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Biomedical subjects

E J Williams

Publications and source records attributed to E J Williams.

At least 37 records · Page 2Linked to original sources
PubMed2000

Linear coupling between functional magnetic resonance imaging and evoked potential amplitude in human somatosensory cortex.

The interpretation of task-induced functional imaging of the brain is critically dependent on understanding the relationship between observed blood flow responses and the underlying neuronal changes. However, the exact nature of this neurovascular coupling relationship remains unknown. In particular, it is unclear whether blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI) responses principally reflect neuronal synaptic activity. In order to address this issue directly in humans, we measured the increase in somatosensory evoked potential amplitude and fMRI BOLD changes to increases in intensity of median nerve electrical stimulation in five healthy non-anaesthetized subjects. We found that mean N20-P22 amplitudes increased significantly with stimulus intensity in all subjects, as did fMRI BOLD percentage signal intensity change. Moreover, the intensity of the BOLD signal was found to correlate linearly with evoked potential amplitude in four of the five subjects studied. This suggests that the BOLD response correlates with synchronized synaptic activity, which is the major energy consuming process of the cortex.

Adult↗
PubMed2000

Incidence and types of adverse events and negligent care in Utah and Colorado.

BACKGROUND: The ongoing debate on the incidence and types of iatrogenic injuries in American hospitals has been informed primarily by the Harvard Medical Practice Study, which analyzed hospitalizations in New York in 1984. The generalizability of these findings is unknown and has been questioned by other studies. OBJECTIVE: We used methods similar to the Harvard Medical Practice Study to estimate the incidence and types of adverse events and negligent adverse events in Utah and Colorado in 1992. DESIGN AND SUBJECTS: We selected a representative sample of hospitals from Utah and Colorado and then randomly sampled 15,000 nonpsychiatric 1992 discharges. Each record was screened by a trained nurse-reviewer for 1 of 18 criteria associated with adverse events. If > or =1 criteria were present, the record was reviewed by a trained physician to determine whether an adverse event or negligent adverse event occurred and to classify the type of adverse event. MEASURES: The measures were adverse events and negligent adverse events. RESULTS: Adverse events occurred in 2.9+/-0.2% (mean+/-SD) of hospitalizations in each state. In Utah, 32.6+/-4% of adverse events were due to negligence; in Colorado, 27.4+/-2.4%. Death occurred in 6.6+/-1.2% of adverse events and 8.8+/-2.5% of negligent adverse events. Operative adverse events comprised 44.9% of all adverse events; 16.9% were negligent, and 16.6% resulted in permanent disability. Adverse drug events were the leading cause of nonoperative adverse events (19.3% of all adverse events; 35.1% were negligent, and 9.7% caused permanent disability). Most adverse events were attributed to surgeons (46.1%, 22.3% negligent) and internists (23.2%, 44.9% negligent). CONCLUSIONS: The incidence and types of adverse events in Utah and Colorado in 1992 were similar to those in New York State in 1984. Iatrogenic injury continues to be a significant public health problem. Improving systems of surgical care and drug delivery could substantially reduce the burden of iatrogenic injury.

Adolescent↗
PubMed1999

Choosing between small, likely rewards and large, unlikely rewards activates inferior and orbital prefrontal cortex.

Patients sustaining lesions of the orbital prefrontal cortex (PFC) exhibit marked impairments in the performance of laboratory-based gambling, or risk-taking, tasks, suggesting that this part of the human PFC contributes to decision-making cognition. However, to date, little is known about the particular regions of the orbital cortex that participate in this function. In the present study, eight healthy volunteers were scanned, using H(2)(15)0 PET technology, while performing a novel computerized risk-taking task. The task involved predicting which of two mutually exclusive outcomes would occur, but critically, the larger reward (and penalty) was associated with choice of the least likely outcome, whereas the smallest reward (and penalty) was associated with choice of the most likely outcome. Resolving these "conflicting" decisions was associated with three distinct foci of regional cerebral blood flow increase within the right inferior and orbital PFC: laterally, in the anterior part of the middle frontal gyrus [Brodmann area 10 (BA 10)], medially, in the orbital gyrus (BA 11), and posteriorly, in the anterior portion of the inferior frontal gyrus (BA 47). By contrast, increases in the degree of conflict inherent in these decisions was associated with only limited changes in activity within orbital PFC and the anterior cingulate cortex. These results suggest that decision making recruits neural activity from multiple regions of the inferior PFC that receive information from a diverse set of cortical and limbic inputs, and that the contribution of the orbitofrontal regions may involve processing changes in reward-related information.

Adult↗
PubMed1999

Evidence for and against a pivotal role of PI 3-kinase in a neuronal cell survival pathway.

PI 3-kinase has emerged as a key enzyme for regulating neuronal cell survival. However, it has not as yet been demonstrated whether activation of the endogenous pool of the enzyme, that is regulated by the p85 subunit, is sufficient to promote a survival response. It is also not known whether the FGF family of growth factors promote survival via a PI 3-kinase-dependent pathway. We have previously developed a cell permeable p85 binding peptide and shown that it can stimulate a mitogenic response in muscle cells that is dependent on a PI 3-kinase/p70 S6 kinase pathway. In the present study we show that this peptide can rescue cerebellar granule cells from death induced by serum deprivation and that this response is comparable to a growth factor response (FGF2). Experiments with wortmannin, LY294002, and rapamycin suggest that the peptide survival response is dependent on PI 3-kinase activity, but not p70 S6 kinase activity. The peptide response was correlated with a PI 3-kinase-dependent phosphorylation of Akt, an established downstream effector in the PI 3-kinase survival cascade. In contrast to the survival response stimulated by the p85 binding peptide, the response stimulated by FGF2 was not inhibited by wortmannin or LY294002, nor was it associated with phosphorylation of Akt. Thus we can conclude that activation of the endogenous pool of PI 3-kinase that is regulated by p85 is sufficient for cell survival; however, growth factors such as FGF2 can clearly support survival in a PI 3-kinase-independent manner.

Animals↗
PubMed1999

MRI in neuro-Behçet's syndrome: comparison of conventional spin-echo and FLAIR pulse sequences.

We compared the sensitivity of a fluid-attenuated inversion-recovery (FLAIR) sequence with that of a conventional dual-echo spin-echo (SE) sequence) to brain lesions in 20 patients with Behçet's syndrome. They underwent 25 MRI examinations. The images were independently analysed for the number, type and anatomical location of lesions shown. There were 18 abnormal studies (13 initial and 5 follow-up). The FLAIR sequence detected significantly more lesions than the SE TE 80 (P < 0.05) and SE TE 20 (P < 0.01) sequences. It was particularly useful for demonstrating lesions in the juxtacortical white matter, which accounted for over half the lesions detected on the FLAIR images. Of patients presenting with nonspecific symptoms such as headache, seven had normal and five had abnormal studies. All patients presenting with focal neurological signs had abnormal imaging. We found supratentorial and, in particular, juxtacortical lesions to be more frequent than previously described.

Adult↗
PubMed1999

MRI - from basic knowledge to advanced strategies: hardware.

There have been remarkable advances in the hardware used for nuclear magnetic resonance imaging scanners. These advances have enabled an extraordinary range of sophisticated magnetic resonance MR sequences to be performed routinely. This paper focuses on the following particular aspects: (a) Magnet system. Advances in magnet technology have allowed superconducting magnets which are low maintenance and have excellent homogeneity and very small stray field footprints. (b) Gradient system. Optimisation of gradient design has allowed gradient coils which provide excellent field for spatial encoding, have reduced diameter and have technology to minimise the effects of eddy currents. These coils can now routinely provide the strength and switching rate required by modern imaging methods. (c) Radio-frequency (RF) system. The advances in digital electronics can now provide RF electronics which have low noise characteristics, high accuracy and improved stability, which are all essential to the formation of excellent images. The use of surface coils has increased with the availability of phased-array systems, which are ideal for spinal work. (d) Computer system. The largest advance in technology has been in the supporting computer hardware which is now affordable, reliable and with performance to match the processing requirements demanded by present imaging sequences.

Echo-Planar Imaging↗
PubMed1999

Efficacy of epidural blood patch in the obstetric population.

A retrospective audit of obstetric epidurals was performed at Royal Surrey County Hospital. The aim was to determine the efficacy of epidural blood patch in the management of post-dural puncture headache following inadvertent dural puncture in the obstetric population, over a 5-year period between March 1993 and February 1998. During that time, there were 55 recognized dural punctures (overall incidence 0.96%). A total of 62 epidural blood patches were performed in 48 patients. Following treatment with one epidural blood patch, 33% of patients obtained complete and permanent relief, 50% partial relief and 12% no relief. Twenty-nine percent of patients required a second epidural blood patch of which 50% were completely successful, 36% were partially successful and 14% gave no relief.

Journal Article↗
PubMed1999

Testing of adult and paediatric ventilators for use in a magnetic resonance imaging unit.

We have assessed the performance of a series of ventilators (modified versions of the ventiPAC, paraPAC and babyPAC ventilators; SIMS pneuPAC Ltd, Luton, UK) in a magnetic resonance imaging (MRI) scanning environment, with MR safety and compatibility issues being addressed. Following initial modifications to remove ferromagnetic components and replace them with MR-safe materials, all three ventilators performed well in a series of tests in static magnetic fields up to 2 T. Ventilator performance was unaffected by static fields, switching gradients or radio frequency fields within the MR suite. Furthermore, the devices produced no degradation of image quality when used during MR scanning. We discuss management strategies for the care of critically ill ventilated patients during MR procedures.

Adult↗
PubMed1999

Infusion pump performance in an MR environment.

Concerns about life support equipment accompanying the critically ill patient have to date made magnetic resonance imaging (MRI) studies of this patient group the exception. We present here a series of tests performed on an IVAC P3000 infusion pump to investigate its suitability for the magnetic resonance imaging environment. We investigate safety, pump performance and image quality issues. The pump was housed at the end of the patient couch to prevent motion towards the scanner. Gravimetric tests found the pump to work within acceptable parameters at a static field of 10 mT. Image interference issues were addressed.

Artifacts↗
PubMed1999

Redefining the functional organization of working memory processes within human lateral prefrontal cortex.

It is widely held that the frontal cortex plays a critical part in certain aspects of spatial and non-spatial working memory. One unresolved issue is whether there are functionally distinct subdivisions of the lateral frontal cortex that subserve different aspects of working memory. The present study used positron emission tomography (PET) to demonstrate that working memory processes within the human mid-dorsolateral and mid-ventrolateral frontal regions are organized according to the type of processing required rather than according to the nature (i.e. spatial or non-spatial), of the information being processed, as has been widely assumed. Two spatial working memory tasks were used which varied in the extent to which they required different executive processes. During a 'spatial span' task that required the subject to hold a sequence of five previously remembered locations in working memory a significant change in blood-flow was observed in the right mid-ventrolateral frontal cortex, but not in the anatomically and cytoarchitectonically distinct mid-dorsolateral frontal-lobe region. By contrast, during a '2-back' task that required the subject to continually update and manipulate an ongoing sequence of locations within working memory, significant blood flow increases were observed in both mid-ventrolateral and mid-dorsolateral frontal regions. When the two working memory tasks were compared directly, the one that emphasized manipulation of information within working memory yielded significantly greater activity in the right mid-dorsolateral frontal cortex only. This dissociation provides unambiguous evidence that the mid-dorsolateral and mid-ventrolateral frontal cortical areas make distinct functional contributions to spatial working memory and corresponds with a fractionation of working memory processes in psychological terms.

Adult↗
PubMed1999

Magnetic resonance imaging compatibility testing of intracranial pressure probes. Technical note.

There is increasing recognition that magnetic resonance (MR) imaging and spectroscopy may provide important information in the assessment of patients with acute brain injury. However, optimum care of the acutely head injured patient requires monitoring of intracranial pressure (ICP). Although many monitoring modalities have been integrated into commercially available MR-compatible systems, there have been no reports of commonly used intraparenchymal ICP sensors in an MR environment. The authors describe the use of an ICP micromanometer probe in an MR environment, with a fiberoptic connection that interfaces the probe with a commercially available MR-compatible monitoring system. Phantom studies were performed to demonstrate the safety and compatibility of the modified MR system at 0.5 tesla. The safety of the device was assessed in relation to its interaction with the static, gradient, and radiofrequency fields used in MR imaging. The MR compatibility was documented by demonstrating that its performance was unaffected by the operation of imaging sequences and by showing that there was no degradation of the diagnostic quality of imaging data obtained during ICP monitoring.

Equipment Design↗
PubMed1999

Costs of medical injuries in Utah and Colorado.

Patient injuries are thought to have a substantial financial impact on the health care system, but recent studies have been limited to estimating the costs of adverse drug events in teaching hospitals. This analysis estimated the costs of all types of patient injuries from a representative sample of hospitals in Utah and Colorado. We detected 459 adverse events (of which 265 were preventable) by reviewing the medical records of 14,732 randomly selected 1992 discharges from 28 hospitals. The total costs (all results are discounted 1996 dollars) were $661,889,000 for adverse events, and $308,382,000 for preventable adverse events. Health care costs totaled $348,081,000 for all adverse events and $159,245,000 for the preventable adverse events. Fifty-seven percent of the adverse event health care costs, and 46% of the preventable adverse event costs were attributed to outpatient medical care. Surgical complications, adverse drug events, and delayed or incorrect diagnoses and therapies were the most expensive types of adverse events. The costs of adverse events were similar to the national costs of caring for people with HIV/AIDS, and totaled 4.8% of per capita health care expenditures in these states.

Colorado↗
PubMed1998

Stimulation of mitogenesis by a cell-permeable PI 3-kinase binding peptide.

The binding of small phosphopeptides to the SH2 domains of the p85 regulatory subunit of PI 3-kinase can activate the enzyme in vitro. In the present study a cell-permeable peptide that binds specifically to the SH2 domains of p85 has been evaluated for its ability to stimulate a mitogenic response in the C2 muscle cell line. This peptide, in contrast to four other SH2-binding peptides, was as effective as serum, EGF, and FGF at stimulating entry into S-phase. The response to the p85 binding peptide, but not FGF, was inhibited by wortmannin and rapamycin, indicating that the peptide activates the PI 3-kinase/S6 kinase signalling pathway. The peptide response was not inhibited by the MEK inhibitor (PD098059) and did not stimulate Erk phosphorylation. Thus, there would appear to be no direct cross-talk between the pathway activated by the p85 binding peptide and the p42/p44 MAPK cascade.

3T3 Cells↗
PubMed1998

Liver cirrhosis.

Liver fibrosis and its related complications continue to represent a significant worldwide healthcare burden. Over the past decade there has been considerable improvement in our understanding of the cellular mechanisms and pathophysiology underlying hepatic fibrosis. This greater insight into the relevant basic sciences may lead to the development of novel treatment strategies designed to block the fibrogenic cascade or even enhance matrix degradation. In addition, there have been significant advances in the management of the complications of cirrhosis, with specific treatments now available for some conditions. Perhaps most notably, liver transplantation is now a highly successful treatment for end-stage liver disease and should be considered in all patients with chronic liver disease.

Esophageal and Gastric Varices↗
PubMed1997

Selective inhibition of growth factor-stimulated mitogenesis by a cell-permeable Grb2-binding peptide.

The activation of the mitogen-activated protein kinase (MAPK) cascade by a variety of growth factors and other agents is central to a mitogenic response. In the case of polypeptide growth factors such as the epidermal growth factor (EGF) and platelet-derived growth factor (PDGF), the steps leading to activation of MAPK require the function of the adaptor protein Grb2 (growth factor receptor binding protein 2), which can bind either directly or indirectly via its Src homology 2 domain to activated receptor tyrosine kinases. A cell-permeable mimetic of the EGF receptor Grb2 binding site has been investigated for its ability to inhibit biological responses stimulated by a variety of growth factors. Pretreatment of cells with this peptide results in the accumulation of the peptide in cells and its association with Grb2. This is associated with a complete inhibition of the mitogenic response stimulated by EGF and PDGF. In contrast, the peptide has no effect on the mitogenic response stimulated by fibroblast growth factor. The peptide could also inhibit the phosphorylation of MAPK stimulated with EGF and PDGF in the absence of an effect on the fibroblast growth factor response. These data demonstrate that cell-permeable mimetics of Src homology 2 binding sites can selectively inhibit growth factor-stimulated mitogenesis, and also directly demonstrate specificity in the coupling of activated receptor tyrosine kinases to the MAPK cascade.

Adaptor Proteins, Signal Transducing↗