(Sub)stellar companions shape the winds of evolved stars.

Binary interactions dominate the evolution of massive stars, but their role is less clear for low- and intermediate-mass stars. The evolution of a spherical wind from an asymptotic giant branch (AGB) star into a nonspherical planetary nebula (PN) could be due to binary interactions. We observed a sample of AGB stars with the Atacama Large Millimeter/submillimeter Array (ALMA) and found that their winds exhibit distinct nonspherical geometries with morphological similarities to planetary nebulae (PNe). We infer that the same physics shapes both AGB winds and PNe; additionally, the morphology and AGB mass-loss rate are correlated. These characteristics can be explained by binary interaction. We propose an evolutionary scenario for AGB morphologies that is consistent with observed phenomena in AGB stars and PNe.

CTCF genetic alterations in endometrial carcinoma are pro-tumorigenic.

CTCF is a haploinsufficient tumour suppressor gene with diverse normal functions in genome structure and gene regulation. However the mechanism by which CTCF haploinsufficiency contributes to cancer development is not well understood. CTCF is frequently mutated in endometrial cancer. Here we show that most CTCF mutations effectively result in CTCF haploinsufficiency through nonsense-mediated decay of mutant transcripts, or loss-of-function missense mutation. Conversely, we identified a recurrent CTCF mutation K365T, which alters a DNA binding residue, and acts as a gain-of-function mutation enhancing cell survival. CTCF genetic deletion occurs predominantly in poor prognosis serous subtype tumours, and this genetic deletion is associated with poor overall survival. In addition, we have shown that CTCF haploinsufficiency also occurs in poor prognosis endometrial clear cell carcinomas and has some association with endometrial cancer relapse and metastasis. Using shRNA targeting CTCF to recapitulate CTCF haploinsufficiency, we have identified a novel role for CTCF in the regulation of cellular polarity of endometrial glandular epithelium. Overall, we have identified two novel pro-tumorigenic roles (promoting cell survival and altering cell polarity) for genetic alterations of CTCF in endometrial cancer.

The ethnicity-specific association of biomarkers with the angiographic severity of coronary artery disease.

BACKGROUND: Risk factor burden and clinical characteristics of patients with coronary artery disease (CAD) differ among ethnic groups. We related biomarkers to CAD severity in Caucasians, Chinese, Indians and Malays. METHODS: In the Dutch-Singaporean UNICORN coronary angiography cohort (n = 2033) we compared levels of five cardiovascular biomarkers: N-terminal pro-brain natriuretic peptide (NTproBNP), high-sensitivity C-reactive protein (hsCRP), cystatin C (CysC), myeloperoxidase (MPO) and high-sensitivity troponin I (hsTnI). We assessed ethnicity-specific associations of biomarkers with CAD severity, quantified by the SYNTAX score. RESULTS: Adjusted for baseline differences, NTproBNP levels were significantly higher in Malays than in Chinese and Caucasians (72.1 vs. 34.4 and 41.1 pmol/l, p < 0.001 and p = 0.005, respectively). MPO levels were higher in Caucasians than in Indians (32.8 vs. 27.2 ng/ml, p = 0.026), hsTnI levels were higher in Malays than in Caucasians and Indians (33.3 vs. 16.4 and 17.8 ng/l, p < 0.001 and p = 0.029) and hsTnI levels were higher in Chinese than in Caucasians (23.3 vs. 16.4, p = 0.031). We found modifying effects of ethnicity on the association of biomarkers with SYNTAX score. NTproBNP associated more strongly with the SYNTAX score in Malays than Caucasians (ß 0.132 vs. ß 0.020 per 100 pmol/l increase in NTproBNP, p = 0.032). For MPO levels the association was stronger in Malays than Caucasians (ß 1.146 vs. ß 0.016 per 10 ng/ml increase, p = 0.017). Differing biomarker cut-off levels were found for the ethnic groups. CONCLUSION: When corrected for possible confounders we observe ethnicity-specific differences in biomarker levels. Moreover, biomarkers associated differently with CAD severity, suggesting that ethnicity-specific cut-off values should be considered.

Comparison of platinum chromium everolimus-eluting stent with cobalt chromium everolimus-eluting stent in unselected patients undergoing percutaneous coronary intervention.

OBJECTIVE: The recent PLATINUM trial has demonstrated that the use of the new generation platinum chromium everolimus-eluting stents (PtCr-EES) yield clinical outcomes similar to those obtained by the use of cobalt chromium everolimus-eluting stents (CoCr-EES) in selected patients with 1 or 2 de novo coronary artery lesions. This study aimed to compare the safety and efficacy of the PtCr-EES and CoCr-EES in unselected patients from a real-life single-center registry. PATIENTS AND METHODS:   From July 2009 through November 2010, 788 consecutive patients in our institution with symptomatic coronary artery disease who were treated with the CoCr-EES (n = 410) or PtCr-EES (n = 378) were enrolled into this study. The primary endpoint of the study was target-lesion failure (TLF) at 12-month follow-up and the secondary endpoints were major adverse cardiovascular events and stent thrombosis. RESULTS: The prevalence of TLF in the PtCr-EES group (4.5%) was similar to that in the CoCr-EES group (3.9%). In addition, there were no significant differences in the 12-month rates of cardiac death (2.1% vs. 1.5%), myocardial infarction (2.4% vs. 3.9%), ischemia-driven target lesion revascularization (2.4% vs. 2.2%), and definite or probable stent thrombosis (0.5% vs. 1.5%, all p > 0.05). CONCLUSIONS: At 12-month follow-up, the PtCr-EES is comparable in safety and efficacy to the CoCr-EES in unselected patients with coronary artery diseases.

A novel troponin T peptide in humans: Assay, biochemistry and preliminary findings in acute coronary syndromes.

INTRODUCTION: High sensitivity assays for cardiac troponin (cTn) have reduced time to diagnosis of myocardial infarction (MI) but at costs to diagnostic specificity. We hypothesised that measurement of an upstream open reading frame peptide (uORF) from the human cTnT gene (TnTuORF) might improve cTn specificity in MI patients. METHODS: A novel immunoassay to TnTuORF was developed and used to document circulating concentrations in normal healthy volunteers (n=150); assess potential trans-organ secretion in patients undergoing cardiac catheterisation (n=16); characterise temporal TnTuORF concentrations during ST-elevation MI (STEMI, n=4) and assess the potential of TnTuORF to assist the diagnosis and prognosis of MI in patients presenting with chest pain suspicious of ACS (n=502). Plasma immunoreactive TnTuORF was characterised on reverse phase and size exclusion HPLC. RESULTS: In normal volunteers and suspected acute coronary syndrome (ACS) patients, TnTuORF had no relationship with TnI or TnT. Trans-organ venous sampling suggested TnTuORF secretion is not exclusively cardiac based. In STEMI patients, TnTuORF concentrations decreased for up to 12h after onset. In suspected ACS patients, TnTuORF could not diagnose MI (ROC AUC=0.446, P=0.117) but could diagnose cardiac disorders other than MI (AUC=0.79, P<0.001). CONCLUSION: This is the first evidence for a circulating uORF peptide. TnTuORF does not appear to aid the diagnosis of MI but further studies to assess its potential in cardiovascular disease are required.

Genetic markers of repolarization and arrhythmic events after acute coronary syndromes.

BACKGROUND: There is a genetic contribution to the risk of ventricular arrhythmias in survivors of acute coronary syndromes (ACS). We wished to explore the role of 33 candidate single nucleotide polymorphisms (SNPs) in prolonged repolarization and sudden death in patients surviving ACS. METHODS: A total of 2,139 patients (1680 white ethnicity) surviving an admission for ACS were enrolled in the prospective Coronary Disease Cohort Study. Extensive clinical, echocardiographic, and neurohormonal data were collected for 12 months, and clinical events were recorded for a median of 5 years. Each SNP was assessed for association with sudden cardiac death (SCD)/cardiac arrest (CA) and prolonged repolarization at 3 time-points: index admission, 1 month, and 12 months postdischarge. RESULTS: One hundred six SCD/CA events occurred during follow-up (6.3%). Three SNPs from 3 genes (rs17779747 [KCNJ2], rs876188 [C14orf64], rs3864180 [GPC5]) were significantly associated with SCD/CA in multivariable models (after correction for multiple testing); the minor allele of rs17779747 with a decreased risk (hazard ratio [HR] 0.68 per copy of the minor allele, 95% CI 0.50-0.92, P = .012), and rs876188 and rs386418 with an increased risk (HR 1.52 [95% CI 1.10-2.09, P = .011] and HR 1.34 [95% CI 1.04-1.82, P = .023], respectively). At 12 months postdischarge, rs10494366 and rs12143842 (NOS1AP) were significant predictors of prolonged repolarization (HR 1.32 [95% CI 1.04-1.67, P = .022] and HR 1.30 [95% CI 1.01-1.66, P = .038], respectively), but not at earlier time-points. CONCLUSION: Three SNPs were associated with SCD/CA. Repolarization time was associated with variation in the NOS1AP gene. This study demonstrates a possible role for SNPs in risk stratification for arrhythmic events after ACS.

Complications of intra-aortic balloon pump use: does the final position of the IABP tip matter?

We report results of a retrospective review of intra-aortic balloon pump (IABP) use in two Australasian centres and evaluate the effect of final IABP tip position on outcome. Indications for counterpulsation, patient demographics and in-hospital outcomes and complications were retrospectively collected. The chest X-ray reports provided the 'final' position of the IABP tip. The position was defined as acceptable (tip was seen just below the aortic arch, at T2-T5 vertebrae), malpositioned (tip > 5 cm below aortic arch or at T5-T6) or severely malpositioned (tip > 10 cm below aortic arch or at T7 or below).?Major complications were considered a composite of death secondary to IABP, major limb ischaemia, major IABP malfunction, balloon rupture or haemorrhage, severe renal dysfunction (rise in creatinine > 200 µmol/l), stroke and mesenteric ischaemia. Six hundred and forty-five cases were reviewed. The overall major complication rate was 26.2% and 24.3%. Severe renal impairment was the most common complication (16.6%), and second, severe catheter dysfunction (5.4%). ?Final IABP position was acceptable in 39.9%, malpositioned in 11.1%,?severely malpositioned in 6.7% and unavailable for 42.4%. Logistic regression analysis showed IABP tip malposition (compared with satisfactory position odds ratio=3.9 [95% confidence interval=2.0-7.6, P < 0.001] and severely malpositioned odds ratio=13.0 [95% confidence interval 5.3-31.7, P < 0.001]) was associated with major complications more than the presence of shock (odds ratio=3.8, confidence interval=2.1-6.8 P < 0.001). The acceptance of a less-than-ideal final position was highly predictive of morbidity directly related to IABP device therapy.

Code blue: Acinetobacter baumannii, a nosocomial pathogen with a role in the oral cavity.

Actinetobacter baumannii is an important nosocomial pathogen that can cause a wide range of serious conditions including pneumonia, meningitis, necrotizing fasciitis and sepsis. It is also a major cause of wound infections in military personnel injured during the conflicts in Afghanistan and Iraq, leading to its popular nickname of 'Iraqibacter'. Contributing to its success in clinical settings is resistance to environmental stresses such as desiccation and disinfectants. Moreover, in recent years there has been a dramatic increase in the number of A. baumannii strains with resistance to multiple antibiotic classes. Acinetobacter baumannii is an inhabitant of oral biofilms, which can act as a reservoir for pneumonia and chronic obstructive pulmonary disease. Subgingival colonization by A. baumannii increases the risk of refractory periodontitis. Pathogenesis of the organism involves adherence, biofilm formation and iron acquisition. In addition, A. baumannii can induce apoptotic cell death in epithelial cells and kill hyphal forms of Candida albicans. Virulence factors that have been identified include pili, the outer membrane protein OmpA, phospholipases and extracellular polysaccharide. Acinetobacter baumannii can sense blue light through a blue-light sensing using flavin (BLUF) domain protein, BlsA. The resulting conformational change in BlsA leads to changes in gene expression, including virulence genes.

High plasma thiocyanate levels are associated with enhanced myeloperoxidase-induced thiol oxidation and long-term survival in subjects following a first myocardial infarction.

Elevated levels of myeloperoxidase (MPO) are associated with poor cardiovascular outcomes. MPO uses H2O2 to generate oxidants including HOCl and HOSCN, from chloride and thiocyanate (SCN(-)) ions, respectively. SCN(-) is the preferred substrate. Elevation of this anion decreases HOCl generation and increases HOSCN formation, a thiol-specific oxidant. Such changes are of potential relevance to people with elevated SCN(-) levels, such as smokers. In this retrospective study, we examined whether elevated plasma MPO and SCN(-) levels increased thiol oxidation as a result of increased HOSCN formation, and impacted on long-term survival in 176 subjects (74 non-smokers, 46 smokers, and 56 previous smokers) hospitalized after a first myocardial infarction. Plasma thiols were not significantly altered in smokers compared to non-smokers or past smokers. However, significant positive correlations were detected between SCN(-) levels and MPO-induced thiol loss in the total population (r = 0.19, P = 0.020) and smokers alone (r = 0.58, P < 0.0001). Twelve-year all-cause mortality data indicate that above median MPO is significantly associated with higher mortality, but below-median MPO and above-median SCN(-) results in increased survival, compared to below-median SCN(-). Cox proportional hazard analysis showed a significant decrease in mortality for each 1 µM increase in SCN(-) (0.991; P = 0.040). Subject age was, as expected, a strong predictor of subject survival. Overall these data suggest that subjects with below-median MPO and above-median SCN(-) have better long-term survival, and that elevated plasma levels of SCN(-) might be protective in at least some populations.

Plasma extracellular vesicle protein content for diagnosis and prognosis of global cardiovascular disease.

Cardiovascular disease is a major public health problem worldwide. Its growing burden is particularly ominous in Asia, due to increasing rates of major risk factors such as diabetes, obesity and smoking. There is an urgent need for early identification and treatment of individuals at risk of adverse cardiovascular events. Plasma extracellular vesicle proteins are novel biomarkers that have been shown to be useful in the diagnosis, risk stratification and prognostication of patients with cardiovascular disease. Ongoing parallel biobank initiatives in European (the Netherlands) and Asian (Singapore) populations offer a unique opportunity to validate these biomarkers in diverse ethnic groups.

Hyperuricaemia and gout in New Zealand rural and urban Maori and non-Maori communities.

BACKGROUND: There are few current data on the prevalence of hyperuricaemia and gout in New Zealand, particularly among the indigenous Maori population. AIMS: To determine the prevalence of gout and hyperuricaemia in rural and urban Maori and non-Maori community samples and describe the treatment and comorbidities of participants with gout. METHODS: Participants aged 20-64 years were recruited by random selection from the electoral roll. Maori samples were selected from among those identified as being of Maori descent on the roll and who self-identified as being of Maori ethnicity at interview. Personal medical history, blood pressure, anthropometrics, fasting lipids, glucose, HbA1c and urate were recorded. RESULTS: There were 751 participants. Mean serum urate (SU) was 0.30 mmol/L (0.06-0.69 mmol/L). Maori had a significantly higher prevalence of hyperuricaemia (SU > 0.40 mmol/L) compared with non-Maori (17.0% vs 7.5%, P = 0.0003). A total of 57 participants had a history of gout, with a higher prevalence in Maori compared with non-Maori (10.3% vs 2.3%, P < 0.0001). Of the participants, 18/57 (31.6%) with gout were receiving urate-lowering therapy, but in 38.9%, SU was >0.36 mmol/L. Participants with gout were more likely to have metabolic syndrome, diabetes, cardiac disease or hypertension. CONCLUSIONS: Gout and hyperuricaemia were more prevalent in Maori, and participants with gout were more likely to have comorbidities. There was not a higher overall adjusted cardiovascular disease risk in Maori participants with gout. Despite the high prevalence of gout, management remains suboptimal.

Impact of age, phenotype and cardio-renal function on plasma C-type and B-type natriuretic peptide forms in an adult population.

CONTEXT: In contrast to the cardiac hormones, atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), variations in plasma concentrations of C-type natriuretic peptide (CNP) in healthy adults are ill-defined, limiting their clinical application. OBJECTIVE: Our objective was to define the effect of age, phenotype (gender, height, BMI), and cardiac and renal function on plasma CNPs in an adults population without renal or cardiovascular disease. DESIGN AND SETTING: This was a prospective cross-sectional observational study of adult volunteers, aged 21-80 years, randomly selected from the electoral roll. SUBJECTS AND METHODS: Plasma CNP and its associated aminoterminal propeptide (NTproCNP) were measured in 258 subjects and related to age, gender, height and plasma creatinine. Subgroup analyses seeking associations with cardiac function (plasma BNP and NTproBNP) and bone turnover bone-specific alkaline phosphatase (bALP) were also determined. RESULTS: Plasma concentrations of CNPs in men continued to decline from adolescent values to reach a nadir in the 5th decade after which values increased. Similar but less marked changes occurred in women. In both sexes, NTproCNP was inversely and independently correlated with height. In contrast to B-type natriuretic peptides (BNPs), NTproCNP was higher in men, significantly related to creatinine and positively related to bALP. CONCLUSIONS: Gender- and age-specific changes affect CNPs in adults. Inverse associations of NTproCNP with adult height, positive correlation with creatinine - and in contrast to CNP - no association with BNP are further unique findings distinguishing NTproCNP, which need to be considered in future studies.

Genetic variation in the renin-angiotensin-aldosterone system is associated with cardiovascular risk factors and early mortality in established coronary heart disease.

This study examined renin-angiotensin-aldosterone (RAAS) system gene variants for associations with cardiovascular risk factors and outcomes in coronary heart disease. Coronary disease patients (n=1186) were genotyped for 21 single-nucleotide polymorphisms (SNPs) within angiotensinogen (AGT), angiotensin-converting enzyme (ACE), angiotensin-II type-1 receptor (AGTR1) and aldosterone synthase (CYP11B2). Associations with all-cause mortality and cardiovascular readmissions were assessed over a median of 3.0 years. The AGT M235T 'T' allele was associated with a younger age of clinical coronary disease onset (P=0.006), and the AGT rs2478545 minor allele was associated with lower circulating natriuretic peptides (P=0.0001-P=0.001) and E/E(1) (P=0.018). Minor alleles of AGT SNPs rs1926723 and rs11122576 were associated with more frequent history of renal disease (P0.04) and type-2 diabetes (P0.02), higher body mass index (P0.02) and greater mortality (P0.007). AGT rs11568054 minor allele carriers had more frequent history of renal disease (P=0.04) and higher plasma creatinine (P=0.033). AGT rs6687360 minor allele carriers exhibited worse survival (P=0.02). ACE rs4267385 was associated with older clinical coronary disease onset (P=0.008) and hypertension (P=0.013) onset, increased plasma creatinine (P=0.01), yet greater mortality (P=0.044). Less history of hypertension was observed with the AGTR1 rs12685977 minor allele (P=0.039). Genetic variation within the RAAS was associated with cardiovascular risk factors and accordingly poorer survival.

Comparative pharmacokinetics and pharmacodynamics of urocortins 1, 2 and 3 in healthy sheep.

BACKGROUND AND PURPOSE The urocortin (Ucn) peptides are emerging as potential therapeutic targets for heart disease. However, pharmacokinetic (PK) and pharmacodynamic (PD) data are lacking. Therefore, we investigated the PK/PD for all three Ucns. EXPERIMENTAL APPROACH Seven sheep received 1 µg·kg(-1) boluses of Ucn1, Ucn2 and Ucn3. Population PK/PD models were developed to describe the time course of the haemodynamic effects. RESULTS The population estimate for Ucn1 clearance (0.486 L·h(-1)) was lower than that for Ucn2 (21.7 L·h(-1)) and Ucn3 (220 L·h(-1)), while steady-state volumes of distribution were similar for Ucn1 and Ucn2 (∼8 L) but substantially larger for Ucn3 (23.5 L). Ucn1 disposition was adequately described by a two-compartment model, with a one-compartment model required for Ucn2 and Ucn3. The half-life for Ucn1 was 2.9 h (α phase) and 8.3 h (ß phase), and 15.7 and 4.4 min for Ucn2 and Ucn3 respectively. All Ucns produced significant increases in heart rate, cardiac output and left ventricular systolic and mean arterial pressures, and decreases in left atrial pressure and peripheral resistance. Delayed-effect pharmacodynamic models best described the time course of haemodynamic responses, with effects more rapid and less prolonged for Ucn2 and Ucn3 than Ucn1. Similar and physiologically plausible estimated baseline (E(0)) effects were exhibited by all Ucns, whereas EC(50) values were generally greater for Ucn1. CONCLUSIONS AND IMPLICATIONS Relative to Ucn1, both the PK and haemodynamic responses to Ucn2 and Ucn3 occurred more rapidly. Our data provide important comparative information, useful to the rational design of future clinical studies.

Pharmacodynamic responses of plasma and tissue C-type natriuretic peptide to GH: correlation with linear growth in GH-deficient rats.

Studies from genetic modification and spontaneous mutations show that C-type natriuretic peptide (CNP) signalling plays an essential part in postnatal endochondral growth, but measurement of CNP proteins and changes in their abundance in tissues and plasma during normal growth has not been reported. Using rodent pups with GH deficiency, we now describe the pharmacodynamic response of CNP and rat amino-terminal proCNP (NTproCNP) in plasma and tissues, and relate these to changes in linear growth (nose-tail length, tibial length and tibial growth plate width) during the course of 1 week of GH or saline (control) administration. Compared with saline, significant increases in plasma and tissue CNP forms were observed after 24 h in GH-treated pups and before any detectable change in linear growth. Whereas CNP abundance was increased in most tissues (muscle, heart and liver) by GH, enrichment was the greatest in extracts from growth plates and kidney. Plasma and tissue concentrations in GH-treated pups were sustained or further increased at 1 week when strong positive associations were found between plasma NTproCNP and linear growth or tissue concentrations. High content of NTproCNP in kidney tissue strongly correlated with plasma concentrations, which is consistent with previous data showing renal extraction of the peptide. In showing a prompt and significant increase in CNP in tissues driving normal endochondral growth, these findings provide further rationale for CNP agonists in the treatment of growth disorders resistant to current therapies and support the use of CNP concentrations as biomarkers of linear growth.

KCNE5 polymorphism rs697829 is associated with QT interval and survival in acute coronary syndromes patients.

INTRODUCTION: The KCNE family is a group of small transmembrane channel proteins involved in potassium ion (K(+)) conductance. The X-linked KCNE5 gene encodes a regulator of the K(+) current mediated by the potassium channel KCNQ1. Polymorphisms in KCNE5 have been associated with altered cardiac electrophysiological properties in human studies. We investigated associations of the common rs697829 polymorphism from KCNE5 with baseline characteristics, baseline electrocardiographic (ECG) measurements, and patient survival in a cohort of post-acute coronary syndromes (ACS) patients (the Coronary Disease Cohort Study cohort). METHODS AND RESULTS: DNA samples (n = 1,740) were genotyped for rs697829 using a TaqMan assay. Baseline ECG data revealed corrected QT (QTc) interval was associated with rs697829 in male, but not female, patients, being extended in the G genotype group (A 416 ± 1.71; G 431 ± 4.25 ms, P = 0.002). Covariate-adjusted survival was poorest in G genotype patients in Cox proportional hazard modeling of mortality data of males (P(overall) = 0.020). Male patients with G genotype had a hazard ratio of 1.44 (1.11-2.33) for death when compared to the A genotype male patients (P = 0.048) after adjustment for age, baseline log-transformed N-terminal pro-B-type natriuretic peptide (NTproBNP), ß-blocker and insulin treatment, QTc interval, history of myocardial infarction, and physical activity score. CONCLUSION: This study suggests an association between rs697829, a common single nucleotide polymorphism (SNP) from KCNE5, and ECG measurements and survival in postacute ACS patients. Prolonged subclinical QT interval may be a marker of adverse outcome in this group of patients.

Regional vascular response to ProAngiotensin-12 (PA12) through the rat arterial system.

ProAngiotensin-12 (PA12) is the most recent peptide to be identified as a functional component of the renin-angiotensin system (RAS). PA12 is reported to constrict rat coronary arteries and the aorta, dependent upon angiotensin II-converting enzyme 1 (ACE1) and chymase. The current study employed myography to determine the direct vascular effects of PA12 on a range of isolated rat arteries extending from the core to periphery. PA12 significantly constricted the descending thoracic aorta, right and left common carotid arteries, abdominal aorta and superior mesenteric artery, with little effect on the femoral and renal arteries. AngII was found to produce similar responses to PA12 when administered at the same dose. A potency gradient in response to PA12 was clearly apparent, with vessels in closest proximity to the heart responding with the greatest constriction; while constrictive potency was lost further form the heart. Inhibition of ACE1 and chymase both significantly attenuated PA12-induced vasoconstriction, with chymostatin displaying lesser potency. We postulate ACE1 primarily regulates RAS activity within the circulation, while chymase may have an important role in local, tissue-based RAS activity.

Subsidence of uncemented stems in osteoporotic and non-osteoporotic cadaveric femora.

The increased use of uncemented stems for hip arthroplasty and of fast-recovery protocols in elderly patients make initial stem stability and resistance to fracture critical factors in osteoporotic bone. In this paper, the subsidence and failure of two uncemented stem designs (M/L Taper and VerSys Fullcoat, Zimmer, Inc, Warsaw, Indiana, USA) in osteoporotic and non-osteoporotic cadaveric femora were compared under simulated walking conditions (axial compression and external rotation). Osteoporotic femora implanted with either stem design failed significantly more frequently than did non-osteoporotic femora. Femora implanted with the M/L stems (seven of ten by 1000 cycles) fractured earlier than did femora implanted with the Fullcoat stem (one of ten by 1000 cycles). The use of early weight-bearing protocols with uncemented stem designs in osteoporotic bone should be approached with caution.

Biomechanical analysis of sacroplasty: does volume or location of cement matter?

BACKGROUND AND PURPOSE: Currently, the effect of the volume of cement used during sacroplasty on the restoration of pelvic strength and stiffness is unknown. The purpose of this study was to measure that effect in a sacral insufficiency fracture model. MATERIALS AND METHODS: Twenty-five osteoporotic cadaveric pelves were potted, and sacral fractures were produced. Specimens were divided into 4 groups: group 0 + 0 (control), no sacroplasty; group 3 + 0, sacroplasty (posterior approach), 3 mL of a bone cement injected bilaterally into the fracture site at S1; group 3 + 3, sacroplasty (posterior approach), 3 mL of the same cement injected bilaterally into the fracture site at S1 and S2; and group 6 + 3, sacroplasty (posterior approach), 6 mL of the same cement injected bilaterally at S1 and 3 mL injected bilaterally at S2. Cement position and extravasation were documented with CT. Specimens were tested to failure to assess the strength and stiffness after sacroplasty. RESULTS: There were no significant differences in strength or stiffness restoration between control and treatment groups. CONCLUSIONS: Sacroplasty does not restore the strength or stiffness of the sacrum in a cadaveric model regardless of the volume or location of cement.

B-type natriuretic peptide infusions in acute myocardial infarction.

BACKGROUND: Natriuretic peptides have actions likely to ameliorate cardiac dysfunction. B-type natriuretic peptide (BNP) is indicated as treatment for decompensated cardiac failure. OBJECTIVE: To determine the utility of BNP in acute myocardial infarction (MI). DESIGN: Double-blind randomised placebo-controlled trial. SETTING: Tertiary hospital coronary care unit. PATIENTS: 28 patients with acute MI with delayed or failed reperfusion and moderate left ventricular dysfunction. INTERVENTIONS: Infusion of BNP or placebo for 60 hours after MI. MAIN OUTCOME MEASURES: Neurohormonal activation and renal function in response to BNP infusion, secondary end points of echocardiographic measures of left ventricular function and dimension. RESULTS: BNP infusion resulted in a significant rise in BNP (276 pg/l vs 86 pg/l, p = 0.001). NT-proBNP levels were suppressed by BNP infusion (p = 0.002). Atrial natriuretic peptide (ANP) and NT-proANP levels fell with a significant difference in the pattern between BNP infusion and placebo during the first 5 days (p<0.005). C-type natriuretic peptide (CNP) and NT-proCNP levels rose during the infusion with higher levels than placebo at all measurements during the first 3 days (p<0.01). Cyclic guanosine monophosphate (cGMP) was raised during the infusion period showing a peak of 23 pmol/l on day 2 (placebo 8.9 pmol/l, p = 0.002), with a correlation between BNP and cGMP levels (p<0.001). Glomerular filtration rate (GFR) fell with BNP infusion but was not significantly lower than with placebo (71.0 (5.6) vs 75.8 (5.4) ml/min/1.73 m2, p = 0.62). Patients receiving nesiritide exhibited favourable trends in left ventricular remodelling. CONCLUSIONS: Nesiritide, given soon after MI, induced increments in plasma cGMP and CNP and decrements in other endogenous cardiac peptides with a neutral effect on renal function and a trend towards favourable ventricular remodelling.