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)

Mechanisms producing hypertriglyceridemia during bacterial sepsis have not been well defined. In this study lipid disposal mechanisms were assessed in 76 infected and 19 control male rhesus monkeys by the ability to dispose of triglycerides after: (1) oral lipid loading; (2) intravenous lipid loading; and (3) by lipolytic enzyme activity tests as measured by postheparin lipolytic activity (PHLA). Studies were performed both before and 48 hr after intravenous inoculation with either Salmonella typhimurium or Diplococcus pneumoniae when illness was uniformly severe and fasting serum triglyceride elevations were increased maximally. S. typhimurium-infected monkeys demonstrated significant fasting hypertriglyceridemia (p is less than 0.001), reduced clearance of orally and intravenously administered lipid and markedly reduced PHLA. During this gram-negative sepsis, mild lethargy, slight diarrhea, and a 2% mortality were observed. During D. pneumoniae sepsis, average fasting triglyceride concentrations were slightly, but not significantly elevated. While oral lipid clearance was impaired, intravenous lipid clearance was unimpaired, and PHLA was slightly reduced. Marked lethargy, agitation, and a 20% mortality were present during this gram-positive infection. Results of this study support the concept that an impairment of lipid disposal mechanisms, particularly during gram-negative sepsis with S. typhimurium, may significantly contribute to the observed hypertriglyceridemia.
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PMID:Defective lipid disposal mechanisms during bacterial infection in rhesus monkeys. 0 48

"Dale's Principle" states that each neuron releases one and only one synaptic transmitter. Mental disorders and behavioral drug effects are attributed to activation or blockade of one or more of these specific transmitters. A series of biochemical, electrophysiological, and behavioral studies suggests the alternative view that at each monoaminergic synapse the action of the transmitter is modulated by several metabolically related substances: amine analogs (2-phenylethylamine [PEA], p-tyramine, etc.), deaminated products (aldehydes, acids, and alcohols), and possibly also amino acid precursors. In support of this view, the authors present evidence for the presence, synthesis, metabolism, and biological activity (at the cellular level, using microelectrode techniques) of amino acid, amines, and deaminated compounds metabolically related to catecholamines and sorotonin. That neuroamino acids exert direct effects (not mediated via their amine metabolites) is illustrated by the rapid effects of microiontophoretic dopa upon cortical unit activity, and by the observation that neither the lethargic effect of 5-hydroxytryptophan (considered to support Jouvet's serotonergic theory of sleep) nor the behavioral stimulant effects of dopa (considered to support the catecholamine theory of affective behavior) are significantly prevented by L-aromatic amino acid decarboxylase inhibitors. The biological activity of the deaminated metabolites of catecholamines and serotonin is illustrated by the effects of their microiontophoretic administration upon cortical units. Further, probenecid (an inhibitor of acid transport across the blood-brain barrier) is shown to qualitatively alter the effects of intraventricularly administered PEA and of its metabolite phenylacetic acid upon visual evoked potentials. Rabbit brain is shown to synthesize a series of pharmacologically active noncatecholic phenylethylamines as by-products of catecholamine metabolism. Amine modulators such as PEA differ from typical transmitters by their ability to cross biological barriers; inhibition of decarboxylase in peripheral tissues only (using alpha-methyldopa hydrazine) markedly depletes brain PEA (but not catecholamines). Because of the homeostatic control of the rate of transmitter synthesis and disposition, physiological, pharmacological, and pathological changes may be expected to affect more the tissue levels of related modulators. This modulator theory of drug action is illustrated by the effect of several psychotropic drugs upon the brain levels of PEA and of norepinephrine. For instance, amphetamine initially decreases and then increases brain PEA levels, without altering brain norepinephrine levels. The authors propose an expanded "Dale's Principle": each neuron is specific in that it releases at all its endings the same pool of chemical messengers, composed of one transmitter and metabolically related modulators, the relative proportion of which is determined by the physiological state of the cell (biochemical plasticity)...
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PMID:Biochemical plasticity of synaptic transmission: a critical review of Dale's Principle. 0 60

In the light of three case histories, other personal observations and the literature, the clinical and electroencephalographical differences between absences in the limited sense and continuous LENNOX petit-mal state are described and the problems of the latter discussed. As a rule, petit-mal state is diagnosed as such in young people or adults, and practically never before the 10th year of life. In about two thirds of cases, its clinical symptomatology consists of a twilight condition lasting some hours to a few days, coupled with inertia and apathy. The remaining third of the patients usually experience milder disturbances, e.g. in the form of concentration difficulties, tiredness, and (more rarely) severe forms including lethargy. The EEG correlate of a petit-mal state is made up of continuous bilaterally synchronous, frontally marked (less frequently with exclusively frontal localization), usually irregular spike waves or poly-spike waves, which frequently occur in only rudimentary forms and register a frequency of 2 1/2-4 c/sec. For the treatment of petit-mal state, benzodiazepines and in particular clonazepam (Rivotril) (1-2 mg i.v.) are recommended. During the interval condition the same therapy as with an absence epilepsy, e.g. succinimides or dipropylacetate (Depakine) is administered. Anti-grand-mal remedies, especially hydantoins, may trigger petit-mal status.
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PMID:[The petit-mal-status]. 1 55

As shown previously, the electrical function of the brain is critically dependent on cerebral blood flow in the sense that reduction beyond an ischemic threshold of approximately 15 ml/100 gm per minute (approximately 35% of control) in the baboon leads to complete failure of the somatosensory evoked response. This study tests the hypothesis that electrical failure in ischemia may be directly associated with a massive release of intracellular K+ or with a critical degree of extracellular acidosis. By microelectrode techniques, measurements of blood flow, extracellular activity of K+ and H+ as well as evoked potential were made in the baboon neocortex. Reductions in blood flow were obtained by occlusion of the middle cerebral artery and depression beyond the ischemic threshold of electrical function achieved by a reduction of systemic blood pressure which, in the ischemic zones, changed local cerebral blood flow proportionally. Abolition of evoked response could not be explained by depolarization by release of intracellular K+, nor was it critically dependent on cortical pH. However, the massive release of intracellular K+ was by itself critically dependent on cortical blood flow and occurred at 18 greater than 6 greater than 2 ml/100 gm per minute (median with 5% confidence limits). Thus a dual threshold in ischemia for neuronal function is described, the threshold for release of K+ being clearly lower than the threshold for complete electrical failure. Further, the findings support the concept of an ischemic penumbra during which the neurons remain structurally intact but functionally inactive. That neurons can survive for some time in this state of lethargy is evidenced by the observations that an increase in rCBF, if sufficient, can restore evoked potential and normalize extracellular K+ activity as well as pH.
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PMID:Cortical evoked potential and extracellular K+ and H+ at critical levels of brain ischemia. 1 21

T cell function of "lethargic" mutant mice which exhibit spontaneous thymic involution was evaluated by skin transplantation and graft-versus-host reaction tests. At 15 to 30 days of age, the mutant mice did not reject skin allografts, but by 45 days of age their response was normal. Spleen cells from 24-day-old mutant donors demonstrated delayed appearance of graft-versus-host induced splenomegaly in F1 recipients. Implications of these results in understanding the immunological status of lethargic mice were considered.
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PMID:Deficiency in the thymus-dependent immunity in "lethargic" mutant mice. 1 25

Cases of otitis media in infants under 12 weeks of age were reviewed to delineate the frequency, clinical features, and etiologic agents involved. Tympanocentesis was performed in 42 infants, 0 to 5 weeks of age, and in 17, from 6 to 11 weeks of age. The most common symptoms were irritability/lethargy (69%), fever (52%), cough (36%), vomiting (21%), diarrhea (20%), tachypnea (20%), and anorexia (18%). Associated illnesses were present in 33 (54%) of the patients, the most common being pneumonia (9), bronchiolitis (7), meningitis (6), conjunctivitis (4), and omphalitis (4). No peripartum infections or severe perinatal problems were found. Common respiratory pathogens were the predominant etiologic organisms, but coliform organisms were identified in 18% of the infants under 6 weeks of age. Cultures were sterile or grew organisms of questionable pathogenicity ("nonpathogens") in 39% of specimens. Since the signs and symptoms of otitis media in children less than 12 weeks of age are nonspecific and frequently associated with other major illnesses, the physician caring for these infants needs to be more aware of this disease and the therapeutic problems it presents.
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PMID:Otitis media in children less than 12 weeks of age. 1 93

All-night sleep was polygraphically monitored from ten normal volunteers who took placebo and three dosage levels of a new benzodiazepine hypnotic, SCH 16134, in a double-blind, crossover design. All dosages of the drug decreased the time to fall asleep, and the two highest dosages also decreased interspersed wakefulness. REM sleep was suppressed, but slow-wave sleep was not affected in this experiment. The subjective quality of sleep was improved by the new hypnotic. One subject reported that he felt lethargic the day after the largest dose.
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PMID:The effect of a new benzodiazepine on the polygraphically monitored sleep of normal volunteers. 1 91

A 5-year-old girl developed a progressive febrile neurological illness consisting of right focal seizures, right hemiparesis, and stupor evolving over a period of six weeks. During the month preceding the onset of her illness she had received two apparently unsuccessful smallpox vaccinations without a skin lesion. Elevation of cerebrospinal fluid gamma globulin and findings on brain biopsy were consistent with postinfectious encephalitis, and a simultaneous increase in serum vaccinia antibody titer suggested that the illness was postvaccinial encephalitis. Clinically, the child developed a severe extrapyramidal movement disorder during the acute phase followed by nine months of stuporous unresponsiveness, yet subsequently made a substantial recovery.
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PMID:Postvaccinal encephalomyelitis without cutaneous vaccination reaction. 3 58

1 The methodology used in studies to assess the effects of drugs on car-driving performance is reviewed. 2 Clobazam 20 mg, diazepam 10 mg or placebo were administered daily for 3 d to 24-male students with a high neuroticism score (on the Cattell Personality Factors Questionnaire). 3 Car driving performance was assessed on the second day in real traffic conditions; tests of attention and concentration and subjective assessments were made on the third day. 4 Diazepam 10 mg significantly impaired braking reaction time in comparison with clobazam 20 mg and placebo (P less than 0.01). Subjects also reported feeling more 'depressed' and lethargic after diazepam.
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PMID:Studies of clobazam and car-driving. 3 13

Two infants with lethargy, vomiting, convulsions, coma and marked metabolic acidosis were found to have very high concentrations of methylmalonic acid in their serum and urine. In vitro studies of fibroblasts demonstrated that the infants had different variants of methylmalonic acidemia.Vitamin B(12) was given in two different forms at 1 month of age and at 12 months of age. Each trial continued for 4 months but neither infant showed a clinical or biochemical response.In both infants hyperglycinemia, neutropenia and thrombocytopenia developed during acute metabolic crises only. Hypoglycemia was found in patient 2. Hyperammonemia was severe in patient 2 during acute crises but never appeared in patient 1. When clinically well, both infants continued to excrete abnormal amounts of methylmalonic acid in the urine and both had persistent compensated metabolic acidosis.Marked hyperuricemia developed in patient 1 at 18 months of age and led to progressive renal failure. Allopurinol therapy was necessary to keep the uric acid concentration within the normal range. Renal function returned to normal, as indicated by a marked increase in the renal clearance of creatinine and uric acid.Patient 1 is physically and mentally retarded, and has moderate hypotonia, hepatomegaly and persistent vomiting. Patient 2 has developed normally.The urine concentrations of methylmalonic acid in the four parents were normal.
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PMID:Methylmalonic acidemia: 6 years' clinical experience with two variants unresponsive to vitamin B12 therapy. 3 17


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