Biomedical subjects

Kenneth McLeod

Publications and source records attributed to Kenneth McLeod.

5 recordsLinked to original sources

PubMed2003

Prevention of postmenopausal bone loss by a low-magnitude, high-frequency mechanical stimuli: a clinical trial assessing compliance, efficacy, and safety.

UNLABELLED: A 1-year prospective, randomized, double-blind, and placebo-controlled trial of 70 postmenopausal women demonstrated that brief periods (<20 minutes) of a low-level (0.2g, 30 Hz) vibration applied during quiet standing can effectively inhibit bone loss in the spine and femur, with efficacy increasing significantly with greater compliance, particularly in those subjects with lower body mass. INTRODUCTION: Indicative of the anabolic potential of mechanical stimuli, animal models have demonstrated that short periods (<30 minutes) of low-magnitude vibration (<0.3g), applied at a relatively high frequency (20-90 Hz), will increase the number and width of trabeculae, as well as enhance stiffness and strength of cancellous bone. Here, a 1-year prospective, randomized, double-blind, and placebo-controlled clinical trial in 70 women, 3-8 years past the menopause, examined the ability of such high-frequency, low-magnitude mechanical signals to inhibit bone loss in the human. MATERIALS AND METHODS: Each day, one-half of the subjects were exposed to short-duration (two 10-minute treatments/day), low-magnitude (2.0 m/s2 peak to peak), 30-Hz vertical accelerations (vibration), whereas the other half stood for the same duration on placebo devices. DXA was used to measure BMD at the spine, hip, and distal radius at baseline, and 3, 6, and 12 months. Fifty-six women completed the 1-year treatment. RESULTS AND CONCLUSIONS: The detection threshold of the study design failed to show any changes in bone density using an intention-to-treat analysis for either the placebo or treatment group. Regression analysis on the a priori study group demonstrated a significant effect of compliance on efficacy of the intervention, particularly at the lumbar spine (p = 0.004). Posthoc testing was used to assist in identifying various subgroups that may have benefited from this treatment modality. Evaluating those in the highest quartile of compliance (86% compliant), placebo subjects lost 2.13% in the femoral neck over 1 year, whereas treatment was associated with a gain of 0.04%, reflecting a 2.17% relative benefit of treatment (p = 0.06). In the spine, the 1.6% decrease observed over 1 year in the placebo group was reduced to a 0.10% loss in the active group, indicating a 1.5% relative benefit of treatment (p = 0.09). Considering the interdependence of weight, the spine of lighter women (<65 kg), who were in the highest quartile of compliance, exhibited a relative benefit of active treatment of 3.35% greater BMD over 1 year (p = 0.009); for the mean compliance group, a 2.73% relative benefit in BMD was found (p = 0.02). These preliminary results indicate the potential for a noninvasive, mechanically mediated intervention for osteoporosis. This non-pharmacologic approach represents a physiologically based means of inhibiting the decline in BMD that follows menopause, perhaps most effectively in the spine of lighter women who are in the greatest need of intervention.

Bone Density↗

PubMed2003

Transmissibility of 15-hertz to 35-hertz vibrations to the human hip and lumbar spine: determining the physiologic feasibility of delivering low-level anabolic mechanical stimuli to skeletal regions at greatest risk of fracture because of osteoporosis.

STUDY DESIGN: Experiments were undertaken to determine the degree to which high-frequency (15-35 Hz) ground-based, whole-body vibration are transmitted to the proximal femur and lumbar vertebrae of the standing human. OBJECTIVES: To establish if extremely low-level (<1 g, where 1 g = earth's gravitational field, or 9.8 ms-2) mechanical stimuli can be efficiently delivered to the axial skeleton of a human. SUMMARY OF BACKGROUND DATA: Vibration is most often considered an etiologic factor in low back pain as well as several other musculoskeletal and neurovestibular complications, but recent in vivo experiments in animals indicates that extremely low-level mechanical signals delivered to bone in the frequency range of 15 to 60 Hz can be strongly anabolic. If these mechanical signals can be effectively and noninvasively transmitted in the standing human to reach those sites of the skeleton at greatest risk of osteoporosis, such as the hip and lumbar spine, then vibration could be used as a unique, nonpharmacologic intervention to prevent or reverse bone loss. MATERIALS AND METHODS: Under sterile conditions and local anesthesia, transcutaneous pins were placed in the spinous process of L4 and the greater trochanter of the femur of six volunteers. Each subject stood on an oscillating platform and data were collected from accelerometers fixed to the pins while a vibration platform provided sinusoidal loading at discrete frequencies from 15 to 35 Hz, with accelerations ranging up to 1 g(peak-peak). RESULTS: With the subjects standing erect, transmissibility at the hip exceeded 100% for loading frequencies less than 20 Hz, indicating a resonance. However, at frequencies more than 25 Hz, transmissibility decreased to approximately 80% at the hip and spine. In relaxed stance, transmissibility decreased to 60%. With 20-degree knee flexion, transmissibility was reduced even further to approximately 30%. A phase-lag reached as high as 70 degrees in the hip and spine signals. CONCLUSIONS: These data indicate that extremely low-level, high-frequency mechanical accelerations are readily transmitted into the lower appendicular and axial skeleton of the standing individual. Considering the anabolic potential of exceedingly low-level mechanical signals in this frequency range, this study represents a key step in the development of a biomechanically based treatment for osteoporosis.

Adult↗

PubMed2003

Decreased skeletal muscle pump activity in patients with postural tachycardia syndrome and low peripheral blood flow.

Standing translocates thoracic blood volume into the dependent body. The skeletal muscle pump participates in preventing orthostatic intolerance by enhancing venous return. We investigated the hypothesis that skeletal muscle pump function is impaired in postural tachycardia (POTS) associated with low calf blood flow (low-flow POTS) and depends in general on muscle blood flow. We compared 12 subjects that have low-flow POTS with 10 controls and 7 patients that have POTS and normal calf blood flow using strain-gauge plethysmography to measure peripheral blood flow, venous capacitance, and calf muscle pump function. Blood volume was estimated by dye dilution. We found that calf circumference was reduced in low-flow POTS (32 +/- 1 vs. 39 +/- 3 and 43 +/- 3 cm) and, compared with controls and POTS patients with normal blood flow, is related to the reduced fraction of calf venous capacity emptied during voluntary muscle contraction (ejection fraction, 0.52 +/- 0.07 vs. 0.76 +/- 0.07 and 0.80 +/- 0.06). We found that blood flow was linearly correlated (r(p) = 0.69) with calf circumference (used as a surrogate for muscle mass). Blood volume measurements were 2.2 +/- 0.3 in low-flow POTS vs. 2.6 +/- 0.5 in controls (P = 0.17) and 2.4 +/- 0.7 in normal-flow POTS patients. Decreased calf blood flow may reduce calf size in POTS and thereby impair the upright ejective ability of the skeletal muscle pump and further contribute to overall reduced blood flow and orthostatic intolerance in these patients.

Adolescent↗

PubMed2003

Fibronectin fibrillogenesis on sulfonated polystyrene surfaces.

Extracellular matrix (ECM) protein adsorption and organization serves as a critical first step in the development and organization of tissues. Advances in tissue engineering, therefore, will depend on the ability to control the rate and pattern of ECM formation. Fibronectin is a prominent component of the ECM, which undergoes fibrillogenesis in the presence of cells. Using sulfonated polysyrene surfaces, we showed that fibronectin undergoes a transition from monolayer to multilayer adsorption at calculated surface charge densities above 0.03 Coulombs (C)/m(2). At charge densities above approximately 0.08 C/m(2), distinct fibronectin fibrillar networks are observed to form with a fibril morphology similar to those observed to form in situ on cell surfaces. This self-organization process is time dependent, with the fibrils achieving dimensions of 30-40 microm in length and 1 microm in height after 72 h of incubation. We suggest that the polarization of charge domains on the polyampholytic fibronectin molecules near high charge density surfaces is sufficient to initiate the multilayer adsorption and the organization of these fibrillar structures. These results suggest that the nonlinear dependence of adsorption on surface charge density may play an important role in the self-organization of many matrix components.

Adsorption↗

PubMed2002

Quantity and quality of trabecular bone in the femur are enhanced by a strongly anabolic, noninvasive mechanical intervention.

The skeleton's sensitivity to mechanical stimuli represents a critical determinant of bone mass and morphology. We have proposed that the extremely low level (< 10 microstrain), high frequency (20-50 Hz) mechanical strains, continually present during even subtle activities such as standing are as important to defining the skeleton as the larger strains typically associated with vigorous activity (>2000 microstrain). If these low-level strains are indeed anabolic, then this sensitivity could serve as the basis for a biomechanically based intervention for osteoporosis. To evaluate this hypothesis, the hindlimbs of adult female sheep were stimulated for 20 minutes/day using a noninvasive 0.3g vertical oscillation sufficient to induce approximately 5 microstrain on the cortex of the tibia. After 1 year of stimulation, the physical properties of 10-mm cubes of trabecular bone from the distal femoral condyle of experimental animals (n = 8) were compared with controls (n = 9), as evaluated using microcomputed tomography (microCT) scanning and materials testing. Bone mineral content (BMC) was 10.6% greater (p < 0.05), and the trabecular number (Tb.N) was 8.3% higher in the experimental animals (p < 0.01), and trabecular spacing decreased by 11.3% (p < 0.01), indicating that bone quantity was increased both by the creation of new trabeculae and the thickening of existing trabeculae. The trabecular bone pattern factor (TBPf) decreased 24.2% (p < 0.03), indicating trabecular morphology adapting from rod shape to plate shape. Significant increases in stiffness and strength were observed in the longitudinal direction (12.1% and 26.7%, respectively; both, p < 0.05), indicating that the adaptation occurred primarily in the plane of weightbearing. These results show that extremely low level mechanical stimuli improve both the quantity and the quality of trabecular bone. That these deformations are several orders of magnitude below those peak strains which arise during vigorous activity indicates that this biomechanically based signal may serve as an effective intervention for osteoporosis.

Animals↗