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)

Postinfectious encephalomyelitis is a kind of demyelinating disease with pathological characteristics and a monophasic clinical course. Herein, we describe a patient who had the symptoms of binge eating, fatigue, memory impairment, hypotalkativeness, hypoactivity, lethargy, incoherent speech, dysphoric mood, and episodic disorientation. Only elevation of CSF protein was noted upon initial admission; however, blurred vision of the eyes developed progressively after discharge. A magnetic resonance image (MRI) scanning of the brain demonstrated scattered lesions of low signal intensity on T1-weighted images and high areas on T2-weighted images in the left thalamus, bilateral hypothalamus and midbrain. The findings of MRI image, CSF, and clinical course all suggested postinfectious encephalomyelitis. After a treatment of prednisolone, a follow-up MRI revealed evidence of improvement, and the binge eating also improved.
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PMID:The binge eating and emotional change in a patient with postinfectious encephalomyelitis. 909 51

Hyperargininemia is a metabolic disorder biochemically characterized by tissue accumulation of arginine (Arg) and other guanidino compounds (GC). Convulsions, lethargy and psychomotor delay are predominant clinical features of this disease. Considering that some GC are epileptogenic and cause a decrease in membrane fluidity and that Na+,K(+)-ATPase, a membrane-bound enzyme, is essential for cellular excitability and is decreased in experimental and human epilepsy, in the present study we determined the in vitro effects of Arg, N-acetylarginine (NAA), argininic acid (AA) and homoarginine (HA) on the activity of Na+,K(+)-ATPase in the synaptic plasma membrane from cerebral cortex of young rats in the hope to identify a possible mechanism for the brain damage in hyperargininemia. The results showed that all GC tested, except Arg, significantly inhibited Na+,K(+)-ATPase activity at concentrations similar to those observed in plasma and CSF of patients with hyperargininemia. In addition, competition between NAA, AA and HA for the binding to the enzyme was observed, suggesting a common binding site for the GC. It is therefore possible that the inhibitory effect of GC on Na+,K(+)-ATPase may be related to the brain dysfunction observed in hyperargininemia.
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PMID:In vitro inhibition of Na+,K(+)-ATPase activity from rat cerebral cortex by guanidino compounds accumulating in hyperargininemia. 1044 19

Sargramostim (GM-CSF) therapy was instituted in a 49-year-old woman with hepatitis C on chronic interferon alpha-2b therapy. Within two weeks, she developed progressive confusion, lethargy, and gait disturbance. At autopsy 4 months later, diffuse perivascular nonmonoclonal lymphoid infiltrates were demonstrated throughout the central nervous system (CNS). As the use of hematopoietic growth factors in clinical practice increases, potential adverse effects, such as the fulminant CNS lymphocytic proliferation in this patient, are more likely to be encountered.
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PMID:Fulminant CNS perivascular lymphocytic proliferation: association with sargramostim, a hematopoietic growth factor. 1051 80

The randomized clinical trial, LU19, conducted by the Medical Research Council Lung Cancer Working Party, was designed to compare ACE (doxorubicin, cyclophosphamide and etoposide) chemotherapy plus G-CSF (granulocyte colony-stimulating factor) at 2-week intervals versus ACE chemotherapy alone at standard 3-week intervals in patients with small-cell lung cancer. This trial investigated whether more intensive administration of ACE would improve overall survival and affect the quality of life of patients. The report on overall survival and other outcome measures will be published in the Journal of Clinical Oncology. In this paper we focus on methods of analysing aspects of data reflecting quality of life. Twelve symptoms of lung cancer and its treatment - cough, haemoptysis, pain, nausea, vomiting, hoarse voice, sore mouth, rash, lethargy, lack of appetite, alopecia, and dysphagia - were scheduled to be assessed on seven occasions for the ACE arm and on eight occasions for the ACE+G-CSF arm by clinicians during the first 18 weeks of the treatment period. However, in practice the number of assessment forms completed per patient ranged from 1 to 9, and assessment time-points were very different from those planned. These 'messy' longitudinal data are explored by both a summary measure approach, in which experience of a symptom is summarized by a single value, and an extensive model-based statistical approach, which explicitly takes into account correlation within repeated measures. These analyses provide a clear picture of symptom comparisons between the two treatments. The application of various methods offers not only an approach to assessing the robustness of the results but also a basis for investigating reasons for inconsistency of results across methods. We conclude that except lethargy, which is worse in the ACE+G-CSF arm, all symptoms are similar across the two arms during the treatment period.
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PMID:Analysis of messy longitudinal data from a randomized clinical trial. MRC Lung Cancer Working Party. 1098 40

The authors present 2 patients with VP shunt-induced subdural hematomas (SDH) treated with pressure-programmable valve implantation and endoscopic third ventriculostomies (TV). The first patient is an 11-year-old girl who developed a shunt-induced SDH. Revision of the shunt valve with a higher-pressure valve resulted in a prolonged deterioration of her consciousness. External ventricular drainage at low pressure led to clinical improvement. A pressure-programmable valve set at 50 mm H(2)O was implanted, and the pressure gradually increased. At a pressure of 120 mm H(2)O symptoms recurred, even though the subdural collection was beginning to decrease in size. An endoscopic TV was performed, and the valve pressure was then increased to 200 mm H(2)O without any neurological symptoms. The second patient, a 7-year-old boy with shunt-induced SDH, had recurrent SDH, even after shunt revision with placement of a higher-pressure valve, which resulted in prolonged lethargy. A pressure-programmable valve was implanted with concurrent endoscopic TV. Gradual valve pressure increases up to 200 mm H(2)O could be performed without recurrent symptoms. Eventually, the shunt system was ligated to resolve residual positional headache, and the TV has been patent for more than 3 years. In both patients, the pressure-programmable valve was useful, since the optimal CSF drainage pressure changed during the period of recovery from symptomatic subdural collections. Concurrent TV appeared to enable increasing the valve pressure gradually without any neurological symptoms. The advantages of this combined approach are discussed.
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PMID:Critical shunt-induced subdural hematoma treated with combined pressure-programmable valve implantation and endoscopic third ventriculostomy. 1102 21

A 53-year-old woman was admitted to the hospital because of headache and disturbance of consciousness. She was afebrile. No inflammatory reaction was identified on serologic examination. Radiological findings showed acute-subacute, massive intracerebral hemorrhage in the right temporal lobe, compressing the brain stem contra-laterally. On the day of admission, she underwent a right temporal craniotomy for the removal of the mass lesion. The resected brain tissue demonstrated a small hemorrhage and edema accompanied by the infiltration of lymphoid cells into the subarachnoid space. Several days after surgery, the patient became lethargic and showed urinary incontinence. Late onset of fever and CSF findings suggested she was suffering from viral encephalitis. Serological findings, however, disclosed no antibody production against HSV, HZV, or CMV. For the diagnosis, a biopsy of the brain was carried out and herpes encephalitis was subsequently proved. Unfortunately, her condition deteriorated quickly and she died without anti-viral treatment.
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PMID:[A case of fatal herpes encephalitis presenting massive cerebral hematoma]. 1132 98

The December 2002 COM. A 19-year-old healthy male fell into stagnant water of the intercostal waterway (salt water of South Florida), following a jet ski accident. He sustained minor superficial injuries but engulfed significant quantities of water and sediment. A few days later he developed bifrontal headaches, vomiting, a stiff neck and a temperature of 102 degrees F. A CT scan on admission without contrast was negative. The CSF had markedly elevated white count but bacterial and fungal cultures were negative. He became progressively lethargic. On the fifth day he developed seizure activity. He expired the next day despite antibiotics. Gross examination of the brain at autopsy revealed edema, cerebellar tonsillar herniation and purulent meningitis. Microscopic examination revealed a massive leptomeningeal inflammatory infiltrate composed of neutrophils, lymphocytes, and numerous histiocyte-like cells. The inflammatory infiltrate extended into the cerebral parenchyma in numerous areas also involving the cerebellum, brainstem and ventricular system. Given the exposure to stagnant water (later confirmed to be a man-made fresh water lake), and the numerous histiocytic-like cells, suspicion for an amebic etiology of the disease process was raised and the CDC identified the ameba as Naegleria Fowleri. Infection by Naegleria Fowleri, a free-living ameba, occurs after exposure to polluted water in man-made fresh water lakes, ponds, swimming pools, particularly during the warm weather months when the thermophilic ameba grows well. The pathologic substrate of the infection is an acute hemorrhagic, necrotizing meningo-encephalitis mainly at the base of the brain, brainstem and cerebellum occurring in young, healthy individuals.
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PMID:December 2002: 19-year old male with febrile illness after jet ski accident. 1274 79

In 1916, von Economo first described encephalitis lethargica (EL), a CNS disorder presenting with pharyngitis followed by sleep disorder, basal ganglia signs (particularly parkinsonism) and neuropsychiatric sequelae. Since the 1916-1927 epidemic, only sporadic cases have been described. Pathological studies revealed an encephalitis of the midbrain and basal ganglia, with lymphocyte (predominantly plasma cell) infiltration. The EL epidemic occurred during the same time period as the 1918 influenza pandemic, and the two outbreaks have been linked in the medical literature. However, von Economo and other contemporary scientists thought that the 1918 influenza virus was not the cause of EL. Recent examination of archived EL brain material has failed to demonstrate influenza RNA, adding to the evidence that EL was not an invasive influenza encephalitis. By contrast, the findings of intrathecal oligoclonal bands (OCB) and beneficial effects of steroid treatments have provoked the hypothesis that EL may be immune-mediated. We have recently seen 20 patients with a similar EL phenotype, 55% of whom had a preceding pharyngitis. The patients had remarkable similarity to the historical descriptions of EL: sleep disorder (somnolence, sleep inversion or insomnia), lethargy, parkinsonism, dyskinesias and neuropsychiatric symptoms. CSF examination commonly showed elevated protein and OCB (75 and 69% respectively). Investigation found no evidence of viral encephalitis or other recognized causes of rapid-onset parkinsonism. MRI of the brain was normal in 60% but showed inflammatory changes localized to the deep grey matter in 40% of patients. We investigated the possibility that this phenotype could be a postinfectious autoimmune CNS disorder, and therefore similar to Sydenham's chorea. Anti-streptolysin-O titres were elevated in 65% of patients. Furthermore, western immunoblotting showed that 95% of EL patients had autoantibodies reactive against human basal ganglia antigens. These antibodies were also present in the CSF in four patients tested. By contrast, antibodies reactive against the basal ganglia were found in only 2-4% of child and adult controls (n = 173, P < 0.0001). Rather than showing polyspecific binding, these antibodies bound to common neural autoantigens of molecular weight 40, 45, 60 and 98 kDa. Regional tissue comparisons showed that the majority of these autoantigens were specific to or enriched in CNS tissue. Immunohistochemistry with secondary staining localized antibody binding to neurons rather than glial populations. Further investigation is required to determine whether these antibodies affect neuronal function (i.e. whether they are pathogenic anti-neuronal antibodies). Histopathology in one case demonstrated striatal encephalitis with perivenous B- and T-lymphocytic infiltration. We believe an EL-like syndrome is still prevalent, and propose that this syndrome may be secondary to autoimmunity against deep grey matter neurons.
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PMID:Encephalitis lethargica syndrome: 20 new cases and evidence of basal ganglia autoimmunity. 1467 31

A 3-year-old spayed female Siberian Husky was presented due to acute vision loss. Examination revealed bilateral optic neuritis and lymphocytic meningoencephalitis. The serum (1:800) and cerebrospinal fluid (CSF; 1:200) immunoglobulin (Ig)G titers for tick-borne encephalitis virus (TBEV) were elevated as were the serum IgG titer for Anaplasma phagocytophilum (1:640) and serum IgM titer for Toxoplasma gondii (1:20). Intracytoplasmic inclusion bodies such as ehrlichial or anaplasmal morulae were not observed in the CSF or blood smear. The dog was treated with methylprednisone and doxycycline. The left eye regained vision; the right eye remained blind. Anti-inflammatory therapy was stopped on day 18 after diagnosis. Four days later the dog showed evidence of hyperesthesia in the cervical region. Analysis of CSF showed no abnormalities and CSF IgG titers for TBEV and A. phagocytophilum were negative. Funduscopic evidence of active papillitis was absent on day 22 in the left eye and on day 86 in the right eye. On day 243, the dog was presented again with lethargy, ataxia, disorientation and temporary head tilt. The IgG titer for TBEV was again elevated in the CSF (1:800) and in serum (1:400). After interpretation of all findings, we assume that meningoencephalitis and optic neuritis in this patient was caused by TBEV and associated immune-mediated inflammation. In endemic areas, TBEV should be considered as cause of optic neuritis in dogs.
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PMID:Tick-borne encephalitis virus as a possible cause of optic neuritis in a dog. 1520 Jun 24

Combination chemotherapy with irinotecan (CPT-11) and platinum compounds is effective for treating cervical cancer. Nedaplatin (254-S) is a new cisplatin analogue that achieves a high response rate (53%) in patients with primary cervical cancer. We performed a phase I-II study of combination chemotherapy with CPT-11 plus 254-S for advanced or recurrent cervical cancer. The inclusion criteria were stage IV disease or recurrence. CPT-11 and 254-S were administered intravenously on day 1, while rhG-CSF (50 microg) was given on days 3-12. This regimen was repeated after 4 weeks. Dose escalation was carried out in tandem (CPT-11/254-S: 50/70, 50/80, and 60/80 mg m(-2)). A total of 27 patients (stage IV=seven, recurrence=20) were enrolled. The phase I study enrolled eight patients. At dose levels 1 and 2, no dose-limiting toxicities were observed. At dose level 3, the first two patients developed DLTs. The maximum tolerated dose of CPT-11 and 254-S was 60 and 80 mg m(-2), respectively, and the recommended doses were 50 and 80 mg m(-2). Grade 3/4 haematologic toxicity occurred in 67% in phase II study, but there were no grade 3 non-haematologic toxicities except for nausea or lethargy. In all 27 patients, there were two complete responses (7%) and 14 Partial responses (52%), for an overall response rate of 59% (95% confidence interval: 39-78%). Among the 12 responders with recurrent disease, the median time to progression and median survival were 161 days (range: 61-711 days) and 415 days (range: 74-801 days). This new regimen is promising for cervical cancer.
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PMID:Phase I-II study of irinotecan (CPT-11) plus nedaplatin (254-S) with recombinant human granulocyte colony-stimulating factor support in patients with advanced or recurrent cervical cancer. 1529 35


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