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E Burns

Publications and source records attributed to E Burns.

At least 19 recordsLinked to original sources
PubMed1999

Selective killing of cancer cells based on loss of heterozygosity and normal variation in the human genome: a new paradigm for anticancer drug therapy.

Most drugs for cancer therapy are targeted to relative differences in the biological characteristics of cancer cells and normal cells. The therapeutic index of such drugs is theoretically limited by the magnitude of such differences, and most anticancer drugs have considerable toxicity to normal cells. Here we describe a new approach for developing anticancer drugs. This approach, termed variagenic targeting, exploits the absolute difference in the genotype of normal cells and cancer cells arising from normal gene sequence variation in essential genes and loss of heterozygosity (LOH) occurring during oncogenesis. The technology involves identifying genes that are: 1) essential for cell survival; 2) are expressed as multiple alleles in the normal population because of the presence of one or more nucleotide polymorphisms; and 3) are frequently subject to LOH in several common cancers. An allele-specific drug inhibiting the essential gene remaining in cancer cells would be lethal to the malignant cell and would have minimal toxicity to the normal heterozygous cell that retains the drug-insensitive allele. With antisense oligonucleotides designed to target two alternative alleles of replication protein A, 70-kDa subunit (RPA70) we demonstrate in vitro selective killing of cancer cells that contain only the sensitive allele of the target gene without killing cells expressing the alternative RPA70 allele. Additionally, we identify several other candidate genes for variagenic targeting. This technology represents a new approach for the discovery of agents with high therapeutics indices for treating cancer and other proliferative disorders.

Antineoplastic Agents↗
PubMed1999

Lack of a pharmacokinetic interaction at steady state between ropinirole and L-dopa in patients with Parkinson's disease.

STUDY OBJECTIVE: To assess the interaction between therapeutic dosages of ropinirole and L-dopa plus a decarboxylase inhibitor administered at steady state in patients with Parkinson's disease. DESIGN. Open, 6-week, overlap trial with random allocation. PATIENTS: Thirty patients with Parkinson's disease not previously treated with dopamine agonists, of whom 28 produced evaluable pharmacokinetic data for ropinirole and 23 for L-dopa. INTERVENTION: Group A (14 patients) received L-dopa for weeks 1-5 and ropinirole in increasing increments for weeks 2-6; group B (16) received ropinirole for weeks 1-5 and L-dopa for weeks 5 and 6. MEASUREMENTS AND MAIN RESULTS: Primary end points were AUC0-8 and Cmax for ropinirole, and AUC0-8, AUC0-infinity and Cmax for L-dopa. Secondary end points were Tmax for ropinirole, and Tmax and half-life for L-dopa. Coadministration with L-dopa at steady state did not affect rate or extent of availability of ropinirole: point estimates of the geometric mean ratio for ropinirole plus L-dopa compared with ropinirole alone for both Cmax and AUC0-8 approximated to unity. The small (16%) increase in peak concentrations of L-dopa on administration with ropinirole is unlikely to be of clinical consequence, as peak concentrations of L-dopa are typically highly variable. CONCLUSION: There are no pharmacokinetic grounds for adjusting dosages of either ropinirole or L-dopa when given in combination.

Aged↗
PubMed1998

Problem of amputations in patients with newly diagnosed diabetes mellitus.

A reduction of 50% or more in diabetes-related amputations is a primary target of the St Vincent Declaration. This is thought to be achievable because both primary and secondary preventative healthcare strategies are effective in reducing the incidence of diabetic foot ulceration and progression to amputation. Unfortunately there is a group who cannot benefit from preventative health care, that is, newly diagnosed diabetic patients with already established severe complications. Using our population-based district diabetes information system we investigated, during the period 1 January 1992 to 31 December 96, the incidence and prevalence of lower extremity amputations (LEAs) and the proportion occurring in patients newly or recently diagnosed as having diabetes. Seventy-nine diabetic patients (59 male, 20 female) were recorded as having had 94 LEAs, the incidence of diabetes-related LEA being 475 per 100,000 diabetic patient-years. Of these LEAs 16 (20.2%) were performed within 1 year of diabetes being diagnosed. This study highlights an appreciable and previously unrecognized problem: patients presenting with established complications of diabetes who cannot benefit from secondary preventative healthcare. These patients pose a potential obstacle to achieving targets for reductions in diabetes-related amputations.

Adult↗
PubMed1997

Gas chromatographic-mass spectrometric identification and quantitation of urinary phenols after derivatization with 4-carbethoxyhexafluorobutyryl chloride, a novel derivative.

Urinary phenol is analyzed widely to determine benzene exposure in humans. Most methods utilize direct measurements of phenols after extraction from urine using gas chromatography or high-performance liquid chromatography. We describe a novel derivatization of urinary phenols using 4-carbethoxyhexafluorobutyryl chloride after extraction from urine and subsequent analysis by gas chromatography-mass spectrometry. The derivative elutes at significantly higher temperature than phenol and the method is free from interferences from more volatile components in urine. We also observed excellent chromatographic properties of these derivatives. In addition, we observed strong molecular ions for the 4-carbethoxyhexafluorobutyryl derivative of phenol (m/z 344), p-cresol (m/z 358) and the internal standard 3,4-dimethylphenol (m/z 372) and other characteristic ions in the electron ionization, thus aiding in unambiguous identification of these compounds. The protonated molecular ions (m/z 373 for derivatized phenol, m/z 359 for derivatized p-cresol and m/z 373 for the internal standard) were the base peaks (relative abundance 100%) in the chemical ionization, although other secondary peaks were less abundant. The assay is linear for phenol concentration of 1-100 mg/l. The within-run and between-run precisions were 4.8% (mean = 52.4, S.D. = 2.5 mg/l) and 8.1% (mean = 53.0, S.D. = 4.3 mg/l) respectively, and the detection limit was 0.5 mg/l.

Acids↗
PubMed1997

Randomised trial of one versus two doses of prostaglandin E2 for induction of labour: 1. Clinical outcome.

OBJECTIVE: To compare the outcome of induction of labour using a single versus two doses of prostaglandin E2 vaginal gel. DESIGN: Prospective randomised trial comparing a single dose of prostaglandin E2 2 mg vaginal gel in the evening with two doses of prostaglandin E2 (2 mg), the second being given after six hours if labour had not started or the cervix was still unripe. Amniotomy and oxytocin titration were performed when necessary for both protocols. Nulliparae and multiparae were analysed separately by treatment intention. SETTING: A maternity unit in a district general hospital annually delivering > 6000 women. PARTICIPANTS: Nine-hundred and ninety-five women with viable singleton pregnancies and cephalic presentation at term without previous history of caesarean section who were advised to have labour induced with prostaglandins. MAIN OUTCOME MEASURES: Need for formal amniotomy and oxytocin augmentation, use of epidural analgesia, rate of intrapartum interventions, mode of delivery and neonatal condition at birth. RESULTS: For multiparae two prostaglandin doses resulted in a significant reduction in the need for formal amniotomy (15% vs 30%) and oxytocin augmentation (28% vs 38%) compared with those receiving a single dose; there was no significant difference for nulliparae. Other interventions during labour, length of labour, and mode of delivery were similar in both protocols. Failed induction occurred only in nulliparae and was similar in both protocols (1%). There was no discernible difference in fetal or neonatal outcome although passage of meconium was more common in labour if two doses had been given, as was neonatal admission to the special care baby unit. CONCLUSIONS: There was little clinical benefit from inducing labour with two doses of prostaglandin E2 at a six-hour interval, compared with a single dose. There may be financial advantages with a two-dose regimen.

Administration, Intravaginal↗
PubMed1997

Randomised trial of one versus two doses of prostaglandin E2 for induction of labour: 2. Analysis of cost.

OBJECTIVE: To compare the impact upon maternity unit resources and finances of two protocols for induction of labour using prostaglandins. DESIGN: A prospective randomised trial comparing a single dose of prostaglandin E2 (2 mg) in the evening with two doses of prostaglandin E2 (2 mg), the second being given after six hours if labour had not started or the cervix was still unripe, followed if necessary by formal induction of labour by amniotomy and oxytocin infusion 14 to 20 hours after the initial prostaglandin E2 dose. Outcome for nulliparae and multiparae were analysed separately, by treatment intention. SETTING: A maternity unit in a district general hospital delivering > 6000 women annually. PARTICIPANTS: Nine hundred and fifty-five women with viable singleton pregnancies and cephalic presentation at term without previous history of caesarean section who were advised to have labour induced with prostaglandins. MAIN OUTCOME MEASURES: Costs incurred in managing all aspects of labour, including time spent on the antenatal ward and, in the delivery unit; costs associated with formal induction, augmentation of labour and epidural analgesia; costs of intrapartum maternal morbidity, mode of delivery and immediate neonatal care. Costs of postpartum hospital stay were estimated from unit statistics. RESULTS: The overall mean cost of induction of labour was Pounds 5.00 and Pounds 7.22 less per woman for nulliparae and multiparae, respectively, if the two dose regimen was used. The main reason for the differences was due to delivery suite costs from the slightly greater rate of assisted deliveries in the single treatment groups. In contrast, costs for neonatal care were marginally lower if only one prostaglandin dose was used. CONCLUSIONS: The increased drug costs providing two prostaglandin E2 doses when required were off-set by reductions in the costs of other intrapartum interventions for both nulliparae and multiparae. The advantages of less time spent on the antenatal ward for multiparae when two prostaglandin E2 doses were used may be eliminated if amniotomy and oxytocin infusion was commenced six hours after the initial prostaglandin dose had been given if labour had not started.

Dinoprostone↗
PubMed1996

Caring for older people. Community services: health.

Many frail or disabled elderly people are now being maintained in the community, partially at least as a consequence of the Community Care Act 1993. This paper details the work of the major health professionals who are involved in caring for older people in the community and describes how to access nursing, palliative care, continence, mental health, Hospital at Home, physiotherapy, occupational therapy, equipment, and optical, dental, and dietetic services. In many areas, services are evolving to meet needs and some examples of innovative practice are included.

Aged↗
PubMed1995

Weekly ventilator circuit changes. A strategy to reduce costs without affecting pneumonia rates.

BACKGROUND: Mechanical ventilator circuits are commonly changed at 48-h intervals. This frequency may be unnecessary because ventilator-associated pneumonia often results from aspiration of pharyngeal secretions and not from the ventilator circuit. We compared the ventilator-associated pneumonia rates and costs associated with 48-h and 7-day circuit changes. METHODS: Ventilator circuits were changed at 48-h intervals during the control period (November 1992 to April 1993) and at 7-day intervals during the study period (June 1993 to November 1993). Nosocomial pneumonias were prospectively identified using the criteria of the Centers for Disease Control and Prevention. The annual cost difference of changing circuits at 48-h and 7-day intervals was calculated using the distribution of ventilator days for the control and study periods. RESULTS: There were 1,708 patients, 9,858 ventilator days, and a pneumonia rate of 9.64 per 1,000 ventilator days in the control group (48-h circuit changes). There were 1,715 patients, 9,160 ventilator days, and 8.62 pneumonias per 1,000 ventilator days when circuits were changed at 1-week intervals (study group). Using a logistic regression model, there were significantly greater odds of developing a ventilator-associated pneumonia in surgical patients (odds ratio 1.77, P = 0.02) and patients in critical care units (odds ratio 1.54, P = 0.05), but no significant risk of ventilator-associated pneumonia in patients in whom circuits were changed at 1-week intervals (odds ratio 0.82, P = 0.22). Changing circuits at 7-day intervals resulted in a 76.6% ($111,530) reduction in the annual cost for materials and salaries. CONCLUSIONS: We found no difference in pneumonia rates with ventilator circuit changes at 48-h and 7-day intervals. Ventilator circuits can be safely changed at weekly intervals, resulting in large cost savings.

Adult↗
PubMed1992

Vitamin C depletion and pressure sores in elderly patients with femoral neck fracture.

OBJECTIVE: To evaluate the contribution of specific nutritional deficiencies (as indicated by zinc; vitamin A, C, and E; albumin; and haemoglobin concentrations) to the risk of pressure sores. DESIGN: Observational cohort study. SETTING: St James's University Hospital, Leeds. SUBJECTS: 21 elderly patients presenting consecutively to the orthopaedic unit with femoral neck fracture. MAIN OUTCOME MEASURE: Full thickness epidermal break over a pressure bearing surface. RESULTS: 10 patients (48%) developed a pressure sore during their hospital stay. Indices of zinc status and concentrations of albumin, haemoglobin, and vitamins A and E were similar in patients who developed a pressure sore and those who did not. Mean leucocyte vitamin C concentration, however, was 6.3 (SD 2.2) micrograms/10(8) cells in patients who developed a pressure sore as compared with 12.8 (4.6) micrograms/10(8) cells in patients who did not. CONCLUSIONS: Low concentrations of leucocyte vitamin C appear to be associated with subsequent development of pressure sores in elderly patients with femoral neck fractures.

Aged↗
PubMed1992

A survey of hospital toilet facilities.

OBJECTIVE: To assess the quality of toilet facilities available for disabled people in a large provincial teaching hospital. DESIGN: Survey of toilet facilities for patients on the wards and in the outpatient department. SETTING: Teaching hospital in Leeds. RESULTS: Although the quality of toilet facilities varied, none met the standards recommended by the British Standards Institution. The worst facilities were found on a ward accommodating elderly patients, where the toilets were unsuitable for use by disabled people and bedside commodes had to be used instead. CONCLUSION: Toilet provision within a major hospital failed to meet standards required for disabled people. Admission to hospital may therefore result in loss of independence and dignity. If hospitals are to be centres of excellence, greater consideration must be given to the requirements of disabled people in the design of new wards, and current inadequate facilities should be upgraded.

Architectural Accessibility↗
PubMed1992

Lymphadenectomy in gastric carcinoma. A prospective and prognostic study.

In 193 gastric resections for adenocarcinoma, lymphadenectomy was prospectively evaluated to quantify the number of lymph nodes and to identify prognostic factors. Overall, 7112 nodes (median, 36.8 per patient) were resected with 27.2% showing metastases. Most nodes were found in the perigastric region. The histologic type and site of the tumor did not influence the number of invaded nodes, but tumor stage and quality of the resection (curative/palliative) did. By multivariate analysis the tumor stage, curative vs palliative resections, and the number of metastatic lymph nodes in curative resections were independent prognostic factors. Patients with less than six metastatic nodes showed a survival not significantly different from that of patients with normal nodes. These patients may be well treated by surgery alone, but the other patients may require multimodal therapy to improve their prognosis.

Adenocarcinoma↗
PubMed1992

The influence of age on policies for admission and thrombolysis in coronary care units in the United Kingdom.

Age is an important factor influencing survival following an acute myocardial infarction. In clinical practice many elderly patients are neither admitted to coronary care nor receive thrombolytic therapy. A postal questionnaire was sent to all 175 consultants in charge of coronary care units in the United Kingdom to determine whether age-related policies are being operated which are limiting the access of elderly patients to life-saving interventions. One hundred and thirty-four questionnaires (77%) were returned. One-fifth of coronary care units operate an age-related admission policy, and two-fifths operate an age-related thrombolysis policy. The age limits used by many of these units are likely to exclude large numbers of patients who could benefit from cardiac monitoring and resuscitation as well as thrombolytic treatment. The abolition of age-related policies would help to ensure that thrombolysis is readily available to the group of patients most likely to benefit from it.

Aged↗
PubMed1992

Practical problems with eye-drops among elderly ophthalmology outpatients.

Many elderly patients have eye-drops prescribed. We have examined the abilities in eye drop application of 43 consecutive outpatients aged 75 years or more who completed a questionnaire and demonstrated their technique in eye-drop application. Less than one-third of patients applied drops themselves, the rest relying on others; one-third of this group lived alone. The majority of patients experienced some difficulty with the application of their drops and it was estimated that half of those who usually applied their own treatment were unlikely to succeed in instilling a drop into the conjunctival sac. Few patients had been prescribed aids or appliances to improve their eye-drop application technique.

Aged↗