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1.
Dysphagia ; 14(4): 204-11, 1999.
Article in English | MEDLINE | ID: mdl-10467045

ABSTRACT

Control of the circulatory and respiratory systems is especially important in severely disabled people. The purpose of this study was to clarify the response of hemoglobin oxygen saturation level (SpO(2)), pulse rate, and respiratory rate during oral feeding in severely disabled persons. Continuous measurement of these variables was done by pulse oximetry and respiratory inductance plethysmography under two experimental settings in eight severely disabled persons aged 14-28 yrs. Setting I consisted of the following three procedures: (a) a 30-min period in the supine position, (b) a 50-min period in a sitting position, and (c) a 30-min period in the supine position. Setting II consisted of the following four procedures: (a) a 30-min period before the meal in the supine position, (b) a nonspecified period in a sitting position during which the meal was taken, (c) a 30-min period after the meal in the same sitting position, and (d) a 30-min period in the supine position. Results showed that mean SpO(2) level decreased and mean pulse rate increased during the meal in almost all subjects. In many cases, pulse rate and SpO(2) level did not return to baseline values in the sitting position after the meal. These findings indicate that oral feeding of severely disabled persons in a sitting position places considerable stress on the circulatory system, the effects of which may last after the meal in some cases.


Subject(s)
Disabled Persons , Eating/physiology , Oxygen/blood , Posture/physiology , Adolescent , Adult , Airway Obstruction/etiology , Apnea/etiology , Blood Circulation/physiology , Cerebral Palsy/physiopathology , Cough/etiology , Epilepsy/physiopathology , Female , Hemoglobins/metabolism , Humans , Male , Oximetry , Parkinson Disease, Postencephalitic/physiopathology , Plethysmography , Pulse , Respiration , Respiratory Sounds/etiology , Supine Position/physiology , Telemetry , Videotape Recording
2.
J Pharm Pharmacol ; 50(7): 795-801, 1998 Jul.
Article in English | MEDLINE | ID: mdl-9720630

ABSTRACT

The in-vitro pharmacological properties of (2,3-dioxo-7-(1H-imidazol-1-yl)-6-nitro-1,2,3,4-tetrahydro-1-quinoxal inyl)-acetic acid monohydrate, YM872, a novel and highly water-soluble alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)-receptor antagonist were investigated. YM872 is highly water soluble (83 mg mL(-1) in Britton-Robinson buffer) compared with 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo(F)quinoxaline (NBQX), 6-(1H-imidazol-1-yl)-7-nitro-2,3(1H,4H)-quinoxalinedione hydrochloride (YM90K) or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). YM872 potently inhibits [3H]AMPA binding with a Ki (apparent equilibrium dissociation constant) value of 0.096 +/- 0.0024 microM. However, YM872 had very low affinity for other ionotropic glutamate receptors, as measured by competition with [3H]kainate (high-affinity kainate binding site, concentration resulting in half the maximum inhibition (IC50) = 4.6 +/- 0.14 microM), [3H]glutamate (N-methyl-D-aspartate (NMDA) receptor glutamate binding site, IC50 > 100 microM) and [3H]glycine (NMDA receptor glycine-binding site, IC50 > 100 microM). YM872 competitively antagonized kainate-induced currents in Xenopus laevis oocytes which express rat AMPA receptors, with a pA2 value of 6.97 +/- 0.01. In rat hippocampal primary cultures, YM872 blocked a 20-microM AMPA-induced increase of intracellular Ca2+ concentration with an IC50 value of 0.82 +/- 0.031 microM, and blocked 300-microM kainate-induced neurotoxicity with an IC50 value of 1.02 microM. These results show that YM872 is a potent and highly water-soluble AMPA antagonist with great potential for treatment of neurodegenerative disorders such as stroke.


Subject(s)
Excitatory Amino Acid Antagonists/pharmacology , Hippocampus/drug effects , Imidazoles/pharmacology , Neuroprotective Agents/pharmacology , Quinoxalines/pharmacology , Receptors, AMPA/antagonists & inhibitors , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors , 6-Cyano-7-nitroquinoxaline-2,3-dione/metabolism , 6-Cyano-7-nitroquinoxaline-2,3-dione/pharmacology , Animals , Binding, Competitive , Buffers , Cells, Cultured , Excitatory Amino Acid Antagonists/metabolism , Hippocampus/metabolism , Kainic Acid , Male , Oocytes/drug effects , Oocytes/metabolism , Quinoxalines/metabolism , Rats , Rats, Wistar , Solubility , Xenopus laevis
3.
J Pharmacol Exp Ther ; 284(2): 467-73, 1998 Feb.
Article in English | MEDLINE | ID: mdl-9454786

ABSTRACT

YM872 ([2,3-dioxo-7-(1H-imidazol-1-yl)-6-nitro-1,2,3, 4-tetrahydro-1-quinoxalinyl]-acetic acid monohydrate), a selective, potent and highly water-soluble competitive alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor antagonist, was investigated for its neuroprotective effect against focal cerebral ischemia in halothane-anesthetized cats. Cats were subjected to permanent occlusion of the left middle cerebral artery for 6 h, then sacrificed and examined histologically. The electroencephalogram and cerebral blood flow were monitored. Intravenous infusion of YM872 starting 10 min after the onset of ischemia at a rate of 2 mg/kg/h for 6 h markedly reduced the volume of ischemic damage by 61% (from 2604 +/- 202 mm3 of the cerebral hemisphere in saline-treated cats to 1025 +/- 277 mm3 in YM872-treated cats; P < .01), as assessed in 12 stereotaxically determined coronal sections. No significant differences were observed between YM872- and saline-treated cats concerning physiological variables including brain temperature. No precipitation of YM872 in the kidney was seen in any YM872-treated animal. The present data further support the notion that the AMPA receptor plays an important role in the progression of focal ischemic damage in a gyrencephalic model. This evidence for the neuroprotective efficacy of YM872 suggests its therapeutic potential in the treatment of acute stroke in humans.


Subject(s)
Brain Ischemia/drug therapy , Imidazoles/pharmacology , Neuroprotective Agents , Quinoxalines/pharmacology , Receptors, AMPA/antagonists & inhibitors , Animals , Brain/blood supply , Cats , Cerebral Cortex/blood supply , Corpus Striatum/blood supply , Male , Regional Blood Flow/drug effects
5.
Brain Dev ; 8(6): 583-9, 1986.
Article in English | MEDLINE | ID: mdl-3826549

ABSTRACT

Polysomnograms were obtained for five severely brain damaged patients, and phasic sleep parameters-body movements (BMs) and rapid eye movements (REMs)-were examined. CT scanning of their brains demonstrated large low density areas in the bilateral hemispheres. In the three patients with flat EEG, sleep could only be classified into two stages; one with REMs[R(+)] and one without REMs[R(-)]. In the other two patients, stage R(-) was further classified into two stages according to the EEG findings. Gross movements (GMs) showed a synchronous pattern in all the patients. GMs and low angle REMs decreased in number while twitch movements and high angle REMs showed almost the same incidences as in normal controls. Localized movements showed marked variations among the patients. It was suggested that, except for normal uncoordinated asymmetrical GMs, BMs did not necessarily require higher brain structures for their generation.


Subject(s)
Brain Damage, Chronic/physiopathology , Sleep/physiology , Adolescent , Child , Child, Preschool , Electroencephalography , Female , Hematoma, Subdural/physiopathology , Humans , Infant , Male , Meningitis/physiopathology , Reye Syndrome/physiopathology , Sleep Stages/physiology , Tomography, X-Ray Computed
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