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Biomedical subjects

B Williams

Publications and source records attributed to B Williams.

At least 37 records · Page 2Linked to original sources
PubMed2003

Bone strength during growth: influence of growth rate on cortical porosity and mineralization.

Although it is well accepted that bone architecture adapts to withstand the loads placed on it, the manner in which this occurs in the immature growing skeleton is not fully understood. To investigate the possible mechanisms, we have compared morphometric differences between tibiae from chickens with fast and those with slow growth potential and also distinguished between the effects of genetic potential and growth rate on their impact on bone quality. Two different fast-growing (ad lib modern) strains, one additionally feed-restricted and one slow-growing (control) strain of chicken, were compared at 15 and 42 days of age. The ad lib modern strains had similar final body weights and were approximately twice the weight of the control and restricted-fed birds. Tibiae from the control and restricted birds had a higher ash content and lower porosity than the ad lib modern strain at 42 days. The porosity was a result of rapid primary osteon formation at the periosteal surface and incomplete infilling of the resultant canal by osteoblasts. When adjusted to average body weight of contemporaries, bones from the control strain and the restricted-fed modern birds were stiffer and at least as strong as those from the fast growing ad lib-fed birds. In conclusion, rapid bone deposition at the periosteal surface was associated with decreased mineralization, increased cortical porosity, and altered biomechanical properties. Our results also indicate that growth rate, and not genetic potential, of the fast growing birds was responsible for the rapid periosteal bone deposition.

Acid Phosphatase↗
PubMed2003

Partnerships with health and private voluntary organizations: what are the issues for health authorities and boards?

BACKGROUND: The number of voluntary organizations active in health care is considerable. There have been recent calls for a new closer working relationship between voluntary bodies and the National Health Service. The relationship between the two healthcare sectors needs to be efficient and harmonious in the interests of patient care; however, little is known about the nature and problems in the current relationship. The present study was undertaken to examine aspects of this relationship from the point of view of health board personnel. OBJECTIVE: To identify the practices and views of Scottish health board staff concerning the funding, role and responsibility of voluntary organizations in the health sector. METHODS: A qualitative study based on in-depth interviews with health board officials in all 15 Scottish health boards. RESULTS: Policies for financial and other relationships with the voluntary sector were often not explicit. The levels and method of funding voluntary health organizations varied across boards, as did the tenure of awards (from 1 to 3 years). Demand for funding far exceeded monies available. Some health boards ensured accountability through audited accounts, annual reports and site visits; however, others thought this inappropriate for small organizations. Health boards recognized the problems of the precariousness of funding and the administrative burden of the monitoring process and the ritual of applying for funding. CONCLUSION: The uncertainties of long-term funding may impede the contribution of voluntary organizations. There is a tension between the requirements of clinical governance and the ability of small voluntary organizations to provide the necessary documentation. One proposed solution, to reduce the number of organizations, might not appeal to the voluntary sector. Future initiatives could address the problem of tailoring funding and accounting to the resources of voluntary organizations.

Governing Board↗
PubMed2003

Attributes of trainers for postgraduate training in general surgery--a national consensus.

BACKGROUND: The aim of this study was to obtain consensus amongst consultant surgeons on the attributes of a good surgical trainer that can be used to inform continuing professional development programmes for trainers. METHODS: good trainer attributes were generated from an intensive qualitative study using a participative inquiry process with consultant general surgeons and specialist registrars in the Tayside region. These good trainer attributes were then used as the basis of a modified Delphi study; the early rounds of the Delphi simultaneously sought participants' views concerning stated attributes and sought to generate new attributes. A final Delphi questionnaire was sent to all 180 consultant general surgeons in Scotland to identify consensus. RESULTS: The first two rounds of the Delphi process produced 45 attributes covering seven themes: interest in training, trainer as a team member, communication, receptiveness to trainee needs, trainer as a role model, reflection on practice and clinical and operative competence. The final survey identified significant consensus among surgeons. Clinical and operative competence achieved the highest consensus with 89.2% of surgeons believing it to be an essential attribute. CONCLUSIONS: The results indicate that there is consensus on the seven themes identified as essential for a trainer in general surgery. The recognition of the importance by trainers of non-surgical trainer attributes in the changed training structure is encouraging. Surgeons' level of awareness of their roles as a trainer will help inform the level and direction of trainer training and support required as part of a flexible and continuing developmental process.

Education, Medical, Graduate↗
PubMed2003

Better blood pressure control: how to combine drugs.

Prospective comparisons of different drug classes have shown that differences in blood pressure control, rather than differences between drug classes, have the over-riding influence on overall outcome. The same studies have also reinforced the need, in the majority of patients, to use combinations of drugs in order to achieve the target of <140/85 mmHg. By contrast, most patients in routine practice receive single agents and consequently fail to achieve target blood pressure. This failure reflects in part the emphasis in individual studies and subsequent guidelines on comparison of individual drugs. In this article we show how the consistency of both theory and a broad range of evidence permits a didactic approach to combination therapy. Our advice is based on the growing recognition that essential hypertension and its treatment fall into two main categories. Younger Caucasians usually have renin-dependent hypertension that responds well to angiotensin-converting-enzyme inhibition or angiotensin receptor blockade (A) or ss blockade (B). Most other patients have low-renin hypertension that responds better to calcium channel blockade (C) or diuretics (D). These latter drugs activate the renin system rendering patients responsive to the addition of renin suppressive therapy. Coincidence of the initials of these main drug classes with the first four letters of the alphabet permits an AB/CD rule, according to which recommended combinations are one drug from each of the "AB" and "CD" categories of drugs. However, the diabetogenic potential of the older "B" and "D" classes leads us to advise against combining "B" and "D" in older patients, and to recommend "A" + "C" + "D" as standard triple therapy for resistant hypertension.

Antihypertensive Agents↗
PubMed2003

Evaluation of personal, environmental and biological exposure of paediatric anaesthetists to nitrous oxide and sevoflurane.

Paediatric anaesthetists are at higher risk of exposure to waste anaesthetic gases, which often exceed set safety limits. Recommended personal diffusive sampling techniques for monitoring exposure to waste anaesthetic gases may not give a true profile of exposure and hence biological sampling may also be necessary. We evaluated the exposure of paediatric anaesthetists to nitrous oxide and sevoflurane as assessed by personal environmental and biological samples. The influence of venue and technique, and the strength of the relationship among the various sampling techniques were analysed. The study found that exposure to nitrous oxide during paediatric anaesthetic inductions is still a major problem, although exposure to sevoflurane was usually within the accepted limits. The type of breathing system used and the presence of scavenging seem to influence this exposure, though surprisingly, the induction technique or the methods of airway control do not. No significant relationship was found between the various biological indicators measured.

Adolescent↗
PubMed2003

Quantification of feto-maternal haemorrhage (FMH) by flow cytometry: anti-fetal haemoglobin labelling potentially underestimates massive FMH in comparison to labelling with anti-D.

Many centres now routinely use flow cytometry to quantify feto-maternal haemorrhage (FMH). However, which flow cytometric method is the most accurate in quantifying FMH is currently unknown. An audit of clinical results in which FMH had been estimated by both directly conjugated monoclonal anti-D and anti-fetal haemoglobin (HbF) labelling suggested that the anti-HbF labelling method may underestimate massive FMH in comparison to labelling with anti-D. Subsequent to this audit, 46 samples of adult D-negative blood were spiked with varying amounts of D-positive cord blood (0.05-10% fetal cells per sample), and the number of fetal cells present was quantified by both labelling methods. The percentage of fetal cells detected by anti-D was not significantly different to the estimated percentage of fetal cells added to each sample (P = 0.636). However, anti-HbF labelling significantly underestimated the percentage of fetal cells present (P = 0.0001). In comparison to anti-D, the percentage of fetal cells detected by anti-HbF was also significantly lower (P < 0.0001). The difference in fetal cell detection between anti-D and anti-HbF labelling was only apparent in the spiked samples containing > or =1% fetal cells per sample. In samples containing < or =0.6% fetal cells, no significant difference in the detection of fetal cells between anti-D and anti-HbF labelling was observed (P = 0.11). To allow adequate immunoprophylaxis in D-negative mothers with massive FMH, we recommend that anti-D labelling should be used in the routine flow cytometric estimation of FMH.

Adult↗
PubMed2003

Potential for an intervention based on male circumcision in a South African town with high levels of HIV infection.

The study aims to investigate the potential for an intervention based on male circumcision in a South African town with a high level of HIV infection. It draws on two cross-sectional studies conducted in August 2000 among a sample of 606 male adults aged 13-59 years, and in August 1999 among a sample of 723 male youth aged 14-24 years. A qualitative study was further conducted on perceptions and attitudes towards male circumcision using focus group discussions and in-depth interview. Among men aged 25-59 years, 36% reported being circumcised The median reported age at circumcision was 20. A total of 42% of 14-24-year-old circumcised men reported having been circumcised in a medical setting. Circumcised and uncircumcised men did not differ in their sexual behaviour or in sociodemographic characteristics, apart from their age and ethnic group. Among 467 uncircumcised adult men, 59% said that they would be circumcised if circumcision reduced the chances of getting HIV and STDs. Focus group discussions showed that circumcision is still important to many people, and is seen as an essential part of the transition into adulthood Reluctance to be circumcised was mainly related to the possibility of adverse outcomes of circumcision performed in non-medical settings, although initiation schools remain attractive for education and transmission of cultural values. Some misconceptions remain, however, especially about the preventative nature of circumcision for STD transmission. The cultural importance of male circumcision has weakened over the last century and when it is done it is often by a medical practitioner. An intervention that would include male circumcision seems feasible in communities such as the one where this study was conducted but needs to be carefully planned in order to ensure that participants understand that circumcision probably reduces, but certainly does not eliminate, the risk of HIV infection.

Adolescent↗
PubMed2003

Risk factors for HIV infection among women in Carletonville, South Africa: migration, demography and sexually transmitted diseases.

We investigate the prevalence of, and risk factors for, HIV infection among women in an urban South African setting. A random sample of 834 women was recruited into a community-based cross-sectional study. HIV prevalence was 37.1% with higher prevalence among migrant women (46.0%) than non-migrant women (34.7%), (odds ratio [OR]=1.61, 95% confidence interval [CI]: 1.11-2.31). The highest HIV prevalence (50.9%) was between ages 26 and 35 years. Having two or more lifetime partners increased the risk of HIV infection (OR=4.88, 95% CI: 3.01-7.89). Migration, age, marital status, alcohol use, syphilis and gonorrhoea were independently associated with HIV infection. Migration increases the risk of HIV infection. Provision of services to treat sexually transmitted diseases and educational empowerment programmes that will promote safer sex among migrant women are urgently needed.

Adolescent↗
PubMed2003

Familial growth and skeletal features associated with SHOX haploinsufficiency.

This study was designed to determine the intrafamilial effect of SHOX haploinsufficiency on stature, by comparing the growth and phenotype of 26 SHOX haploinsufficient individuals with 45 relatives and population standards. It confirmed that SHOX haploinsufficiency leads to growth restriction from birth to final height. Compared to unaffected siblings, the SHOX haploinsufficient cohort was 2.14 SDS (3.8 cm) shorter at birth and 2.1 SDS shorter through childhood. At final height females were 2.4 SDS (14.4 cm) shorter and males 0.8 SDS (5.3 cm) shorter than normal siblings. The family height analysis suggests that the effect of SHOX haploinsufficiency on growth may have been previously underestimated at birth and overestimated in males at final height. SHOX haploinsufficiency leads to short arms in 92%, bilateral Madelung deformity in 73% and short stature in 54%. Females were more severely affected than males. We conclude that SHOX is a major growth gene and that mutations are associated with a broad range of phenotype.

Adolescent↗
PubMed2003

Effect of indapamide SR on microalbuminuria--the NESTOR study (Natrilix SR versus Enalapril Study in Type 2 diabetic hypertensives with micrOalbuminuRia)--rationale and protocol for the main trial.

In type 2 diabetic hypertensive patients, microalbuminuria can be due to hypertension and/or diabetic nephropathy. Angiotensin-converting enzyme (ACE) inhibitors act preferentially on microalbuminuria due to diabetic nephropathy. The objective is to demonstrate the efficacy of a thiazide-like diuretic, indapamide sustained release (SR), at reducing microalbuminuria in hypertensive type 2 diabetic patients in comparison with an ACE inhibitor, enalapril. The study is an international multicentre, 12-month, randomized, double-blind, controlled, two parallel group study of type 2 diabetic patients with hypertension (140 mmHg < or = systolic blood pressure <180 mmHg and diastolic blood pressure <110 mmHg) and microalbuminuria. Intervention is after a 4-week placebo period, patients with microalbuminuria > or = 20 and < or = 200 microg/min are randomized to indapamide SR 1.5 mg or to enalapril 10 mg once a day for a one-year treatment period. An additional label treatment by amlodipine 5-10 mg (1st step) and atenolol 50-100 mg (2nd step) a day is permitted after 6 weeks of treatment based upon blood pressure response. The main outcome measures are microalbuminuria expressed as urinary albumin to creatinine ratio, albumin fractional clearance, and albumin excretion rate evaluated on overnight urine collections. Secondary criteria are supine and standing systolic, diastolic and mean blood pressure; and biological and clinical safety. This study will complete the knowledge of the efficacy of indapamide SR in hypertension and target organ damage and will provide valuable information on the management of type 2 diabetic hypertensives with microalbuminuria.

Adult↗
PubMed2002

Therapeutic benefit of blocking interleukin-6 activity with an anti-interleukin-6 receptor monoclonal antibody in rheumatoid arthritis: a randomized, double-blind, placebo-controlled, dose-escalation trial.

OBJECTIVE: To investigate the safety and efficacy of MRA, a recombinant human anti-interleukin-6 (anti-IL-6) receptor monoclonal antibody of the IgG1 subclass that inhibits the function of IL-6, in patients with established rheumatoid arthritis (RA). METHODS: A randomized, double-blind, placebo-controlled, dose-escalation trial was conducted in 45 patients with active RA, as defined by the American College of Rheumatology (ACR) revised criteria. Patients were sequentially allocated to receive a single intravenous dose of either 0.1, 1, 5, or 10 mg/kg of MRA or placebo. The primary efficacy end point was meeting the ACR 20% response criteria at week 2 after treatment. RESULTS: Demographic features were similar between treatment groups. At week 2, a significant treatment difference was observed between the 5 mg/kg of MRA and placebo, with 5 patients (55.6%) in the MRA cohort and none in the placebo cohort achieving ACR 20% improvement. There was no statistically significant difference in the ACR 20% response between the other 3 MRA cohorts and placebo at week 2. The mean disease activity score at week 2 in those who received 5 mg/kg and 10 mg/kg of MRA was 4.8 and 4.7 (P < 0.001 and P < 0.001 by analysis of variance), respectively. These mean scores were statistically significantly lower than those in the 0.1- and 1-mg/kg MRA and the placebo cohorts (6.4, 6.2, and 7.0, respectively). The erythrocyte sedimentation rate and C-reactive protein values fell significantly in the 5- and 10-mg/kg MRA cohorts and normalized 2 weeks after treatment. Seventeen patients (5, 4, 6, 2, and 0 patients in the placebo, 0.1-, 1-, 5-, and 10-mg/kg MRA cohorts, respectively) required corticosteroid or disease-modifying antirheumatic drug treatment because of active disease before study end. They were regarded as nonresponders from the time they received these treatments. Diarrhea was the most common adverse event, occurring in 8% of patients. Seven patients (15.6%) reported a severe adverse event (3, 1, 2, and 2 patients in the placebo, 0.1-, 1-, and 10-mg/kg MRA cohorts). There were no serious adverse events that were thought to be related to the study drug. CONCLUSION: This is the first randomized controlled trial showing that inhibition of IL-6 significantly improved the signs and symptoms of RA and normalized the acute-phase reactants. Further research with multiple dosing is necessary to define the most appropriate therapeutic regimen of MRA in RA.

Acute-Phase Reaction↗
PubMed2002

CD45 fraction bone marrow cells as potential delivery vehicles for genetically corrected dystrophin loci.

Targeted correction of mutations in muscle can be delivered by direct i.m. injection of corrective DNA to the dystrophic muscle or by autologous injection of cells that have been genetically corrected after isolation from the individual with the dystrophic muscle. The successful application of chimeraplasty and short fragment homologous replacement to correct the exon 23 nonsense mdx transition at the mouse dys locus has opened up the possibility that with further development, targeted gene correction may have some future application for the treatment of muscular dystrophies. In vitro, application of targeted gene correction at the mdx dys locus results in better correction efficiencies than when applied directly to dystrophic muscle. This suggests that at least for the time being, a strategy involving ex vivo correction may be advantageous over a direct approach for delivery of gene correction to dystrophic muscle. This, particularly in view of recent developments indicating that bone-marrow-derived cells are able to systemically remodel dystrophic muscle, whilst penetration of DNA introduced to muscle is limited to individually injected muscles. Application of targeted gene correction to Duchenne dystrophy needs to account for the fact that about 65% of Duchenne muscular dystrophy cases involve large frame-shift deletion of gene sequence at the dys locus. Traditionally, whilst targeted gene correction is able to restore point mutations entirely, it remains to be seen as to whether a strategy for the 'correction' of frame shift deletions may be engineered successfully. This communication discusses the possibility of applying targeted gene correction to dystrophic muscle in Duchenne dystrophy.

Animals↗
PubMed2002

In vivo imaging and radioiodine therapy following sodium iodide symporter gene transfer in animal model of intracerebral gliomas.

Radioactive iodide uptake (RAIU) in thyroid follicular epithelial cells, mediated by the sodium iodide symporter (NIS), is the first rate-limiting step in iodide accumulation which provides a mechanism for effective radioiodide treatment for patients with thyroid cancer. We hypothesize that NIS gene transfer to non-thyroid tumor cells will enhance intracellular radioiodide accumulation and result in better tumor control. Here, we performed non-invasive tumor imaging and (131)I therapy studies using rats bearing intracerebral F98 gliomas that have been retrovirally transduced with human NIS. Our results show that: (1) NIS is expressed in the intracerebral F98/NIS gliomas; (2) F98/NIS gliomas can be imaged by (99m)TcO(4) (whose uptake is also mediated by NIS) and (123)I scintigraphy; (3) significant amounts of radioiodide were retained in the tumors at 24 h after (123)I injection; (4) RAIU and NIS expression in the thyroid gland can be reduced by feeding a thyroxine-supplemented diet; and (5) survival time was increased in rats bearing F98/hNIS tumors by (131)I treatment. These studies warrant further investigating tumor imaging and therapeutic strategies based on NIS gene transfer followed by radioiodide administration in a variety of human cancers.

Animals↗
PubMed2002

Regulation of microvascular permeability by vascular endothelial growth factors.

Generation of new blood vessels from pre-existing vasculature (angiogenesis) is accompanied in almost all states by increased vascular permeability. This is true in physiological as well as pathological angiogenesis, but is more marked during disease states. Physiological angiogenesis occurs during tissue growth and repair in adult tissues, as well as during development. Pathological angiogenesis is seen in a wide variety of diseases, which include all the major causes of mortality in the west: heart disease, cancer, stroke, vascular disease and diabetes. Angiogenesis is regulated by vascular growth factors, particularly the vascular endothelial growth factor family of proteins (VEGF). These act on two specific receptors in the vascular system (VEGF-R1 and 2) to stimulate new vessel growth. VEGFs also directly stimulate increased vascular permeability to water and large-molecular-weight proteins. We have shown that VEGFs increase vascular permeability in mesenteric microvessels by stimulation of tyrosine auto-phosphorylation of VEGF-R2 on endothelial cells, and subsequent activation of phospholipase C (PLC). This in turn causes increased production of diacylglycerol (DAG) that results in influx of calcium across the plasma membrane through store-independent cation channels. We have proposed that this influx is through DAG-mediated TRP channels. It is not known how this results in increased vascular permeability in endothelial cells in vivo. It has been shown, however, that VEGF can stimulate formation of a variety of pathways through the endothelial cell, including transcellular gaps, vesiculovacuolar organelle formation, and fenestrations. A hypothesis is outlined that suggests that these all may be part of the same process.

Animals↗
PubMed2002

Is social capital a useful conceptual tool for exploring community level influences on HIV infection? An exploratory case study from South Africa.

This paper reports on an exploratory study investigating links between sexual health and social capital in a South African mining community. In this study, social capital is defined in terms of people's membership of voluntary community organizations (e.g. church, residents' associations, youth groups). Using biomedical and social survey data from a stratified random sample of 1,211 Carletonville residents, we tested the hypothesis that organizational members were less likely to have HIV. Multivariate analysis of variance sought to identify significant associations between nine organizational memberships and HIV infection, as well as three risk factors for infection (casual partners, condom use with casual partners and alcohol consumption). Analysis yielded a range of significant results, but findings varied across age and gender, and were not all in the hypothesized direction. For example, young men and young women who belonged to sports clubs were less likely to be HIV-positive, and young women who belonged to sports clubs were more likely to use condoms with casual partners than non-members. Amongst members of stokvels (voluntary savings clubs accompanied by social festivities), however, young men were more likely to be HIV-positive, women of all ages were more likely to have a casual partner, and both young men and young women were more likely to drink alcohol than non-members. While our exploratory study has produced sufficient evidence to justify the need for further research in this area, it also highlights that the interface between HIV infection and social capital is a complex area that defies easy generalization.

Adolescent↗
PubMed2002

Paracetamol versus paracetamol-codeine in the treatment of post-operative dental pain: a randomized, double-blind, prospective trial.

BACKGROUND: Codeine is frequently added to paracetamol to treat post-operative dento-alveolar pain; studies have shown effectiveness in relief of post-operative pain at high doses but at the expense of central nervous and gastrointestinal side effects. There has been no trial to compare the efficacy and safety of paracetamol 1000 mg with paracetamol 1000 mg combined with codeine 30 mg. METHOD: A randomized, single centre, double-blind prospective parallel group trial was performed to compare paracetamol 1000 mg with paracetamol 1000 mg with codeine 30 mg for the relief of pain following surgical removal of impacted third molars, and analysed on an intention-to-treat (ITT) basis. Eighty-two patients were assigned randomly to receive either drug for a maximum of three doses. Patients recorded their pain intensity one hour after surgery and hourly thereafter for 12 hours. RESULTS: The average increase in pain intensity over 12 hours was significantly less in patients receiving paracetamol plus codeine than in those receiving paracetamol alone (p=0.03) -1.81 cm/h compared with 0.45 cm/h - a difference of 1.13 cm/h (95 per cent CI: 0.18 to 2.08). Of the patients who received the paracetamol codeine combination, 62 per cent used escape medication compared with 75 per cent of those on paracetamol alone (p=0.20). There was no significant difference between the two groups in the proportion of patients experiencing adverse events (p=0.5). CONCLUSION: A combination of 1000 mg paracetamol and 30 mg codeine was significantly more effective in controlling pain for 12 hours following third molar removal, with no significant difference of side effects during the 12 hour period studied.

Acetaminophen↗