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Introduction Chronic wounds lead to devastating health and economic consequences for individuals and the healthcare system. These wounds do not heal within expected timeframes, often recur, and/or are complicated by underlying comorbidities. There is a significant need to identify and implement evidence-based practice in the prevention and management of chronic wounds in Australia to minimise the impact to persons and healthcare systems. Objectives This scoping review aims to identify (i) current research activity and outcomes in assessment, management and prevention of chronic wounds and (ii) gaps in chronic wound research relevant to Australia. Methods The Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Review (PRISMAS-ScR) framework will be used to guide this scoping review. Searches will be conducted in Medline, Embase, CINAHL, Joanna Briggs Institute Library, Cochrane Library, APA PsycInfo databases, websites and publications of relevant professional organisations, and clinical trial registries for publications between 2010-2021. Two independent researchers will review the identified records based on the inclusion criteria and any conflicts will be resolved by a third researcher. This scoping review will include Australian original studies, international and national systematic review and evidence-based guidelines or consensus statements on the assessment, management or prevention of chronic wounds. [ABSTRACT FROM AUTHOR]

Aim: To assess the prevalence of metabolic syndrome in type 1 diabetes, and its age‐related association with diabetes complications. Methods: Australian National Diabetes Information Audit and Benchmarking (ANDIAB) was a well‐established quality audit programme. It provided cross‐sectional data on people attending specialist diabetes services across Australia. We determined the prevalence of metabolic syndrome (WHO criteria) in adults with type 1 diabetes and its associations with diabetes complications across age groups. Results: Metabolic syndrome prevalence was 30% in 2120 adults with type 1 diabetes. Prevalence increased with age: 21% in those aged <40 years, 35% in those aged 40–60 years, and 44% in those aged >60 years (P<0.001), which was driven by an increase in hypertension rate. Metabolic syndrome was associated with a higher prevalence of microvascular, macrovascular and foot complications, with the greatest impact at a younger age. The odds ratio for macrovascular complications with metabolic syndrome, compared with without, was 5.9 (95% CI 2.1–16.4) in people aged <40 years, 2.7 (95% CI 1.7–4.2) in those aged 40–60 years, and 1.7 (95% CI 1.1–2.7) in those aged >60 years (all P < 0.05). Metformin use was higher in those with metabolic syndrome (16% vs 4%; P<0.001). Conclusions: In this large Australian cohort, metabolic syndrome was common in type 1 diabetes and identified people at increased risk of the spectrum of diabetes complications, particularly in young to middle‐aged adults. Potential clinical implications are that therapies targeting insulin resistance in this high‐risk group may reduce diabetes complications and should be explored. [ABSTRACT FROM AUTHOR]

Aim: To systematically evaluate research investigating the accuracy of the ankle–brachial index (ABI) for diagnosing peripheral artery disease (PAD) in people with diabetes, as the accuracy is thought to be reduced in this cohort. Methods: A database search of EBSCO Megafile Premier, Embase and The Cochrane Library was conducted to 28 February 2019. Prospective and retrospective investigations of the diagnostic accuracy of the ABI for PAD in people with diabetes using an imaging reference standard were eligible. Sensitivity and specify of the ABI and bivariate meta‐analysis against reference tests, or a standard summary receiver operating curve analysis (SROC) was performed. Results: Thirty‐three studies met the inclusion criteria. ABI was compared with angiography in 12 studies and with colour duplex ultrasound (CDUS) in 21 studies. A SROC analysis of studies using angiography as the reference standard found a diagnostic odds ratio (DOR) of 9.06 [95% confidence interval (CI) 3.61 to 22.69], and area under the curve (AUC) of 0.76 (95% CI 0.66 to 0.86). Bivariate analysis of studies using CDUS demonstrated mean sensitivity of 0.60 (95% CI 0.48 to 0.71; P = 0.097) and mean specificity of 0.87 (95% CI 0.78 to 0.92; P < 0.001) with a DOR of 9.76 (95% CI 5.24 to 18.20; P < 0.0001) and AUC 0.72. Conclusions: These results suggest the ABI has a high specificity but lower sensitivity in detecting imaging diagnosed PAD in people with diabetes. The low probability of the testing being able to rule diagnosis in or out suggest that the ABI has limited effectiveness for early detection of PAD in this cohort. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes diagnosed during youth and early adulthood is aggressive and associated with a high burden of vascular complications. The increase in complications is often attributed to long disease duration and poor metabolic control. Whether people with young‐onset type 2 diabetes are inherently more susceptible to long‐term complications than those diagnosed in later adulthood is unclear. Methods: Prospective data from 3322 individuals, diagnosed between the age of 15 and 70 years and collected 10–25 years after diabetes diagnosis, were analysed. The cross‐sectional associations between age at diagnosis and microvascular and macrovascular complications were analysed using logistic regression models, adjusted for duration of diabetes exposure and metabolic risk factors including blood pressure, cholesterol and updated mean HbA1c. Results: The prevalence of retinopathy was highest in those with young‐onset type 2 diabetes (diagnosed at age 15 to <40 years). After 10–15 years' diabetes duration, the adjusted odds ratio for retinopathy in this population was 2.8 (95% CI 1.9–4.1; reference group those diagnosed at 60 to <70 years of age). The odds of retinopathy remained higher in people with young‐onset type 2 diabetes after longer durations of diabetes exposure; the odds decreased with increasing age at diagnosis. This pattern was not observed in models of other complications: after 10–15 years' diabetes exposure, the adjusted odds ratios for albuminuria, peripheral neuropathy and macrovascular disease in people with young‐onset type 2 diabetes were 0.5 (95% CI 0.4–0.8), 0.7 (95% CI 0.5–1.1) and 0.2 (95% CI 0.1–0.3), respectively. Conclusion: After accounting for disease duration and other important confounders, people with type 2 diabetes diagnosed in youth and early adulthood (or with a younger current age) appeared to be inherently more susceptible to retinopathy. For other complications, adjusted risk appears highest in the oldest age of diagnosis group. These data have screening and treatment target implications. What's new?: Young‐onset type 2 diabetes is an aggressive disease, associated with a higher burden of complications than that seen in older‐onset diabetes.It is not known whether young people have an underlying increased susceptibility to complications or whether their long‐term excess risk of complications can be explained by glycaemia and longer duration of disease exposure.Unlike other complications, risk of retinopathy in young‐onset type 2 diabetes (or those with a younger current age) is twofold higher than in older‐onset type 2 diabetes, after adjustment for duration of diabetes exposure, glycaemia and other known risk factors. This finding supports an underlying increased susceptibility to retinal complications for young people.This increased risk of retinopathy indicates a need for more frequent surveillance and aggressive management of known risk factors, and supports a reconsideration of the diabetic retinopathy guidelines for young people and those with a younger age at diagnosis.A search for as yet unidentified contributing factors for retinopathy risk in young people is warranted. [ABSTRACT FROM AUTHOR]

Skeletal muscle extracellular matrix remodelling has been proposed as a new feature associated with obesity and metabolic dysfunction. Exercise training improves muscle function in obesity, which may be mediated by regulatory effects on the muscle extracellular matrix. This review examined available literature on skeletal muscle extracellular matrix remodelling during obesity and the effects of exercise. A non-systematic literature review was performed on PubMed of publications from 1970 to 2015. A total of 37 studies from humans and animals were retained. Studies reported overall increases in gene and protein expression of different types of collagen, growth factors and enzymatic regulators of the skeletal muscle extracellular matrix in obesity. Only two studies investigated the effects of exercise on skeletal muscle extracellular matrix during obesity, with both suggesting a regulatory effect of exercise. The effects of exercise on muscle extracellular matrix seem to be influenced by the duration and type of exercise training with variable effects from a single session compared with a longer duration of exercise. More studies are needed to elucidate the mechanisms behind skeletal muscle extracellular matrix remodelling during obesity and the effects of exercise. [ABSTRACT FROM AUTHOR]

Aims To determine whether alanine aminotransferase or gamma-glutamyltransferase levels, as markers of liver health and non-alcoholic fatty liver disease, might predict cardiovascular events in people with Type 2 diabetes. Methods Data from the Fenofibrate Intervention and Event Lowering in Diabetes study were analysed to examine the relationship between liver enzymes and incident cardiovascular events (non-fatal myocardial infarction, stroke, coronary and other cardiovascular death, coronary or carotid revascularization) over 5 years. Results Alanine aminotransferase measure had a linear inverse relationship with the first cardiovascular event occurring in participants during the study period. After adjustment, for every 1 sd higher baseline alanine aminotransferase measure (13.2 U/l), the risk of a cardiovascular event was 7% lower (95% CI 4-13; P = 0.02). Participants with alanine aminotransferase levels below and above the reference range 8-41 U/l for women and 9-59 U/l for men, had hazard ratios for a cardiovascular event of 1.86 (95% CI 1.12-3.09) and 0.65 (95% CI 0.49-0.87), respectively ( P = 0.001). No relationship was found for gamma-glutamyltransferase. Conclusions The data may indicate that in people with Type 2 diabetes, which is associated with higher alanine aminotransferase levels because of prevalent non-alcoholic fatty liver disease, a low alanine aminotransferase level is a marker of hepatic or systemic frailty rather than health. [ABSTRACT FROM AUTHOR]

Aims/Hypothesis. Topical application of CTGF/CCN2 to rodent diabetic and control wounds was examined. In parallel research, correlation of CTGF wound fluid levels with healing rate in human diabetic foot ulcers was undertaken. Methods. Full thickness cutaneous wounds in diabetic and nondiabetic control rats were treated topically with 1 μg rhCTGF or vehicle alone, on 2 consecutive days. Wound healing rate was observed on day 14 and wound sites were examined for breaking strength and granulation tissue. In the human study across 32 subjects, serial CTGF regulation was analyzed longitudinally in postdebridement diabetic wound fluid. Results. CTGF treated diabetic wounds had an accelerated closure rate compared with vehicle treated diabetic wounds. Healed skin withstood more strain before breaking in CTGF treated rat wounds. Granulation tissue from CTGF treatment in diabetic wounds showed collagen IV accumulation compared with nondiabetic animals. Wound α-smooth muscle actin was increased in CTGF treated diabetic wounds compared with untreated diabetic wounds, as was macrophage infiltration. Endogenous wound fluid CTGF protein rate of increase in human diabetic foot ulcers correlated positively with foot ulcer healing rate (r=0.406; P<0.001). Conclusions/Interpretation. These data collectively increasingly substantiate a functional role for CTGF in human diabetic foot ulcers. [ABSTRACT FROM AUTHOR]

Craniofrontonasal syndrome (CFNS) is an X-linked developmental malformation, caused by mutations in the EFNB1 gene, which have only been described since 2004. A genotype-phenotype correlation seems not to be present. As it is of major importance to adequately counsel patients with EFNB1 mutations and their parents, and to improve diagnosis of new patients, more information about the phenotypic features is needed. This study included 23 patients (2 male, 21 female) with confirmed EFNB1 mutations. All patients underwent a thorough physical examination and photographs were taken. If available, radiological images were also consulted. Hypertelorism, longitudinal ridging and/or splitting of nails, a (mild) webbed neck and a clinodactyly of one or more toes were the only consistent features observed in all patients. Frequently observed phenotypic features were bifid tip of the nose (91%), columellar indentation (91%) and low implantation of breasts (90%). In comparison with anthropometric data of facial proportions, patients with CFNS had a significantly different face in multiple respects. An overview of all phenotypic features is shown. Patients with EFNB1 mutations have a clear phenotype. This study will facilitate genetic counseling of parents and patients, and contribute to the diagnostic and screening process of patients with suspected CFNS. [ABSTRACT FROM AUTHOR]

Aims To review the incidence and evidence for screening for thyroid autoimmunity and thyroid dysfunction in Type 1 diabetes. Methods Systematic review and meta-analysis. Inclusion criteria were prospective cohort studies screening for thyroid autoimmunity and/or dysfunction (defined as an abnormal thyroid-stimulating hormone level) in Type 1 diabetes. Exclusion criteria included pregnancy and thyroid dysfunction before diabetes onset. Outcomes examined were: incidence of thyroid autoimmunity and/or dysfunction; association between thyroid autoimmunity and dysfunction; and cost-effectiveness. Data sources were MEDLINE, EMBASE, the Cochrane Library, manual searching and contact with authors, with limitations to English language and human studies. Meta-analysis was performed using random effects models. Results We identified 14 eligible studies, involving 2972 young people and 789 adults with Type 1 diabetes. Follow-up ranged from 1-18 years. None of the studies were of good methodological quality (Newcastle Ottowa Scale score > 7). The incidence of thyroid dysfunction (11 studies) ranged from 27 (95% CI 15-45) to 246 (95% CI 118-453) per 10 000 patient-years and thyroid autoimmunity (four studies) from 13 (95% CI 0.3-71) to 326 (95% CI 194-510). The risk of thyroid dysfunction was higher in those with thyroid autoimmunity: summary risk ratio 25 (95% CI 9-71) and was higher in children (49, 95% CI 16-150) compared with adults (7, 95% CI 3-13). No studies examined cost-effectiveness of screening. Conclusions There is a markedly increased risk of thyroid dysfunction in people with Type 1 diabetes and thyroid autoimmunity. The optimal method or frequency of screening could not be determined from available data. Future studies should examine whether screening improves clinical outcomes in this population. [ABSTRACT FROM AUTHOR]

Abstact Aim Diabetic ketoacidosis is a life-threatening complication of Type 1 diabetes. Blood β-hydroxybutyrate testing is now widely available as an alternative to urine acetoacetate testing for detecting ketosis. The aim of this study was to review the effectiveness of capillary or serum β-hydroxybutyrate compared with urine acetoacetate testing in prevention and management of diabetic ketoacidosis. Methods MEDLINE, EMBASE, EBM Reviews, The Cochrane Library and CINAHL (until April 2012, no language restrictions, studies in humans) were searched for experimental and observational studies comparing the effectiveness of blood β-hydroxybutyrate and urine acetoacetate testing. Outcomes examined were prevention of diabetic ketoacidosis, time to recovery from diabetic ketoacidosis, healthcare costs and patient or caregiver satisfaction. Additional sources included reference lists, conference proceedings and contact with experts in the field. Results Four studies (two randomized controlled trials and two cohort studies) met eligibility criteria, including 299 participants across 11 centres. Risk of bias was low to moderate. Blood ketone testing compared with urine testing was associated with reduced frequency of hospitalization (one study), reduced time to recovery from diabetic ketoacidosis (three studies), cost benefits (one study) and greater satisfaction (one study, intervention group only). No study assessed prevention of diabetic ketoacidosis. Meta-analysis could not be performed because of heterogeneity in study design and published data. Conclusions There is evidence suggesting that blood β-hydroxybutyrate testing is more effective than urine acetoacetate testing in reducing emergency department assessment, hospitalization and time to recovery from diabetic ketoacidosis, as well as potentially lowering healthcare expenditure. Further research in both young people and adults is needed. [ABSTRACT FROM AUTHOR]

We report the use of the Novalung interventional Lung Assist extracorporeal carbon dioxide removal device, (Novalung GmbH, Lotzenacker 3, D-72379 Hechingen, Germany) to treat a 46-year-old female with life-threatening bronchospasm secondary to influenza infection. Despite maximal treatment she developed severe hypercapnia and acidosis. The necessity for high inflation pressures led to the development of gross surgical emphysema. Use of the interventional Lung Assist enabled a rapid correction of hypercapnoea and acidosis, allowing a reduction in airway pressures, reducing further barotrauma. Subsequent resolution of the inflammatory process allowed removal of the interventional Lung Assist after 11 days. She was successfully weaned from mechanical ventilation and made a full recovery. [ABSTRACT FROM AUTHOR]

Diabet. Med. 28, 1272-1276 (2011) Abstract Aims Icodextrin is a glucose polymer used to maintain an osmotic gradient in peritoneal dialysis. Metabolites of icodextrin are known to cause overestimation of blood glucose in glucose meters using glucose dehydrogenase/pyrroloquinolinequinone systems. The aim of this study is to determine the extent of icodextrin interference in glucose meters using the newer glucose dehydrogenase/NAD or glucose oxidase systems. This has not been established previously. Methods Fasting blood samples ( n = 4) were spiked with either one icodextrin metabolite (maltose, maltotriose or maltotetraose) or a combination, at various blood concentrations expected during dialysis. Samples were tested in triplicate on: five glucose-meters, a Radiometer® (glucose oxidase/hydrogen peroxide) and laboratory (hexokinase) analysers. Each meter was also tested on blood from six patients undergoing dialysis. Accuracy was evaluated as % Bias = [(meter glucose - laboratory glucose)/laboratory glucose] × 100. Results A single icodextrin metabolite affected glucose measurements and, in combination, the interferences were additive in the two Accu-Chek® and Optium® Xceed meters by > 10%. Amongst these meters, the Optium Xceed 5-s machine was less affected. Meters using glucose oxidase were least affected by interference. A similar trend in interference was observed in vivo. Conclusion While meters using glucose dehydrogenase/NAD are less affected by icodextrin metabolites, interference can still be demonstrated. The degree of interference can vary in different glucose meters using this enzyme/cofactor system, as seen in the Optium Xceed machines. Icodextrin is an important source of interference that sometimes even experienced professionals are unaware of and which leads to clinically significant errors in insulin dose adjustment. Awareness of this interference and selection of the most appropriate glucose meters are crucial to minimize this hazard. [ABSTRACT FROM AUTHOR]

Lymphocoele of the thoracic duct, alternatively referred to as thoracic duct cyst, is an uncommon abnormality that can present occasionally as a left supraclavicular fossa mass. Recognition of the origin of such a neck mass on imaging is crucial to avert unnecessary intervention. A case of such a mass is presented with discussion of the fascinating variable anatomy of the thoracic duct. [ABSTRACT FROM AUTHOR]

Following the recent Ongoing Telmistartan Alone and in Combination With Ramipril Global Endpoint Trial (ONTARGET) finding of adverse renal outcomes, dual renin-angiotensin blockade has fallen out of favour, despite antihypertensive and antiproteinuric efficacy. However, in high-risk severe hypertension, not studied in ONTARGET, whether combination treatment should be withheld or withdrawn is not clear. We examine the renal effects of angiotensin-converting enzyme inhibitor (ACE-I) and angiotensin II receptor blocker (ARB) monotherapy versus combination therapy in patients with type 2 diabetes and varying degrees of hypertension. Subjects attending a hospital diabetes centre were selected as case (combination therapy, n = 120) and control (monotherapy, n = 480). Subjects were matched for age, gender, ethnicity, estimated glomerular filtration rate (eGFR), blood pressure (BP) and study duration. Patients were stratified by BP, hypertension stage 1 (BP < 160/100, n = 506) and stage 2 (≥160/100, n = 94), and by treatment group. Data were analysed for the primary renal outcome of eGFR decline ≥20 ml/min, over a median of 3.7 years. In keeping with the ONTARGET study, for stage 1 hypertension, combination treatment is significantly worse than monotherapy for the primary outcome of eGFR decline ≥20 ml/min (20 vs. 10.7%, p = 0.01). In contrast, for stage 2 hypertension, this endpoint was reached less often for combination versus monotherapy (12.0 vs. 23.2%, p = 0.2). Combination treatment was also not detrimental in patients with proteinuria or eGFR < 60 ml/min and was associated with fewer macrovascular events. Given that hypertension control is paramount and in the spirit of primum non nocere, these data are reassuring should clinicians choose to use ACE-I and ARB combination therapy in the very hypertensive diabetic patient. [ABSTRACT FROM AUTHOR]

CD147 is a highly glycosylated transmembrane protein that is known to play a role in regulation of many protein families. It has the unique ability to maintain functional activity in both the membrane bound state and in the soluble form. CD147 is known to play a role in regulation of matrix metalloproteinase (MMP) expression, but whether its expression is affected by the diabetic milieu is not known, and its role in regulation of monocyte MMPs in this environment has not been investigated. Therefore, in this study we investigated the effect of advanced glycation end products (AGEs) and high glucose (HG; 25 mM), on monocyte CD147 expression. Culture of THP-1 monocytes in the presence of AGEs or HG significantly increased CD147 at the gene and protein level. THP-1 cell results were confirmed using freshly isolated monocytes from human volunteers. The effect of AGEs and HG on CD147 expression was also mimicked by addition of proinflammatory cytokines. Addition of AGEs or HG also increased expression of monocyte MMP-1 and MMP-9 but not MMP-2. This increase in MMPs was significantly attenuated by inhibition of CD147 using either a small interfering RNA or an anti-CD147 antibody. Inhibition of NF-B or addition of antibodies to either TNF or the receptor for AGE (RAGE) each significantly prevented in a dose-dependent manner the induction of CD147 gene and protein by AGE and also decreased MMP-1 and MMP-9. This novel result shows that AGEs can induce monocyte CD147 expression, an effect mediated by inflammatory pathways and RAGE. Because MMPs play a role in monocyte migration, inhibition of their regulator CD147 may assist in the prevention of diabetic complications, particularly those where monocyte infiltration is an early initiating event. [ABSTRACT FROM AUTHOR]

Date written: April 2009 Final submission: April 2009 [ABSTRACT FROM AUTHOR]

Date written: April 2009 Final submission: April 2009 [ABSTRACT FROM AUTHOR]

Date written: April 2009 Final submission: April 2009 [ABSTRACT FROM AUTHOR]

Chronic non-healing wounds are a common complication of diabetes. Prolonged inflammation and decreased matrix accumulation may contribute. Connective tissue growth factor (CTGF) is induced during normal wound healing, but its regulation in diabetic wounds is unknown. We developed a primate model for the study of in vivo wound healing in baboons with long diabetes duration. Drum implants were placed subcutaneously into thighs of diabetic and non-diabetic control baboons. After 2 and 4 weeks the skin incision sites were removed for measurement of breaking strength and epithelial thickness. Drum implants were removed for analysis of granulation tissue and inflammatory cells, CTGF and tissue inhibitor of matrix metalloproteinase (TIMP-1). Degradation of added CTGF by wound fluid was also examined. Healed incision site skin was stiffer (less elastic) in diabetic baboons and epithelial remodelling was slower compared with controls. Granulation tissue from diabetic baboons was reduced at 2 and 4 weeks, with increased vessel lumen areas at 4 weeks. Macrophages were reduced while neutrophils persisted in diabetic tissue. In diabetic wound tissue at 4 weeks there was less CTGF induced, as shown by immunohistochemistry, compared with controls. In contrast, immunoreactive fragments of CTGF were significantly increased in whole tissue lysate in diabetic baboons, suggesting that CTGF is redistributed in diabetes from granulation tissue into wound fluid. When recombinant human CTGF was co-incubated with wound fluid, increased CTGF degradation products were observed in both control and diabetic samples. This baboon model of wound healing reflects the abnormal microenvironment seen in human diabetic wounds and provides insights into the dysregulation of CTGF in diabetic wounds. [ABSTRACT FROM AUTHOR]

We examined whether age of type 2 diabetes onset is related to mitochondrial DNA content in peripheral blood monocytes (PBMCs). PBMCs were isolated from 65 patients with type 2 diabetes. To minimise age as a confounder, only patients aged ≥50 years were studied. Sample mitochondrial DNA (mtDNA) content was determined by amplification of the mitochondrial gene CYT-B (also known as MT-CYB) and adjusted for single-copy nuclear control genes ( 36B4 [also known as RPLPO] and GAPDH). Age of diabetes onset ranged from 25 to 69 years. There was a significant positive relationship between age of diabetes onset in quartiles and mtDNA content for the whole group ( p = 0.02 for trend). When stratified by the presence of diabetes complications, a strong positive relationship was observed between age of diagnosis and mtDNA content for participants without diabetic complications ( r = 0.7; p = 0.0002), but not for those with complications ( r = −0.04; p = 0.8). Multivariate analysis confirmed age of onset and complication status as independent determinants. There was co-linearity between age of onset and disease duration, with similar relationships also seen between duration and mtDNA content. An earlier age of type 2 diabetes onset is associated with a lower PBMC mtDNA content, but only in patients without diabetes complications. This may reflect a differing biology of PBMC mtDNA in those with early-onset diabetes and those who are prone to complications. PBMC mtDNA depletion may accelerate diabetes onset; however the independent effect of diabetes duration remains to be evaluated. [ABSTRACT FROM AUTHOR]

Aim: Diabetic cardiomyopathy is an increasingly recognized entity. The pathogenic factors that may contribute to its development, especially the earliest changes of diastolic dysfunction (DD), have not been clearly defined. Microvessel dysfunction and upregulation of profibrotic growth factors have been described as possible causes. The aim of this study was therefore to determine whether microvascular dysfunction and/or upregulation of the profibrotic connective tissue growth factor (CTGF) are associated with subclinical DD in subjects with type 2 diabetes. Methods: Forty subjects with type 2 diabetes and 20 age-matched non-diabetic controls, all of whom had no clinical evidence of ischaemic heart disease, cardiac failure or echo evidence of systolic ventricular dysfunction, were recruited. Microvascular function was measured by laser Doppler velocimetry, with examination of endothelium-dependent increase in blood flow following iontophoresis of acetylcholine (ACh) and endothelium-independent increase in blood flow in response to the nitric oxide donor sodium nitroprusside (SNP). CTGF levels were determined by Western immunoblotting. Results: DD determined on the basis of traditional echocardiographic criteria was similar in diabetic subjects compared with controls (28 vs. 20%, p = 0.5). Using left ventricular myocardial tissue Doppler-based indices for DD, the E/ E′ and the E′/ A′ ratios (where E is the flow related to early ventricular filling and E′ and A′ are early and late diastolic velocities, respectively) in diabetic subjects revealed evidence of more DD than controls (p = 0.046 and p = 0.007 respectively) . Comparing controls with no DD by conventional echocardiographic criteria (Group I), diabetes and no DD (Group II) and diabetes with DD (Group III), there was a significant trend in reduction of both endothelium-dependent (ACh fold change; p = 0.04) and endothelium-independent (SNP fold change; p = 0.0004) blood flow across the groups. The ACh and SNP responses, however, were not correlated significantly with quartiles of the E/ E′ ratio or the E′/ A′ ratio. CTGF plasma levels did not differ across the groups and CTGF did not correlate with parameters of microvascular function. Conclusions: This study indicates that while there is a significant association between DD and measures of microvascular function, the relationship between endothelial dysfunction, CTGF and subtle measures of DD is not strong. Other factors are therefore likely to play an important role in the early pathogenesis of subclinical cardiac DD in type 2 diabetes. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is associated with extensive vascular pathology, yet little is known about its long-term effects on liver sinusoidal endothelial cells (LSECs). Potential diabetic changes in LSECs are important because of the role played by fenestrations in the LSECs in hepatic disposition of lipoproteins. Surgical liver biopsies for electron microscopy and immunohistochemistry were obtained from baboons with long-standing streptozotocin-induced, insulin-treated diabetes mellitus and compared with those from age-matched control animals. There was an increase in the thickness of LSECs (170 ± 17 vs 123 ± 10 nm, p < 0.01). Fenestrations in LSECs, as determined by overall porosity, were markedly reduced (1.4 ± 0.1% vs 2.6 ± 0.2%, p < 0.01). Increased numbers of stellate cells were seen on electron microscopy, and this finding was corroborated by increased smooth muscle actin expression. Diabetes mellitus was also associated with increased endothelial production of von Willebrand factor and caveolin-1. Diabetes mellitus in the non-human primate is associated with marked changes in LSECs, including a reduction in fenestrations. Such changes provide an additional and novel mechanism for impaired hepatic lipoprotein clearance and post-prandial hyperlipidaemia in diabetes mellitus. [ABSTRACT FROM AUTHOR]

Aims: Young adults with type 2 diabetes (T2Dm) present the clinician with the problem of when to start therapies for the primary prevention of vascular disease and how to identify those at most vascular risk. We examine whether the metabolic syndrome (MetS) can be a useful clinical tool to stratify vascular risk in this context. Methods: Data were collected from 5928 subjects with T2Dm, and subjects were categorized as having MetS by World Health Organization criteria (body mass index criteria modified for Asians using >23 kg/m2). The prevalence of macrovascular disease was examined by MetS status and age. Results: The overall MetS prevalence was 72.3%. MetS was associated with an increased prevalence of ischaemic heart disease (IHD) (17.2% MetS vs. 11.6% no MetS, p < 0.0001), coronary artery bypass graft (7.6 vs. 4.7%, p < 0.0003), peripheral vascular disease (PVD) (4.7 vs. 3.7%, p = 0.08) and stroke (6 vs. 3.9%, p = 0.002) across all age groups. MetS subjects had an IHD prevalence equivalent to that seen in subjects who were one decade older without MetS. The most significant impact of MetS was for the age group of 40–49 years with much lesser impact seen with progressively increasing age [odds ratio (OR) = 2.1 for IHD in MetS compared with no MetS at age 40–50 years, p < 0.05; falling progressively to OR = 1.5 at age >70 years, p > 0.05]. Similar trends were seen for coronary artery by-pass graft (CABG) and PVD. There was a strong relationship between the number of MetS risk factors and IHD prevalence (r = 0.99, p = 0.0001). Conclusions: These data suggest that MetS is particularly useful in stratifying vascular risk in younger T2Dm patients and in those with a high number of MetS components. For patients with MetS, especially those with a full house of MetS risk factors, commencing risk-lowering interventions 10 years earlier than their MetS-free counterparts could be considered. [ABSTRACT FROM AUTHOR]

Young women with type 1 diabetes are at twice the risk for the development of an eating disorder compared with their peers. When an eating disorder co-exists with diabetes there is an increased risk of earlier onset of diabetes-related complications as well as more severe complications. There is limited knowledge of how to detect eating disorders in individuals with diabetes and how best to manage the condition. This paper discusses our experiences in managing young adults, with type 1 diabetes and an eating disorder, at the specialist in-patient level where team members are experienced in managing both illnesses. We highlight specific management issues at the in-patient level and present a case example. It is challenging to manage such patients because the day-to-day management issues of diabetes often tend to overwhelm psychiatric interventions, particularly if eating disorder staff are less experienced in diabetes management. As psychiatric issues are difficult to manage by the diabetes team, the needs of a young adult with diabetes and an eating disorder are hard to meet. Addressing diabetes specific concerns as well as weight and shape concerns is essential, as is a well co-ordinated management team addressing both eating disorders and diabetes. Copyright © 2005 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Matrix accumulation in the renal tubulointerstitium is predictive of a progressive decline in renal function. Transforming growth factor-β1 (TGF-β1) and, more recently, connective tissue growth factor (CTGF) are recognized to play key roles in mediating the fibrogenic response, independently of the primary renal insult. Further definition of the independent and interrelated effects of CTGF and TGF-β1 is critical for the development of effective antifibrotic strategies. CTGF (20 ng/ml) induced fibronectin and collagen IV secretion in primary cultures of human proximal tubule cells (PTC) and cortical fibroblasts (CF) compared with control values (P < 0.005 in all cases). This effect was inhibited by neutralizing antibodies to either TGF-β or to the TGF-β type II receptor (TβRII). TGF-β1 induced a greater increase in fibronectin and collagen IV secretion in both PTC (P < 0.01) and CF (P < 0.01) compared with that observed with CTGF alone. The combination of TGF-β1 and CTGF was additive in their effects on both PTC and CF fibronectin and collagen IV secretion. TGF-β1 (2 ng/ml) stimulated CTGF mRNA expression within 30 min, which was sustained for up to 24 h, with a consequent increase in CTGF protein (P < 0.05), whereas CTGF had no effect on TGF-β1 mRNA or protein expression. TGF-β1 (2 ng/ml) induced phosphorylated (p)Smad-2 within 15 min, which was sustained for up to 24 h. CTGF had a delayed effect on increasing pSmad-2 expression, which was evident at 24 h. In conclusion, this study has demonstrated the key dependence of the fibrogenic actions of CTGF on TGF-β. It has further uniquely demonstrated that CTGF requires TGF-β, signaling through the TβRII in both PTCs and CFs, to exert its fibrogenic response in this in vitro model. [ABSTRACT FROM AUTHOR]

The article comments that dysregulation of growth factors is one of the changes which occur in diabetes. The identification of the key growth factor which cause a particular type and stage of diabetic tissue damage is important in the prevention and treatment of diabetes complications, for which connective tissue growth factor is a prime candidate.

Objective: To determine the accuracy of clinical diagnosis compared to post mortem findings in intensive care patients.Design: A retrospective and blinded review of medical records.Setting: A nine-bed combined high dependency and intensive care unit in a district general hospital in Gloucester, England.Patients and Participants: Ninety-seven patients who died on the intensive care unit and subsequently underwent post mortem examination.Results: Suspected cause of death and main clinical diagnoses were determined and compared with findings at post mortem examination. All patients in whom a discrepancy was found had their cases reviewed to determine the significance of the discrepancy using the Goldman classification of post mortem discrepancies. Between June 1996 and May 1999 there were 1718 admissions with 252 deaths (14.7%), where 102 post mortem examinations were performed (40.5%). Five patients were not studied. Of the 97 patients, 4 (4.1%) had Goldman I discrepancies and 19 (19.6%) had Goldman II discrepancies. Complete agreement between pre and post mortem diagnosis was found in 74 (76.3%). Discrepancies fell into four main groups; unrecognised haemorrhage (7 patients), myocardial infarction (5), thromboembolic disease (5) and infectious complications (4).Conclusions: This study reveals that in an intensive care unit important diagnostic discrepancies were found in 19.6% of patients who underwent a post mortem examination. In a fifth of these (4.1%), survival may have been adversely affected. Haemorrhage was the most commonly missed diagnosis. Despite technological advances in intensive care medicine the post mortem examination continues to have an important role in auditing clinical practice and diagnostic performance. [ABSTRACT FROM AUTHOR]

Multiple daily home blood glucose monitoring (HBGM) on a long-term basis places a heavy burden on people with diabetes. This study questions whether multiple daily testing is superior to once-daily testing for the purposes of clinical decision-making once a patient is established on insulin therapy. The HBGM data of 12 IDDM patients treated with three or more insulin injections daily were studied to determine whether once-daily HBGM at a variable time each day (Var1/day) gave adequate information for clinical use. How the type of patient and the different prescribing habits of health professionals affected the outcome were also examined. We found that there was no significant difference in the estimate of mean blood glucose levels derived from Var 1/day and four times daily (4/day) HBGM data. Comparison of insulin dosage adjustments made by six health professionals (based on pairs of glycaemic profiles derived from these two frequencies of monitoring) showed some discrepancies. However, the discrepancies were not greater than those found when the same health professionals adjusted insulin dosage on two different occasions using the same glycaemic profile. By contrast, insulin adjustment was more dependent on whether the patient was suitable for tight glycaemic control (p < 0.05) and on the prescribing habits of health professionals (p < 0.05). Once-daily HBGM at a variable time of the day gave adequate information for clinical intervention and has the advantage of reducing the heavy demand on people with diabetes. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor reporting a change in the design of the dilators for pediatric triple lumen central venous lines.

Evaluates the performance of single-use laryngoscopes in simulated easy and difficult intubation. Comparison of single-use laryngoscopes with the standard Macintosh laryngoscope; Attempts by anesthetists to intubate the simulator.

Discusses the directive by the British Department of Health to use only single-airway devices during tonsillectomy or to dispose of reusable devices if they are used. Use of tracheal tubes and disposable laryngoscopes for tonsillectomy; Anecdotes of problems associated with the use of single-use laryngoscopes.