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Biomedical subjects

A Scott

Publications and source records attributed to A Scott.

At least 91 records · Page 5Linked to original sources

Chronic low back pain assessment using surface electromyography.

This investigation examined surface electromyography as an additional tool in the comprehensive clinical evaluation of patients with chronic low back pain (CLBP). Electromyographic signals from electrodes placed in the lumbar area of 30 CLBP patients and 30 non-pain control subjects were compared. Patients and controls were matched for age, gender, and body mass index. Paired t test showed a statistically significant difference between the two groups. The muscle activity mean values were threefold higher in CLBP patients than in controls (P < 0.00001) in the static testing, and twofold higher in CLBP patients than in controls (P < 0.00001) in the dynamic testing. Our findings indicate that surface electromyography assessment of the paraspinal muscle activity may be a useful objective diagnostic tool in the comprehensive evaluation of CLBP.

Adult↗

An evaluation of needs of female BRCA1 and BRCA2 carriers undergoing genetic counselling.

BACKGROUND: The discovery of the breast and ovarian cancer susceptibility genes BRCA1 and BRCA2 has improved our ability to counsel women at increased risk of developing breast and ovarian cancer. The objective of our study was to identify the needs of women who have undergone genetic counselling and testing for BRCA1/2 and to determine the impact of receiving a positive BRCA1/2 result. This is the first study to report on a large group of women who have received positive BRCA1/2 mutation results. METHODS: Questionnaires were distributed to 105 women who had received pre- and post-test genetic counselling for a positive BRCA1/2 result at the University of Toronto or at McGill University in Montreal, Canada between the years of 1994 and 1998. The questionnaire items included patient motivation for seeking genetic services, information needs, screening and prophylactic surgery practices, satisfaction with access to services and support, the desire for a support group, and overall client satisfaction. RESULTS: Seventy nine female carriers were surveyed. The majority of the respondents (77%) were satisfied with the information they received during the genetic counselling process. Women with a previous diagnosis of cancer indicated that they needed more information relating to cancer treatment compared to women without cancer (p=0.05). Nineteen percent of the women felt they needed more support than was received. Fifty eight percent of the women reported that their screening practices had changed since they received their result. Young women (below the age of 50) and women with no previous diagnosis of cancer were most likely to have changed their screening practices. Nearly two thirds of the respondents said they had considered prophylactic surgery of the breasts or ovaries. Twenty eight percent of the women had prophylactic mastectomy and 54% had undergone prophylactic oophorectomy. Women with an educational level of high school or more were more likely to have undergone prophylactic bilateral mastectomy than those with less education (p=0.07) but were less likely to undergo prophylactic oophorectomy (p=0.0007). CONCLUSION: These findings have a direct impact on the counselling and risk management of female BRCA mutation carriers. Age, education, and a previous diagnosis of cancer are important determinants in a woman's decision making after receiving positive genetic test results.

BRCA1 Protein↗

Do physician practice styles persist over time? Continuities in patterns of clinical decision-making among general practitioners.

OBJECTIVES: This study seeks to determine whether there are identifiable differences in patterns of clinical decision-making among family physicians, and whether these patterns persist over time. METHODS: A representative cross-sectional survey of general practice encounters in the Waikato region of New Zealand in 1979-1980 was repeated in 1991-1992. Patterns of clinical decision-making were operationalised as practitioner rates for writing a prescription, ordering a laboratory test or radiological examination and the recommendation of a future follow-up office visit at a specified date. Comparable data were available for a cohort of 50 physicians in both surveys. Multi-level techniques and a simulation exercise were used to study the patterns of decision-making over time. RESULTS: Raw, unadjusted correlations for the 50 family physicians between the two surveys were 0.24, 0.14 and 0.55 for rates of prescribing, investigations and follow-up, respectively. However, these correlations increased substantially, to 0.55, 0.41 and 0.70, once account was taken of case mix, data clustering and inter-practitioner variation in patient sample size. The extent of this recovery of the underlying correlations was confirmed in a parallel simulation exercise. CONCLUSIONS: This study confirms the existence of substantial and durable individual practice styles in primary medical care, with implications for the development and successful implementation of clinical guidelines.

Cross-Sectional Studies↗

Cytoskeletal abnormalities in chondrocytes with EXT1 and EXT2 mutations.

The EXT genes are a group of putative tumor suppressor genes that previously have been shown to participate in the development of hereditary multiple exostoses (HME), HME-associated and isolated chondrosarcomas. Two HME disease genes, EXT1 and EXT2, have been identified and are expressed ubiquitously. However, the only known effect of mutations in the EXT genes is on chondrocyte function as evidenced by aberrant proliferation of chondrocytes leading to formation of bony, cartilage-capped projections (exostoses). In this study, we have characterized exostosis chondrocytes from three patients with HME (one with EXT1 and two with EXT2 germline mutations) and from one individual with a non-HME, isolated exostosis. At the light microscopic level, exostosis chondrocytes have a stellate appearance with elongated inclusions in the cytoplasm. Confocal and immunofluorescence of in vitro and in vivo chondrocytes showed that these massive accumulations are composed of actin bundled by 1.5-microm repeat cross-bridges of alpha-actinin. Western blot analysis shows that exostosis chondrocytes from two out of three patients aberrantly produce high levels of muscle-specific alpha-actin, whereas beta-actin levels are similar to normal chondrocytes. These findings suggest that mutations in the EXT genes cause abnormal processing of cytoskeleton proteins in chondrocytes.

Actinin↗

Development of sustained delivery system as a novel technique for tissue culture.

One of the greatest advances for biomedical research has been the use of tissue culture to study the effects and the mode of action of various organic compounds. However, there are myriad problems associated with the classical approach to pharmaceutical studies in tissue culture, such as contamination, the logistical problems inherent in intermittent dosing, and near-lethal drug doses required to achieve effective physiological doses. This has given impetus to a search for better means of effective delivery routes in a tissue culture setting. The specific objectives of this investigation were: (1) to develop a ceramic delivery system for the novel purpose of releasing sustained levels of the anti-cancer drug combination inositol hexaphosphate (IP6) + inositol (I) in a tissue culture setting; (2) to assess the proliferation rate and viability of HTB 122 Intraductile Breast Cancer (IBC) cells exposed to sustained levels of IP6 + I compared to conventional means of drug delivery (dissolved in media); (3) to evaluate the morphological changes associated with this treatment process. Sterile aseptic techniques were employed during the entire study (72 hours of incubation). Data obtained from this investigation suggests the following: (1) TCPL delivery system can be utilized in the tissue culture setting to deliver IP6 + I in a sustained manner for 72 hours; (2) the use of IP6 + I at the physiological dose did not induce any significant change in the biochemical marker (MDA); (3) morphological evaluation of cells treated with sustained delivery resulted in cellular atrophy, as well as fragmentation, compared to the treatment by conventional means and to the sham group (empty capsule); and (4) regardless of route of administration, treatment with IP6 + I resulted in a decrease in total protein content compared to the sham capsules and control groups. In conclusion, this approach is a novel use of ceramic delivery systems in tissue culture that gives breakthrough information for basic research on limiting and eliminating contamination and the logistical problems associated with intermittent dosing in tissue culture.

Antineoplastic Agents↗

TCPL drug delivery system: the effects of synthetic DHEA and Diosgenin using an ovariectomized rat model.

Dehydroepiandrosterone (DHEA) has been shown in numerous studies to exhibit a host of benefits at the vital and reproductive organ levels. However, the use of naturally occurring DHEA is hindered by its inability to survive the first-pass metabolic process of the liver. One possible alternative means that deserves consideration is the administration of DHEA's precursor, namely, Diosgenin (DG). The specific objectives of this investigation were: 1) to deliver DHEA and DG at sustained levels by Tri-Calcium Phosphate Lysine (TCPL) drug delivery systems using ovariectomized (OVX) adult rats as a model, and 2) to evaluate the biochemical and histopathological changes associated with the sustained delivery of DHEA and DG. A total of 30 adult female rats were used in this investigation. The animals were further divided into 8 groups. Groups 1 and 2 animals served as intact control groups while each rat in groups 3-8 was ovariectomized (sham (33), n = 3 [group 3], sham (47), n = 4 [group 4]). Groups 5 and 6 were implanted with DHEA (group 5) and DG (group 6) loaded TCPL capsules immediately following the OVX procedure. Groups 7 and 8 were implanted with DHEA (group 7) and DG (group 8) loaded capsules 14 days following OVX. Surgical aseptic technique was employed according to standard laboratory protocols. Maliondialdehyde (MDA) and hormonal levels were measured from serum, collected semi-weekly, during the entire investigation (for 47 days) and X-rays were performed weekly. Pap smears were collected daily for 47 days to assess endometrial changes associated with DHEA and DG treatment. Following sacrifice (at day 33 for groups 1, 3, 5, and 6 and at day 47 for groups 2, 4, 7, and 8), routine H and E staining was conducted for histopathological evaluation of the reproductive and vital organs. Results of this investigation demonstrated: 1) OVX resulted in an increase in total body weight, and the use of DHEA and DG returned the body weight to near normal levels as compared to the intact control groups, 2) TCPL capsules delivered DHEA and DG at a sustained level during the 47 day study, 3) serum levels of MDA are as follows: DG > DHEA = OVX > control for the 33 day phase and OVX > DG > DHEA > control for the 47 day phase, 4) no significant changes were observed in total wet weights, as well as the morphology of the spleen, kidney, adrenal, heart, liver, and lung tissues, 5) OVX resulted in an atrophy and non-keratinization trend in the reproductive tissues, and sustained delivery of DHEA and DG showed no remarkable change in these tissues, 6) the use of sustained delivery of DHEA and DG resulted in higher weights of uteri compared to the OVX group. In conclusion, this study provided more information regarding the interrelationship between DHEA and DG, and the physiological responses encountered when they are administered continuously using the adult OVX rat as a model.

Animals↗

Assessment of endometrial function during sustained delivery of estradiol and estradiol plus progesterone in ovariectomized rats.

Previous studies conducted in our laboratories have documented that tricalcium phosphate lysine (TCPL) delivery system can be utilized to deliver estrogen (E) and combination of estrogen with progesterone (E + P) at sustained levels for long duration in intact rats. The specific aim of this investigation was to attempt to reverse the endometrial changes resulted from post-ovariectomy by exogenously delivering sustained levels of E and E + P. A total of 27 adult female rats were used in this study. The animals were randomly divided into seven different groups: groups 1 animals served as intact control group, groups 2 and 6 animals were ovariectomized, 3 and 7 were ovariectomized (OVX) and implanted with TCPL loaded with E (20 mg loaded TCPL), and group 4 was OVX and implanted with E (TCPL, 20 mg) + P (TCPL, 40 mg.) treatment. Group 5 animals served, as intact control group. Blood samples were collected biweekly for 47 days. Vaginal smears were taken and screened daily during the entire investigation. Histopathological evaluations were conducted on reproductive as well as vital organs (H & E). Data obtained from this investigation suggest the following: (I) OVX resulted in an increase in total body weight, however E and E + P maintained the body weights at prior ovariectomy level, (II) sustained delivery of E resulted in maturation of vaginal epithelium and the smears exhibited the estrus at the end of 72 hours post implantation and continued this trend for the duration of the study, (III) E + P treatment induced no estrus and the epithelial changes resembled the OVX group, and (IV) E and E + P treatment resulted in a significant different (P < 0.05) in MDA levels compared to OVX and intact control groups. Results of this investigation conclude that sustained delivery of E and E + P by TCPL can be utilized to maintain the normal function of the reproductive organs and could serve as an efficient and safe therapy in estrogen deficient patients.

Animals↗

The effects of shifts in the balance of care on general practice workload.

BACKGROUND: The consequences of the move towards a primary-care-led NHS are shifts in activity from secondary care to primary care and more involvement of GPs in purchasing decisions. Although there are many anecdotal reports of an increasing primary care workload, there is little empirical evidence on the extent of such shifts. This paper reports the results of a survey of GPs in Grampian, in the north-east of Scotland, in which we attempted to gather information on the effects of shifts in the balance of care on general practice. OBJECTIVE: We aimed to examine GPs perceptions of the extent to which general practice workload has changed due to planned and unplanned shifts in the balance of care. METHODS: The design of the study was a self-reported questionnaire, which was administered in general practices in the Grampian Health Board, Scotland. The subjects were senior partners of all general practices and the main outcome measures were the types of changes which have taken place in general practice, their source, their effect on practice workload and how practices have reacted. RESULTS: A 60% response rate was achieved (52/86); 85% (44/52) of GPs claimed that their workload had increased due to shifts in the balance of care and that 72% of the shifts were initiated outside the practice. Geriatric care, early discharge and psychiatric and psychology services, as well as nursing home care, were reported to have had the greatest impact on workload. The main aspects of practice workload which had increased included the number of GP consultations, general stress at work and number of home visits, whereas the net income of the practice and health outcome of patients were reported to have decreased. Practices have dealt with the increase in workload by shifting tasks from GPs to nurses and absorbing the workload into existing practices/patterns. Responders reported that ideally more nursing and GP staffing would be required. Overall, GPs welcomed the shifts in the balance of care, were more concerned about poor communication rather than actual increases in workload and claimed that morale had fallen. CONCLUSION: GPs perceive that the move towards a primary-care-led NHS is increasing the workload in general practice. If the shift in the balance of care away from secondary care is to be successful, then more information is required about such shifts to support practices as change continues.

Attitude of Health Personnel↗

A comparison of the plasma disappearance of iohexol and 99mTc-DTPA for the measurement of glomerular filtration rate (GFR) in diabetes.

BACKGROUND: Changes in glomerular filtration rate (GFR) provide a valuable indicator of the progression of diabetic nephropathy. GFR is most commonly measured by the plasma clearance of radioisotopes, however, use of iohexol, a non-ionic radiocontrast medium, is a recently described alternative and has shown good agreement with inulin clearance. A one-compartment model is used for calculating GFR in most Australian centres but a two-compartment model is more accurate. AIMS: To set up a non-radioisotopic method for assessment of GFR using iohexol, and to compare this with the currently used 99mTc-diethylene-triamine-penta-acetic acid (DTPA) method. Secondly, to compare GFR results using an unmodified one-compartment model with a one-compartment model subjected to the Brochner-Mortensen modification. METHODS: Twenty-one patients with diabetes had assessment of GFR with simultaneous measurements of 99mTc-DTPA and iohexol plasma clearance. Plasma clearance was determined by the slope intercept method and then modified according to the Brochner-Mortensen equation. Plasma iohexol concentrations were determined by capillary electrophoresis. RESULTS: There was no significant difference between iohexol and 99mTc-DTPA derived GFR values, difference 4.3+/-7.7 mL/minute (mean+/-SD). This was despite 99mTc-DTPA protein binding demonstrated in the range of 5-10%. Comparison of GFR results using an unmodified one-compartment model with a Brochner-Mortensen corrected one-compartment model showed higher GFR values with the former, in the range of 20-30% for GFR values > 100 mL/minute. CONCLUSION: Iohexol provides an efficient alternative to radioisotopic methods for serial measurement of GFR in diabetic patients with hyperfiltration, incipient and overt nephropathy. A one-compartment model with its inherent overestimation of GFR should be replaced by the Brochner-Mortensen modified one-compartment model.

Adult↗

A mobile screening unit, practicalities and problems.

The need for a mobile screening unit to travel throughout Scotland to measure and modify cardiovascular risk factors in the apparently healthy working population was fulfilled by the conversion of a double-decker bus. The aim of the project was to assess the incidence of risk factors in healthy individuals and to modify their risk factors by individual counselling. Many unforeseen practical problems were encountered and overcome during the planning stage and during the project. The team of specially trained staff spent three and a half years screening more than 20,000 people throughout Scotland. This project provides a model for other screening projects involving a multicentre/scattered cohort.

Adult↗

Undifferentiated dementia, Alzheimer's disease and vascular dementia: age- and gender-related incidence in Liverpool. The MRC-ALPHA Study.

BACKGROUND: Does incidence of dementia follow the age pattern of prevalence? Is gender a risk factor? Do patterns of incidence differ between dementias? AIMS: To assess age-specific incidence rates of undifferentiated dementias, Alzheimer's disease and vascular dementia. METHOD: 5222 individuals aged > or = 65 years, were interviewed using the Geriatric Mental State/History and Aetiology Schedule. The AGECAT package was used to identify cases at three interviewing waves at two-year intervals. Diagnoses were made using ICD-10 Research Criteria and validated against neurological and psychological examination, with imaging and neuropathology on unselected subsamples. RESULTS: Incidence rates of the dementias increase with age. Age patterns are similar between Alzheimer's disease and vascular dementia. Gender appears influential in Alzheimer's disease. In England and Wales, 39,437 new cases of Alzheimer's disease (4.9/1000 person-years at risk); 20,513 of vascular dementia (2.6/1000 person-years) and 155,169 of undifferentiated dementia (19/1000 person-years) can be expected each year. CONCLUSIONS: Incidence rates for Alzheimer's disease and vascular dementia appear to behave differently, with an increased risk of Alzheimer's disease for women compared to vascular dementia.

Age Factors↗

Activity and kinetics of dissociation and transfer of amphotericin B from a novel delivery form.

Recently it has been demonstrated that moderate heat treatment of Amphotericin B/deoxycholate solutions (HAmB-DOC ) leads to a therapeutically interesting supramolecular rearrangement that can be observed by significant changes in light scattering, CD, and absorbance. In this study, we continue the investigation of the physical properties of this new form by evaluating the activity and kinetics of dissociation and dispersion of HAmB-DOC and AmB-DOC in saline, serum, and in model mammalian or fungal lipid biomimetic membrane vesicles. Stopped-flow spectrophotometry combined with singular value decomposition (SVD) and global analysis were used to resolve the components of this process. The dissociation kinetics for both states are complex, requiring multi-exponential fits, yet in most cases SVD indicates only two significant changing species representing the monomer and the aggregate. The kinetic mechanism could involve dissociation of monomers from coexisting spectroscopically similar but structurally distinct aggregates or sequential rearrangements in supramolecular structure of aggregates. Rate constants and amplitudes of dissociation from aggregates to monomer in buffer, whole serum, 10% cholesterol, and ergosterol membrane vesicles are generally greater for AmB-DOC, demonstrating its greater kinetic instability. In addition, at comparable low concentrations, HAmB-DOC and AmB-DOC are nearly equally active at promoting cation selective permeability in ergosterol-containing membranes; however, HAmB-DOC is much less active against mammalian mimetic cholesterol-containing vesicles, despite a higher level of self-association, supporting previous observations that there exists a specific "toxic aggregate" structure.

Amphotericin B↗

Model system for plant cell biology: GFP imaging in living onion epidermal cells.

The ability to visualize organelle localization and dynamics is very useful in studying cellular physiological events. Until recently, this has been accomplished using a variety of staining methods. However, staining can give inaccurate information due to nonspecific staining, diffusion of the stain or through toxic effects. The ability to target green fluorescent protein (GFP) to various organelles allows for specific labeling of organelles in vivo. The disadvantages of GFP thus far have been the time and money involved in developing stable transformants or maintaining cell cultures for transient expression. In this paper, we present a rapid transient expression system using onion epidermal peels. We have localized GFP to various cellular compartments (including the cell wall) to illustrate the utility of this method and to visualize dynamics of these compartments. The onion epidermis has large, living, transparent cells in a monolayer, making them ideal for visualizing GFP. This method is easy and inexpensive, and it allows for testing of new GFP fusion proteins in a living tissue to determine deleterious effects and the ability to express before stable transformants are attempted.

Cloning, Molecular↗

Can patient registers give an improved measure of internal migration in England and Wales?

This article describes a new source of internal migration data for England and Wales. These data are extracted from the 98 Family Health Service Authority (FHSA) patient registers that hold the details of people in England and Wales who are registered with the National Health Service. Migration estimates are derived from changes in postcodes on the patients' records. The findings presented in the article show that the registers provide high quality estimates of migration into and out of the constituent areas of the FHSAs (as compared to other sources). Where limitations are identified, compensatory adjustments can be introduced to further enhance the quality of the estimates.

England↗