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)

Interferon (IFN) related neurotoxicity includes somnolence and confusion, fatigue, lethargy, psychiatric symptoms, conceptual disorganization, neurological deficits, cortical blindness, coma and, rarely, death. The neurologic syndromes seem to be more common in elderly patients, following intramuscular or intravenous administration, at higher doses of frequent injections of IFN-alpha and in primary renal cell carcinoma. The duration of the treatment was not strongly related to neurotoxicity. Computed tomography findings were non-specific and included atrophy or periventricular lucencies. Electroencephalograph studies demonstrated a generalized increase in slow wave activity which returned to normal after cessation of treatment. Behavioral and mental changes in patients treated with IFN are warning signs, and indicate the need to withdraw treatment.
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PMID:Neurotoxicity of interferon-alpha. 128 26

Thirty-five patients with advanced malignant disease have been treated as outpatients with increasing doses (0.1-100 mcg) of interleukin 2 (IL2) by once daily self-administered subcutaneous (s.c.) injection, 5 days weekly for 8 weeks followed by a 4 week observation period. Systemic side effects were not experienced by patients at the 3 lower doses. Three patients required dose reduction from 100 mcg daily because of intolerance (fever, rash, lethargy, nausea and vomiting) and one patient was discontinued because of dyspnoea. We observed immunological effects at the 100 mcg dose (but not at the lower doses). These consisted of (a) a modest sustained lymphocytosis, (b) eosinophilia in six (out of nine) patients and (c) a significant rise in IL2-stimulated peripheral blood lymphocyte activated killer (LAK) cell activity in six (out of nine) patients to a mean of 2.0 times pretreatment levels (P less than 0.01). Two (out of nine) patients with renal cell carcinoma treated with 100 mcg daily had partial responses of duration 4 and 9 months respectively and a further three had disease stabilisation for at least 3 months. Low dose long-term s.c. IL2 is clinically and immunologically active, and in comparison to other IL2 regimens it has minor toxicity and is easy to administer. These characteristics make low dose s.c. IL2 suitable for study in the adjuvant setting.
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PMID:The clinical effects of prolonged treatment of patients with advanced cancer with low-dose subcutaneous interleukin-2 [corrected]. 199 6

Eighteen patients with advanced renal cell carcinoma were treated with human lymphoblastoid interferon (Wellferon) and continuous fusion vinblastine. All patients received vinblastine as a continuous infusion at a dose of 1.5 mg/m2/day on days 1 to 5. The interferon was given by daily intramuscular injections on days 1 to 10. Three patients were treated with a dose escalation scheme that reached a maximum daily dose by day 3 of 5 X 10(6) units/m2/day and that was then continued until day 10. Fifteen patients received 3 X 10(6) units/m2/day on day, 1, and 5 X 10(6) units/m2/day on days 3 to 10. Treatments were repeated every 28 days. Neutropenia (less than 1,500/mm3) occurred in 14 of 18 patients. Transient increases in serum glutamic-oxaloacetic transaminase levels to greater than four times baseline were noted in nine patients. Thrombocytopenia (less than 100,000 platelets/mm3) occurred in one patient. Fatigue, lethargy, and decline in performance status were marked in four of the patients. None of the patients in the low-dose interferon group and only 1 of the 15 patients in the high-dose interferon group had an objective response (7%, with a 95% confidence interval of 0 to 31%). Of the 12 patients completing at least two courses of therapy, 10 were in the high-dose group, which included the 1 objective (partial) response. This response noted at the start of the fourth course. Ten others developed progressive disease and one stopped treatment because of neurologic toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interferon-alpha-n1 and continuous infusion vinblastine for treatment of advanced renal cell carcinoma. 231 58

A phase I-II study of human recombinant interferon gamma (rIFN-gamma) was conducted in patients with various advanced cancer refractory to standard chemotherapies. In the phase I study, seven patients received 14 courses of escalating doses ranging from 2 X 10(6)U/m2 to 64 X 10(6)U/m2 by 1-hour intravenous infusion for 5 consecutive days. The toxicities were high fever with chills, anorexia, occasional nausea and vomiting, elevation of serum GOT, and dose-related leukopenia and neurotoxic symptoms such as heavy fatigue with somnolence or lethargy, both of which were reversible. The pharmacokinetics showed that the peak levels of serum rIFN-gamma activity were dose-related but decreased rapidly to below measurable levels within 6 hours after infusion in patients receiving less than 12 X 10(6)U/m2. Considering these data, the dosage of rIFN-gamma 6 X 10(6) U/m2 by daily intramuscular injection for more than 4 weeks was selected for the early phase II study. There was no partial response out of 11 evaluable patients but a stable condition was observed in 2 cases of renal cell carcinoma and one case each of breast cancer and ovarian cancer. All toxicities seen were similar to those observed in the phase I study, but no tachyphylaxis developed with continued dosage. The antitumor effect of rIFN-gamma remains to be evaluated in a further study employing higher doses.
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PMID:[Phase I-II study of recombinant interferon gamma]. 298 59

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

A 51-year-old man with renal cell carcinoma developed lethargy, disorientation, and fever; shortly thereafter, he had several episodes of sudden-onset catatonia. He was found to have bacterial meningoencephalitis and frontal lobe EEG abnormalities. Treatment with antibiotic and phenytoin was started, and the catatonic episodes subsided. The authors emphasize the need for a diligent investigation of all possible causes of sudden-onset catatonic syndrome and recommend that bacterial meningoencephalitis be added to the list of differential diagnoses of acute catatonia.
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PMID:A case of catatonia induced by bacterial meningoencephalitis. 369 35

In 17 nonhuman primates, nine females and eight males from 5 to 22 years old, there were 10 cases of renal carcinoma, four of renal adenoma, one nephroblastoma, one hamartoma and one transitional cell papillomatous hyperplasia. The most frequent clinical signs were anorexia, lethargy, weight loss, depression, and dehydration. Tumors were 0.1 to 10.0 cm in diameter. In neoplasms of tubular cell origin, papillary, tubular and solid histologic growth patterns occurred either separately or in combination. Thirty previously reported cases of primary renal tumors in nonhuman primates also were reviewed.
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PMID:Primary renal tumors in nonhuman primates. 628 11

Broad phase II trial of methylglyoxal-bi (guanylhydrazone) (MGBG) is under way at the Memorial Sloan-Kettering Cancer Center. Studies in renal cell carcinoma, lymphomas, and non-small-cell lung cancer are completed, and substantial numbers of patients with esophageal and head and neck cancer have been treated. Small numbers of patients with other solid tumors have also been entered into the study. MGBG has significant antineoplastic activity against lymphomas, with 16/40 heavily pretreated patients (40%) having partial remissions (PR) lasting 1 to 8+ months. MGBG has also demonstrated more modest activity in non-small-cell lung cancer, esophageal, and head and neck carcinoma; it appears to have little or no therapeutic value in renal cell cancer. Toxicities have been manageable, and included mild nausea and vomiting, diarrhea, mucositis, and myelosuppression. The dose-limiting toxicity, seen most frequently in those patients with impaired renal function, was lethargy and fatigue. MGBG has demonstrated activity in lymphomas, lung, esophageal, and head and neck cancer. Further trials of this agent are indicated, both alone and in combination.
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PMID:Phase II trials of methylglyoxal-bis (guanylhydrazone). 704 14

In order to determine the natural history and results of treatment of intracerebral metastases in solid-tumor patients, the records of 191 patients with an antemortem diagnosis of intracerebral metastasis made during the period from August 1974 to November 1978 were reviewed. Malignancies included lung (122 patients), breast (26), unknown primary (16), melanoma (8), colorectal (6), hypernephroma (4), and others (12). Favorable prognostic factors included solitary brain metastasis (P less than 0.001), ambulatory performance status (P less than 0.001), symptoms of headache (P less than 0.001), or visual disturbances (P less than 0.02), and estrogen receptor positivity in breast cancer patients (P = 0.055). Poor prognostic factors included advanced age (P less than 0.04) and evidence of impaired consciousness, i.e., disorientation, lethargy, stupor, or coma (P less than 0.007). Median survival time after diagnosis of intracerebral metastasis was 3.7 months for the entire series. In those patients with a single intracerebral metastasis and minimal tumor burden, the type of treatment used had a significant impact on survival. Those cases treated with surgery and radiation had a median survival time of 9.7 months versus 3.7 months for those treated with radiation alone (P less than 0.02). When using a proportional hazard regression analysis to adjust for the three most important prognostic factors, treatment (surgery and radiation versus radiation alone) still appeared to be important. Intracerebral metastases were the immediate or contributing cause of death in 50% of the patients in this series. Patients at greater risk of dying of intracerebral metastases included those in whom the brain was the first site of distant metastasis, those with an intracerebral metastasis from an unknown primary site, and those whose presentation of malignancy was with symptoms of a brain metastasis. Although the therapeutic goal in intracerebral metastases is generally palliative, it appears that there are categories of cases that may benefit from more aggressive treatment.
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PMID:Intracerebral metastases in solid-tumor patients: natural history and results of treatment. 723 7

Concurrent renal adenocarcinoma and polycythemia were diagnosed in a 19-month-old, female Rhodesian ridgeback. An unusually early presentation for this neoplasm, it is the second reported case of renal adenocarcinoma in a dog less than two years of age. Concurrent renal adenocarcinoma and polycythemia have been reported previously in four older dogs. In the dog of this report, clinical signs included brick-red mucous membranes, lethargy, a periodic systolic heart murmur, and engorged retinal vessels. A large retroperitoneal mass and pulmonary metastatic nodules were present at the time of diagnosis. Red blood cell count, packed cell volume, and hemoglobin concentration were greatly increased (12,940,000 red blood cells/microliter; 73.2%; and 26.6 g/dl, respectively). Histopathological diagnosis was renal adenocarcinoma. Polycythemia was the result of excessive erythropoietin production by the neoplasm.
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PMID:Concurrent renal adenocarcinoma and polycythemia in a dog. 782 Jul 61


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