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Biomedical subjects

F Scott

Publications and source records attributed to F Scott.

At least 19 recordsLinked to original sources
PubMed2006

Successful treatment of Candida krusei fungemia with amphotericin B and caspofungin.

We report a leukemic patient with C. krusei fungemia who failed to respond to liposomal amphotericin B therapy alone. The addition of caspofungin eradicated infection and was well tolerated. Our report is the first to describe successful treatment of a patient with invasive C. krusei infection using this combination of antifungals. Combination therapy could be a useful treatment option for invasive candidosis, particularly when caused by more resistant species such as C. krusei.

Adult↗
PubMed2005

Association between age and knee structural change: a cross sectional MRI based study.

OBJECTIVE: To describe the associations between age, knee cartilage morphology, and bone size in adults. METHODS: A cross sectional convenience sample of 372 male and female subjects (mean age 45 years, range 26-61) was studied. Knee measures included a cartilage defect five site score (0-4 respectively) and prevalence (defect score of > or =2 at any site), cartilage volume and thickness, and bone surface area and/or volume. These were determined at the patellar, medial, and lateral tibial and femoral sites using T(1)weighted fat saturation MRI. Height, weight, and radiographic osteoarthritis (ROA) were measured by standard protocols. RESULTS: In multivariate analysis, age was significantly associated with knee cartilage defect scores (beta = +0.016 to +0.073/year, all p<0.01) and prevalence (OR = 1.05-1.10/year, all p<0.05) in all compartments. Additionally, age was negatively associated with knee cartilage thickness at all sites (beta = -0.013 to -0.035 mm/year, all p<0.05), and with patellar (beta = -11.5 microl/year, p<0.01) but not tibial cartilage volume. Lastly, age was significantly positively associated with medial and lateral tibial surface bone area (beta = +3.0 to +4.7 mm(2)/year, all p<0.05) and patellar bone volume (beta = +34.4 microl/year, p<0.05). Associations between age and tibiofemoral cartilage defect score, cartilage thickness, and bone size decreased in magnitude after adjustment for ROA, suggesting these changes are directly relevant to OA. CONCLUSION: The most consistent knee structural changes with increasing age are increase in cartilage defect severity and prevalence, cartilage thinning, and increase in bone size with inconsistent change in cartilage volume. Longitudinal studies are needed to determine which of these changes are primary and confirm their relevance to knee OA.

Adult↗
PubMed2005

Factors associated with infection by Pseudomonas aeruginosa in adult cystic fibrosis.

Cross-infection with Pseudomonas aeruginosa is an emerging issue in the care of patients with cystic fibrosis (CF). This study sought to determine the extent of, and patient factors associated with, cross-infection in a tertiary referral adult CF centre. P. aeruginosa isolates were genotyped into two groups between November 2001 and February 2003, using pulsed-field gel electrophoresis after DNA digestion by the SpeI endonuclease, and identified as clustered if there was >80% homology in the macrorestriction profiles. Patient factors and measures of disease severity were identified a priori. In total, 157 out of 227 patients had a P. aeruginosa isolate genotyped. Of these, 94 patients (60%) were infected with clustered genotypes and 47 (30%) were infected with the newly described "Midlands 1" (Md1) genotype. A further 18 patients were infected with the previously identified "Liverpool" genotype and two with the "Manchester" genotype. Logistic regression analysis revealed that the predominant predictor of infection with Md1 was age at the time of referral to the centre, suggesting that infection may have occurred prior to referral in some patients. Md1 demonstrated a relatively benign anti-biogram and did not appear to be associated with more severe disease. In conclusion, the present study provides further evidence of the emerging importance of Pseudomonas aeruginosa cross-infection in cystic fibrosis.

Adult↗
PubMed2004

Early radiographic osteoarthritis is associated with substantial changes in cartilage volume and tibial bone surface area in both males and females.

OBJECTIVE: To describe the association between early radiographic osteoarthritis of the knee (ROA), knee cartilage volume and tibial bone surface area. METHODS: Cross-sectional convenience sample of 372 male and female subjects (mean age 45 years, range 26-61). Articular cartilage volume, bone area and volume were determined at the patella, medial tibial and lateral tibial compartments by processing images acquired in the sagittal plane using T1-weighted fat saturation MRI. ROA was assessed with a standing semiflexed radiograph and the OARSI atlas for joint space narrowing and osteophytosis. Both radiographs and MRIs were performed in the right knee and read by different observers. RESULTS: ROA (predominantly grade 1) was present in 17% of subjects of which medial joint space narrowing was most common (14%) followed by medial osteophytes (6%). Grade one medial joint space narrowing was associated with substantial reductions in cartilage volume at both the medial and lateral tibial and patellar sites within the knee (adjusted mean difference 11-13%, all P<0.001) while grade one osteophytosis was associated with substantial increases in both lateral and medial tibial joint surface area (adjusted mean difference 10-16%, all P<0.001). In contrast, osteophytosis was not associated with a significant change in cartilage volume and joint space narrowing was not associated with a significant change in tibial bone area (all P>0.05). CONCLUSIONS: Early medial compartment ROA is associated with substantial reductions in cartilage volume and increases in bone area. These large changes, when combined with similar measurement error for MRI and radiographs, suggest that MRI may be superior at detecting and hence understanding early osteoarthritis of the knee in humans.

Adult↗
PubMed2004

Differential regulation of caspase-3 by pharmacological and developmental stimuli as demonstrated using humanised caspase-3 mice.

Caspase-3 is a potential therapeutic target for a number of degenerative diseases. However the development of specific caspase-3 inhibitors has been hampered by inter-species differences and the high degree of homology shared by different caspases. To circumvent these issues, we have produced and characterised a humanised caspase-3 mouse line (possessing one copy of the human gene with both copies of the murine gene disrupted) by crossing human caspase-3 transgenic mice with nullizygous caspase-3 knock-out mice. Humanised mice appeared normal and survived to adulthood. Analysis of the human gene revealed that human pro-caspase-3 was expressed in the same tissues as its murine counterpart. However humanised mice retained the hypercellularity of frontal cortex seen in their knock-out parental line and there was no biochemical evidence of human protein processing during naturally occurring neuronal death taking place during brain development. In contrast, the human protein was cleaved by the mouse machinery following anti-Fas treatment of adult mice. These data suggest that there is a fundamental difference between the activation pathways leading to caspase-3 cleavage during naturally occurring cell death in development/embryogenesis and following an apoptotic stimulus in the adult.

Animals↗
PubMed2004

Genetic mechanisms of knee osteoarthritis: a population based case-control study.

OBJECTIVE: To compare subjects who had at least one parent with a total knee replacement for severe primary knee osteoarthritis with age and sex matched controls who had no family history of knee osteoarthritis DESIGN: Population based case-control study of 188 matched pairs (mean age 45 years, range 26 to 60). METHODS: Articular cartilage volume and bone size were determined at the patella and at the medial tibial and lateral tibial compartments by processing images acquired using T1 weighted, fat saturated magnetic resonance imaging. Radiographic osteoarthritis (ROA) was assessed from a standing semiflexed radiograph scored for joint space narrowing and osteophytosis. Knee pain was assessed by questionnaire. Height, weight, body mass index (BMI), lower limb muscle strength, and endurance fitness were measured by standard protocols. RESULTS: Compared with the controls, index offspring had higher BMI (27.8 v 26.0 kg/m(2), p = 0.02), weaker lower limb muscles (127 v 135 kg, p = 0.006), more knee pain (47% v 22%, p<0.001), and greater medial tibial bone area (17.6 v 17.1 cm(2), p = 0.01). With the exception of BMI, these differences persisted in multivariate analysis. There was a non-significant trend to higher cartilage volume at tibial sites and increased ROA in the offspring in the total and subgroup analyses, but no difference in height and endurance fitness. CONCLUSIONS: BMI, muscle strength, knee pain, and medial tibial bone area, but not cartilage volume, appear to play a role in the genetic regulation and development of knee osteoarthritis.

Adult↗
PubMed2003

Sex differences in knee cartilage volume in adults: role of body and bone size, age and physical activity.

OBJECTIVE: To test the hypothesis that sex differences in knee cartilage volume may be mediated through body and bone size, age and/or physical activity. METHODS: A cross-sectional convenience sample of 372 subjects (males 43%; mean age 45 yr, range 26-61) was studied. Articular cartilage volumes and bone size were determined at the patella, medial and lateral tibia by processing images acquired in the sagittal plane using T1-weighted fat saturation magnetic resonance imaging. Height, weight, physical activity (lower limb muscle strength, endurance fitness and questionnaire items) and radiographic osteoarthritis (ROA) were measured. RESULTS: Gender explained 33-42% of the variation in knee cartilage volumes (all P < 0.001). Males had 33-42% higher cartilage volume than females at all sites. In the whole group, the magnitude of sex differences decreased to 8-18% after adjustment for body height, weight and bone size, but remained significant (all P < 0.05). Further adjustment for physical activity had no effect on the sex differences. The sex differences in cartilage volume were greater in those aged over 50 compared with those aged under 50 (P < 0.05 for age-sex interaction at all sites) and were independent of ROA. CONCLUSIONS: Men have substantially higher knee cartilage volumes than women. These sex differences appear to be mediated in part by body and bone size but a significant amount remains unexplained. Furthermore, the differences become more marked over the age of 50 yr suggesting that both cartilage development and cartilage loss in later life contribute to sex differences in cartilage volume. Further longitudinal studies in large samples will be required to confirm these findings.

Adult↗
PubMed2002

Attitudes toward tuberculosis of final year medical students from Canada, India, and Uganda.

BACKGROUND: Tuberculosis, although both preventable and treatable, continues to be the world's leading cause of death from an infectious agent. PURPOSE: To extend the results of our previous study of knowledge and practices of final year medical students regarding tuberculosis at three medical schools from endemic and nonendemic areas and to describe their attitudes. METHODS: Eight statements assessing attitudes, as part of a larger survey, were administered to final year medical students at McMaster University in Canada, Christian Medical College in India, and Makerere University in Uganda. RESULTS: One hundred sixty surveys were returned with 155 completed attitude responses. The response rate was 68.4% (65 of 95) for McMaster University, 39.7% (23 of 58) for the Christian Medical College, and 78.3% (72 of 92) for Makerere University. Analysis showed that six of eight attitude items were slightly statistically different among the schools with minimal effect of curriculum time and patient exposure. CONCLUSIONS: Despite quite varied exposure to tuberculosis, students from endemic and nonendemic areas responded similarly on statements addressing attitudes toward tuberculosis.

Awareness↗
PubMed2001

Serine proteinase inhibitor 3 and murinoglobulin I are potent inhibitors of neuropsin in adult mouse brain.

Extracellular serine protease neuropsin (NP) is expressed in the forebrain limbic area of adult brain and is implicated in synaptic plasticity. We screened for endogenous NP inhibitors with recombinant NP (r-NP) from extracts of the hippocampus and the cerebral cortex in adult mouse brain. Two SDS-stable complexes were detected, and after their purification, peptide sequences were determined by amino acid sequencing and mass spectrometry, revealing that target molecules were serine proteinase inhibitor-3 (SPI3) and murinoglobulin I (MUG I). The addition of the recombinant SPI3 to r-NP resulted in an SDS-stable complex, and the complex formation followed bimolecular kinetics with an association rate constant of 3.4 +/- 0.22 x 10(6) M(-1) s(-1), showing that SPI3 was a slow, tight binding inhibitor of NP. In situ hybridization histochemistry showed that SPI3 mRNA was expressed in pyramidal neurons in the hippocampal CA1-CA3 subfields, as was NP mRNA. Alternatively, the addition of purified plasma MUG I to r-NP resulted in an SDS-stable complex, and MUG I inhibited degradation of fibronectin by r-NP to 24% at a r-NP/MUG I molar ratio of 1:2. Immunofluorescence histochemistry showed that MUG I localized in the hippocampal neurons. These findings indicate that SPI3 and MUG I serve to inactivate NP and control the level of NP in adult brain, respectively.

Animals↗
PubMed2001

Measurement of comfort levels by means of electrical stapedial reflex in children.

BACKGROUND: Patient success and satisfaction with a cochlear implant largely depend on the adequacy of the speech-processing program. The program is generated by means of behaviorally determined threshold and comfort levels for each electrode. As the minimum age for implantation continues to decrease, behavioral methods of measuring comfort levels have become more problematic, and so the need for objective ways to program speech processors has become more important. OBJECTIVES: To evaluate the use of electrically evoked stapedial reflexes (ESRs) to measure comfort levels for children and compare these results with behavioral measurements, and to report the results of a questionnaire assessing the acceptability and general performance of program before and after adjustment of comfort levels measured with ESRs. DESIGN AND SETTING: Before-after trial in the cochlear implant unit of a tertiary hospital. PATIENTS AND METHODS: Programming with the ESR technique was successfully completed in 20 of a consecutive sample of 26 children undergoing programming of their cochlear implants. OUTCOME MEASURES: Programming units as measured by the 2 programming techniques and numerical score of questionnaire. RESULTS: Comfort levels with the ESR method were found to be consistently lower than those obtained with behavioral techniques. Children using programs set with ESRs wore their implants longer and had fewer episodes of discomfort to environmental sounds. CONCLUSION: Comfort level estimation by means of ESRs is reliable and objective and hence a valuable programming tool in the pediatric population.

Child↗
PubMed2001

Fluorescent amplified fragment length polymorphism genotyping of Salmonella Enteritidis: a method suitable for rapid outbreak recognition.

OBJECTIVE: To perform fluorescent amplified fragment length polymorphism (FAFLP) analysis on phage type (PT) reference strains of Salmonella enterica subsp. enterica serotype Enteritidis (S. Enteritidis), and S. Enteritidis PT 6 and 6a recent clinical isolates to determine its usefulness for primary characterization of clinical S. Enteritidis isolates, and then to determine whether FAFLP is suitable for rapid characterization of strains in an outbreak situation. METHODS: Twenty-five PT reference strains of S. Enteritidis and 20 S. Enteritidis PT 6 and 6a clinical isolates were subjected to FAFLP analysis using the selective primer combinations Eco + 0-Mse + T and Eco + 0-Mse + TA. RESULTS: FAFLP successfully separated each one of the 25 S. Enteritidis PT strains into distinct profiles, while macrorestriction and PFGE using XbaI identified 20 pulsed-field profiles. FAFLP also resolved cases and outbreaks due to S. Enteritidis PTs 6 and 6a. CONCLUSIONS: The resolving power of FAFLP was higher than that of PFGE. FAFLP is a highly discriminatory genotyping method and, in conjunction with phage typing for primary subdivision of S. Enteritidis, provides a rapid and powerful tool for strain differentiation, both for outbreak investigation and for epidemiologic surveillance.

Bacterial Typing Techniques↗
PubMed2001

Cost-effectiveness of high-dose chemotherapy in first-line treatment of advanced multiple myeloma.

The cost-effectiveness of high-dose chemotherapy in multiple myeloma was considered as part of a UK National Health Service Executive regional evidence-based appraisal process. The use of high-dose chemotherapy supported by autologous stem cell transplantation in patients under 65 years of age was shown to provide a marginal benefit of 0.7 life-years over conventional chemotherapy. This corresponded to an incremental cost 'per life-year gained' figure of approximately pound15 000, based upon initial treatment costs and trial-period data only. The use of high-dose chemotherapy in the first-line treatment of advanced multiple myeloma improves event-free and overall survival and appears to be a cost-effective treatment option.

Antineoplastic Agents↗
PubMed2001

Knowledge and practices regarding tuberculosis: a survey of final-year medical students from Canada, India and Uganda.

CONTEXT: Tuberculosis is one of the most common infectious diseases worldwide and is responsible for the largest number of deaths from a single infectious cause. OBJECTIVE: The objective of this study was to compare the knowledge of and practices regarding tuberculosis in final-year medical students at schools from endemic and non-endemic areas. SUBJECTS: Final-year medical students at McMaster University in Canada, the Christian Medical College in India, and Makerere University in Uganda. METHODS: A questionnaire consisting of 20 multiple-choice questions assessing knowledge, practices, and exposure. A total knowledge score (maximum=13) and a total practice score (maximum=5) were created for each study site. RESULTS: 160 questionnaires were returned; the response rate was 68.4% (65/95) for McMaster University, 39.7% (23/58) for the Christian Medical College and 78.3% (72/92) for Makerere University. Students from Makerere University had the highest knowledge scores but differences were non-significant after adjustment for patient exposure and curriculum time (F(2,153)= 1.80, P=0.16). Differences in practice scores, however, remained significant after adjusting for curriculum time and patient exposure (F(2,153)=5.14, P=0.006). Knowledge score (F(1,156)=5.05, P=0.02), patient exposure (F(1,153)=9.11, P=0.003), and curriculum time and patient exposure (F(2,153)=5.14, P=0.006) were statistically significant positive predictors of the total practice score. CONCLUSIONS: This study demonstrated significant differences in undergraduate exposure to tuberculosis, total knowledge, and practice competency at three medical schools in Canada, India, and Uganda. In general, the knowledge base and practice competency of all three graduating classes was adequate.

Analysis of Variance↗
PubMed2001

Factors associated with delays in accessing HIV primary care in rural Arkansas.

While debate continues at what stage of human immunodeficiency virus (HIV) disease to begin combination antiretroviral therapy, a number of clinical and public health benefits are linked to early entry into primary care soon after first testing HIV positive. However, HIV-infected patients continue to test late and delay entry into care. We used routinely collected demographic and clinical information to examine which factors are associated with delays in seeking care in a predominantly rural, economically poor area of Arkansas. The study population is 75% African American and male and 70% lack health insurance; nearly one fourth were referred from prison. At diagnosis, two thirds of the population had CD4 counts below 500 cells per microliter. Days from initial HIV diagnosis to entry into care declined from a median of 178 in 1994 to 24 in 1998. In 1998, 75% of the population entered into primary care within 2 months of diagnosis. However, CD4 counts at HIV diagnosis also declined in this period, from a median of 427 in 1995 to 208 cells per microliter in 1998. More recent year of diagnosis was associated with a shorter delay in seeking care; males, and individuals lacking health insurance took significantly longer to enter into care than females and those with insurance, respectively. Our univariate finding of extensive delays in seeking care in the prison population did not hold in the multivariate analysis. We found significant delays in time to initial HIV diagnosis, and further considerable delays in males and those lacking health insurance in the time taken to enter into primary care.

Adolescent↗
PubMed2001

Work correlates of back problems and activity restriction due to musculoskeletal disorders in the Canadian national population health survey (NPHS) 1994-5 data.

OBJECTIVES: To describe the prevalence of musculoskeletal problems in the Canadian working population and to determine cross sectional associations between such problems and work factors, particularly job strain and physical demand variables. METHODS: The Canadian 1994 national population health survey (NPHS) sampled 4230 working men and 4043 working women (ages 18-64) who answered an abbreviated version of the job content questionnaire. Workers were classified into four strain categories: high, passive, active, and low. Outcomes were restricted activity due to musculoskeletal disorders and the diagnosis of a back problem (both yes or no). Survey weights were incorporated to allow for different probabilities of selection. Logistic regression analyses were carried out separately for women and men, controlling for sociodemographic factors. RESULTS: Prevalence of chronic back problems diagnosed by a health practitioner was 14.5% among men and 12.5% among women. Men had a 6.6% prevalence of restricted activity due to musculoskeletal disorders, whereas the corresponding figure for women was 5.3%. Women, but not men, in high strain jobs were more likely to report both back problems (odds ratio (OR) 1.60, 95% confidence interval (95% CI) 1.14 to 2.28) and restricted activity (OR 1.98, 95% CI 1.16 to 3.48) compared with those in low strain jobs. High physical exertion was an independent predictor of back problems in both sexes. For both men and women, low social support at work and high job insecurity were independent predictors of restricted activity due to musculoskeletal disorders. Conversely, chronic back problems contributed to explanation of high job strain among women (OR 1.76, 95% CI 1.30 to 2.39) and high physical exertion among men (OR 1.39, 95% CI 1.09 to 1.77), whereas restricted activity due to musculoskeletal disorders contributed to explanation of high job insecurity in both sexes. CONCLUSIONS: Associations of interest between work stressors and musculoskeletal problems in this cross sectional study provide evidence for physical and psychosocial factors both affecting disability and being affected by disability in a working population.

Activities of Daily Living↗
PubMed2001

Drawing ability in autism: a window into the imagination.

This study investigated imagination via drawing tasks, in 15 children with autism and 15 children with Asperger Syndrome, compared to verbal mental age matched normal children and children with moderate learning difficulties (MLD). Experiment 1 used the Draw an Impossible Man Task. While children with autism were impaired relative to the normal group, they were not impaired relative to the children with MLD. In order to probe for an imagination deficit, Experiment 2 employed a more challenging measure of imaginative drawing, a task involving mixing categories to produce drawings of real or unreal entities (e.g., drawing half-fish/half-mouse). This revealed an autism-specific deficit. Experiment 3 confirmed this was not due to difficulties in combining elements per se. Experiment 4 required subjects to transform a picture (e.g., a cloud into a swan) and again found an autism-specific deficit. Children with Asperger Syndrome were only impaired when required to make such transformations spontaneously.

Adolescent↗