Biomedical subjects

Peter M Smith

Publications and source records attributed to Peter M Smith.

8 recordsLinked to original sources

PubMed2006

Extended duration of efficacy of vardenafil when taken 8 hours before intercourse: a randomized, double-blind, placebo-controlled study.

OBJECTIVES: This study explored the efficacy of vardenafil in men with erectile dysfunction (ED) when taken 8 hours before sexual intercourse. METHODS: A 10-week, randomized, double-blind, placebo-controlled, parallel-group, flexible-dose study of vardenafil (5, 10 or 20mg) was conducted in men with ED for >6 months who failed >or=50% of intercourse attempts during a 4-week treatment-free run-in period. Sexual Encounter Profile Question 3 (SEP3) was the primary efficacy measure; secondary measures included SEP2, International Index of Erectile Function-Erectile Function (IIEF-EF) domain score, Global Assessment Question (GAQ), Global Confidence Question (GCQ) and Erection Quality Scale (EQS). Adverse-event and safety monitoring were conducted throughout. RESULTS: 383 patients were randomized to vardenafil (n=194) or placebo (n=189). Patients treated with vardenafil 8 hours before sexual activity achieved clinically meaningful (>or=18%) and statistically significantly greater least-squares mean per-patient SEP3 and SEP2 success rates over weeks 2-10, compared with patients receiving placebo (SEP3 69% vs 34%; SEP2 81% vs 51%; both p<0.001). SEP3 and SEP2 measures demonstrated the significant superiority of vardenafil over placebo from week 2 onwards (p<0.001). Measurements of IIEF-EF domain score, GAQ, GCQ and EQS showed that vardenafil led to significantly greater improvements in erectile function, compared with placebo (all p<0.001). Vardenafil was generally well tolerated. CONCLUSIONS: The extended duration of efficacy of vardenafil up to 8 hours postdose may provide couples with more flexibility in their sexual life than anticipated.

Adult↗

PubMed2006

Finite difference time domain methods for piezoelectric crystals.

The numerical simulation of acoustic wave propagation through piezoelectric crystals using the finite-difference time-domain (FDTD) method is introduced. The update equations for the velocity and stress fields are derived and applied to the propagation of ultrasonic waves in three substrates. The concept of the perfectly matched layer (PML), first introduced for the simulation of electromagnetic waves, is extended to the simulation of mechanical waves. The technique is shown to be effective for some crystals, but the PML is found to exhibit numerical instabilities for others.

Journal Article↗

PubMed2006

Histological and ultrastructural analysis of white matter damage after naturally-occurring spinal cord injury.

Detailed analysis of the structural changes that follow human clinical spinal cord injury is limited by difficulties in achieving adequate tissue fixation. This study bypasses this obstacle by examining the spinal cord from paraplegic domestic animals, enabling us to document the ultrastructural changes at different times following injury. In all but one case, injury resulted from a combination of contusion and compression. There was infarction and hemorrhage, followed by gray matter destruction and the rapid development of a variety of white matter changes including axon swelling and myelin degeneration. Axons greater than 5 microm in diameter were more susceptible to degenerative changes, whereas smaller axons, particularly those in the subpial region, were relatively well preserved. Demyelinated axons were seen within 2 weeks after injury and, at later time points, both Schwann cell and oligodendrocyte remyelination was common. More subtle white matter abnormalities were identified by examining sagittal sections, including focal accumulation of organelles in the axoplasm and partial and paranodal myelin abnormalities. These observations serve to validate observations from experimental models of spinal contusion but also highlight the complexity of naturally occurring (ie, clinical) spinal injury. They also raise the possibility that focal abnormalities such as paranodal demyelination may contribute to early axonal dysfunction and possibly to progressive tissue damage.

Animals↗

PubMed2003

Questioning the stability of sense of coherence--the impact of socio-economic status and working conditions in the Canadian population.

BACKGROUND: Much debate exists about the stability of the sense of coherence measure. This study examined changes in sense of coherence (SOC), and the variables associated with these changes, over a 4-year period, in a representative sample of the Canadian labour force (n=6,790). METHODS: Two methods were used to assess change in SOC: (1) Change outside of that which could be considered as indistinguishable from measurement error, and (2) Change of more than 10%, which was originally proposed by Antonovksy, the scales designer. RESULTS: Over the study period, 35.4% of the population reported changes in SOC outside the range we consider possible due to measurement error, with 58% reporting change greater than 10%. Unskilled occupations were associated with declines in SOC, with household income demonstrating a curvilinear relationship with decline in SOC in the female population only. None of the variables used predicted increases in SOC. CONCLUSIONS: Given the degree of change in SOC, and the representativeness of the study sample, we suggest that SOC has a large state component. Given this lack of stability, we recommend caution if using the SOC to represent a stable global orientation within a causal context.

Adolescent↗

PubMed2003

Meningeal cells enhance limited CNS remyelination by transplanted olfactory ensheathing cells.

Olfactory ensheathing cells (OECs) are candidate cells for transplant-mediated repair of persistent demyelination in diseases such as multiple sclerosis. If this approach is to make the transition from laboratory to clinic, an important issue is the most suitable composition of the OEC transplant. Isolation of OECs involves concurrent isolation of other cell types, and specific selection techniques are required to produce purified OECs. In this study we address whether the purity of the OEC transplant affects their ability to remyelinate. Surprisingly, we find that a purified preparation of OECs, selected on the basis of low-affinity nerve growth factor receptor (p75) expression, results in less extensive remyelination than an unpurified preparation following transplantation into areas of persistent demyelination in rodent CNS in the X-irradiation/ethidium bromide (X-EB) model. A distinctive feature of the unpurified preparation both in vitro and following transplantation is the presence of meningeal cells. When meningeal cells are added to purified OECs there is a significant improvement in the extent of remyelination compared with the purified OECs, although if the cells are present in too great an abundance this beneficial effect is lost. These results highlight the important concept that the regenerative properties of OECs are profoundly influenced by the cells with which they are transplanted.

Animals↗

PubMed2002

Correlations between the functional integrity of the endoplasmic reticulum and polarized Ca2+ signalling in mouse lacrimal acinar cells: a role for inositol 1,3,4,5-tetrakisphosphate.

Ca(2+) signalling in exocrine acinar cells has been shown to be both polarized and pulsatile in all cell types tested, except acutely isolated mouse lacrimal acinar cells. Lacrimal cells are also unusual in that they display a very low sensitivity to Ins(1,4,5) P (3) (Ins P (3)) that may be enhanced by placing the cells in primary culture for 12-72 h or by intracellular infusion of a low concentration of Ins(1,3,4,5) P (4) (Ins P (4)). We have proposed previously that this atypical behaviour stemmed from vesiculation of the endoplasmic reticulum (ER) incurred during isolation of the cells and, furthermore, that time in culture or Ins P (4) increased sensitivity to Ins P (3) by increasing ER integrity [Smith, Harmer, Letcher and Irvine (2000) Biochem. J. 347, 77-82]. We have measured the half time for fluorescence recovery after photobleaching (FRAP) of a fluorescent marker (Mag-fluo 4) loaded into the ER lumen in order to determine directly the functional integrity of the ER in lacrimal cells. The half-time for FRAP was increased (indicating a reduction in the functional integrity of the ER) following exposure to anti-microtubule agents (taxol and nocodazole) known to perturb ER structure and decreased (indicating an increase in the functional integrity of the ER) by time in culture and exposure to Ins P (4). The action of Ins P (4) was particularly pronounced because it occurred under patch-clamp whole-cell conditions that were themselves found to reduce ER functional integrity. These data show that ER remodelling could be a physiological regulator of Ca(2+) signalling and indicate a role for Ins P (4) in control of this process.

Animals↗

PubMed2002

Component architecture in drug discovery informatics.

This paper reviews the characteristics of a new model of computing that has been spurred on by the Internet, known as Netcentric computing. Developments in this model led to distributed component architectures, which, although not new ideas, are now realizable with modern tools such as Enterprise Java. The application of this approach to scientific computing, particularly in pharmaceutical discovery research, is discussed and highlighted by a particular case involving the management of biological assay data.

Databases, Factual↗

PubMedDate not supplied

Methods for estimating the labour force insured by the Ontario Workplace Safety and Insurance Board: 1990-2000.

This paper presents a methodology for estimating the size and composition of the Ontario labour force eligible for coverage under the Ontario Workplace Safety & Insurance Act (WSIA). Using customized tabulations from Statistics Canada's Labour Force Survey (LFS), we made adjustments for self-employment, unemployment, part-time employment and employment in specific industrial sectors excluded from insurance coverage under the WSIA. Each adjustment to the LFS reduced the estimates of the insured labour force relative to the total Ontario labour force. These estimates were then developed for major occupational and industrial groups stratified by gender. Additional estimates created to test assumptions used in the methodology produced similar results. The methods described in this paper advance those previously used to estimate the insured labour force, providing researchers with a useful tool to describe trends in the rate of injury across differing occupational, industrial and gender groups in Ontario.

Absenteeism↗