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Biomedical subjects

S Ashwal

Publications and source records attributed to S Ashwal.

At least 73 records · Page 4Linked to original sources
PubMed1992

Bacterial meningitis in children: pathophysiology and treatment.

Recent studies of the pathophysiology of bacterial meningitis have suggested that the development of neuronal injury is related to the release of vasoactive substances or alteration of blood-brain barrier permeability. Cerebral edema, increased intracranial pressure (ICP), systemic hypotension, decreased cerebral perfusion pressure, vascular inflammation, thrombosis, and a variety of other vascular changes may result in global or regional reductions in cerebral blood flow (CBF), which contribute to this insult. Approximately one-third of infants and children with bacterial meningitis will have markedly reduced CBF, and even in those children with normal total flow, regional hypoperfusion is common. Reduced CBF is associated with cerebral edema and a poor prognosis. A poor prognosis also is associated with reduced cerebral perfusion pressure. This occurs early in the course of meningitis and is primarily due to increased ICP rather than systemic hypotension. Autoregulation is preserved, suggesting that local ischemic tissue injury is more related to factors such as regional edema formation, focal vascular pathology, or specific intrinsic flow/metabolic abnormalities than to a reduction in systemic blood pressure. In contrast with other acute CNS insults, CBF/PCO2 reactivity is well preserved in many patients with meningitis; this raises the possibility that hyperventilation may cause further ischemic injury in those patients with marginal CBF. Although it is still unclear that treatment of increased ICP will affect outcome, we propose a treatment paradigm based on the results of neuroimaging studies and ICP measurements.

Animals↗
PubMed1990

Cerebral blood flow and carbon dioxide reactivity in children with bacterial meningitis.

We examined total and regional cerebral blood flow (CBF) by stable xenon computed tomography in 20 seriously ill children with acute bacterial meningitis to determine whether CBF was reduced and to examine the changes in CBF during hyperventilation. In 13 children, total CBF was normal (62 +/- 20 ml/min/100 gm) but marked local variability of flow was seen. In five other children, total CBF was significantly reduced (26 +/- 10 ml/min/100 gm; p less than 0.05), with flow reduced more in white matter (8 +/- 5 ml/min/100 gm) than in gray matter (30 +/- 15 ml/min/100 gm). Autoregulation of CBF appeared to be present in these 18 children within a range of mean arterial blood pressure from 56 to 102 mm Hg. In the remaining two infants, brain dead within the first 24 hours, total flow was uniformly absent, averaging 3 +/- 3 ml/min/100 gm. In seven children, CBF was determined at two carbon dioxide tension (PCO2) levels: 40 (+/- 3) mm Hg and 29 (+/- 3) mm Hg. In six children, total CBF decreased 33%, from 52 (+/- 25) to 35 (+/- 15) ml/min/100 gm; the mean percentage of change in CBF per millimeter of mercury of PCO2 was 3.0%. Regional variability of perfusion to changes in PCO2 was marked in all six children. The percentage of change in CBF per millimeter of mercury of PCO2 was similar in frontal gray matter (3.1%) but higher in white matter (4.5%). In the seventh patient a paradoxical response was observed; total and regional CBF increased 25% after hyperventilation. Our findings demonstrate that (1) CBF in children with bacterial meningitis may be substantially decreased globally, with even more variability noted regionally, (2) autoregulation of CBF is preserved, (3) CBF/CO2 responsitivity varies among patients and in different regions of the brain in the same patient, and (4) hyperventilation can reduce CBF below ischemic thresholds.

Bacterial Infections↗
PubMed1990

Prognostic implications of hyperglycemia and reduced cerebral blood flow in childhood near-drowning.

We retrospectively examined the clinical courses of 20 children with severe near-drowning and divided their outcomes into 3 groups: normal (4), persistent vegetative state (9), and dead (7). We reviewed serial blood glucose levels and cerebral blood flow measured by stable xenon computed tomography within the 1st 48 hours of admission to determine whether they were predictive of outcome. Total, frontal gray, frontal white, and temporal and parietal gray matter cerebral blood flows were significantly decreased in children who died compared with those who completely recovered. Only 1/2 the children surviving in a vegetative state had decreased flows compared with those who recovered. An elevated initial blood glucose was highly predictive of those patients who died (mean, 511 +/- 110 mg%) or those with vegetative survival (465 +/- 104 mg%) compared with those who recovered completely (238 +/- 170 mg%). The predictive value of initial blood glucose alone (68%) or CBF alone (50%) was similar to that of clinical rating scales or immersion/resuscitation times. The combination of blood glucose with CBF improved predictability to 79%. Our results suggest that CBF measurements are predictive of eventual death but cannot differentiate normal from vegetative survival. Combining multiple laboratory studies may be of value in predetermining the eventual outcome in near-drowning.

Blood Glucose↗
PubMed1990

Effects of hypoxia on contractility of isolated fetal lamb cerebral arteries.

We studied the contractile properties of isolated cerebral arteries in near term fetal lambs, as well as the magnitudes and rates of relaxation during moderate hypoxia. Paired 5-mm segments of basilar, middle cerebral, posterior communicating, and common carotid arteries were suspended in a temperature controlled bath and isometric tension measured during 122 mM K(+)-induced contractions. In one vessel of each pair hypoxia was imposed by switching the bubbling gas from 95% O2 + 5% CO2 to 95% N2 + 5% CO2 4 minutes into a K+ contraction, thus lowering the bath PO2 to approximately 15 Torr. After 15 min exposure to hypoxia the middle cerebral artery had relaxed 61%, the posterior communicating 46%, the basilar 44%, and the common carotid only 18% compared to normoxic controls. All cerebral arteries relaxed relatively rapidly (relaxation rates of 42-45 x 10(-4) s-1), whereas the common carotid relaxed slowly (20 x 10(-4) sec-1). The data indicate that these cerebral arteries play an important role in regulating blood flow responses during hypoxemia in intact fetuses.

Animals↗
PubMed1989

Experience with anencephalic infants as prospective organ donors.

Recent advances have made organ transplantation in newborns feasible, but the paucity of organs small enough for this age group remains a major limitation. Because anencephalic infants can survive for no more than a few weeks, they have been considered as possible organ donors for other infants. Under current law, however, they cannot be used as donors until their brain-stem activity ceases and the criteria for total brain death are thereby met. If anencephalic infants receive customary care, their solid organs usually undergo irreversible hypoxic injury during the process of dying and become unsuitable for donation by the time of death. We modified the medical care of 12 live-born anencephalic infants for one week to determine whether organ viability could be maintained and whether the criteria of total brain death could be met. Six received intensive care from birth, and six only when signs of imminent death developed. Only two infants met the criteria for total brain death within one week, and no solid organs were procured. Most organs were suitable for transplantation at birth. When intensive care was provided from birth, organ function was maintained; however, brain-stem activity ceased in only one infant within the first week. When intensive care was delayed until death was imminent, most organs were damaged to an extent that made them no longer suitable for transplantation. Our findings suggest that it is usually not feasible, with the restrictions of current law, to procure solid organs for transplantation from anencephalic infants.

Anencephaly↗
PubMed1989

Xenon computed tomography measuring cerebral blood flow in the determination of brain death in children.

Local cerebral blood flow was measured using stable xenon computed tomography in 21 children, 10 of whom were clinically brain dead and had electrocerebral silence as determined by electroencephalography. Radioisotopic brain scanning in 9 patients showed no visible cerebral activity in all patients and minimal residual sagittal sinus activity in 4. In this population, mean cerebral blood flow as measured by xenon computed tomography was 1.3 +/- 1.6 ml/min/100 gm. Respiratory support was discontinued in 8 patients, and 2 patients had cardiac arrest. Eleven profoundly comatose children who did not meet all clinical criteria for brain death and who had markedly suppressed but not isoelectric electroencephalograms had an average cerebral blood flow of 33.5 +/- 16.3 ml/min/100 gm. There was no difference in cerebral blood flow in those children who survived (30.4 +/- 16.3 ml/min/100 gm; n = 7) compared with those who died acutely (38.3 +/- 14.3 ml/min/100 gm; n = 4). Two patients who survived had average total flows of only 11.8 and 12.1 ml/min/100 gm. Our findings suggest that in infants and children older than 1 month, (1) cerebral blood flow below approximately 10 ml/min/100 gm is consistent with clinical brain death, (2) cerebral blood flow of less than 5 ml/min/100 gm is consistent with no flow as demonstrated by radionuclide techniques, and (3) flow of more than 10 to 15 ml/min/100 gm is associated with the potential for survival.

Brain Death↗
PubMed1989

Spinal cord tumor-associated syrinx mimicking abdominal epilepsy: a rare cause of childhood abdominal pain.

A 10-year-old child presented with recurrent abdominal pain. Abdominal epilepsy was suspected as conventional criteria for the diagnosis were met, including an apparent therapeutic response to anticonvulsant medication. Seven months later the patient developed recurrent abdominal pain, a gait disorder, and atrophy of the right thigh and calf. Magnetic resonance imaging of the spine revealed a thoracic syringomyelia. Anticonvulsant medications were discontinued and a syringoperitoneal shunt was placed with resolution of symptoms. This appears to be a previously undescribed presentation for syringomyelia and emphasizes the importance of considering alternative central nervous system disorders before the diagnosis of abdominal epilepsy is made.

Abdominal Pain↗
PubMed1989

Direct effects of graded hypoxia on intact and denuded rabbit cranial arteries.

In isolated rabbit common carotid, internal carotid, and basilar arteries denuded of endothelium, mounted for measurement of contractile activity, and contracted with 10 microM serotonin (common and internal carotid) or 100 microM uridine 5'-triphosphate (UTP; basilar), 20 min of severe (PO2 = 15 Torr) and moderate (PO2 = 35 Torr) hypoxia relaxed initial tensions to 17, 6, and 16% and 18, 7, and 61% of control, respectively. The corresponding values in arteries contracted with 120 mM potassium-Krebs solution were 42, 60, and 73% and 57, 72, and 88%. These data indicate that the main determinants of the responses to hypoxia were intrinsic to the vessel walls of these arteries and that complete depolarization attenuated but did not eliminate the effects of these mechanisms. Superimposed on these intrinsic mechanisms were the effects of the endothelium, which were evaluated by several methods, including integration of the area between the 20-min response time courses of corresponding intact and denuded segments. Positive and negative integrated area values indicated endothelial vasoconstrictor [endothelium-derived contracting factor (EDCF)] and vasodilator [endothelium-derived relaxing factor (EDRF)] influences, respectively. In common carotid, internal carotid, and basilar segments contracted with serotonin and/or UTP, these areas averaged 770, 354, and 44 min% during severe and 491, 189, and -411 min% during moderate hypoxia. Corresponding values during potassium contraction were 217, -271, and -356 min% and 52, -177, and -54 min%. Together, these findings suggest that 1) intrinsic vascular mechanisms contribute significantly to hypoxic cerebral vasodilation in the rabbit, 2) EDCF is more prominent but also may be more sensitive to depolarization than EDRF, 3) hypoxia promotes the simultaneous release of both EDCF and EDRF, and 4) the ratio of EDCF to EDRF released during hypoxia decreases as one moves from the rabbit common carotid to the internal carotid to the basilar arteries.

Animals↗
PubMed1989

Brain death in the newborn.

It is likely that extension of the current Task Force guidelines for the determination of brain death can include the preterm infant greater than 32 weeks' gestation and the term infant. Brain death in this age group can be ascertained solely on a clinical basis; an observation period of at least three days in the preterm infant and two days in the term infant are necessary. Neurodiagnostic testing demonstrating ECS, coupled with absence of radionuclide uptake by dynamic brain scanning, could potentially shorten these periods of observation to 24 hours.

Brain Death↗
PubMed1989

Brain death in the newborn.

The clinical courses of 18 preterm and term infants less than 1 month of age in whom brain death was diagnosed were retrospectively reviewed. Clinical diagnosis was determined neurologically and included (1) coma, (2) apnea, manifested by inability to sustain respiration, and (3) absent brainstem reflexes. Electroencephalograms were performed in all patients; 17 patients had adequate cerebral blood flow as estimated by radionuclide imaging. The results indicate that (1) neurodiagnostic tests such as electroencephalograms and radionuclide scanning reconfirmed clinically determined brain death in only one half to two thirds of patients; (2) electrocerebral silence in the absence of barbiturates, hypothermia, or cerebral malformations during 24 hours was confirmatory of brain death if the clinical findings remained unchanged; (3) absence of radionuclide uptake associated with initial electrocerebral silence was associated with brain death; (4) term infants clinically brain dead for 2 days and preterm infants brain dead for 3 days did not survive despite electroencephalogram or cerebral blood flow status; and (5) phenobarbital levels greater than 25 micrograms/mL may suppress electroencephalographic activity in this age group. The findings suggest that determination of brain death in the newborn can be made solely by using clinical criteria. Confirmatory neurodiagnostic studies are of value because they can potentially shorten the period of observation.

Apnea↗
PubMed1988

Maprotiline poisoning in a child.

A 6-year-old girl presented with tonic-clonic seizures and generalized convulsions lasting several minutes. A serum drug screen revealed maprotiline, and the estimated intake was 12 mg/kg. Despite initial neurologic impairment on discharge, follow-up 6 months later showed normal neurologic function in the patient. This report describes that case and discusses the toxicity associated with maprotiline and its management.

Anthracenes↗