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Biomedical subjects

S Ashwal

Publications and source records attributed to S Ashwal.

At least 55 records · Page 3Linked to original sources
PubMed1995

A new model of neonatal stroke: reversible middle cerebral artery occlusion in the rat pup.

Neonatal stroke remains a complex pathophysiologic process that is poorly understood and difficult to investigate. The primary animal model used to study this phenomenon is that of unilateral carotid artery ligation with 2-3 hours exposure to severe hypoxia. A new model of neonatal stroke was developed based on transient middle cerebral artery occlusion without craniectomy. In this model a #6-0 (0.07 mm) nylon filament is passed via the carotid artery to occlude reversibly the middle cerebral artery for 4 hours under conditions of normoxia in 14- to 18-day-old spontaneously hypertensive rat pups. After removal of the filament and reperfusion for 24 hours, the infarct volume was determined using the mitochondrial stain, 2,3,5-triphenyltetrazolium chloride. Using this technique, a neocortical and caudoputamenal infarct affecting 49% of hemispheric volume that measured 180 +/- 29 mm3 (hemisphere volume = 359 +/- 16 mm3, mean +/- SEM) was created in 90% of animals (n = 8) undergoing this procedure. This model has the advantage of being relatively noninvasive, of not requiring global exposure of brain to hypoxia, and of using temporary rather than permanent occlusion. This technique should improve the ability to study the acute and long-term pathophysiology of neonatal stroke, particularly the phenomenon of reperfusion injury, as well as its sequelae in the developing nervous system.

Animals↗
PubMed1995

Proton magnetic resonance spectroscopy in children with acute central nervous system injury.

Single voxel proton magnetic resonance spectroscopy (1H-MRS) was used in 30 infants and children with acute central nervous system injuries to determine the value of changes in specific metabolite ratios in predicting outcome. The mean age of all patients was 38 +/- 52 months and the mean time of study after insult was 7 +/- 5 days. 1H-MRS was determined in the occipital gray and parietal white matter (8 cm3 volume, STEAM sequence with TE = 20 ms, TR = 3,000 ms). Data were expressed as ratios of different metabolite peak areas including N-acetylaspartate (NA), choline-containing compounds (Ch), creatine and phosphocreatine (Cr), and lactate (Lac). Statistically significant differences were observed when patients with good/moderate (G/M) outcomes (n = 17; mean age: 46 months) were compared to patients with bad outcomes (n = 10; mean age: 26 months). NA/Cr and NA/Ch were significantly lower in the bad outcome group (NA/Cr = 1.15 +/- 0.38; NA/Ch = 1.18 +/- 0.52) compared to the G/M group (NA/Cr = 1.41 +/- 0.28, P < .05; NA/Ch = 1.98 +/- 0.81, P < .01). Lactate was present in 80% of bad outcome patients and in none of the G/M group (P < .0001). Using a linear discriminant analysis and combining 4 clinical variables (Glasgow Coma Scale score, initial pH and glucose, number of days unconscious at time of 1H-MRS) allows classification of 94% of patients into their correct outcome group. Use of spectroscopy variables (NA/Cr, NA/Ch, Ch/Cr, presence of lactate) alone correctly classified 81% of patients. The combination of clinical and 1H-MRS variables correctly classified 100% of patients. Our findings suggest that 1H-MRS adds information which, in combination with clinical examination, may be useful in outcome assessment in children with serious acute central nervous system injury.

Acute Disease↗
PubMed1995

Historical aspects of the neonatal neurological examination: why child neurologists are not 'little' adult neurologists.

The origins of the neonatal neurological examination are described with their common basis attributable to evolutionary theory, the classical neurosciences, clinical neurology, and developmental psychology. It is shown that not only have the techniques of the bedside examination changed over the past half century but the purpose of the examination has also evolved; initially the examination was used to assess maturation of the developing infant, now it is used to determine whether cerebral pathology may be present and whether examination abnormalities are helpful in outcome assessment. The development of several of the current neonatal neuroogical examinations are reviewed and their cllinical and scientific basis examined.

History, 20th Century↗
PubMed1995

Neuropharmacology of progressive myoclonus epilepsy: response to 5-hydroxy-L-tryptophan.

Low concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF) of patients with progressive myoclonus epilepsy (PME) suggest hypofunctional serotonergic neurotransmission. To study this hypothesis, we enrolled 6 patients with PME [Unverricht-Lündborg disease (U-L), mitochondrial encephalomyopathy, or Lafora disease] in a controlled, double-blinded, dose-ranging, cross-over add-on pilot clinical trial of 5-hydroxy-L-tryptophan (L-5-HTP) plus carbidopa after 2 other patients had received open-label L-5-HTP for compassionate use. Prestudy CSF 5-HIAA concentrations were low (< 20 ng/ml) in 6 patients regardless of the etiology of PME. One patient with U-L disease showed clinical improvement and a fivefold increase in CSF 5-HIAA, and 1 with Lafora disease showed a twofold increase in CSF 5-HIAA without improvement. A patient with Lafora disease reported enough improvement in myoclonus-evoked convulsions to continue chronic use of the drug. One patient with mitochondrial encephalomyopathy developed status epilepticus during treatment with L-5-HTP. As a group, patients had no statistically significant changes in myoclonus evaluation scale scores, subjective and objective measures of ataxia, seizure frequency, antiepileptic drug (AED) levels, or routine blood tests. These data suggest a serotonergic abnormality regardless of the underlying etiology of PME, but one that seldom responds to acute treatment with L-5-HTP.

5-Hydroxytryptophan↗
PubMed1995

L-NAME reduces infarct volume in a filament model of transient middle cerebral artery occlusion in the rat pup.

The importance of nitric oxide (NO) during focal cerebral ischemia remains controversial as studies have suggested both a neurotoxic and neuroprotective role. In the 7 d old rat pup, NG-nitro-L-arginine, a nitric oxide synthase inhibitor, reduced infarct volume in a model of unilateral carotid ligation with 2.5 h exposure to 8% O2. The current study examined whether NO is neurotoxic in a filament model of transient middle cerebral artery occlusion (MCAO) in the 14-18-d-old rat pup. We developed a reproducible filament model of transient MCAO in 14-18-d-old spontaneously hypertensive rats (35 g) by passing a no. 6-0 (0.07-mm) nylon filament via the carotid artery to occlude the middle cerebral artery for 4 h under normoxic conditions. After filament removal and reperfusion for 24 h, we determined infarct volume using the mitochondrial stain 2,3,5-triphenyltetrazolium chloride. NO synthesis was inhibited using NG-nitro-L-arginine methyl ester (L-NAME) at a dose of 3 mg/kg, intraperitoneally, 1 h before MCAO. We measured infarct volume in control (n = 7) and L-NAME (n = 7) groups. L-NAME reduced infarct volume by 55% (p < 0.01). In the control group, infarct volume (180 +/- 29 mm3) averaged 49 +/- 7% of the left hemisphere (359 +/- 16 mm3). In the L-NAME-treated group, infarct volume (77 +/- 19 mm3) was 22 +/- 5% of the left hemispheric volume (344 +/- 2 mm3). These findings support earlier studies that used models of neonatal hypoxic-ischemic brain injury and suggest a neurotoxic role of NO. They extend these observations by demonstrating a significant reduction in infarct volume in a stroke model in the immature rat pup.

Animals↗
PubMed1995

Neurologic evaluation of the patient with acute bacterial meningitis.

Major advances in our understanding of the pathophysiology of bacterial meningitis have been made in the past decade. It is likely that interventional strategies that mediate the effects of vasoactive metabolites and neuronal and glial toxins will improve the outcome of patients with meningitis as well as other neurologic disorders. Of critical importance, as demonstrated in the case history, is the realization that many of the serious complications of meningitis occur very early in the course of the disease. If new treatment strategies are to be effective, they should be started as soon as possible. Emerging technologies such as proton magnetic resonance spectroscopy may be of benefit in helping physicians decide which patients require treatment.

Adrenal Cortex Hormones↗
PubMed1994

Life expectancy of children in a persistent vegetative state.

The persistent vegetative state (PVS) is a state of wakeful unconsciousness occurring in adults and children. Despite preservation of vegetative functions, PVS patients have a shortened life-span, although accurate information concerning this issue remains limited. The survival of children in PVS was examined to determine whether age, etiology of the vegetative state, or type of residence in which the patient lived affected the estimated survival. The data of 155,851 developmentally disabled California state residents were reviewed using the Client Development Evaluation Report (CDER). Criteria from the CDER were selected to define the vegetative state and included: lack of interaction with peers; absence of auditory, visual, and expressive or receptive language function; no hand or arm use; inability to eat, sit, roll over, or lift head; and no bowel or bladder control. There were 847 patients who met these criteria on the initial and follow-up CDERs. A product limit survival model was used to develop survival curves and to calculate the median survival time for patients grouped by age, etiology, and type of residence. Median survival (yrs) for patients who remained in PVS for the following age groups was: < 1 yr: 2.6, 1 < 2 yrs: 4.2, 2-6 yrs: 5.2, 7-18 yrs: 7.0, > or = 19 yrs: 9.9. Median survival based on etiology varied from 3.0 to 8.6 years; no consistent relationship existed between etiology and duration of survival. Survival (yrs) for patients younger than age 18 years based on type of residence included: own home: 4.5, institutions: 5.2, skilled nursing facility/private hospital: 3.2, and other community care facilities: 3.7.(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of Daily Living↗
PubMed1994

Dual effects of L-NAME during transient focal cerebral ischemia in spontaneously hypertensive rats.

The role of nitric oxide (NO) in ischemic neuronal injury is unclear. In permanent focal ischemia models, NO release has been reported to be both neuroprotective, by virtue of actions to improve cerebral blood flow (CBF) within ischemic tissue, and neurotoxic. Very little attention has been given to determining the role of NO in transient focal ischemia. In the present studies, low-dose NO inhibition using NG-nitro-L-arginine methyl ester (L-NAME; 0.1 mg/kg bolus, 0.01 mg.kg-1.min-1 iv) reduced infarct volume after 180 min of middle cerebral arterial occlusion (MCAO) and 120 min of reperfusion as measured via 2,3,5-triphenyltetrazolium chloride by 55% (P < 0.0001). Similar reductions occurred whether L-NAME was given throughout MCAO-reperfusion or just 30 or 60 min before reperfusion. L-NAME reduced CBF in the area of infarction at 30 and 180 min of MCAO by 36 and 33% (P < 0.02). In contrast, 15 min into reperfusion, L-NAME increased CBF in the area of infarction by 69% (P < 0.03) and by 27% in the contralateral homologous right hemisphere. Although vascular effects are present, these findings suggest a neurotoxic role for NO primarily during reperfusion after transient focal ischemic injury.

Animals↗
PubMed1993

Low dose L-NAME reduces infarct volume in the rat MCAO/reperfusion model.

In a variety of recent studies, inhibitors of nitric oxide (NO) synthesis have ameliorated neuronal injury during permanent focal cerebral ischemia, suggesting that NO may contribute to ischemic damage. In other studies, however, these inhibitors increased infarct volume during permanent middle cerebral artery occlusion (MCAO). One complication in these studies was that high-dose NO synthase inhibitors increased mean arterial blood pressure (MAP) by 20-30 mm Hg. Thus, it is possible that variations in the effects of NO synthesis inhibitors on infarct volume could be related to effects of these inhibitors on MAP and cerebral perfusion during or after ischemia. The present study compared the effects of control (Ringer's lactate solution) versus low-dose NO inhibition (0.1 mg/kg bolus followed by 0.01 mg/kg/min) on cerebral infarct volume using L-NAME (NG-nitro-L-arginine methyl ester) administered during a 1-h baseline period, 3-h of MCAO, and 2 h of reperfusion in the spontaneously hypertensive rat. Infarct volume was determined using the TTC (2,3,5-triphenyltetrazolium chloride) method performed 5 h after onset of occlusion. L-NAME reduced infarct volume by 55%. In the control group (n = 7), infarct volume measured 116 +/- 4 (SEM) mm3 which was 29 +/- 1% of the left hemispheric volume (400.5 +/- 0.3 mm3). In the L-NAME group (n = 7), infarct volume measured 53 +/- 8 mm3 which was only 13 +/- 2% of the left hemispheric volume (400.4 +/- 0.5 mm3).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

The persistent vegetative state in children: report of the Child Neurology Society Ethics Committee.

Increasing concern about children in a persistent vegetative state (PVS) prompted a survey of members of the Child Neurology Society regarding aspects of the diagnosis and management of this disorder. Major findings of those responding to this survey (26% response rate) were as follows: (1) 93% believed that a diagnosis of PVS can be made in children, but only 16% believed that this applied to infants younger than 2 months and 70% in the 2-month to 2-year group; (2) a period of 3 to 6 months was believed to be the minimum observation period required before a diagnosis of PVS could be made; (3) 86% believed that the age of the patient would affect the duration of time needed to make the diagnosis of PVS; (4) 78% thought a diagnosis of PVS could be made in children with severe congenital brain malformations; (5) 75% believed that neurodiagnostic studies would be of value and supportive of the clinical diagnosis of PVS; (6) members' opinions as to the average life expectancy (in years) for the following age groups after the patients were considered vegetative were: newborn to 2 months, 4.1; 2 months to 2 years, 5.5; 2 to 7 years, 7.3; and more than 7 years, 7.4; (7) 20% believed that infants and children in a PVS experience pain and suffering; and (8) 75% "never" withhold fluid and nutrition from infants and children in a PVS and 28% "always" give medication for pain and suffering.(ABSTRACT TRUNCATED AT 250 WORDS)

Advisory Committees↗
PubMed1992

Hypoxia inhibits calcium influx in rabbit basilar and carotid arteries.

We examined the hypothesis that hypoxia inhibits Ca2+ influx in isolated rabbit common carotid, internal carotid, and basilar arteries. In arteries mounted for measurement of isometric tension and exposed to 122 mM K+ in Ca(2+)-free Krebs, cumulative addition of Ca2+ produced Ca(2+)-force relations that were right-shifted by hypoxia (PO2 approximately 15 Torr) with no decrease in maximum force attained. In arteries precontracted with 122 mM K+, exposure to hypoxia produced relaxations whose rates and magnitudes were enhanced by reductions in bath Ca2+ from 8.0 to 0.8 mM. Using an ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid method for 3-min 45Ca influx measurements, modified for use in rabbit basilar and carotid arteries, we found that resting levels of Ca2+ influx (mumol.min-1.kg dry wt-1) were significantly higher in basilar (67 +/- 1, n = 10) than in internal carotid (27 +/- 1, n = 12) or common carotid (33 +/- 1, n = 12) arteries. K+ stimulation increased Ca2+ influx more than two-fold compared with control in all three artery types, and hypoxia inhibited this increase by 74% in basilar, 49% in internal carotid, and 33% in common carotid arteries. Exposure to 10 microM serotonin and 100 microM uridine 5'-triphosphate (UTP) also increased Ca2+ influx, but these increases were less than observed during K+ contractions and averaged 10 (basilar), 31 (internal carotid), and 82% (common carotid) above control. Hypoxia completely inhibited serotonin- and/or UTP-induced increases in Ca2+ influx in basilar and internal carotid segments and inhibited 47% of this increase in the common carotid segments.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗