Search PubMed⌕ Search

Biomedical subjects

D Williams

Publications and source records attributed to D Williams.

At least 55 records · Page 3Linked to original sources
PubMed2002

Anti-aromatase chemicals in red wine.

Estrogen synthesized in situ plays a more important role in breast cancer cell proliferation than does circulating estrogen. Aromatase is the enzyme that converts androgen to estrogen and is expressed at a higher level in breast cancer tissue than in surrounding noncancer tissue. A promising route of chemoprevention against breast cancer may be through the suppression of in situ estrogen formation using aromatase inhibitors. A diet high in fruits and vegetables may reduce the incidence of breast cancer, because they contain phytochemicals that can act as aromatase inhibitors. In our previous studies, we found that grapes and wine contain potent phytochemicals that can inhibit aromatase. We show that red wine was more effective than white wine in suppressing aromatase activity. Interestingly, our results from white wine studies suggest a weak inductive effect of alcohol on aromatase activity. On the other hand, the potent effect of anti-aromatase chemicals in red wine overcomes the weak inductive effect of alcohol in wine. Several purification procedures were performed on whole red wine to separate active aromatase inhibitors from non-active compounds. These techniques included liquid-liquid extraction, silica gel chromatography, various solid phase extraction (SPE) columns, and high performance liquid chromatography. An active Pinot Noir red wine SPE C18 column fraction (20% acetonitrile:water) was more effective than complete Pinot Noir wine in suppressing aromatase assay. This red wine extract was further analyzed in a transgenic mouse model in which aromatase was over-expressed in mammary tissue. Our gavaged red wine extract completely abrogated aromatase-induced hyperplasia and other neoplastic changes in mammary tissue. These results suggest that red wine or red wine extract may be a chemopreventive diet supplement for postmenopausal women who have a high risk of breast cancer. Further research is underway to purify and characterize the active compounds in red wine that are responsible for the inhibition of aromatase.

Aromatase Inhibitors↗
PubMed2002

Death, dying and donation: organ transplantation and the diagnosis of death.

Refusal of organ donation is common, and becoming more frequent. In Australia refusal by families occurred in 56% of cases in 1995 in New South Wales, and had risen to 82% in 1999, becoming the most important determinant of the country's very low organ donation rate (8.9/million in 1999). Leading causes of refusal, identified in many studies, include the lack of understanding by families of brain death and its implications, and subsequent reluctance to relegate the body to purely instrumental status. It is an interesting paradox that surveys of the public continue to show considerable support for organ donation programmes--in theory we will, in practice we won't (and don't). In this paper we propose that the Australian community may, for good reason, distrust the concept of and criteria for "whole brain death", and the equation of this new concept with death of the human being. We suggest that irreversible loss of circulation should be reinstated as the major defining characteristic of death, but that brain-dead, heart-beating entities remain suitable organ donors despite being alive by this criterion. This presents a major challenge to the "dead donor rule", and would require review of current transplantation legislation. Brain dead entities are suitable donors because of irreversible loss of personhood, accurately and robustly defined by the current brain stem criteria. Even the dead are not terminally ill any more.

Attitude to Death↗
PubMed2002

Usage of triptans among migraine patients: an audit in nine GP practices.

A retrospective audit was carried out to investigate triptan usage over a period of one year among 360 adult patients with migraine in nine GP practices in the UK and the Republic of Ireland. Data from patient records were analysed, in conjunction with replies to a questionnaire about patients' perceptions of their migraine and its treatment. The majority of patients included in the audit were women (83%), and most patients (81%) were aged between 35 and 64 years. Most patients in the audit population (60%) were in the lowest band of triptan usage (1-36 tablets prescribed over 12 months); 7% had moderate usage (37-53 tablets). A minority of patients appeared to be taking triptans in higher quantities: about 15% of patients had been prescribed 54-94 triptan tablets over a year, 9% had received prescriptions for 95-149 tablets and 7% had received prescriptions for 150 or more tablets. These results indicated that some migraine patients were using triptans at higher than expected rates, and suggested that some patients might have been using their prescribed triptans inappropriately to treat a headache that they incorrectly perceived as migraine (e.g. chronic daily headache). Analyses were carried out to identify predictors of high usage. Predictors identified included the use of several other (non-triptan) medications to treat conditions other than migraine, one triptan dose being reported as sufficient to treat an attack, patient's perception of all headaches as migraine and lack of concern about taking too much medication. Patients identified as using triptans at a higher than expected rate can be called in for review of migraine diagnosis, identification of possible causes of any increased frequency of attacks, and investigation of suspected non-migrainous headaches, such as chronic daily headache and medication-induced headaches. For GPs, such actions would help achieve and maintain a high standard of care for their migraine patients, thus helping to contribute towards meeting the demands of the clinical governance agenda. Audit of triptan usage may also offer financial benefits for the practice, since helping patients to avoid the inappropriate use of triptans could lead to reductions in the overall costs of triptan prescribing within the practice. The high usage predictors could be developed into a checklist of potential indicators for GPs to identify patients who may become high users if prescribed triptans and who might require closer monitoring. We recommend that patients identified as having a potential for high usage should be routinely reviewed, every 3-6 months, to ensure that they are using triptans appropriately to treat migraine. Although triptans are generally safe and well tolerated, unnecessary use of any medication should be avoided.

Adolescent↗
PubMed2002

Inequalities in prescribing of secondary preventative therapies for ischaemic heart disease in Ireland.

The study aim is to quantify the variation in prescribing rates of secondary preventative therapies for Ischaemic Heart Disease (IHD) across regions, age and gender. Patients receiving any prescriptions for a nitrate during a one year period (September 1999-August 2000) were considered using a national primary care prescribing database. Age-sex standardised prescribing rates of four secondary preventative therapies for IHD (Ace inhibitors, beta-blockers, aspirin, statins) were calculated for each region. Wide variations between regions were observed with significantly higher variability for Ace inhibitors compared with aspirin (F-ratio=22.8, p<0.001). Men were more likely to prescribed these therapies and the elderly were less likely (except Ace inhibitors). The study suggests that access to secondary preventative therapy is not equitable across regions, gender and age in Ireland. The wide variability may be due to uncertainty in prescribing secondary preventative therapies and/or variability in clinical need between regions.

Adrenergic beta-Antagonists↗
PubMed2001

Novel spermine-amino acid conjugates and basic tripeptides enhance cleavage of the hairpin ribozyme at low magnesium ion concentration.

Combinations of the polyamine spermine and magnesium ions synergize to dramatically enhance cleavage of the hairpin ribozyme. Certain synthetic basic tripeptides stimulate hairpin cleavage significantly at limiting magnesium ion concentration, notably the tripeptide of L-diaminobutyric acid (Dab). Of a range of novel synthetic spermine-amino acid conjugates, L-Dab-spermine (but not D-Dab nor other amino acid conjugates) was more effective than spermine itself.

Amino Acids↗
PubMed2001

Integrated therapy for locally advanced bladder cancer: final report of a randomized trial of cystectomy plus adjuvant M-VAC versus cystectomy with both preoperative and postoperative M-VAC.

PURPOSE: We conducted a phase III trial to investigate the timing of chemotherapy with respect to surgery for patients with resectable but high-risk urothelial cancer. The trial was also designed to evaluate the accuracy of clinical staging in patients with locally advanced cancer and the prognostic significance of chemotherapy-induced downstaging. PATIENTS AND METHODS: A total of 140 uniformly evaluated patients with locally advanced urothelial cancer were studied. Planned treatment was five cycles of chemotherapy (M-VAC: methotrexate, vinblastine, doxorubicin, and cisplatin) plus radical cystectomy and pelvic lymph node dissection. Patients were randomly assigned to receive either two courses of neoadjuvant M-VAC followed by surgery plus three additional cycles of chemotherapy, or, alternatively, to have initial cystectomy followed by five cycles of adjuvant chemotherapy. RESULTS: There were no significant differences in outcome between the two groups. By intent-to-treat, 81 patients (58%) remain disease-free, with median follow-up of 6.8 years. We confirmed a high rate of clinical understaging in this cohort, especially among patients showing lymphovascular invasion on biopsy. Patients with no residual muscle-invasive disease at cystectomy after neoadjuvant chemotherapy were likely to be cured. CONCLUSION: These results lend further support to the impression from small randomized trials that, in a high-risk cohort, there is an improved cure fraction by the combination of multiagent chemotherapy and surgery, although we found no preferred sequence. Importantly, it is possible to select appropriate patients for such therapy on the basis of clinical staging information. These results establish a benchmark of outcome for this cohort.

Adult↗
PubMed2001

Effectiveness of home based support for older people: systematic review and meta-analysis.

OBJECTIVE: To evaluate the effectiveness of home visiting programmes that offer health promotion and preventive care to older people. DESIGN: Systematic review and meta-analysis of 15 studies of home visiting. PARTICIPANTS: older people living at home, including frail older people at risk of adverse outcomes. OUTCOME MEASURES: Mortality, admission to hospital, admission to institutional care, functional status, health status. RESULTS: Home visiting was associated with a significant reduction in mortality. The pooled odds ratio for eight studies that assessed mortality in members of the general elderly population was 0.76 (95% confidence interval 0.64 to 0.89). Five studies of home visiting to frail older people who were at risk of adverse outcomes also showed a significant reduction in mortality (0.72; 0.54 to 0.97). Home visiting was associated with a significant reduction in admissions to long term institutional care in members of the general elderly population (0.65; 0.46 to 0.91). For three studies of home visiting to frail, "at risk" older people, the pooled odds ratio was 0.55 (0.35 to 0.88). Meta-analysis of six studies of home visiting to members of the general elderly population showed no significant reduction in admissions to hospital (odds ratio 0.95; 0.80 to 1.09). Three studies showed no significant effect on health (standardised effect size 0.06; -0.07 to 0.18). Four studies showed no effect on activities of daily living (0.05; -0.07 to 0.17). CONCLUSION: Home visits to older people can reduce mortality and admission to long term institutional care.

Aged↗
PubMed2001

Notification of gastrointestinal illness by Canterbury and West Coast general practitioners.

AIM: To identify factors influencing notification of enteric diseases by general practitioners (GPs). METHODS: The 'laboratory-based notification rate' was calculated for each GP by dividing the number of cases they notified by their number of laboratory detected cases of selected enteric diseases during 1997 and 1998. The 'annual full time equivalent (FTE) notification rate' was defined as the number of notifications received during the study period adjusted for the proportion of that time spent in clinical practice. These measures were compared with responses to a questionnaire posted to 395 Canterbury and West Coast GPs. RESULTS: 82% responded to the questionnaire. Higher 'laboratory-based notification rates' and 'annual FTE notification rates' were associated with the practice nurse being responsible for notifying and with GPs who were more recent graduates or who practised in rural areas. Few respondents identified high risk groups in their criteria for requesting a specimen. CONCLUSIONS: Communicable disease control could be enhanced by emphasising the importance of specimen collection in high risk groups, encouraging delegation of notification to practice nurses and encouraging the development of public health based guidelines to determine the need for specimen request

Communicable Disease Control↗
PubMed2001

Fatal portal hypertension, liver failure, and mitochondrial dysfunction after HIV-1 nucleoside analogue-induced hepatitis and lactic acidaemia.

Acute hepatitis with lactic acidosis is a life-threatening but reversible toxic effect on mitochondria of HIV-1 nucleoside-analogue treatment. We report fatal portal hypertension, liver failure, and persistent mitochondrial dysfunction in a man aged 65 years with HIV-1 infection who had recovered from nucleoside-analogue-induced acute hepatitis and lactic acidaemia more than 18 months previously. We believe that symptom free patients who receive nucleoside-analogue therapy should have hepatic function constantly monitored, especially those with past or present lactic acidaemia.

Acute Disease↗
PubMed2001

Observation of the Askaryan effect: coherent microwave Cherenkov emission from charge asymmetry in high-energy particle cascades.

We present the first direct experimental evidence for the charge excess in high-energy particle showers and corresponding radio emission predicted nearly 40 years ago by Askaryan. We directed picosecond pulses of GeV bremsstrahlung photons at the SLAC Final Focus Test Beam into a 3.5 ton silica sand target, producing electromagnetic showers several meters long. A series of antennas spanning 0.3 to 6 GHz detected strong, subnanosecond radio-frequency pulses produced by the showers. Measurements of the polarization, coherence, timing, field strength vs shower depth, and field strength vs frequency are completely consistent with predictions. These measurements thus provide strong support for experiments designed to detect high-energy cosmic rays such as neutrinos via coherent radio emission from their cascades.

Journal Article↗
PubMed2001

Ventricular and myocardial function following treatment of hypertension.

This study assesses and evaluates left ventricular (LV) contractile function after treatment of hypertension, with an emphasis on LV midwall mechanics. Although prior studies have assessed cardiac function after hypertension treatment, none has performed an analysis of LV midwall mechanics. The Veterans Affairs Study of monotherapy in hypertension was a study large enough to permit analysis of midwall mechanics across a wide spectrum of mass changes accompanying hypertension treatment. LV chamber function was assessed by computing fractional shortening at the endocardial surface; LV midwall shortening was used to define myocardial function. Both shortening indexes were related to end-systolic circumferential stress in the entire population by partitioning values of mass and relative wall thickness changes. Two hundred sixty-eight patients were studied at baseline and again after a 1- or 2-year period. In the entire group, there was no significant change in circumferential shortening either at the endocardium (38 +/- 8% at baseline vs 37 +/- 7% at follow up, p = 0.29) or in shortening at the midwall (20 +/- 3% vs 20 +/- 3%, p = 0.53). However, 83 patients had a reduction in relative wall thickness and an increase in midwall shortening. The change in midwall shortening was significantly related to changes in relative wall thickness (r = -0.53, p = 0.0001). Thus, reductions in LV mass associated with antihypertensive therapy are generally not accompanied by a decrement in LV chamber or myocardial function. Improvement in midwall shortening is more closely related to normalization of LV geometry than to reduction in LV mass.

Analysis of Variance↗
PubMed2001

Ratiometric analysis of the ferrocene boronate esters of 2- and 4-hydroxyestradiol by tandem electrospray mass spectrometry.

A method has been developed for the semiquantitative analysis of the catechol estrogens, 2- and 4-hydroxyestradiol, using tandem electrospray mass spectrometry in a quadrupole ion trap mass analyzer. The implication of catechol estrogens in the biogenesis of breast and prostate cancer makes these labile lipophilic compounds important analytical targets. Ferrocene boronic acid is reacted with 2- and 4-hydroxyestradiol to form their cyclic boronate esters. Sample ionization is accomplished during the electrospray process by a one-electron oxidation of the ferrocene functionality to form the radical cation. The analysis depends on a non-aqueous solvent system consisting of 90% acetonitrile and 10% dichloromethane with 100 microM lithium triflate as the supporting electrolyte. The sensitivity of the analysis is greatly increased by the use of a novel electrospray interface with a large surface area stainless steel electrode coupled to a pulled fused-silica needle. Collision-induced dissociation of the selected molecular ion within the ion trap produces fragment ion spectra that can be used to distinguish between the two isobaric isomers and ultimately determine the relative amounts in mixtures containing both components. The method is sensitive to analyte concentrations in the low nM range.

Esters↗
PubMed2001

Left ventricular geometry and operative mortality in patients undergoing mitral valve replacement.

BACKGROUND: Distortion of left ventricular (LV) shape is often associated with LV dysfunction and is thought to be an independent predictor of survival in patients with coronary disease. HYPOTHESIS: The purpose of this study was to examine the relationship between LV geometry and hospital mortality in patients with mitral regurgitation (MR) undergoing mitral valve surgery. METHODS: A consecutive series of patients (aged 68+/-12 years, 47% men) (n = 149) with MR who underwent cardiac catheterization, left ventriculography, and mitral valve surgery from 1995 to 1996 at Mount Sinai Medical Center was studied. Left ventriculograms, clinical records, and hemodynamics were reviewed. Left ventricular volumes and ejection fraction were calculated using standard techniques. Left ventricular shape in diastole and systole was evaluated using the sphericity index, which is defined as the end-systolic LV volume (x 100) divided by the volume of a sphere whose diameter is equal to the LV long axis. RESULTS: In the patients studied, the etiology of mitral insufficiency was mitral valve prolapse in 40.9%, ischemic heart disease in 40.3%, rheumatic heart disease in 11.4%, and prosthetic valvular dysfunction in 7.4%. The average ejection fraction was 65%+/-17. Systolic sphericity index (SSI) was 36%+/-15 in patients who died, compared with 25%+/-11 in patients who lived (p < 0.001). A multivariate model was constructed using hemodynamic and angiographic indices derived during preoperative cardiac catheterization. Systolic sphericity index (odds ratio = 1.6 for each point increase, p < 0.01) was found to be an independent predictor of postoperative survival in the global population, as well as in patients with coronary disease (p<0.01). CONCLUSION: Left ventricular geometry is an independent angiographic risk factor for survival following mitral valve replacement. Sphericity index is a simple method for assessing LV geometry which should be calculated in patients as part of risk stratification.

Adult↗
PubMed2001

Pharmacoepidemiology--an Irish perspective.

The Irish healthcare system is a mixture of free, state-supported and private medicine. The state-supported General Medical Services (GMS) scheme maintains a large prescription database, which has been used to conduct pharmacoepidemiological studies in Ireland. The dataset is anonymized thus maintaining patient and prescriber confidentiality. Three recent studies using this data are described, two of which outline the effect of regulatory advice and the media on prescribing patterns and one which describes the development of an index of prescribing quality which may be applied to prescription data. The GMS prescription database is presently being complemented by a database for some 0.7 million people who seek reimbursement for prescriptions from individuals or families in excess of 42 Pounds per month which together will have an important role for the continued development of pharmacoepidemiology in Ireland.

Clinical Trials as Topic↗
PubMed2001

Initial uptake in use of sildenafil in general practice.

OBJECTIVE: To assess the initial uptake in use and co-prescribing patterns of sildenafil. METHODS: We examined prescription details of the Eastern Health Board Region (including Dublin) of the General Medical Services (GMS) in Ireland, which provides detail on prescriptions dispensed in primary care for this population (n = 334,031). We identified 1422 patients who received 3740 prescriptions for sildenafil over a 6-month period (July 1999-December 1999) and determined the percentage of patients who were co-prescribed nitrate therapy, medications which may interact with sildenafil and medications associated with impotence. RESULTS: We identified 1422 (1.4% of the male population over 16 years who might be expected to suffer from erectile dysfunction given an overall prevalence of 10%) who received a prescription for sildenafil over the study period at a cost of 0.14% of the annual drug budget. Up to 2.5%, 6% and 25% of patients were co-prescribed, respectively, nitrate therapy, potentially interacting drugs and drugs associated with impotence. CONCLUSION: The initial uptake and cost associated with sildenafil was lower than expected. The rate of prescribing of nitrates and other potentially interacting medications was found to be low. Medication use may also contribute to erectile dysfunction in this population of patients.

Adolescent↗