Protecting substrates from enzymatic cleavage: hydrogels of low molecular weight gelators do the trick.
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Chymotrypsin↗
Biomedical subjects
M Stuart
Publications and source records attributed to M Stuart.
[Prevalence of Helicobacter pylori infection in Corsica].
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Adult↗
Anastrozole ('Arimidex') blocks oestrogen synthesis both peripherally and within the breast in postmenopausal women with large operable breast cancer.
The effect of anastrozole on peripheral and tumour aromatase activity and oestrogen levels in postmenopausal patients with oestrogen receptor-rich breast tumours was investigated. Twenty-six patients were randomly allocated to treatment with anastrozole 1 mg (n=13) or 10 mg (n=13), once daily. Before and after 12 weeks' treatment, patients were infused with 3H-Delta4 androstenedione (20 MBq) and 14C-oestrone (E1) (1 MBq) for 18 h. Oestrogens were purified from excised tumours and plasma samples taken after each infusion. Peripheral and tumour aromatase activity and tumour E1 uptake were calculated from levels of 3H and 14C in purified E1 fractions from tumour and plasma. Endogenous tumour oestrogens were measured by radioimmunoassay. Twenty-three patients were available for analysis (1 mg group, n=12; 10 mg group, n=11). Following treatment, anastrozole (1 and 10 mg) markedly inhibited peripheral aromatase in all patients (the difference between pre- and on-treatment values being highly significant P<0.0001). In situ aromatase activity was also profoundly decreased by anastrozole treatment in 16 of 19 tumours (the difference with treatment also being highly significant P=0.0009). Most tumours were able to concentrate E1 beyond levels in the circulation; anastrozole treatment had no consistent effect on uptake of E1. Endogenous tumour levels of both E1 and oestradiol (E2) were significantly reduced with therapy (P=0.028 for E1 and P=0.0019 for E2). Anastrozole (1 and 10 mg daily) effectively suppresses aromatase activity, and subsequently oestrogen levels, within the breast tissue of postmenopausal women with large or locally advanced, operable, oestrogen receptor-rich breast cancers.
Aged↗
Effect of neoadjuvant treatment with anastrozole on tumour histology in postmenopausal women with large operable breast cancer.
Anastrozole is an orally active, non-steroidal aromatase inhibitor which appears effective as neoadjuvant treatment of breast cancer. Histological changes have been evaluated in biopsies from large, oestrogen-receptor rich, operable breast tumours in postmenopausal women following 12 weeks of neoadjuvant anastrozole treatment (1 mg (n=12) or 10 mg (n=11)). Of the 23 patients, 18 had a clinical response following treatment. Compared with pre-treatment biopsies anastrozole-treated specimens displayed decreased cellularity and/or increased fibrosis in 15 tumours; changes in gland formation, nuclear pleomorphism, or mitoses, in 12 cases; and a reduction in Mib1 score in all tumours. Marked changes in apoptotic scores were seen following treatment but the direction of effect was inconsistent. In all 17 tumours which were positive for progesterone receptors before therapy, treatment was associated with reduced staining for progesterone receptors. There was no consistent effect of treatment on oestrogen-receptor expression. It is concluded that neoadjuvant anastrozole treatment in this patient group has marked effects on tumour histopathology but these do not always correlate with clinical response.
Aged↗
Results of a collaborative study of the EDNAP group regarding the reproducibility and robustness of the Y-chromosome STRs DYS19, DYS389 I and II, DYS390 and DYS393 in a PCR pentaplex format.
A collaborative exercise was carried out by the European DNA Profiling Group (EDNAP) in the frame work of the STADNAP program, i.e. standardization of DNA profiling in Europe, in order to evaluate the performance of a Y-chromosome STR pentaplex, which includes the loci DYS19, DYS389 I and II, DYS390 and DYS393 and to determine whether uniformity of results could be achieved among different European laboratories. Laboratories were asked to analyze the five Y-STRs using singleplex and multiplex conditions in three bloodstains and one mixed stain (95% female and 5% male). All the laboratories reported the same results even for the mixed stain included in the exercise. This demonstrates the reproducibility and robustness of Y-chromosome STR typing even with multiplex formats and proves the usefulness of Y-STR systems for analyzing mixed stains with a male component.A total of 930 male samples from 10 different populations from Europe were also analysed for all the loci included in the pentaplex. Eight of these ten populations also included haplotype data. As for single gene analysis, haplotype diversity was higher in Germany and Italy and lower in Western European countries and Finland. Pairwise haplotype analysis shows the Finnish departure from the rest of the populations and a relatively homogeneity in the other European populations with F(ST) estimates lower than 0.05.UPGMA analysis shows an association of Western European population (Ireland, UK, Portugal and Galicia) on the one hand and central European populations on the other.
Blood Stains↗
Home- and community-based long-term care: lessons from Denmark.
PURPOSE: Denmark is cited as a model in the development of home- and community-based systems for the frail elderly population. We examined the results of this natural experiment and considered implications for U.S. policy. DESIGN AND METHODS: We used international comparative policy analysis, including site visits and semistructured interviews with Danish leadership in conjunction with a review of published literature, reports, and administrative data from Denmark and the United States. RESULTS: After 12 years of implementing integrated systems for home- and community-based services in 275 municipalities, growth in Danish long-term care expenditures has leveled off; expenditures appear to be decreasing for the over-80 population and have dropped as a percentage of the gross domestic product. Access to and quality of long-term care services appear to remain generally satisfactory. During this period, comparable expenditures in the United States have increased, and deficits in access and quality persist. IMPLICATIONS: These findings should be of interest to state and federal policy makers considering strategies to reduce the rate of growth in Medicaid and Medicare expenditures for elders and to expand home- and community-based services.
Aged↗
Protecting the most vulnerable: home mechanical ventilation as a case study in disability and medical care: report from an NIH conference.
Patients requiring chronic mechanical ventilation represent a particularly vulnerable segment of the expanding population of individuals with chronic disabilities. Many of these individuals can live successfully at home, but face significant obstacles. Current policies in health care coverage, durable medical equipment coverage, eligibility for assisted living, and licensing of caregivers all restrict the abilities of these individuals to live in the community. Prolonged home mechanical ventilation was pioneered in France, where a current international "best practice" provides a model for developing comprehensive, cost-effective care for these individuals.
Home Care Services↗
Home is where the help is: community-based care in Denmark.
Policy regarding long-term care has been an issue of rising national concern. In this paper we examine the transition of Danish long-term care policy with special attention to Skaevinge, the first community in Denmark to integrate institutional and community-based services for the elderly. Recent studies on the variation between costs and services in Danish communities and the results of U.S. studies on community-based care suggest that successful implementation of integrated institutional and community-based long-term care is feasible in the United States. Lessons from Denmark highlight conditions that will facilitate success in this endeavor.
Aged↗
The role of scaffolding errors in reading development: evidence from a longitudinal and a correlational study.
BACKGROUND: Identification of patterns of early reading behaviour that predict later reading success is clearly important. Reading errors of 6-year-olds represent a source of such early assessment information, but their significance as predictors of later reading is unknown. AIMS: The relationship between word reading errors at age 6 and accurate word reading at age 8 is investigated here. SAMPLES, METHODS, RESULTS: In study 1, 44 children completed word reading tests at 6 and 8 years. 'Scaffolding errors' preserving both initial and final phonemes (e.g., 'bark' misread as 'bank'); errors preserving either initial or final phonemes (e.g., 'bark' misread as 'bed' or 'like'); distant or unrelated errors (e.g., 'bark' misread as 'can' or 'men') and non-responses were measured at age 6. Scaffolding errors were the best predictors of word reading at age 8. Study 2 investigated the correlations between word and nonsense word reading, and scaffolding errors in 30 children aged 6 years. Scaffolding errors predicted unique variance in word reading after nonword reading was entered. CONCLUSIONS: Scaffolding errors represent a significant qualitative indicator of later word reading success. Implications of findings for early identification of reading difficulties, and facilitating reading interventions are discussed.
Child↗
ARMS allele-specific amplification-based detection of mutant p53 DNA and mRNA in tumors of the breast.
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Biomarkers, Tumor↗
Provision of methadone treatment in primary care medical practices: review of the Scottish experience and implications for US policy.
CONTEXT: Under new proposed regulations, US physicians outside of traditional methadone clinics could prescribe methadone to patients with opioid dependence. No large-scale evaluations of US programs in which methadone maintenance is provided by primary care physicians are available, but primary care physicians in Scotland have participated in such programs on a large scale. OBJECTIVE: To review the history, operation, and outcome data on the efficacy and safety of 2 Scottish primary care-based opioid agonist treatment programs to derive lessons for the US context. DESIGN AND SETTING: Naturalistic study of programs in Edinburgh and Glasgow, Scotland, with data obtained through site visits and interviews conducted in 1996 and 1998, as well as from published reports and retrospective analysis of electronic databases. MAIN OUTCOME MEASURES: Proportions of injection drug users who were enrolled in the methadone maintenance programs, average methadone doses in the programs, and methadone-related deaths. RESULTS: A total of 60% to 80% of injection drug users in Edinburgh and 41% to 73% of those in Glasgow were enrolled in methadone maintenance in 1998-1999. Dose levels are consistent with US recommendations (for Edinburgh in 1998, 61 mg; for Glasgow in 1994-1996, 54 mg). The Glasgow program required supervised consumption of methadone in community pharmacies for the first year and experienced significantly fewer methadone-related deaths than Edinburgh in 1997 (17 vs 30 deaths; P<.0001). Programs in both Edinburgh and Glasgow provided support to primary care physicians and achieved levels of general practitioner participation of 59% (1998) and 30% (1999), respectively. CONCLUSIONS: The Scottish experience indicates that prescription of methadone in office-based settings can expand access to an important treatment modality. Primary care physicians safely prescribed methadone for maintenance treatment when provided with adequate support. Diversion of methadone was minimized by requiring supervised consumption in community pharmacies.
Delivery of Health Care↗
Renewing the model employer. Changing employment relations and "partnership" in the health and private sectors.
Drawing from original empirical data this paper compares the changing nature of employment relations in the health and private sectors. A key concern is to assess the extent to which the emergence of partnership-type arrangements between employers and trade unions lays the basis for the "renewal" of the traditional public sector concept of the model employer. Empirically, the paper draws on a survey of trade union representatives from 238 workplaces and a case study of a hospital trust. The data reveal that employment relations in the NHS are more collectivist when compared with the private sector. However, the development of partnership in the NHS is hamstrung by ongoing training and involvement gaps and widespread work intensification.
Employment↗
Suggested curriculum guidelines on complementary and alternative medicine: recommendations of the Society of Teachers of Family Medicine Group on Alternative Medicine.
BACKGROUND AND OBJECTIVES: The widespread use of alternative and complementary therapies by the public provides a new challenge to medical education. No standardized curriculum is available for medical educators in this field. Providing an adequate background on these therapies and reliable, useful information to our learners was a task addressed by the Society of Teachers of Family Medicine (STFM) Group on Alternative Medicine over the past 2 years. METHODS: The group met at conferences and communicated via e-mail to develop a consensus of recommended knowledge, skills, and attitudes in complementary and alternative medicine for incorporation into the family practice residency training curriculum. CONCLUSION: This article suggests guidelines as developed by this STFM group to assist programs wishing to include formal training in complementary and alternative medicine in residency training.
Attitude of Health Personnel↗
The effects of neoadjuvant anastrozole (Arimidex) on tumor volume in postmenopausal women with breast cancer: a randomized, double-blind, single-center study.
Anastrozole, an orally active, nonsteroidal aromatase inhibitor, was evaluated in a randomized, double-blind, single-center study to determine its efficacy as neoadjuvant therapy in postmenopausal women with newly diagnosed, estrogen receptor-rich, locally advanced or large (>3 cm), operable breast cancers. Twenty-four eligible patients were recruited into the study and received either 1 mg (n = 12) or 10 mg (n = 12) of anastrozole daily over a 3-month period. Tumor volumes were estimated clinically, by using caliper measurements and ultrasound (at baseline and after 1, 2, and 3 months' treatment) and by mammography (at baseline and after 3 months). Tumor volume was also measured in surgical specimens. Twenty-one patients were classified as T2, two patients as T3, and one patient as T4B at baseline. Three patients had clinical evidence of lymph node involvement. When considering the difference between the volume as measured by each assessment and the actual pathological volume, the interquartile range and the difference between the maximum and minimum values were smaller for ultrasound when compared with those measured with calipers and mammography. Therefore, of the three clinical assessments of tumor volume used in this study, the data suggest that ultrasound may be the most accurate. The median reductions in tumor volumes as measured by ultrasound for those patients with a measurable 12-week assessment were 80.5 and 69.6% for anastrozole (1 and 10 mg, respectively) after 12 weeks of treatment and 75.5% when both doses were grouped together. Moreover, of these patients, 11 of 12 given 1 mg and 7 of 11 given 10 mg of anastrozole were found on ultrasound to have a >50% reduction in tumor volume after 12 weeks of treatment. Of the 17 patients who would have required a mastectomy at initiation of treatment, 15 were suitable for breast conservation after anastrozole treatment. These results suggest that anastrozole is highly effective as neoadjuvant therapy in postmenopausal women with estrogen receptor-rich, large, operable breast cancer. Future studies comparing anastrozole with tamoxifen as a neoadjuvant treatment should be considered.
Aged↗
Reproducibility of a self-report questionnaire for upper extremity musculoskeletal disorder risk factors.
A self-report questionnaire was developed to evaluate the potential for assessment of possible risk factors for musculoskeletal disorders. Visual-analog and categorical scales were designed to represent responses relating to primary work as well as a second job and hobbies or non-work activities. 71 tree nursery workers completed the scales twice in consecutive weeks. Agreement between means of the two questionnaire administrations was 0.80 or higher for all scales. Intraclass correlation coefficients ranged between 0.59 and 0.69 for the primary job hand/wrist responses and between 0.49 and 0.82 for non-work/hobby neck and upper arm scales. These results show potential for future application of similar scales in industry or temporary and seasonal work to evaluate exposure to upper extremity risk factors.
Adult↗
Inferring sublexical correspondences from sight vocabulary: evidence from 6- and 7-year-olds.
We report an experiment designed to investigate 6-to-7-year-old children's ability to acquire knowledge of sublexical correspondences between print and sound from their reading experience. A computer database containing the printed word vocabulary of children taking part in the experiment was compiled and used to devise stimuli controlled for grapheme-phoneme correspondence (GPC) frequency and rime neighbourhood consistency according to the children's reading experience. Knowledge of GPC rules and rime units was compared by asking children to read aloud three types of nonword varying in regularity of GPC and consistency of rime pronunciation. Results supported the view that children can acquire knowledge of both GPC rules and rime units from their reading experience. GPC rule strength affects the likelihood of a GPC response; rime consistency affects the likelihood of a rime response.
Analysis of Variance↗
Morphological observations on liposomes bearing covalently bound protein: studies with freeze-fracture and cryo electron microscopy and small angle X-ray scattering techniques.
The appearance of protein bound to the surface of intact and microfluidized liposomes and its possible influence on their morphology was examined by freeze-fracture electron microscopy, cryo electron microscopy and small angle X-ray scattering (SAXS) techniques. Results obtained by the two microscopy techniques were in agreement with one another in terms of vesicle size and localization of protein (tetanus toxoid or immunoglobulin G) on the surface of vesicles. Surface-bound protein was observed as particles (10-12 nm diameter) by freeze-fracture electron microscopy and was confirmed by immunogold cryo microscopy. SAXS was shown to be a suitable means to further characterize liposomes with, or without bound protein.
Animals↗
Monoamine oxidase-A-positive retinal ganglion cells projecting to the superior colliculus and dorsolateral geniculate nucleus of the rat brain.
Detailed morphology and distribution of monoamine oxidase type A (MAO-A) positive retinal ganglion cells, and their synaptic terminals in the superior colliculus and the lateral geniculate nucleus, were investigated by light and electron microscopy. In addition, the differences in various retinal ganglion cells with respect to the projection site were examined by the injection of colloidal gold into the superior colliculus and the lateral geniculate nucleus. The effects of unilateral enucleation were also examined. In the retina, small, medium and large sized MAO-A-positive ganglion cells were observed; the large sized cells were distributed evenly throughout the retina, while the small and medium sized cells were most numerous in a ring surrounding the central retina and decreased in density near the optic disc and the peripheral retina. The MAO-A-positive terminals in the superior colliculus were smaller in size than those in the lateral geniculate nucleus. From colloidal gold injection, it was apparent that the MAO-A-positive ganglion cells projecting to the superior colliculus were generally smaller in size than those projecting to the lateral geniculate nucleus. Fourteen days after unilateral enucleation, the MAO-A-positive terminals in the superior colliculus and lateral geniculate nucleus contralateral to the enucleated eye had almost disappeared, whereas those in the ipsilateral regions remained unaffected. These findings demonstrate the distribution and projections of the MAO-A-positive ganglion cells.
Animals↗