Peter R. Cavanagh, Ph.D. - US grants

Alcohol has been implicated in the etiology of many falls in the elderly yet little is known concerning the acute effects of alcohol on gait and posture. This study is designed to identify the mechanisms involved in falling in the aged under both normal conditions and when postural stability and gait are degraded by alcohol. Year 1 will be spent gaining experience and collecting baseline data on the biomechanical and visual effects of acute alcohol consumption in 15 young males. Years 2 and 3 will then focus on a group of 30 elderly subjects (aged 65 to 75) to investigate the effects of alcohol on gait and posture under both normal and altered visual conditions. Detailed medical histories will be collected through administration of the DIS schedule and through thorough physical examinations, including measures of sensation and proprioception. The subjects will be asked to perform various postural and locomotor tasks after having consumed ethanol to raise their blood alcohol levels to 0.75 mg/ml (1.00 mg/ml for young male subjects). A variety of perturbations will be used to define the role of various control and feedback systems in the tasks. the effects of placebo and one month repeatability of the alcohol condition will also be assessed. Conduct of and recovery from all alcohol experiments will be closely supervised according to accepted practices in alcohol research. It is anticipated that this series of experiments will provide new information on a number of levels. First, we will develop specialized protocols for alcohol administration and testing of gait and posture on both young and elderly subjects. Second, new information is expected to be gained on the mechanisms controlling gait and posture in the elderly. Third, the effects of alcohol on gait and posture in the elderly will be defined. Fourth, the data are expected to provide a better basis for the understanding of falls in a variety of degradation conditions and to shed light on how they may be prevented.

DESCRIPTION (Adapted from applicant's abstract): Diabetes mellitus is primarily responsible for at least 50,000 non-traumatic lower extremity amputations in the US per year, yet it is now widely believed that many of these amputations are preventable. In particular, there are many statements in the literature suggesting that appropriate footwear can reduce the risk of plantar skin ulceration, which is often the critical event that initiates that path to amputation. Such statements are based on clinical experience from several specialized centers where the use of footwear empirically designed to reduce the likelihood of foot injury by cushioning the plantar surface of the foot has been pioneered. There are, however, very few studies in the literature which have attempted to evaluate the effects of specific footwear modifications in diabetic patients in an objective manner. Despite this paucity of objective information which could guide the practitioner in the prescription and evaluation of footwear designed to alleviate a particular foot problem, a major demonstration supported by HCFA is currently underway to determine if prophylactic footwear is cost effective in diabetics deemed to be at risk for foot injury. The proposed study is designed to fill this void by a systematic investigation of footwear typically prescribed for the diabetic foot. Based on the assumption that a reduction in plantar pressure is the desired mechanical effect of footwear that may reduce plantar ulceration, the applicants will test the hypothesis that elevated plantar pressure in the diabetic neuropathic foot can be reduced to normal levels by appropriate footwear intervention. Standards for normal plantar pressure' barefoot and in standard shoes will first be developed in a healthy control population. Diabetic patients who have lost protective sensation in their feet and who have elevated plantar pressure (but who are free of current significant foot lesions) will then be invited to participate in the study. Starting with the collection of plantar pressure in barefoot walking, the effects on plantar pressure of a standard shoe, a running shoe, an extra depth shoe with standard and custom insoles will be examined in all subjects and compared to the normal group. In the later stages of the study, patients with significant foot deformity will be studied while walking in custom shoes with custom molded insoles and another sub-group of the diabetics will be used to study the effects on plantar pressure of various configurations of the rocker bottom shoe, a frequently prescribed footwear modification in diabetic patients with marked foot deformity. The effects of the various footwear conditions will be examined using analyses of variance. A secondary analysis will also examine the relationship between deformity and plantar pressure, a relationship which has been often implied but never clearly proven. It is anticipated that the results of this study will have wide ranging implications for the prescription of footwear for the diabetic patient which is, at present, an almost entirely empirical process.

posture; proprioception /kinesthesia; diabetes mellitus; diabetic neuropathy; aging; ankle; limb movement; human subject;

DESCRIPTION (Adapted from the Applicant's Abstract): Stairs often present a formidable physical and psychological obstacle to elders, who are intuitively aware that falls from stairs account for the highest proportion of fall related injuries when compared to all other fall causations. In particular, stair descent is the most common dangerous locomotor activity and accidents during descent outnumber those during ascent by over 3 to 1. Despite these facts, there are little data available on this topic. The investigators in this proposal, therefore, propose a study which after assembling a suitable experimental setting will attempt to define the presently unknown biomechanical characteristics of stair descent. Essentially, three major groups of subjects will be studied. A healthy group of individuals, both young and elderly (70-79 years of age), an elderly group with a single prominent disability, and an elderly group with multiple deficits. Their specific aims are 1) to construct an experimental staircase that will enable the investigation of important biomechanical and visual aspects of stair use to be measured in a valid, safe and effective manner, 2) to define the biomechanical characteristics of stair descent under optimal, extrinsic conditions in healthy, unimpaired young and elderly subjects, 3) to define the biomechanical characteristics of stair descent under non-optimal, extrinsic and visual conditions in healthy, unimpaired young and elderly subjects, and 4) to understand how motor (osteoarthritic patients), somatosensory (neuropathic diabetic model), and multiple impairments (frail elderly) together with degraded extrinsic conditions affect the safety of elders during the different phases of stair descent.

bone density; exercise; biomechanics; bone metabolism; clinical research; female; young adult human (21-34); human subject;

Foot problems are widespread in the elderly and have an important influence on mobility. In persons with diabetes, foot deformities are of particular significance because they are widely believed to contribute to plantar ulceration which significantly increases the risk of lower extremity amputation. The proposed research is designed to examine the putative role of intrinsic muscle atrophy in the progression of foot deformity. We will first examine the status of symmetrical distal sensory motor neuropathy, foot deformity, and the ability to develop toe flexor torque in a carefully chosen group of subjects with diabetes. MRI's of the feet will then be quantified to assess cross sectional areas of important intrinsic muscles and plantar pressure during gait will be measured. We hypothesize that sensory and motor neuropathy will proceed broadly in parallel, and that motor neuropathy is associated with intrinsic muscle atrophy, elevated plantar pressure, and clawing of the toes. There are three components to the significance of this research. First, it will enhance our basic understanding of an important disease process that leads to loss of limbs in the elderly. Second, it will contribute to a better understanding of diabetic peripheral neuropathy and its sequelae. Third, it should ultimately lead to an improvement in early recognition of feet that are at risk for ulceration.

DESCRIPTION(Provided by Applicant): The Orthopaedic Research Center of The Cleveland Clinic Foundation (CCF) plans a coordinated, training effort for which we request 2 pre-doctoral and 2 post-doctoral scientists, one clinician scientist, and three 12 week research experiences for medical students in Year 1. Investigators and clinician/scientists from the Departments of Biomedical Engineering and Orthopaedic Surgery are already actively collaborating in 3 broad areas: (1) bone biology and biomechanics, (2) soft tissue biology and biomechanics, (3) joint and whole-body biomechanics. These highly interactive areas offer substantial opportunities for didactic and bench-level training in areas ranging from cell/molecular biological techniques to in vivo or in vitro models and clinical research projects. Recruitment plans include incentives for a post-residency clinician-scientist to participate in one of a rich array of clinical-basic science partnerships. We outline the projected organizational and administrative structures necessary to ensure the success of these training opportunities. In addition to focused activities in each of the three topic areas, a range of integrative activities are planned to build upon an established record of education and training in the orthopaedic sciences at CCF. These include a 40-lecture basic science curriculum, two seminar series, bioethics and biostatistics lectures, grant preparation workshops, inventorship forums, teaching opportunities, and mandatory abstract submission to professional meetings. Institutional support will be provided for the salaries of the program directors and mentors, and for books and journals and for salary supplementation for the clinician-scientist. The goals outlined in this proposal align closely with the institution's efforts to encourage clinical and translational research in a General Clinical Research Center (approved in early 2003) and in the new Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, a research-based, 5-year program that will admit its first class in 2004.

Abstract The first metatarsophalangeal joint (MTPJ1) is one of the sites most commonly affected with osteoarthritis (OA). Worldwide, more than 1 in 5 people are estimated to have pain and functional deficits from MTPJ1 OA. In contrast to the widely performed joint replacement arthroplasties for degenerative OA at the hip and knee joints, the two most common surgical treatments for MTPJ1 osteoarthritis are cheilectomy and, for more severe cases, arthrodesis. Neither of these approaches have high rates of patient satisfaction. To date, various designs for MTPJ1 arthroplasty have been proposed, but none have been particularly successful. This is partly because of the relatively small amount of bone in the metatarsal head and proximal phalanx, making it difficult to achieve adequate fixation of the prosthetic components, leading to loosening of the implant over time. Hemi- caps are also available for both the metatarsal head and the phalangeal base and involve the removal of less bone, however failure rates remain high. Development of new implants that can address these problems is limited by the sparseness of the literature describing the mechanical environment of the MTPJ1, and there are no standardized open source models of the MTPJ1 available to the research community. Similarly, there is very little detailed information in the literature on the required 3D movement of the MTPJ1 during locomotor activities and what data is available is either from cadaver studies or from surface markers attached to the feet of walking subjects. It is likely that these approaches do not adequately capture the range or complexity of MTPJ1 movement due to unrealistic function and soft tissue artifacts. In this proposal we intend to fill these voids and to generate design criteria for MTPJ1 arthroplasty by: 1) building detailed, parametric models of the MTPJ1 using OpenSim and FEBio; 2) measuring the 3D motion of the first proximal phalanx and the 1st metatarsal bones in different footwear conditions during locomotion using biplane fluoroscopy. In the final phase of the project we will combine information from these two approaches and develop prototypes for new prostheses designed to overcome some of the limitations of previous devices. Specifically, we will explore methods to utilize screw fixation, similar to locking plates. Prototypes of these designs will be 3D printed in stainless steel and tested to assess feasibility and integrity in loading experiments with cadaver feet. We believe that the proposed work has the potential to reinvigorate the innovative study of MTPJ1 replacement, which is, at present, primarily driven by ideas not by data.