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1.  Diabetic Peripheral Neuropathy and Gait: Does Footwear Modify This Association? 
Gait-related fall risk is the leading cause of mortality among patients with diabetes, especially those older than 65 years. Deterioration in balance and loss of protective sensation in lower extremities contribute significantly to fall risk in patients with diabetic peripheral neuropathy (DPN). This study aimed to explore the impact of neuropathy and foot ulcer on gait.
We recruited 39 participants (age, 56.9 ± 8.2 years; body mass index, 29.6.3 ± 4.7 kg/m2), including 15 DPN patients without foot ulcers, 16 DPN patients with foot ulcers, and 8 healthy aged-matched controls. Patients with active foot ulcers wore an offloading device during gait examination, including removable cast walker.
Results suggest that neuropathy alters gait mainly by increasing gait initiation, gait variability (coefficient of variation of gait velocity), and double support (DS) time, while reducing knee range of motion and center of mass sway (p < .05). Interestingly, the presence of foot ulcer does not impact gait velocity (p > .1) but enhances some of the gait parameters such as gait variability and DS time.
This study demonstrates that neuropathy deteriorates gait, but the presence of foot ulcers does not alter gait parameters further than neuropathy. In addition, patients with foot ulcers demonstrated a better gait compared with DPN patients without ulcers. We speculate that offloading footwear may be enhancing the somatosensory feedback from sensate skin, thereby positively affecting gait parameters. A study with a larger sample is required to explore the effect of prescribed footwear in the DPN population in order to validate the findings of this research study.
PMCID: PMC3876356  PMID: 24124939
diabetes; foot ulcer; gait; offloading; wearable sensors
2.  Electrical Stimulation as an Adjunctive Treatment of Painful and Sensory Diabetic Neuropathy 
The objective of this review is to evaluate the use of electrical stimulation to treat diabetic neuropathy. Application of electrical stimulation may provide a novel treatment option for large and small fiber neuropathy in persons with diabetes. Large and small nerve neuropathy alters pain, proprioception, touch perception, and motor function, which cause burning foot pain and serve as protective mechanisms from ulcerations.
A content search for clinical trials involving electrical stimulation, neuropathy, and diabetes was conducted through PubMed. Randomized clinical trials and prospective studies with outcome measures affecting the lower extremity function were selected for review.
We identified eight studies in which electrical stimulation was used to treat diabetic neuropathy. Six studies evaluated small fiber neuropathy. Two studies evaluated patients with both small and large fiber neuropathy and reported significant improvement in vibration and monofilament testing and reduction in symptoms in the electrical stimulation treatment group. Six of the eight painful neuropathy studies identified significant improvement in symptoms. There were no studies that evaluated electrical stimulation to treated diabetic motor neuropathy, fall prevention or postural instability.
Electrical stimulation may be an effective alternative and adjunctive therapy to current interventions for diabetic peripheral neuropathy.
PMCID: PMC3876364  PMID: 24124947
diabetes; electrical stimulation; fall; infection; neuropathy; prevention; ulcer
3.  Virtualizing the Assessment: A Novel Pragmatic Paradigm to Evaluate Lower Extremity Joint Perception in Diabetes 
Gerontology  2012;58(5):463-471.
Persons with diabetes have a higher risk of falls and fall related injuries. People with diabetes often develop peripheral neuropathy (DPN) as well as nerve damage throughout the body. In particular, reduced lower extremity proprioception due to DPN may cause a misjudgment of foot position and thus increase the risk of fall.
An innovative virtual obstacle crossing (VOC) paradigm using wearable sensors was developed in attempt to assess lower extremity position perception damage due to DPN.
Sixty-seven participants (Age: 55.4±8.9; BMI: 28.1±5.8) including diabetes with and without DPN as well as aged matched healthy controls were recruited. Severity of neuropathy was quantified using vibratory perception threshold (VPT) test. The ability of perception of lower extremity was quantified by measuring obstacle crossing success rate (OCSR), toe-obstacle clearance (TOC), and reaction time (TR) while crossing a series of virtual obstacles with heights at 10% and 20% of the subject’s leg length.
No significant difference was found between groups for age and BMI. The data revealed that DPN subjects had a significantly lower OCSR compared to diabetes with no neuropathy and controls at obstacle size of 10% (p<0.05). DPN subjects also demonstrated longer TR compared to other groups and for both obstacle sizes. In addition TOC was reduced in neuropathy groups. Interestingly, a significant correlation between TR and VPT (r=0.5, p<10-5) was observed indicating delay in reaction by increasing neuropathy severity. The delay becomes more pronounced by increasing the size of obstacle. Using regression model suggests that the change in reaction time between obstacle sizes of 10% and 20% of leg size is the most sensitive predictors for neuropathy severity with an odds ratio of 2.70 (p=0.02).
The findings demonstrate proof of concept of virtual reality application as a promising method for objective assessment of neuropathy severity, however; a further study is warranted to establish a stronger relationship between the measured parameters and neuropathy.
PMCID: PMC3955209  PMID: 22572476
Virtual Reality; Diabetes Peripheral Neuropathy; Lower Extremity Joint Perception; Body Worn Sensors; Fall Prevention; Obstacle crossing
4.  Effect of P2X4 and P2X7 receptor antagonism on the pressure diuresis relationship in rats 
Reduced glomerular filtration, hypertension and renal microvascular injury are hallmarks of chronic kidney disease, which has a global prevalence of ~10%. We have shown previously that the Fischer (F344) rat has lower GFR than the Lewis rat, and is more susceptible to renal injury induced by hypertension. In the early stages this injury is limited to the pre-glomerular vasculature. We hypothesized that poor renal hemodynamic function and vulnerability to vascular injury are causally linked and genetically determined. In the present study, normotensive F344 rats had a blunted pressure diuresis relationship, compared with Lewis rats. A kidney microarray was then interrogated using the Endeavour enrichment tool to rank candidate genes for impaired blood pressure control. Two novel candidate genes, P2rx7 and P2rx4, were identified, having a 7− and 3− fold increased expression in F344 rats. Immunohistochemistry localized P2X4 and P2X7 receptor expression to the endothelium of the pre-glomerular vasculature. Expression of both receptors was also found in the renal tubule; however there was no difference in expression profile between strains. Brilliant Blue G (BBG), a relatively selective P2X7 antagonist suitable for use in vivo, was administered to both rat strains. In Lewis rats, BBG had no effect on blood pressure, but increased renal vascular resistance, consistent with inhibition of some basal vasodilatory tone. In F344 rats BBG caused a significant reduction in blood pressure and a decrease in renal vascular resistance, suggesting that P2X7 receptor activation may enhance vasoconstrictor tone in this rat strain. BBG also reduced the pressure diuresis threshold in F344 rats, but did not alter its slope. These preliminary findings suggest a physiological and potential pathophysiological role for P2X7 in controlling renal and/or systemic vascular function, which could in turn affect susceptibility to hypertension-related kidney damage.
PMCID: PMC3807716  PMID: 24187541
purinergic; ATP; kidney disease; renal injury; renal vascular resistance
5.  Improving immunisation timeliness in Aboriginal children through personalised calendars 
BMC Public Health  2013;13:598.
Delayed immunisation and vaccine preventable communicable disease remains a significant health issue in Aboriginal children. Strategies to increase immunisation coverage and timeliness can be resource intensive. In a low cost initiative at the Aboriginal Medical Service Western Sydney (AMSWS) in 2008–2009, a trial of personalised calendars to prompt timely childhood immunisation was undertaken.
Calendars were generated during attendances for early childhood immunisations. They were designed for display in the home and included the due date of the next immunisation, a photo of the child and Aboriginal artwork. In a retrospective cohort design, Australian Childhood Immunisation Register data from AMSWS and non-AMSWS providers were used to determine the delay in immunisation and percentage of immunisations on time in those who received a calendar compared to those who did not. Interviews were undertaken with carers and staff.
Data on 2142 immunisation doses given to 505 children were analysed, utilising pre-intervention (2005–2007) and intervention (2008–2009) periods and a 2 year post-intervention observation period. 113 calendars were distributed (30% of eligible immunisation attendances). Improvements in timeliness were seen at each schedule point for those children who received a calendar. The average delay in those who received a calendar at their previous visit was 0.6 months (95% CI -0.8 to 2.6) after the due date, compared to 3.3 months (95% CI −0.6 to 7.5) in those who did not. 80% of doses were on time in the group who received a calendar at the preceding immunisation, 66% were on time for those who received a calendar at an earlier point and 57% of doses were on time for those who did not receive a calendar (P<0.0001, Cochran-Armitage trend test). Interview data further supported the value and effectiveness of the calendars as both a prompt to timely immunisations and a community health education project without undue resource implications.
Personalised calendars can increase the timeliness of immunisations in Aboriginal children. This simple, low cost tool appears practicable and effective in an Aboriginal community setting in improving early childhood vaccination timeliness and has high potential for local adaptation to suit the needs of diverse communities.
PMCID: PMC3704958  PMID: 23786829
Immunisation; Indigenous; Aboriginal; Timeliness of immunisation; Delayed immunisation
6.  No evidence of increasing Haemophilus influenzae non-b infection in Australian Aboriginal children 
International Journal of Circumpolar Health  2013;72:10.3402/ijch.v72i0.20992.
High, or increasing, rates of invasive Haemophilus influenzae (Hi) type a disease have been reported from North American native children from circumpolar regions, raising the question of serotype replacement being driven by vaccination against Hi type b (Hib). Indigenous Australians from remote areas had high rates of invasive Hib disease in the past, comparable to those in North American Indigenous populations.
Evaluate incidence rates of invasive Hi (overall and by serotype) in Indigenous Australian children over time.
Descriptive study of Hi incidence rates by serotype, in the Northern Territory (NT) and South Australia (SA) from 2001 to 2011. Comparison of NT data with a study that was conducted in the NT in 1985–1988, before Hib vaccine was introduced.
The average annual rate of invasive Hi type a (Hia) disease in Indigenous children aged <5 years was 11/100,000 population. Although the incidence of Hi infection in Indigenous children in 2001–2003 was lower than during 2004–2011, this may be due to changes in surveillance. No other trend over time in individual serotypes or total invasive Hi disease, in Indigenous or non-Indigenous people, was identified. Compared to 1985–1988, rates in 2001–2011 were lower in all serotype groupings, by 98% for Hib, 75% for Hia, 79% for other serotypes and 67% for non-typeable Hi.
There is no evidence of increases in invasive disease due to Hia, other specific non-b types, or non-typeable Hi in Australian Indigenous children. These data suggest that the increase in Hia some time after the introduction of Hib vaccine, as seen in the North American Arctic Region, is not common to all populations with high pre-vaccine rates of invasive Hib disease. However, small case numbers and the lack of molecular subtyping and PCR confirmation of pre-vaccine results complicate comparisons with North American epidemiology.
PMCID: PMC3753125  PMID: 23984279
Haemophilus influenza; oceanic ancestry group; epidemiology
7.  Plantar Temperature Response to Walking in Diabetes with and without Acute Charcot: The Charcot Activity Response Test 
Journal of Aging Research  2012;2012:140968.
Objective. Asymmetric plantar temperature differences secondary to inflammation is a hallmark for the diagnosis and treatment response of Charcot foot syndrome. However, little attention has been given to temperature response to activity. We examined dynamic changes in plantar temperature (PT) as a function of graduated walking activity to quantify thermal responses during the first 200 steps. Methods. Fifteen individuals with Acute Charcot neuroarthropathy (CN) and 17 non-CN participants with type 2 diabetes and peripheral neuropathy were recruited. All participants walked for two predefined paths of 50 and 150 steps. A thermal image was acquired at baseline after acclimatization and immediately after each walking trial. The PT response as a function of number of steps was examined using a validated wearable sensor technology. The hot spot temperature was identified by the 95th percentile of measured temperature at each anatomical region (hind/mid/forefoot). Results. During initial activity, the PT was reduced in all participants, but the temperature drop for the nonaffected foot was 1.9 times greater than the affected side in CN group (P = 0.04). Interestingly, the PT in CN was sharply increased after 50 steps for both feet, while no difference was observed in non-CN between 50 and 200 steps. Conclusions. The variability in thermal response to the graduated walking activity between Charcot and non-Charcot feet warrants future investigation to provide further insight into the correlation between thermal response and ulcer/Charcot development. This stress test may be helpful to differentiate CN and its response to treatment earlier in its course.
PMCID: PMC3413979  PMID: 22900177
8.  Resistance Exercise and Lipoproteins in Postmenopausal Women 
The specific aims of this study were to quantify the effects of 12 weeks of resistance training, as well as a single session of resistance exercise on lipids and lipoproteins in obese, postmenopausal women. Twenty-one obese, postmenopausal women, not on hormone replacement therapy (age = 65.9 ± 0.5 yr; BMI = 32.7 ± 0.8 kg/m2), were randomly assigned to control (n=12) and exercise (n=9) groups matched for age and BMI. For 12 weeks, 3 days/week, the exercise group performed 10 whole body resistance exercises (3 sets at 8-RM). Fasting (10 hr) blood samples were collected immediately prior to and 24 hr after the first and last exercise and control session. Serum was assayed for concentrations of total cholesterol, triglycerides, LDL-C, HDL-C, HDL2-C, HDL3-C, non-HDL-C and TC:HDL and LDL:HDL ratios. The exercise group exhibited a significant (P < 0.01) improvement in muscular strength, but no change in BMI, body mass or body composition post-training. Total cholesterol, LDL-C and non-HDL-C were significantly (P < 0.05) lower in the exercise compared to the control group following the 12 weeks of resistance training. Whole body resistance training provides obese, postmenopausal women a non-pharmacological approach for the reduction of lipid and lipoprotein-cholesterol concentrations.
PMCID: PMC3354704  PMID: 21086242
cholesterol; exercise; menopause; obesity
9.  Activation of Thiazide-Sensitive Co-Transport by Angiotensin II in the cyp1a1-Ren2 Hypertensive Rat 
PLoS ONE  2012;7(4):e36311.
Transgenic rats with inducible expression of the mouse Ren2 gene were used to elucidate mechanisms leading to the development of hypertension and renal injury. Ren2 transgene activation was induced by administration of a naturally occurring aryl hydrocarbon, indole-3-carbinol (100 mg/kg/day by gastric gavage). Blood pressure and renal parameters were recorded in both conscious and anesthetized (butabarbital sodium; 120 mg/kg IP) rats at selected time-points during the development of hypertension. Hypertension was evident by the second day of treatment, being preceded by reduced renal sodium excretion due to activation of the thiazide-sensitive sodium-chloride co-transporter. Renal injury was evident after the first day of transgene induction, being initially limited to the pre-glomerular vasculature. Mircoalbuminuria and tubuloinsterstitial injury developed once hypertension was established. Chronic treatment with either hydrochlorothiazide or an AT1 receptor antagonist normalized sodium reabsorption, significantly blunted hypertension and prevented renal injury. Urinary aldosterone excretion was increased ∼20 fold, but chronic mineralocorticoid receptor antagonism with spironolactone neither restored natriuretic capacity nor prevented hypertension. Spironolactone nevertheless ameliorated vascular damage and prevented albuminuria. This study finds activation of sodium-chloride co-transport to be a key mechanism in angiotensin II-dependent hypertension. Furthermore, renal vascular injury in this setting reflects both barotrauma and pressure-independent pathways associated with direct detrimental effects of angiotensin II and aldosterone.
PMCID: PMC3338649  PMID: 22558431
10.  Mannequins have feelings too 
BMJ : British Medical Journal  2008;336(7636):145.
PMCID: PMC2206256
11.  The intubating laryngeal mask: is there a role for paramedics? 
Emergency Medicine Journal : EMJ  2007;24(3):198-199.
To compare the ability of UK paramedics to intubate a simulated difficult airway using a Mackintosh laryngoscope versus an intubating laryngeal mask airway (ILMA).
A randomised controlled trial.
100% of the paramedics were able to intubate a simulated difficult airway using the ILMA versus 0% of those using the Mackintosh laryngoscope.
This study has demonstrated the ability of paramedics to use the ILMA when faced with a difficult intubation. However, further evaluation of this potential role for the ILMA is required.
PMCID: PMC2660028  PMID: 17351226
17.  Anesthesia 
PMCID: PMC2306199

Results 1-17 (17)