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Biomedical subjects

C E Williams

Publications and source records attributed to C E Williams.

At least 73 records · Page 4Linked to original sources
PubMed1994

Two models for determining the mechanisms of damage and repair after hypoxic-ischaemic injury in the developing rat brain.

Hypoxic-ischaemic (HI) brain injury can lead to selective neuronal loss or pannecrosis. Different mechanisms of damage and recovery may be associated with either pattern of cell loss. Two preparations were developed to investigate the role of growth factors and other mechanisms associated with either of these patterns of damage in the developing brain. Twenty-one-day-old Wistar rats underwent permanent unilateral right carotid artery ligation. Following surgery, ligated rats were warmed for 2 h at 34 degrees C with 85 +/- 5% relative humidity and then exposed to either 15 or 60 min of 8% O2. The rats were killed and brains perfusion fixed 5 days post-hypoxia for histological analysis. Rats exposed to 15 min of hypoxia-ischaemia suffered no mortality and 90% developed selective neuronal loss in the frontoparietal cortex and hippocampal CA1 region of the ipsilateral hemisphere. Rats exposed to 60 min of hypoxia consistently developed cortical pannecrosis and cellular loss in the striatum, thalamus, hippocampus and dentate gyrus of the ipsilateral hemisphere. The advantage of these models were ease of preparation, consistent neuronal loss scores and low mortality. The ability to induce either selective neuronal loss or pannecrosis provides an opportunity to investigate the mechanisms of damage or recovery associated with each pattern of cell loss.

Animals↗
PubMed1994

Monosialoganglioside GM1 treatment after a hypoxic-ischemic episode reduces the vulnerability of the fetal sheep brain to subsequent injuries.

OBJECTIVE: A transient hypoxic-ischemic episode can markedly sensitize regions of the fetal brain, particularly the striatum, to further insults occurring in close succession. The purpose of this study was to determine whether ganglioside GM1 given to the fetus after a hypoxic-ischemic episode can counteract this sensitization and protect against subsequent insults. STUDY DESIGN: Chronically instrumented near-term fetal sheep (119 to 133 days) were subjected to three 10-minute episodes of reversible cerebral ischemia at 1-hour intervals. Six were given 30 mg/kg ganglioside GM1 through the umbilical vein, commencing immediately after the release of the occluder, over the next 2 hours, followed by a continuous infusion of 30 mg/kg/day over 60 hours after ischemia; these were compared with seven vehicle-treated controls. The time course of electrocorticographic activity and cytotoxic edema within the parasagittal cortex were determined with real-time spectral analysis and continuous impedance measurements, respectively. The degree and distribution of neuronal death was assessed histologically 72 hours later. RESULTS: Ganglioside GM1 improved recovery of primary edema and markedly reduced histologic damage (p < 0.001), particularly in the striatum, hippocampus, and cortex. At 72 hours after ischemia electrocorticographic activity had returned to normal in the ganglioside GM1-treated group but was still depressed (p < 0.001) in the control group. CONCLUSION: These results showed that ganglioside GM1 treatment initiated immediately after a transient hypoxic-ischemic episode stabilized membrane function and markedly improved neuronal outcome after subsequent insults, suggesting its potential therapeutic value in acute situations of repeated hypoxia-ischemia in the perinatal period.

Animals↗
PubMed1994

Increased vulnerability to neuronal damage after umbilical cord occlusion in fetal sheep with advancing gestation.

OBJECTIVE: The purpose of this study was to compare systemic responses and neurologic consequences of umbilical cord occlusion in fetal sheep with advancing gestation. STUDY DESIGN: The umbilical cord was occluded for 10 minutes in nine midgestation (90 to 92 days) and 10 late-gestation (135 to 136 days) chronically instrumented fetuses. Systemic and cortical electrophysiologic effects were compared by analysis of variance. The extent of neuronal loss was determined 3 days later. RESULTS: During occlusion, hypotension (23 +/- 2 mm Hg) and cortical cytotoxic edema were more marked in older fetuses (p < 0.001). On reperfusion, the edema, rebound tachycardia, and hypertension resolved within 20 minutes. Recovery of electroencephalographic activity (3.1 +/- 0.8 hours) and lactate levels (> 2 hours) was slower in late-gestation fetuses (p < 0.05). Neuronal loss, which was observed only in the older group, was predominantly in the hippocampus and was associated with the severity of hypotension during umbilical occlusion but not with systemic lactate levels. CONCLUSION: Late-gestation fetal sheep are neurologically more susceptible to umbilical cord occlusion than are midgestation fetal sheep. Possibly the lesser ability of the older fetuses to maintain blood pressure and cerebral plasma membrane function during asphyxia contributes to the greater vulnerability in the gray matter.

Analysis of Variance↗
PubMed1994

Flunarizine, a calcium channel antagonist, is partially prophylactically neuroprotective in hypoxic-ischemic encephalopathy in the fetal sheep.

Calcium antagonist therapy has been reported to reduce neuronal death after hypoxia-ischemia; however, its potential use in prenatal hypoxic-ischemic events has received little attention. We examined the effect of pretreatment with flunarizine in chronically instrumented late gestation fetal sheep subjected to 30 min of cerebral ischemia. Eight fetuses were given 0.11 mmol (45 mg) of flunarizine over 2 h preischemia (high dose), 10 were given 0.07 mmol (30 mg) over 3 h preischemia (low dose), 17 were given nothing (ischemia controls), and 5 received neither the ischemic insult nor any treatment (sham controls). The fetal electrocorticogram was monitored for 3 d postinsult. Histologic outcome was quantified after 72 h. Low-dose, but not high-dose, flunarizine therapy was associated with an overall reduction in cerebral damage (p < 0.01), a greater final electrocorticogram intensity, and a reduction in the incidence of seizures (p < 0.02) compared with ischemia controls. High-dose, but not low-dose, flunarizine was associated with a significant acute mortality and a decrease in fetal blood pressure (p < 0.05) at the time of occlusion, although there was no effect on the initial hypertensive response to occlusion. These observations suggest that flunarizine is partially neuroprotective when given before severe global ischemia in utero, but that its hypotensive effects make it unsuitable for prophylactic administration in utero.

Animals↗
PubMed1993

Intraosseous lipomas.

Intraosseous lipomas are considered to be rare tumours. We describe four cases and discuss their appearances and diagnosis. It is likely with the increasing frequency of computed tomography and magnetic resonance examinations of the lumbar spine that many more asymptomatic lesions will present to the radiologist and that these tumours are not as rare as the literature would suggest.

Adult↗
PubMed1993

RFLP analysis of chromosomal segregation in progeny from an interspecific hexaploid somatic hybrid between Solanum brevidens and Solanum tuberosum.

Segregation of restriction fragment length polymorphism (RFLP) loci was monitored to determine the degree of homeologous pairing and recombination in a hexaploid somatic hybrid, A206, the result of protoplast fusion between Solanum tuberosum (PI 203900, a tetraploid cultivated potato) and Solanum brevidens (PI 218228), a diploid, sexually incompatible, distant relative harboring several traits for disease resistance. Somatic hybrid A206 was crossed to Katahdin, a tetraploid potato cultivar, to generate a segregating population of pentaploid progeny. Although the clones of the tetraploid S. tuberosum lines PI 203900 and Katahdin were highly polymorphic, the diploid S. brevidens clone was homozygous at all but two of the tested RFLP loci. Thus, homeologous recombination could be detected only when S. tuberosum and S. brevidens chromosomes paired and the S. brevidens homologs then segregated into separate gametes. A bias toward homologous pairing was observed for all 12 chromosomes. At least four and perhaps six chromosomes participated in homologous pairing only; each of 24 progeny contained all S. brevidens-derived RFLP markers for chromosomes 4, 8, 9 and 10. The remaining six chromosomes paired with their homolog(s) about twice as often as expected if hexaploid pairings were completely random. Where detectable with RFLPs, homeologous recombination (both single and double) occurred at a frequency of 1.31 per chromosome. Cytological observations of meiosis I in the somatic hybrid indicated that homeologous pairing had occurred. Enhanced recombinational activity was observed for chromosome 2. A specific small deletion from chromosome 4 was detected in A206 and 11 other somatic hybrids out of 14 screened.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromosomes↗
PubMed1993

Frequent episodes of brief ischemia sensitize the fetal sheep brain to neuronal loss and induce striatal injury.

We examined the neuronal consequences of repeated brief episodes of in utero cerebral hypoxia-ischemia. Chronically instrumented fetal sheep were subjected to three 10-min episodes of reversible cerebral ischemia, repeated at either 1-h (n = 8) or 5-h (n = 5) intervals. Four fetuses were subjected to a single 10-min of ischemia and 17 fetuses to a single 30-min of ischemia. Repeated insults altered the distribution of damage with relatively marked striatal injury compared with isolated episodes of ischemia (p < 0.01). Frequent insults were associated with greater neuronal loss (p < 0.01) and a failure to restore electrocorticographic activity and resolve cortical cytotoxic edema between insults. Intermittent cortical hyperexcitability developed after repeated insults irrespective of the interval between insults. These findings emphasize that repeated brief episodes of ischemia alter the distribution of damage and sensitize the fetal brain to neuronal injury, particularly if the episodes are frequent. Striatal damage may be a feature of multiple but not single insults.

Animals↗
PubMed1993

Pretreatment with monosialoganglioside GM1 protects the brain of fetal sheep against hypoxic-ischemic injury without causing systemic compromise.

The purpose of this study was to determine whether prophylaxis with monosialoganglioside GM1 can protect the fetus from hypoxic-ischemic encephalopathy in utero. Because some protective strategies can compromise the fetus, the effect of GM1 treatment on metabolic status and blood pressure was also evaluated. Chronically instrumented near-term fetal sheep (119-133 d) were subjected to 30 min of severe cerebral ischemia. Six were given 30 mg/kg GM1 through the umbilical vein 2 h before insult followed by continuous infusion of 30 mg/kg/d over the next 60 h, and these were compared with seven vehicle-treated control sheep. The time course of electrocorticographic activity and cytotoxic edema within the parasagittal cortex were determined with real-time spectral analysis and continuous impedance measurements, respectively. Histologic outcome was assessed 72 h later. Pretreatment with GM1 improved recovery of primary edema, reduced the duration of epileptiform activity (15 +/- 2 versus 31 +/- 5 h; p < 0.05) and the magnitude of secondary edema (p < 0.05). At 72 h, histologic damage was reduced, particularly in the cortex (p < 0.05) and hippocampus (p < 0.01), and residual electrocorticographic activity was increased in the GM1-treated group (-5 +/- 1 versus -9 +/- 3 dB, p < 0.01). GM1 infusion did not alter arterial blood pressure or metabolic status. These results indicate that GM1 can protect the fetal brain against hypoxic-ischemic injury without causing hypotension or metabolic compromise.

Animals↗
PubMed1993

Pathophysiology of perinatal asphyxia.

Following a severe asphyxial episode many cells can recover metabolically, and a cascade of processes are triggered in which intervention, even some hours later, can allow rescue of some cells that would otherwise die. A number of principles, however, needs to be carefully considered before extrapolating from animal to human trials. In particular, the effects on long-term outcome and on those who are compromised by intrauterine growth retardation need to be determined. It is critical to be able to identify rapidly those infants in terms of nature and severity of injury who are most likely to benefit from treatment. The dimension of time and phase of injury or recovery are key factors to effective intervention. Novel continuous cerebral function monitoring techniques such as those based on real-time spectral analysis of the EEG activity, cortical impedance monitoring, and near-infrared spectroscopy have considerable potential for determining the severity and pathophysiologic phase of injury on line.

Adaptation, Physiological↗
PubMed1992

Outcome after ischemia in the developing sheep brain: an electroencephalographic and histological study.

The role of seizures occurring with perinatal hypoxic-ischemic encephalopathies is unclear. We examined the relationships between the time course of parasagittal electroencephalographic (EEG) activity and pathological outcome following transient cerebral ischemia, which was induced in 33 chronically instrumented fetal sheep by occluding the carotid arteries after ligation of the vertebral-carotid anastomoses. The EEG was quantified with real-time spectral analysis. Histological outcome was assessed 72 hours later. After 10 or 20 minutes of ischemia, EEG activity was depressed and then progressively recovered and mild selective neuronal loss was seen. The length of this depression correlated with the duration of ischemia (r = 0.88). After 30 or 40 minutes of ischemia, EEG activity remained depressed for 8 +/- 2 hours, followed by a rapid transition to low-frequency epileptiform activity that reached maximum intensity at 10 +/- 3 hours. By 72 hours, EEG intensity had fallen below control levels. This sequence of prolonged depression, epileptiform activity, and then loss of intensity was associated with the development of laminar necrosis of the underlying cortex. These electrophysiological sequelae may have prognostic value. The results indicate that after a severe hypoxic-ischemic insult, the parasagittal cortex becomes hyperexcitable before the final loss of activity. Secondary neuronal death may occur in this phase.

Animals↗
PubMed1992

Suppression of postischemic epileptiform activity with MK-801 improves neural outcome in fetal sheep.

To determine the effect of suppression of epileptiform activity that develops after hypoxic-ischemic injury in the immature brain, chronically instrumented near-term fetal sheep (119-133 days) were subjected to 30 minutes of complete cerebral ischemia: 6 were given a 0.3-mg/kg bolus of MK-801 at 6 hours after the insult followed by continuous infusion of 1 mg/kg over the next 36 hours, and were compared to 6 control sheep. Electrocorticographic activity and edema within the parasagittal region of the cortex were quantified with real-time spectral analysis and impedance measurements, respectively. Histological outcome was assessed 72 hours later. The intense epileptiform activity seen from 9 +/- 2 to 30 +/- 3 hours in the control group was completely suppressed in the MK-801-treated group. The onset of secondary cortical edema was delayed from 9.4 +/- 1.1 hours to 14.8 +/- 0.7 hours (p < 0.01). Neuronal damage was reduced, particularly in the lateral cortex and hippocampus (p < 0.05). Infarction of the parasagittal cortex was not prevented. These results suggest that N-methyl-D-aspartate-mediated epileptiform activity that develops after a global hypoxic-ischemic insult worsens neuronal outcome in the immature brain.

Animals↗
PubMed1992

Transient umbilical cord occlusion causes hippocampal damage in the fetal sheep.

OBJECTIVE: The purpose of our study was to examine the neuronal outcome after a standardized period of umbilical cord occlusion. STUDY DESIGN: The umbilical cord was clamped for 10 minutes in nine experimental and four control chronically instrumented fetal sheep. Three days later the animals were killed for histologic interpretation. Systemic, electrophysiologic, and neurohistologic effects were compared by analysis of variance. RESULTS: Clamping of the cord resulted in transient severe asphyxia, hypotension (24 +/- 5 mm Hg, p < 0.01), bradycardia (72 +/- 14 beats/min, p < 0.001), depressed electroencephalographic activity (-17 +/- 2 dB, p < 0.001), and an increase in cortical impedance. The electroencephalographic activity was depressed for 5 +/- 2 hours in spite of rapid recovery of arterial oxygen content. Neuronal loss was found in the hippocampus. Neither epileptiform electroencephalographic activity nor infarction were observed. Three animals with poor blood gas levels died during the occlusion. CONCLUSION: An isolated and brief period of umbilical cord occlusion in utero can cause predominantly hippocampal damage without persistent functional changes in cortical activity and with rapid recovery of other potential indicators of fetal asphyxia.

Analysis of Variance↗
PubMed1992

Disability and the diagnostic quality of barium meals in elderly patients.

It is often assumed that the diagnostic quality of a barium meal is likely to be impaired in elderly or disabled patients. We related the technical and diagnostic quality of 76 consecutive barium meals to the physical and mental status of the elderly patients undergoing the investigation. Fifty-three (70%) of the examinations were of good or excellent diagnostic quality and we found no association between diagnostic quality of the barium meal and the patient's age, mobility score, activities of daily living score or mental test score.

Activities of Daily Living↗