Worldwide assessment of dalbavancin activity and spectrum against over 6,000 clinical isolates

Continuing emergence of new antimicrobial resistance mechanisms and the increased frequency of existing resistances, requires the development of alternative antimicrobial agents. Dalbavancin is an amide glycopeptide derivative with a markedly extended serum elimination half-life. Dalbavancin and selected comparators were tested against 6,339 recent clinical isolates (2002) from the Americas and Europe using reference susceptibility testing methods. The general characteristics of this Gram-positive organism collection were: oxacillin (OXA)-resistant Staphylococcus aureus (ORSA) at 39% of strains; vancomycin-resistant enterococci (VRE) at 10%; and penicillin-nonsusceptible pneumococci at 28%. The overall distribution of dalbavancin minimum inhibitory concentration (MIC) values ranged from < or = 0.015 to > 32 microg/ml, but > 99% of MIC results were at < or =1 microg/ml. S. aureus and coagulase-negative staphylococci were extremely susceptible to dalbavancin (MIC90, 0.06 microg/ml) despite resistance patterns to other agents. Dalbavancin was the most potent compound (by weight) against vancomycin-susceptible Enterococcus faecalis and E. faecium (MIC90, 0.06 and 0.12 microg/ml, respectively); however, VRE strains showed decreased dalbavancin susceptibility (MIC50, 4 or 8 microg/ml). All streptococcal isolates were inhibited at < or =0.25 microg/ml of dalbavancin. This reported dalbavancin activity indicates that the new glycopeptide has significant activity, superior to available agents in the class, and a potency that was uniform across geographically sampled organisms. Some VRE were inhibited by very low dalbavancin concentrations (< or = 1 microg/ml; Van B phenotypes). Further clinical development seems warranted for this once-weekly administered agent.     

The Importance of Early Carotid Endarterectomy in Symptomatic Patients

INTRODUCTION

Early carotid endarterectomy (CEA) in symptomatic patients may prevent repeat cerebral events. This study investigates the relationship between waiting time for CEA and the incidence of repeat cerebral events prior to surgery in symptomatic patients.

PATIENTS AND METHODS

A prospective database of consecutive patients undergoing CEA between January 2002 and December 2006 was reviewed. Repeat event rates prior to surgery were calculated using Kaplan–Meier analysis and predictive factors identified using Cox regression analysis.

RESULTS

A total of 118 patients underwent CEA for non-disabling stroke, TIA and amaurosis fugax. Repeat cerebral events occurred in 34 of 118 (29%) patients at a median 51 days (range, 2–360 days) after the first event. The estimated risk of repeat events was 2% at 7 days and 9% at 1 month after first event (Kaplan–Meier survival analysis). Age (HR 1.059; 95% CI 1.014–1.106; P = 0.009] was identified as a predictor of repeat events. Patients underwent surgery at median 97 days (range, 7–621 days) after the first event. Eleven of 60 (18%) patients waiting ≤?97 days for surgery and 23 of 58 (40%) patients waiting >?97 days had repeat events. (P = 0.011, chi-squared test).

CONCLUSIONS

Delays in surgery should be reduced in order to minimise repeat cerebral events in patients with symptomatic carotid stenosis, particularly in the elderly population.     

Prenatal Programming of Metabolic Syndrome in the Common Marmoset Is Associated With Increased Expression of 11��-Hydroxysteroid Dehydrogenase Type 1

OBJECTIVE

Recent studies in humans and animal models of obesity have shown increased adipose tissue activity of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), which amplifies local tissue glucocorticoid concentrations. The reasons for this 11β-HSD1 dysregulation are unknown. Here, we tested whether 11β-HSD1 expression, like the metabolic syndrome, is “programmed” by prenatal environmental events in a nonhuman primate model, the common marmoset monkey.

RESEARCH DESIGN AND METHODS

We used a “fetal programming” paradigm where brief antenatal exposure to glucocorticoids leads to the metabolic syndrome in the offspring. Pregnant marmosets were given the synthetic glucocorticoid dexamethasone orally for 1 week in either early or late gestation, or they were given vehicle. Tissue 11β-HSD1 and glucocorticoid receptor mRNA expression were examined in the offspring at 4 and 24 months of age.

RESULTS

Prenatal dexamethasone administration, selectively during late gestation, resulted in early and persistent elevations in 11β-HSD1 mRNA expression and activity in the liver, pancreas, and subcutaneous—but not visceral—fat. The increase in 11β-HSD1 occurred before animals developed obesity or overt features of the metabolic syndrome. In contrast to rodents, in utero dexamethasone exposure did not alter glucocorticoid receptor expression in metabolic tissues in marmosets.

CONCLUSIONS

These data suggest that long-term upregulation of 11β-HSD1 in metabolically active tissues may follow prenatal “stress” hormone exposure and indicates a novel mechanism for fetal origins of adult obesity and the metabolic syndrome.The metabolic syndrome and its component features (central obesity, insulin resistance/type 2 diabetes, hypertension, dyslipidemia) have been causally linked to early life events as marked by low birth weight and other features of an adverse intrauterine environment (1,2). Two major etiological hypotheses of the “developmental origins” effects have been proposed: malnutrition and glucocorticoid overexposure (3,4). These mechanisms of “programming” may be linked because maternal undernutrition increases maternal glucocorticoid concentrations and reduces the placental enzymatic barrier to maternal glucocorticoids in rats, thus increasing fetal glucocorticoid exposure (5). Moreover, maternal glucocorticoid administration reduces food intake in rodents (6).The processes that link intrauterine insults and later risk of the metabolic syndrome are not yet understood. The metabolic syndrome resembles the rare Cushing''s syndrome of circulating glucocorticoid excess, but in uncomplicated metabolic syndrome, plasma cortisol levels are not raised, spawning the suggestion that increased tissue sensitivity to glucocorticoid action may be important in its pathogenesis (7). In the major metabolic organs, tissue sensitivity and exposure to glucocorticoids are determined by the density of intracellular glucocorticoid receptors and the activity of the microsomal enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) which catalyzes the regeneration of active cortisol (corticosterone in rodents) from inert cortisone (11-dehydrocorticosterone) (7). 11β-HSD1 is highly expressed in liver and adipose tissue, where glucocorticoids reduce insulin sensitivity and action (7).In obese humans and in monogenic obesity in rodents, there is a selective increase in 11β-HSD1 mRNA and activity in adipose tissues (8–10). Increased 11β-HSD1 in liver is found in other causes of metabolic syndrome, such as myotonic dystrophy (11). Transgenic overexpression of 11β-HSD1 selectively in adipose tissue in mice recapitulates all the major features of metabolic syndrome without changes in circulating steroid levels (12), whereas overexpression of 11β-HSD1 in liver alone produces an attenuated syndrome with insulin resistance, dyslipidemia, and hypertension, but not hyperglycemia or obesity (13). Conversely, 11β-HSD1 knockout mice are insulin sensitized and resist metabolic syndrome with dietary obesity (14).However, genetic variation in the HSD1B1 gene does not associate with obesity (15), suggesting the cause of increased 11β-HSD1 in adipose tissue in obesity is environmentally determined. Although many factors may upregulate 11β-HSD1 in the short term, attempts to chronically induce 11β-HSD1 in adipose tissue by nongenetic approaches have been unsuccessful. In particular, high-fat diets in rodents downregulate 11β-HSD1 in adipose tissue (16), although this does not appear to occur in humans (17), underlining the importance of relevant models of the human situation.Here, we have explored the early life antecedents of metabolic syndrome and especially 11β-HSD1 expression in metabolic tissues in a nonhuman primate model (the common marmoset monkey) of fetal programming.     

Hepatitis B Immunisation in Health Care Workers

Background

Hepatitis B virus (HBV) infection is an important occupational risk in health care workers (HCW). In spite of HBV vaccine availability in Armed Forces, the high prevalence of HBV infection in HCW continues to be a problem. The study was undertaken to study the HBV vaccine-compliance among HCW.

Methods

A cross-sectional study was conducted at a tertiary care hospital. HCW were requested to fill up the pre set questionnaire to assess the HBV vaccination coverage.

Result

Amongst 254 HCW, only 57.7% were vaccinated against HBV. The vaccine compliance was lowest among housekeeping professionals. The mean age at vaccination was high (30.5 years). Amongst the vaccine non-compliant subjects, 34.3% were above 30 years of age. 32.2% HCW completed primary vaccination after spending more than 10 years in the profession. Accessibility of HBV vaccine, knowledge and perception of HBV risk were important factors in vaccine non-compliance.

Conclusion

Due to low and delayed HBV vaccine-compliance, HCW continue to be at the risk of occupational HBV. Health education highlighting occupational risk of HBV, accessibility of vaccine and mandatory vaccination of HCW is recommended to increase HBV vaccine compliance among HCW.Key Words: Health care workers, Hepatitis B virus, Occupational risk, Hepatitis B vaccine     

Maxillary expansion in cleft lip and palate using Quad helix and rapid palatal expansion screw

Background: Management of patients with cleft lip and palate (CLP) includes orthodontic treatment prior to bone grafting. Palatal expansion is done using slow or rapid palatal expansions (RPE). Controversy still exists regarding choice of expansion appliances used. This study was conducted to find out whether the Quad helix appliance represents a reasonable alternative to using conventional rapid maxillary expansion appliance among cleft lip and palate patients.     

Denosumab对绝以后骨质疏松妇女发生骨折的预防作用

背景及目的：Denosumab为一种人类单克隆抗体,它是核因子B配体(TANK)的受体激活剂(RANKL),RANKL,能够阻断该受体与RANK结合,从而抑制破骨细胞的生长及作用,减少骨的再吸收,增强骨密度.本研究分析了该药物对绝经后妇女骨质疏松症的预防作用.