Clinical factors associated with a conservative gait pattern in older male veterans with diabetes

<p>Abstract</p> <p>Background</p> <p>Patients with diabetes and peripheral neuropathy are at higher risk for falls. People with diabetes sometimes adopt a more conservative gait pattern with decreased walking speed, widened base, and increased double support time. The purpose of this study was to use a multivariate approach to describe this conservative gait pattern.</p> <p>Methods</p> <p>Male veterans (mean age = 67 years; SD = 9.8; range 37–86) with diabetes (n = 152) participated in this study from July 2000 to May 2001 at the Veterans Affairs Medical Center, White River Junction, VT. Various demographic, clinical, static mobility, and plantar pressure measures were collected. Conservative gait pattern was defined by visual gait analysis as failure to demonstrate a heel-to-toe gait during the propulsive phase of gait.</p> <p>Results</p> <p>Patients with the conservative gait pattern had lower walking speed and decreased stride length compared to normal gait. (0.68 m/s v. 0.91 m/s, <it>p </it>< 0.001; 1.04 m v. 1.24 m, <it>p </it>< 0.001) Age, monofilament insensitivity, and Romberg's sign were significantly higher; and ankle dorsiflexion was significantly lower in the conservative gait pattern group. In the multivariate analysis, walking speed, age, ankle dorsiflexion, and callus were retained in the final model describing 36% of the variance. With the inclusion of ankle dorsiflexion in the model, monofilament insensitivity was no longer an independent predictor.</p> <p>Conclusion</p> <p>Our multivariate investigation of conservative gait in diabetes patients suggests that walking speed, advanced age, limited ankle dorsiflexion, and callus describe this condition more so than clinical measures of neuropathy.</p

Foot kinematics in patients with two patterns of pathological plantar hyperkeratosis

Background: The Root paradigm of foot function continues to underpin the majority of clinical foot biomechanics practice and foot orthotic therapy. There are great number of assumptions in this popular paradigm, most of which have not been thoroughly tested. One component supposes that patterns of plantar pressure and associated hyperkeratosis lesions should be associated with distinct rearfoot, mid foot, first metatarsal and hallux kinematic patterns. Our aim was to investigate the extent to which this was true. Methods: Twenty-seven subjects with planter pathological hyperkeratosis were recruited into one of two groups. Group 1 displayed pathological plantar hyperkeratosis only under metatarsal heads 2, 3 and 4 (n = 14). Group 2 displayed pathological plantar hyperkeratosis only under the 1st and 5th metatarsal heads (n = 13). Foot kinematics were measured using reflective markers on the leg, heel, midfoot, first metatarsal and hallux. Results: The kinematic data failed to identify distinct differences between these two groups of subjects, however there were several subtle (generally <3°) differences in kinematic data between these groups. Group 1 displayed a less everted heel, a less abducted heel and a more plantarflexed heel compared to group 2, which is contrary to the Root paradigm. Conclusions: There was some evidence of small differences between planter pathological hyperkeratosis groups. Nevertheless, there was too much similarity between the kinematic data displayed in each group to classify them as distinct foot types as the current clinical paradigm proposes

Reliability of capturing foot parameters using digital scanning and the neutral suspension casting technique

<p>Abstract</p> <p>Background</p> <p>A clinical study was conducted to determine the intra and inter-rater reliability of digital scanning and the neutral suspension casting technique to measure six foot parameters. The neutral suspension casting technique is a commonly utilised method for obtaining a negative impression of the foot prior to orthotic fabrication. Digital scanning offers an alternative to the traditional plaster of Paris techniques.</p> <p>Methods</p> <p>Twenty one healthy participants volunteered to take part in the study. Six casts and six digital scans were obtained from each participant by two raters of differing clinical experience. The foot parameters chosen for investigation were cast length (mm), forefoot width (mm), rearfoot width (mm), medial arch height (mm), lateral arch height (mm) and forefoot to rearfoot alignment (degrees). Intraclass correlation coefficients (ICC) with 95% confidence intervals (CI) were calculated to determine the intra and inter-rater reliability. Measurement error was assessed through the calculation of the standard error of the measurement (SEM) and smallest real difference (SRD).</p> <p>Results</p> <p>ICC values for all foot parameters using digital scanning ranged between 0.81-0.99 for both intra and inter-rater reliability. For neutral suspension casting technique inter-rater reliability values ranged from 0.57-0.99 and intra-rater reliability values ranging from 0.36-0.99 for rater 1 and 0.49-0.99 for rater 2.</p> <p>Conclusions</p> <p>The findings of this study indicate that digital scanning is a reliable technique, irrespective of clinical experience, with reduced measurement variability in all foot parameters investigated when compared to neutral suspension casting.</p

Hallux rigidus: A cross-sectional study to evaluate clinical parameters

Background: Hallux rigidus (HR) is a common condition with history and physical examination used to help evaluate pathology, grade clinical changes and to inform treatment. Method: A cross-sectional study was undertaken to evaluate the demographics of and clinical parameters encountered in HR. In 110 subjects (180 feet) aged 18–70 years (mean 52 years) a standardized history and physical examination was undertaken. Clinical parameters associated with HR were evaluated. The Foot Health Status Questionnaire (FHSQ) was used to measure health-related quality-of-life dimensions. Results: Seventy (64%) subjects had bilateral HR and 73 (66%)were female. Mean HR onsetwas 44 (14–68 years) years and median HR duration 6 years (1–33 years). A history of 1st MTPJ trauma presented in 22% of subjects; 74% of whom had unilateral HR. Eighty-four (47%) feet had pes planus based on a positive Foot Posture Index. A correlation between pes planus and 1st MTPJ pain was found (r = 0.84, p = 0.05). In 74% of feet, hallux abductus interphalangeus angle (HAI◦) was greater than normal (≤10◦). A correlation between HAI and reduced 1st MTPJ ROM was found (r = 0.92, p = 0.05). Second toe length was the same as the hallux in 111 feet (62%). A correlation between valgus hallucal rotation and 1st MTP joint pain in HR was found (r = .78, p = .05). A positive relationship was found between 2nd toe length and 1st MTPJ pain (p = 0.001 < 0.05). A correlation between hallucal interphalangeal joint (IPJ) hyperextension and 1st MTPJ pain was found (r = 0.78, p = 0.01). A positive relationship was found between lesser MTPJ pain and supination at propulsion (p < 0.001). There was no evidence of Achilles tendon contracture. The FHSQ results concur with clinical findings. Conclusions: HR was associated with female gender, bilateral involvement, older age groups, increased HAI◦, 2nd toe length similar to hallux, hallucal IPJ hyperextension, lesser MTP joint pain, flat foot and certain gait alterations. HR was not associated with Achilles tendon tightness or footwear. The content validity of clinical parameters of HR needs to be established by formal research prior to their inclusion in a classification of H

A case-series study to explore the efficacy of foot orthoses in treating first metatarsophalangeal joint pain

Background: First metatarsophalangeal (MTP) joint pain is a common foot complaint which is often considered to be a consequence of altered mechanics. Foot orthoses are often prescribed to reduce 1 stMTP joint pain with the aim of altering dorsiflexion at propulsion. This study explores changes in 1 stMTP joint pain and kinematics following the use of foot orthoses.Methods: The effect of modified, pre-fabricated foot orthoses (X-line ®) were evaluated in thirty-two patients with 1 stMTP joint pain of mechanical origin. The primary outcome was pain measured at baseline and 24 weeks using the pain subscale of the foot function index (FFI). In a small sub-group of patients (n = 9), the relationship between pain and kinematic variables was explored with and without their orthoses, using an electromagnetic motion tracking (EMT) system.Results: A significant reduction in pain was observed between baseline (median = 48 mm) and the 24 week endpoint (median = 14.50 mm, z = -4.88, p &lt; 0.001). In the sub-group analysis, we found no relationship between pain reduction and 1 stMTP joint motion, and no significant differences were found between the 1 stMTP joint maximum dorsiflexion or ankle/subtalar complex maximum eversion, with and without the orthoses.Conclusions: This observational study demonstrated a significant decrease in 1 stMTP joint pain associated with the use of foot orthoses. Change in pain was not shown to be associated with 1 stMTP joint dorsiflexion nor with altered ankle/subtalar complex eversion. Further research into the effect of foot orthoses on foot function is indicated. © 2010 Welsh et al; licensee BioMed Central Ltd

Histone Deacetylase Inhibitor Modulates NKG2D Receptor Expression and Memory Phenotype of Human Gamma/Delta T Cells Upon Interaction With Tumor Cells

The functional plasticity and anti-tumor potential of human γδ T cells have been widely studied. However, the epigenetic regulation of γδ T-cell/tumor cell interactions has been poorly investigated. In the present study, we show that treatment with the histone deacetylase inhibitor Valproic acid (VPA) significantly enhanced the expression and/or release of the NKG2D ligands MICA, MICB and ULBP-2, but not ULBP-1 in the pancreatic carcinoma cell line Panc89 and the prostate carcinoma cell line PC-3. Under in vitro tumor co-culture conditions, the expression of full length and the truncated form of the NKG2D receptor in γδ T cells was significantly downregulated. Furthermore, using a newly established flow cytometry-based method to analyze histone acetylation (H3K9ac) in γδ T cells, we showed constitutive H3K9aclow and inducible H3K9achigh expression in Vδ2 T cells. The detailed analysis of H3K9aclow Vδ2 T cells revealed a significant reversion of TEMRA to TEM phenotype during in vitro co-culture with pancreatic ductal adenocarcinoma cells. Our study uncovers novel mechanisms of how epigenetic modifiers modulate γδ T-cell differentiation during interaction with tumor cells. This information is important when considering combination therapy of VPA with the γδ T-cell-based immunotherapy for the treatment of certain types of cancer

Movement of the human foot in 100 pain free individuals aged 18–45 : implications for understanding normal foot function

Background: Understanding motion in the normal healthy foot is a prerequisite for understanding the effects of pathology and thereafter setting targets for interventions. Quality foot kinematic data from healthy feet will also assist the development of high quality and research based clinical models of foot biomechanics. To address gaps in the current literature we aimed to describe 3D foot kinematics using a 5 segment foot model in a population of 100 pain free individuals. Methods: Kinematics of the leg, calcaneus, midfoot, medial and lateral forefoot and hallux were measured in 100 self reported healthy and pain free individuals during walking. Descriptive statistics were used to characterise foot movements. Contributions from different foot segments to the total motion in each plane were also derived to explore functional roles of different parts of the foot. Results: Foot segments demonstrated greatest motion in the sagittal plane, but large ranges of movement in all planes. All foot segments demonstrated movement throughout gait, though least motion was observed between the midfoot and calcaneus. There was inconsistent evidence of movement coupling between joints. There were clear differences in motion data compared to foot segment models reported in the literature. Conclusions: The data reveal the foot is a multiarticular structure, movements are complex, show incomplete evidence of coupling, and vary person to person. The data provide a useful reference data set against which future experimental data can be compared and may provide the basis for conceptual models of foot function based on data rather than anecdotal observations

Inhibition of Dehydration-Induced Water Intake by Glucocorticoids Is Associated with Activation of Hypothalamic Natriuretic Peptide Receptor-A in Rat

Atrial natriuretic peptide (ANP) provides a potent defense mechanism against volume overload in mammals. Its primary receptor, natriuretic peptide receptor-A (NPR-A), is localized mostly in the kidney, but also is found in hypothalamic areas involved in body fluid volume regulation. Acute glucocorticoid administration produces potent diuresis and natriuresis, possibly by acting in the renal natriuretic peptide system. However, chronic glucocorticoid administration attenuates renal water and sodium excretion. The precise mechanism underlying this paradoxical phenomenon is unclear. We assume that chronic glucocorticoid administration may activate natriuretic peptide system in hypothalamus, and cause volume depletion by inhibiting dehydration-induced water intake. Volume depletion, in turn, compromises renal water excretion. To test this postulation, we determined the effect of dexamethasone on dehydration-induced water intake and assessed the expression of NPR-A in the hypothalamus. The rats were deprived of water for 24 hours to have dehydrated status. Prior to free access to water, the water-deprived rats were pretreated with dexamethasone or vehicle. Urinary volume and water intake were monitored. We found that dexamethasone pretreatment not only produced potent diuresis, but dramatically inhibited the dehydration-induced water intake. Western blotting analysis showed the expression of NPR-A in the hypothalamus was dramatically upregulated by dexamethasone. Consequently, cyclic guanosine monophosphate (the second messenger for the ANP) content in the hypothalamus was remarkably increased. The inhibitory effect of dexamethasone on water intake presented in a time- and dose-dependent manner, which emerged at least after 18-hour dexamethasone pretreatment. This effect was glucocorticoid receptor (GR) mediated and was abolished by GR antagonist RU486. These results indicated a possible physiologic role for glucocorticoids in the hypothalamic control of water intake and revealed that the glucocorticoids can act centrally, as well as peripherally, to assist in the normalization of extracellular fluid volume

Glucocorticoids promote structural and functional maturation of foetal cardiomyocytes: a role for PGC-1α

Glucocorticoid levels rise dramatically in late gestation to mature foetal organs in readiness for postnatal life. Immature heart function may compromise survival. Cardiomyocyte glucocorticoid receptor (GR) is required for the structural and functional maturation of the foetal heart in vivo, yet the molecular mechanisms are largely unknown. Here we asked if GR activation in foetal cardiomyocytes in vitro elicits similar maturational changes. We show that physiologically relevant glucocorticoid levels improve contractility of primary-mouse-foetal cardiomyocytes, promote Z-disc assembly and the appearance of mature myofibrils, and increase mitochondrial activity. Genes induced in vitro mimic those induced in vivo and include PGC-1α, a critical regulator of cardiac mitochondrial capacity. SiRNA-mediated abrogation of the glucocorticoid induction of PGC-1α in vitro abolished the effect of glucocorticoid on myofibril structure and mitochondrial oxygen consumption. Using RNA sequencing we identified a number of transcriptional regulators, including PGC-1α, induced as primary targets of GR in foetal cardiomyocytes. These data demonstrate that PGC-1α is a key mediator of glucocorticoid-induced maturation of foetal cardiomyocyte structure and identify other candidate transcriptional regulators that may play critical roles in the transition of the foetal to neonatal heart