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)

Typical clinical characteristics, neuroradiologic findings, and initial neuroradiologic studies were reviewed for 40 patients <3 years of age with intracranial ependymomas, who were treated in the Pediatric Oncology Group (prolonged postoperative chemotherapy and delayed radiation for children <3 years of age with malignant brain tumors). The study included 16 females and 24 males, aged 3 to 35 months, who were diagnosed and registered in the study between 1986 and 1990. Commonly, patients presented with vomiting (70%), ataxia (53%), headache (28%), lethargy (28%), increased head circumference (23%), and irritability (23%). Duration of symptoms before diagnosis ranged from 1 day to 11 months. Thirty-five tumors (88%) were infratentorial; average tumor size was 4.3 (+/-1.4) x 4.2 (+/-1.7) x 4.1 (+/-1.8) cm at presentation. Noncontrast CT scans were performed on 23 patients; 13 (57%) were isodense to surrounding brain tissue and 13 (57%) were calcified. Contrast CT scans of 29 patients revealed that 28 (97%) were enhanced. Of the 15 T1-weighted MRI scans, 10 (67%) demonstrated low-signal intensity tumors, and 15 (94%) of the 16 T2-weighted scans revealed high-signal tumors. Forty-three percent of the tumors were cystic. Blood was observed within only 2 tumors and peritumoral edema was uncommon. Twenty-five percent of the ependymomas extended out to involve the dura, and 97% of the infratentorial tumors showed characteristic plasticity. Hydrocephalus was present in 34 (85%) children.
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PMID:Clinical and neuroradiologic findings in infants with intracranial ependymomas. Pediatric Oncology Group. 949 87

Analysis of the molecular defects in mouse mutants can identify candidate genes for human neurological disorders. During the past 2 years, mutations in sodium channels, calcium channels and potassium channels have been identified by positional cloning of the spontaneous mouse mutants motor endplate disease, tottering, lethargic and weaver. The phenotypes of four allelic mutations identified in the sodium channel gene Scn8a range from ataxia and muscle weakness through severe dystonia and progressive paralysis, indicating that human mutations in this gene could be associated with a variety of clinical syndromes. Mutations of the calcium channel subunits beta 4 in the lethargic mouse and alpha 1A in the tottering mouse have specific effects on cerebellar function. Targeted mutation of ligand-gated ion channels has also been used to generate new models of neurological disease. We will review these recent achievements and their implications for human neurological disease. The mouse studies indicate that mutations in ion channel genes are likely to be responsible for a broad spectrum of clinical phenotypes in human neurological disorders.
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PMID:Ion channel mutations in mouse models of inherited neurological disease. 956 26

A 18-year-old Dutch Warmblood mare was referred for colic. Upon arrival, lethargy, blindness, head pressing, ataxia, and circling were the main clinical signs. On rectal examination a hard mass and oedema around the cranial mesenteric artery were palpated. Plasma liver enzyme activities and the ammonia level were elevated. Atrial fibrillation with a pulse frequency of 36-52 beats per minute was noticed. On both sides a holosystolic murmer with the maximum intensity on the right side could be auscultated. Postmortem examination revealed eccentric hypertrophy of the right atrium and a pale spotted myocardium, most prominently of the right ventricle, with secondary venous congestion of the azygos and mesenteric veins. The liver changes were indicative of chronic congestion. Despite the normal pulse rate, it appeared that congestive heart failure due to cardiomyopathy, was responsible for the presenting symptoms of this patient.
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PMID:Atrial fibrillation associated with central nervous symptoms and colic in a horse: a case of equine cardiomyopathy. 956 65

We presented a case of Creutzfeldt-Jakob disease (CJD) associated with ocular dipping (OD). A 65-year-old woman was hospitalized with two months history of progressive ataxia and mental deterioration. On admission, she was bed-ridden and stuporous with rigidity of the four limbs. Her both eyes were noted to deviate downward slowly from midpossition, taking 1 to 3 seconds to reach the nadir and rapidly returned to midpossition. It was felt that these abnormal eye movements are compatible with OD. Findings of EOG were compatible with that of typical OD. Electroencephalogram obtained a few months later revealed periodic synchronous discharge. Magnetic resonance imaging of the brain which had demonstrated mild cerebral atrophy in the beginning subsequently revealed full-brown cerebral atrophy. Hence, she was diagnosed of having CJD. There has been no report of CJD associated with OD. The OD was observed to last as long as 110 days. When the above described abnormal eye movements were noted, there was no signs indicative of brain stem dysfunction present. Therefore, we feel that the present case suggest that a diffuse cerebral dysfunction involving the cerebral cortex and basal ganglia may underlie in the development of OD.
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PMID:[Creutzfeldt-Jakob disease associated with ocular dipping--a case report]. 959 17

The mouse neurological mutant lethargic (lh) is characterized by ataxia, focal myoclonus, and absence epilepsy due to a loss-of-function mutation in the beta4 subunit of the voltage-gated calcium channel. To evaluate the role of this channel subunit in human neurological disease, we determined the chromosomal location and intron/exon structure of the human CACNB4 gene. The 1560-bp open reading frame of the CACNB4 cDNA predicts a 58-kDa protein with an amino acid sequence that is 99% identical to the rat protein. The 13 coding exons of CACNB4 span >55 kb of genomic DNA. Human cerebellar RNA contains one major CACNB4 transcript that is 9 kb in length. Expression of CACNB4 was detected in cerebellum, kidney, testis, retina, lymphoblasts, and circulating lymphocytes. Retinal transcripts were localized by in situ hybridization to ganglion cells and the inner nuclear layer. Analysis of the GeneBridge 4 radiation hybrid mapping panel localized CACNB4 to position 791 cR on human chromosome 2, in a conserved linkage group on human 2q22-q31 and mouse chromosome 2. We localized CACNB4 to the 1.3-Mb YAC clone 952F10 in Whitehead contig WC861, along with the polymorphic markers D2S2236 and D2S2299. The chromosomal linkage of three of the four beta subunit genes to homeobox gene clusters associates the evolutionary origin of the beta gene family with the events that generated the four HOX clusters early in vertebrate evolution.
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PMID:Calcium channel beta 4 (CACNB4): human ortholog of the mouse epilepsy gene lethargic. 962 18

Immune-mediated hemolytic anemia secondary to bee envenomation developed in 2 dogs. Clinical signs included lethargy, hematuria, ataxia, and seizures; 1 dog died. Clinicopathologic data included nonregenerative anemia, spherocytosis, positive results for Coombs' test, and occult hematuria. Treatment included oral administration of corticosteroids at immunosuppressive dosages and supportive care. The surviving dog initially responded to corticosteroids, but hemolysis recurred as the dosage was tapered. Hemolysis resolved with prolonged administration of corticosteroids. Bee venom contains hyaluronidase, histamines, and hemolysins that cause toxic and hemolytic effects. Envenomation should be considered in any dog with hemolytic anemia in which other causes are ruled out and exposure to bees is known.
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PMID:Bee sting envenomation resulting in secondary immune-mediated hemolytic anemia in two dogs. 1020 Jul 97

A 5-month-old 22-kg (48.4-lb) sexually intact male Collie was examined after ingesting a moxidectin-containing deworming medication. The dog was comatose and had respiratory arrest after progressively worsening lethargy, ataxia, and seizures. Exposure was confirmed by isolation of moxidectin from a biopsy specimen of adipose tissue, using liquid chromatography-mass spectroscopy methods. Treatment included use of intermittent positive-pressure ventilation, activated charcoal and cathartic administered enterally, nutrients administered via nasogastric tube, and intensive supportive care. The dog was weaned from a ventilator on day 6 after ingestion and was discharged on day 10. The dog was considered clinically normal during examination 24 days after ingestion. On the basis of the dog reported here and toxicologic data provided by the manufacturer of the deworming product, some Collies may have increased susceptibility to products containing high doses of moxidectin.
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PMID:Respiratory failure attributable to moxidectin intoxication in a dog. 1061 13

Inactivation of the beta4 subunit of the calcium channel in the mouse neurological mutant lethargic results in a complex neurological disorder that includes absence epilepsy and ataxia. To determine the role of the calcium-channel beta4-subunit gene CACNB4 on chromosome 2q22-23 in related human disorders, we screened for mutations in small pedigrees with familial epilepsy and ataxia. The premature-termination mutation R482X was identified in a patient with juvenile myoclonic epilepsy. The R482X protein lacks the 38 C-terminal amino acids containing part of an interaction domain for the alpha1 subunit. The missense mutation C104F was identified both in a German family with generalized epilepsy and praxis-induced seizures and in a French Canadian family with episodic ataxia. These coding mutations were not detected in 255 unaffected control individuals (510 chromosomes), and they may be considered candidate disease mutations. The results of functional tests of the truncated protein R482X in Xenopus laevis oocytes demonstrated a small decrease in the fast time constant for inactivation of the cotransfected alpha1 subunit. Further studies will be required to evaluate the in vivo consequences of these mutations. We also describe eight noncoding single-nucleotide substitutions, two of which are present at polymorphic frequency, and a previously unrecognized first intron of CACNB4 that interrupts exon 1 at codon 21.
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PMID:Coding and noncoding variation of the human calcium-channel beta4-subunit gene CACNB4 in patients with idiopathic generalized epilepsy and episodic ataxia. 1076 41

Many important aspects of our life are regulated by the free cytosolic Ca2+ concentration. The intracellular Ca2+ signal is regulated both in space, frequency and amplitude. Each cell chooses a unique set of Ca2+ signals to control its function. Ca2+ signal transduction is based on rises in free cytosolic Ca2+ concentration. Ca2+ can come from the extracellular space or be released from intracellular stores. Extracellular Ca2+ enters the cell through various types of plasma-membrane Ca2+ channels and leaves the cell using Ca2+ pumps and Na+/Ca(2+)-exchangers. Ca2+ is accumulated in intracellular stores by means of Ca2+ pumps and is released via inositol 1,4,5-trisphosphate (IP3) and ryanodine receptors. Mutations or abnormalities in one of the above mentioned Ca(2+)-transporting proteins can lead to disease. Skeletal-muscle pathology can be caused by abnormal ryanodine receptors (malignant hyperthermia, porcine stress syndrome, central core disease), plasma-membrane Ca2+ channels (hypokalemic periodic paralysis, muscular dysgenesis mice, paraneoplastic Lambert-Eaton myasthenia syndrome) or Ca2+ pumps (Brody disease). Neurologic disorders can be related to altered function of plasma-membrane Ca2+ channels (episodic ataxia type 2, spinocerebellar ataxia type 6, familial hemiplegic migraine, glutamate excitotoxicity, tottering, leaner, lethargic and stargazer mice), IP3 receptors (Lowe's oculocerebrorenal syndrome, manic depression, Alzheimer's disease, opisthotonos mice) and Ca2+ pumps (deafwaddler mouse and wriggle mouse sagami). Two skin diseases are caused by Ca(2+)-pump mutations (Darier disease and Hailey-Hailey disease). Incomplete X-linked congenital stationary night blindness is caused by a mutation in the plasma-membrane Ca2+ channels in rods and cones.
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PMID:[Intracellular calcium: physiology and physiopathology]. 1119 78

Estimates of epilepsy incidence among the U.S. population range between 0.5% and 1%. The most common type of seizure in adult patients is partial onset. Approximately 20% of these patients are refractory to antiepileptic drug therapy and experience intolerable side effects such as confusion, dizziness, weight gain, lethargy, and ataxia. The ketogenic diet appears to be beneficial for children but is not considered a standard option for adults. Epilepsy surgery can be an option for many and may offer control or a reduction in seizures. However, many patients are opposed to cranial surgery or may not tolerate the ketogenic diet. Recent advances in biomedical technology and perfection in surgical techniques have shown vagus nerve stimulation (VNS) using the Neuro Cybernetic Prosthesis (NCP) system is an effective new treatment option in reducing seizure frequency. On July 16, 1997, the U.S. Food and Drug Administration (FDA) approved the use of the NCP for vagus nerve stimulation, as an adjunctive treatment for refractory partial onset seizures in adults and adolescents over 12 years of age. Murphy et al. and Wheless have reported similar results in children younger than 12 years. VNS represents the first therapy using a medical device approved by the FDA for the treatment of refractory seizures. An estimated 10,000 patients have been implanted with the device.
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PMID:Practical issues and concepts in vagus nerve stimulation: a nursing review. 1132 19


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