Safety of short 3-hour recovery and same-day discharge following lower-limb angioplasty in outpatients with intermittent claudication and critical limb ischaemia.

AIM: To investigate the safety and efficacy of short recovery day-case pathway following lower-limb angioplasty in both intermittent claudication and critical limb ischaemia patients. MATERIALS AND METHODS: A retrospective analysis was undertaken of the medical records of consecutive outpatients treated with lower-limb angioplasty over a 1-year period within an interventional radiology (IR) day-case unit in a high-volume vascular centre. Standard post-angioplasty care at York Teaching Hospital is discharge 3 h after puncture site haemostasis without the routine use of closure devices. The rates of successful same-day discharge, procedure success, complications, and re-admissions were calculated with 30-day follow-up. RESULTS: The cohort included 301 patients (57% intermittent claudication and 43% critical limb ischaemia) undergoing 605 angioplasties using access sheath size ranging from 4 to 7 F. Closure devices were used in only 7% of patients. Successful same-day discharge achieved in 98% of patients (294/301), with seven admitted overnight because of complications. Eleven patients (3.6%) were re-admitted within 30 days. Technical success rates were 92%, and 96% when including partially successful interventions, with 4% technical failure. Twelve patients (4%) developed minor complications and four major complications (1%). There were no significant differences in complication rates between small and larger sheath sizes (p>0.05). No procedure-related death was recorded within 30 days. CONCLUSION: Lower-limb angioplasty can be performed safely as day-case procedure with a short recovery protocol within IR departments for both patients with intermittent claudication (IC) and critical limb ischaemia (CLI). This may significantly increase patient throughput and alleviate pressure on stretched hospital inpatient resources by safely discharging patients on the day of procedure.

Do we know how scabies outbreaks in residential and nursing care homes for the elderly should be managed? A systematic review of interventions using a novel approach to assess evidence quality.

Currently no national guidelines exist for the management of scabies outbreaks in residential or nursing care homes for the elderly in the United Kingdom. In this setting, diagnosis and treatment of scabies outbreaks is often delayed and optimal drug treatment, environmental control measures and even outcome measures are unclear. We undertook a systematic review to establish the efficacy of outbreak management interventions and determine evidence-based recommendations. Four electronic databases were searched for relevant studies, which were assessed using a quality assessment tool drawing on STROBE guidelines to describe the quality of observational data. Nineteen outbreak reports were identified, describing both drug treatment and environmental management measures. The quality of data was poor; none reported all outcome measures and only four described symptom relief measures. We were unable to make definitive evidence-based recommendations. We draw on the results to propose a framework for data collection in future observational studies of scabies outbreaks. While high-quality randomised controlled trials are needed to determine optimal drug treatment, evidence on environmental measures will need augmentation through other literature studies. The quality assessment tool designed is a useful resource for reporting of outcome measures including patient-reported measures in future outbreaks.

Severe group A streptococcal infections in mothers and their newborns in London and the South East, 2010-2016: assessment of risk and audit of public health management.

OBJECTIVE: We describe cases of invasive group A Streptococcus (iGAS) in mothers or neonates and assess management according to national guidelines, which recommend administering antibiotics to both mother and neonate if either develops iGAS infection within 28 days of birth and investigation of clusters in maternity units. DESIGN: Cross-sectional retrospective study. SETTING AND POPULATION: Notified confirmed iGAS cases in either mothers or neonates with onset within 28 days of birth in London and the South East of England between 2010 and 2016 METHOD: Review of public health records of notified cases. MAIN OUTCOME MEASURES: Incidence and onset time of iGAS in postpartum mothers and babies, proportion given prophylaxis, maternity unit clusters within 6 months. RESULTS: We identified 134 maternal and 21 neonatal confirmed iGAS infections. The incidence (in 100 000 person years) of iGAS in women within 28 days postpartum was 109 (95% CI 90-127) compared with 1.3 in other females aged 15-44. For neonates the incidence was 1.5 (95% CI 9-23). The median onset time was 2 days postpartum [interquartile range (IQR) 0-5 days] for mothers and 12 days (IQR 7-15 days) for neonates. All eligible mothers and most (109, 89%) eligible neonates received chemoprophylaxis. Of 20 clusters (59 cases of GAS and iGAS) in maternity units, two clusters involved possible transmission. However, in 6 of 15 clusters, GAS isolates were not saved for comparison even after relevant guidance was issued. CONCLUSIONS: iGAS infection remains a potential postpartum risk. Prophylaxis among neonates and storage of isolates from maternity cases can be improved. TWEETABLE ABSTRACT: Are public health guidelines being followed in the management of mothers and their newborns to reduce the risk of iGAS infection?

The management of scabies outbreaks in residential care facilities for the elderly in England: a review of current health protection guidelines.

Commonly thought of as a disease of poverty and overcrowding in resource-poor settings globally, scabies is also an important public health issue in residential care facilities for the elderly (RCFE) in high-income countries such as the UK. We compared and contrasted current local Health Protection Team (HPT) guidelines for the management of scabies outbreaks in RCFE throughout England. We performed content analysis on 20 guidelines, and used this to create a quantitative report of their variation in key dimensions. Although the guidelines were generally consistent on issues such as the treatment protocols for individual patients, there was substantial variation in their recommendations regarding the prophylactic treatment of contacts, infection control measures and the roles and responsibilities of individual stakeholders. Most guidelines did not adequately address the logistical challenges associated with mass treatment in this setting. We conclude that the heterogeneous nature of the guidelines reviewed is an argument in favour of national guidelines being produced.

Investigation of an outbreak of vomiting in nurseries in South East England, May 2012.

On 30 May 2012, Surrey and Sussex Health Protection Unit was called by five nurseries reporting children and staff with sudden onset vomiting approximately an hour after finishing their lunch that day. Over the following 24 h 50 further nurseries supplied by the same company reported cases of vomiting (182 children, 18 staff affected). Epidemiological investigations were undertaken in order to identify the cause of the outbreak and prevent further cases. Investigations demonstrated a nursery-level attack rate of 55 out of 87 nurseries (63·2%, 95% confidence interval 52·2-73·3). Microbiological tests confirmed the presence of Bacillus cereus in food and environmental samples from the catering company and one nursery. This was considered microbiologically and epidemiologically consistent with toxin from this bacterium causing the outbreak. Laboratory investigations showed that the conditions used by the caterer for soaking of pearl haricot beans (known as navy bean in the USA) used in one of the foods supplied to the nurseries prior to cooking, was likely to have provided sufficient growth and toxin production of B. cereus to cause illness. This large outbreak demonstrates the need for careful temperature control in food preparation.

The mechanism of action for hyaluronic acid treatment in the osteoarthritic knee: a systematic review.

BACKGROUND: Knee osteoarthritis (OA) is one of the leading causes of disability within the adult population. Current treatment options for OA of the knee include intra-articular (IA) hyaluronic acid (HA), a molecule found intrinsically within the knee joint that provides viscoelastic properties to the synovial fluid. A variety of mechanisms in which HA is thought to combat knee OA are reported in the current basic literature. METHODS: We conducted a comprehensive literature search to identify currently available primary non-clinical basic science articles focussing on the mechanism of action of IA-HA treatment. Included articles were assessed and categorized based on the mechanism of action described within them. The key findings and conclusions from each included article were obtained and analyzed in aggregate with studies of the same categorical assignment. RESULTS: Chondroprotection was the most frequent mechanism reported within the included articles, followed by proteoglycan and glycosaminoglycan synthesis, anti-inflammatory, mechanical, subchondral, and analgesic actions. HA-cluster of differentiation 44 (CD44) receptor binding was the most frequently reported biological cause of the mechanisms presented. High molecular weight HA was seen to be superior to lower molecular weight HA products. HA derived through a biological fermentation process is also described as having favorable safety outcomes over avian-derived HA products. CONCLUSIONS: The non-clinical basic science literature provides evidence for numerous mechanisms in which HA acts on joint structures and function. These actions provide support for the purported clinical benefit of IA-HA in OA of the knee. Future research should not only focus on the pain relief provided by IA-HA treatment, but the disease modification properties that this treatment modality possesses as well.

Effect of B-type natriuretic peptide-guided treatment of chronic heart failure on total mortality and hospitalization: an individual patient meta-analysis.

AIMS: Natriuretic peptide-guided (NP-guided) treatment of heart failure has been tested against standard clinically guided care in multiple studies, but findings have been limited by study size. We sought to perform an individual patient data meta-analysis to evaluate the effect of NP-guided treatment of heart failure on all-cause mortality. METHODS AND RESULTS: Eligible randomized clinical trials were identified from searches of Medline and EMBASE databases and the Cochrane Clinical Trials Register. The primary pre-specified outcome, all-cause mortality was tested using a Cox proportional hazards regression model that included study of origin, age (<75 or ≥75 years), and left ventricular ejection fraction (LVEF, ≤45 or >45%) as covariates. Secondary endpoints included heart failure or cardiovascular hospitalization. Of 11 eligible studies, 9 provided individual patient data and 2 aggregate data. For the primary endpoint individual data from 2000 patients were included, 994 randomized to clinically guided care and 1006 to NP-guided care. All-cause mortality was significantly reduced by NP-guided treatment [hazard ratio = 0.62 (0.45-0.86); P = 0.004] with no heterogeneity between studies or interaction with LVEF. The survival benefit from NP-guided therapy was seen in younger (<75 years) patients [0.62 (0.45-0.85); P = 0.004] but not older (≥75 years) patients [0.98 (0.75-1.27); P = 0.96]. Hospitalization due to heart failure [0.80 (0.67-0.94); P = 0.009] or cardiovascular disease [0.82 (0.67-0.99); P = 0.048] was significantly lower in NP-guided patients with no heterogeneity between studies and no interaction with age or LVEF. CONCLUSION: Natriuretic peptide-guided treatment of heart failure reduces all-cause mortality in patients aged <75 years and overall reduces heart failure and cardiovascular hospitalization.

B-type natriuretic peptide forms within the heart, coronary sinus, and peripheral circulation in humans: evidence for degradation before secretion.

BACKGROUND: The B-type natriuretic peptides (BNP and N-terminal pro-BNP) are secreted by the heart and, in the case of BNP, serve to maintain circulatory homeostasis through renal and vascular actions and oppose many effects of the renin-angiotensin system. Recent evidence suggests that in patients with severe heart failure, circulating immunoreactive BNP is made up mainly of metabolites that may have reduced bioactivity. We hypothesized that BNP may be degraded before it even leaves the heart. METHODS: Peripheral venous plasma plus atrial and ventricular tissue, obtained from explanted hearts at the time of transplantation, were collected from 3 patients with end-stage heart failure. In a separate study, plasma was collected from the coronary sinus and femoral artery of 3 separate patients undergoing cardiac catheterization. Plasma C18 reverse-phase extracts were separated on reverse-phase HPLC, and the collected fractions were subjected to RIAs with highly specific antisera directed to the amino- and carboxy-terminal ends of BNP(1-32). RESULTS: ProBNP, BNP(1-32), and 2 major BNP metabolites were present in atrial and ventricular tissue, where BNP(1-32) represented 45% and 70% of total processed BNP, respectively. Neither BNP(1-32) nor the 2 metabolites were detected in peripheral venous plasma. Nor was BNP(1-32) detected in matching coronary sinus and femoral artery plasma from the 3 patients undergoing cardiac catheterization. CONCLUSIONS: BNP(1-32) is partly degraded within the hearts of patients with end-stage heart failure, and even in patients with relatively well-preserved left ventricular systolic function, only BNP metabolites enter the systemic circulation.

Whole-genome sequencing links cases dispersed in time, place, and person while supporting healthcare worker management in an outbreak of Panton-Valentine leucocidin meticillin-resistant Staphylococcus aureus; and a review of literature.

This is a report on an outbreak of Panton-Valentine leucocidin-producing meticillin-resistant Staphylococcus aureus (PVL-MRSA) in an intensive care unit (ICU) during the COVID-19 pandemic that affected seven patients and a member of staff. Six patients were infected over a period of ten months on ICU by the same strain of PVL-MRSA, and a historic case identified outside of the ICU. All cases were linked to a healthcare worker (HCW) who was colonized with the organism. Failed topical decolonization therapy, without systemic antibiotic therapy, resulted in ongoing transmission and one preventable acquisition of PVL-MRSA. The outbreak identifies the support that may be needed for HCWs implicated in outbreaks. It also demonstrates the role of whole-genome sequencing in identifying dispersed and historic cases related to the outbreak, which in turn aids decision-making in outbreak management and HCW support. This report also includes a review of literature of PVL-MRSA-associated outbreaks in healthcare and highlights the need for review of current national guidance in the management of HCWs' decolonization regimen and return-to-work recommendations in such outbreaks.

Haemodynamic, endocrine and renal actions of adrenomedullin 5 in an ovine model of heart failure.

AM5 (adrenomedullin 5), a newly described member of the CGRP (calcitonin gene-related peptide) family, is reported to play a role in normal cardiovascular physiology. The effects of AM5 in HF (heart failure), however, have not been investigated. In the present study, we intravenously infused two incremental doses of AM5 (10 and 100 ng/min per kg of body weight each for 90 min) into eight sheep with pacing-induced HF. Compared with time-matched vehicle control infusions, AM5 produced progressive and dose-dependent increases in left ventricular dP/dt(max) [LD (low dose), +56 mmHg/s and HD (high dose), +152 mmHg/s] and cardiac output (+0.83 l/min and +1.81 l/min), together with decrements in calculated total peripheral resistance (-9.4 mmHg/min per litre and -14.7 mmHg/min per litre), mean arterial pressure (-2.8 mmHg and -8.4 mmHg) and LAP (left atrial pressure; -2.6 mmHg and -5.6 mmHg) (all P<0.001). HD AM5 significantly raised PRA (plasma renin activity) (3.5-fold increment, P<0.001), whereas plasma aldosterone levels were unchanged over the intra-infusion period and actually fell in the post-infusion period (70% decrement, P<0.01), resulting in a marked decrease in the aldosterone/PRA ratio (P<0.01). Despite falls in LAP, plasma atrial natriuretic peptide and B-type natriuretic peptide concentrations were maintained relative to controls. AM5 infusion also induced significant increases in urine volume (HD 2-fold increment, P<0.05) and urine sodium (2.7-fold increment, P<0.01), potassium (1.7-fold increment, P<0.05) and creatinine (1.4-fold increment, P<0.05) excretion and creatinine clearance (60% increment, P<0.05). In conclusion, AM5 has significant haemodynamic, endocrine and renal actions in experimental HF likely to be protective and compensatory in this setting. These results suggest that AM5 may have potential as a therapeutic agent in human HF.

Stickiness to hydrophobic surfaces varies widely among peptides and proteins.

To determine whether there are differences in stickiness to hydrophobic surfaces among peptides and proteins under immunoassay conditions, peptides and proteins were radio-labeled with (125)I and competitive adsorption with human serum albumin (HSA) in polystyrene or polypropylene tubes was used to determine the IC (50), the concentration of HSA required to reduce the adsorption of the labeled polypeptides to 50% of maximal. Stickiness was defined as log(10)(10(9) IC (50)). Stickiness varied significantly between the labeled polypeptides (p < 0.00001) and ranged (±sem) from 0.99 ± 0.07 for angiotensin II to 5.30 ± 0.07 for tyr(0)-urocortin II. The stickiness of HSA and γ globulin was 1.62 ± 0.09 and 1.92 ± 0.05, respectively. No significant difference in stickiness between polystyrene and polypropylene was found. We conclude that some peptides are sufficiently sticky to risk adsorptive loss during sampling and analysis, and there may exist peptides so sticky that they remain uncharacterized.

Development and operation of the defence COVID-19 lab as a SARS-CoV-2 diagnostic screening capability for UK military personnel.

BACKGROUND: In the face of the COVID-19 pandemic, the Defence Science and Technology Laboratory (Dstl) and Defence Pathology combined to form the Defence Clinical Lab (DCL), an accredited (ISO/IEC 17025:2017) high-throughput SARS-CoV-2 PCR screening capability for military personnel. LABORATORY STRUCTURE AND RESOURCE: The DCL was modular in organisation, with laboratory modules and supporting functions combining to provide the accredited SARS-CoV-2 (envelope (E)-gene) PCR assay. The DCL was resourced by Dstl scientists and military clinicians and biomedical scientists. LABORATORY RESULTS: Over 12 months of operation, the DCL was open on 289 days and tested over 72 000 samples. Six hundred military SARS-CoV-2-positive results were reported with a median E-gene quantitation cycle (Cq) value of 30.44. The lowest Cq value for a positive result observed was 11.20. Only 64 samples (0.09%) were voided due to assay inhibition after processing started. CONCLUSIONS: Through a sustained effort and despite various operational issues, the collaboration between Dstl scientific expertise and Defence Pathology clinical expertise provided the UK military with an accredited high-throughput SARS-CoV-2 PCR test capability at the height of the COVID-19 pandemic. The DCL helped facilitate military training and operational deployments contributing to the maintenance of UK military capability. In offering a bespoke capability, including features such as testing samples in unit batches and oversight by military consultant microbiologists, the DCL provided additional benefits to the UK Ministry of Defence that were potentially not available from other SARS-CoV-2 PCR laboratories. The links between Dstl and Defence Pathology have also been strengthened, benefitting future research activities and operational responses.

B-type natriuretic peptide signal peptide circulates in human blood: evaluation as a potential biomarker of cardiac ischemia.

BACKGROUND: The diagnosis of cardiac necrosis such as myocardial infarction can be difficult and relies on the use of circulating protein markers like troponin. However, there is a clear need to identify circulating, specific biomarkers that can detect cardiac ischemia without necrosis. METHODS AND RESULTS: Using specific immunoassay and tandem mass spectrometry, we show that a fragment derived from the signal peptide of B-type natriuretic peptide (BNPsp) not only is detectable in cytosolic extracts of explant human heart tissue but also is secreted from the heart into the circulation of healthy individuals. Furthermore, plasma levels of BNPsp in patients with documented acute ST-elevation myocardial infarction (n=25) rise to peak values ( approximately 3 times higher than the 99th percentile of the normal range) significantly earlier than the currently used biomarkers myoglobin, creatine kinase-MB, and troponin. Preliminary receiver-operating characteristic curve analysis comparing BNPsp concentrations in ST-elevation myocardial infarction patients and other patient groups was positive (area under the curve=0.97; P<0.001), suggesting that further, more rigorous studies in heterogeneous chest pain patient cohorts are warranted. CONCLUSIONS: Our results demonstrate for the first time that BNPsp exists as a distinct entity in the human circulation and could serve as a new class of circulating biomarker with the potential to accelerate the clinical diagnosis of cardiac ischemia and myocardial infarction. Clinical Trial Registration- URL: http://www.anzctr.org.au. Unique identifier: ACTRN12609000040268.

Population-wide dietary sodium restriction: a cautious view.

"What I tell you three times is true"-Lewis Carroll. How many times have we been told that reducing dietary sodium intake will improve the health of whole populations? But is there adequate evidence to support this idea? Some recent studies have indicated that caution is needed. Targeting those most likely to benefit should prevent inadvertent harm and free the rest of the population from yet another nagging plea to alter their lifestyle.

Imbalance of the autonomic nervous system at night in women with gestational diabetes.

AIMS: Autonomic nervous system dysfunction is observed in Type 2 diabetes. As gestational diabetes is a potent risk factor of later Type 2 diabetes, we set out to determine whether autonomic nervous system imbalance could already be observed in women with this condition. Because activity of the sympathetic nervous system tends to be relatively stable in the nocturnal hours, we performed the study at night. RESEARCH DESIGN AND METHODS: We studied 41 women with gestational diabetes, 22 healthy pregnant controls and 14 non-pregnant controls. We assayed plasma noradrenaline at 24.00, 04.00 and 07.00 h and performed an overnight Holter recording for heart rate variability analysis. In addition, we assayed plasma adrenomedullin, a cardiovascular protective hormone. RESULTS: Compared with non-pregnant controls, plasma noradrenaline levels were increased at 04.00 and 07.00 h in the gestational diabetic (P = 0.003) and pregnant control (P = 0.002) groups, with no difference between them. Heart rate variability, very-low-frequency and low-frequency power were lower in pregnant groups compared to the non-pregnant controls. Heart rate variability remained unchanged between specified sampling times in the gestational diabetic group, in contrast to fluctuation seen in the control groups. CONCLUSIONS: Gestational diabetes, compared with normal pregnancy, seems not to be a state of overall sympathetic nervous system activation. At the heart level, however, an inhibitory effect on autonomic nervous system modulation was seen. Plasma noradrenaline and heart rate variability correlated well, supporting the use of this function in future studies of overall sympathetic activity during pregnancy.

Renal and cardiac function for long-term (10 year) risk stratification after myocardial infarction.

Aims To determine whether combined renal and cardiac function after acute myocardial infarction (MI) predicts 10 year mortality and heart failure (HF). Methods and results Estimated glomerular filtration rate (eGFR), plasma amino terminal pro-brain natriuretic peptide (NT-proBNP), and radionuclide ventriculography were obtained in 1063 patients with MI between 24-96 h of symptom onset. Mortality and HF were documented over follow-up of 9.3 years. Estimated GFR, NT-proBNP, and left ventricular ejection fraction (LVEF) each independently predicted 10 year mortality. Reduced eGFR (below 60 mL/min/1.73 m(2)) combined with increased NT-proBNP (above 1000 pg/mL) was associated with higher mortality rate compared with preserved eGFR together with lower NT-proBNP (60 vs. 14%, P < 0.001). Similar results for mortality were identified for eGFR combined with LVEF (dichotomized about 50%) (58 vs. 17%, P < 0.001). Corresponding analysis combining eGFR and NT-proBNP to predict HF yielded rates of 34 and 7% for high- and low-risk groups, respectively (P < 0.001). Similar risk stratification for HF was observed when combining eGFR with LVEF (35 vs. 7%, P < 0.001). Conclusion Ten year rates of mortality and HF are 5-10 times higher when lower eGFR is present together with increased NT-proBNP or depressed LVEF.

Intermedin (adrenomedullin-2): a potential protective role in human aortic endothelial cells.

BACKGROUND/AIMS: Intermedin (IMD) is a novel peptide with significant vasodilator and cardiac protective actions similar to the related peptide adrenomedullin (ADM). Unlike those of ADM the actions and expression of IMD in endothelial cells are poorly characterised. ADM expression can be increased during cardiovascular disease/stress in vitro and in vivo where it may have a role in several cardiovascular protective actions. To characterise IMD mRNA expression cultured human aortic endothelial cells (HAEC) were stressed by removing serum and bicarbonate, and the addition of hydrogen peroxide. The responses were compared to those of ADM mRNA. We also compared the effects of ADM and IMD on caspase activity and cell viability, and investigated if IMD actions could be altered by a CGRP receptor antagonist. METHODS/RESULTS: Using the cell immunoblot assay, immunoreactive IMD was shown to be secreted by HAEC. IMD mRNA expression was also detected in HAEC grown in endothelial growth media (but at markedly lower levels than that of ADM). Absence of bicarbonate, a redox-mediated regulator of endothelial response to various stresses, increased IMD mRNA and ADM mRNA expression. However IMD mRNA, but not ADM mRNA, was markedly increased over time in HAEC in conditions of cell stress including incubation with serum-free Dulbecco's modified Eagle's medium (DMEM) and in response to hydrogen peroxide (H2O2). These vigorous responses in IMD mRNA expression were further enhanced by incubation in 5% serum in DMEM without bicarbonate, but in a selective manner since ADM expression was suppressed by serum. We also observed that IMD mRNA was markedly increased and ADM mRNA suppressed in HAEC following a period of suspension and replating. Finally, we observed that IMD, like ADM, increased cell viability in HAEC in DMEM without serum but only IMD reduced caspase activity, perhaps via and a yet to be defined receptor system. CONCLUSION: HAECs express IMD mRNA and secrete IMD peptide. IMD mRNA expression is markedly dependent on metabolic conditions and is selectively regulated in a contrary fashion to ADM mRNA. IMD mRNA expression in endothelial cells is markedly sensitive to oxidative stress, and IMD peptide itself has antiapoptotic activity in human endothelial cells. Our data suggest that IMD has a different role to ADM and may perform a protective function in humans.

Ouabain, a circulating hormone secreted by the adrenals, is pivotal in cardiovascular disease. Fact or fantasy?

Substantial evidence points to the presence in human plasma of an inhibitor of the sodium/potassium pump which plays a central role in the pathophysiology of circulatory disorders, including essential hypertension. Studies from the 1980/90s claimed that this inhibitor was identical or very similar in structure to plant-derived ouabain and was synthesized by the adrenal cortex. However, the physical evidence in studies reporting isolation and identification of ouabain in human plasma appears insecure on closer examination. Additionally, reported circulating levels of immunoreactive ouabain in humans vary greatly, the ability of the human adrenal glands to secrete ouabain is questionable and the original commercial assay for measuring immunoreactive ouabain is no longer available. We submit that the position of ouabain as an endogenous, adrenally produced regulator of the sodium pump is of such importance that the current evidence needs either to put on a more secure footing or to lose its current status.

Serum 25-hydroxyvitamin D is not related to cardiac natriuretic peptide in nulliparous and lactating women.

BACKGROUND: Vitamin D deficiency is associated with heightened risk of cardiovascular disease. Potential mechanisms include involvement of vitamin D in regulation of renin-angiotensin system and manufacture and secretion of cardiac natriuretic peptides. Our aim was to document relationships between 25 hydroxyvitamin [25(OH)D] and N-terminal pro B-type natriuretic peptide (NT-proBNP) and plasma renin activity (PRA) levels and to document the effect of vitamin D administration on NT-proBNP and PRA levels in vitamin D deficient subjects. METHODS: Serum 25(OH)D, parathyroid hormone (PTH), plasma or serum NT-proBNP and PRA levels were measured at baseline in nulliparous and lactating women and after 2 months of oral vitamin D2 (2,000 IU/day or 60,000 IU/month) supplementation to lactating women. RESULTS: Baseline levels of 25(OH)D were low (<50 nmol/L) in most women whereas PRA and NT-proBNP levels were within the normal range. There were no significant correlations between baseline 25(OH)D or PTH with NT-proBNP and PRA. Vitamin D administration over a 2-month period in lactating women was associated with a decline in NT-proBNP (by 9.1 +/- 2.0 pmol/L; p < 0.001) and PRA (by 0.32 +/- 0.17 nmol/L/hr; p = 0.064). However, there were no significant correlations between the changes from baseline in 25(OH)D and either NT-proBNP (r = -0.04, p = 0.8) or PRA (r = -0.04, p = 0.8). CONCLUSION: We found no significant correlations between 25(OH)D or PTH with NT-proBNP and PRA in vitamin D deficient women. Further information is required to clarify the effects of vitamin D administration on cardiac structure and function.

Plasma aldosterone levels during hospitalization are predictive of survival post-myocardial infarction.

AIMS: Plasma aldosterone levels have been shown to be associated with adverse clinical outcomes after ST-elevation myocardial infarction (STEMI). We investigated whether aldosterone levels in patients presenting with STEMI or non-STEMI, are predictive of mortality during prolonged follow-up. METHODS AND RESULTS: Aldosterone levels were assayed in plasma taken from 583 patients within 24-96 h following acute myocardial infarction (MI). The median plasma aldosterone level was 108 pmol/L and all values were below the upper limit of the normal range (800 pmol/L) except for five patients (0.9%). Aldosterone tertile was significantly associated with increasing plasma levels of NTproBNP (N-terminal pro-B-type natriuretic peptide), BNP (B-type natriuretic peptide), epinephrine, and endothelin-1 (P or=25.3% mortality, P >or= 0.026). CONCLUSION: Plasma aldosterone levels post-MI are independent predictors of survival and hospitalization for heart failure over a 5-year-follow-up period.