A treatment strategy with nifedipine versus labetalol for women with pregnancy hypertension: study protocol for a randomised controlled trial (Giant PANDA).

BACKGROUND: Approximately one in ten women have high blood pressure during pregnancy. Hypertension is associated with adverse maternal and perinatal outcomes, and as treatment improves maternal outcomes, antihypertensive treatment is recommended. Previous trials have been unable to provide a definitive answer on which antihypertensive treatment is associated with optimal maternal and neonatal outcomes and the need for robust evidence evaluating maternal and infant benefits and risks remains an important, unanswered question for research and clinical communities. METHODS: The Giant PANDA study is a pragmatic, open-label, multicentre, randomised controlled trial of a treatment initiation strategy with nifedipine (calcium channel blocker), versus labetalol (mixed alpha/beta blocker) in 2300 women with pregnancy hypertension. The primary objective is to evaluate if treatment with nifedipine compared to labetalol in women with pregnancy hypertension reduces severe maternal hypertension without increasing fetal or neonatal death or neonatal unit admission. Subgroup analyses will be undertaken by hypertension type (chronic, gestational, pre-eclampsia), diabetes (yes, no), singleton (yes, no), self-reported ethnicity (Black, all other), and gestational age at randomisation categories (11 + 0 to 19 + 6, 20 + 0 to 27 + 6, 28 + 0 to 34 + 6 weeks). A cost-effectiveness analysis using an NHS perspective will be undertaken using a cost-consequence analysis up to postnatal hospital discharge and an extrapolation exercise with a lifetime horizon conditional on the results of the cost-consequence analysis. DISCUSSION: This trial aims to address the uncertainty of which antihypertensive treatment is associated with optimal maternal and neonatal outcomes. The trial results are intended to provide definitive evidence to inform guidelines and linked, shared decision-making tools, thus influencing clinical practice. TRIAL REGISTRATION: EudraCT number: 2020-003410-12, ISRCTN: 12,792,616 registered on 18 November 2020.

No evidence of racial disparities in blood pressure salt sensitivity when potassium intake exceeds levels recommended in the US dietary guidelines.

On average, black individuals are widely believed to be more sensitive than white individuals to blood pressure (BP) effects of changes in salt intake. However, few studies have directly compared the BP effects of changing salt intake in black versus white individuals. In this narrative review, we analyze those studies and note that when potassium intake substantially exceeds the recently recommended US dietary goal of 87 mmol/day, black adults do not appear more sensitive than white adults to BP effects of short-term or long-term increases in salt intake (from an intake ≤50 mmol/day up to 150 mmol/day or more). However, with lower potassium intakes, racial differences in salt sensitivity are observed. Mechanistic studies suggest that racial differences in salt sensitivity are related to differences in vascular resistance responses to changes in salt intake mediated by vasodilator and vasoconstrictor pathways. With respect to cause and prevention of racial disparities in salt sensitivity, it is noteworthy that 1) on average, black individuals consume less potassium than white individuals and 2) consuming supplemental potassium bicarbonate, or potassium rich foods can prevent racial disparities in salt sensitivity. However, the new US dietary guidelines reduced the dietary potassium goal well below the amount associated with preventing racial disparities in salt sensitivity. These observations should motivate research on the impact of the new dietary potassium guidelines on racial disparities in salt sensitivity, the risks and benefits of potassium-containing salt substitutes or supplements, and methods for increasing consumption of foods rich in nutrients that protect against salt-induced hypertension.

Small Amounts of Inorganic Nitrate or Beetroot Provide Substantial Protection From Salt-Induced Increases in Blood Pressure.

To reduce the risk of salt-induced hypertension, medical authorities have emphasized dietary guidelines promoting high intakes of potassium and low intakes of salt that provide molar ratios of potassium to salt of ≥1:1. However, during the past several decades, relatively few people have changed their eating habits sufficiently to reach the recommended dietary goals for salt and potassium. Thus, new strategies that reduce the risk of salt-induced hypertension without requiring major changes in dietary habits would be of considerable medical interest. In the current studies in a widely used model of salt-induced hypertension, the Dahl salt-sensitive rat, we found that supplemental dietary sodium nitrate confers substantial protection from initiation of salt-induced hypertension when the molar ratio of added nitrate to added salt is only ≈1:170. Provision of a low molar ratio of added nitrate to added salt of ≈1:110 by supplementing the diet with beetroot also conferred substantial protection against salt-induced increases in blood pressure. The results suggest that on a molar basis and a weight basis, dietary nitrate may be ≈100× more potent than dietary potassium with respect to providing substantial resistance to the pressor effects of increased salt intake. Given that leafy green and root vegetables contain large amounts of inorganic nitrate, these findings raise the possibility that fortification of salty food products with small amounts of a nitrate-rich vegetable concentrate may provide a simple method for reducing risk for salt-induced hypertension.

Hydrogel Contact Lens Water Content is Dependent on Tearfilm pH.

Introduction: Based on clinical inferences, investigators theorized in situ soft lens hydration was linked to the precorneal tearfilm pH. Methods: Forty-one myopic subjects at Fort Rucker, AL, USA were fitted with one of two types of extended-wear soft contact lenses, and were followed quarterly for a period of 33 mo. The anterior soft contact lens surface pH was measured in situ, while the in vitro lens water content was measured immediately after lens removal, using a hand-held refractometer on one lens, and a gravimetric means of hydration measurement on the other lens. Results: The in situ pH increased logarithmically across extended wearing time, reaching an asymptote at approximately 5 d' wearing time at a pH of 7.45 ± 0.03. Lens water content was shown to similarly decrease at an inversely logarithmic rate, leveling off at 4-5 d' extended wearing time. Both means of hydration assessment correlated well with each other across days' extended wearing time (R = 0.98; p < 0.0001). Discussion: A log-log dual conversion yielded significantly different linear slopes (p < 0.001), based on a multifactorial analysis of both lens types, by the pH, and by their water content. The differing ionic status of each material accentuated their varied polar attraction characteristics. Two soft lenses, identical in all patient-based parameters, could provide differing oxygen availability, as well as differing physical fits in patients of identical physical characteristics, as a result of their unique tearfilm pH differences. Conclusion: The in situ hydrogel lens water content is directly dependent on the precorneal tearfilm pH.

Exploring the effect of laryngeal neuromuscular electrical stimulation on voice.

OBJECTIVE: This study was conducted to explore the potential use of neuromuscular electrical stimulation as an adjunctive treatment for muscle tension dysphonia. METHODS: Voice data and ratings of fatigue and soreness were obtained for two experiments. Experiment one examined the vocal effects of neuromuscular electrical stimulation applied to the neck for 15 minutes. Experiment two examined the recovery effect of laryngeal neuromuscular electrical stimulation following a vocal loading task among normophonic women. RESULTS: No significant differences in vocal function following 15 minutes of laryngeal neuromuscular electrical stimulation were found. Six of 11 participants receiving laryngeal neuromuscular electrical stimulation exhibited improved recovery following the vocal loading task. CONCLUSION: A short session of laryngeal neuromuscular electrical stimulation may be beneficial in reducing muscle fatigue for some individuals. Further investigation is warranted to determine the applicability of laryngeal neuromuscular electrical stimulation in voice therapy.

Chemical characterisation and the anti-inflammatory, anti-angiogenic and antibacterial properties of date fruit (Phoenix dactylifera L.).

ETHNOPHARMACOLOGICAL RELEVANCE: Date fruit, Phoenix dactylifera L. has traditionally been used as a medicine in many cultures for the treatment of a range of ailments such as stomach and intestinal disorders, fever, oedema, bronchitis and wound healing. AIM OF THE REVIEW: The present review aims to summarise the traditional use and application of P. dactylifera date fruit in different ethnomedical systems, additionally the botany and phytochemistry are identified. Critical evaluation of in vitro and in vitro studies examining date fruit in relation to anti-inflammatory, anti-angiogenic and antimicrobial activities are outlined. KEY FINDINGS: The ethnomedical use of P. dactylifera in the treatment of inflammatory disease has been previously identified and reported. Furthermore, date fruit and date fruit co-products such as date syrup are rich sources of polyphenols, anthocyanins, sterols and carotenoids. In vitro studies have demonstrated that date fruit exhibits antibacterial, anti-inflammatory and anti-angiogenic activity. The recent interest in the identification of the numerous health benefits of dates using in vitro and in vivo studies have confirmed that date fruit and date syrup have beneficial health effects that can be attributed to the presence of natural bioactive compounds. CONCLUSIONS: Date fruit and date syrup have therapeutic properties, which have the potential to be beneficial to health. However, more investigations are needed to quantify and validate these effects.

Date syrup-derived polyphenols attenuate angiogenic responses and exhibits anti-inflammatory activity mediated by vascular endothelial growth factor and cyclooxygenase-2 expression in endothelial cells.

Bioactive components such as polyphenols, present in many plants, are purported to have anti-inflammatory and antiangiogenic properties. Date syrup, produced from date fruit of the date palm tree, has traditionally been used to treat a wide range of diseases with etiologies involving angiogenesis and inflammation. It was hypothesized that polyphenols in date syrup reduce angiogenic responses such as cell migration, tube formation, and matrix metalloproteinase activity in an inflammatory model by exhibiting anti-inflammatory activity mediated by vascular endothelial growth factor (VEGF) and the prostaglandin enzyme cyclooxygenase-2 (COX-2) in endothelial cells. Date syrup polyphenols at 60 and 600µg/mL reduced inflammation and suppressed several stages of angiogenesis, including endothelial cell migration, invasion, matrix metalloproteinase activity, and tube formation, without evidence of cytotoxicity. VEGF and COX-2 expression induced by tumor necrosis factor-alpha at both gene expression and protein level was significantly reduced by date syrup polyphenols in comparison to untreated cells. In conclusion, polyphenols in date syrup attenuated angiogenic responses and exhibited anti-inflammatory activity mediated by VEGF and COX-2 expression in endothelial cells.

Does case management for patients with heart failure based in the community reduce unplanned hospital admissions? A systematic review and meta-analysis.

OBJECTIVES: The aim of this systematic review of randomised controlled trials (RCTs) and controlled trials (non-RCTs, NRCTs) is to investigate the effectiveness and related costs of case management (CM) for patients with heart failure (HF) predominantly based in the community in reducing unplanned readmissions and length of stay (LOS). SETTING: CM initiated either while as an inpatient, or on discharge from acute care hospitals, or in the community and then continuing on in the community. PARTICIPANTS: Adults with a diagnosis of HF and resident in Organisation for Economic Co-operation and Development countries. INTERVENTION: CM based on nurse coordinated multicomponent care which is applicable to the primary care-based health systems. PRIMARY AND SECONDARY OUTCOMES: Primary outcomes of interest were unplanned (re)admissions, LOS and any related cost data. Secondary outcomes were primary healthcare resources. RESULTS: 22 studies were included: 17 RCTs and 5 NRCTs. 17 studies described hospital-initiated CM (n=4794) and 5 described community-initiated CM of HF (n=3832). Hospital-initiated CM reduced readmissions (rate ratio 0.74 (95% CI 0.60 to 0.92), p=0.008) and LOS (mean difference -1.28 days (95% CI -2.04 to -0.52), p=0.001) in favour of CM compared with usual care. 9 trials described cost data of which 6 reported no difference between CM and usual care. There were 4 studies of community-initiated CM versus usual care (2 RCTs and 2 NRCTs) with only the 2 NRCTs showing a reduction in admissions. CONCLUSIONS: Hospital-initiated CM can be successful in reducing unplanned hospital readmissions for HF and length of hospital stay for people with HF. 9 trials described cost data; no clear difference emerged between CM and usual care. There was limited evidence for community-initiated CM which suggested it does not reduce admission.

Establishing how psychological therapies work: the importance of mediation analysis.

This editorial reviews the literature regarding psychological studies that are designed to address the question of not just whether, psychological interventions effect change, but how. The practicalities and implications of assessing mechanisms of treatments are considered with examples from the fields of Cognitive Behavioural Therapy (CBT) and Mindfulness. The potential for elucidating theoretical mechanisms, developing new theoretical models and modifying treatment approaches are described. In addition an overview of different types of statistical methods available to researchers for assessing mediation is given. Structural Equation Modelling (SEM) is a recommended approach. The review concludes with a summary of optimum study conditions adopted by researchers for establishing mediating effects.

Distress improves after mindfulness training for progressive MS: A pilot randomised trial.

BACKGROUND: Mindfulness-based interventions have been shown to effectively reduce anxiety, depression and pain in patients with chronic physical illnesses. OBJECTIVES: We assessed the potential effectiveness and cost-effectiveness of a specially adapted Skype distant-delivered mindfulness intervention, designed to reduce distress for people affected by primary and secondary progressive MS. METHODS: Forty participants were randomly assigned to the eight-week intervention (n = 19) or a waiting-list control group (n = 21). Participants completed standardised questionnaires to measure mood, impact of MS and symptom severity, quality of life and service costs at baseline, post-intervention and three-month follow-up. RESULTS: Distress scores were lower in the intervention group compared with the control group at post-intervention and follow-up (p < 0.05), effect size -0.67 post-intervention and -0.97 at follow-up. Mean scores for pain, fatigue, anxiety, depression and impact of MS were reduced for the mindfulness group compared with control group at post-therapy and follow-up; effect sizes ranged from -0.27 to -0.99 post-intervention and -0.29 to -1.12 at follow-up. There were no differences in quality-adjusted life years, but an 87.4% probability that the intervention saves on service costs and improves outcome. CONCLUSIONS: A mindfulness intervention delivered through Skype video conferences appears accessible, feasible and potentially effective and cost-effective for people with progressive MS.

Effectiveness of folic acid supplementation in pregnancy on reducing the risk of small-for-gestational age neonates: a population study, systematic review and meta-analysis.

OBJECTIVES: To assess the effect of timing of folic acid (FA) supplementation during pregnancy on the risk of the neonate being small for gestational age (SGA). DESIGN: A population database study and a systematic review with meta-analysis including the results of this population study. SETTING AND DATA SOURCES: A UK regional database was used for the population study and an electronic literature search (from inception until August 2013) for the systematic review. PARTICIPANTS AND INCLUDED STUDIES: Singleton live births with no known congenital anomalies; 111,736 in population study and 188,796 in systematic review. OUTCOME MEASURES, DATA EXTRACTION AND ANALYSIS: The main outcome was SGA based on customised birthweight centile. Associations are presented as odds ratios (OR) and adjusted odds ratios (aOR), adjusted for maternal and pregnancy-related characteristics. RESULTS: Of 108,525 pregnancies with information about FA supplementation, 92,133 (84.9%) had taken FA during pregnancy. Time of commencement of supplementation was recorded in 39,416 pregnancies, of which FA was commenced before conception in 10,036, (25.5%) cases. Preconception commencement of FA supplementation was associated with reduced risk of SGA <10th centile (aOR 0.80, 95% CI 0.71-0.90, P < 0.01) and SGA <5th centile (aOR 0.78, 95% CI 0.66-0.91, P < 0.01). This result was reproduced when the data were pooled with other studies in the systematic review, showing a significant reduction in SGA (<5th centile) births with preconception commencement of FA (aOR 0.75, 95% CI 0.61-0.92, P < 0.006). In contrast, postconception folate had no significant effect on SGA rates. CONCLUSION: Supplementation with FA significantly reduces the risk of SGA at birth but only if commenced preconceptually independent of other risk factors. SYSTEMATIC REVIEW REGISTRATION: This systematic review was prospectively registered with PROSPERO number CRD42013004895.

Which cognitions and behaviours mediate the positive effect of cognitive behavioural therapy on fatigue in patients with multiple sclerosis?

BACKGROUND: Chronic fatigue is a common symptom of multiple sclerosis (MS). A randomized controlled trial (RCT) showed that cognitive behavioural therapy (CBT) was more effective in reducing MS fatigue than relaxation training (RT). The aim of the current study was to analyse additional data from this trial to determine whether (1) CBT compared to RT leads to significantly greater changes in cognitions and behaviours hypothesized to perpetuate MS fatigue; (2) changes in these variables mediate the effect of CBT on MS fatigue; and (3) these mediation effects are independent of changes in mood. METHOD: Seventy patients (CBT, n=35; RT, n=35) completed the Cognitive and Behavioural Responses to Symptoms Questionnaire (CBSQ), the Brief Illness Perception Questionnaire (B-IPQ) modified to measure negative representations of fatigue, the Hospital Anxiety and Depression Scale (HADS), and the Chalder Fatigue Questionnaire (CFQ), pre- and post-therapy. Multiple mediation analysis was used to determine which variables mediated the change in fatigue. RESULTS: Avoidance behaviour and three cognitive variables (symptom focusing, believing symptoms are a sign of damage and a negative representation of fatigue) improved significantly more in the CBT than the RT group. Mediation analysis showed that changing negative representations of fatigue mediated the decrease in severity of fatigue. Change in anxiety covaried with reduction in fatigue but the mediation effect for negative representations of fatigue remained when controlling for improvements in mood. CONCLUSIONS: Change in beliefs about fatigue play a crucial role in CBT for MS fatigue. These beliefs and the role of anxiety deserve more attention in the further development of this intervention.

Neuronal responses in the brainstem and hypothalamic nuclei following insulin treatment during the late follicular phase in the ewe.

The aim of this study was to determine the neuronal responses following insulin administration during the late follicular phase. Intact ewes were given either saline or insulin (5 IU/kg, i.v.) at 35 h after progesterone withdrawal and killed 3 h later. There was a marked increase in the number of Fos-positive noradrenergic neurones in the caudal brainstem of insulin-treated ewes. In the hypothalamic paraventricular nucleus, insulin treatment increased the presence of Fos-positive corticotrophin-releasing hormone neurones (from 2% to 98%) and Fos-positive arginine vasopressin parvocellular neurones (from 2% to 46%). Interestingly, after insulin treatment, despite a general increase in Fos-positive neurones in the arcuate nucleus (ARC), there was a marked reduction (from 47% to 1%) in Fos-positive ß-endorphin neurones. Similarly, colocalized Fos and oestradiol receptor (ER) α-positive neurones decreased in the ARC after insulin (from 7% to 3%). Conversely, in the ventromedial nucleus, ERα-positive neurones with Fos increased (from 7% to 22%) alongside a general increase in Fos-positive neurones. Overall, a complex system of neurones in brainstem and hypothalamus is activated following insulin administration during the late follicular phase.

Integration between different hypothalamic nuclei involved in stress and GnRH secretion in the ewe.

This study investigated possible integrated links in the neuroanatomical pathways through which the activity of neurones in the paraventricular nucleus and arcuate nucleus may modulate suppression of gonadotrophin-releasing hormone (GnRH) secretion during stressful situations. Double-label immunofluorescence and laser scanning confocal microscopy were used to examine the hypothalamic sections from the follicular phase ewes. Noradrenergic terminals were in close contact with 65.7 ± 6.1% corticotrophin-releasing hormone (CRH) and 84.6 ± 3.2% arginine vasopressin (AVP) cell bodies in the paraventricular nucleus but not with ß-endorphin cell bodies in the arcuate nucleus. Furthermore, γ-amino butyric acid (GABA) terminals were close to 80.9 ± 3.5% CRH but no AVP cell bodies in the paraventricular nucleus, as well as 60.8 ± 4.1%ß-endorphin cell bodies in the arcuate nucleus. Although CRH, AVP and ß-endorphin cell terminals were identified in the medial pre-optic area, no direct contacts with GnRH cell bodies were observed. Within the median eminence, abundant CRH but not AVP terminals were close to GnRH cell terminals in the external zone; whereas, ß-endorphin cells and terminals were in the internal zone. In conclusion, neuroanatomical evidence is provided for the ewe supporting the hypothesis that brainstem noradrenergic and hypothalamic GABA neurones are important in modulating the activity of CRH and AVP neurones in the paraventricular nucleus, as well as ß-endorphin neurones in the arcuate nucleus. These paraventricular and arcuate neurones may also involve interneurones to influence GnRH cell bodies in medial pre-optic area, whereas the median eminence may provide a major site for direct modulation of GnRH release by CRH terminals.

Relationship and interaction between sodium and potassium.

Compared with the Stone Age diet, the modern human diet is both excessive in NaCl and deficient in fruits and vegetables which are rich in K+ and HCO3- -yielding organates like citrate. With the modern diet, the K+/Na+ ratio and the HCO3-/Cl- ratio have both become reversed. Yet, the biologic machinery that evolved to process these dietary electrolytes remains largely unchanged, genetically fixed in Paleolithic time. Thus, the electrolytic mix of the modern diet is profoundly mismatched to its processing machinery. Dietary potassium modulates both the pressor and hypercalciuric effects of the modern dietary excess of NaCl. A marginally deficient dietary intake of potassium amplifies both of these effects, and both effects are dose-dependently attenuated and may be abolished either with dietary potassium or supplemental KHCO3. The pathogenic effects of a dietary deficiency of potassium amplify, and are amplified by, those of a dietary excess of NaCl and in some instances a dietary deficiency of bicarbonate precursors. Thus, in those ingesting the modern diet, it may not be possible to discern which of these dietary electrolytic dislocations is most determining of salt-sensitive blood pressure and hypercalciuria, and the hypertension, kidney stones, and osteoporosis they may engender. Obviously abnormal plasma electrolyte concentrations rarely characterize these dietary electrolytic dislocations, and when either dietary potassium or supplemental KHCO3 corrects the pressor and hypercalciuric effects of these dislocations, the plasma concentrations of sodium, potassium, bicarbonate and chloride change little and remain well within the normal range.

In vitro and in vivo activity and cross resistance profiles of novel ruthenium (II) organometallic arene complexes in human ovarian cancer.

Ruthenium complexes offer the potential of reduced toxicity, a novel mechanism of action, non-cross resistance and a different spectrum of activity compared to platinum containing compounds. Thirteen novel ruthenium(II) organometallic arene complexes have been evaluated for activity (in vitro and in vivo) in models of human ovarian cancer, and cross-resistance profiles established in cisplatin and multi-drug-resistant variants. A broad range of IC50 values was obtained (0.5 to >100 microM) in A2780 parental cells with two compounds (RM175 and HC29) equipotent to carboplatin (6 microM), and the most active compound (HC11) equipotent to cisplatin (0.6 microM). Stable bi-dentate chelating ligands (ethylenediamine), a more hydrophobic arene ligand (tetrahydroanthracene) and a single ligand exchange centre (chloride) were associated with increased activity. None of the six active ruthenium(II) compounds were cross-resistant in the A2780cis cell line, demonstrated to be 10-fold resistant to cisplatin/carboplatin by a mechanism involving, at least in part, silencing of MLH1 protein expression via methylation. Varying degrees of cross-resistance were observed in the P-170 glycoprotein overexpressing multi-drug-resistant cell line 2780AD that could be reversed by co-treatment with verapamil. In vivo activity was established with RM175 in the A2780 xenograft together with non-cross-resistance in the A2780cis xenograft and a lack of activity in the 2780AD xenograft. High activity coupled to non cross-resistance in cisplatin resistant models merit further development of this novel group of anticancer compounds.

Cultural ecology of Whitethroat (Sylvia communis) habitat management by farmers: winter in farmland trees and shrubs in Senegambia.

The presence of Whitethroats and their potential invertebrate prey in farmland trees and shrubs was investigated. The management of this vegetation by farmers, and their motivation for that management, was explored using participatory techniques. Whitethroats were associated with Guiera senegalensis, the shrub species which supports most caterpillars and spiders. Farmers reported declines in trees and shrubs since the 1950s, loss of fallow areas, declines in soil fertility and crop yields, and increases in the use of fire for clearing fields. Trees are valued by people for their cultural and medicinal uses and some species used by Whitethroats and other birds have potential for restoring soil fertility, although this was not recognised by farmers. More sustainable use of savanna farmland could have both agronomic and wider conservation benefits, and the provision of information that accommodates farmers' cultural and economic incentives could benefit both farmers and wildlife.

Management of acute cardiac failure with mechanical assist: experience with the ABIOMED BVS 5000.

BACKGROUND: Mechanical circulatory assist industries have developed ventricular assist devices (VAD) for short-, intermediate-, and long-term use. The purpose of this report is to describe the progress made with the ABIOMED Biventricular System (BVS) 5000 (ABIOMED, Inc, Danvers, MA) short-term VAD. METHODS: From June 1994 through August 2000, all cardiogenic shock patients who required short-term mechanical assist were supported with the ABIOMED BVS 5000. Insertion criteria included any condition that may potentially result in cardiac recovery. A formal algorithm for timing of insertion was established to standardize implantation criteria. RESULTS: A total of 45 patients were supported at Hahnemann University Hospital, Philadelphia, PA. There were 26 male and 19 female patients, with a mean age of 57.9 years (range 33 to 80 years). Devices were inserted for postcardiotomy shock in 36 patients (80%) and precardiotomy shock in 9 patients (20%). The average duration of support was 8.3 days (range 1 to 31 days). Overall, there were 22 (49%) patients weaned from support and 14 (31%) discharged from the hospital. For patients in whom the device was implanted in accordance with an established protocol (group A), the wean and discharge rates were 60% and 43%, respectively. The most common morbidities included bleeding and adverse neurologic events. CONCLUSIONS: The ABIOMED BVS 5000 VAD continues to be a valuable form of short-term mechanical assist for acute cardiogenic shock. The formation of a uniform VAD insertion algorithm has helped to standardize protocols in management.

Design of a novel mammalian screening system for the detection of bioavailable, non-cytotoxic streptogramin antibiotics.

Screening and development of new antibiotic activities to counteract the increasing prevalence of multidrug-resistant (MDR) human pathogenic bacteria has once again become a priority in human chemotherapy. Here we describe a novel mammalian cell culture-based screening platform for the detection of streptogramin antibiotics. Quinupristin-dalfopristin (Synercid), a synthetically modified streptogramin, is presently the sole effective agent in the treatment of some MDR nosocomial infections. A Streptomyces coelicolor transcriptional regulator (Pip) has been adapted to modulate reporter gene expression (SEAP, secreted alkaline phosphatase) in Chinese hamster ovary cells (CHO) in response to streptogramin antibiotics. This CHO cell-based technology was more sensitive in detecting the production of the model streptogramin pristinamycin, from Streptomyces pristinaespiralis, than antibiogram tests using a variety of human pathogenic bacteria as indicator strains. The reporter system was able to detect pristinamycin compound produced by a single S. pristinaespiralis colony. The assay was rapid (17 hours) and could be carried out in a high-throughput 96-well plate assay format or a 24-well transwell set-up. This novel mammalian cell-based antibiotic screening concept enables detection of bioavailable and non-cytotoxic representatives of a particular class of antibiotics in a single assay and represents a promising alternative to traditional antibiogram-based screening programs.