bluuebunny/crossref_metadata_2025 huggingface dataset:
Review: Severe mental illness, antipsychotic drugs and the metabolic syndrome
Authors: Holt Richard Ig
Published: August 2008

The prevalence of the metabolic syndrome is increased 2—3-fold among people with severe mental illness (SMI) and may explain the high risk of cardiovascular disease in this patient group. The reason for the increase in the metabolic syndrome in people with SMI is unclear but is likely to be multifactorial, including both hereditary and environmental factors. There are concerns that antipsychotic medication may be responsible for the increased prevalence of diabetes, the metabolic syndrome and cardiovascular disease in people with SMI. While the evidence linking the antipsychotics with diabetes remains inconclusive, certain antipsychotics, notably olanzapine and clozapine are associated with weight gain and hypertriglyceridaemia. At present there is little systematic monitoring of cardiovascular risk factors in people with SMI and consequently there is a high prevalence of undiagnosed metabolic problems. The burden of cardiovascular disease and diabetes could be reduced in people with SMI if lifestyle intervention was instituted and pharmacotherapy used when indicated. The adverse effects of antipsychotic medication should be balanced with the therapeutic benefits which may be important in ensuring that patients are able to make the necessary changes to reduce the burden of diabetes and cardiovascular disease.
Review: Non-alcoholic fatty liver disease in childhood
Authors: Baumann Ulrich , Brown Rachel
Published: August 2008

Non-alcoholic fatty liver disease (NAFLD) is an often undiagnosed entity of chronic liver disease with an uncertain prognosis. Recently NAFLD has probably become the most frequent cause of chronic liver disease in children. The term NAFLD covers a spectrum of non-alcoholic fatty liver disease from benign static disease to more aggressive forms that can progress to cirrhosis within childhood. The term non-alcoholic steatohepatitis (NASH) is nowadays reserved to describe these progressive forms of NAFLD. Insulin resistance is a significant aetiological factor and hence a majority of patients with diabetes, obesity and the metabolic syndrome have the disease. Histological confirmation of NAFLD requires 5% steatosis to support the diagnosis and distinguishes an adult (NASH type 1) and a paediatric form (NASH type 2). Current treatment options focus on lifestyle changes to improve underlying obesity and glucose intolerance. This article provides an overview of currently existing data regarding diagnosis and management of children with suspected NAFLD.
Assessment of arterio-ventricular coupling by tissue Doppler and wave intensity in type 2 diabetes
Authors: Avgeropoulou Catherine , Illmann Alexander , Schumm-Draeger Petra-Maria , Kallikazaros Jannis , Von Bibra Helene
Published: August 2008

Aim

To evaluate ventricular-arterial coupling in preclinical cardiovascular disease, we used a new wave intensity approach and tissue Doppler in patients with and without type 2 diabetes mellitus (DM).

Methods

Sixty-five type 2 diabetes patients and 57 control individuals with normal systolic left ventricular function and without overt coronary or peripheral artery disease were assessed by tissue Doppler for myocardial velocities and by a combined Doppler and echo-tracking system (Aloka SSD-5500, Tokyo) for local arterial stiffness (epsilon, pulse wave velocity) and the characteristic peaks W1 and W2 of pulse wave intensity.

Results

Diabetes patients had significantly higher systolic blood pressure and pressure derivates (p<0.002). Diastolic myocardial velocity (Ve) was decreased (p<0.001). Epsilon and pulse wave velocity (p<0.001) were higher and so was W1 (11785±7491 vs. 9191±4299, p<0.04) but not W2. In the pooled data, independent predictors for Ve were age, septal wall thickness, Vs and HbA1C (R2 duration of diabetes (R2 0.479). 0.426) and for W1 systolic blood pressure, Vs, W2 and duration of diabetes (R2 0.479).

Conclusion

In type 2 diabetes pump function is preserved and maintained against increased arterial stiffness and impedance at the expense of increased myocardial oxygen requirements. Tissue Doppler and wave intensity measurements may be useful for therapeutic monitoring.
Review: Pharmacological and non-pharmacological treatment of endothelial dysfunction: relevance to diabetes
Authors: Gkaliagkousi Eugenia , Shah Ashish , Ferro Albert
Published: August 2008

Vascular disease is the most important complication of both type 1 and type 2 diabetes, with both micro- and macrovascular disease underlying most of the death and disability observed in diabetic patients. Endothelial dysfunction is a cardinal feature of both types of diabetes, and is believed to be involved in the aetiology and pathophysiology of diabetic vasculopathy. Therefore, measures which improve endothelial dysfunction in diabetes are currently the subject of much interest and research. In this article, we review both drug and non-drug therapies for endothelial dysfunction, along with evidence of their effectiveness in diabetes. We suggest that those therapies for which good evidence of endothelial benefit exists should be more widely used in diabetic patients, and that the maximum benefit will be derived by using multiple such therapies in combination.
Rational therapy of mixed dyslipidaemia in a patient with diabetes
Authors: Reasner Charles
Published: August 2008

Diabetic dyslipidaemia refers to the triad of elevated levels of triglycerides and small, dense LDL-C particles and low levels of HDL-C. These lipid abnormalities are largely responsible for the increased risk of cardiovascular complications in patients with diabetes. This case study outlines a rational approach to the treatment of each of these lipid abnormalities and emphasises the importance of both lowering the LDL-C and raising the HDL-C in high-risk individuals. Combination drug therapy will often be necessary to achieve treatment goals in these patients.
PET scan before CABG in diabetes
Authors: Hegazy Hesham , Refaei Ayman , Assedique Azza , Alsaif Shukri , Taha Mayada , Refaei Mostafa , Elkum Nasser , Alomran Hamed , Al-Halees Zohair
Published: August 2008

Background and objectives

Since the role of positron emission tomography (PET) scanning in diabetes is not clear, this study sought to assess the usefulness of PET scanning for viability in this patient group.

Methods

Forty-four per cent insulin-treated, and 56% non-insulin-treated diabetic patients with severely impaired left ventricular function (LVEF 29± 9%) underwent first coronary artery bypass grafting (CABG). Pre-operative viability was assessed by PET scan.

Results

Eighty-two per cent of patients received ≥3 grafts. Twenty-seven patients were discharged home and followed for a mean 3.5±1.6 years. Postoperative LVEF improved to 40±9 (p<0.0001). Multiple regression analysis indicated that the only variable that predicted improvement in global LV function was presence of hibernating segments at PET scan. The single variable that predicted deterioration of LVEF was the number of segments with reduced perfusion and metabolism at PET scan.

Conclusion

PET scan is an accurate tool for prediction of global left ventricular function recovery following CABG in people with diabetes.
Improving outcomes of pregnancy for women with type 1 and type 2 diabetes
Authors: Murphy Helen R , Temple Rosemary C , Roland Jonathan M
Published: August 2008

The pregnancy outcomes for women with type 1 diabetes remain poor with increased risk of major congenital malformation, stillbirth, premature delivery and perinatal death compared to the background maternity population. Despite clear evidence that women who attend prepregnancy care have improved blood glucose control with reduced risk of serious adverse outcomes, only a minority of women attend these clinics. For women with type 2 diabetes who are older, more obese and more likely to belong to an ethnic minority or live in an area of social deprivation, pregnancy outcomes are at least as poor as for women with type 1 diabetes. This is important as the prevalence of type 2 diabetes in women of reproductive years is increasing and even fewer women with type 2 diabetes attend prepregnancy care or take folic acid supplementation. Greater awareness regarding the risks among women with diabetes as well as primary and secondary healthcare professionals is required, if pregnancy outcomes are to be improved.
Review: New anticoagulants: a story of promise and disappointment
Authors: Watson Henry G , Greaves Mike
Published: August 2008

The anticoagulant drugs which are available currently — coumarins and heparins — are reasonably effective but are insufficiently specific and often inconvenient to manage. An improved understanding of the physiology of blood coagulation and its control mechanisms has led to the identification of target enzymes for novel, specific and potentially safer antithrombotics. These targets include the pivotal coagulation enzyme thrombin as well as other enzymes and co-factors within the tissue factor dependent coagulation pathway. In addition, analogues of physiological anticoagulants hold promise as therapeutic agents. It is likely that the range of drugs available for the management of thrombosis will expand over the next decade. There is the very real possibility of the introduction of orally active agents which may be used in fixed dosage regimens with no requirement for laboratory monitoring.
Review: Insulin glulisine — the potential for improved glycaemic control
Authors: Owens David R
Published: August 2008

Tight glycaemic control is essential to reduce the risk of developing the micro- and macrovascular complications of diabetes. Plasma levels of glycosylated haemoglobin (HbA 1C) are a marker for long-term glycaemia; controlling these levels within tight limits forms the cornerstone of long-term diabetes management. As a result of evidence from key clinical trials in type 1 and type 2 diabetes, HbA1C targets ranging from < 6.5 to < 7.5% have been set by various authorities. To achieve these targets, insulin regimens need to reflect normal physiological insulin release. Several rapid- and long-acting insulin analogues have been developed to mimic aspects of insulin secretion. Insulin glulisine is a genetically engineered insulin which has a rapid onset and short lived action, allowing it to closely mimic prandial release of insulin. In addition to the structural change in the insulin molecule, the absence of excess zinc and the addition of polysorbate 20 as a surfactant facilitates its disassociation in the subcutaneous tissue and inhibits its aggregation when used in subcutaneous insulin delivery systems due to improved physical stability.
Treating to target in type 2 diabetes
Authors: Keigher Carol , Avalos Gloria , Dunne Fidelma
Published: August 2008

Patients with type 2 diabetes have a three-fold increased risk of developing vascular disease with death in 75% due to a vascular complication. Large prospective studies have demonstrated the benefits of treating patients with type 2 diabetes to strict targets regarding blood pressure (BP), lipids and glucose. Using both American Diabetes Association and Joint British Societies/Guidelines we assessed the effectiveness of this `treat-to-target' policy in diabetic patients attending secondary care. Of 321 patient notes analysed 54—87% were within target for total cholesterol, 80—84% for LDL cholesterol, 77% for HDL cholesterol, 51% for triglycerides, 44—61% for systolic BP, 62% for diastolic BP and 30—44% for HbA1C. In the secondary care setting we are performing well for lipids, less well for BP and poorly for HbA1C.
Good diabetes control in practice: a survey of healthcare professionals
Authors: Kirby Mike
Published: August 2008

Maintaining tight glycaemic control is essential for reducing the risk of chronic complications in both type 1 and type 2 diabetes. However, in practice this poses a major challenge for healthcare professionals. Professor Mike Kirby discusses findings from a survey, to gain insight into current opinion amongst healthcare professionals concerning diabetes control. Strategies for overcoming barriers to good diabetes control are discussed.
Sitagliptin — enhancing incretin action
Authors: Campbell Ian W , Day Caroline
Published: August 2008

DPP-4 inhibition offers a new approach to the treatment of type 2 diabetes. Sitagliptin is the first in this new class of agent that lowers hyperglycaemia mainly via enhancing the action of endogenous incretin hormones. Sitagliptin improves glycaemic control with a low risk of hypoglycaemia or weight gain.
Review: Imaging to assess effect of medical therapy in patients with diabetes mellitus
Authors: Raggi Paolo , Bellasi Antonio
Published: August 2008

The incidence of type 2 diabetes is rapidly increasing throughout the world. As an independent risk factor for cardiovascular disease both at the microvascular and macrovascular level, diabetes is a condition that deserves the most aggressive medical management. The effectiveness of risk factor modification and glycaemic control on retarding atherosclerosis progression has been assessed by several invasive and non-invasive imaging methods that will be reviewed in this article.
Review: Microvascular complications: evaluation and monitoring relevance to clinical practice, clinical trials, and drug development
Authors: Greenstein Adam , Tavakoli Mitra , Mojaddidi Moaz , Al-Sunni Ahmed , Matfin Glenn , Malik Rayaz A
Published: August 2008

The long-term microvascular complications of diabetes pose a major health burden. Although, much of the focus has been on the macrovascular much of the focus has been on the macrovascular complications, it is clear that the microvascular complications have a significant impact on both morbidity and mortality amongst diabetic patients. Indeed retinopathy, nephropathy, and neuropathy compete as the leading causes of premature blindness, end-stage renal disease, and non-traumatic lower-limb amputation, respectively. Furthermore, complications develop and progress in unison and indeed share many common risk factors. Effective evaluation and monitoring of these complications in clinical practice is clearly important, however, it is also relevant to clinical addressing microvascular complications, Novel intervention studies, and drug development programs diagnostic and therapeutic strategies are continually evolving in this area and will be discussed in more detail in this review.
Review: 50 years later: is metformin a vascular drug with antidiabetic properties?
Authors: Wiernsperger Nicolas F
Published: August 2008

Since the clinical demonstration of a protective effect of metformin against chronic diabetic angiopathy in the United Kingdom Prospective Diabetes Study, many data have accumulated which confirm such effects in acute or chronic situations as diverse as ischaemia, non-diabetic insulin resistant states and diabetes. Recent years have provided several mechanisms of action and further documented some unique properties of this compound such as improvements in microcirculatory flow, glycation and oxidative stress. In particular, the latter effect could be shown in mitochondria, i.e. the most important sources of reactive oxygen species in diabetes. Specific, non-toxic actions of metformin at the level of the mitochondrial respiratory chain also prevent apoptosis, another mechanism to explain the long-term protection afforded by metformin. Noteworthy, most of these effects of metformin are unrelated to drug dosage and largely independent of its antihyperglycaemic effect (intrinsic properties). These new data open potential avenues for larger therapeutic utilisations of this drug, 50 years after its launch for the treatment of type 2 diabetes.
Review: Acute metabolic derangement and the heart
Authors: Cubbon Richard M , Kearney Mark T
Published: August 2008

Complex metabolic disturbances are an important feature of critical illness, though simpler abnormalities, such as hypokalaemia are present in a significant proportion of patients. Whilst increasing the complexity of management plans, these circumstances also increase the risk of cardiac complications, such as arrhythmia, and furthermore are associated with increased mortality. Arrhythmic risk is promoted by electrolyte, acid base and fluid balance disturbance, increased sympathetic drive and cardiac ischaemia. Moreover, complex pharmacological regimes may exacerbate the situation. On rarer occasions metabolic disarray can impair myocardial excitation-contraction coupling resulting in cardiac failure. Management of the underlying pathology may be all that is required to allow rapid normalisation of the metabolic profile. However, targeted metabolic intervention may be required on occasions to prevent or assist in the correction of cardiac compromise.
Negative pressure wound therapy
Authors: Kirby Michael
Published: August 2008

iabetic foot disease is a major global burden. Foot ulcers frequently develop complications and become chronic, representing a considerable challenge as these are typically very difficult to treat. New therapies are needed to address these wounds and there is an increasing focus on negative pressure wound therapy (NPWT). This technique has been shown to accelerate wound healing and although its costs are significant, there is also evidence to show that it compares favourably with more conventional alternatives. However, most studies to date have been small, and larger trials are needed before NPWT becomes more routine. In the meantime, the procedure may be most suitable for large, chronic, heavily exuding wounds that do not respond to established therapies.
Peripheral arterial disease — a cardiovascular time bomb
Authors: Belch Jill , Stansby Gerry , Shearman Cliff , Brittenden Julie , Dugdill Shiela , Fowkes Gerry , Jarvis Sarah , Mccann Terrie , Mimnagh Andrew , Monkman David , Morrell Jonathan
Published: August 2008

Peripheral arterial disease (PAD) is a reliable marker of future vascular disease and is a substantial public health issue. In Europe and North America, 27 million people are estimated to have PAD, and in the UK around 100,000 people are diagnosed every year. People with PAD are six times more likely to die from cardiovascular disease within 10 years than people without PAD. Evidence suggests that aggressive risk factor management will prevent many premature deaths and associated morbidity. Therefore, it is vital to identify patients and initiate effective management strategies swiftly. However, whilst 40% of PAD patients have symptomatic disease ranging from intermittent claudication to critical limb ischaemia, around 60% are asymptomatic. As a result of the low rates of detection PAD is underdiagnosed and undertreated in the UK. The gravity of the problem has prompted the formation of professional bodies to address this situation through the development of national clinical guidelines. Indeed, with the focus of general practitioners' work covered by the quality and outcomes framework in the General Medical Services (GMS) contract, many consider that the inclusion of PAD in the GMS contract is critical to raising awareness and improving the management of PAD in primary care.
Review: Targeting therapeutics against glutathione depletion in diabetes and its complications
Authors: Livingstone Callum , Davis James
Published: August 2008

Glutathione (GSH) is the most abundant intracellular antioxidant, the dysregulation of which is widely implicated in disease states. There is in vitro and clinical evidence that abnormal glutathione status is involved in β-cell dysfunction and in the pathogenesis of long-term complications of diabetes. Interest has developed in the potential for therapeutic modification of glutathione status in the treatment of diabetes. There is evidence which supports the use of glutathione pro-drugs, lipoic acid and vitamin supplementation but further studies are required before these enter widespread use. Studies into the role of oxidative stress in diabetes rely heavily on the ability to measure glutathione, which has been a problematic analyte to measure in the laboratory. New electrochemical methods being developed should speed up the rate at which data can be accumulated and will help define clinical utility for its measurement.
Providing diabetes care to Arab migrants in the UK: cultural and clinical aspects
Authors: Goenka Nirupam , Thomas Sherine , Shaikh Sakera , Morrisey John , Patel Vinod
Published: August 2008

Arab migrants make up a significant minority of the Muslim population of the UK. As the result of recent conflicts in the Middle East there has been an increase in the number of Arab refugee's seeking asylum in the UK, and therefore this population is expected to increase in the future. Whilst UK Arabs share the increased diabetes and cardiovascular risk that is seen in South Asian migrants, they are distinct in terms of customs and traditions. Culturally appropriate, validated, evidence-based management strategies in order to aggressively control the cardiovascular risk factors in this high risk diabetic population are required.
Vasodilator prostanoids compensate for attenuated nitric oxide mediated vasodilation in type 1 diabetes
Authors: Browne Duncan L , Meeking Darryl R , Allard Sharon , Munday Linda J , Shaw Kenneth M , Cummings Michael H
Published: August 2008

Background Previous research examining endothelial function and the biochemical pathways mediating vasodilation in type 1 diabetes has been conflicting. Both impaired and preserved nitric oxide (NO) mediated vasodilation have been reported whilst some authors have suggested enhanced vasodilator prostanoid (P) activity. The aim of this study was to determine the relative contributions of NO and P to endothelial function in a homogenous group of type 1 diabetic patients free of other confounding factors that may influence vascular behaviour.^f ^

Methods and results Endothelial function was assessed using forearm venous plethysmography in 16 patients with uncomplicated type 1 (duration of diabetes 16.8±2.5 years (mean±SEM), HbA1C 7.53±0.21% ) and 15 non-diabetic age and sex matched healthy control subjects. Forearm responses to the endothelium-dependent vasodilator, acetylcholine (ACh) (7.5, 15 and 30 µg/min), were recorded at baseline and after intra-arterial infusion of L-NMMA (a NO synthase inhibitor). Responses to ACh were re-examined following co-infusion of L-NMMA and indomethacin (a cyclo-oxygenase inhibitor). Responses to ACh were calculated as areas under the curve (AUC). At baseline vasodilator responses to ACh were similar (p=0.3) in diabetic and non-diabetic subjects. However, L-NMMA reduced ACh mediated responses to a lesser extent in diabetic subjects than control subjects (3±6% versus 18±3%; p<0.03 respectively). Co-infusion with indomethacin further reduced blood flow, but the relative decrease in AUC was greater in the diabetic group (28±3% vs. 14±3%; p<0.001). The contribution of biochemical pathways other than NO and P were similar in both diabetic and control groups (69±7% vs. 68±4%; p=0.45).

Conclusions Vasodilator responses to ACh were unchanged in type 1 diabetes but this was reliant up on enhanced P mediated activity compensating for attenuated NO activity. Furthermore, vasoactive substances in addition to NO and P contribute significantly to vascular tone in both diabetic and non-diabetic subjects.
Review: Postprandial glycaemia and cardiovascular risk
Authors: Peter Rajesh , Rees Alan
Published: August 2008

Cardiovascular disease (CVD) accounts for almost 75% of mortality in subjects with type 2 diabetes. There is emerging evidence (epidemiological and There is emerging evidence (epidemiological and experimental studies) that postprandial glucose (PPG) contributes significantly to CVD risk, although to date there are no large scale interventional studies with the primary objective of reducing cardiovascular complications by targeting PPG. There is still continuing debate about the definition of postprandial hyperglycaemia. Moreover, we now know more of the cellular mechanisms being triggered in response to glucose excursions which may offer an explanation to this increased susceptibility to CVD. The contribution of PPG to glycosylated haemoglobin, is predominant in relatively well controlled subjects with type 2 diabetes. Hence, PPG is emerging as a legitimate therapeutic target to minimise CVD risk.

This review looks at the evidence linking postprandial hyperglycaemia to CVD, the cellular mechanisms explaining this enhanced risk and a therapeutic strategy to address PPG.
Review: The role of fenofibrate in reducing cardiovascular risk in type 2 diabetes
Authors: Pedro-Botet Juan
Published: August 2008

Dyslipidaemia (elevated triglycerides, low high-density lipoprotein-cholesterol [HDL-C] and an increase in small, dense low-density lipoprotein [LDL] particles) is an important contributor to the increased cardiovascular risk associated with type 2 diabetes. Lowering LDL-C levels with a statin is the main focus of lipid-modifying intervention. Fibrates are effective against all components of this atherogenic mixed dyslipidaemia. Adding a fibrate to primary statin therapy is a logical approach to achieving all lipid targets. Evidence from the Fenofibrate Invention and Event Lowering in Diabetes trial also shows that fenofibrate is a well-tolerated option with potential benefits on the progression of microvascular complications of type 2 diabetes. Thus fenofibrate-statin combination therapy may translate into greater reductions in vascular risk.fenofibrate, safety, type 2 diabetes.
Thiazolidinediones and cardiovascular outcomes
Authors: Barnett Anthony H
Published: August 2008

Diabetes mellitus is associated with a number of serious microvascular and macrovascular complications that have a devastating effect on quality of life and impose a heavy burden on healthcare systems. In order to decrease the risk of diabetes-related complications, individuals with diabetes should normally receive intensive and effective treatment for all metabolic disturbances, including hyperglycaemia. Thiazolidinediones are an important part of this therapeutic armamentarium, but are currently the subject of intense scrutiny following the publication of a meta-analysis reporting increased cardiovascular risk with rosiglitazone. Based on available data, the FDA has concluded that the use of rosiglitazone for the treatment of type 2 diabetes may be associated with a greater risk of myocardial ischaemic events than placebo, metformin or sulphonylureas and have added label warnings to the prescribing information until the results of long-term cardiovascular outcome trials become available. To date, increased cardiovascular risk has not been reported with pioglitazone and indeed there is evidence suggestive of cardiovascular protection. Thiazolidinediones are effective glucose-lowering agents, complementing existing treatment approaches and thus have a continuing role to play in the management of diabetes.
Review: Early-onset type 2 diabetes mellitus: a condition with elevated cardiovascular risk?
Authors: Song Soon H
Published: August 2008

The age of onset of type 2 diabetes mellitus is falling and this condition has become increasingly common among those aged under 30 years including children and adolescents. Early-onset type 2 diabetes has been reported in various countries from different ethnic and cultural backgrounds reflecting the effects of sedentary lifestyle as part of globalisation and industrialisation affecting all societies. The pathophysiological features of early-onset type 2 diabetes is similar to the later-onset cohort characterised by β-cell failure and obesity-induced insulin resistance but the decline in β-cell function appears to be more rapid. Early-onset type 2 diabetes may be a more aggressive disease phenotype to develop cardiovascular complications than later-onset cohort, reflected by more adverse cardiovascular risk profile and higher relative risk for myocardial infarction. Given the paucity of clinical trial evidence in this population, clinical judgement is required to initiate treatments to prevent cardiovascular complications guided by assessment of global cardiovascular risk. Future research strategies should include exploration of cardiovascular risk factors. its natural history, development of complications and outcome studies pertaining to the treatment of cardiovascular risk factors.
Review: Gluten and glucose management in type 1 diabetes
Authors: Waldron-Lynch Frank , O'Loughlin Aonghus , Dunne Fidelma
Published: August 2008

The prevalence of coeliac disease in patients with type 1 diabetes is significantly increased when compared to the general population. Ancompared to the general population. An explanation of the association between the development of both diseases may be explained by the inheritance of common major histocompatibility complex immunogenotypes that influence the presentation of auto antigens to CD4+ T-Cells. The subsequent loss of self tolerance results in destruction of the small bowel villi and pancreatic β-cells in coeliac and type 1 diabetes respectively. The diagnosis of coeliac disease in type 1 diabetic patients occurs commonly as a result of screening of individuals with subclinical coeliac disease. Recent studies have demonstrated the clinical benefit of treating subclinical coeliac disease in children with improvement in growth parameters, resolution of anaemia and fewer hypoglycaemic episodes. There is no current clinical evidence supporting routine screening of adult type 1 diabetic patients for coeliac disease. After the diagnosis of coeliac disease, type 1 diabetic patients should be commenced on a gluten-free diet with care co-ordinated between a dietician, gastroenterologist anddiabetologist.
Inflammation is associated with liver function markers, independent of other metabolic risk factors in overweight women
Authors: Browning Lucy M , Krebs Jeremy D , Siervo Mario , Hall Rosemary M , Finer Nicholas , Allison Michael ED , Jebb Susan A
Published: August 2008

Non-alcoholic fatty liver disease, common in Nobesity, is characterised by fatty infiltration to the liver and can progress to steatohepatitis. Inflammation is a predictor of metabolic disease, but the relationship between inflammation and liver disease is unclear. This study determines whether liver function enzymes are associated with markers of systemic inflammation. In a group of 249 overweight women, fasting blood samples were collected and analysed for insulin, glucose, lipids, C-reactive protein (CRP), sialic acid (SA), alanine aminotransferase, alkaline phosphatase (ALP) and γ-glutamyltransferase.

SA and CRP were significant predictors of ALP concentrations, independent of metabolic syndrome features (β=0.35, p<0.0001 and β=0.20, p=0.004). SA and CRP showed significant incremental increases across groups based on the number of features of metabolic disease, which persisted after adjustement for body mass index (β=0.32, p<0.0001 and =0.16, p=0.02). These data suggest that systemic inflammation is significantly associated with liver function markers, Independent of other metabolic risk factors.
Economic costs of diabetes in the US in 2007 — Implications for Europe
Authors: Bottomley Julia
Published: August 2008

In March 2008 the latest American Diabetes Association (ADA) commissioned economic study of the costs of diabetes in 2007 was published. The economic burden of diabetes was quantified in terms of its increased healthcare resource use (direct costs) and lost productivity (indirect costs) and provided a detailed breakdown of the costs attributed to diabetes. In the five years since the ADA published a similar analysis, the number of Americans with diagnosed diabetes has risen from 12.1 to 17.1 million and the economic cost has risen from $132 billion (equivalent to $153 billion in 2007 dollars) to $174 billion. This major analysis is reviewed and the implications for Europe are considered. The findings are similar to those described in earlier US studies and also landmark European economic studies in diabetes. The results are also discussed in the context of the well accepted association of type 2 diabetes and overweight and obesity and because obesity has reached epidemic proportions in developed and developing countries
Investigation of peripheral vascular disorders using thermal imaging
Authors: Bagavathiappan Subramaniam , Saravanan Thangavelu , Philip John , Jayakumar Tammana , Raj Baldev , Karunanithi Rajamanickam , Panicker Thaze Mr , Korath Paul , Jagadeesan Kesavan
Published: August 2008

Infrared thermal imaging has been used to study non-invasive diagnosis of peripheral vascular diseases. Temperature gradients indicating abnormal blood flow in the affected regions of patients with vascular disorders are well correlated with clinical findings. The temperature in the affected regions was about 0.7—1°C above the normal regions, due to slow blood circulation. Thermal imaging is an effective technique for detecting small temperature changes due to vascular disorders, it is non-invasive, portable, compact and safe.
HIV-associated lipodystrophy - a new metabolic syndrome
Authors: Hakeem Lukman , Campbell Ian W , Bhattacharyya Diptendu Nath
Published: August 2008

Human immunodeficiency virus (HIV) associated lipodystrophy may affect up to half or even more HIV-infected patients receiving antiretroviral therapy. However, a simple practical definition for this condition is still lacking. Features of lipoatrophy and lipohypertrophy may be seen in this condition. Intrinsic host factors and disease status, as well as treatment duration and type, probably play key roles in the aetiology. Several metabolic abnormalities such as dyslipidaemia and insulin resistance have been commonly reported in these patients. Most attempts to improve or reverse abnormal fat distribution have so far only shown modest success. Therefore, choosing optimal antiretroviral therapy is vital. There are too few reasons to support widespread use of rosiglitazone and metformin in these patients except on an individual basis. However, lipid lowering agents should be considered in the treatment of severe hypertriglyceridaemia and elevated low-density lipoprotein-cholesterol or a combination of both as lipid abnormalities are commonly seen in thesepatients. Advances in plastic surgery are attractive treatment options as they give immediate results.
Staphylococcus aureus Brain Abscess in an HIV-Infected Patient Exposed to Enfuvirtide
Authors: Denoeud Lise , Pacanowski Jérôme , Welker Yves , Moulignier Antoine , Girard Pierre-Marie
Published: August 2008

Brain abscesses are common among HIV-infected immunocompromised patients. Encephalitis caused by Toxoplasma gondii infection has to be presumed, on which treatment is initiated. The authors report an unusual case of a brain abscess caused by Staphylococcus aureus in an HIV-infected patient exposed to enfuvirtide, for which this empirical strategy failed.
Risk of lymphoproliferative disorders among first-degree relatives of lymphoplasmacytic lymphoma/Waldenström macroglobulinemia patients: a population-based study in Sweden
Authors: Kristinsson Sigurdur Y. , Björkholm Magnus , Goldin Lynn R. , McMaster Mary L. , Turesson Ingemar , Landgren Ola
Published: August 2008

A role for genetic factors in the etiology of lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM) is implicated based on prior findings from multiply affected families and small case-control and cohort studies. We identified 2144 LPL/WM patients (1539 WM [72%] and 605 LPL [28%]) diagnosed in Sweden, 8279 population-based matched controls, and linkable first-degree relatives of patients (n = 6177) and controls (n = 24 609). Using a marginal survival model, we calculated relative risks and 95% confidence intervals as measures of familial aggregation. We found first-degree relatives of LPL/WM patients to have 20-fold (4.1-98.4), 3.0-fold (2.0-4.4), 3.4-fold (1.7-6.6), and 5.0-fold (1.3-18.9) increased risks of developing LPL/WM, non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL), and monoclonal gammopathy of undetermined significance (MGUS), respectively. However, there was no evidence of an increased risk of developing multiple myeloma or Hodgkin lymphoma. In analyses stratified by type of first-degree relative (parent, sibling, offspring), age at diagnosis of the probands (greater or less than 70 years), and sex of the first-degree relative, we did not observe the risk estimates to be significantly different compared with the overall analyses. Our findings of highly increased risks of developing LPL/WM, NHL, CLL, and MGUS support the operation of shared susceptibility genes that predispose to LPL/WM and other lymphoproliferative disorders.
Distribution of the transposable elements bilbo and gypsy in original and colonizing populations of Drosophila subobscura
Authors: García Guerreiro María Pilar , Chávez-Sandoval Blanca E , Balanyà Joan , Serra Lluís , Fontdevila Antonio
Published: August 2008

Background

Transposable elements (TEs) constitute a substantial amount of all eukaryotic genomes. They induce an important proportion of deleterious mutations by insertion into genes or gene regulatory regions. However, their mutational capabilities are not always adverse but can contribute to the genetic diversity and evolution of organisms. Knowledge of their distribution and activity in the genomes of populations under different environmental and demographic regimes, is important to understand their role in species evolution. In this work we study the chromosomal distribution of two TEs,gypsyandbilbo, in original and colonizing populations ofDrosophila subobscurato reveal the putative effect of colonization on their insertion profile.

Results

Chromosomal frequency distribution of two TEs in one original and three colonizing populations ofD. subobscura, is different. Whereas the original population shows a low insertion frequency in most TE sites, colonizing populations have a mixture of high (frequency ≥ 10%) and low insertion sites for both TEs. Most highly occupied sites are coincident among colonizing populations and some of them are correlated to chromosomal arrangements. Comparisons of TE copy number between the X chromosome and autosomes show thatgypsyoccupancy seems to be controlled by negative selection, butbilboone does not.

Conclusion

These results are in accordance that TEs inDrosophila subobscuracolonizing populations are submitted to a founder effect followed by genetic drift as a consequence of colonization. This would explain the high insertion frequencies ofbilboandgypsyin coincident sites of colonizing populations. High occupancy sites would represent insertion events prior to colonization. Sites of low frequency would be insertions that occurred after colonization and/or copies from the original population whose frequency is decreasing in colonizing populations. This work is a pioneer attempt to explain the chromosomal distribution of TEs in a colonizing species with high inversion polymorphism to reveal the putative effect of arrangements in TE insertion profiles. In general no associations between arrangements and TE have been found, except in a few cases where the association is very strong. Alternatively, founder drift effects, seem to play a leading role in TE genome distribution in colonizing populations.
Multiple actions of lysophosphatidic acid on fibroblasts revealed by transcriptional profiling
Authors: Stortelers Catelijne , Kerkhoven Ron , Moolenaar Wouter H
Published: August 2008

Background

Lysophosphatidic acid (LPA) is a lipid mediator that acts through specific G protein-coupled receptors to stimulate the proliferation, migration and survival of many cell types. LPA signaling has been implicated in development, wound healing and cancer. While LPA signaling pathways have been studied extensively, it remains unknown how LPA affects global gene expression in its target cells.

Results

We have examined the temporal program of global gene expression in quiescent mouse embryonic fibroblasts stimulated with LPA using 32 k oligonucleotide microarrays. In addition to genes involved in growth stimulation and cytoskeletal reorganization, LPA induced many genes that encode secreted factors, including chemokines, growth factors, cytokines, pro-angiogenic and pro-fibrotic factors, components of the plasminogen activator system and metalloproteases. Strikingly, epidermal growth factor induced a broadly overlapping expression pattern, but some 7% of the genes (105 out of 1508 transcripts) showed differential regulation by LPA. The subset of LPA-specific genes was enriched for those associated with cytoskeletal remodeling, in keeping with LPA's ability to regulate cell shape and motility.

Conclusion

This study highlights the importance of LPA in programming fibroblasts not only to proliferate and migrate but also to produce many paracrine mediators of tissue remodeling, angiogenesis, inflammation and tumor progression. Furthermore, our results show that G protein-coupled receptors and receptor tyrosine kinases can signal independently to regulate broadly overlapping sets of genes in the same cell type.
Lung cancer mortality in towns near paper, pulp and board industries in Spain: a point source pollution study
Authors: Monge-Corella Susana , García-Pérez Javier , Aragonés Nuria , Pollán Marina , Pérez-Gómez Beatriz , López-Abente Gonzalo
Published: August 2008

Background

This study sought to ascertain whether there might be excess lung cancer mortality among the population residing in the vicinity of Spanish paper and board industries which report their emissions to the European Pollutant Emission Register (EPER).

Methods

This was an ecological study that modelled the Standardised Mortality Ratio (SMR) for lung cancer in 8073 Spanish towns over the period 1994–2003. Population exposure to industrial pollution was estimated on the basis of distance from town of residence to pollution source. An exploratory, near-versus-far analysis was conducted, using mixed Poisson regression models and an analysis of the effect of municipal proximity within a 50-kilometre radius of each of the 18 installations.

Results

Results varied for the different facilities. In two instances there was an increasing mortality gradient with proximity to the installation, though this was exclusively observed among men.

Conclusion

The study of cancer mortality in areas surrounding pollutant foci is a useful tool for environmental surveillance, and serves to highlight areas of interest susceptible to being investigated by ad hoc studies. Despite present limitations, recognition is therefore due to the advance represented by publication of the EPER and the study of pollutant foci.
Restriction by APOBEC3 proteins of endogenous retroviruses with an extracellular life cycle: ex vivo effects and in vivo"traces" on the murine IAPE and human HERV-K elements
Authors: Esnault Cécile , Priet Stéphane , Ribet David , Heidmann Odile , Heidmann Thierry
Published: August 2008

Background

APOBEC3 cytosine deaminases have been demonstrated to restrict infectivity of a series of retroviruses, with different efficiencies depending on the retrovirus. In addition, APOBEC3 proteins can severely restrict the intracellular transposition of a series of retroelements with a strictly intracellular life cycle, including the murine IAP and MusD LTR-retrotransposons.

Results

Here we show that the IAPE element, which is the infectious progenitor of the strictly intracellular IAP elements, and the infectious human endogenous retrovirus HERV-K are restricted by both murine and human APOBEC3 proteins in an ex vivo assay for infectivity, with evidence in most cases of strand-specific G-to-A editing of the proviruses, with the expected signatures. In silico analysis of the naturally occurring genomic copies of the corresponding endogenous elements performed on the mouse and human genomes discloses "traces" of APOBEC3-editing, with the specific signature of the murine APOBEC3 and human APOBEC3G enzymes, respectively, and to a variable extent depending on the family member.

Conclusion

These results indicate that the IAPE and HERV-K elements, which can only replicate via an extracellular infection cycle, have been restricted at the time of their entry, amplification and integration into their target host genomes by definite APOBEC3 proteins, most probably acting in evolution to limit the mutagenic effect of these endogenized extracellular parasites.
Arch height change during sit‐to‐stand: an alternative for the navicular drop test
Authors: McPoil Thomas G , Cornwall Mark W , Medoff Lynn , Vicenzino Bill , Forsberg Kelly , Hilz Dana
Published: August 2008

Background

A study was conducted to determine the reliability and validity of a new foot mobility assessment method that utilizes digital images to measure the change in dorsal arch height measured at 50% of the length of the foot during the Sit‐to‐Stand test.

Methods

Two hundred – seventy five healthy participants participated in the study. The medial aspect of each foot was photographed with a digital camera while each participant stood with 50% body weight on each foot as well as in sitting for a non‐weight bearing image. The dorsal arch height was measured at 50% of the total length of the foot on both weight bearing and non‐weight bearing images to determine the change in dorsal arch height. The reliability and validity of the measurements were then determined.

Results

The mean difference in dorsal arch height between non‐weight bearing and weight bearing was 10 millimeters. The change in arch height during the Sit‐to‐Stand test was shown to have good to high levels of intra‐ and inter‐reliability as well as validity using x‐rays as the criterion measure.

Conclusion

While the navicular drop test has been widely used as a clinical method to assess foot mobility, poor levels of inter‐rater reliability have been reported. The results of the current study suggest that the change in dorsal arch height during the Sit‐to‐Stand test offers the clinician a reliable and valid alternative to the navicular drop test.
Maturation of dendritic cells depends on proteolytic cleavage by cathepsin X
Authors: Obermajer Nataša , Švajger Urban , Bogyo Mathew , Jeras Matjaž , Kos Janko
Published: August 2008

The maturation status of dendritic cells (DCs) is crucial for effective antigen presentation and initiation of the primary immune response. Maturation stimuli cause the adhesion of immature DCs to the extracellular matrix, which is accompanied by recruitment of the CD11b/CD18 [macrophage antigen-1 (Mac-1)] integrin receptor, cytoskeleton reorganization, and podosome formation. Cathepsin X, a cysteine protease expressed in DCs and other APCs, is involved in Mac-1 activation. We have shown that during maturation, cathepsin X translocates to the plasma membrane of maturing DCs, enabling Mac-1 activation and consequently, cell adhesion. In mature DCs, cathepsin X redistributes from the membrane to the perinuclear region, which coincides with the de-adhesion of DCs, formation of cell clusters, and acquisition of the mature phenotype. Inhibition of cathepsin X activity during DC differentiation and maturation resulted in an altered phenotype and function of mature DCs. It reduced surface expression of costimulatory molecules, increased expression of inhibitory Ig-like transcripts 3 and 4 (ILT3 and ILT4), almost completely abolished cytokine production, diminished migration, and reduced the capacity of DCs to stimulate T lymphocytes. These results stress the importance of cathepsin X in regulating DC adhesion, a crucial event for their maturation and T cell activation.