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L Pickard

Publications and source records attributed to L Pickard.

At least 19 recordsLinked to original sources
PubMed2003

The association between osteoporotic fractures and health-related quality of life as measured by the Health Utilities Index in the Canadian Multicentre Osteoporosis Study (CaMos).

Osteoporotic fractures can be a major cause of morbidity. It is important to determine the impact of fractures on health-related quality of life (HRQL). A total of 3,394 women and 1,122 men 50 years of age and older, who were recruited for the Canadian Multicentre Osteoporosis Study (CaMos), participated in this cross-sectional study. Minimal trauma fractures of the hip, pelvis, spine, lower body (included upper and lower leg, knee, ankle, and foot), upper body (included arm, elbow, sternum, shoulder, and clavicle), wrist and hand (included forearm, hand, and finger), and ribs were studied. Participants with subclinical vertebral deformities were also examined. The Health Utilities Index Mark II and III Systems were used to assess HRQL. Past osteoporotic fractures varied in prevalence from 1.2% (pelvis) to 27.8% (lower body) in women and 0.3% (pelvis) to 29.3% (wrist) in men. Multivariate linear regression analyses [parameter estimates and corresponding 95% confidence intervals (CI)] indicated that minimal trauma fractures were negatively associated with HRQL and that this relationship depends on fracture type and gender. The multi-attribute scores for the Mark II system were negatively related to hip (-0.05; 95% CI: -0.09, -0.01), lower body (-0.02; 95% CI: -0.03, -0.000), and subclinical vertebral fractures (-0.02; 95% CI: -0.03, -0.00) for women. The multi-attribute scores for the Mark III system were negatively related to hip (-0.09; 95% CI: -0.14, -0.03) and rib fractures (-0.06; 95% CI: -0.11, -0.00) for women, and rib fractures (-0.06; 95% CI: -0.12, -0.00) for men. In conclusion, this study demonstrates a negative association between osteoporotic fractures and quality of life in both women and men.

Aged↗
PubMed2003

Associations among disease conditions, bone mineral density, and prevalent vertebral deformities in men and women 50 years of age and older: cross-sectional results from the Canadian Multicentre Osteoporosis Study.

This cross-sectional cohort study of 5566 women and 2187 men 50 years of age and older in the population-based Canadian Multicentre Osteoporosis Study was conducted to determine whether reported past diseases are associated with bone mineral density or prevalent vertebral deformities. We examined 12 self-reported disease conditions including diabetes mellitus (types 1 or 2), nephrolithiasis, hypertension, heart attack, rheumatoid arthritis, thyroid disease, breast cancer, inflammatory bowel disease, neuromuscular disease, Paget's disease, and chronic obstructive pulmonary disease. Multivariate linear and logistic regression analyses were performed to determine whether there were associations among these disease conditions and bone mineral density of the lumbar spine, femoral neck, and trochanter, as well as prevalent vertebral deformities. Bone mineral density measurements were higher in women and men with type 2 diabetes compared with those without after appropriate adjustments. The differences were most notable at the lumbar spine (+0.053 g/cm2), femoral neck (+0.028 g/cm2), and trochanter (+0.025 g/cm2) in women, and at the femoral neck (+0.025 g/cm2) in men. Hypertension was also associated with higher bone mineral density measurements for both women and men. The differences were most pronounced at the lumbar spine (+0.022 g/cm2) and femoral neck (+0.007 g/cm2) in women and at the lumbar spine (+0.028 g/cm2) in men. Although results were statistically inconclusive, men reporting versus not reporting past nephrolithiasis appeared to have clinically relevant lower bone mineral density values. Bone mineral density differences were -0.022, -0.015, and -0.016 g/cm2 at the lumbar spine, femoral neck, and trochanter, respectively. Disease conditions were not strongly associated with vertebral deformities. In summary, these cross-sectional population-based data show that type 2 diabetes and hypertension are associated with higher bone mineral density in women and men, and nephrolithiasis may be associated with lower bone mineral density in men. The importance of these associations for osteoporosis case finding and management require further and prospective studies.

Aged↗
PubMed2001

GABA(B) receptors couple directly to the transcription factor ATF4.

The inhibitory neurotransmitter gamma-aminobutyric acid (GABA), acts at ionotropic (GABA(A) and GABA(C)) and metabotropic (GABA(B)) receptors. Functional GABA(B) receptors are heterodimers of GABA(B(1)) and GABA(B(2)) subunits. Here we show a robust, direct, and specific interaction between the coiled-coil domain present in the C-terminus of the GABA(B(1)) subunit and the transcription factor ATF4 (also known as CREB2). ATF4 and GABA(B(2)) binding to the GABA(B(1)) subunit were mutually exclusive. In rat hippocampal neurons native GABA(B(1)) showed surprisingly little similarity to GABA(B(2)) in its subcellular distribution. GABA(B(1)) and ATF4, however, were highly colocalized throughout the cell and displayed a punctate distribution within the dendrites. Activation of GABA(B) receptors in hippocampal neurons caused a dramatic translocation of ATF4 out of the nucleus into the cytoplasm. These data suggest a novel neuronal signaling pathway that could regulate the functional expression of GABA(B) receptors and/or modulate gene transcription.

Activating Transcription Factor 4↗
PubMed2001

The influence of osteoporotic fractures on health-related quality of life in community-dwelling men and women across Canada.

Health-related quality of life (HRQL) was examined in relation to prevalent fractures in 4816 community-dwelling Canadian men and women 50 years and older participating in the Canadian Multicentre Osteoporosis Study (CaMos). Fractures were of three categories: clinically recognized main fractures, subclinical vertebral fractures and fractures at other sites. Main fractures were divided and analyzed at the hip, spine, wrist/forearm, pelvis and rib sites. Baseline assessments of anthropometric data, medical history, therapeutic drug use, spinal radiographs and prevalent fractures were obtained from all participants. The SF-36 instrument was used as a tool to measure HRQL. A total of 652 (13.5%) main fractures were reported. Results indicated that hip, spine, wrist/forearm, pelvis and rib fractures had occurred in 78 (1.6%), 40 (0.8%), 390 (8.1%), 19 (0.4%) and 125 (2.6%) individuals, respectively (subjects may have had more than one main fracture). Subjects who had experienced a main prevalent fracture had lower HRQL scores compared with non-fractured participants. The largest differences were observed in the physical functioning (-4.0; 95% confidence intervals (CI): -6.0, -2.0) and role-physical functioning domains (-5.8; 95% CI: -9.5, -2.2). In women, the physical functioning domain was most influenced by hip (-14.9%; 95% CI: -20.9, -9.0) and pelvis (-18.1; 95% CI: -27.6, -8.6) fractures. In men, the role-physical domain was most affected by hip fractures (-35.7; 95% CI: -60.4, -11.1). Subjects who experienced subclinical vertebral fractures had lower HRQL scores than those without prevalent fractures. In conclusion, HRQL was lower in the physical functioning domain in women and the role-physical domain in men who sustained main fractures at the hip. Subclinical vertebral fractures exerted a moderate effect on HRQL.

Aged↗
PubMed2001

Transient synaptic activation of NMDA receptors leads to the insertion of native AMPA receptors at hippocampal neuronal plasma membranes.

The molecular mechanisms underlying long-term potentiation (LTP) of excitatory synaptic transmission in the hippocampus are not well understood. Transient depolarisation of cultured postnatal hippocampal neurones (3x1 s exposure to 90 mM K+) induces a form of LTP that is manifest primarily as an increase in mEPSC frequency. Site-directed antibodies that recognise an extracellular region of all AMPA receptor (AMPAR) subunits (GluR1-4) were used for the immunolabelling of living neurones. These antibodies were raised in two species to enable sequential immunofluorescent labelling of individual living neurones before and after the induction of LTP. High K+ treatment resulted in the appearance of new AMPAR clusters at sites on the neuronal surface that previously lacked detectable AMPARs. The appearance of new AMPAR clusters was NMDA receptor (NMDAR)-dependent since it was antagonised by the application of NMDAR antagonists. Our data indicate that the transient synaptic activation of NMDARs can lead to the insertion of native AMPARs at sites on the neuronal membrane that initially lacks AMPARs.

Animals↗
PubMed2001

An electrophysiological characterisation of long-term potentiation in cultured dissociated hippocampal neurones.

Long-term potentiation (LTP) of synaptic transmission is under intense investigation. It is believed that the mechanisms involved in its induction and expression are critically involved in synaptic processes that are important for learning and memory and other physiological functions. A reliable means of inducing LTP in dissociated cultured neurones would facilitate investigations into the molecular basis of LTP but has been hard to achieve. Here we report a mechanism for inducing LTP in postnatal dissociated hippocampal neurones using transient depolarisation. This form of LTP is prevented by NMDA receptor antagonists and by chelating Ca2+ in the postsynaptic neurone. It is manifest primarily as an increase in the frequency of mEPSCs.

Animals↗
PubMed2000

Developmental changes in synaptic AMPA and NMDA receptor distribution and AMPA receptor subunit composition in living hippocampal neurons.

AMPA and NMDA receptors mediate most excitatory synaptic transmission in the CNS. We have developed antibodies that recognize all AMPA or all NMDA receptor variants on the surface of living neurons. AMPA receptor variants were identified with a polyclonal antibody recognizing the conserved extracellular loop region of all four AMPA receptor subunits (GluR1-4, both flip and flop), whereas NMDA receptors were immunolabeled with a polyclonal antibody that binds to an extracellular N-terminal epitope of the NR1 subunit, common to all splice variants. In non-fixed brain sections these antibodies gave labeling patterns similar to autoradiographic distributions with particularly high levels in the hippocampus. Using these antibodies, in conjunction with GluR2-specific and synaptophysin antibodies, we have directly localized and quantified surface-expressed native AMPA and NMDA receptors on cultured living hippocampal neurons during development. Using a quantitative cell ELISA, a dramatic increase was observed in the surface expression of AMPA receptors, but not NMDA receptors, between 3 and 10 d in culture. Immunocytochemical analysis of hippocampal neurons between 3 and 20 d in vitro shows no change in the proportion of synapses expressing NMDA receptors (approximately 60%) but a dramatic increase (approximately 50%) in the proportion of them that also express AMPA receptors. Furthermore, over this period the proportion of AMPA receptor-positive synapses expressing the GluR2 subunit increased from approximately 67 to approximately 96%. These changes will dramatically alter the functional properties of hippocampal synapses.

Animals↗
PubMed1999

Surface expression of AMPA receptors in hippocampal neurons is regulated by an NSF-dependent mechanism.

Here, we show that disruption of N-ethylmaleimide-sensitive fusion protein- (NSF-) GluR2 interaction by infusion into cultured hippocampal neurons of a blocking peptide (pep2m) caused a rapid decrease in the frequency but no change in the amplitude of AMPA receptor-mediated miniature excitatory postsynaptic currents (mEPSCs). N-methyl-D-aspartate (NMDA) receptor-mediated mEPSCs were not changed. Viral expression of pep2m reduced the surface expression of alpha-amino-3-hydroxy-5-methyl-isoxazolepropionate (AMPA) receptors, whereas NMDA receptor surface expression in the same living cells was unchanged. In permeabilized neurons, the total amount of GluR2 immunoreactivity was unchanged, and a punctate distribution of GluR2 was observed throughout the dendritic tree. These data suggest that the NSF-GluR2 interaction is required for the surface expression of GluR2-containing AMPA receptors and that disruption of the interaction leads to the functional elimination of AMPA receptors at synapses.

Adenoviridae↗
PubMed1998

Chlamydial cervicitis: testing the practice guidelines for presumptive diagnosis.

OBJECTIVE: To test the recommendation from the Canadian guidelines for sexually transmitted diseases (STDs) that mucopurulent endocervical discharge and 10 or more polymorphonuclear leukocytes (PMNs) per high-power field of a Gram-stained endocervical smear or, when Gram staining is not possible, the presence of endocervical discharge and one of edema, erythema or induced mucosal bleeding of the cervix can be considered diagnostic for chlamydial cervicitis. METHODS: A total of 596 consecutive women attending 2 family planning clinics for routine care underwent vaginal speculum examination and were tested for Chlamydia trachomatis and Neisseria gonorrhoeae. PMN counts from Gram-stained endocervical smears and the presence or absence of putative indicators of chlamydial infection were recorded. RESULTS: The prevalence of chlamydial cervicitis was 6.2% (37/596), and no women tested positive for N. gonorrhoeae. Presumptive diagnosis of chlamydial cervicitis based on the guidelines criteria of mucopurulent endocervical discharge and 10 or more PMN per high-power microscopic field had a sensitivity and specificity of 18.9% and 97.0% respectively, a positive predictive value of 29.2% and a positive likelihood ratio (LR) of 6.2 (p = 0.003). Presumptive diagnosis based on endocervical discharge with edema, erythema or induced mucosal bleeding of the cervix had a sensitivity and specificity of 43.2% and 80.0% respectively, a positive predictive value of 12.5% and a positive LR of 2.2 (p = 0.002). In the presence of bacterial vaginosis or vaginitis, the LR for the criteria of mucopurulent endocervical discharge and 10 or more PMN per high-power field was 5.4 (p = 0.04), whereas the LR was 4.3 (p = 0.10) if bacterial vaginosis and vaginitis were absent. CONCLUSIONS: In this setting, the practice of making a presumptive diagnosis of chlamydial cervicitis on the basis of the criteria given in the Canadian STD guidelines was not supported.

Adult↗
PubMed1997

Understanding and enhancing compliance with the second dose of hepatitis B vaccine: a cohort analysis and a randomized controlled trial.

OBJECTIVE: To determine the predictors and extent of noncompliance with a second dose of hepatitis B vaccine and the effectiveness of a compliance enhancement strategy. DESIGN: Cohort analysis and randomized clinical trial. SUBJECTS: A total of 256 consecutive adults attending a sexually transmitted diseases clinic from October 1992 to July 1993 who were seronegative for hepatitis B virus and agreed to receive hepatitis B vaccination. SETTING: Hamilton, Ont. INTERVENTION: Subjects were followed up for 4 months. Those who did not return for the second dose of vaccine by 6 weeks after the first (2 weeks overdue) were randomly assigned to the enhanced intervention group (telephone and mail reminders) or the regular intervention group (mail reminder only). Subjects were considered noncompliant if they did not return for the second dose by 4 months after the first. RESULTS: The risk of not returning for the second dose of vaccine within 4 months after the first was strongly and linearly associated with level of education (p = 0.004). The noncompliance rate among those with less than a grade 10 education was 50%, grade 10-13 education 34%, some college education 15% and some university education 9%. In the randomized controlled trial the enhanced intervention group had twice the compliance rate of the regular intervention group (48% v. 25%; p = 0.008). Subjects with no postsecondary education were highly responsive to the enhanced intervention (relative risk 2.1; p = 0.02) compared with those with a higher level of education (relative risk 1.0; p = 1.0). CONCLUSION: Hepatitis B vaccine recipients with lower educational levels are at increased risk of noncompliance with the second dose of vaccine but are highly responsive to telephone reminders.

Adult↗
PubMed1997

Factors associated with appropriate physician management of sexually transmitted diseases in an urban Canadian center.

BACKGROUND AND OBJECTIVES: To explore physicians' management of selected sexually transmitted diseases (STDs), because previous studies suggest that physicians' management practices could be improved. GOALS: To determine the estimated annual incidence of STD seen by family/general practitioners (FPs), gynecologists (GYNs) and urologists (UROLs), adequacy of STD management practices, and any associations with demographic and other characteristics. STUDY DESIGN: A self-administered questionnaire was mailed to GYNs, UROLs, and a random sample of FPs in Hamilton, Ontario. RESULTS: Eighty-one of 102 (79.4%) FPs, 27 of 32 (84.4%) GYNs, and 7 of 8 (87.5%) UROLs responded. Vaginitis, male urethritis, and genital warts in women were the most frequently observed STDs. The treatment of bacterial vaginosis and pelvic inflammatory disease were most frequently at variance with published guidelines. CONCLUSIONS: Deficiencies exist in physicians' management of both common and potentially serious STD problems.

Attitude↗
PubMed1994

Role of confirmatory PCRs in determining performance of Chlamydia Amplicor PCR with endocervical specimens from women with a low prevalence of infection.

The role of confirmatory PCR assays for determining the performance of Chlamydia Amplicor PCR for endocervical specimens from women with a low prevalence of infection was evaluated. An endocervical swab was collected from 770 women and tested by culture or direct fluorescent antibody (DFA) staining. A second swab was tested by Chlamydia Amplicor PCR (Roche Molecular Systems, Branchburg, N.J.). Discordant results were resolved by three confirmatory PCRs: one targeting the plasmid by using different primers and two directed to the major outer membrane protein (MOMP) gene. Of the 30 swabs that were positive by culture or DFA (3.9%), 27 were positive by Amplicor PCR. An additional five swabs were positive by Amplicor PCR but negative by culture or DFA. Both plasmid and MOMP confirmatory PCRs identified the five culture-DFA negatives and the three Amplicor negatives as true positives. The three specimens originally classified as negative by Amplicor PCR were positive on repeat Amplicor testing. After resolution of the discordant results by confirmatory PCR testing, the sensitivity of the initial Amplicor PCR was 91.4% (32 of 35 specimens), changing to 100% after storage and repeat testing. The specificity of Amplicor PCR was 100% (735 of 735 specimens). Our results demonstrated that plasmid and MOMP confirmatory PCRs worked equally well in resolving false-positive and false-negative Amplicor PCR results. Some specimens may contain inhibitors of Amplicor PCR which may disappear with time.

Adult↗
PubMed1993

Effect of time elapsed since previous voiding on the detection of Chlamydia trachomatis antigens in urine.

To determine if the time elapsed since previous voiding affects the sensitivity of an enzyme immunoassay (EIA) to detect Chlamydia trachomatis in urine, 882 women and 428 men were tested for chlamydial infection in urethral specimens by isolation in cell culture (women and men) and EIA with blocking confirmation (women only). Of the 36 women (4.1%) and 38 men (8.9%) who were positive for Chlamydia trachomatis in the urethra, 55.5% (20/36) and 81.6% (31/38) respectively were positive in the first void urine (FVU) sediment by confirmed EIA. In women the sensitivity of the EIA performed on FVU was 67.8% (19/28) if the urine had been in the bladder < 3 hours and decreased to 12.5% (1/8) if longer times had elapsed (odds ratio 13.7; 95% confidence interval 1.4 to 700.0) with no obvious confounding. In men a weaker association was present (odds ratio 2.7; 95% confidence interval 0.4 to 22.3). These findings should enable investigators to optimize the analysis of urine to diagnose chlamydial infections.

Antigens, Bacterial↗
PubMed1992

Effectiveness and efficiency of selective vs universal screening for chlamydial infection in sexually active young women.

BACKGROUND: Since chlamydial cervicitis is not associated with specific complaints, screening asymptomatic women is an important initiative to prevent pelvic inflammatory disease and its sequelae. Compared with universal screening, selective screening is less costly but less effective so the cost savings vs the consequences of missing infected women need to be weighed carefully. METHODS: In two family planning clinics, 1002 women were surveyed for chlamydial infection (prevalence, 7%) and its predictors to determine whether universal or selective screening is the most efficient strategy. Two rules for the selection of patients were determined by logistic regression modeling and their relative efficiencies were compared by incremental cost-effectiveness and sensitivity analysis. The validity of the screening rules was tested in 191 students attending a university health clinic. RESULTS: If those with cervical friability, suspicious discharge, urinary frequency, or intermenstrual bleeding had been tested, 55.3% of all women would have been screened and 83.3% of all cases would have been detected. If those reporting a new sex partner in the preceding year had also been tested, 75.4% would have been screened, identifying 93.3% of all cases. The predictive power and practicality of the selection rules were validated in the university health clinic sample. Sensitivity analyses showed selective screening using cervical enzyme immunoassay with blocking confirmation was efficient if the prevalence of chlamydial infection was 16% or less, 11% or less, or 5% or less depending on whether base analyses, overestimated costs, or worst performance scenarios, respectively, were used. CONCLUSIONS: Selective screening based on four or five predictors and confirmed cervical enzyme immunoassay is an effective and efficient strategy in low prevalence settings.

Adult↗
PubMed1991

Comparison of cervical, urethral, and urine specimens for the detection of Chlamydia trachomatis in women.

Cervical, urethral, and first void urine (FVU) specimens from 937 women were tested for Chlamydia trachomatis by culture or EIA to determine the most sensitive combination of tests and specimens. For cervical and urethral specimens the prevalence of infection by culture or confirmed EIA was 7.2% (67/937) at either site, 6.8% (64/937) at the cervix, and 4.3% (40/937) at the urethra. Of 67 specimens, 37 (55.2%) yielded a positive test from both the cervical and urethral swabs. Three (4.5%) of the 67 infections were only at the urethra and none were only in FVU. Only 37.3% (25/67) of all positive women had a positive FVU. The most sensitive combination was cervical swab culture and EIA, which detected 95.5% (64/67) of the infections, a substantial increase over culture only (76.1%) or EIA of the cervical swab (79.1%). The testing of urethral and FVU specimens apparently offers only minimal advantage over testing of cervical specimens only for chlamydia.

Adolescent↗
PubMed1991

Community health nursing audit: issues encountered during the selection and application of an audit instrument.

Several issues were encountered by nurse-managers in a community agency while implementing an audit of community health nursing charts. They included the following: (1) what is the purpose of the audit? (2) are the required resources available to implement the audit process? (3) what is the selection process for charts to be audited? (4) how many charts have to be audited? (5) is the audit tool based on relevant and measurable criteria and standards? (6) have the measurement properties of the audit tool been determined, including validity and reliability? The validity, reliability, and weighting of scores of the Craig audit tool are explored. Results of an assessment of this tool's reliability are presented.

Community Health Nursing↗