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Biomedical subjects

G Lawrence

Publications and source records attributed to G Lawrence.

At least 19 recordsLinked to original sources
PubMed2003

The National Health Service Breast Screening Programme and British Association of Surgical Oncology audit of quality assurance in breast screening 1996-2001.

BACKGROUND: The National Health Service Breast Screening Programme (NHSBSP) is an example of a nationally coordinated quality assurance programme in which all the professional groups involved participate. METHODS: Surgeons, radiologists and pathologists defined the clinical outcome measures against which they would subsequently be audited. The NHSBSP and the Association of Breast Surgery at BASO are jointly responsible for coordinating an annual audit of all surgical activities undertaken within the NHSBSP. RESULTS: The trends for key outcome measures between 1996 and 2001 are provided. The preoperative diagnosis rate (minimum standard 70 per cent or more) improved from 63 to 87 per cent. This rise was mirrored by an increase in the use of core biopsy in preference to fine-needle cytology. The proportion of patients in whom lymph node status was recorded improved from 81 to 93 per cent. There was no significant change in the number of women treated by low case-load surgeons and waiting times for surgery increased through the study interval. CONCLUSION: The BASO-NHSBSP Breast Audit has recorded major changes in clinical practice over 5 years. A key feature has been the dissemination of good practice through feedback of the results at local and national level.

Biopsy, Needle↗
PubMed2003

Clinical and economic choices in anaesthesia for day surgery: a prospective randomised controlled trial.

We compared the cost-effectiveness of general anaesthetic agents in adult and paediatric day surgery populations. We randomly assigned 1063 adult and 322 paediatric elective patients to one of four (adult) or two (paediatric) anaesthesia groups. Total costs were calculated from individual patient resource use to 7 days post discharge. Incremental cost-effectiveness ratios were expressed as cost per episode of postoperative nausea and vomiting (PONV) avoided. In adults, variable secondary care costs were higher for propofol induction and propofol maintenance (propofol/propofol; p < 0.01) than other groups and lower in propofol induction and isoflurane maintenance (propofol/isoflurane; p < 0.01). In both studies, predischarge PONV was higher if sevoflurane/sevoflurane (p < 0.01) was used compared with use of propofol for induction. In both studies, there was no difference in postdischarge outcomes at Day 7. Sevoflurane/sevoflurane was more costly with higher PONV rates in both studies. In adults, the cost per extra episode of PONV avoided was pound 296 (propofol/propofol vs. propofol/ sevoflurane) and pound 333 (propofol/sevoflurane vs. propofol/isoflurane).

Adolescent↗
PubMed2002

Appraisal of compliance with the UICC/AJCC staging system in the staging of gastric cancer. Union Internacional Contra la Cancrum/American Joint Committee on Cancer.

BACKGROUND: In the surgical management of gastric carcinoma, regional lymphatic spread is of prognostic importance. The fifth edition of the Union Internacional Contra la Cancrum classification has been shown to be reproducible, practical and of significant prognostic use. The tumour node metastasis (TNM) system requires at least 15 lymph nodes to be acquired and examined for staging to be accurate. This has raised concern over the consistency with which the requisite numbers of nodes would be acquired. This study was performed to assess how consistently surgically managed cases of gastric cancer in the West Midlands fulfilled this requirement to allow accurate staging. METHODS: Data from the West Midlands Cancer Intelligence Unit on all cases of gastric cancer registered from 1998 to 1999 were obtained and the number of lymph nodes documented for each surgically managed case was assessed. RESULTS: Overall, only 31.0 per cent of surgically resected cases could be assessed accurately according to the TNM system. The proportion staged accurately varied widely across hospitals from 10.9 to 76.0 per cent. CONCLUSION: These results reflect the need for improved N staging across the region to aid the appropriate multimodal treatment of patients.

Guideline Adherence↗
PubMed2001

Enteral human IgG for prevention of necrotising enterocolitis: a placebo-controlled, randomised trial.

BACKGROUND: Neonatal necrotising enterocolitis is a serious, commonly fatal disease in premature neonates. Although feeding with expressed breast milk and other good nursery practices are partly protective, preventive measures are needed. Treating neonates enterally with a mixture of human IgA and IgG, prepared from donated blood, has been claimed to protect against necrotising enterocolitis. However, no IgA preparation is available in Australia. Our aim, therefore, was to identify whether or not enteral IgG could prevent the disorder. METHODS: We did a multicentre, double-blind, placebo- controlled trial. We randomly assigned 768 infants to receive human IgG 1200 mg/kg daily, and 761 to receive placebo, for up to 28 days. Treatment began at the same time as enteral feeding. The primary outcome measure was the proportion of infants who developed definite necrotising enterocolitis during the trial, and any deaths that resulted from the disorder in the treatment and placebo groups. Analysis was on an intention-to-treat basis. FINDINGS: 43 infants developed definite necrotising enterocolitis in the IgG group, ten of whom died. In the placebo group, 41 infants contracted the disorder and six died (p=0.47). 25 infants on IgG and 36 on placebo had suspect necrotising enterocolitis (p=0.14). INTERPRETATION: Supplementation of enteral feeds with human IgG does not reduce necrotising enterocolitis.

Double-Blind Method↗
PubMed2001

Recombinant forms of tetanus toxin engineered for examining and exploiting neuronal trafficking pathways.

Tetanus toxin is a fascinating, multifunctional protein that binds to peripheral neurons, undergoes retrograde transport and trans-synaptic transfer to central inhibitory neurons where it blocks transmitter release, thereby, causing spastic paralysis. As a pre-requisite for exploiting its unique trafficking properties, a novel recombinant single chain was expressed at a high level in Escherichia coli as a soluble, easily purifiable protein. It could be activated with enterokinase to produce a dichain that matched native toxin in terms of proteolytic and neuroinhibitory activities, as well as induction of spastic paralysis in mice. Importantly, nicking was not essential for protease activity. Substitution of Glu(234) by Ala created a protease-deficient atoxic form, which blocked the neuroparalytic action of tetanus toxin in vitro, with equal potency to its heavy chain; but, the mutant proved >30-fold more potent in preventing tetanus in mice. This observation unveils differences between the intoxication processes resulting from retrograde transport of toxin in vivo and its local uptake into peripheral or central nerves in vitro, dispelling a popularly held belief that the heavy chain is the sole determinant for efficient trafficking. Thus, this innocuous mutant may be a useful vehicle, superior to the heavy chain, for drug delivery to central neurons.

Amino Acid Sequence↗
PubMed2001

Comparative incidence of Type I diabetes in children aged under 15 years from South Asian and White or Other ethnic backgrounds in Leicestershire, UK, 1989 to 1998.

AIMS/HYPOTHESIS: Estimates of incidence of Type I (insulin-dependent) diabetes mellitus in childhood populations vary around the world. This study aimed to estimate and compare the incidence of Type I diabetes in Leicestershire of children of South Asian and White or Other ethnic backgrounds. METHODS: All new cases of childhood-onset Type I diabetes diagnosed before 15 years of age in Leicestershire during the period 1989-98 were studied. Population data for Leicestershire from the 1991 census was used. Ethnicity was assigned to all children in the study according to their surnames. Incidence rates (95%-Confidence limits) for the South Asian and white or other ethnic group were estimated and compared. RESULTS: Over the 10-year period, 46 South Asian children and 263 children who were white or from another ethnic group fulfilled the criteria for inclusion in the study. Crude incidence rates per 100,000 person-years were 19.2 (12.0, 29.1) girls and 20.3 (13.0, 30.3) boys for South Asians and 17.7 (14.8, 21.1) girls and 17.7 (14.8, 20.9) boys for whites/others. Age and sex-specific rates were higher for South Asians over 5 years of age but differences were not statistically significant. CONCLUSION/INTERPRETATION: Type I diabetes incidence rates for South Asian children in Leicestershire were very similar to those for children who were in the white/other ethnic group, in contrast to very low rates reported from Asia. The convergence of rates for South Asians with other ethnic groups in Leicestershire suggests that environmental factors are more important than genetic predisposition in causing Type I diabetes in people of South Asian ethnic background.

Adolescent↗
PubMed2001

Improving outcomes in gynaecological cancer: the impact of centralisation on patient flows and service provision.

Responses to a postal questionnaire and cancer registry data were utilised to evaluate the impact of the recent NHS Executive guidelines for the management of gynaecological malignancies on patient flows and service provision in the West Midlands. They were also used to assess the service provision in the west midlands in relation to these guidelines. Eighty-nine per cent (16/18) trusts returned completed questionnaires. Seventy-two per cent (46/64) of recommendations were achieved by all four centres; 18% (10/57) by all 12 units. The cancer registration data revealed 404 cases that would need to be transferred to the cancer centres per annum in order to implement the guidelines. A more detailed analysis for the northern area of the region estimated that a further 120 cases per annum would need to be managed at the main centre. This study has shown that implementation of the guidelines will require significant shifts in patient flows. This will increase workloads for the cancer centre and have an impact on service provision and resource allocation.

Journal Article↗
PubMed2001

Measles: how many hospitalised cases are we missing?

We aimed to determine whether the Victorian measles surveillance system had missed hospitalised cases of measles during an inter-epidemic period. We searched the Victorian Inpatient Minimum Dataset (VIMD) for the period 1 January 1997 to 30 June 1998 to identify patients with ICD-9 discharge codes for measles (055). The data were compared with that held in the Victorian measles surveillance dataset. The hospital case notes of patients identified in the VIMD but not in the measles surveillance dataset were reviewed systematically to determine whether the patients met case definitions for laboratory-confirmed or clinically compatible measles. Sixteen admissions (15 patients) were identified with a measles ICD-9 code. Eight patients were not identified in the measles surveillance dataset. Of these, one was a laboratory confirmed case of measles and two met a clinical case definition but all should have been notified to the Department of Human Services as suspected cases. While the small number of missed notifications is encouraging in terms of overall measles surveillance, it highlights important deficiencies in the awareness of hospital staff of their role in the control of measles, particularly as Australia moves towards the elimination of measles.

Adult↗
PubMed2000

Effect of vaccination with 3 recombinant asexual-stage malaria antigens on initial growth rates of Plasmodium falciparum in non-immune volunteers.

A placebo controlled, randomised, double blind trial was conducted in human volunteers to test a mixture of three recombinant Plasmodium falciparum blood stage antigens for its ability to reduce the initial growth rates of parasites. The vaccine contained recombinant MSP2 (3D7 allele), a portion of MSP1 (190LCS.T3) and part of the RESA antigen (C terminal 771 amino acids) in the Montanide ISA 720 adjuvant (SEPPIC). Twelve volunteers received two doses of the vaccine, 6 weeks apart. The five participants in the placebo group received an equivalent volume of the adjuvant emulsion using the same schedule. Antibody responses were low, as has been reported in earlier studies with this combination, while T cell responses were stronger. All the volunteers were challenged with approximately 140 ring infected red cells of the 3D7 cloned line, 4 weeks after the second dose. Parasitaemia was determined once daily from day 4 using a sensitive and quantitative PCR assay. All the volunteers were infected and were treated on day 8, before any developed symptoms. There was no significant difference in initial parasite growth rates between the verum and placebo groups, nor was there any significant correlation between parasite growth rates and any of the measured immunological responses. These results suggest that the formulation tested in this trial did not generate immune responses that were strong enough to reduce parasite growth in naive volunteers.

Adult↗
PubMed2000

Legal and ethical issues involved when counseling minors in nonschool settings.

Many counselors in non-school settings will work with children at some time during their practice; therefore, it is essential that they understand the legal and ethical issues relevant to working with minors. Major court cases and legislation are presented, and 4 critical ethical issues--counselor competence, the client's rights to confidentiality and informed consent, and duties related to child abuse--are addressed. Suggestions for working ethically with minors in order to limit legal liability are presented.

Child↗
PubMed2000

The use of the Liverpool University Neuroleptic Side-Effect Rating Scale (LUNSERS) in clinical practice.

Forty-four mental health clients completed the Liverpool University Neuroleptic Side-Effect Rating Scale (LUNSERS)--a self-rating scale to assess the prevalence and intensity of neuroleptic side-effects. In the month prior to the study, 50% of the clients surveyed had experienced more than half of the side-effects outlined on the 41-item scale. A prevalence profile allowed us to rank the frequency of individual side-effects across the sample. Some side-effects such as 'difficulty concentrating', 'difficulty remembering', 'tiredness' and 'restlessness' were experienced by most of the clients in the study while 'unusual skin marks', 'difficulty passing water', 'rashes' were experienced by a few. A prevalence profile may be a useful guide in developing strategies for managing side-effects more effectively in small groups of clients. In addition, the use of the LUNSERS in clinical practice would enable case managers to establish baseline measures for individual clients and evaluate changes in medication and other non-medical strategies for reducing unwanted side-effects. The identification and assessment of antipsychotic side-effects is an important area for client and professional carer education.

Adolescent↗
PubMed2000

Gender and drought: experiences of Australian women in the drought of the 1990s.

A unique collaborative, sociological study undertaken during 1995-7, explored the social construction of drought as a disaster, looking at farm families in two Australian states: Queensland (beef producers) and New South Wales (sheep/wheat producers). A decision was made to interview the women and men separately to test our hypothesis that there would be gender issues in any analysis of a disaster, but particularly one which has had so much long-term impact on individuals, families and communities, such as drought. Interviews were conducted with over 100 individuals male and female. We conclude that drought as a disaster is a gendered experience. The paper draws on the narratives of some women involved in the study to identify 'themes of difference' which confirm the necessity to maintain gender as a variable in all studies of the social impacts of disaster.

Adaptation, Psychological↗
PubMed2000

'Sending the wrong signal': analysis of print media reportage of the ACT heroin prescription trial proposal, August 1997.

OBJECTIVE: To analyse and compare newspaper coverage about heroin during a period spanning two government policy decisions to approve, then prevent, a trial of heroin prescription to dependent users. METHOD: All articles published about heroin spanning the two policy decisions (1-19 August 1997) were collected from seven major Australian newspapers. Analyses included content and orientation analyses of all articles and discourse analysis of articles (excluding letters) containing value-laden statements about heroin prescription. Comparisons were made of content, orientation and subtextual themes employed by opponents and proponents of heroin prescription. RESULTS: 231 articles with references to heroin were identified from seven newspapers, 28% were published by The Daily Telegraph. This newspaper campaigned against the heroin prescription trial with 66% of news articles and 100% of opinion items negative in orientation, compared to averages of 11% and 16% of news and opinion articles published by comparison newspapers. Seven subtexts were identified in coverage opposing heroin prescription including "surrender in the war on drugs", "government as drug pedlar" and "deserving/undeserving citizens". Six subtexts supportive of heroin prescription were identified including "failure of prohibition" and "time for new approaches". CONCLUSION: The mid-1997 policy reversal on heroin prescription was due, in part, to the higher activity of opponents following approval of the trial and because proponents did not reframe discourses used to denigrate the proposal. IMPLICATIONS: To be successful, advocates of new policy need to recognise and reframe negative discourses to create new dominant themes which address the concerns of the public.

Australia↗
PubMed2000

Determination of a site-specific reference dose for methylmercury for fish-eating populations.

Environmental risk-management decisions in the U.S. involving potential exposures to methylmercury currently use a reference dose (RfD) developed by the U.S. Environmental Protection Agency (USEPA). This RfD is based on retrospective studies of an acute poisoning incident in Iraq in which grain contaminated with a methylmercury fungicide was inadvertently used in the baking of bread. The exposures, which were relatively high but lasted only a few months, were associated with neurological effects in both adults (primarily paresthesia) and infants (late walking, late talking, etc.). It is generally believed that the developing fetus represents a particularly sensitive subpopulation for the neurological effects of methylmercury. The USEPA derived an RfD of 0.1 microg/kg/day based on benchmark dose (BMD) modeling of the combined neurological endpoints reported for children exposed in utero. This RfD included an uncertainty factor of 10 to consider human pharmacokinetic variability and database limitations (lack of data on multigeneration effects or possible long-term sequelae of perinatal exposure). Alcoa signed an Administrative Order of Consent for the conduct of a remedial investigation/feasibility study (RI/FS) at their Point Comfort Operations and the adjacent Lavaca Bay in Texas to address the effects of historical discharges of mercury-containing wastewater. In cooperation with the Texas Natural Resource Conservation Commission and USEPA Region VI, Alcoa conducted a baseline risk assessment to assess potential risk to human health and the environment. As a part of this assessment. Alcoa pursued the development of a site-specific RfD for methylmercury to specifically address the potential human health effects associated with the ingestion of contaminated finfish and shellfish from Lavaca Bay. Application of the published USEPA RfD to this site is problematic; while the study underlying the RfD represented acute exposure to relatively high concentrations of methylmercury, the exposures of concern for the Point Comfort site are from the chronic consumption of relatively low concentrations of methylmercury in fish. Since the publication of the USEPA RfD, several analyses of chronic exposure to methylmercury in fish-eating populations have been reported. The purpose of the analysis reported here was to evaluate the possibility of deriving an RfD for methylmercury, specifically for the case of fish ingestion, on the basis of these new studies. In order to better support the risk-management decisions associated with developing a remediation approach for the site in question, the analysis was designed to provide information on the distribution of acceptable ingestion rates across a population, which could reasonably be expected to be consistent with the results of the epidemiological studies of other fish-eating populations. Based on a review of the available literature on the effects of methylmercury, a study conducted with a population in the Seychelles Islands was selected as the critical study for this analysis. The exposures to methylmercury in this population result from chronic, multigenerational ingestion of contaminated fish. This prospective study was carefully conducted and analyzed, included a large cohort of mother-infant pairs, and was relatively free of confounding factors. The results of this study are essentially negative, and a no-observed-adverse-effect level (NOAEL) derived from the estimated exposures has recently been used by the Agency for Toxic Substances and Disease Registry (ATSDR) as the basis for a chronic oral minimal risk level (MRL) for methylmercury. In spite of the fact that no statistically significant effects were observed in this study, the data as reported are suitable for dose-response analysis using the BMD method. Evaluation of the BMD method used in this analysis, as well as in the current USEPA RfD, has demonstrated that the resulting 95% lower bound on the 10% benchmark dose (BMDL) represents a conservative estimate of the traditional NOAEL, and that it is superior to the use of "average" or "grouped" exposure estimates when dose-response information is available, as is the case for the Seychelles study. A more recent study in the Faroe Islands, which did report statistically significant associations between methylmercury exposure and neurological effects, could not be used for dose-response modeling due to inadequate reporting of the data and confounding from co-exposure to polychlorinated biphenyls (PCBs). BMD modeling over the wide range of neurological endpoints reported in the Seychelles study yielded a lowest BMDL for methylmercury in maternal hair of 21 ppm. This BMDL was then converted to an expected distribution of daily ingestion rates across a population using Monte Carlo analysis with a physiologically based pharmacokinetic (PBPK) model to evaluate the impact of interindividual variability. The resulting distribution of ingestion rates at the BMDL had a geometric mean of 1.60 microg/kg/day with a geometric standard deviation of 1.33; the 1st, 5th, and 10th percentiles of the distribution were 0.86, 1.04, and 1.15 microg/kg/day. In place of the use of an uncertainty factor of 3 for pharmacokinetic variability, as is done in the current RfD, one of these lower percentiles of the daily ingestion rate distribution provides a scientifically based, conservative basis for taking into consideration the impact of pharmacokinetic variability across the population. On the other hand, it was felt that an uncertainty factor of 3 for database limitations should be used in the current analysis. Although there can be high confidence in the benchmark-estimated NOAEL of 21 ppm in the Seychelles study, some results in the New Zealand and Faroe Islands studies could be construed to suggest the possibility of effects at maternal hair concentrations below 10 ppm. In addition, while concerns regarding the possibility of chronic sequelae are not supported by the available data, neither can they be absolutely ruled out. The use of an uncertainty factor of 3 is equivalent to using a NOAEL of 7 ppm in maternal hair, which provides additional protection against the possibility that effects could occur at lower concentrations in some populations. Based on the analysis described above, the distribution of acceptable daily ingestion rates (RfDs) recommended to serve as the basis for site-specific risk-management decisions at Alcoa's Point Comfort Operations ranges from approximately 0.3 to 1.1 microg/kg/day, with a population median (50th percentile) of 0.5 microg/kg/day. By analogy with USEPA guidelines for the use of percentiles in applications of distributions in exposure assessments, the 10th percentile provides a reasonably conservative measure. On this basis, a site-specific RfD of 0.4 microg/kg/day is recommended.

Adult↗
PubMed2000

Trachynilysin mediates SNARE-dependent release of catecholamines from chromaffin cells via external and stored Ca2+.

Trachynilysin, a 159 kDa dimeric protein purified from stonefish (Synanceia trachynis) venom, dramatically increases spontaneous quantal transmitter release at the frog neuromuscular junction, depleting small clear synaptic vesicles, whilst not affecting large dense core vesicles. The basis of this insensitivity of large dense core vesicles exocytosis was examined using a fluorimetric assay to determine whether the toxin could elicit catecholamine release from bovine chromaffin cells. Unlike the case of the motor nerve endings, nanomolar concentrations of trachynilysin evoked sustained Soluble N-ethylmaleimide-sensitive fusion protein Attachment Protein REceptor-dependent exocytosis of large dense core vesicles, but only in the presence of extracellular Ca2+. However, this response to trachynilysin does not rely on Ca2+ influx through voltage-activated Ca2+ channels because the secretion was only slightly affected by blockers of L, N and P/Q types. Instead, trachynilysin elicited a localized increase in intracellular fluorescence monitored with fluo-3/AM, that precisely co-localized with the increase of fluorescence resulting from caffeine-induced release of Ca2+ from intracellular stores. Moreover, depletion of the latter stores inhibited trachynilysin-induced exocytosis. Thus, the observed requirement of external Ca2+ for stimulation of large dense core vesicles exocytosis from chromaffin cells implicates plasma membrane channels that signal efflux of Ca2+ from intracellular stores. This study also suggests that the bases of exocytosis of large dense core vesicles from motor nerve terminals and neuroendocrine cells are distinct.

Animals↗