Is the cure worse than the disease? Caveats in the move from laboratory to clinic.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
C E Williams
Publications and source records attributed to C E Williams.
Cerebral histologic and electrocorticographic changes after asphyxia in fetal sheep.
Asphyxia can cause neurologic damage in the fetus, but there are few data relating severity or duration of asphyxia to the degree of cerebral damage. We report cerebral histologic and electrophysiologic changes after asphyxia in chronically instrumented late-gestation fetal sheep. We reduced uterine blood flow to produce an ascending aortic blood oxygen content less than 1.5 mM for either 30 or 60 min (n = 13). In a subsequent protocol (n = 6), if full occlusion of the common uterine artery for 15 min did not reduce the EEG voltage to less than 20% of baseline, supplementary maternal hypoxia was added for a maximum of 120 min. Histologic outcome was assessed 3 d postinsult. Uterine artery occlusion resulted in severe hypoxemia, hypercarbia, acidosis, and an initial hypertension and bradycardia. Eight of 14 surviving fetuses showed neuronal damage, with greatest loss in the parasagittal cortex, striatum, and the CA1/2 region of the hippocampus. Neuronal damage was strongly associated with the percentage of decrease in blood pressure during the insult (r = 0.75, p less than 0.005) but not with the degree of hypoxia. No other factor was independently predictive, but, when considered separately, pH (r = 0.54; p less than 0.05) and loss of intensity of the EEG (r = 0.61, p less than 0.02) at the end of asphyxia were also correlated with outcome. The pH fell to less than 7.0 in six of eight fetuses with damage, whereas it remained greater than 7.0 in five of six without damage (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Acidosis↗
Quantitative magnetic resonance studies of lumbar vertebral marrow in patients with refractory or relapsed Hodgkin's disease.
Lumbar vertebral (LV) bone marrow proton relaxation times were measured from midline sagittal magnetic resonance images of the lumbar spine of 20 patients with refractory or relapsed Hodgkin's disease (HD) referred for autologous bone marrow transplantation (ABMT) and 18 aged-matched normal volunteers. Two patients with positive bone marrow biopsies had markedly elevated mean LV marrow T1 and T1 variation. Elevated mean LV marrow T1 or T1 variation, consistent with bone marrow involvement with HD, was also seen in four other patients with negative bilateral posterior iliac crest bone marrow biopsies. Four patients with abnormal quantitative MR studies were examined serially following treatment. Mean LV marrow T1 and T1 variation normalised post ABMT, consistent with a good response to treatment. Quantitative MR studies of LV marrow may improve the detection of bone marrow involvement with lymphoma and be a complementary examination to bone marrow biopsy. Serial studies allow an objective and non-invasive assessment of treatment response.
Adult↗
Time course of intracellular edema and epileptiform activity following prenatal cerebral ischemia in sheep.
The role of edema in the pathogenesis of hypoxic-ischemic injury in the immature brain is controversial. We studied 15 chronically instrumented fetal sheep following transient cerebral ischemia, to estimate changes in extracellular space using an impedance technique, to quantify the electroencephalogram with real-time spectral analysis, and to assess histologic outcome 3 days after the insult. These measurements were made in the parasagittal cortex. There was a rapid loss of extracellular space from 5 +/- 2 minutes after the onset of ischemia. Following 10 minutes of ischemia (n = 7) the intracellular edema peaked but then quickly resolved (6 +/- 4 minutes), and mild selective neuronal loss was seen. In contrast, the swelling was biphasic after 30-40 minutes of ischemia (n = 8). The early edema resolved slowly (28 +/- 12 minutes) but incompletely, and secondary swelling began at 7 +/- 2 hours and peaked at 28 +/- 6 hours. The early swelling was the more severe. Postinsult epileptiform activity began at 8 +/- 2 hours and peaked at 10 +/- 3 hours; later there was laminar necrosis of the underlying cortex. The secondary decrease of extracellular space indicates that a progressive loss of membrane function started with the onset of postischemic epileptiform activity. The increased metabolic load of the epileptiform activity may have worsened this delayed deterioration.
Animals↗
Electrophysiological responses of the fetus to hypoxia and asphyxia.
To study the effect of transient hypoxia on neural function in utero, we examined brainstem auditory and somatosensory evoked potentials in chronically instrumented fetal sheep subject to altered maternal inspired gases. Moderate hypoxia without acidosis for 1 h, in 10 fetuses (fetal arterial pH = 7.37 +/- 0.03, PaO2 = 1.4 +/- 0.27 kPa) caused a transient depression of the later components of the evoked potentials. These recovered within 1 h. However, in 6 fetuses exposed to a second, acidotic, insult 2 days later, associated with a higher inspired PCO2 (fetal pH = 7.25 +/- 0.05, PaO2 = 1.17 +/- 0.28 kPa), there was greater impairment of the later components of the evoked potentials, with significant changes still observable 72 h later. In 4 fetuses a non-acidotic hypoxia was repeated instead and in these fetuses no persisting deficit was seen. These data suggest that there is a narrow threshold between a degree of intrauterine hypoxaemia associated with no sequelae and an insult causing persistent cerebral impairment, and that even mild acidosis may contribute to this.
Acidosis↗
Comparison of mathematical indices of fetal heart rate variability with visual assessment in the human and sheep.
Mathematical indices for quantitation of fetal heart rate variability have been proposed by numerous authors, but there have only been infrequent attempts to determine which such indices correspond to the semi-subjective evaluation of variability observed by clinicians. We have previously examined most of the published indices by using them for calculation of the variability of sets of computer-generated numbers, and seeing if they fulfill certain criteria of validity. Two sets of indices (each measuring short-term and long-term variability) were selected as acceptable. Segments of fetal heart rate records from both humans and sheep, with a wide range of subjective variability, were used to compare the mathematically derived indices with the semi-subjective evaluation of three observers. The results show that the mathematical indices of short-term variability compare closely to its subjective evaluation of being present or absent. The long-term variability of indices also increase progressively with the observers' evaluations of increasing variability. The agreement among observers, measured by Cohen's kappa test, is generally "substantial", although for some indices the agreement was "moderate" to "almost perfect". We conclude that the two sets of indices examined do quantitate what is clinically regarded as fetal heart rate variability.
Animals↗
Real-time spectral intensity analysis of the EEG on a common microcomputer.
An inexpensive system for quantitative electroencephalogram (EEG) analysis over long time periods is described. This system continuously analyses EEG for intensity versus frequency content, and saves averaged 'data reduced' intensity spectra to disk at regular intervals. The method had adequate frequency resolution for EEG analysis and demonstrated useful data reduction. In the example presented 1 day of sampled EEG data (20 megabytes) were reduced to 125 kilobytes of averaged spectra, thus illustrating the utility of the system for long term EEG studies. The system uses a low cost microcomputer (IBM AT compatible) with data acquisition board and a simple multitasking program developed with Asyst software.
Animals↗
Delayed seizures occurring with hypoxic-ischemic encephalopathy in the fetal sheep.
The pathogenesis of perinatal hypoxic-ischemic encephalopathy is poorly understood. Most insults are thought to occur before or during birth. We have investigated the evolution of parasagittal EEG activity and distribution of neuronal damage after cerebral ischemia in chronically instrumented fetal sheep (119-126 d gestation). The vertebral-carotid anastomoses were ligated and cerebral ischemia was induced by inflating occluder cuffs around the carotid arteries for 30 min. Parietal cortical EEG activity was analyzed with real-time spectral analysis with reference to control fetuses. After ischemia, EEG activity was suppressed, then rapidly increased in intensity at 8 +/- 1 h to a peak at 9 +/- 1 h postischemia. There was increased intensity of the lower frequencies (1-7 Hz) apparent as epileptiform activity with convulsions. This low-frequency hyperactivity gradually resolved by 28 +/- 7 h postinsult. After 72 h, the loss of intensity at all frequencies and laminar necrosis of the underlying parasagittal cortex indicated irreversible brain injury. Ranking the structures in order of decreasing amounts of damage: parasagittal cortex greater than hippocampal CA1, 2, and 3 regions greater than lateral cortex, hippocampal CA4 region and striatum greater than amygdala, dentate gyrus, thalamus, and cerebellum. The evolution of EEG activity and the distribution of damage after cerebral ischemia closely resembles the time course and pathology of hypoxic-ischemic encephalopathy seen in some severely asphyxiated term neonates. The consistent electrophysiologic and histologic outcome should allow this experimental approach to be valuable in testing a number of current hypotheses relating to perinatal asphyxial encephalopathy.
Animals↗
Pelvic actinomycosis: beware the intrauterine contraceptive device.
Explore the source record for details and available documents.
Actinomycosis↗
Benign cholangioma of the liver.
The ultrasonic, computed tomographic, magnetic resonance and angiographic appearances of a case of benign cholangioma of the liver are presented. They have not been previously described.
Adenoma, Bile Duct↗
Quantitative magnetic resonance imaging in autologous bone marrow transplantation for Hodgkin's disease.
Fifteen consecutive patients with refractory or relapsed Hodgkin's disease (HD) referred for autologous bone marrow transplantation (ABMT) underwent quantitative magnetic resonance (MR) studies of the lumbar vertebral bone marrow. Markedly elevated lumbar vertebral marrow T1 values suggestive of bone marrow involvement with HD were seen in four patients, two of whom had no evidence of HD on bilateral iliac crest bone marrow biopsy. Serial studies showed normalisation of T1 values in the post-transplant period. T1 relaxation rate correlated positively with time to engraftment following ABMT and a significant correlation (r = 0.73, 0.02 greater than P greater than 0.01) between T2 relaxation rate and granulocyte and macrophage colony forming units (CFU-GM) of processed bone marrow was seen. This preliminary study illustrates the potential role of quantitative MRI both in the pre-transplant assessment of patients considered for ABMT and in the post-transplant evaluation of tumour response when marrow involvement with HD is present.
Adult↗
Bone marrow disorders: characterization with quantitative MR imaging.
Thirty patients with various hematologic disorders and 15 healthy control subjects underwent quantitative magnetic resonance (MR) imaging of the lumbar spine with spin-echo techniques. Images of patients with infiltrative bone marrow disorders showed significantly more prolonged T1 times than those of control subjects (P less than .001). It was not possible to distinguish different diffuse infiltrative bone marrow disorders on the basis of T1 values. Aplastic anemia could be distinguished from normality because of significantly shortened T1 (P less than .001). A significant correlation was seen between T1 and bone marrow cellularity (r = .74, P less than .001). T2 was of no value in the characterization of bone marrow disorders. Quantitative MR imaging dose not improve the diagnostic potential of bone marrow imaging in the detection of diffuse marrow infiltrates.
Adult↗
Venous thrombosis in the neck. The role of real time ultrasound.
Real time ultrasound is being increasingly used in the diagnosis of venous thrombosis. We have studied its role in six patients with jugular and/or subclavian vein thrombosis and conclude that ultrasound is a useful, non-invasive first line imaging technique and may negate the need for venography in this small but important group of patients.
Adult↗
Metatarsal periosteal reactions: a common non-specific finding in radiographs of the diabetic foot.
Explore the source record for details and available documents.
Adult↗
Ultrasound demonstration of pericardial empyema in an infant with pyrexia of undetermined origin.
An infant with pyrexia of unknown origin presented to the Paediatric Unit. The initial infection screen was unhelpful and he was, therefore, referred for abdominal ultrasound to look for occult sepsis. During epigastric scanning, a large loculated fluid collection was demonstrated in the pericardium. A pericardial empyema should not be forgotten as a possible source of infection in the infant with undetermined pyrexia.
Empyema↗
"Pseudocatheter" due to inadvertent ventricular catheter placement.
Ultrasound is frequently used in the routine follow-up of patients who have been shunted for obstructive hydrocephalus. We report a case with "pseudocatheter" appearance due to the initial incorrect placement of the ventricular catheter. To our knowledge, such an appearance has not been previously described.
Catheters, Indwelling↗
Perinatal cerebral asphyxia: pharmacological intervention.
Perinatal asphyxia is associated with an increased risk of cerebral palsy and significant mortality. We investigated the use of flunarizine, a calcium antagonist and MK-801, an excitatory amino acid antagonist, in preventing the sequelae of severe hypoxic/ischemic insults. Flunarizine was neuroprotective in the infant rat subjected to unilateral carotid ligation and 2 h of hypoxia. Preliminary analysis of experiments in a novel model of cerebral ischemia in the fetal sheep suggests that prophylactic treatment with flunarizine greatly modified the outcome after 30 min of total ischemia. Treatment with MK-801 prevented post-ischemic seizures. The background to these developments is outlined and future prospects considered.
Animals↗