These symptoms were not so dose-dependent and tended to become more severe with prolonged treatment. Objective toxicity consisted of myelosuppression and liver dysfunction. Granulocyte counts below 1.0 X 10(9)/l were seen in three patients at the 30-million-U level, with platelet counts less than 100 X 10(9)/l in two of these. Elevation of the liver enzymes were seen in all five patients treated at 30 million U, but returned to normal after 1 week without IFN in all but one patient. A tolerable dose (IM) for phase II/III studies lies between 3 and 10 million U for daily scheduling and between 10 and 30 million U for twice-weekly injections.
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PMID:A phase I toxicity study of human rDNA interferon in patients with solid tumours. 646 93

Self-administered questionnaires were used to find out the prevalence among employees working in the three local authority premises in a Health District of self-reported illness which could be associated with sick building syndrome. Eye symptoms were found to be more common among employees working in a typing centre using VDUs. The symptoms tiredness, lethargy and influenza-like ('flu-like) illness, including aches in the limbs, were reported in significantly higher numbers by employees working in areas where there was evidence of increased pressure of work and worries over job losses. Dry throat and blocked or stuffy nose were symptoms reported in significantly higher proportions by employees working in certain buildings, where anecdotal evidence suggested that there could be problems with temperature regulation. This study also confirmed findings by other studies that for some symptoms women complain in significantly higher numbers than men. It was concluded that the type of work people do, in addition to the type of building they work in, play an important role in self-reported illnesses. Causation of sick building syndrome is complex and probably of multifactorial origin.
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PMID:An investigation into sick building syndrome among local authority employees. 797 93

19 patients with advanced cancer were entered into a phase I study of recombinant human interleukin-4 (rhu IL-4). The predominant clinical side-effects included flu-like symptoms, gastrointestinal upset, lethargy and transient hypotension. In addition, there were several cases of capillary leak syndrome. 2 cases of gastrointestinal haemorrhage occurred; this was life threatening in 1 patient. The maximum tolerated dose (MTD) was 400 micrograms/m2/day. Biochemical toxicity was limited to asymptomatic elevation of liver enzymes suggesting IL-4 induced liver damage. Pharmacokinetic analysis following the intravenous bolus injection has shown that IL-4 is rapidly cleared (mean T1/2 = 19 +/- 8.7 min) from a small compartment (mean Vd = 4.9 +/- 3.68 l) probably indicating that IL-4 is retained in the systemic circulation or at most the extracellular fluid volume. 2 patients with non-Hodgkin lymphomas (NHL) showed a transient response to IL-4 whilst a third patient with NHL showed transient disease progression.
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PMID:Recombinant human interleukin-4 (rhu IL-4) administered by the intravenous and subcutaneous routes in patients with advanced cancer--a phase I toxicity study and pharmacokinetic analysis. 839 97

Interferon-alpha-2a is a recombinant interferon with antiviral, antitumour and immunomodulatory properties. Clinical studies have demonstrated that the drug offers therapeutic benefit in patients with some forms of chronic viral hepatitis. Remission, as measured by clearance of viral DNA and hepatitis B 'e' antigen (HBeAg), and normalisation of serum alanine aminotransferase levels, is observed in approximately 30 to 45% of patients with chronic hepatitis B receiving interferon-alpha-2a (2.5 to 18MU administered 3 times/week); about 5 to 15% of untreated controls remit spontaneously every year. Complete recovery [with loss of hepatitis B surface antigen (HBsAg)] is usually noted in < 20% of treated individuals. Similar response rates have been reported in the relatively small number of children evaluated to date. Although numerous studies have shown that interferon-alpha-2a (at various dosages) induces biochemical amelioration of chronic hepatitis C in approximately 50 to 75% of patients, relapse is common. Thus, long term remission may only be observed in about 15 to 30% of treated patients. On the other hand, this disorder remits spontaneously in only a few patients. The role of interferon-alpha-2a in the treatment of chronic hepatitis D remains unclear. Although preliminary data suggest it may be beneficial, cessation of therapy is generally followed by relapse. As with other types of interferons, most patients receiving interferon-alpha-2a experience an 'influenza-like' syndrome, which tends to diminish with continuing therapy. Other effects such as fatigue, lethargy, anorexia and weight loss are usually dose-limiting. Serum neutralising antibodies develop in approximately 10 to 20% of treated patients. Thus, although response rates are less than optimal, interferon-alpha-2a is a drug of first choice amongst the limited therapeutic options available for the management of well-compensated chronic viral hepatitis B or C.
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PMID:Interferon-alpha-2a. A review of its pharmacological properties and therapeutic use in the management of viral hepatitis. 858 31

Fifty-one patients with histologically confirmed epithelial stage III or IV ovarian cancer were entered into a study in which gemcitabine 800 mg/m2 was given as a 30 min intravenous infusion in a cycle once a week for 3 weeks followed by a week of rest. Patients were aged 58 years (range 23-70 years) with WHO performance status 0-2, and had received up to two different chemotherapy regimens. Thirty-eight patients had received only one prior platinum-containing chemotherapy regimen whereas 9 had received a first-line regimen on more than one occasion. A further 3 patients had received two different regimens. Of 42 patients evaluable for response, 8 (19%; 95% CI: 9%-34%) were partial responders. Seven of the 8 responders were resistant to first-line platinum-based therapy. Median duration of response was 8.1 months (range 4.4-12.5 months). Median progression-free survival was 2.8 months (range 0.2-12.5 months). Haematological toxicity with gemcitabine was modest, with grade 3 leukopenia (11 patients) and grades 3 and 4 thrombocytopenia (6 patients). Grade 3 non-haematological toxicity included nausea/vomiting (6 patients) and elevated AST/ALT (1 patient), while dose-limiting non-haematologic toxicity consisted of flu-like symptoms (2 patients), peripheral oedema (1 patient) and lethargy (1 patient). The activity and modest haematological and non-haematological toxicity seen with gemcitabine suggest that this agent should be further evaluated in the treatment of patients with ovarian cancer and in combination chemotherapy regimens, primarily in combination with platinum.
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PMID:Phase II study of gemcitabine in previously platinum-treated ovarian cancer patients. 871 27


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