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Background and purpose: The reduction of delay between onset and hospital arrival and adequate pre‐hospital care of persons with acute stroke are important for improving the chances of a favourable outcome. The objective is to recommend evidence‐based practices for the management of patients with suspected stroke in the pre‐hospital setting. Methods: The GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology was used to define the key clinical questions. An expert panel then reviewed the literature, established the quality of the evidence, and made recommendations. Results: Despite very low quality of evidence educational campaigns to increase the awareness of immediately calling emergency medical services are strongly recommended. Moderate quality evidence was found to support strong recommendations for the training of emergency medical personnel in recognizing the symptoms of a stroke and in implementation of a pre‐hospital ‘code stroke’ including highest priority dispatch, pre‐hospital notification and rapid transfer to the closest ‘stroke‐ready’ centre. Insufficient evidence was found to recommend a pre‐hospital stroke scale to predict large vessel occlusion. Despite the very low quality of evidence, restoring normoxia in patients with hypoxia is recommended, and blood pressure lowering drugs and treating hyperglycaemia with insulin should be avoided. There is insufficient evidence to recommend the routine use of mobile stroke units delivering intravenous thrombolysis at the scene. Because only feasibility studies have been reported, no recommendations can be provided for pre‐hospital telemedicine during ambulance transport. Conclusions: These guidelines inform on the contemporary approach to patients with suspected stroke in the pre‐hospital setting. Further studies, preferably randomized controlled trials, are required to examine the impact of particular interventions on quality parameters and outcome. [ABSTRACT FROM AUTHOR]

Key points Early physical mobilization of mechanically ventilated intensive care unit (ICU) patients can reduce the length of stay in the ICU and hospital and improve muscle strength and functional outcomes., A unique experimental rat ICU model has been used to study the effects and underlying mechanisms of unilateral passive mechanical loading on skeletal muscle size and function at durations varying between 6 h and 2 weeks., Passive mechanical loading attenuated the loss of muscle mass and force-generation capacity associated with the ICU intervention., The maintained muscle mass and function by passive loading is probably due to lower oxidative stress and a reduced loss of the molecular motor protein myosin., The beneficial effects of passive mechanical loading on muscle size and function strongly support the importance of early and intense physical therapy in immobilized ICU patients., Abstract The response to mechanical stimuli, i.e. tensegrity, plays an important role in regulating cell physiological and pathophysiological function, and the mechanical silencing observed in intensive care unit (ICU) patients leads to a severe and specific muscle wasting condition. This study aims to unravel the underlying mechanisms and the effects of passive mechanical loading on skeletal muscle mass and function at the gene, protein and cellular levels. A unique experimental rat ICU model has been used allowing long-term (weeks) time-resolved analyses of the effects of standardized unilateral passive mechanical loading on skeletal muscle size and function and underlying mechanisms. Results show that passive mechanical loading alleviated the muscle wasting and the loss of force-generation associated with the ICU intervention, resulting in a doubling of the functional capacity of the loaded versus the unloaded muscles after a 2-week ICU intervention. We demonstrate that the improved maintenance of muscle mass and function is probably a consequence of a reduced oxidative stress revealed by lower levels of carbonylated proteins, and a reduced loss of the molecular motor protein myosin. A complex temporal gene expression pattern, delineated by microarray analysis, was observed with loading-induced changes in transcript levels of sarcomeric proteins, muscle developmental processes, stress response, extracellular matrix/cell adhesion proteins and metabolism. Thus, the results from this study show that passive mechanical loading alleviates the severe negative consequences on muscle size and function associated with the mechanical silencing in ICU patients, strongly supporting early and intense physical therapy in immobilized ICU patients. [ABSTRACT FROM AUTHOR]

Precise measurement of low enrichment of stable isotope labeled amino-acid tracers in tissue samples is a prerequisite in measuring tissue protein synthesis rates. The challenge of this analysis is augmented when small sample size is a critical factor. Muscle samples from human participants following an 8 h intravenous infusion of L-[ring-13C6]phenylalanine and a bolus dose of L-[ring-13C6]phenylalanine in a mouse were utilized. Liquid chromatography tandem mass spectrometry (LC/MS/MS), gas chromatography (GC) MS/MS and GC/MS were compared to the GC-combustion-isotope ratio MS (GC/C/IRMS), to measure mixed muscle protein enrichment of [ring-13C6]phenylalanine enrichment. The sample isotope enrichment ranged from 0.0091 to 0.1312 molar percent excess. As compared with GC/C/IRMS, LC/MS/MS, GC/MS/MS and GC/MS showed coefficients of determination of R2 = 0.9962 and R2 = 0.9942, and 0.9217 respectively. However, the precision of measurements (coefficients of variation) for intra-assay are 13.0%, 1.7%, 6.3% and 13.5% and for inter-assay are 9.2%, 3.2%, 10.2% and 25% for GC/C/IRMS, LC/MS/MS, GC/MS/MS and GC/MS, respectively. The muscle sample sizes required to obtain these results were 8 µg, 0.8 µg, 3 µg and 3 µg for GC/C/IRMS, LC/MS/MS, GC/MS/MS and GC/MS, respectively. We conclude that LC/MS/MS is optimally suited for precise measurements of L-[ring-13C6]phenylalanine tracer enrichment in low abundance and in small quantity samples. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

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We investigated age and sex effects and determined whether androgen replacement in elderly individuals (≥ 60 yr) could augment protein synthesis. Thirty young men and 32 young women (18-31 yr) were studied once, whereas 87 elderly men were studied before and after 1 yr of treatment with 5 mg/day testosterone (T), 75 mg/day dehydroepiandrosterone (DHEA), or placebo (P); and 57 elderly women were studied before and after 1 yr of treatment with 50 mg/day DHEA or [15N]Phenytalanine and [²H4]tyrosine tracers were infused, with measurements in plasma and vastus lateralis muscle. Whole-body protein synthesis per fat-free mass and muscle protein fractional synthesis rate (FSR) were lower in elderly than in young individuals (P<0.001), not significantly affected by hormone treatments, and higher in women than in men (P<0.0001), with no sex X age interaction. In regression analyses, peak O2 consumption (VO2peak), resting energy expenditure (REE), and sex were independently associated with muscle FSR, as were VO2peak, REE, and interactions of sex with insulin-like growth factor-II and insulin for whole-body protein synthesis. Women maintain higher protein synthesis than men across the lifespan as rates decline in both sexes, and neither full replacement of DHEA (in elderly men and women) nor partial replacement of bioavailable T (in elderly men) is able to amend the age-related declines. [ABSTRACT FROM AUTHOR]

The demonstration of the ischaemic penumbra in animal models and the effectiveness of reperfusion therapy in humans led to considerable optimism for neuroprotection in acute stroke. Initial experience with failure of phase II and III trials led to the STAIR recommendations for pre-clinical and clinical studies. Review of pre-clinical studies suggests that selection of agents for clinical development may not have been optimal. The neuroprotective agent NXY-059 fulfilled pre-clinical and many clinical STAIR criteria but a second large phase III study failed to demonstrate any benefit. Many of the STAIR criteria have not been fulfilled in the development of recent neuroprotective agents. Other issues not addressed include the use of animal models more reflective of older stroke patients with physiological derangement, demonstration of drug distribution to the proposed site of action in humans, selection of patients with salvageable tissue, achieving very early treatment, refinement of measurement of neurological impairment and disability, and physiological optimization in proof of concept human studies. Increasing the number and quality of clinical centres undertaking acute stroke research, use of surrogate imaging markers and adaptive dose designs in phase II trials could improve the likelihood of identifying an effective neuroprotective. Neuroprotection in acute stroke remains a significant challenge but has not been clearly shown to be ineffective. Given the profound burden of stroke and limited applicability of reperfusion to currently at best 10% patients, further proof of concept studies of neuroprotection remain indicated with careful review of pre-clinical data and more rigorous phase II trial design. [ABSTRACT FROM AUTHOR]

The aims of this study were to determine the motor outcome of extremely-low-birthweight (ELBW; <1000g) or very preterm (<28wks) children compared with normal birthweight (NBW) children, to establish the perinatal associations of developmental coordination disorder (DCD) and its cognitive and behavioural consequences. Participants were consecutive surviving ELBW or very preterm children and randomly selected NBW(>2499g) children born in the state of Victoria, Australia, in 1991 or 1992. Main outcomes were: (1) results of the Movement Assessment Battery for Children (MABC) at 8 years of age; (2) cognitive function; (3) academic progress; and (4) behaviour. Of 298 consecutive ELBW/very preterm survivors, 255 (85.6%; 117 males, 138 females) had the MABC at a mean age of 8 years 8 months. More ELBW/very preterm children (9.5%) had DCD than the NBW group (2%, p=0.001). Only male sex increased the likelihood of DCD in ELBW/very preterm children ( p=0.017). ELBW/very preterm children with DCD had worse cognitive function and academic test scores (up to 1SD below those without DCD); they also had more adaptive behaviour and externalizing problems, but not internalizing problems. DCD is more common in ELBW/very preterm children, has few perinatal correlates, and is associated with poor cognitive and academic performance as well as increased behaviour problems. [ABSTRACT FROM AUTHOR]

Objectives: Methylxanthines, including theophylline, have been used extensively and successfully to treat apnoea in preterm infants. However, long-term consequences of such therapy are largely unknown. The aim of this study was to determine the relationship between theophylline therapy and outcome at 14 years of age in surviving preterm children of birthweight < 1501 g.Methodology: The subjects of this study were 154 consecutive survivors with birthweights < 1501 g born from 1 October 1980 to 31 March 1982; 130 (84.4%) were assessed at 14 years of age. Outcomes included motor function, psychological test scores, and growth.Results: Of the 130 children assessed, 69 (53.1%) had been exposed to theophylline; 13.0% had cerebral palsy, significantly higher than 1.6% in the 61 children not exposed to theophylline (P < 0.02). This difference remained statistically significant after adjusting for potential confounding variables including the presence of cerebroventricular haemorrhage. In contrast, after adjusting for known confounding variables, children who had received theophylline achieved higher psychological test scores. There was no association between theophylline therapy and growth.Conclusions: Theophylline therapy in the newborn period is associated with some evidence of harmful, but also helpful sensorineural effects at 14 years of age. [ABSTRACT FROM AUTHOR]

Objective: To determine the changes in the rates of survival, cranial ultrasound abnormalities and cerebral palsy in very low birthweight (VLBW) (birthweight 500-1499 g) infants between the early 1980s and the early 1990s.Methodology: A cohort study of consecutive VLBW live births in one tertiary perinatal hospital during two distinct eras was performed at The Royal Women's Hospital, Melbourne, a level-III perinatal centre. Consecutive VLBW infants born over the 18-month period from 1 October 1980 (n = 222), and over the 12-month period from 1 January 1992 (n = 202) were identified. The main outcome measures were the proportions of live births surviving to 5 years of age, rates of cranial ultrasound abnormalities, and rates of cerebral palsy at 5 years of age.Results: Over the 18 months from 1 October 1980, 68% (150/222) VLBW live births survived to 5 years of age. The survival rate rose substantially to 82% (165/202) during 1992 (odds ratio 2.1, 95% confidence interval 1.4-3.2). The survival rate increased over time more for those of 500-999 g birthweight than for those of 1000-1499 g birthweight. The rates of cerebroventricular haemorrhage (CVH) were similar inlive births and survivors from both eras, as were the rates of cerebral palsy (7.5% in 1980-82; 7.8% in 1992) in survivors seen at 5 years of age. The positive predictive value of CVH for cerebral palsy was low, but cystic periventricular leucomalacia was followed by cerebral palsy in seven of eight survivors from the 1992 cohort.Conclusions: Despite the increasing survival rate with improvements in perinatal care, including more antenatal steroid therapy and the introduction of exogenous surfactant, the rates of CVH and of cerebral palsy in survivors have not diminished. [ABSTRACT FROM AUTHOR]

Summary We report the characterization of a naturally occurring polymorphism in CD40 ligand (CD40L, CD154) expressed by activated T cells from a young female patient. This polymorphism encodes a nonconservative Gly → Arg substitution in amino acid 219 in the extracellular, CD40 binding domain of the molecule. Studies carried out with 293 epithelial cells ectopically expressing the polymorphic protein (CD154/G219R) revealed reduced levels of binding to different anti‐CD154 monoclonal antibodies (mAb) and CD40‐immunoglobulin (CD40‐Ig). However, recognition of the polymorphic and wild‐type CD154 molecules by a polyclonal antiserum was comparable, suggesting that the polymorphism affects the ability of the protein to interact with CD40 but does not significantly alter its surface expression. To determine if reduced cross‐linking of CD40 mediated decreased functional effects, three CD40‐dependent properties were measured. We found that pathways leading to the induction of surface CD23, CD80, and Iγ transcription were activated in response to CD154/G219R signalling. However, the decrease in affinity for CD40 by the mutated CD154 affected the ability of CD40‐Ig to efficiently interfere with the binding and effectively block induced CD80 expression. In contrast, we found that the 5c8 mAb, which recognized the polymorphic molecule to a similar extent as wild‐type CD154, effectively blocked the interaction between CD154/G219R and CD40 as measured by CD80 expression. These findings suggest that naturally occurring polymorphisms in the CD154 molecule may affect the ability of CD40‐mediated functions to be blocked by soluble CD40 or anti‐CD154 mAb in the therapeutic treatment of disease and graft rejection. [ABSTRACT FROM AUTHOR]

The incidence of positive patch test reactions to Quaternium 15 has increased by a factor of 3 within a relatively stable population over 2 years, while the incidence of reactions to Bronopol and Germall 115 has remained static. The problem of interpreting an apparent positive reaction to a formaldehyde-releasing preservative in a formaldehyde-sensitive patient is discussed. [ABSTRACT FROM AUTHOR]

Light transmission through several sands, soils and size classes of glass beads was investigated. The glass beads served as a highly reflective model system for the sands. Light penetration was significantly better through sands than through either sandy or silty loams. For sandy soils, there was a shift in the spectrum leading to a change in the red- to-far-red photon ratio with increase in depth: this ratio dropped by more than 30% in the first few millimetres, and in some cases increased again with further increases in depth. The depths at which these changes occurred in the soil profile were specific for a given soil type. Similar spectral changes were obtained when sample depth for a sandy soil was held constant, and particle (ped) size of that soil was decreased. No such changes, either with sample depth or ped size, were observed with loams. Per cent transmittance in the blue (442 nm) was more than three orders of magnitude lower than in the red (632.8 nm) for sandy soils. When dry sandy soils were water-saturated, their transmittance increased by up to three orders of magnitude, and the red/far-red ratios in the transmitted light increased in all cases. By contrast, water-saturated loams were essentially opaque. The possible significance of these spectral properties of soils in seed germination and seedling photomorphogenesis is discussed. [ABSTRACT FROM AUTHOR]

Aims The study was designed to investigate the effects of the H2-receptor antagonists, cimetidine and ranitidine on the pharmacokinetics and pharmacodynamics of nebivolol in healthy volunteers. Methods Twelve healthy volunteers took part in a randomized placebo-controlled cross-over study. Each subject received on three separate occasions placebo, cimetidine (400 mg twice daily) or ranitidine (150 mg twice daily) for 24 h before and 48 h after a single oral dose of nebivolol (5 mg). Nebivolol and its individual (+) and (−) enantiomers were determined tby h.p.l.c. Results Ranitidine had no significant effect on nebivolol pharmacokinetics. Cimetidine, however, resulted in a 21-23% increase in Cmax of unchanged nebivolol and of each enantiomer plus its hydroxylated metabolites. Cimetidine significantly ( P<0.05) increased the AUC [mean±s.d. (95% C.I. of differences in mean)] for unchanged (±)-nebivolol [7.76±3.07 ng ml−1h with placebo; 11.50±5.40 (1.75, 8.76) ng ml−1h with cimetidine], (+)-nebivolol plus its hydroxylated metabolites [73.0±18.0 ng ml−1h with placebo; 91.5±25.7 (1.0, 23.1) ng ml−1h with cimetidine] and (−)-nebivolol plus its hydroxylated metabolites [101±32 ng ml−1h with placebo; 123±38 (3.3, 27.0) ng ml−1h with cimetidine]. Statistical analysis of the resting blood pressure and heart rate and exercise data did not suggest any consistent effects of ranitidine or cimetidine upon the pharmacodynamic effects of nebivolol. Conclusions There was no interaction between ranitidine and nebivolol. Although cimetidine inhibited nebivolol metabolism, it did not have a significant influence on the pharmacodynamics of the drug. [ABSTRACT FROM AUTHOR]

SUMMARY The effect of treatment with either gypsum or sodium chloride on the saturated hydraulic conductivity ( Ks) of repacked soil columns and modulus of rupture (MOR) was studied on surface samples of two red-brown earth soils from SE wheat belt in Australia. When the exchangeable sodium percentage (ESP) of the two soils was increased to >80, KS was substantially reduced and MOR increased relative to the untreated soil; the values of the parameters were nearly equal for these pairs of high ESP soils. However, after treatment with gypsum the Raywood soil had a Ks twice, and a MOR less than half, the corresponding values for the Glenloth soil. Micromorphological and scanning electron microscope (SEM) observations suggest that the increase in Ks following gypsum treatment is associated with an increase in visible macropores and reduced clay dispersion; Na treatment increased dispersion at the soil surface, with the clay particles forming an impermeable surface seal and illuviation argillans. [ABSTRACT FROM AUTHOR]

Partially humified material can be separated from other soil material by flotation on a bromoform-petroleum spirit mixture of density 2·0 g cm-3. Maximum recovery of partially humified material requires ultrasonic dispersion and the addition of a surfactant to the suspension. For large-scale work'Nemagon' may be used in place of the bromoform-petroleum spirit mixture. [ABSTRACT FROM AUTHOR]

Of 12 Gymnospermae seed and leaf oils, only 2 contained cyclopropene fatty acids. All- cis 5, 11, 14, 17-eicosatetraenoic acid occurred in concentrations up to 11.9% in 6 seed oils, and up to 61% in 2 leaf oils. The structure of this acid, as its methyl ester, was established by the combination of physical (UV, IR,H- andC-NMR and mass spectra) and chemical techniques. Arachidonic acid also occurred in 2 seed oils. [ABSTRACT FROM AUTHOR]

The occurrence of allergic contact dermatitis from topical and systemic steroids is described. The case was examined in a 61-year-old-lady who had a past history of clothing dye dermatitis. She found that topical steroids had aggravated her current hand dermatitis. She was patch tested with European standard series. Related to it, another case was examined who had inner thigh eczema. He was patch tested with a supplemented European standard and steroid series. It is found that there is increasing awareness of allergic contact dermatitis from topical steroids than from systemic steroids.

Analyzing Santalum obtusifolium seed oil led to the identification of 12 fatty acids; only ximenynic (71.5%) and oleic (14.3%) acids were present in substantial amounts. Data on the mass spectrum andH- andC-NMR (nuclear magnetic resonance) spectra of methyl ximenynate are given. [ABSTRACT FROM AUTHOR]

The article deals with a case report dealing with contact sensitivity to aluminum acetate eardrops. A 9 year old boy had a 2 year old history of eczema of the external auditory meati. He was congenitally deaf and had worn hearing aids since infancy. He had chronic bilateral discharging otitis media. 5 percent aluminum acetate drops were effective in drying up the secretions for a little while but otitis externa developed and persisted. The use of aluminum acetate eardrops was discontinued and the otitis externa was resolved.