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Biomedical subjects

R Williams

Publications and source records attributed to R Williams.

At least 163 records · Page 9Linked to original sources
PubMed2000

Acute liver failure: targeted artificial and hepatocyte-based support of liver regeneration and reversal of multiorgan failure.

Acute liver failure (ALF) still represents a major therapeutic challenge for hepatologists due to its high mortality rate as a result of multiorgan failure. Although emergency orthotopic liver transplantation represents a major advance in the management of selected patients, it is not applicable to all candidates due to limited organ availability. Therefore, new therapeutic options should be developed to bridge selected patients to transplantation or to treat patients not candidates for liver transplantation. Although new techniques for cell culture and perfusion have resulted in a number of promising devices for the provision of temporary liver support in acute liver failure, their clinical efficacy is as yet uncertain. Controlled trials on a multi-centre basis in well-defined patient groups and with standardised outcome measures, including the extent to which treatment influences cell damage and regeneration and prevents or reverses multiorgan failure, will be essential to properly evaluate the clinical value of current and evolving artificial and bioartificial devices. The same considerations must also apply to the assessment of therapeutic efficacy of hepatocyte transplantation. A better understanding of mechanisms responsible for the development of liver cell death, along with cellular and molecular mechanisms allowing surviving cells to proliferate in a hostile environment, will be required if a more targeted therapeutic approach to decreasing hepatocellular injury and enhancing liver regeneration is to be achieved. Whether extracorporeal devices or the transplantation of primary hepatocytes, stem cells or cells genetically engineered to over-express key metabolic functions, a proliferative phenotype and/or cytoprotective pathways will be best suited to meeting these demanding challenges remains to be determined.

Acute Disease↗
PubMed2000

Fulminant hepatic failure.

In recent years, considerable progress has been made in developing specific and supportive medical measures that have improved prognosis in FHF. Although new techniques for cell culture and perfusion have also resulted in a number of promising devices for the provision of temporary liver support, their clinical efficacy is as yet uncertain. Controlled multicenter trials in well-defined patient groups and with standardized outcome measures will be essential to evaluate the clinical value of these devices properly. The same considerations must also apply in assessing the efficacy of hepatocyte transplantation in FHF. A better understanding of mechanisms responsible for liver cell death and multiorgan failure, and the development of strategies to enhance liver regeneration may, in the future, allow a more targeted approach to therapy.

Clinical Trials as Topic↗
PubMed2000

October 18, 2000 8:30-8:45. Problem Solving with FDG Positron Emission Mammography.

Purpose: To examine one potential clinical application of dedicated devices for positron emission mammography.Background: Dedicated devices for breast imaging with FDG have technical specifications that appear well-suited for detecting small breast cancers, including registration with x-rays, high count sensitivity, and spatial resolution in the 2-3 mm range.Methods: In IRB-approved clinical trials, patients who were scheduled for biopsy for suspicious findings on x-ray mammograms were injected with 10-20 mCi FDG intravenously one to two hours prior to x-ray guided core biopsy or lumpectomy. Positron emission mammograms using a dedicated device were performed just before biopsy, and results compared to final histopathology.Results: Three patients whose cancers were missed on initial x-ray mammograms or whose mammograms contained subtle abnormalities that were not strongly suspicious for cancer, were shown to have very suspicious hot spots on positron emission mammograms. These patients were later confirmed to have cancer.Discussion: The role for dedicated devices for positron emission mammography is evolving. Finding cancers that are either mammographically occult or have low indices of suspicion is a potential application for this technique. Further clinical and technical work will be needed to better define the strengths and weaknesses of the device in this application.

Journal Article↗
PubMed2000

Hepatocyte growth factor/scatter factor-induced intracellular signalling.

Hepatocyte growth factor (HGF) identical to scatter factor (SF) is a glycoprotein involved in the development of a number of cellular phenotypes, including proliferation, mitogenesis, formation of branching tubules and, in the case of tumour cells, invasion and metastasis. This fascinating cytokine transduces its activities via its receptor encoded by the c-met oncogene, coupled to a number of transducers integrating the HGF/SF signal to the cytosol and the nucleus. The downstream transducers coupled to HGF/MET, most of which participate in overlapping pathways, determine the development of the cell's phenotype, which in most cell types is dual.

Animals↗
PubMed2000

Acute liver failure: established and putative hepatitis viruses and therapeutic implications.

Any virus that can cause an acute hepatitis will, on occasion, give rise to acute liver failure. Such infections can be separated into those due to the primary hepatitis viral infections A to E and those where hepatitis occurs as part of a systemic viral infection, as with infection with, for instance, Epstein-Barr virus, cytomegalovirus, Varicella zoster virus, adenovirus and Herpes simplex virus. In general, the frequency with which the different hepatitis viruses are responsible for acute liver failure is related to their underlying prevalence in particular countries. An apparent exception is the striking geographical variation in the reported prevalence of acute liver failure due to hepatitis C virus infection, with a much higher proportion of cases generally attributed to this agent in Japan and Taiwan than in Western countries. Recent work has focused on the possible importance of mutant hepatitis B viral strains, co- and super-infection with known hepatitis viruses and certain newly described agents that may account for otherwise unexplained cases of acute liver failure. Despite an improved understanding of the pathogenesis of complicating cerebral oedema and advances in general supportive care, it is likely that the most severely affected patients with acute liver failure due to viral causes will survive only with liver transplantation, at least until approaches for promoting adequate liver regeneration are successfully developed and implemented.

Brain Edema↗
PubMed2000

Early social mixing and childhood Type 1 diabetes mellitus: a case-control study in Yorkshire, UK.

AIMS: Evidence from animal models shows an increased risk of Type 1 diabetes mellitus associated with the absence of early life exposure to pathogens. To test this 'hygiene hypothesis', patterns of social mixing and infections in the first year of life and the risk of developing autoimmune diabetes in childhood were examined. METHODS: Personal interviews were conducted with the mothers of 220 children with Type 1 diabetes (0-15 years) and 433 age/sex matched controls from a population-based case control study in Yorkshire, UK. Social mixing including attendance at daycare, and infections occurring under 1 year of age were measures of exposure. Adjusted odds ratios (OR) were derived using conditional logistic regression. RESULTS: Frequency of attendance at daycare during the 1st year of life was inversely associated with childhood diabetes (OR 0.71, 95% confidence interval 0.51-1.00, P = 0.05), a finding not explained by mother's age, level of education or maternal diabetes. Increasing numbers of children in the daycare setting and numbers of sessions attended were significantly associated with increasing protection from diabetes. The strongest effect was observed in children with diabetes diagnosed aged 0-4 years. CONCLUSIONS: Social mixing through attendance at daycare in early infancy appears to confer protection against the development of childhood diabetes. This may be mediated through exposure to infectious agent(s) as a significant dose-response effect was evident with increasing numbers of child 'contacts'. These findings suggest early infectious exposure may play a role in the development of immunoregulatory mechanisms which protect against diabetes and further work is warranted.

Adolescent↗
PubMed2000

Correlating physiology with gene expression in striatal cholinergic neurones.

The expression of 34 transmitter-related genes has been examined in the cholinergic neurones of rat striatal brain slices, with the aim of correlating gene expression with functional activity. The mRNAs encoding types I, II/IIA, and III alpha subunits of the voltage-sensitive sodium channels were detected, suggesting the presence of these three types of sodium channel. Similarly, mRNAs encoding all four alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)-type glutamate receptor subunits and the NR1 and NR2A, 2B, and 2D subunits of the NMDA-type glutamate receptors were detected, suggesting that various combinations of these subunits mediate the cellular response to synaptically released glutamate. Other mRNAs detected included the NK1 and NK3 tachykinin receptors, all four known adenosine receptors, and the GABA-synthesising enzyme glutamate decarboxylase. Subpopulations of these cholinergic neurones have been identified on the basis of the expression of the NK3 tachykinin receptor in 5% and the trkC neurotrophin receptor in 12% of the cells investigated.

Action Potentials↗
PubMed2000

Efficacy of hydroquinone cream (USP 4%) used alone or in combination with salicylic acid peels in improving photodamage on the neck and upper chest.

BACKGROUND: Salicylic acid, hydroquinone, and glycolic acid have been proved effective in the treatment of photodamaged facial skin. Few reports are available on the treatment of photodamage on the neck and upper chest. OBJECTIVE: This study's purpose was to evaluate the efficacy of a cream containing 4% hydroquinone and 2% glycolic acid (LUSTRA) used alone or with salicylic acid peels in reversing actinic damage on the neck and upper chest. METHODS: Nineteen women with moderate to advanced photodamage on the neck and upper chest applied a cream containing 4% hydroquinone and 2% glycolic acid twice daily on photodamaged areas for 12 weeks. Nine of these subjects had salicylic acid peels every 3 weeks. Improvements were assessed by the investigator, the subjects, and Mexameter readings measuring melanin and erythema levels. RESULTS: The result shows that there was a 33-71% improvement in photodamage, hyperpigmentation, texture, fine lines, dryness, tone, and clarity in both groups. There were no significant differences between the two treatments. CONCLUSION: Hydroquinone 4% cream with 2% glycolic acid is safe and effective in improving photodamage on the neck and upper chest when used alone or in combination with salicylic acid peels.

Chemexfoliation↗
PubMed2000

Morphology and DNA content analysis in the evaluation of first trimester placentas for partial hydatidiform mole (PHM).

Partial hydatidiform moles (PHM) have defined villous abnormalities and are usually triploid. Their diagnosis often can be made by morphology alone, without confirmation of ploidy, but considerable interobserver variability exists. Other genetic abnormalities such as trisomy can result in placentas with abnormal villous morphology (AVM) similar to that seen in PHMs, leading to diagnostic confusion. Twenty-three cases originally diagnosed as either PHM or AVM were independently reviewed by 3 pathologists. The consensus diagnosis was PHM in 14 cases and AVM in 9. Cases with AVM showed insufficient features for an unequivocal diagnosis of PHM. DNA content was determined on paraffin-embedded tissue by fluorescence in situ hybridization (fsSH) using a chromosome 1 centromeric probe and by image cytometry (IC). Thirteen of 14 cases (93%) classified as PHM were triploid by both FISH and IC. Seven cases of AVM were diploid by FISH and IC, and 1 was triploid by FISH and IC. One of the 9 cases of AVM was determined to be trisomy 18 by karyotyping. This good correlation of consensus diagnosis with ploidy data was much greater than that obtained based on original diagnoses. Comparative genomic hybridization performed on 6 cases of AVM showed gain of chromosome 21 in 1 case and loss of X in another. PHMs displayed at least 3 of the following histologic features: 2 discrete populations of villi, circumferential mild trophoblastic hyperplasia, trophoblastic inclusions, prominent scalloping of villi, cistern formation. Nontriploid AVMs displayed at most 2 of the diagnostic features of PHM. Placentas with genetic abnormalities other than triploidy can display morphologic changes suggestive of PHM and can be misinterpreted as such by routine light microscopy. Stringent application of morphologic criteria improves the correlation of the diagnosis of PHM with triploidy.

Chorionic Villi↗
PubMed2000

The systemic inflammatory response syndrome in acute liver failure.

The systemic inflammatory response syndrome (SIRS) in acute liver failure (ALF), in which infection is common, has not been studied. In this study, SIRS components were recorded on admission and during episodes of infection, in 887 ALF patients admitted to a single center during an 11-year period. Overall, 504 (56.8%) patients manifested a SIRS during their illness, with a maximum of 1, 2, and 3 concurrent SIRS components in 166, 238, and 100 patients, respectively. In 353 (39.8%) patients who did not become infected, a SIRS on admission was associated with a more critical illness, subsequent worsening of encephalopathy, and death. Infected patients more often developed a SIRS and one of greater magnitude. The magnitude of the SIRS in 273 patients with bacterial infection correlated with mortality, being 16.7%, 28.4%, 41.2%, and 64.7% in patients with 0, 1, 2, and 3 maximum concurrent SIRS components, respectively. Similar correlations with mortality were seen for SIRS associated with fungal infection, bacteremia, and bacterial chest infection. Fifty-nine percent of patients with severe sepsis died, as did 98% of those with septic shock. A significant association was found between progressive encephalopathy and infection. Infected patients with progressive encephalopathy manifested more SIRS components than other infected patients. For patients with a SIRS, the proportions of infected and noninfected patients manifesting worsening encephalopathy were similar. In ALF, the SIRS, whether or not precipitated by infection, appears to be implicated in the progression of encephalopathy, reducing the chances of transplantation and conferring a poorer prognosis.

Acetaminophen↗
PubMed2000

Incubation phase of acute hepatitis B in man: dynamic of cellular immune mechanisms.

After hepatitis B virus (HBV) infection, liver injury and viral control have been thought to result from lysis of infected hepatocytes by virus-specific cytotoxic T cells. Patients are usually studied only after developing significant liver injury, and so the viral and immune events during the incubation phase of disease have not been defined. During a single-source outbreak of HBV infection, we identified patients before the onset of symptomatic hepatitis. The dynamics of HBV replication, liver injury, and HBV-specific CD8+ and CD4+ cell responses were investigated from incubation to recovery. Although a rise in alanine transaminase (ALT) levels was present at the time of the initial fall in HBV-DNA levels, maximal reduction in virus level occurred before significant liver injury. Direct ex vivo quantification of HBV-specific CD4+ and CD8+ cells, by using human leukocyte antigen (HLA) class I tetramers and intracellular cytokine staining, showed that adaptive immune mechanisms are present during the incubation phase, at least 4 weeks before symptoms. The results suggest that the pattern of reduction in HBV replication is not directly proportional to tissue injury during acute hepatitis B in humans. Furthermore, because virus-specific immune responses and significant reductions in viral replication are seen during the incubation phase, it is likely that the immune events central to viral control occur before symptomatic disease.

Acute Disease↗
PubMed2000

Subclinical seizure activity and prophylactic phenytoin infusion in acute liver failure: a controlled clinical trial.

Subclinical seizure activity in the patient with encephalopathy and on ventilation with acute liver failure (ALF) is a poorly recognized entity. Its importance lies in the likely exacerbation of cerebral hypoxia and the contribution of such seizure activity to the development of cerebral edema. The aim of the present study was to document the frequency of subclinical seizure activity in a cohort of patients with ALF by using a cerebral function and activity monitor that allows continuous recording of electroencephalogram activity at the bedside and to determine whether the prophylactic administration of the antiepileptic agent phenytoin would reduce its occurrence. Forty-two patients were enrolled in a controlled clinical trial: 20 patients were given phenytoin and 22 acted as controls. Subclinical seizure activity was recorded in 3 and 10 patients, respectively, of the treated and control groups. Pupillary abnormalities indicative of seizure activity and/or raised intracranial pressure (ICP) were also seen less frequently in the phenytoin-treated group compared with the controls (5 and 11 patients, respectively). Autopsy examinations available in 19 patients showed signs of cerebral edema in only 2 (22%) of the phenytoin-treated patients compared with 7 (70%) of the controls (P <.033). Based on these findings, we recommend that patients with ALF, on reaching the stage of grade III or IV encephalopathy, should be routinely monitored for subclinical seizure activity. In this study, prophylaxis with phenytoin reduced the frequency of such seizure activity and its effects, and proved to be safe with the regimen used.

Acute Disease↗
PubMed2000

Quality of life after liver transplantation for alcoholic liver disease.

There are few data on predictive factors for alcohol relapse or long-term functional outcome after liver transplantation for alcoholic liver disease (ALD). In all 56 surviving UK patients (47 men, 9 women; mean age: 51 years; range: 33 to 69 years) who underwent transplantation for ALD at King's College Hospital over a 10-year period, alcohol relapse and outcome were assessed by outpatient and case-note review and by postal questionnaire containing (1) the Nottingham Health Profile (NHP), (2) the Short-Form-36 (SF-36) Health Survey, and (3) a drug and alcohol questionnaire. At a median of 2.5 years (range: 0.5 to 10 years), 13 of the 47 respondents (28%) and 2 of the 9 nonrespondents (22%) had evidence of potentially harmful drinking (>3 units daily) at some time posttransplantation. An additional 13 patients admitted to drinking some alcohol at least once, corresponding to an overall relapse rate of 50%. The patients with harmful drinking (1) had started drinking regularly at a younger age (18 v 25 years; P =.01), (2) began drinking heavily at a younger age (30 v 40 years; P =.01), (3) had shorter pretransplantation abstinence periods (10 v 23 months; P =.02), and (4) had a longer time since transplantation (median, 5.7 v 1.5 years; P =.0004) than those with no or mild alcohol relapse. They were also more likely to report sleep disturbance (NHP sleep problem score, 45 v 16; P =.01) and use benzodiazepines regularly (7 of 13 v 3 of 34 patients; P =.002). Despite these differences, health dimension scores in the SF-36 and NHP posttransplantation were similar between the groups and to those of UK community controls. In the long term, at least 50% of the patients will drink again at some time posttransplantation, although at lower levels of alcohol intake than previously. Those patients with multiple predictive factors for alcohol relapse may be at greatest risk for harmful drinking and be the group that would benefit most from professional counseling. Overall, the quality of life after liver transplantation for ALD is high and broadly similar to the levels expected in the normal population.

Adult↗
PubMed2000

The changing role of the medical illustrator.

The annual meeting of the Australian Institute of Medical and Biological Illustration in Melbourne in November 1998 included keynote addresses from Richard Morton and Robin Williams. Both speakers looked at the future of the medical illustration profession, and in particular the impact of new technology. This matter was also addressed by Joe Nicholls in a presentation given at the Institute of Medical Illustrators' Annual Symposium in Warwick, UK, in September 1998. This paper is a synthesis of the ideas presented by these three speakers and elaborates on common themes in their presentations.

Education, Medical↗
PubMed2000

Psychiatric treatment outcome following traumatic brain injury.

The relationship between self-reported history of traumatic brain injury (TBI) and psychiatric treatment outcome was investigated. TBI was hypothesized to be frequent, associated with cognitive deficits on neuropsychological testing, and less amenable to standard psychiatric treatment. Subjects were 42 psychiatric patients with a self-reported history of TBI and 25 psychiatric patients with no TBI history. Subjects received approximately 2 weeks of inpatient psychiatric treatment. Subjects received neuropsychological testing and completed the Brief Symptom Inventory weekly. TBI was frequent (66% of subjects); multiple injuries were common. Neuropsychological performance was generally average in both groups with few group differences. Subjects, on average, reported significantly decreased psychiatric symptoms on discharge. However, the TBI group appeared to improve less than the control group; group status was a significant predictor of treatment outcome. Implications of results for assessment and treatment of psychiatric disorders in patients with a history of TBI are discussed.

Adult↗
PubMed2000

Correlation of MRI lesions with visual psychophysical deficit in secondary progressive multiple sclerosis.

The aim of this work was, first, to clarify the nature of the relationship between the sensory deficit in the demyelinated visual pathway and morphological changes revealed by MRI and, secondly, to test whether there was a preferential effect of demyelination for either the magnocellular or parvocellular pathway in established multiple sclerosis. Twenty-four patients with secondary progressive multiple sclerosis were studied psychophysically and by MRI of the optic nerve and brain. MRI was performed with a Phillips (0.5T) scanner. Visual pathway MRI lesion load was evaluated independently using the total optic nerve lesion length and lesion area seen on STIR (short inversion time inversion recovery) images of the optic nerve and the total post-chiasmal lesion area on T(1)-, T(2)- and proton-density-weighted images of the brain. Psychophysical tests determined 75%-seeing thresholds for horizontal gratings consisting of isoluminant red and green sinusoids of the same spatial frequency combined out-of-phase for preferential stimulation of the parvocellular system and in-phase for preferential stimulation of the magnocellular system. It was found that, in this group of patients, visual psychophysical loss was significantly correlated with lesion area seen on proton density MRI sequences of the post-chiasmal visual pathway, and that the parvocellular pathway was more affected than the magnocellular pathway, especially at lower spatial frequencies.

Adolescent↗