bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of albuminuria with all-cause and cardiovascular disease mortality in diabetes: the Strong Heart Study
Authors: Xu Jiaqiong , Lee Elisa T , Best Lyle G , Begum Momotaz , Knowler William C , Fabsitz Richard R , Howard Barbara V
Published: August 2008

Objectives — To estimate the relative risks of albuminuria with all-cause and cardiovascular disease (CVD) mortality in a large cohort of American Indians with diabetes. Methods — A total of 1,953 diabetic participants in the Strong Heart Study were evaluated based on albuminuria categories at baseline examination. The Cox proportional hazards model was used to examine associations. Results — Of the 1,953 participants, 605 (31%) and 410 (21%) had microalbuminuria and macroalbuminuria, respectively, at baseline examination. Microalbuminuria (HR=1.42, 95% CI 1.15—1.77 for all-cause, and HR=1.48, CI 1.01—2.17 for CVD), and macroalbuminuria (HR=3.39, CI 2.71—4.25 for all-cause, and HR=3.74, CI 2.56—5.47 for CVD) were significant predictors for all-cause and CVD mortality after adjustment for other CVD risk factors. Conclusions — Results from the present study suggest that albuminuria is a strong independent predictor of all-cause and CVD Mortality in American Indians with diabetes.
Reducing cardiovascular risk in patients with type 2 diabetes: the potential contribution of nicotinic acid
Authors: Van Gaal Luc F , Peiffer Frida , Ballaux Dominique
Published: August 2008

Current treatment guidelines highlight the increased cardiovascular risk associated with type 2 diabetes and identify the need for intensive risk factor management. Dyslipidaemia characterised by elevated serum triglycerides, low levels of high-density lipoprotein cholesterol (HDL-C) and an increase in small, dense low-density lipoprotein cholesterol (LDL-C) particles (the lipid triad), is one of the most important modifiable cardiovascular risk factors in patients with type 2 diabetes. Statins, which are effective in reducing LDL-C, are currently considered the foundation of lipid-lowering treatment in type 2 diabetes, in addition to lifestyle modification. Increasingly, guidelines also identify low HDL-C as an important secondary priority for treatment. Of the available treatment options, both fibrates and nicotinic acid are effective in treating dyslipidaemia associated with type 2 diabetes, although the latter has greater potency in raising HDL-C. Based on its profile of activity, addition of nicotinic acid to primary statin therapy would be a logical strategy in the treatment of diabetic dyslipidaemia. Outcome data from large prospective studies are awaited to confirm the potential morbidity and mortality benefits of this approach.
Review: Fibrates: therapeutic review
Authors: Chapman M John
Published: August 2008

As agonists of the peroxisome proliferator-activated receptor α (PPARα), fibrates are established, effective and well-tolerated agents in the management of atherogenic dyslipidaemia. Key actions of fibrates include a reduction in elevated triglyceride levels (by up to 50%) and a rise in high-density lipoprotein cholesterol (HDL-C) concentrations (typically by 5—15%). Fibrates promote a shift from small, dense low-density lipoprotein (LDL) to larger more buoyant particles, which are less susceptible to oxidation and possess higher binding affinity for removal by the non-atherogenic LDL receptor pathway. Thus, fibrates can correct lipid abnormalities commonly observed in patients with type 2 diabetes and metabolic syndrome. Clinical evidence has demonstrated the value of fibrate therapy in secondary and primary prevention settings, as well as in patients with type 2 diabetes. However, FIELD, the largest fibrate study to date in diabetic patients, predominantly in a primary prevention setting, showed a non-significant 11% reduction in the primary end point of coronary heart disease death and non-fatal myocardial infarction with fenofibrate, although total cardiovascular events, corresponding to the secondary end point, were significantly reduced by 11% (p=0.035). It is possible that risk reduction with fenofibrate may have been attenuated by the two-fold greater drop-in use of statin therapy in the placebo group. However, the interesting results of fenofibrate on attenuation of microangiographic symptomatology potentially suggest a new recommendation for fibrate therapy, although further studies are required to validate these findings.
AUDIT study. Evidence of global undertreatment of dyslipidaemia in patients with type 2 diabetes mellitus
Authors: Leiter Lawrence A , Betteridge D John , Chacra Antonio R , Chait Alan , Ferrannini Eleuterio , Haffner Steven M , Kadowaki Takashi , Tuomilehto Jaakko , Zimmet Paul , Newman Connie B , Hey-Hadavi Judith , Walkinshaw Caroline ,   On Behalf Of The Audit Study Steering Committee
Published: August 2008

The Analysis and Understanding of Diabetes and Dyslipidaemia: Improving Treatment (AUDIT) study was a confidential, web-based, cross-sectional survey involving 2,043 diabetes specialists in 50 countries. The study investigated the attitudes of physicians specialising in the treatment of patients with type 2 diabetes mellitus towards the management of dyslipidaemia and other cardiovascular risk factors in these patients. Physicians reported obtaining lipid profiles in 91% of patients with type 2 diabetes and estimated that 62% of type 2 diabetic patients have dyslipidaemia. Across all regions, stated low-density lipoprotein cholesterol (LDL-C), triglyceride and total cholesterol targets were lower for type 2 diabetic patients with than without cardiovascular disease (CVD). Fewer physicians reported having an LDL-C target of < 2.6 mmol/L (≤100 mg/dL) for patients without CVD (59%) than with CVD (85%). Physicians reported that 54% of patients achieve LDL-C targets, with significantly more estimated to achieve their LDL-C goal in North America (69%) than in any other region (43—61%; p<0.001). When setting targets, 58% of physicians stated that they were most influenced by lipid management guidelines, although a large proportion of physicians from Eastern Europe (54%) and Africa/Middle East (50%) cited a personal read of the literature. Patient compliance was the most commonly perceived barrier to lipid goal attainment in most regions (42—61%); financial constraints were cited most often in South America (76%), Africa/Middle East (65%) and Eastern Europe (63%). The AUDIT study revealed a disparity between lipid screening and control in type 2 diabetic patients. Physicians reported that they treated patients without CVD less intensively than patients with CVD, suggesting that type 2 diabetes was not widely considered a coronary heart disease risk equivalent. A reassessment of guideline implementation is needed for physicians worldwide to improve lipid control to decrease cardiovascular risk in type 2 diabetes.
Mortality rates in hospital patients with hyperglycaemia and MRSA bacteraemia
Authors: Varughese George I , Miltsios Kostos , Buch Harit N , Orendi Jeorge M , Scarpello John Hb
Published: August 2008

Methicillin Resistant Staphylococcus Aureus (MRSA) infections in the hospital population have shown a dramatic increase. This pilot study determined whether random/fasting blood glucose measurements were performed on patients admitted to hospital with MRSA bacteraemia. We also examined mortality in relationship to hyperglycaemia, defined as random glucose ≥ 11 mmol/L. Retrospective data for all in-patients aged ≥ 16 years for the three years; 2000—2002 identified 309 patients with MRSA bacteraemia and all of them had laboratory blood glucose concentrations recorded on admission in all cases. A random blood glucose ≥ 11 mmol/L was noted in 129 (42%) patients of whom 82 (64%) died. The mortality was significantly more likely to be in the highest tertile (p<0.05) of blood glucose distributions.
Review: Thinking around abdominal obesity and cardiovascular risk
Authors: Broom Iain
Published: August 2008

Obesity, particularly intra-abdominal (visceral) obesity, is a leading cause of cardiovascular disease (CVD), insulin resistance, type 2 diabetes, dyslipidaemia, inflammation and thrombosis. A useful indicator for visceral fat is waist circumference, which is associated with all-cause mortality. Pro-inflammatory adipokines play a causal role in the development of pathologies associated with insulin resistance, type 2 diabetes and CVD. In addition to established anti-obesity therapies, namely orlistat and sibutramine, a new type of agent that inhibits the cannabinoid receptor (CB1) is advanced in development to reduce appetite and act predominantly against intra-abdominal adiposity.
Review: Inhaled insulin: overcoming barriers to insulin therapy?
Authors: Bellary Srikanth , Barnett Anthony H
Published: August 2008

nhaled insulin is a new route of insulin delivery that can be used in the treatment of type 1 and type 2 diabetes. It offers an alternative and additional means of insulin administration, and has been received with particular satisfaction by patients who dislike injections. Trials indicate that inhaled insulin can be used effectively for pre-meal bolus intensification of treatment. Pre-meal inhaled insulin with Exubera® has shown faster absorption and similar duration of action to regular subcutaneous insulin with an overall similar glucodynamic effect. Although bioavailability is lower, mainly due to losses in the upper airways, this is compensated for by dose. The commonest side effect reported with inhaled insulin, as with subcutaneous insulin, was hypoglycaemia, almost a quarter of patients noted a cough which settled with continued treatment. Increased antibody titres and changes in lung function return to normal on discontinuation of inhaled insulin. Quality of life scores indicate patient preference for inhaled versus injected insulin, thus increased choice may improve adherence to treatment regimens. However, true cost:benefit analyses have to be undertaken as do studies in children, smokers and people with respiratory conditions, e.g. asthma.
Review: Pharmacological approaches to reduce adiposity
Authors: Day Caroline , Bailey Clifford J
Published: August 2008

A catalogue of antiobesity agents came and went during the last century. The current weight loss agents orlistat and sibutramine are now to be joined by rimonabant, a cannabinoid-1 (CB1) receptor antagonist that acts centrally to decrease appetite and peripherally to reduce lipogenesis in adipose tissue. Use of rimonabant is based on evidence that the endogenous cannabinoid system is overactive in obesity, mainly due to increased expression of CB1 receptors. Weight loss attributed to rimonabant (about 5 kg over one year) was associated with improved insulin sensitivity, reduced triglyceride and increased high density lipoprotein cholesterol. Like other antiobesity agents rimonabant should be used as an adjunct to lifestyle advice. Although there are several potential antiobesity agents in development these are mostly at an early stage of clinical evaluation.
Goodbye glitazars?
Authors: Conlon Deane
Published: August 2008

Glitazars are dual peroxisome proliferator-activated receptors (PPAR) alpha/gamma agonists that improve the lipid profile and exert an antidiabetic action — similar to a combination of a fibrate and a thiazolidinedione. In May 2006 the two glitazars most advanced in development, muraglitazar (Pargluva) and tesaglitazar (Galida) were discontinued. Muraglitazar was associated with an increased incidence of heart failure and tesaglitazar was associated with decreased glomerular filtration.
Review: Heart failure complicating acute myocardial infarction in patients with diabetes: pathophysiology and management strategies
Authors: Sulfi Sreekumar , Timmis Adam D
Published: August 2008

iabetes mellitus increases the risk of acute coronary events and is similar to that of people without diabetes who have experienced a myocardial infarction (MI). Left ventricular failure is a major contributor to the excess mortality observed in diabetic MI. This review explores this excess risk and considers strategies for its prevention and treatment.
Heart failure and diabetes in primary care
Authors: Kirby Mike
Published: August 2008

Diabetes and cardiovascular disease, such as heart failure share many common denominators and they cannot therefore be managed 'in isolation'. The management of overall cardiovascular risk is now the cornerstone to any treatment approach. With the prevalence of both diabetes and heart failure predicted to rise, in a bid to avoid the associated increase in hospital admissions, the onus for effective diagnosis and management of both of these conditions will increasingly fall to those working in primary care. This article explores the current guidelines on managing heart failure in primary care, and specifically looks at the prevention and treatment of heart failure in those with diabetes. Current guidelines recommend angiotensin-converting enzyme (ACE) inhibitors as first-line therapy for heart failure. There is good evidence for this, as well as alternative treatments for those who cannot tolerate ACE inhibitors, or who require additional treatment.
DREAM — a diabetes prevention study
Authors: Conlon Deane
Published: August 2008

he Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study reported in September 2006. This international, multicentre, randomised, double blind, placebo controlled, 2-by-2 factorial prospective three-year study examined the effect of rosiglitazone (8 mg/day) and/or ramipril (15 mg/day) to prevent progression to type 2 diabetes in 5,269 adults with impaired glucose tolerance (IGT), impaired fasting glucose (IFG) or both. The primary end point (incidence of diabetes or death) was reduced by 60% on rosiglitazone (11.6% on rosiglitazone vs. 26.0% on placebo, p<0.0001), and more subjects regained normoglycaemia on rosiglitazone (50.5%) than placebo (30.3%, p<0.0001). Ramipril did not alter the incidence of diabetes or death (18.1% on ramipril vs. 19.5% on placebo) but more subjects regained normoglycaemia on ramipril (42.5%) than placebo (38.2%, p=0.001). There were no apparent interactions between ramipril and rosiglitazone. Although overall cardiovascular event rates were not significantly different between rosiglitazone and placebo there was an increase in heart failure (0.5% on rosiglitazone vs. 0.1% on placebo, p<0.01) and more oedema on rosiglitazone (6.8%) than placebo (4.9%, p<0.003).
Hypoglycaemia: insulin and conflicts with the law
Authors: Marks Vincent
Published: August 2008

ypoglycaemia can bring patients into contact with the law in a variety of ways. It can be used as a defence against almost any criminal charge especially those involved with driving or with violence. It has also been used as an offensive weapon. Allegations of murder by insulin are easy to make but difficult to substantiate as methods of analysis that are appropriate for clinical use are not necessarily adequate for forensic purposes.
Review: Type 2 diabetes in India: regional disparities
Authors: Gupta Rajeev , Misra Anoop
Published: August 2008

Type 2 diabetes mellitus epidemic in India is a result of societal influences and changing lifestyles. Diabetes has been known in India for centuries as a disease of the affluent class. Epidemiological studies in the 1960's and 1970's using random and post-load blood glucose estimations reported diabetes prevalence varying from 1—4% in urban populations and 1—2% in rural populations. More standardised epidemiological studies since the 1990's reported prevalence rates that vary from 5—15% among urban populations, 4—6% in semi-urban populations and 2—5% in rural populations with large location-based disparities within urban and rural populations. There is a significantly increasing trend in urban populations (exponential trend R2=0.744) while among rural populations the prevalence is increasing at a slower rate (R2=0.289). At the turn of this century diabetes in adult urban Indian populations varies from a low of 5.4% in a northern state to a high of 12.3—15.5% in Chennai, South India, and 12.3—16.8% in Jaipur, Central India. This scenario is similar to other South Asian countries and evolving populations in East Asia, Middle-East, Americas, Australasia and Pacific Islands. Gene-environment interactions appear to be responsible for this rapid increase. The insulin-resistant state that was meant to be protective mechanism for regulation of calorie and fat metabolism at times of famine has turned deleterious as affluence has increased among these populations leading to diabetes epidemic. Population based measures to prevent the control of a diabetes epidemic include avoidance of adiposity by enhanced physical activity and regulated calorie intake.
Review: DPP IV inhibitors - current evidence and future directions
Authors: Vilsbøll Tina , Knop Filip K
Published: August 2008

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are responsible for the higher insulin response after oral versus intravenous glucose administration. This effect is called the incretin effect. An impaired incretin effect in patients with type 2 diabetes focused attention on the possible importance of GIP and GLP-1 in diabetes mellitus. Metabolic control can be markedly improved by administration of exogenous GLP-1, but the native peptide is almost immediately degraded by the enzyme dipeptidyl peptidase IV (DPP IV) and, therefore, has little clinical value. Orally active inhibitors of DPP IV have now been developed and have been shown to enhance endogenous levels of GLP-1, resulting in improved glucose tolerance, lasting improvement of HbA1C and improved beta-cell function. In general the DPP IV inhibitors are weight neutral, and well tolerated. One DPP IV inhibitor, sitagliptin, was approved as a once-daily oral therapy for the treatment of type 2 diabetes mellitus in Mexico and USA in 2006, and Europe in 2007. Other DPP IV inhibitors are in late-stage clinical development.
Review: Pre-diabetes: clinical relevance and therapeutic approach
Authors: Pratley Richard E , Matfin Glenn
Published: August 2008

Type 2 diabetes mellitus is epidemic in most developed and many developing countries. The associated morbidity, mortality and high costs of care, make type 2 diabetes an important global public health challenge and target for prevention. Patients at high risk for type 2 diabetes can be diagnosed by fasting glucose levels or responses to an oral glucose tolerance test (OGTT). Such patients are also at increased risk for cardiovascular disease (CVD). Since obesity and physical inactivity are important risk factors for type 2 diabetes, lifestyle interventions, emphasising modest weight loss and increases in physical activity, should be recommended for most patients with pre-diabetes. Such interventions are safe and effective and also reduce risk factors for CVD. Several oral antidiabetic agents have been shown to be effective at delaying onset of type 2 diabetes. Thiazolidinediones (TZDs) reduced incident diabetes by ~60%, whilst metformin, acarbose and orlistat are only about half as effective as the TZDs. Pharmacological interventions may be appropriate for patients at particular risk for developing diabetes, but the benefits of treatment need to be balanced against the safety and tolerability of the intervention. If pharmacological treatment is warranted, metformin should be considered first because of its favourable overall safety, tolerability, efficacy, and cost profile.
Why we need a new model for diabetes care
Authors: Matthews David R
Published: August 2008

MODEL (Management Of Diabetes for ExceLlence) is a group of healthcare professionals calling for a higher ideal of diabetes care in England and Wales. Its report, published in May 2007, finds that while diabetes care is good in many aspects and regions, there are still significant gaps and shortcomings, particularly in the care of children and young people. The scale of growth of diabetes and its growing impact on healthcare costs indicate that a much more forward-looking approach is needed if the NHS is to meet future demands.
Review: Statin plus thiazolidinedione use in patients with diabetes at high cardiovascular risk
Authors: Erdmann Erland
Published: August 2008

People with type 2 diabetes carry an excess burden of cardiovascular risk that warrants close attention to risk factors in the majority of patients. Despite multifactorial intervention, often including statin therapy, a substantial residual risk remains, highlighting the need for novel therapies. Thiazolidinediones (TZDs) are activators of the peroxisome proliferator-activated receptor-gamma that have multiple potentially beneficial effects on established and emerging metabolic risk factors. Available evidence suggests that, even in the presence of statin therapy, TZDs can improve risk factor profiles, reduce atherosclerosis and have a beneficial effect on cardiovascular outcomes. This article reviews the evidence supporting the use of therapy combining a TZD with a statin in patients with type 2 diabetes.
Tolerability of prolonged-release metformin (Glucophage® SR) in individuals intolerant to standard metformin — results from four UK centres
Authors: Feher Michael D , Al-Mrayat Ma'en , Brake Julie , Leong King Sun
Published: August 2008

Advances in drug formulation have improved the tolerability of many commonly used agents. Metformin is recommended as initial drug therapy for type 2 diabetes and has proven long-term efficacy and safety. However, gastrointestinal (GI) side-effects of standard, immediate-release (IR) metformin often reduce medication adherence and limit dose titration. A prolonged-release metformin formulation may improve tolerability over its IR counterpart. We report the results of two prospective and two retrospective clinic-based evaluations of the tolerability of metformin in a total of 95 patients intolerant to standard IR metformin assessed over three to six months following a switch from IR to prolonged-release metformin (Glucophage® SR). Between 62% and 100% of patients from the centres tolerated the prolonged-release formulation. Glycaemia following the switch was improved or unchanged. Prolonged-release metformin represents a useful option for patients intolerant of standard IR metformin due to GI side-effects. This improved tolerance of prolonged-release metformin may improve medication adherence and thereby enhance treatment outcomes.
Review: Pharmacotherapy as part of a weight management programme: a UK perspective
Authors: Barnett Anthony H
Published: August 2008

Rates of obesity and overweight continue to rise and substantially increase the risk of morbidity and mortality from type 2 diabetes, coronary and mortality from type 2 diabetes, coronary heart disease and stroke. On the other hand, a sustained weight loss of 5—10% in the obese confers marked health benefits. Current strategies for the management of obesity include lifestyle interventions and pharmacotherapy. At present, three drugs are approved for the medical management of obesity in the UK: orlistat, sibutramine and rimonabant. All three agents are efficacious in reducing body weight but by different mechanisms. Although weight loss is an important treatment outcome, a major goal of obesity management should be to improve cardiovascular and metabolic risk factors in order to reduce obesity-related morbidity and mortality. Given the similar levels of weight loss achievable with currently approved agents, treatment decisions should include careful assessment of the effects of these agents on cardiovascular and metabolic risk factors and on their long-term safety profiles. Br J Diabetes Vasc Dis 2007;7:268-77
Insulin initiation in primary care for patients with type 2 diabetes: six month follow-up audit
Authors: Dale Jeremy , Gadsby Roger , Shepherd Jonathan
Published: August 2008

Aim

To evaluate the impact of the initiation of basal insulin therapy on glycaemic control (HbA1C) and weight gain in patients with poorly controlled weight gain in patients with poorly controlled type 2 diabetes who were registered with practices that volunteered to participate in an insulin initiation training programme.

Methods

Data at baseline, three and six months post-insulin initiation were collected from log diaries and analysed, for up to 10 patients per practice for each trained healthcare professional (HCP).

Results

Out of 132 participating HCP, 94 (71.2%) provided baseline and three-month data. In 835 patients, of these, 475 (56.9%) also had six-month data. The mean HbA1C at baseline was 9.6%, at three months post insulin initiation it was 8.6%, and at six months it was 7.9%. Out of 381 patients with data on weight change, 1.9% gained weight (mean gain of 1.5 kg over six months). HCPs reported confidence in initiating insulin. They perceived that there was a high level of acceptability to patients.

Conclusion

Attending an insulin initiation training programme may prepare primary HCPs to initiate insulin therapy for patients with poorly controlled type 2 diabetes.

Br J Diabetes Vasc Dis 2008;8:28-31.
Initial and sustained cardiovascular risk reduction in a pharmacist-led diabetes cardiovascular risk clinic
Authors: Mcgowan Neil , Cockburn Alison , Strachan Mark Wj , Padfield Paul L , Mcknight John A
Published: August 2008

Background

The atherogenic milieu of hypertension, hyperglycaemia and dyslipidaemia results in an excess of cardiovascular deaths in the diabetic population.

Objective

To determine the efficacy and long-term success of a pharmacist-delivered cardiovascular risk reduction clinic.

Methods

Patients with diabetes not achieving blood pressure (BP) and lipid targets at a standard diabetes clinic had a mean of four visits to the pharmacist-delivered clinic.

Results

BP was significantly reduced by attending the clinic (mean reduction in clinic BP 23/10 mmHg). Ambulatory BP monitoring demonstrated a mean reduction of 13/9 mmHg from clinic entry to discharge and this effect was sustained six months post-discharge .

Total cholesterol was reduced by 0.4 mmol/L (p=0.002) during clinic attendances and remained unchanged post discharge.

Conclusion

Patients previously thought to be `resistant' to treatment can have significant reductions in cardiovascular risk factors when enrolled in a short-lived, intense clinic set-up. This is maintained
Vascular complications of diabetes in Lebanon: Experience at the American University of Beirut
Authors: Taleb Nadine , Salti Haytham , Al-Mokaddam Mona , Merheb Marie , Salti Ibrahim , Nasrallah Mona
Published: August 2008

Aim To examine the metabolic control and presence of

complications, among a cohort of diabetic patients in Lebanon. Method A total of 313 diabetic patients presenting for their usual care were screened in a cross-sectional manner for metabolic control and presence of complications at the American University of Beirut.

Results Only 235 subjects completed their data of whom 220 (93%) had type 2 diabetes with mean duration of disease of 8.2 (±6.6) years. Only 30% had haemoglobin A1C < 7%, and 35.5% had low-density lipoprotein Cholesterol < 2.6 mmol/L. About 50.5% were obese, 34.9% current smokers, and 40.7% had blood pressure ≥ 140/90 mmHg. Microvascular complications were present as 46.3, 39.9 and 33% for albuminuria, neuropathy, 33% for albuminuria, neuropathy, and retinopathy, respectively. Macrovascular complications were as follows: 19.3, 18.3 and 4.1% for coronary artery disease, peripheral vascular disease and cerebrovascular disease, respectively.

Conclusions This study highlights the poor control and high prevalence of vascular complications among adult type 2 diabetic patients in Lebanon.
Pharmacist-led structured care for patients with diabetic nephropathy
Authors: Kelly Christopher JG , Booth Gillian
Published: August 2008

Intensive multifactorial intervention reduces end points in patients with diabetic nephropathy. Traditional clinics struggle to provide the intensity of care required to meet targets for this growing patient group. We designed a pharmacist-led, protocol driven clinic to offer stepwise intensive treatment to patients with diabetic nephropathy picked up at the traditional secondary care clinic. One hundred and sixteen individuals received more than one review. The clinic achieved significant improvements in blood pressure (BP): systolic 151±19 mmHg vs.133±15 mmHg (p<0.001), diastolic 80±10 mmHg vs. 68±10 mmHg (p<0.001) and total cholesterol 4.56 mmol/L±1.05 mmol/L vs. 4.03±1.07 mmol/L (p<0.001). Albumin:creatinine ratio also improved 27±44 vs. 20±31 (p=0.02). Structured intervention within a pharmacist-led clinic has led to a rapid and significant reduction in BP and cholesterol in microalbuminuric patients. This format of care can form the basis of patient focused, target driven, care.
Review: Clinical aspects of the management of HIV lipodystrophy
Authors: Wierzbicki Anthony S , Purdon Scott D , Hardman Timothy C , Kulasegaram Ranjababu , Peters Barry S
Published: August 2008

Chronic complications of human immunodeficiency virus (HIV) and highly active retroviral therapy have become increasingly relevant as life expectancy for HIV patients has improved and the affected population ages. HIV-associated lipodystrophy syndrome is characterised by an abnormal fat distribution syndrome associated with metabolic disturbances including insulin resistance, and deranged glucose and lipid metabolism. It is associated with increased risks of progression to type 2 diabetes and cardiovascular disease.

Lipodystrophy is a clinical diagnosis and mostly subjective as standardised diagnostic criteria have not yet been defined. Several therapeutic interventions have been investigated including lifestyle therapy, vitamin supplements, switching antiretroviral therapy and specific therapies for insulin resistance and hyperlipidaemia. Current management options for HIV associated lipodystrophy are limited and are mostly based on avoidance of risk factors and switching of antiretroviral drugs. Therapies to improve insulin resistance have been tried but they are frequently ineffective as are lipid-lowering drugs. Interest in anabolic agents has been resurrected and new clinical data suggest that HIV-associated lipodystrophy growth hormone releasing factor therapy may have a beneficial role in the treatment of HIV-associated lipodystrophy. However, there still remains a need for robust prospective cohort studies and well designed intervention trials to resolve the aetiology and define the best treatment for this complication of HIV disease and its treatment.
The MERCURY I open-label extension study — subgroup analysis in patients with diabetes
Authors: Schuster Herbert , Palmer Mike K , Ditmarsch Marc
Published: August 2008

Background The MERCURY I open-label extension study provides safety and efficacy data on hypercholesterolaemic patients with type 2 diabetes treated with rosuvastatin for up to three years.

Methods A total of 2,492 hypercholesterolaemic patients, including 665 (26.7%) with type 2 diabetes, on rosuvastatin 10 mg or 20 mg were followed for a mean of 672 days in an open-label extension study during which the dose could be increased to 20 or 40 mg to reach the 1998 European low-density lipoprotein-cholesterol (LDL-C) target of < 3.0 mmol/L (< 115 mg/dL)

Results Most diabetic and non-diabetic patients started (85.4 % and 88.7%) and finished (78.3% and 77.6%) on rosuvastatin 10 mg. Adverse event (9.8% and 12.3%) and treatment discontinuation (2.2% and 3.5%) rates were similar in diabetic and non-diabetic patients. No myopathy or rhabdomyolysis was observed. Mean serum creatinine decreased in both subgroups. Proteinuria was reported as an adverse event in five (0.7%) diabetic patients and eight (0.4%) non-diabetic patients. Fasting plasma glucose did not change markedly in either subgroup. LDL-C decreased by 51.1% and 47.4% in diabetic and non-diabetic patients, respectively, with 92.4% and 90.3% reaching target LDL-C.

Conclusion Long-term rosuvastatin treatment is effective and well tolerated in diabetic patients.
RNA STRAND: The RNA Secondary Structure and Statistical Analysis Database
Authors: Andronescu Mirela , Bereg Vera , Hoos Holger H , Condon Anne
Published: August 2008

Background

The ability to access, search and analyse secondary structures of a large set of known RNA molecules is very important for deriving improved RNA energy models, for evaluating computational predictions of RNA secondary structures and for a better understanding of RNA folding. Currently there is no database that can easily provide these capabilities for almost all RNA molecules with known secondary structures.

Results

In this paper we describe RNA STRAND – the RNA secondary STRucture and statistical ANalysis Database, a curated database containing known secondary structures of any type and organism. Our new database provides a wide collection of known RNA secondary structures drawn from public databases, searchable and downloadable in a common format. Comprehensive statistical information on the secondary structures in our database is provided using the RNA Secondary Structure Analyser, a new tool we have developed to analyse RNA secondary structures. The information thus obtained is valuable for understanding to which extent and with which probability certain structural motifs can appear. We outline several ways in which the data provided in RNA STRAND can facilitate research on RNA structure, including the improvement of RNA energy models and evaluation of secondary structure prediction programs. In order to keep up-to-date with new RNA secondary structure experiments, we offer the necessary tools to add solved RNA secondary structures to our database and invite researchers to contribute to RNA STRAND.

Conclusion

RNA STRAND is a carefully assembled database of trusted RNA secondary structures, with easy on-line tools for searching, analyzing and downloading user selected entries, and is publicly available at http://www.rnasoft.ca/strand.
Angiotensin-converting enzyme genotype and late respiratory complications of mustard gas exposure
Authors: Hosseini-khalili Ali Reza , Thompson Julian , Kehoe Anthony , Hopkinson Nicholas S , Khoshbaten A , Soroush Mohammad Reza , Humphries Steve E , Montgomery Hugh , Ghanei Mostafa
Published: August 2008

Background

Exposure to mustard gas frequently results in long-term respiratory complications. However the factors which drive the development and progression of these complications remain unclear. The Renin Angiotensin System (RAS) has been implicated in lung inflammatory and fibrotic responses. Genetic variation within the gene coding for the Angiotensin Converting Enzyme (ACE), specifically the Insertion/Deletion polymorphism (I/D), is associated with variable levels of ACE and with the severity of several acute and chronic respiratory diseases. We hypothesized that the ACE genotype might influence the severity of late respiratory complications of mustard gas exposure.

Methods

208 Kurdish patients who had suffered high exposure to mustard gas, as defined by cutaneous lesions at initial assessment, in Sardasht, Iran on June 29 1987, underwent clinical examination, spirometric evaluation and ACE Insertion/Deletion genotyping in September 2005.

Results

ACE genotype was determined in 207 subjects. As a continuous variable, FEV1 % predicted tended to be higher in association with the D allele 68.03 ± 20.5%, 69.4 ± 21.4% and 74.8 ± 20.1% for II, ID and DD genotypes respectively. Median FEV1 % predicted was 73 and this was taken as a cut off between groups defined as having better or worse lung function. The ACE DD genotype was overrepresented in the better spirometry group (Chi2 4.9 p = 0.03). Increasing age at the time of exposure was associated with reduced FEV1 %predicted (p = 0.001), whereas gender was not (p = 0.43).

Conclusion

The ACE D allele is associated with higher FEV1 % predicted when assessed 18 years after high exposure to mustard gas.
A SYBR Green RT-PCR assay in single tube to detect human and bovine noroviruses and control for inhibition
Authors: Scipioni Alexandra , Mauroy Axel , Ziant Dominique , Saegerman Claude , Thiry Etienne
Published: August 2008

Background

Noroviruses are single-stranded RNA viruses belonging to the family Caliciviridae. They are a major cause of epidemic and sporadic gastroenteritis in humans and clinical signs and lesions of gastroenteritis were reported in bovines. Due to their genetic proximity, potential zoonotic transmission or animal reservoir can be hypothesized for noroviruses. RT-PCR has become the "gold standard" for the detection of noroviruses in faecal and environmental samples. With such samples, the control for inhibition of the reaction during amplification and detection is crucial to avoid false negative results, which might otherwise not be detected. The aim of the reported method is to detect, with a SYBR Green technology, a broad range of noroviruses with a control for inhibition.

Results

A SYBR Green real-time RT-PCR assay was developed making use of a foreign internal RNA control added in the same tube. This assay is able to detect human and bovine noroviruses belonging to genogroups I, II and III and to distinguish between norovirus and internal control amplicons using melting curve analysis. A 10-fold dilution of samples appears to be the method of choice to remove inhibition. This assay was validated with human and bovine stool samples previously tested for norovirus by conventional RT-PCR.

Conclusion

This SYBR Green real-time RT-PCR assay allows the detection of the most important human and bovine noroviruses in the same assay, and avoids false negative results making use of an internal control. Melting curves allow the discrimination between the internal control and norovirus amplicons. It gives preliminary information about the species of origin. The sensitivity of the developed assay is higher than conventional RT-PCR and a 10-fold dilution of samples showed a better efficiency and reproducibility to remove RT-PCR inhibition than addition of bovine serum albumin.
Differential wedging of vertebral body and intervertebral disc in thoracic and lumbar spine in adolescent idiopathic scoliosis – A cross sectional study in 150 patients
Authors: Modi Hitesh N , Suh Seung Woo , Song Hae-Ryong , Yang Jae-Hyuk , Kim Hak-Jun , Modi Chetna H
Published: August 2008

Background

Hueter-Volkmann's law regarding growth modulation suggests that increased pressure on the end plate of bone retards the growth (Hueter) and conversely, reduced pressure accelerates the growth (Volkmann). Literature described the same principle in Rat-tail model. Human spine and its deformity i.e. scoliosis has also same kind of pattern during the growth period which causes wedging in disc or vertebral body.

Methods

This cross sectional study in 150 patients of adolescent idiopathic scoliosis was done to evaluate vertebral body and disc wedging in scoliosis and to compare the extent of differential wedging of body and disc, in thoracic and lumbar area. We measured wedging of vertebral bodies and discs, along with two adjacent vertebrae and disc, above and below the apex and evaluated them according to severity of curve (curve < 30° and curve > 30°) to find the relationship of vertebral body or disc wedging with scoliosis in thoracic and lumbar spine. We also compared the wedging and rotations of vertebrae.

Results

In both thoracic and lumbar curves, we found that greater the degree of scoliosis, greater the wedging in both disc and body and the degree of wedging was more at apex supporting the theory of growth retardation in stress concentration area. However, the degree of wedging in vertebral body is more than the disc in thoracic spine while the wedging was more in disc than body in lumbar spine. On comparing the wedging with the rotation, we did not find any significant relationship suggesting that it has no relation with rotation.

Conclusion

From our study, we can conclude that wedging in disc and body are increasing with progression on scoliosis and maximum at apex; however there is differential wedging of body and disc, in thoracic and lumbar area, that is vertebral body wedging is more profound in thoracic area while disc wedging is more profound in lumbar area which possibly form 'vicious cycle' by asymmetric loading to spine for the progression of curve.
Power of grammatical evolution neural networks to detect gene-gene interactions in the presence of error
Authors: Motsinger-Reif Alison A , Fanelli Theresa J , Davis Anna C , Ritchie Marylyn D
Published: August 2008

Background

With the advent of increasingly efficient means to obtain genetic information, a great insurgence of data has resulted, leading to the need for methods for analyzing this data beyond that of traditional parametric statistical approaches. Recently we introduced Grammatical Evolution Neural Network (GENN), a machine-learning approach to detect gene-gene or gene-environment interactions, also known as epistasis, in high dimensional genetic epidemiological data. GENN has been shown to be highly successful in a range of simulated data, but the impact of error common to real data is unknown. In the current study, we examine the power of GENN to detect interesting interactions in the presence of noise due to genotyping error, missing data, phenocopy, and genetic heterogeneity. Additionally, we compare the performance of GENN to that of another computational method – Multifactor Dimensionality Reduction (MDR).

Findings

GENN is extremely robust to missing data and genotyping error. Phenocopy in a dataset reduces the power of both GENN and MDR. GENN is reasonably robust to genetic heterogeneity and find that in some cases GENN has substantially higher power than MDR to detect functional loci in the presence of genetic heterogeneity.

Conclusion

GENN is a promising method to detect gene-gene interaction, even in the presence of common types of error found in real data.
Normative values for the Foot Posture Index
Authors: Redmond Anthony C , Crane Yvonne Z , Menz Hylton B
Published: August 2008

Background

The Foot Posture Index (FPI) is a validated method for quantifying standing foot posture, and is being used in a variety of clinical settings. There have however, been no normative data available to date for comparison and reference. This study aimed to establish normative FPI reference values.

Methods

Studies reporting FPI data were identified by searching online databases. Nine authors contributed anonymised versions of their original datasets comprising 1648 individual observations. The datasets included information relating to centre, age, gender, pathology (if relevant), FPI scores and body mass index (BMI) where available. FPI total scores were transformed to interval logit scores as per the Rasch model and normal ranges were defined. Comparisons between groups employed t‐tests or ANOVA models as appropriate and data were explored descriptively and graphically.

Results

The main analysis based on a normal healthy population (n = 619) confirmed that a slightly pronated foot posture is the normal position at rest (mean back transformed FPI raw score = +4). A ‘U’ shaped relationship existed for age, with minors and older adults exhibiting significantly higher FPI scores than the general adult population (F = 51.07, p < 0.001). There was no difference between the FPI scores of males and females (2.3 versus 2.5; t = ‐1.44, p = 0.149). No relationship was found between the FPI and BMI. Systematic differences from the adult normals were confirmed in patients with neurogenic and idiopathic cavus (F = 216.981, p < 0.001), indicating some sensitivity of the instrument to detect a posturally pathological population.

Conclusion

A set of population norms for children, adults and older people have been derived from a large sample. Foot posture is related to age and the presence of pathology, but not influenced by gender or BMI. The normative values identified may assist in classifying foot type for the purpose of research and clinical decision making.
Emphysematous pyelonephritis, a rare cause of pneumoperitoneum: a case report and review of literature
Authors: Strofilas Alexandros , Manouras Andreas , Lagoudianakis Emmanuel E , Kotzadimitriou Aikaterini , Pappas Apostolos , Chrysikos Ioannis , Menenakos Evangelos
Published: August 2008

Introduction

Emphysematous pyelonephritis is a gas-producing necrotizing bacterial infection that involves the renal parenchyma and perirenal tissue.

Case presentation

We report on a case of a 55 year old Caucasian male with no prior medical history presented with left flank pain and malaise. He was diagnosed with emphysematous pyelonephritis, and was successfully treated in our department. The case is presented along with a literature review.

Conclusion

Prompt diagnosis and early treatment is crucial because of the high rate of mortality. Therapeutic modalities and prognostic factors regarding emphysematous pyelonephritis remain controversial.
Sphingosine-1-phosphate receptors regulate individual cell behaviours underlying the directed migration of prechordal plate progenitor cells during zebrafish gastrulation
Authors: Kai Masatake , Heisenberg Carl-Philipp , Tada Masazumi
Published: August 2008

During vertebrate gastrulation, cells forming the prechordal plate undergo directed migration as a cohesive cluster. Recent studies revealed that E-cadherin-mediated coherence between these cells plays an important role in effective anterior migration, and that platelet-derived growth factor (Pdgf)appears to act as a guidance cue in this process. However, the mechanisms underlying this process at the individual cell level remain poorly understood. We have identified miles apart (mil) as a suppressor of defective anterior migration of the prospective prechordal plate in silberblick (slb)/wnt11 mutant embryos, in which E-cadherin-mediated coherence of cell movement is reduced. milencodes Edg5, a sphingosine-1-phosphate (S1P) receptor belonging to a family of five G-protein-coupled receptors (S1PRs). S1P is a lipid signalling molecule that has been implicated in regulating cytoskeletal rearrangements,cell motility and cell adhesion in a variety of cell types. We examined the roles of Mil in anterior migration of prechordal plate progenitor cells and found that, in slb embryos injected with mil-MO, cells migrate with increased motility but decreased directionality, without restoring the coherence of cell migration. This indicates that prechordal plate progenitor cells can migrate effectively as individuals, as well as in a coherent cluster of cells. Moreover, we demonstrate that Mil regulates cell motility and polarisation through Pdgf and its intracellular effecter PI3K,but modulates cell coherence independently of the Pdgf/PI3K pathway, thus co-ordinating cell motility and coherence. These results suggest that the net migration of prechordal plate progenitors is determined by different parameters, including motility, persistence and coherence.
Chato, a KRAB zinc-finger protein, regulates convergent extension in the mouse embryo
Authors: García-García María J. , Shibata Maho , Anderson Kathryn V.
Published: August 2008

In Xenopus and zebrafish embryos, elongation of the anterior-posterior body axis depends on convergent extension, a process that involves polarized cell movements and is regulated by non-canonical Wnt signaling. The mechanisms that control axis elongation of the mouse embryo are much less well understood. Here, we characterize the ENU-induced mouse mutation chato, which causes arrest at midgestation and defects characteristic of convergent extension mutants, including a shortened body axis, mediolaterally extended somites and an open neural tube. The chato mutation disrupts Zfp568, a Krüppel-associated box (KRAB)domain zinc-finger protein. Morphometric analysis revealed that the definitive endoderm of mouse wild-type embryos undergoes cell rearrangements that lead to convergent extension during early somite stages, and that these cell rearrangements fail in chato embryos. Although non-canonical Wnt signaling is important for convergent extension in the mouse notochord and neural plate, the results indicate that chato regulates body axis elongation in all embryonic tissues through a process independent of non-canonical Wnt signaling.