Search PubMed⌕ Search

Biomedical subjects

M Price

Publications and source records attributed to M Price.

At least 19 recordsLinked to original sources
PubMed2006

Role of the JNK pathway in NMDA-mediated excitotoxicity of cortical neurons.

Excitotoxic insults induce c-Jun N-terminal kinase (JNK) activation, which leads to neuronal death and contributes to many neurological conditions such as cerebral ischemia and neurodegenerative disorders. The action of JNK can be inhibited by the D-retro-inverso form of JNK inhibitor peptide (D-JNKI1), which totally prevents death induced by N-methyl-D-aspartate (NMDA) in vitro and strongly protects against different in vivo paradigms of excitotoxicity. To obtain optimal neuroprotection, it is imperative to elucidate the prosurvival action of D-JNKI1 and the death pathways that it inhibits. In cortical neuronal cultures, we first investigate the pathways by which NMDA induces JNK activation and show a rapid and selective phosphorylation of mitogen-activated protein kinase kinase 7 (MKK7), whereas the only other known JNK activator, mitogen-activated protein kinase kinase 4 (MKK4), was unaffected. We then analyze the action of D-JNKI1 on four JNK targets containing a JNK-binding domain: MAPK-activating death domain-containing protein/differentially expressed in normal and neoplastic cells (MADD/DENN), MKK7, MKK4 and JNK-interacting protein-1 (IB1/JIP-1).

Adaptor Proteins, Signal Transducing↗
PubMed2006

Cost-effectiveness of migraine prevention: the case of topiramate in the UK.

The aim of this study was to assess the cost-effectiveness of topiramate vs. no preventive treatment in the UK. Model inputs included baseline migraine frequency, treatment discontinuation and response, preventive and acute medical cost per attack [2005 GBP ( pound)] and gain in health utility. Outcomes included monthly migraines averted, acute and preventive treatment costs and cost per quality-adjusted life year (QALY). Topiramate was associated with 1.8 fewer monthly migraines and a QALY gain of 0.0384. The incremental cost of topiramate vs. no preventive treatment was about 10 UK pounds per migraine averted and 5700 UK pounds per QALY. Results are sensitive to baseline monthly migraine frequency, triptan use rate and the gain in utility. Incorporating savings from reduced work loss (about 36 UK pounds per month) suggests that topiramate would be cost saving compared with no preventive treatment. This analysis suggests that topiramate is a cost-effective treatment for migraine prevention compared with no preventive treatment.

Adult↗
PubMed2005

Patients' preference for administration of endocrine treatments by injection or tablets: results from a study of women with breast cancer.

BACKGROUND: Endocrine therapies for advanced breast cancer include tablets and intramuscular injections. When treatments have similar efficacy and tolerability profiles, addressing preferences about routes of administration is important. PATIENTS AND METHODS: Two hundred and eight women>2 years post-breast cancer diagnosis were interviewed about their preferences for daily tablets or monthly intramuscular injections. Health-care professionals treating the women estimated patients' preferences. RESULTS: Sixty-three per cent of patients preferred tablets, 24.5% preferred the injection and 12.5% had no preference. The most cited reasons for tablet preference were convenience and dislike of needles; for injection preference, adherence and convenience. Variables associated with preferences were body mass index, educational level, attitudes towards injections and efficacy perceptions. Estimates about patients' preferences by health-care professionals varied widely. When asked to imagine scenarios where injections produced fewer hot flushes, or where two injections monthly improved efficacy, injection preference increased to 60.6% and 74.5%, respectively. Disturbingly, approximately 50% of patients admitted they sometimes forgot or chose not to take their current oral medication. CONCLUSIONS: The majority of breast cancer patients preferred hormone therapy via daily tablets rather than monthly injections. Information about side-effects or improved efficacy altered these preferences. Adherence to treatment cannot be assumed; patients' preferences about drug administration may influence this.

Administration, Oral↗
PubMed2005

C1 inhibitor deficiency: consensus document.

We present a consensus document on the diagnosis and management of C1 inhibitor deficiency, a syndrome characterized clinically by recurrent episodes of angio-oedema. In hereditary angio-oedema, a rare autosomal dominant condition, C1 inhibitor function is reduced due to impaired transcription or production of non-functional protein. The diagnosis is confirmed by the presence of a low serum C4 and absent or greatly reduced C1 inhibitor level or function. The condition can cause fatal laryngeal oedema and features indistinguishable from gastrointestinal tract obstruction. Attacks can be precipitated by trauma, infection and other stimulants. Treatment is graded according to response and the clinical site of swelling. Acute treatment for severe attack is by infusion of C1 inhibitor concentrate and for minor attack attenuated androgens and/or tranexamic acid. Prophylactic treatment is by attenuated androgens and/or tranexamic acid. There are a number of new products in trial, including genetically engineered C1 esterase inhibitor, kallikrein inhibitor and bradykinin B2 receptor antagonist. Individual sections provide special advice with respect to diagnosis, management (prophylaxis and emergency care), special situations (childhood, pregnancy, contraception, travel and dental care) and service specification.

Adolescent↗
PubMed2004

Spatial and temporal structure of edge-localized modes.

This Letter provides information on the spatial and temporal structure of periodic eruptions observed in magnetically confined laboratory fusion plasmas, called edge-localized modes (ELMs), and highlights similarities with solar eruptions. Taken together, the observations presented in this Letter provide strong evidence for ELMs being associated with a filamentlike structure. These filaments are extended along a field line, are generated on a 100 micros time scale, erupt from the outboard side, and connect back into the plasma. Such structures are predicted by a theoretical model based on the "ballooning" instability, developed for both solar and tokamak applications.

Journal Article↗
PubMed2003

A Markov model of treatment of newly diagnosed epilepsy in the UK. An initial assessment of cost-effectiveness of topiramate.

Long-term comparative trials among newer antiepileptic drugs are lacking; therefore decision models are needed to guide treatment decisions. The goal of this study was to develop an economic model of newly diagnosed epilepsy in the UK and to provide the first assessment of topiramate. A Markov model was developed combining data from clinical trials, cost-of illness, mortality, and utility studies. Expected costs and utilities associated with treatment strategies (first- and second-line treatments) were compared to find the cost-effectiveness frontier. First- and second-line monotherapy with topiramate or carbamazepine in partial seizures was less costly and more effective than other scenarios. In generalised seizures first-line topiramate was cost-effective with valproate or lamotrigine as second-line treatments depending on the set of utilities used. Models provide a relevant framework within which costs and health gains of antiepileptic drugs treatment options can be studied. Our findings are further evidence of the promising role of topiramate for patients with newly diagnosed epilepsy.

Journal Article↗
PubMed2003

Protecting the terminus: t-loops and telomere end-binding proteins.

Telomeric DNA is composed of a region of duplex telomeric tract followed by a single-strand overhang on the 3' G-rich strand. The DNA is packaged by proteins that associate directly with the single- and double-strand regions of the telomeric tract and by their associated proteins. This review discusses the evidence that G-strand overhangs are present on both ends of eukaryotic chromosomes and the steps needed to generate these overhangs. The overhangs are protected by specialized G-overhang-binding protein and/or invasion by the overhang of the duplex region of the telomeric tract to form a structure called a 't-loop'. The G-overhang-binding proteins identified from different species are described, and their properties compared. The data supporting the existence of t-loops at native telomeres is discussed, and the conditions required to promote their in vitro formation are presented.

Animals↗
PubMed2003

Measuring costs and consequences in economic evaluation in asthma.

Formal economic evaluation is playing an increasingly important role in health-care decision-making. This is shown by the requirement to present economic data to support applications for public reimbursement for new pharmaceuticals in Australia and the provinces of Canada, and by the appraisal process initiated by the National Institute for Clinical Excellence in the U.K. This growing role of economic analysis applies as much to the field of asthma as anywhere. This paper provides a detailed review of applied economic studies in asthma. The review is used to explore a range of methodological issues in the field including the choice of perspective and maximand, whether to use disease-specific or generic measures of outcome and whether decision-makers should receive disaggregated cost and consequence data or results that focus on an incremental cost-effectiveness ratio. It is concluded that, given the heterogeneity in decision-makers' objectives and constraints, economic studies should be planned and executed in such a way as to maximize flexibility in how results are presented.

Anti-Asthmatic Agents↗
PubMed2003

Attitudes to prophylactic surgery and chemoprevention in Australian women at increased risk for breast cancer.

BACKGROUND: Because of the uncertain efficacy of breast cancer screening in women at increased risk of developing breast cancer, bilateral prophylactic oophorectomy and mastectomy are considered management options for high-risk women. Data on the attitudes to prophylactic strategies of high-risk women who have not attended specialist clinics are needed to ascertain the need for patient education and provide the basis for planning of support services. METHODS: Three hundred seventy-one women unaffected by cancer and with unknown mutation status from families with a dominantly inherited susceptibility to breast cancer, recruited through a large Australian population-based, epidemiological study, were assessed using a mailed self-administered questionnaire with validated measures of psychological outcome. RESULTS: Sixteen percent of women reported considering prophylactic mastectomy, and 1% had already had the procedure. Among women with a family history of breast/ovarian cancer, 33% had considered and 5% had already had a prophylactic oophorectomy. Twenty-three percent of women reported considering taking tamoxifen if it were shown to prevent breast cancer. Consideration of prophylactic oophorectomy (OR = 1.51 for a 10% change in perceived risk, 95% CI 1.14-1.99, p = 0.0045) and tamoxifen (OR = 1.14 for a 10% change in perceived risk, 95% CI 1.002-1.30, p = 0.047) were positively associated with perceived cancer risk. CONCLUSIONS: Attitudes to prophylactic surgery and psychological distress levels in high-risk women participating in an epidemiological study appear to be comparable to those of women attending familial cancer clinics and indicate that women attending high-risk clinics may be representative of the larger population of women at increased risk.

Adult↗
PubMed2003

Extended formulary nurse prescribing--another saliva substitute roadblock.

United Kingdom family physicians, General Practitioners (GPs), are allowed to prescribe from a Department of Health-approved list of non-medicines (the 'ACBS' list) which includes a majority of proprietary saliva substitutes. Independent nurse prescribing, introduced in 2001, has improved patient access to effective remedies for a wide range of common medical problems. Further qualified 'extended formulary nurse prescribers' have access to a limited range of prescription medicines, and all non-prescription medicines that GPs may currently prescribe. Despite their specified role in the management of oral complications encountered in palliative care, a similar anomaly in NHS rules that prevents dental practitioners from prescribing ACBS listed saliva substitutes also prevents nurses from prescribing them. Sadly, patients are suffering poorer access to simple and effective remedies to conditions such as xerostomia - a condition that has recognised impact on their quality of life.

Drug Prescriptions↗
PubMed2003

Use of videotape to assess mobility in a controlled randomized crossover trial of physiotherapy in chronic multiple sclerosis.

OBJECTIVES: To determine to what degree assessment of mobility based on comparison of videotape recordings before and after courses of physiotherapy in patients with chronic multiple sclerosis (MS) is reliable, correlates with 'live' assessments and indicates benefit. DESIGN: Prospective data collection within a randomized crossover controlled trial of physiotherapy at home, as an outpatient, or 'no therapy' in 40 patients. SETTING: Hospital outpatients: outpatient and home physiotherapy. OUTCOMES: Mobility change based on a comparison of short video recordings before and after each treatment period was scored independently by two physiotherapists blinded to therapy type and other measures of outcome. Scores were compared with changes in the Rivermead Mobility Index (RMI) and other indices assessed by a physiotherapist in the patient's home. RESULTS: The two video observers agreed substantially on patient outcome. Changes in walking based on video correlated with RMI for home treatment (r = 0.41, p = 0.008) but not for hospital or no treatment periods (r = 0.14 and 0.15): video changes correlated with the 'live' assessor's global change score inconsistently ('no therapy' r = 0.48, p = 0.002, hospital r = 0.30, p = 0.06 and home r = 0.17, p = 0.30 treatment periods). Based on video data alone, improved mobility was evident following home therapy for only one observer but not for the other or the averaged scores of both. CONCLUSION: There was substantial agreement between two observers deciding on change in mobility based on independent blinded evaluation of short video sequences. However the correlations of these with 'live' assessments were variable. Physiotherapy had a less clear benefit on mobility based on video analysis alone compared with 'live' assessments. The study highlights the need for more objective measures of habitual mobility over longer periods.

Adult↗
PubMed2002

Xenoendocrine disrupters-tiered screening and testing: filling key data gaps.

The US Environmental Protection Agency (EPA) is developing a screening and testing program for endocrine disrupting chemicals (EDCs) to detect alterations of hypothalamic-pituitary-gonadal (HPG) function, estrogen (ER), androgen (AR) and thyroid hormone synthesis and AR and ER receptor-mediated effects in mammals and other animals. High priority chemicals would be evaluated in the Tier 1 Screening (T1S) battery and chemicals positive in T1S would then be tested (Tier 2). T1S includes in vitro ER and AR receptor binding and/or gene expression, an assessment of steroidogenesis and mammalian (rat) and nonmammalian in vivo assays (Table 1). In vivo, the uterotropic assay detects estrogens and antiestrogens, while steroidogenesis, antithyroid activity, (anti)estrogenicity and HPG function are assessed in a 'Pubertal Female Assay'. (Anti-) androgens are detected in the Hershberger Assay (weight of AR-dependent tissues in castrate-immature-male rats). Fish and amphibian assays also are being developed. The fathead minnow assay can identify EDCs displaying several mechanisms of concern, including AR and ER receptor agonists and antagonists and inhibitors of steroid hormone synthesis. An amphibian metamorphosis assay is being developed to detect thyroid-active substances. Several alternative mammalian in vivo assays have been proposed. Of these, a short-term pubertal male rat assay appears most promising. An in utero-lactational screening protocol also is being evaluated. For Tier 2, the numbers of endocrine sensitive endpoints and offspring (F1) examined in multigenerational tests need to be expanded for EDCs. Consideration should be given to tailoring T2, based on the results of T1S. Tier 1 and 2 also should examine relevant mixtures of EDCs. Toxicants that induce malformations in AR-dependent tissues produce cumulative effects even when two chemicals act via different mechanisms of action.

Animals↗
PubMed2002

Budget impact model for determining the costs of introducing inhaled salmeterol/fluticasone propionate combination for the management of persistent asthma in France.

A budget impact model was used to estimate the effect of introducing inhaled salmeterol/fluticasone propionate combination on asthma drug-related costs in France. The model is based on disease prevalence, drug use, drug acquisition cost and sales forecasting data specific to France. It takes the perspective of social security and has a time horizon of 1 year. All drug acquisition costs are adjusted for the average rate of reimbursement of asthma medications in France (77.3%). All costs are expressed in euros. The model shows that if patients receiving concurrent salmeterol plus fluticasone propionate (or budesonide plus formoterol switch to combined salmeterol/fluticasone propionate, the anticipated annual savings would be 2,691,580 and 1,916,966 euros, respectively. On a fixed budget 4067 additional patients could be treated if salmeterol/fluticasone propionate is substituted for concurrent salmeterol plus fluticasone propionate and an additional 2939 patients if the combination is used to replace concurrent budesonide plus formoterol. Overall, using sales forecasting data to estimate how many patients will switch to the new combination from their current therapy, it is estimated that the introduction of salmeterol/fluticasone propionate will increase the national expenditure in France on asthma medications by a maximum of 3%. This budget impact model shows that the introduction of inhaled salmeterol/fluticasone propionate combination is likely to have minimal impact on asthma-related medication costs in France. Moreover, the available data on the salmeterol/fluticasone propionate combination suggest that it is clinically effective, cost-effective and affordable to the French healthcare system.

Journal Article↗
PubMed2002

How many years do students study before graduating in medicine?

OBJECTIVES: The Faculty of Health Sciences at the University of the Witwatersrand is considering changing from a 6-year medical degree to a mainly graduate-entry 4-year degree. The objective of this study was to determine how long students currently take to qualify and how many years are spent studying for each medical graduate produced. DESIGN: A retrospective study of 691 students registered in medicine at the University of the Witwatersrand in 1988, 1989 and 1990 was conducted by examining student progress records. RESULTS: The study found that an average of 7.89 years was spent studying for each graduate produced, including tertiary studies before medicine, repeated years and intercalated science degrees. Five hundred and eighty-nine students (85%) graduated and 102 (15%) did not. Forty-eight per cent studied for 7 or more years before graduating, 21% completed degrees before or during their medical studies, and 21% of students repeated years. CONCLUSION: The costs to the individual and society of the new 3 + 4-year degree structure would not be very different from those of the current 6-year structure.

Curriculum↗
PubMed2001

Questionnaire survey of the views of the delegates at the European Cervical Spine Research Society meeting on the administration of methylprednisolone for acute traumatic spinal cord injury.

STUDY DESIGN: A questionnaire survey. OBJECTIVES: To collate and analyze the views of the delegates who attended the European Cervical Spine Research Society (CSRS) meeting on the use of methylprednisolone for acute traumatic spinal cord injury. SUMMARY OF BACKGROUND DATA: The NASCIS II and III studies reported improved neurologic recovery in patients who were treated with methylprednisolone within 8 hours of their acute traumatic spinal cord injury. A number of reported commentaries have criticized these trials. A recent audit in the authors' regional spinal injuries unit in the United Kingdom found that a large percentage of patients were not receiving methylprednisolone. The authors decided to collate the views of the delegates at the CSRS regarding the use of steroids for acute traumatic spinal cord injury. METHODOLOGY: A questionnaire was created that took into account the positive reported findings as well as the criticisms of the NASCIS studies. Delegates who attended the European CSRS meeting completed this questionnaire. RESULTS: Seventy-five percent of the delegates answered that they used or recommended methylprednisolone in the treatment of acute traumatic spinal cord injury. Nevertheless, the delegates had an average of 1.5 reservations about administering methylprednisolone. The most common reservation was that they did not think the improvement conferred to the patients by administering methylprednisolone had been clinically or functionally proven. There were reservations about the validity of the statistical analysis used in the NASCIS studies and by the omission of a placebo group in NASCIS III. The majority of the delegates thought it was not medicolegally negligent to withhold the administration of methylprednisolone in the treatment of acute traumatic spinal cord injury. CONCLUSION: The use of methylprednisolone in the treatment of acute traumatic spinal cord injury is still controversial. It would appear from a recent prospective audit at the authors' spinal injuries unit that a large percentage of patients in the United Kingdom are not receiving methylprednisolone. Because so much doubt exists, the NASCIS studies should be repeated.

Acute Disease↗
PubMed2001

Volunteer-based universal newborn hearing screening program.

OBJECTIVE: To evaluate efficacy and costs of a volunteer-based universal newborn hearing screening program. METHODS: The Lucile Packard Children's Hospital at Stanford newborn hearing screening program database was reviewed. Results and costs of the hearing screens were analyzed. RESULTS: Hearing screens were performed on 5771 newborns treated in the well-baby nursery and nine infants from this population were identified with hearing loss, seven of whom had no risks factors for hearing loss. Using volunteers to perform the first-line screen with the automated auditory brainstem response (AABR) technology, 91% of infants registered for screening were evaluated prior to discharge. An additional 4% of infants were screened as outpatients. If an infant failed the AABR on two occasions, he or she was rescreened with the AABR or transient evoked otoacoustic emissions by a licensed audiologist, often while the infant was still in the hospital. Using this algorithm, 5% of infants tested in the well-baby nursery needed additional follow-up as an outpatient. Cost analysis of this volunteer-based program reveals a per/baby screening cost of $27.41. CONCLUSIONS: A volunteer-based hearing screening program is a viable option for hearing screening in well-baby nurseries but does not result in significant cost savings during the first 2 years of the program.

Audiometry↗
PubMed2001

Detection of leukemic cells in the CD34(+)CD38(-) bone marrow progenitor population in children with acute lymphoblastic leukemia.

Successful autologous hematopoietic stem cell (HSC) transplantation in childhood acute lymphoblastic leukemia (ALL) requires the ability to either selectively kill the leukemia cells or separate normal from leukemic HSC. Based on previous studies showing that more than 95% of childhood B-lineage ALL express CD38, this study evaluated whether normal CD34(+)CD38(-) progenitors from children with B-lineage ALL could be isolated by flow cytometry. CD34(+) cells from bone marrow samples from 10 children with B-lineage ALL were isolated at day 28 of treatment, when clinical remission had been attained. The CD34(+) progenitor cells were flow cytometrically sorted into CD34(+)CD38(+) and CD34(+)CD38(-) populations. The absolute numbers of CD34(+)CD38(-) cells that could be isolated ranged from 401 to 6245. The cells were then analyzed for the presence of clonotypic rearrangements of the T-cell receptor (TCR) Vdelta2-Ddelta3 locus. Only patients whose diagnostic marrow had an informative TCR Vdelta2-Ddelta3 rearrangement were included in this study. Detection thresholds were typically 10(-4) to 10(-5) leukemic cells in normal marrow. In 6 of 10 samples analyzed, the sorted CD34(+)CD38(-) cells had no detectable Vdelta2-Ddelta3 rearrangements. In 4 cases, the clonotypic leukemic Vdelta2-Ddelta3 rearrangement was detected in the CD34(+)CD38(-) population, indicating that the putative normal HSC population also contained leukemic cells. The data indicate that although most childhood ALL cells express CD34 and CD38, leukemic cells are also frequently present in the CD34(+)CD38(-) population. Therefore, strategies to isolate and transplant normal HSC from children with ALL will require a more stringent definition of the normal HSC than the CD34(+)CD38(-) phenotype. (Blood. 2001;97:3925-3930)

ADP-ribosyl Cyclase↗