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1.  Complications of Diabetes 
Journal of Diabetes Research  2015;2015:189525.
PMCID: PMC4515299  PMID: 26247036
2.  Inhibition of TNF-α Reverses the Pathological Resorption Pit Profile of Osteoclasts from Patients with Acute Charcot Osteoarthropathy 
Journal of Diabetes Research  2015;2015:917945.
We hypothesised that tumour necrosis factor-α (TNF-α) may enhance receptor activator of nuclear factor-κβ ligand- (RANKL-) mediated osteoclastogenesis in acute Charcot osteoarthropathy. Peripheral blood monocytes were isolated from 10 acute Charcot patients, 8 diabetic patients, and 9 healthy control subjects and cultured in vitro on plastic and bone discs. Osteoclast formation and resorption were assessed after treatment with (1) macrophage-colony stimulating factor (M-CSF) and RANKL and (2) M-CSF, RANKL, and neutralising antibody to TNF-α (anti-TNF-α). Resorption was measured on the surface of bone discs by image analysis and under the surface using surface profilometry. Although osteoclast formation was similar in M-CSF + RANKL-treated cultures between the groups (p > 0.05), there was a significant increase in the area of resorption on the surface (p < 0.01) and under the surface (p < 0.01) in Charcot patients compared with diabetic patients and control subjects. The addition of anti-TNF-α resulted in a significant reduction in the area of resorption on the surface (p < 0.05) and under the surface (p < 0.05) only in Charcot patients as well as a normalisation of the aberrant erosion profile. We conclude that TNF-α modulates RANKL-mediated osteoclastic resorption in vitro in patients with acute Charcot osteoarthropathy.
PMCID: PMC4468294  PMID: 26137498
3.  The Charcot Foot in Diabetes 
Diabetes Care  2011;34(9):2123-2129.
The diabetic Charcot foot syndrome is a serious and potentially limb-threatening lower-extremity complication of diabetes. First described in 1883, this enigmatic condition continues to challenge even the most experienced practitioners. Now considered an inflammatory syndrome, the diabetic Charcot foot is characterized by varying degrees of bone and joint disorganization secondary to underlying neuropathy, trauma, and perturbations of bone metabolism. An international task force of experts was convened by the American Diabetes Association and the American Podiatric Medical Association in January 2011 to summarize available evidence on the pathophysiology, natural history, presentations, and treatment recommendations for this entity.
PMCID: PMC3161273  PMID: 21868781
4.  Changes in the Incidence of Lower Extremity Amputations in Individuals With and Without Diabetes in England Between 2004 and 2008 
Diabetes Care  2010;33(12):2592-2597.
To describe recent trends in the incidence of nontraumatic amputations among individuals with and without diabetes and estimate the relative risk of amputations among individuals with diabetes in England.
We identified all patients aged >16 years who underwent any nontraumatic amputation in England between 2004 and 2008 using national hospital activity data from all National Health Service hospitals. Age- and sex-specific incidence rates were calculated using the total diabetes population in England every year. To test for time trend, we fitted Poisson regression models.
The absolute number of diabetes-related amputations increased by 14.7%, and the incidence decreased by 9.1%, from 27.5 to 25.0 per 10,000 people with diabetes, during the study period (P > 0.2 for both). The incidence of minor and major amputations did not significantly change (15.7–14.9 and 11.8–10.2 per 10,000 people with diabetes; P = 0.66 and P = 0.29, respectively). Poisson regression analysis showed no statistically significant change in diabetes-related amputation incidence over time (0.98 decrease per year [95% CI 0.93–1.02]; P = 0.12). Nondiabetes-related amputation incidence decreased from 13.6 to 11.9 per 100,000 people without diabetes (0.97 decrease by year [0.93–1.00]; P = 0.059). The relative risk of an individual with diabetes undergoing a lower extremity amputation was 20.3 in 2004 and 21.2 in 2008, compared with that of individuals without diabetes.
This national study suggests that the overall population burden of amputations increased in people with diabetes at a time when the number and incidence of amputations decreased in the aging nondiabetic population.
PMCID: PMC2992196  PMID: 20833865
5.  A Prospective Study of Calcaneal Bone Mineral Density in Acute Charcot Osteoarthropathy 
Diabetes Care  2010;33(10):2254-2256.
To measure prospectively bone mineral density (BMD) of the Charcot and non-Charcot foot in 36 diabetic patients presenting with acute Charcot osteoarthropathy.
Calcaneal BMD was measured with quantitative ultrasound at presentation, at 3 months of casting, and at the time of the clinical resolution.
BMD of the Charcot foot was significantly reduced compared with BMD of the non-Charcot foot at presentation (P = 0.001), at 3 months of casting (P < 0.001), and at the time of clinical resolution (P < 0.001). Overall, from the time of presentation to the time of resolution there was a significant fall of BMD of the Charcot foot (P < 0.001) but not of the non-Charcot foot (P = 0.439).
Although the Charcot foot was treated with casting until clinical resolution, there was a significant fall of BMD only from presentation up until 3 months of casting.
PMCID: PMC2945169  PMID: 20628091
7.  The treatment of diabetic foot infections: focus on ertapenem 
Clinically, 3 distinct stages of diabetic foot infection may be recognized: localized infection, spreading infection and severe infection. Each of these presentations may be complicated by osteomyelitis. Infection can be caused by Gram-positive aerobic, and Gram-negative aerobic and anaerobic bacteria, singly or in combination. The underlying principles are to diagnose infection, culture the bacteria responsible and treat aggressively with antibiotic therapy. Localized infections with limited cellulitis can generally be treated with oral antibiotics on an outpatient basis. Spreading infection should be treated with systemic antibiotics. Severe deep infections need urgent admission to hospital for wide-spectrum intravenous antibiotics. Clinical and microbiological response rates have been similar in trials of various antibiotics and no single agent or combination has emerged as most effective. Recently, clinical and microbiological outcomes for patients treated with ertapenem were equivalent to those for patients treated with piperacillin/tazobactam. It is also important to judge the need for debridement and surgery, to assess the arterial supply to the foot and consider revascularization either by angioplasty or bypass if the foot is ischemic. It is also important to achieve metabolic control. Thus infection in the diabetic foot needs full multidisciplinary treatment.
PMCID: PMC2788600  PMID: 19997576
diabetes; foot; infection; antibiotics; ertapenem
8.  Diabetic foot ulcers 
BMJ : British Medical Journal  2006;332(7538):407-410.
PMCID: PMC1370976  PMID: 16484268
10.  Personal View 
British Medical Journal  1977;2(6096):1213.
PMCID: PMC1632188
11.  What Should I Do? 
British Medical Journal  1965;1(5428):187.
PMCID: PMC2165103

Results 1-11 (11)