Eleftheriadou I.,National and Kapodistrian University of Athens |
Tentolouris N.,National and Kapodistrian University of Athens |
Argiana V.,National and Kapodistrian University of Athens |
Jude E.,Tameside General Hospital |
Boulton A.J.,Royal Infirmary
Drugs | Year: 2010
Diabetic foot ulcers are often complicated by infection. Among pathogens, Staphylococcus aureus predominates. The prevalence of methicillin-resistant S. aureus (MRSA) in infected foot ulcers is 1530 and there is an alarming trend for increase in many countries. There are also data that recognize new strains of MRSA that are resistant to vancomycin. The risk for MRSA isolation increases in the presence of osteomyelitis, nasal carriage of MRSA, prior use of antibacterials or hospitalization, larger ulcer size and longer duration of the ulcer. The need for amputation and surgical debridement increases in patients infected with MRSA. Infections of mild or moderate severity caused by community-acquired MRSA can be treated with cotrimoxazole (trimethoprimsulfamethoxazole), doxycycline or clindamycin when susceptibility results are available, while severe community-acquired or hospital-acquired MRSA infections should be managed with glycopeptides, linezolide or daptomycin. Dalbavancin, tigecycline and ceftobiprole are newer promising antimicrobial agents active against MRSA that may also have a role in the treatment of foot infections if more data on their efficacy and safety become available. © 2010 Adis Data Information BV. All rights reserved.
Ndip A.,Royal Infirmary |
Ndip A.,University of Manchester |
Williams A.,University of Manchester |
Jude E.B.,University of Manchester |
And 7 more authors.
Diabetes | Year: 2011
OBJECTIVE - The receptor activator of nuclear factor-κB (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) signaling pathway (RANKL/RANK/OPG signaling) is implicated in the osteolysis associated with diabetic Charcot neuroarthropathy (CN); however, the links with medial arterial calcification (MAC) seen in people with CN are unclear. This study aimed to investigate the role of RANKL/OPG in MAC in patients with CN. RESEARCH DESIGN AND METHODS - Enzyme-linked immunosorbent assay and Bio-plex multiarray technology were used to quantify a range of cytokines, including RANKL and OPG in sera from 10 patients with diabetes, 12 patients with CN, and 5 healthy volunteers. Human tibial artery segments were immunohistochemically stained with Alizarin red and human RANKL antibody. Human vascular smooth muscle cells (VSMCs) were also explanted from arterial segments for in vitro studies. RESULTS - We demonstrate colocalization and upregulation of RANKL expression in areas displaying MAC. Systemic levels of RANKL, OPG, and inflammatory cytokines (interleukin-8, granulocyte colony-stimulating factor) were elevated in those with CN compared with diabetic patients and healthy control subjects. Human VSMCs cultured in CN serum showed accelerated osteoblastic differentiation (alkaline phosphatase activity) and mineralization (alizarin red staining) compared with cells treated with diabetic or control serum (P < 0.05). Coincubation with OPG, the decoy receptor for RANKL, attenuated osteogenic differentiation of VSMCs and was independent of a high calcium-phosphate milieu. The accelerated mineralization induced by RANKL and CN serum correlated with nuclear translocation of nuclear factor-κB, a process abrogated by OPG. CONCLUSIONS - Our data provide direct evidence that RANKL/ RANK/OPG signaling is modulated in patients with CN and plays a role in vascular calcification. This study highlights this pathway as a potential target for intervention. © 2011 by the American Diabetes Association.
Ndip A.,Royal Infirmary |
Ndip A.,University of Manchester |
Ndip A.,Manchester Diabetes Center |
Wilkinson F.L.,Manchester Metropolitan University |
And 7 more authors.
Diabetologia | Year: 2014
Type 2 diabetes is associated with increased cardiovascular morbidity and mortality and early vascular ageing. This takes the form of atherosclerosis, with progressive vascular calcification being a major complication in the pathogenesis of this disease. Current research and drug targets in diabetes have hitherto focused on atherosclerosis, but vascular calcification is now recognised as an independent predictor of cardiovascular morbidity and mortality. An emerging regulatory pathway for vascular calcification in diabetes involves the receptor activator for nuclear factor κB (RANK), RANK ligand (RANKL) and osteoprotegerin (OPG). Important novel biomarkers of calcification are related to levels of glycation and inflammation in diabetes. Several therapeutic strategies could have advantageous effects on the vasculature in patients with diabetes, including targeting the RANKL and receptor for AGE (RAGE) signalling pathways, since there has been little success—at least in macrovascular outcomes—with conventional glucose-lowering therapy. There is substantial and relevant clinical and basic science evidence to suggest that modulating RANKL–RANK–OPG signalling, RAGE signalling and the associated proinflammatory milieu alters the natural course of cardiovascular complications and outcomes in people with diabetes. However, further research is critically needed to understand the precise mechanisms underpinning these pathways, in order to translate the anti-calcification strategies into patient benefit. © 2014, Springer-Verlag Berlin Heidelberg.
Jude E.B.,Tameside General Hospital |
Eleftheriadou I.,National and Kapodistrian University of Athens |
Tentolouris N.,National and Kapodistrian University of Athens
Diabetic Medicine | Year: 2010
Diabetic patients are at high risk for peripheral arterial disease (PAD) characterized by symptoms of intermittent claudication or critical limb ischaemia. Given the inconsistencies of clinical findings in the diagnosis of PAD in the diabetic patient, measurement of ankle-brachial pressure index (ABI) has emerged as the relatively simple, non-invasive and inexpensive diagnostic tool of choice. An ABI < 0.9 is not only diagnostic of PAD even in the asymptomatic patient, but is also an independent marker of increased morbidity and mortality from cardiovascular diseases. With better understanding of the process of atherosclerosis, avenues for treatment have increased. Modification of lifestyle and effective management of the established risk factors such as smoking, dyslipidaemia, hyperglycaemia and hypertension retard the progression of the disease and reduce cardiovascular events in these patients. Newer risk factors such as insulin resistance, hyperfibrinogenaemia, hyperhomocysteinaemia and low-grade inflammation have been identified, but the advantages of modifying them in patients with PAD are yet to be proven. Therapeutic angiogenesis, on the other hand, represents a promising therapeutic adjunct in the management of PAD in these patients. Outcomes after revascularization procedures, such as percutaneous transluminal angioplasty and surgical bypasses in diabetic patients, are poorer, with increased perioperative morbidity and mortality compared with that in non-diabetic patients. Amputation rates are higher due to the distal nature of the disease. Efforts towards increasing awareness and intensive treatment of the risk factors will help to reduce morbidity and mortality in diabetic patients with PAD. © 2010 Diabetes UK.
Malone M.,Liverpool Hospital |
Malone M.,Podiatric Surgery Unit |
Bowling F.L.,University of Manchester |
Gannass A.,Podiatric Surgery Unit |
And 2 more authors.
Diabetes/Metabolism Research and Reviews | Year: 2013
Background: Osteomyelitis is a major complication in patients with diabetic foot ulceration. Accurate pathogenic identification of organisms can aid the clinician to a specific antibiotic therapy thereby preventing the need for amputation. Methods: All diabetic patients with bone biopsy-confirmed osteomyelitis were included into the study: biopsies were performed either during surgical removal of infected bone or percutaneously under guided fluoroscopy through non-infected tissue. The depth and extent of the ulcer was assessed using a sterile blunt metal probe. Deep wound cultures were taken from the wound base after sharp debridement. Results: Of 66 cases of suspected osteomyelitis in 102 joints, 34 patients had both bone biopsies and deep wound cultures over the study period. Thirty two of 34 (94%), had a history of preceding foot ulceration, and in 25 of the cases a positive probe to bone test was recorded. In a high proportion of patients, at least one similar organism was isolated from both the deep wound culture and bone biopsy procedures (25 of 34 cases, 73.5%, p<0.001). When organisms were isolated from both wound cultures and bone biopsies, the identical strain was identified in both procedures in a significant proportion of cases (16 of 25 cases, 64%, p<0.001, total sample analysis in 16 of 34 cases, 47%). Conclusions: Deep wound cultures correlate well with osseous cultures and provide a sensitive method in assessing and targeting likely pathogens that cause osseous infections. This will help aid the clinician in guiding antibiotic therapy in centers where bone biopsies may not be readily available. © 2013 John Wiley & Sons, Ltd.
Ahmad G.,Pennine Acute Trust |
Attarbashi S.,Tameside General Hospital |
O'Flynn H.,University of Manchester |
Watson A.J.S.,Tameside General Hospital
European Journal of Obstetrics Gynecology and Reproductive Biology | Year: 2011
Hysteroscopy, hysterosalpingography (HSG), sonohysterography and endometrial ablation are increasingly performed in an outpatient setting. The primary reason for failure to complete these procedures is pain. The objective of this review was to compare the effectiveness and safety of different types of pharmacological intervention for pain relief in office gynaecological procedures. A systematic search of medical databases including PubMed, EMBASE, Cochrane Central register of controlled trials, PsychInfo and CINHAL was conducted in 2009. Randomised controlled trials (RCTs) investigating the use of local anaesthetics, opioid analgesics, non-opioid analgesics and intravenous sedation for pain relief during and after hysteroscopy, HSG, sonohysterography and endometrial ablation were reviewed. Secondary outcomes included adverse effects and failure to complete procedures. Where RCTs were not identified, the best available evidence was sought. Each study was assessed against inclusion criterion. Results for each study were expressed as a standardised mean difference (SMD) with 95% confidence intervals and combined for meta-analysis with Revman 5 software. Meta-analysis revealed beneficial effect of the use of local anaesthetics during and within 30 min after hysteroscopy; SMD -0.45 (95% CI -0.73, -0.17) and SMD -0.51 (95% CI -0.81, -0.21) respectively. No beneficial effect was noted during HSG. One RCT found evidence of benefit for pain relief during hysterosalpingo-contrastsonography; SMD -1.04 [95% CI -1.44, -0.63]. There was no significant difference in failure to complete hysteroscopy due to cervical stenosis between the intervention and control groups (OR 1.31 (95% CI 0.66, 2.59)), but the incidence of failure to complete the procedure due to pain was significantly less in the intervention group (OR 0.29 (0.12, 0.69)). There is evidence of benefit for the use of local anaesthetics for outpatient hysteroscopy and hysterosalpingo-contrastsonography. Local anaesthetics may be considered when performing hysteroscopy in postmenopausal women to reduce the failure rate. © 2010 Published by Elsevier Ireland Ltd.
Game F.L.,University of Nottingham |
Catlow R.,East Lancashire Healthcare Trust |
Jones G.R.,East Lancashire Healthcare Trust |
Edmonds M.E.,King's College |
And 3 more authors.
Diabetologia | Year: 2012
Aims/hypothesis We studied factors associated with the development and resolution of acute Charcot foot using a web-based observational study. Methods Clinicians managing cases of acute Charcot foot in the UK and Ireland between June 2005 and February 2007 were invited to register anonymised details on asecure website. Results A total of 288 cases (age 57.0±11.3 years [mean±SD]; 71.2% male) were registered from 76 centres. Of these, 36% of patients recalled an episode of relevant trauma in the preceding 6 months, while 12% had had surgery to the affected foot. In 101 (35%) cases, ulceration was present at registration and 20% of these had osteomyelitis. Non-removable off-loading devices were used at presentation in 35.4% of cases, with removable off-loading used in 50%. Data on resolution were available for 219 patients. The median time to resolution was 9 months in patients whose initial management included the use of non-removable off-loading, compared with 12 months in the remainder (p=0.001). Bisphosphonates were administered intravenously in 25.4% and orally in 19.4% of cases. The median time to resolution in patients who received bisphosphonates was 12 months and was longer than in those who did not (10 months, p=0.005). Conclusions/interpretation The median time to resolution was longer than in earlier series. Although limited by being observational and non-randomised, these data suggest that the use of non-removable off-loading at presentation may shorten the time to resolution. They provide no evidence to indicate that the use of bisphosphonates is beneficial. .© 2011 Springer-Verlag.
Scott M.J.,Tameside General Hospital |
El-Hassan M.,Tameside General Hospital |
Khan A.A.,Tameside General Hospital
BMJ Case Reports | Year: 2011
This report summarises the case of a 19-year-old male, with a history of gastro-oesophageal reflux disease, who presented to hospital with an acute chest pain. An electrocardiographic and biochemical diagnosis of ST elevation myocardial infarction was made; however, subsequent coronary angiography and echocardiography were both normal. In the week preceding the admission, the patient had consumed large quantities of a popular energy drink and the authors believe this may have implicated the development of his coronary event. This is an association that has been suggested previously and this report briefly summarises the evidence supporting the connection. Copyright 2011 BMJ Publishing Group. All rights reserved.
Shelton C.L.,Tameside General Hospital |
Raistrick C.,Tameside General Hospital |
Warburton K.,9 Poplin Drive |
Siddiqui K.H.,Tameside General Hospital
Journal of Hospital Infection | Year: 2010
Research has shown that healthcare workers' clothes can become contaminated with pathogens. This study aimed to determine whether hospital doctors can change their attire to reduce the possibility of cross-infection without jeopardising the doctor-patient relationship. In this experimental repeated-measures study, 55 male and 45 female inpatients (mean age: 52.89 years) were randomly selected. Participants were shown photographs of medical dresscodes and asked to rate their appropriateness on a 5-point Likert scale. They were then read a standardised statement regarding the significance of attire to cross-infection and the exercise was repeated. Pre statement, there was no significant difference between the majority of dress options, though casual dress (male and female) and short-sleeved top (female) were considered significantly less appropriate. Post statement, surgical 'scrubs' and short-sleeved top/shirt were deemed most appropriate (P < 0.0001). There was no significant difference between short-sleeved shirt and scrubs for males. For females, scrubs were preferred (P = 0.0005). Participants expressed no significant preference for medical attire, with the exception of a dislike of casual dress. However, once informed of the significance of attire to cross-infection, preference changes to favour dresscodes which may minimise infection risk. © 2009 The Hospital Infection Society.
Dhebri A.,Tameside General Hospital
BMJ case reports | Year: 2012
Invasive lobular carcinoma (ILC) of breast is known to present with atypical clinical findings in the breast, making it difficult to diagnose. It is also known to have unusual sites of metastases arising de novo or in patients treated for known ILC. Skin lesion in axilla could be a cutaneous metastasis from ILC or ILC in ectopic breast tissue (EBT). We present two cases with skin lesion in axillas which after excision were surprisingly reported as ILC. On further investigations these were found to be primary in EBT. Though such cases are reported, carcinoma arising from EBT is a very rare presentation and one should be aware of this, when dealing with a skin lesion.