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Low 25-Hydroxyvitamin D and Risk of Type 2 Diabetes:

A Prospective Cohort Study and MetaanalysisShoaib Afzal 1, Stig E. Bojesen , and Brge G. Nordestgaard .

ABSTRACT:

BACKGROUND: Vitamin D deficiency has been implicated in decreased insulinsecretion and increased insulin resistance, hallmarks of type 2 diabetes mellitus. Wetested the hypothesis that low plasma 25-hydroxyvitamin D [25(OH)D] is associatedwith increased risk of type 2 diabetes in the general population.

METHODS: We measured 25(OH)D in 9841 participants from the general population, ofwhom 810 developed type 2 diabetes during 29 years of follow-up. Analyses wereadjusted for sex, age, smoking status, body mass index, income, physical activity, HDLcholesterol, and calendar month of blood draw.

RESULTS: Lower 25(OH)D concentrations, by clinical categories or seasonallyadjusted quartiles, were associated with higher cumulative incidence of type 2 diabetes(trend, P = 210 7 and P = 410 10). Multivariable adjusted hazard ratios of type 2diabetes were 1.22 (95% CI 0.85 1.74) for 25(OH)D

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Prognostic Utility of Secretory Phospholipase A 2 in Patients with Stable CoronaryArtery Disease

Michelle L. O'Donoghue , Ziad Mallat , David A. Morrow , Joelle Benessiano , SarahSloan , Torbjrn Omland , Scott D. Solomon , Eugene Braunwald , Alain Tedgui ,

and Marc S. Sabatine .

ABSTRACT:

BACKGROUND: Secretory phospholipase A 2 (sPLA 2) may contribute to atherogenesis.

To date, few prospective studies have examined the utility of sPLA 2 for risk stratificationin coronary artery disease (CAD).

The phospholipase A 2 enzymes are members of a large family that hydrolyze the sn-2ester of glycerophospholipids to release free fatty acids and lysophospholipids. Thesecretory phospholipase A 2 (sPLA 2)7 family consists of 10 isoenzymes that are involvedin a variety of biological processes that include hydrolysis of phospholipids, release ofarachidonic acid, and eicosanoid generation (1). sPLA 2 enzymes are distinct fromlipoprotein-associated phospholipase A 2 (Lp-PLA 2), another biomarker that has beenextensively studied for risk stratification and is now being evaluated as a potentialtherapeutic target (2).

Growing evidence suggests that sPLA 2 may play a causal role in the development ofatherosclerosis. sPLA 2-X has been shown to promote macrophage foam cell formationin murine models (3), and upregulated sPLA 2-IIA or sPLA2-V expression has beenshown to increase atherosclerotic lesion size in transgenic mice (4, 5). Additionally,genetic deletion of sPLA 2-V or direct inhibition of sPLA 2 activity has been shown toreduce atherosclerotic lesion progression in animals (5, ,7).To date, a small number of studies have evaluated the utility of sPLA 2 for riskstratification in primary prevention populations and in patients with acute coronarysyndrome (ACS) (1). However, the prognostic utility of sPLA 2 activity has not been wellestablished in a large population of patients with stable coronary artery disease (CAD).

Determination of this association is particularly relevant given the interest in sPLA 2 as apossible therapeutic target for helping to delay the progression of atherosclerosis (8).Furthermore, the relative prognostic utility of sPLA 2 compared with other well-established markers of risk, including those measured using new high-sensitivityassays, remains unknown. We hypothesized that sPLA 2 activity would provideincremental information for risk stratification beyond established clinical risk factors andbiomarkers in a large cohort of subjects with stable CAD.

http://www.clinchem.org/search?author1=Michelle+L.+O%27Donoghue&sortspec=date&submit=Submithttp://www.clinchem.org/search?author1=Michelle+L.+O%27Donoghue&sortspec=date&submit=Submithttp://www.clinchem.org/search?author1=Ziad+Mallat&sortspec=date&submit=Submithttp://www.clinchem.org/search?author1=Ziad+Mallat&sortspec=date&submit=Submithttp://www.clinchem.org/search?author1=Ziad+Mallat&sortspec=date&submit=Submithttp://www.clinchem.org/search?author1=David+A.+Morrow&sortspec=date&submit=Submithttp://www.clinchem.org/search?author1=David+A.+Morrow&sortspec=date&submit=Submithttp://www.clinchem.org/search?author1=David+A.+Morrow&sortspec=date&submit=Submithttp://www.clinchem.org/search?author1=Joelle+Benessiano&sortspec=date&submit=Submithttp://www.clinchem.org/search?author1=Joelle+Benessiano&sortspec=date&submit=Submithttp://www.clinchem.org/search?author1=Joelle+Benessiano&sortspec=date&submit=Submithttp://www.clinchem.org/search?author1=Sarah+Sloan&sortspec=date&submit=Submithttp://www.clinchem.org/search?author1=Sarah+Sloan&sortspec=date&submit=Submithttp://www.clinchem.org/search?author1=Sarah+Sloan&sortspec=date&submit=Submithttp://www.clinchem.org/search?author1=Sarah+Sloan&sortspec=date&submit=Submithttp://www.clinchem.org/search?author1=Torbj%C3%B8rn+Omland&sortspec=date&submit=Submithttp://www.clinchem.org/search?author1=Torbj%C3%B8rn+Omland&sortspec=date&submit=Submithttp://www.clinchem.org/search?author1=Torbj%C3%B8rn+Omland&sortspec=date&submit=Submithttp://www.clinchem.org/search?author1=Scott+D.+Solomon&sortspec=date&submit=Submithttp://www.clinchem.org/search?author1=Scott+D.+Solomon&sortspec=date&submit=Submithttp://www.clinchem.org/search?author1=Scott+D.+Solomon&sortspec=date&submit=Submithttp://www.clinchem.org/search?author1=Eugene+Braunwald&sortspec=date&submit=Submithttp://www.clinchem.org/search?author1=Eugene+Braunwald&sortspec=date&submit=Submithttp://www.clinchem.org/search?author1=Eugene+Braunwald&sortspec=date&submit=Submithttp://www.clinchem.org/search?author1=Alain+Tedgui&sortspec=date&submit=Submithttp://www.clinchem.org/search?author1=Alain+Tedgui&sortspec=date&submit=Submithttp://www.clinchem.org/search?author1=Alain+Tedgui&sortspec=date&submit=Submithttp://www.clinchem.org/search?author1=Marc+S.+Sabatine&sortspec=date&submit=Submithttp://www.clinchem.org/search?author1=Marc+S.+Sabatine&sortspec=date&submit=Submithttp://www.clinchem.org/search?author1=Marc+S.+Sabatine&sortspec=date&submit=Submithttp://www.clinchem.org/content/57/9/1311.full#fn-4http://www.clinchem.org/content/57/9/1311.full#fn-4http://www.clinchem.org/content/57/9/1311.full#fn-4http://www.clinchem.org/content/57/9/1311.full#ref-1http://www.clinchem.org/content/57/9/1311.full#ref-1http://www.clinchem.org/content/57/9/1311.full#ref-1http://www.clinchem.org/content/57/9/1311.full#ref-2http://www.clinchem.org/content/57/9/1311.full#ref-2http://www.clinchem.org/content/57/9/1311.full#ref-2http://www.clinchem.org/content/57/9/1311.full#ref-3http://www.clinchem.org/content/57/9/1311.full#ref-3http://www.clinchem.org/content/57/9/1311.full#ref-3http://www.clinchem.org/content/57/9/1311.full#ref-4http://www.clinchem.org/content/57/9/1311.full#ref-4http://www.clinchem.org/content/57/9/1311.full#ref-4http://www.clinchem.org/content/57/9/1311.full#ref-5http://www.clinchem.org/content/57/9/1311.full#ref-5http://www.clinchem.org/content/57/9/1311.full#ref-5http://www.clinchem.org/content/57/9/1311.full#ref-5http://www.clinchem.org/content/57/9/1311.full#ref-5http://www.clinchem.org/content/57/9/1311.full#ref-6http://www.clinchem.org/content/57/9/1311.full#ref-6http://www.clinchem.org/content/57/9/1311.full#ref-7http://www.clinchem.org/content/57/9/1311.full#ref-7http://www.clinchem.org/content/57/9/1311.full#ref-7http://www.clinchem.org/content/57/9/1311.full#ref-1http://www.clinchem.org/content/57/9/1311.full#ref-1http://www.clinchem.org/content/57/9/1311.full#ref-1http://www.clinchem.org/content/57/9/1311.full#ref-8http://www.clinchem.org/content/57/9/1311.full#ref-8http://www.clinchem.org/content/57/9/1311.full#ref-8http://www.clinchem.org/content/57/9/1311.full#ref-8http://www.clinchem.org/content/57/9/1311.full#ref-1http://www.clinchem.org/content/57/9/1311.full#ref-7http://www.clinchem.org/content/57/9/1311.full#ref-6http://www.clinchem.org/content/57/9/1311.full#ref-5http://www.clinchem.org/content/57/9/1311.full#ref-5http://www.clinchem.org/content/57/9/1311.full#ref-4http://www.clinchem.org/content/57/9/1311.full#ref-3http://www.clinchem.org/content/57/9/1311.full#ref-2http://www.clinchem.org/content/57/9/1311.full#ref-1http://www.clinchem.org/content/57/9/1311.full#fn-4http://www.clinchem.org/search?author1=Marc+S.+Sabatine&sortspec=date&submit=Submithttp://www.clinchem.org/search?author1=Alain+Tedgui&sortspec=date&submit=Submithttp://www.clinchem.org/search?author1=Eugene+Braunwald&sortspec=date&submit=Submithttp://www.clinchem.org/search?author1=Scott+D.+Solomon&sortspec=date&submit=Submithttp://www.clinchem.org/search?author1=Torbj%C3%B8rn+Omland&sortspec=date&submit=Submithttp://www.clinchem.org/search?author1=Sarah+Sloan&sortspec=date&submit=Submithttp://www.clinchem.org/search?author1=Sarah+Sloan&sortspec=date&submit=Submithttp://www.clinchem.org/search?author1=Joelle+Benessiano&sortspec=date&submit=Submithttp://www.clinchem.org/search?author1=David+A.+Morrow&sortspec=date&submit=Submithttp://www.clinchem.org/search?author1=Ziad+Mallat&sortspec=date&submit=Submithttp://www.clinchem.org/search?author1=Michelle+L.+O%27Donoghue&sortspec=date&submit=Submit

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METHODS: We measured plasma sPLA 2 activity at baseline in 3708 subjects in thePEACE randomized trial of trandolapril vs placebo in stable CAD. Median follow-up was4.8 years. We used Cox regression to adjust for demographics, clinical risk factors,apolipoprotein B, apolipoprotein A1, and medications.

RESULTS: After multivariable adjustment, sPLA 2 was associated with an increased riskof cardiovascular death, myocardial infarction, or stroke (adjusted hazard ratio Q4:Q11.55, 95% CI 1.13 2.14) and cardiovascular death or heart failure (1.91, 1.20 3.03). Infurther multivariable assessment, increased activity levels of sPLA 2 were associatedwith the risk of cardiovascular death, myocardial infarction, or stroke (adjusted hazardratio 1.47, 95% CI 1.06 2.04), independent of lipoprotein-associated phospholipaseA2 mass and C-reactive protein, and modestly improved the area under the curve (AUC)beyond established clinical risk factors (AUC 0.668 0.675, P = 0.01). sPLA 2, N-terminalpro-B-type natriuretic peptide, and high-sensitivity cardiac troponin T all wereindependently associated with cardiovascular death or heart failure, and each improved

risk discrimination (P = 0.02, P < 0.001, P < 0.001, respectively). CONCLUSIONS: sPLA 2 activity provides independent prognostic information beyondestablished risk markers in patients with stable CAD. These data are encouraging forstudies designed to evaluate the role of sPLA 2 as a therapeutic target.

Received for publication March 31, 2011.Accepted for publication June 29, 2011.

2011 The American Association for Clinical Chemistry

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Determination of Antimicrobial Resistance Pattern and Production of Extended-

Spectrum -Lactamases amongst Esche-richia coli and Klebsiella pneumoniaefrom Clinical Isolates

Anand Kalaskar, Kandi Vramana

ABSTRACT:

Background: The prevalence of antibiotic resistance among extended- spectrum -lactamase (ESBL) producing Escherichia coliand Klebsiella pneumoniae has beenincreased markedly in recent years. The present study was done to know the

prevalence of ESBL production among isolates of E. coli and K. pneumoniae and tostudy the susceptibility pattern of isolates against different antibiotics.

Methods: Extended- spectrum -lactamase producing E. coli and K. pneumoniae wereisolated from various samples obtained from outdoor and indoor patients of thePrathima Institute of medical sciences, Andhra Pradesh, India. They were tested forESBL production by double disc synergy test and resistance to various antibiotics likefluoroquinolones, cephalosporins, aminoglycosides and -lactamase inhibitorcombinations and susceptibility to carbapenems were determined by Kirby-Bauer discdiffusion method.

Results: A total of 94 ESBL producing isolates were obtained. Of them 60 were E.coli and 34 K. pneumoniae. They were obtained from urine, sputum, pus, wound swabsblood & tracheal aspirates. Urine (38.29%) was the main source of ESBL-producingisolates from all patients, followed by sputum (34.04%). About 37.23% of these isolateswere collected from medical wards and 27.65% were collected from outdoor. All isolateswere susceptible to imipenem. The resistance to cephalosporins (1-4 generations) wasalmost 100%. Resistance to Aztreonam, Ampicillin and Co-amoxyclav was also 100%.A high degree of resistance was observed to other antibiotics.

Conclusion: The highest prevalence of resistance to ESBL in E. coli and K.pneumonia is associated with a multitude of infections in hospitalized patients with asignificant longer duration of hospital stay, increased morbidity and greater hospitalcharges. Advanced drug resistance surveillance and molecular characteristics of ESBLisolates is necessary to guide the proper and judicious antibiotic use.