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)

Advanced renal cell carcinoma is a chemoresistant disease. Immunotherapy with alpha interferon or interleukin (IL)-2 has produced response rates of approximately 15%, but better treatments are needed. IL-4 is a cytokine produced by activated CD4+ lymphocytes and has pluripotent activities including inhibiting the in vitro proliferation of human renal cell carcinoma cell lines. In this trial, patients were required to have a histologic diagnosis of renal cell adenocarcinoma with measurable disease and performance status (SWOG) of 0-1. Patients had to have adequate bone marrow, renal, and hepatic function as well as no clinically significant pulmonary or cardiac dysfunction. IL-4 was given by subcutaneous injection at a dose of 5 micorg/kg/d, daily for 28 days followed by a 7-day rest period. Fifty-eight patients were registered with seven patients ineligible and two patients not analyzable because they did not receive treatment. In the 49 eligible and analyzable patients, there were no confirmed complete or partial responses. There was one unconfirmed partial response in retro-caval lymph nodes, but no verifying measurement was done. There were seven patients with stable disease, no response, 25 with increasing disease/progression, and 16 patients whose assessment was inadequate to determine response. The median time to progression was 3 months, and the median survival was 13 months. Toxicity was significant with the most common side effects nausea, vomiting, or diarrhea, followed by headache/pain and malaise/fatigue/lethargy. There were 13 instances of grade 4 toxicity that occurred in nine different patients. Unique toxicities included Bell's palsy in three patients and hypoglycemia in a previously well-controlled diabetic. Despite promising growth inhibitory and immunologic effects, IL-4 in this dose and schedule is not useful for the treatment of patients with disseminated renal cell carcinoma.
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PMID:Phase II trial of recombinant human interleukin-4 in patients with advanced renal cell carcinoma: a southwest oncology group study. 1214 58

In the summer of 1999/2000, an epizootic occurred in cultured juvenile redclaw crayfish Cherax quadricarinatus on one commercial crayfish farm in northern Queensland, Australia. Mortalities occurred over 4 wk, with up to 96% cumulative mortalities in 2 earthen ponds stocked with juveniles. The crayfish were weak, anorexic and lethargic. A transmission trial was conducted, using filtered, cell-free extract prepared from infected crayfish as inoculum. The disease was reproduced, with on-going mortalities occurring in inoculated crayfish over 55 d. Experimentally inoculated crayfish showed gross signs of malaise, anorexia and disorientation before dying. Two types of intranuclear inclusion bodies (INIBs) were seen in tissues of endodermal, ectodermal and mesodermal origin by light microscopy with haematoxylin and eosin (H&E) stained sections. 'Early'-stage INIBs were eosinophilic, rounded and located centrally within slightly enlarged nuclei while 'late'-stage INIBs were well-rounded and deeply basophilic. The gills, cuticular epithelium and epithelial cells of the foregut, midgut and hindgut were the most heavily infected tissues. By transmission electron microscopy, virions with an average diameter of 19.5 nm were seen within electron-dense granular inclusion bodies within enlarged nuclei of both naturally and experimentally infected crayfish. The size of the virions and cytopathology are consistent with characteristics of viruses in the Family Parvoviridae. This is the first reported case of mass mortality caused by a parvo-like virus infection in C. quadricarinatus.
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PMID:A parvo-like virus in cultured redclaw crayfish Cherax quadricarinatus from Queensland, Australia. 1218 Jul 8

Tuberculous meningitis (TBM) presents clinically as either acute meningitis syndrome characterized by coma, raised intracranial pressures, seizures, and focal neurological deficits, or as a slowly progressive dementing illness. When the infection presents as the former, characteristic signs and symptoms are headache, malaise meningismus, papilloedema, vomiting, confusion, seizures, and cranial nerve deficits. Patients admitted with lethargy or stupor may enter coma in a matter of days, and fever may or may not be present. However, TBM more commonly presents as a slowly progressive dementing illness, with memory deficits and personality changes typical of frontal lobe-like disease. TBM is described with regard to its history, clinical presentations, complications, diagnosis, C.S.F. abnormalities, treatment, prognostic factors, and indications of steroids. Combination drug therapy involving isoniazid, rifampin, pyrazinamide, and pyridoxine is the recommended treatment strategy for adults. The patient's level of consciousness at the start of therapy is the most important prognostic factor reported in TBM cases, with the greater the change in mental status, the worse the outcome. The mortality rate of patients who are comatose before the initiation of therapy is 50-70%.
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PMID:Tuberculous meningitis. 1229 51

Posttransplant erythrocytosis (PTE) is defined as a persistently elevated hematocrit to a level greater than 51% after renal transplantation. It occurs in 10% to 15% of graft recipients and usually develops 8 to 24 months after engraftment. Spontaneous remission of established PTE is observed in one fourth of the patients within 2 years from onset, whereas in the remaining three fourths it persists for several years, only to remit after loss of renal function from rejection. Predisposing factors include male gender, retention of native kidneys, smoking, transplant renal artery stenosis, adequate erythropoiesis prior to transplantation, and rejection-free course with well-functioning renal graft. Just as in other forms of erythrocytosis, a substantial number (approximately 60%) of patients with PTE experience malaise, headache, plethora, lethargy, and dizziness. Thromboembolic events occur in 10% to 30% of the cases; 1% to 2% eventually die of associated complications. Posttransplant erythrocytosis results from the combined trophic effect of multiple and interrelated erythropoietic factors. Among them, endogenous erythropoietin appears to play the central role. Persistent erythropoietin secretion from the diseased and chronically ischemic native kidneys does not conform to the normal feedback regulation, thereby establishing a form of "tertiary hypererythropoietinemia." However, erythropoietin levels in most PTE patients still remain within the "normal range," indicating that erythrocytosis finally ensues by the contributory action of additional growth factors on erythroid progenitors, such as angiotensin II, androgens, and insulin-like growth factor 1 (IGF-1). Inactivation of the renin-angiotensin system (RAS) by an angiotensin-converting enzyme (ACE) inhibitor, or an angiotensin II type 1 AT1 receptor blocker represents the most effective, safe, and well-tolerated therapeutic modality.
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PMID:Posttransplant erythrocytosis. 1263 34

Clinical data adequate for analysis were available in 386 laboratory-confirmed cases of arthropod-borne encephalitis - 38 St. Louis and 348 western equine. Consistently observed symptoms varied with the age of the patient. Symptoms that occurred in a high proportion of patients in each age group were:LESS THAN ONE YEAR OF AGE: Fever and convulsions. (None had the St. Louis disease.)ONE THROUGH FOUR YEARS: Fever, headache, vomiting, drowsiness, irritability, restlessness, nuchal rigidity, tremor, and sometimes convulsions. FIVE THROUGH FOURTEEN YEARS: Headache, fever, and drowsiness. Sometimes the disease progressed no further, but if it did, nausea, vomiting, muscular pain, photophobia and limitation of neck and back flexion often were noted; and sometimes convulsions and intention tremors. FIFTEEN YEARS AND OLDER: Drowsiness, lethargy, malaise, fever, stiffness at the back of the neck and, almost always, severe intractable occipital headache associated with nausea, disturbance of vision, photophobia and vertigo. The extreme difficulty of differential diagnosis on the basis of clinical observation was indicated by the wide range of diagnoses made in these cases before the invading organism was identified by laboratory studies.
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PMID:The 1952 outbreak of encephalitis in California; differential diagnosis. 1306 16

Hereditary haemochromatosis is a very common genetic defect in the Caucasian population, with an autosomal recessive inheritance. It is characterized by inappropriately increased iron absorption from the duodenum and upper intestine, with consequent deposition in various parenchymal organs, notably the liver, pancreas, joints, heart, pituitary gland and skin, with resultant end-organ damage. Clinical features may be non-specific and include lethargy and malaise, or reflect target organ damage and present with abnormal liver tests, cirrhosis, diabetes mellitus, arthropathy, cardiomyopathy, skin pigmentation and gonadal failure. Early recognition and treatment (phlebotomy) is essential to prevent irreversible complications such as cirrhosis and hepatocellular carcinoma. The history of this condition dates as far back as 1865, but in the last decade great advances have been made. We discuss the genetics, pathophysiology, clinical features, diagnosis and management of a condition that could easily present to a generalist, and is an important diagnosis not to miss.
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PMID:Hereditary haemochromatosis. 1583 70

We describe the case of a 30-month-old boy who developed acute disseminated encephalomyelitis (ADEM) after hepatitis A virus (HAV) infection and ultimately died. As far as we know, this is only the second case of HAV-associated ADEM to be reported in the literature. The child was brought to hospital with fever, lethargy and weakness of 2 days duration. He had developed jaundice, abdominal pain and malaise 2 weeks beforehand and these problems had resolved within 2 days. Neurological examination revealed lethargy, generalised weakness and positive Babinski's signs bilaterally. Cerebrospinal fluid examination showed mild lymphocytic pleocytosis, increased protein and elevated anti-HAV IgM and IgG titres. Serum HAV IgM and IgG titres were also elevated. Despite aggressive treatment with ceftriaxone, acyclovir and anti-oedema measures, he developed papilloedema and coma within 24 hours of admission. Magnetic resonance imaging of the brain revealed diffuse cerebral oedema and multifocal hyperintensities on T2-weighted images, with most lesions in the white matter of both cerebral hemispheres. The diagnosis of ADEM was established and high-dose steroids and intravenous immunoglobulin were added to the treatment regimen. However, his clinical condition continued to deteriorate and he died on the 20th day in hospital. This case shows that HAV infection can be linked with ADEM. Patients with HAV infection should be examined carefully for central nervous system symptoms during follow-up. Likewise, the possibility of HAV infection should be investigated in cases of ADEM.
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PMID:Acute disseminated encephalomyelitis associated with hepatitis A virus infection. 1518 42

A 4-year-old spayed female Irish Setter was examined because of acute onset of lethargy, anorexia, and weakness. The dog had eaten an adult rabbit 36 hours earlier. Tularemia was suspected because of the rabbit exposure; however, other common diseases characterized by fever, malaise, and lymphadenopathy of acute onset were also considered (ie, ehrlichiosis and Rocky Mountain spotted fever). The dog was treated with doxycycline (5 mg/kg [2.3 mg/lb], PO, q 24 h) for 14 days as well as supportive treatment with a balanced electrolyte solution (lactated Ringer's solution [200 mL, SC]). The diagnosis was first established by results of bacteriologic cultures of fine-needle aspirates obtained from lymph nodes and confirmed by results of ELISA and a polymerase chain reaction assay Successful and timely antemortem diagnosis of tularemia in dogs can be accomplished through lymph node aspiration and bacteriologic culture.
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PMID:Naturally occurring tularemia in a dog. 1534 61

To determine the prevalence and vulnerability of symptoms from thiazide-induced hyponatremia, we reviewed 223 cases of symptomatic hyponatremia enrolled between January 1996 and April 2002. There was a high frequency of neurologic manifestation of thiazide-induced hyponatremia, whereas clinical dehydration was not a discernible feature. Female patients presented with lower serum sodium levels than male counterparts (114+/-8 versus 117+/-8 mmol/L, P=0.02), although the frequency of central nervous system manifestation was comparable between two gender groups. The most frequent symptoms were malaise and lethargy (49%), followed by dizzy spells (47%) and vomiting (35%). Degree of hyponatremia upon presentation predicted the development of confusion and vomiting symptoms. Serum sodium concentration < or =115 mmol/L was significantly associated with the development of confusion (odds ratio 2.6, 95% confidence interval 1.3 to 5.1, P=0.004). Our results show that symptoms from thiazide-induced hyponatremia primarily reflect osmotic water shift into brain cells rather than extracellular fluid volume depletion.
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PMID:Clinical studies of thiazide-induced hyponatremia. 1554 Aug 81

Although drug withdrawal may induce an anxiety-like state, decreased locomotion in tests of anxiety-like behavior is an almost universal finding in rodent studies of ethanol withdrawal. Decreased locomotion in many behavioral apparatus, either as a result of a withdrawal-induced lethargy, malaise, or reduced motivation to explore confounds interpreting the effects of withdrawal as specifically increasing an anxiety-like state. To address this issue, we measured home cage activity levels as well as food and water intake for 3 days prior to and up to 5 days after chronic ethanol vapor exposure in genetically heterogeneous mice. In the first experiment, ethanol-withdrawing WSC-2 mice drank less water than controls, but did not differ from controls on any other behavioral measure during the withdrawal assessments. When the dose of ethanol was elevated in a subsequent experiment in WSC-2 mice, a similar temporary decrease in food and water intake, but not in locomotion, was observed during withdrawal. These results differed from those of mice placed into activity monitors during peak withdrawal, which exhibited profoundly reduced activity levels compared to controls. Finally, home cage activity levels during withdrawal were only transiently decreased in a mouse line that has been selectively bred to display high ethanol withdrawal handling-induced convulsion severity (WSP mice). The reduction in food and water consumption seen in most experiments suggests that withdrawal may induce a temporary malaise-like state, but this state is not reflected in altered home cage activity levels. Further, even in a relatively severe mouse model of alcohol withdrawal, any decreases in general home cage activity are short-lived.
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PMID:Home cage activity and ingestive behaviors in mice following chronic ethanol vapor inhalation. 1600 34


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