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1.  Heel pain and HIV-associated lipodystrophy: a report of two cases 
Plantar fasciitis is diagnosed based on a pathognomonic clinical presentation and physical examination including plantar heel pain with the initial few steps after a period of inactivity. People living with HIV/AIDS, who are taking anti-retroviral medications, often have an associated redistribution of body fat (lipodystrophy). Lipoatrophy of the extremities may involve the heel fat-pad in this population and result in the signs and symptoms of plantar fasciitis. Two cases of plantar heel pain in HIV-associated lipodystrophy are presented to discuss the possible clinical association between the two conditions. Although conservative therapies have limited evidence, they are commonly used and have been seen, clinically, to result in a resolution of symptoms. In the presented cases, the individuals benefited from soft tissue therapy, modalities, activity modification and education on proper footwear. Clinicians should be aware that the association between these two conditions may be a significant cause of morbidity in a population of patients with HIV.
PMCID: PMC2391020  PMID: 18516231
heel pain; lipodystrophy; HIV; chiropractic
2.  Clinical Characteristics of the Causes of Plantar Heel Pain 
Annals of Rehabilitation Medicine  2011;35(4):507-513.
The objectives of this study were to investigate the causes of plantar heel pain and find differences in the clinical features of plantar fasciitis (PF) and fat pad atrophy (FPA), which are common causes of plantar heel pain, for use in differential diagnosis.
This retrospective study analyzed the medical records of 250 patients with plantar heel pain at the Foot Clinic of Rehabilitation Medicine at Bundang Jesaeng General Hospital from January to September, 2008.
The subjects used in this study were 114 men and 136 women patients with a mean age of 43.8 years and mean heel pain duration of 13.3 months. Causes of plantar heel pain were PF (53.2%), FPA (14.8%), pes cavus (10.4%), PF with FPA (9.2%), pes planus (4.8%), plantar fibromatosis (4.4%), plantar fascia rupture (1.6%), neuropathy (0.8%), and small shoe syndrome (0.8%). PF and FPA were most frequently diagnosed. First-step pain in the morning, and tenderness on medial calcaneal tuberosity correlated with PF. FPA mainly involved bilateral pain, pain at night, and pain that was aggravated by standing. Heel cord tightness was the most common biomechanical abnormality of the foot. Heel spur was frequently seen in X-rays of patients with PF.
Plantar heel pain can be provoked by PF, FPA, and other causes. Patients with PF or FPA typically show different characteristics in clinical features. Plantar heel pain requires differential diagnosis for appropriate treatment.
PMCID: PMC3309235  PMID: 22506166
Plantar heel pain; Plantar fasciitis; Fat pad atrophy
3.  Fat Pad Entrapment at the Hip: A New Diagnosis 
PLoS ONE  2014;9(2):e83503.
To establish if a positive impingement sign in femoroacetabular impingement (FAI) may result from entrapment of the fat pad located at the anterior head-neck junction of the upper femur. This fat pad is routinely removed before any cam lesion excision.
We report a prospective study of 142 consecutive hip arthroscopies for symptomatic FAI where the aim was to remove the arthroscopically identified area of impingement, not necessarily to create a spherical femoral head. Patients were divided into two groups. Group 1 (n = 92; 34 females, 58 males), where a cam-type bony FAI lesion was identified and excised in addition to the fat pad which overlay it, and Group 2 (n = 50; 29 females, 21 males) where the only identified point of impingement was a prominent fat pad. In this situation the fat pad was excised in isolation and the underlying bone preserved. Patients were assessed preoperatively, at six weeks, six months, one year and two years with a modified Harris hip score (mHHS).
Both groups were comparable preoperatively for mean age, mean alpha angle and mean anterior offset ratio. Both groups improved significantly after surgery at all time points. However, Group 1 (fat pad and bone resection) demonstrated 16.0% improvement in mHHS by two years while for Group 2 (fat pad resection only) the improvement was 18.9% (p = 0.628).
The fat pad found at the anterior head/neck junction of the hip joint can be a source of pain and we propose fat pad entrapment as a new, previously undescribed diagnosis. Our findings also suggest that a large number of cam lesions are being excised unnecessarily and that further efforts should be made to understand the role of the fat pad as a source of groin discomfort.
Level of Evidence
Level IV, case series.
PMCID: PMC3935831  PMID: 24586225
4.  The impact of increasing body mass on peak and mean plantar pressure in asymptomatic adult subjects during walking 
Diabetic Foot & Ankle  2010;1:10.3402/dfa.v1i0.5518.
The implication of high peak plantar pressure on foot pathology in individuals both with and without diabetes has been recognized. The aim of this study was to investigate and clarify the relationship between increasing body mass and peak and mean plantar pressure in an asymptomatic adult population during walking.
Thirty adults without any relevant medical history, structural foot deformities or foot posture assessed as highly pronated or supinated, and within a normal body mass index range were included in the study. An experimental, same subjects, repeated measures design was used. Peak and mean plantar pressure were evaluated with the F-Scan in-shoe plantar pressure measurement system under four different loading conditions (0, 5, 10, and 15 kg) simulated with a weighted vest. Pressure data were gathered from three stances utilizing the mid-gait protocol.
There were statistically significant increases in peak pressure between the 10 and 15 kg load conditions compared to the control (0 kg) within the heel and second to fifth metatarsal regions. The first metatarsal and hallux regions only displayed statistically significant increases in peak pressure between 15 kg and the control (0 kg). The midfoot and lesser digits regions did not display any statistically significant differences in peak pressure between any load conditions compared to the control (0 kg). The second to fifth metatarsal region displayed statistically significant increases in mean pressure in the 5, 10 and 15 kg groups compared to the control (0 kg). A statistically significant increase in peak pressure between the 15 kg and control (0 kg) group was evident in all other regions.
The relationship between increasing body mass and peak and mean plantar pressure was dependent upon the plantar region. This study provides more detail outlining the response of peak and mean pressure to different loading conditions than previously reported in the literature. Further research including measurement of temporal parameters is warranted.
PMCID: PMC3284282  PMID: 22396809
plantar pressure; body mass index; obesity; diabetes; body weight; distribution
5.  Effect of Footwear and Orthotic Devices on Stress Reduction and Soft Tissue Strain of the Neuropathic Foot 
Ground reaction forces from walking result in stress (pressure) and soft tissue strain at the plantar aspect of the foot. Excessive plantar pressure and tissue strain on the insensate foot may lead to ulceration. Our study investigated the effect of therapeutic footwear and custom-made orthotic inserts on pressure and tissue strain along the second ray of the plantar foot, and how these two variables are associated.
Twenty subjects (mean age 57.3 [SD 9.3], 12 male, 8 female, body mass index 32.5 [SD 7.4]) with diabetes mellitus, peripheral neuropathy, and a history of a plantar ulcer participated. Plantar pressure data were recorded during computed tomography scans for four conditions (barefoot, shoe, shoe+total contact insert, and shoe+total contact insert+metatarsal pad). For each condition tested, tissue strain and plantar pressure were determined at the second metatarsal head and at 15 other points along the second ray.
Differences were noted between the 4 conditions for pressure (p < 0.004) and soft tissue strain (p < 0.042) at the second metatarsal head. Correlation coefficients demonstrated an association between pressure and strain (Barefoot r = 0.81, Shoe r = 0.75, Shoe+total contact insert r = 0.73, and Shoe+total contact insert+metatarsal pad r = 0.44).
Footwear and orthotic devices tested in this study decreased pressure and soft tissue strain at the second ray of the foot, and these two variables were strongly related. A better understanding of the role tissue strain plays in distributing plantar forces may lead to improvements in the design of orthotic devices.
PMCID: PMC1847616  PMID: 17182156
Plantar ulceration; Diabetes mellitus; Metatarsal pad; Total contact insert
6.  Foot Type Biomechanics Part 2: Are structure and anthropometrics related to function? 
Gait & posture  2012;37(3):10.1016/j.gaitpost.2012.09.008.
Many foot pathologies are associated with specific foot types. If foot structure and function are related, measurement of either could assist with differential diagnosis of pedal pathologies.
Biomechanical measures of foot structure and function are related in asymptomatic healthy individuals.
Sixty-one healthy subjects' left feet were stratified into cavus (n = 12), rectus (n = 27) and planus (n = 22) foot types. Foot structure was assessed by malleolar valgus index, arch height index, and arch height flexibility. Anthropometrics (height and weight), age, and walking speed were measured. Foot function was assessed by center of pressure excursion index, peak plantar pressure, maximum force, and gait pattern parameters. Foot structure and anthropometric variables were entered into stepwise linear regression models to identify predictors of function.
Measures of foot structure and anthropometrics explained 10–37% of the model variance (adjusted R2) for gait pattern parameters. When walking speed was included, the adjusted R2 increased to 45–77% but foot structure was no longer a factor. Foot structure and anthropometrics predicted 7–47% of the model variance for plantar pressure and 16–64% for maximum force parameters. All multivariate models were significant (p < 0.05), supporting acceptance of the hypothesis.
Discussion and conclusion
Foot structure and function are related in asymptomatic healthy individuals. The structural parameters employed are basic measurements that do not require ionizing radiation and could be used in a clinical setting. Further research is needed to identify additional predictive parameters (plantar soft tissue characteristics, skeletal alignment, and neuromuscular control) and to include individuals with pathology.
PMCID: PMC3878980  PMID: 23107624
Foot and ankle; Gait; Foot type; Plantar pressures; Structure and function
7.  Challenges associated with peripheral arterial disease in women 
Peripheral arterial disease (PAD) is an increasingly recognized disorder that is associated with functional impairment, quality-of-life deterioration, increased risk of cardiovascular ischemic events, and increased risk of total and cardiovascular mortality. Although earlier studies suggested that PAD was more common in men, recent reports based on more sensitive tests have shown that the prevalence of PAD in women is at least the same as in men, if not higher. PAD tends to present itself asymptomatically or with atypical symptoms more frequently in women than in men, and is associated with comorbidities or situations particularly or exclusively found in the female sex, such as osteoporosis, hypothyroidism, the use of oral contraceptives, and a history of complications during pregnancy. Fat-distribution patterns and differential vascular characteristics in women may influence the interpretation of diagnostic methods, whereas sex-related vulnerability to drugs typically used in subjects with PAD, differences in risk-factor distribution among sexes, and distinct responses to revascularization procedures in men and women must be taken into account for proper disease management. All these issues pose important challenges associated with PAD in women. Of note, this group has classically been underrepresented in research studies. As a consequence, several sex-related challenges regarding diagnosis and management issues should be acknowledged, and research gaps should be addressed in order to successfully deal with this major health issue.
Video abstract
PMCID: PMC3956880  PMID: 24648743
peripheral arterial disease; women; diagnosis; management
8.  Fibrolipoma with Osseous and Cartilaginous Metaplasia of Hoffa's Fat Pad: A Case Report 
Case Reports in Orthopedics  2012;2012:547963.
The most common benign tumors of the mesenchyme are the lipomas. Benign fatty tumors can arise in any location in which fat is present. Fibrolipomas are characterised by fat modules. Most patients affected by such tumors are in the fifth or sixth decade of life. When very close to vital structures such as joints, they may cause functional limitations as well as pain. Osseous and chondroid metaplasia can infrequently manifest after chronic persistence. Given the rarity of this condition, a case of a big fibrolipoma of Hoffa's fat pad with osseous and cartilaginous metaplasia is reported. A 44-year-old woman presented with an enlarging soft mass on the right knee in the infrapatellar fat pad. After a thorough preoperative clinical and imaging examination, the mass was removed and sent to laboratory where the diagnosis was put. One year after surgery, both local and general condition of the patient were good and no signs of recurrence were found.
PMCID: PMC3504234  PMID: 23259124
9.  Interface corrective force measurements in Boston brace treatment 
European Spine Journal  2002;11(4):332-335.
Brace application has been reported to be effective in treating idiopathic adolescent scoliosis. The exact working mechanism of a thoracolumbo spinal orthosis is a result of different mechanisms and is not completely understood. One of the supposed working mechanisms is a direct compressive force working through the brace upon the body and thereby correcting the scoliotic deformity, achieving optimal fit of the individual orthosis. In this study we measured these direct forces exerted by the pads in a Boston brace in 16 patients with idiopathic adolescent scoliosis, using the electronic PEDAR measuring device (Novel, Munich, Germany). This is designed as an in-shoe measuring system consisting of two shoe insoles (size 8 1/2), wired to a computer, recording static and dynamic pressure distribution under the plantar surface of the foot. After positioning the inserts between the lumbar and thoracic pads and the body, we measured the forces acting upon the body in eight different postures. In all positions the mean corrective force through the lumbar brace pad was larger than the mean corrective force over the thoracic brace pad. Some changes in body posture resulted in statistically significant alterations in the exerted forces. There was no significant correlation between the magnitude of the compressive force over the lumbar and thoracic brace-pad and the degree of correction of the major curve. Comparing the corrective forces in a relatively new (<6 months) and old (>6 months) brace, there was no statistically relevant difference, although the corrective force was slightly larger in the new braces. We think that the use of this pressure measurement device is practicable and of value for studies of the working mechanism of brace treatment, and in the future it might be of help in achieving optimal fit of the individual orthosis.
PMCID: PMC3610478  PMID: 12193994
Idiopathic scoliosis Brace treatment Corrective force measurements
10.  Pathological anatomy and dynamic effect of the displaced plantar plate and the importance of the integrity of the plantar plate-deep transverse metatarsal ligament tie-bar. 
Normal and deformed forefeet have been investigated by cadaver anatomical dissections and experiments, by radiographs, CT and MRI scanning, and by clinical studies. Evidence is presented to show that the skeleton of the foot rests on and is controlled by a multi-segmental ligamentous and fascial tie-bar system. Transversely across the plantar aspect of the forefoot, the plantar plates and the deep transverse metatarsal ligaments form a strong ligamentous structure which prevents undue splaying of the forefoot. Longitudinally, the five digital processes of the deeper layer of the plantar fascia are inserted into the plantar plates and control the longitudinal arch of the foot. It is suggested that many forefoot deformities result from the failure of parts of the tie-bar system and the dynamic effect of displacement of the plantar plates. Understanding this allows a more logical approach to their treatment.
PMCID: PMC2502622  PMID: 9038498
11.  Subcalcaneal Bursitis With Plantar Fasciitis Treated by Arthroscopy 
Arthroscopy Techniques  2013;2(2):e135-e139.
We report the successful arthroscopic treatment of a case of subcalcaneal bursitis with plantar fasciitis. To our knowledge, this is the first report on arthroscopic excision of a subcalcaneal bursa. Right heel pain developed in a 50-year-old woman, without any obvious cause. She reported that the heel pain occurred immediately after waking and that the heel ached when she walked. Magnetic resonance imaging showed an extra-articular, homogeneous, high-intensity lesion in the fat pad adjacent to the calcaneal tubercle on T2-weighted sagittal and coronal images and thickening of the plantar fascia on T2-weighted sagittal images. A diagnosis of a recalcitrant subcalcaneal bursitis with plantar fasciitis was made, and surgery was performed. The arthroscope was placed between the calcaneus and the plantar fascia. With the surgeon viewing from the lateral portal and working from the medial portal, the dorsal surface of the degenerative plantar fascia was debrided and the medial half of the plantar fascia was released, followed by debridement of the subcalcaneal bursal cavity through the incised plantar fascia. Full weight bearing and gait were allowed immediately after the operation. At the latest follow-up, the patient had achieved complete resolution of heel pain without a recurrence of the mass, confirmed by magnetic resonance imaging.
PMCID: PMC3716222  PMID: 23875139
12.  Age-associated increases in the size of the infrapatellar fat pad in knee osteoarthritis as measured by 3T MRI 
Obesity, as a primary risk factor for osteoarthritis, has been shown to alter joint loading, but may also result in metabolic changes characterized by chronic, low-level inflammation due to increased circulating levels of adipose-derived cytokines, or “adipokines”. The presence of the infrapatellar fat pad in the knee suggests that local changes in adipokine concentrations may influence knee osteoarthritis. This study examined the hypotheses that the volume of the infrapatellar fat pad is correlated to the body mass index (BMI) of osteoarthritis patients, and that fat pad volume is greater in subjects with osteoarthritis. Fat pad volume was measured in sequential magnetic resonance images taken over one year in a cohort of 15 control and 15 knee osteoarthritis subjects. No differences were observed in the fat pad volume between the two groups at baseline, 3, 6, or 12 months. In control subjects, no significant correlations were present between any parameters (age, BMI, weight, volume of fat pad at any time point). However, in the osteoarthritic group, fat pad volume was correlated with age at every time point. One possible explanation is that local factors related to knee osteoarthritis may also induce enlargement of the fat pad with age. Alternatively, subjects who are prone to growth or enlargement of the fat pad may also be more prone to symptomatic osteoarthritis. These findings provide intriguing preliminary data on the potential role of the infrapatellar fat pad in osteoarthritis, although additional study is required to better understand the mechanisms of this relationship.
PMCID: PMC3625521  PMID: 20225314
arthritis; obesity; Hoffa’s fat pad; leptin; adipokine; cytokine; magnetic resonance imaging
Circulation  2009;120(12):1048-1055.
Associations of pathophysiologic calf muscle characteristics with functional decline in people with lower extremity peripheral arterial disease (PAD) are unknown.
Three hundred seventy participants with PAD underwent baseline measurement of calf muscle area, density, and percent fat using computed tomography. Participants were followed annually for two years. The outcome of mobility loss was defined as becoming unable to walk ¼ mile or walk up and down one flight of stairs without assistance, among those without baseline mobility limitations. Additional outcomes were ≥ 20% decline in six-minute walk distance and becoming unable to walk for six minutes continuously among participants who walked continuously for six minutes at baseline. Adjusting for age, sex, race, body mass index, the ankle brachial index, smoking, physical activity, relevant medications, and comorbidities, lower calf muscle density (p trend < 0.001) and lower calf muscle area (p trend =0.039) were each associated with increased mobility loss rates. Compared to participants in the highest baseline tertiles, participants in the lowest tertile of calf muscle percent fat had a hazard ratio of 0.18 for incident mobility loss (95% CI = 0.06–0.55, p=0.003), and participants in the lowest tertile of muscle density had a 3.50 hazard ratio for incident mobility loss (95% CI= 1.28–9.57, p=0.015). No significant associations of calf muscle characteristics with six-minute walk outcomes were observed.
Our findings suggest that interventions to prevent mobility loss in PAD should focus on reversing pathophysiologic findings in calf muscle.
PMCID: PMC3246405  PMID: 19738138
Intermittent claudication; mobility; peripheral arterial disease; physical functioning
14.  Mid foot kinetics characterize structural polymorphism in diabetic foot disease 
Diabetic foot disease is characterized by progressive foot deformities that lead to amputation and disabling morbidity. The purpose is to investigate the classification of two distinct phenotypes of mid foot structural polymorphism in individuals using plantar kinetic and pressure distribution and tarsal bone density assessments.
Twenty-two individuals (26 ft) with diabetes mellitus, peripheral neuropathy and at least one mid foot deformity were compared to 29 age-, gender- and race-matched healthy controls (58 ft). Eleven subjects with diabetes mellitus and peripheral neuropathy (11 ft) had lateral deformity; 11 subjects (15 ft) had medial deformity. Each subject had calcaneal bone mineral density and plantar force and pressure assessments walking barefoot over an EMED-ST P-2 platform.
Control subjects had lower mid foot vertical forces and pressures despite significantly higher preferred walking speed. In subjects with diabetes and neuropathy, maximum vertical force was 6-fold greater, force–time integral 9.5-fold greater, peak pressure 6.7-fold higher, pressure–time integral was 9.7-fold greater, contact area 2-fold greater and contact time 1.9-fold higher than controls. Pressure values were larger in involved vs uninvolved (P ≤ 0.05). During stance in the mid foot, subjects with medial column phenotype showed greater pressure in the medial mask; subjects with lateral column phenotype had greater pressures in the lateral mask (P < 0.05). Calcaneal bone density was lower for the deformity foot vs the non-deformity foot; bone mineral density was lower in medial column phenotype vs lateral column phenotype (P = 0.02).
Diabetic foot disease can be classified as stereotypical, structurally-distinct phenotypes of deformities of the medial and lateral columns of the mid foot. Assessments of pedal bone density and plantar mid foot force and pressure during barefoot walking can characterize the structural polymorphic phenotypes and may assist the foot care specialist in clinical decision making.
PMCID: PMC2517423  PMID: 17602806
Mid foot deformity; Plantar pressure; Tarsal bone density
We studied whether lower calf muscle density and poorer upper and lower extremity strength are associated with higher mortality rates in men and women with PAD.
Men and women with lower extremity peripheral arterial disease (PAD) have lower calf muscle density and reduced lower extremity strength compared to individuals without PAD.
At baseline, participants underwent measurement of calf muscle density with computed tomography in addition to knee extension power, and isometric knee extension, plantar flexion, and hand grip strength measures. Participants were followed annually for up to four years. Results are adjusted for age, sex, race, body mass index, the ankle brachial index (ABI), smoking, physical activity, and comorbidities.
Among 434 PAD participants, 103 (24%) died during a mean follow-up of 47.6 months. Lower calf muscle density was associated with higher all-cause mortality (lowest density tertile-hazard ratio (HR)=1.80 (95% Confidence Interval (CI)-1.07-3.03), 2nd tertile-HR=0.91 (95% CI-0.51-1.62); highest density tertile (HR=1.00), P trend=0.020) and higher cardiovascular disease mortality (lowest density tertile-HR=2.39 (95% CI-0.90-6.30), 2nd tertile-HR=0.85 (95% CI-0.27-2.71); highest density tertile (HR=1.00), P trend=0.047). Poorer plantar flexion strength (P trend=0.004), lower baseline leg power (P trend=0.046), and poorer handgrip (P trend=0.005) were associated with higher all-cause mortality.
These data demonstrate that lower calf muscle density and weaker plantar flexion strength, knee extension power, and hand grip are associated with increased mortality in participants with PAD, independently of the ABI and other confounders.
PMCID: PMC3465664  PMID: 22440216
Mortality; intermittent claudication; prognosis; Physical functioning
16.  Diverse and Active Roles for Adipocytes During Mammary Gland Growth and Function 
The mammary gland is unique in its requirement to develop in close association with a depot of adipose tissue that is commonly referred to as the mammary fat pad. As discussed throughout this issue, the mammary fat pad represents a complex stromal microenvironment that includes a variety of cell types. In this article we focus on adipocytes as local regulators of epithelial cell growth and their function during lactation. Several important considerations arise from such a discussion. There is a clear and close interrelationship between different stromal tissue types within the mammary fat pad and its adipocytes. Furthermore, these relationships are both stage- and species-dependent, although many questions remain unanswered regarding their roles in these different states. Several lines of evidence also suggest that adipocytes within the mammary fat pad may function differently from those in other fat depots. Finally, past and future technologies present a variety of opportunities to model these complexities in order to more precisely delineate the many potential functions of adipocytes within the mammary glands. A thorough understanding of the role for this cell type in the mammary glands could present numerous opportunities to modify both breast cancer risk and lactation performance.
PMCID: PMC2941079  PMID: 20717712
Mammary fat pad; Adipose; Epithelial-stromal; Adipokine
17.  Correlations between subjective treatment responses and plantar pressure parameters of metatarsal pad treatment in metatarsalgia patients: a prospective study 
Metatarsalgia is related to repetitive high-pressure loading under the metatarsal head (MH) that causes pain. The high pressure under the MH can be reduced by adequately applying metatarsal pads (MPs). Plantar pressure measurements may provide a method to objectively evaluate pressure loading under the MH. However, it is still unclear if the decrease in plantar pressure under the MH after MP treatment is associated with subjective improvement. This study aims to explore the correlations between subjective pain improvement and outcome rating, and the plantar pressure parameters in metatarsalgia patients treated using MPs.
Thirteen patients (a total of 18 feet) with secondary metatarsalgia were included in this study. Teardrop-shaped MPs made of polyurethane foam were applied just proximal to the second MH by an experienced physiatrist. Insole plantar pressure was measured under the second MH before and after MP application. Visual analog scale (VAS) scores of pain were obtained from all subjects before and after 2 weeks of MP treatment. The subjects rated using four-point subjective outcome scales. The Wilcoxon signed-rank test was used to analyze the difference between the plantar pressure parameters and VAS scores before and after treatment. The Kruskal-Wallis test was applied to compare the plantar pressure parameters in each outcome group. Pearson's correlation was applied to analyze the correlation between the changes in plantar pressure parameters and VAS scores. Statistical significance was set as p < 0.05.
MP application decreased the maximal peak pressure (MPP) and pressure-time integral (PTI) under the second MH and also statistically improved subjective pain scores. However, neither the pre-treatment values of the MPP and PTI shift in the position of the MPP after treatment, nor the age, gender and body mass index (BMI) of the subjects were statistically correlated with subjective improvement. Declines in the PTI and MPP values after MP application were statistically correlated with the improvement in VAS scores (r = 0.77, R2 = 0.59, p < 0.001; r = 0.60, R2 = 0.36, p = 0.009).
We found that the successful decline in the PTI and MPP under the second MH after MP application was correlated to subjective pain improvement. This study provides a strategy for the further design and application of MPs for metatarsalgia treatment.
PMCID: PMC1712337  PMID: 17147793
18.  Elastic modulus of tree frog adhesive toe pads 
Previous work using an atomic force microscope in nanoindenter mode indicated that the outer, 10- to 15-μm thick, keratinised layer of tree frog toe pads has a modulus of elasticity equivalent to silicone rubber (5–15 MPa) (Scholz et al. 2009), but gave no information on the physical properties of deeper structures. In this study, micro-indentation is used to measure the stiffness of whole toe pads of the tree frog, Litoria caerulea. We show here that tree frog toe pads are amongst the softest of biological structures (effective elastic modulus 4–25 kPa), and that they exhibit a gradient of stiffness, being stiffest on the outside. This stiffness gradient results from the presence of a dense network of capillaries lying beneath the pad epidermis, which probably has a shock absorbing function. Additionally, we compare the physical properties (elastic modulus, work of adhesion, pull-off force) of the toe pads of immature and adult frogs.
Electronic supplementary material
The online version of this article (doi:10.1007/s00359-011-0658-1) contains supplementary material, which is available to authorized users.
PMCID: PMC3176399  PMID: 21667266
Tree frog; Adhesion; Micro-indentation; Effective elastic modulus; Litoria caerulea
19.  The effect of different depths of medial heel skive on plantar pressures 
Foot orthoses are often used to treat lower limb injuries associated with excessive pronation. There are many orthotic modifications available for this purpose, with one being the medial heel skive. However, empirical evidence for the mechanical effects of the medial heel skive modification is limited. This study aimed to evaluate the effect that different depths of medial heel skive have on plantar pressures.
Thirty healthy adults (mean age 24 years, range 18–46) with a flat-arched or pronated foot posture and no current foot pain or deformity participated in this study. Using the in-shoe pedar-X® system, plantar pressure data were collected for the rearfoot, midfoot and forefoot while participants walked along an 8 metre walkway wearing a standardised shoe. Experimental conditions included a customised foot orthosis with the following 4 orthotic modifications: (i) no medial heel skive, (ii) a 2 mm medial heel skive, (iii) a 4 mm medial heel skive and (iv) a 6 mm medial heel skive.
Compared to the foot orthosis with no medial heel skive, statistically significant increases in peak pressure were observed at the medial rearfoot – there was a 15% increase (p = 0.001) with the 4 mm skive and a 29% increase (p < 0.001) with the 6 mm skive. No significant change was observed with the 2 mm medial heel skive. With respect to the midfoot and forefoot, there were no significant differences between the orthoses.
This study found that a medial heel skive of 4 mm or 6 mm increases peak pressure under the medial rearfoot in asymptomatic adults with a flat-arched or pronated foot posture. Plantar pressures at the midfoot and forefoot were not altered by a medial heel skive of 2, 4 or 6 mm. These findings provide some evidence for the effects of the medial heel skive orthotic modification.
PMCID: PMC3431235  PMID: 22889267
Foot orthoses; Medial heel skive; Foot pronation; Flat-feet; Plantar pressures
20.  Peri-Aortic Fat Deposition Is Associated with Peripheral Arterial Disease: The Framingham Heart Study 
Central obesity is associated with peripheral arterial disease (PAD), suggesting that ectopic fat depots may be associated with localized diseases of the aorta and lower extremity arteries. We hypothesized that individuals with greater amounts of peri-aortic fat are more likely to have clinical peripheral arterial disease (PAD) and a low ankle-brachial index (ABI).
Methods and Results
We quantified peri-aortic fat surrounding the thoracic aorta using a novel volumetric quantitative approach in 1205 individuals from the Framingham Heart Study Offspring cohort (mean age 65.9 years, 54% women); visceral abdominal fat (VAT) was also measured. Clinical PAD was defined as a history of intermittent claudication and ABI was dichotomized as low ABI≤0.9 or lower extremity revascularization vs normal ABI >0.9 to < 1.4. Regression models were created to examine the association between peri-aortic fat and intermittent claudication or low ABI (n=66 participants). In multivariable logistic regression, per 1 standard deviation increase in peri-aortic fat, the odds ratio (OR) for the combined end-point was 1.52 (p-value=0.004); these results were strengthened with additional adjustment for BMI (OR 1.69, p=0.002) or visceral abdominal fat (OR 1.67, p=0.009) whereas no association was observed for VAT (p=0.16). Similarly, per standard deviation increase in BMI or waist circumference, no association was observed after accounting for VAT (p=0.35 [BMI]; p=0.49 [waist circumference]).
Peri-aortic fat is associated with low ABI and intermittent claudication.
PMCID: PMC3060043  PMID: 20639302
obesity; atherosclerosis; peripheral arterial disease
21.  Distribution and correlates of plantar hyperkeratotic lesions in older people 
Plantar hyperkeratotic lesions are common in older people and are associated with pain, mobility impairment and functional limitations. However, little has been documented in relation to the frequency or distribution of these lesions. The aim of this study was to document the occurrence of plantar hyperkeratotic lesions and the patterns in which they occur in a random sample of older people.
A medical history questionnaire was administered to a random sample of 301 people living independently in the community (117 men, 184 women) aged between 70 and 95 years (mean 77.2, SD 4.9), who also underwent a clinical assessment of foot problems, including the documentation of plantar lesion locations, toe deformities and the presence and severity of hallux valgus.
Of the 301 participants, 180 (60%) had at least one plantar hyperkeratotic lesion. Those with plantar lesions were more likely to be female (χ2 = 18.75, p < 0.01; OR = 2.86), have moderate to severe hallux valgus (χ2 = 6.15, p < 0.02; OR = 2.95), a larger dorsiflexion range of motion at the ankle (39.4 ± 9.3 vs 36.3 ± 8.4°; t = 2.68, df = 286, p < 0.01), and spent more time on their feet at home (5.1 ± 1.0 vs 4.8 ± 1.3 hours, t = -2.46, df = 299, p = 0.01). No associations were found between the presence of plantar lesions and body mass index, obesity, foot posture, dominant foot or forefoot pain. A total of 53 different lesions patterns were observed, with the most common lesion pattern being "roll-off" hyperkeratosis on the medial aspect of the 1st metatarsophalangeal joint (MPJ), accounting for 12% of all lesion patterns. "Roll-off" lesions under the 1st MPJ and interphalangeal joint were significantly associated with moderate to severe hallux valgus (p < 0.05), whereas lesions under the central MPJs were significantly associated with deformity of the corresponding lesser toe (p < 0.05). Factor analysis indicated that 62% of lesion patterns could be grouped under three broad categories, relating to medial, central and lateral locations.
Plantar hyperkeratotic lesions affect 60% of older people and are associated with female gender, hallux valgus, toe deformity, increased ankle flexibility and time spent on feet, but are not associated with obesity, limb dominance, forefoot pain or foot posture. Although there are a wide range of lesion distribution patterns, most can be classified into medial, central or lateral groups. Further research is required to determine whether these patterns are related to the dynamic function of the foot or other factors such as foot pathology or morphology.
PMCID: PMC2669075  PMID: 19331676
22.  Blepharochalasis. 
Blepharochalasis is an uncommon disorder distinguished by recurrent episodes of eyelid oedema in young patients. A hypertrophic form, manifested as fat herniation, and an atrophic form, manifested as fat atrophy, have been described. Ptosis with excellent levator function, laxity of the lateral canthal structures with rounding of the lateral canthal angle, nasal fat pad atrophy, and redundant eyelid skin develop after many episodes of eyelid swelling. Fine wrinkling, atrophy, and telangiectasias characterise the excess eyelid skin. We describe four cases of this syndrome in which external levator aponeurosis tuck, blepharoplasty, lateral canthoplasty, and dermis fat grafts were used to correct atrophic blepharochalasis after the syndrome had run its course.
PMCID: PMC1041607  PMID: 3207663
23.  Lower Extremity Ischemia, Calf Skeletal Muscle Characteristics, and Functional Impairment in Peripheral Arterial Disease 
To determine whether lower ankle brachial index (ABI) levels are associated with lower calf skeletal muscle area and higher calf muscle percentage fat in persons with and without lower extremity peripheral arterial disease (PAD).
Three Chicago-area medical centers.
Four hundred thirty-nine persons with PAD (ABI<0.90) and 265 without PAD (ABI 0.90–1.30).
Calf muscle cross-sectional area and the percentage of fat in calf muscle were measured using computed tomography at 66.7% of the distance between the distal and proximal tibia. Physical activity was measured using an accelerometer. Functional measures included the 6-minute walk, 4-meter walking speed, and the Short Physical Performance Battery (SPPB).
Adjusting for age, sex, race, comorbidities, and other potential confounders, lower ABI values were associated with lower calf muscle area (ABI<0.50, 5,193 mm2; ABI 0.50–0.90, 5,536 mm2; ABI 0.91–1.30, 5,941 mm2; P for trend <.001). These significant associations remained after additional adjustment for physical activity. In participants with PAD, lower calf muscle area in the leg with higher ABI was associated with significantly poorer performance in usual- and fast-paced 4-meter walking speed and on the SPPB, adjusting for ABI, physical activity, percentage fat in calf muscle, muscle area in the leg with lower ABI, and other confounders (P<.05 for all comparisons).
These data support the hypothesis that lower extremity ischemia has a direct adverse effect on calf skeletal muscle area. This association may mediate previously established relationships between PAD and functional impairment.
PMCID: PMC2645649  PMID: 17341243
physical functioning; peripheral vascular disease; intermittent claudication; sarcopenia
24.  Age-Related Changes in the Epithelial and Stromal Compartments of the Mammary Gland in Normocalcemic Mice Lacking the Vitamin D3 Receptor 
PLoS ONE  2011;6(1):e16479.
The vitamin D3 receptor (VDR) serves as a negative growth regulator during mammary gland development via suppression of branching morphogenesis during puberty and modulation of differentiation and apoptosis during pregnancy, lactation and involution. To assess the role of the VDR in the aging mammary gland, we utilized 12, 14, and 16 month old VDR knockout (KO) and wild type (WT) mice for assessment of integrity of the epithelial and stromal compartments, steroid hormone levels and signaling pathways. Our data indicate that VDR ablation is associated with ductal ectasia of the primary mammary ducts, loss of secondary and tertiary ductal branches and atrophy of the mammary fat pad. In association with loss of the white adipose tissue compartment, smooth muscle actin staining is increased in glands from VDR KO mice, suggesting a change in the stromal microenviroment. Activation of caspase-3 and increased Bax expression in mammary tissue of VDR KO mice suggests that enhanced apoptosis may contribute to loss of ductal branching. These morphological changes in the glands of VDR KO mice are associated with ovarian failure and reduced serum 17β-estradiol. VDR KO mice also exhibit progressive loss of adipose tissue stores, hypoleptinemia and increased metabolic rate with age. These developmental studies indicate that, under normocalcemic conditions, loss of VDR signaling is associated with age-related estrogen deficiency, disruption of epithelial ductal branching, abnormal energy expenditure and atrophy of the mammary adipose compartment.
PMCID: PMC3027678  PMID: 21298063
25.  Hepatic fibrosis, glomerulosclerosis, and a lipodystrophy-like syndrome in PEPCK-TGF-beta1 transgenic mice. 
Journal of Clinical Investigation  1997;100(11):2697-2713.
Transgenic mice overexpressing a constitutively active human TGF-beta1 under control of the rat phosphoenolpyruvate carboxykinase regulatory sequences developed fibrosis of the liver, kidney, and adipose tissue, and exhibited a severe reduction in body fat. Expression of the transgene in hepatocytes resulted in increased collagen deposition, altered lobular organization, increased hepatocyte turnover, and in extreme cases, hemorrhage and thrombosis. Renal expression of the transgene was localized to the proximal tubule epithelium, and was associated with tubulointerstitial fibrosis, characterized by excessive collagen deposition and increased fibronectin and plasminogen activator inhibitor-1 immunoreactivity. Pronounced glomerulosclerosis was evident, and hydronephrosis developed with low penetrance. Expression of TGF-beta1 in white and brown adipose tissue resulted in a lipodystrophy-like syndrome. All white fat depots and brown fat pads were severely reduced in size, and exhibited prominent fibroplasia. This reduction in WAT was due to impaired adipose accretion. Introduction of the transgene into the ob/ob background suppressed the obesity characteristic of this mutation; however, transgenic mutant mice developed severe hepato- and splenomegaly. These studies strengthen the link between TGF-beta1 expression and fibrotic disease, and demonstrate the potency of TGF-beta1 in modulating mesenchymal cell differentiation in vivo.
PMCID: PMC508473  PMID: 9389733

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