Characterisation of aluminium release by the enFlow® fluid-warming system in crystalloids and blood products.

The use of uncoated aluminium-heated plates in an intravenous fluid-warming system has been shown to produce high levels of aluminium in Sterofundin 1/1E, a balanced crystalloid solution. However, the effect of this fluid-warming device on other balanced crystalloid solutions and blood products has not been studied. Using mass spectrometry we measured aluminium levels in Plasma-Lyte 148, compound sodium lactate solution, 4% human albumin solution, expired resuspended packed red cells and fresh frozen plasma that were pumped through an enFlow® fluid-warming system at 2 ml.min-1 . Samples were taken at baseline before heating and then at 10-min intervals up to 60 min with the system set to warm the fluids to 40 °C. High concentrations of aluminium were found for Plasma-Lyte 148 and compound sodium lactate solutions (mean (SD) 223 (0.6) µmol.l-1 and 163 (0.2) µmol.l-1 at 60 min, respectively); both concentrations were significantly greater than the United States Food and Drug Administration recommended maximum limit for aluminium in intravenous nutrition of 25 µg.l-1 (0.9 µmol.l-1 ). Lower aluminium levels were found in 4% human albumin solutions, expired resuspended red cells and fresh frozen plasma at 60 min (mean (SD) 5.7 (0.1) µmol.l-1 , 2.7 (0.0) µmol.l-1 and 2.3 (0.4) µmol.l-1 , respectively). The process allowing addition of aluminium to be added to Sterofundin 1/1E by the enFlow fluid warmer also occurs in Plasma-Lyte 148 and compound sodium lactate solutions and to a lesser degree in blood products. The exact mechanism facilitating this process and its clinical significance remain unclear.

Vox Sanguinis International Forum on the use of prehospital blood products and pharmaceuticals in the treatment of patients with traumatic haemorrhage.

While specific practices and transported blood products vary around the world, most of the respondents in this International Forum transported at least one blood product for the transfusion to bleeding patients en route to the hospital. The most commonly carried product was RBCs, while the use of whole blood will likely increase given the recent reports of its successful use in the civilian setting, and because of the change in the AABB's Standards regulating its use. It will be interesting to see if plasma use in the prehospital setting becomes more widely used given today's enhanced appreciated of the coagulopathy of trauma and plasma's beneficial effect in reversing it, and if blood products are transported to the scene of injury by more vehicles, that is, not just predominantly in helicopters. It was not surprising that TXA is being widely administered as close to the time of injury as possible given its potential benefit in these patients. This International Forum highlights the importance of focusing attention on prehospital transfusion management with a need to further high­quality research in this area to guide optimal resuscitation strategies.

Machine Learning of Infant Spontaneous Movements for the Early Prediction of Cerebral Palsy: A Multi-Site Cohort Study.

BACKGROUND: Early identification of cerebral palsy (CP) during infancy will provide opportunities for early therapies and treatments. The aim of the present study was to present a novel machine-learning model, the Computer-based Infant Movement Assessment (CIMA) model, for clinically feasible early CP prediction based on infant video recordings. METHODS: The CIMA model was designed to assess the proportion (%) of CP risk-related movements using a time-frequency decomposition of the movement trajectories of the infant's body parts. The CIMA model was developed and tested on video recordings from a cohort of 377 high-risk infants at 9-15 weeks corrected age to predict CP status and motor function (ambulatory vs. non-ambulatory) at mean 3.7 years age. The performance of the model was compared with results of the general movement assessment (GMA) and neonatal imaging. RESULTS: The CIMA model had sensitivity (92.7%) and specificity (81.6%), which was comparable to observational GMA or neonatal cerebral imaging for the prediction of CP. Infants later found to have non-ambulatory CP had significantly more CP risk-related movements (median: 92.8%, p = 0.02) compared with those with ambulatory CP (median: 72.7%). CONCLUSION: The CIMA model may be a clinically feasible alternative to observational GMA.

Premature ejaculation: definition and prevalence.

Premature ejaculation (PE) is likely the most common sexual dysfunction in men, with a worldwide prevalence of approximately 30%. To date, the lack of a universally acknowledged definition of PE has complicated the examination and analysis of PE in clinical and research-related settings. The impact of PE on men and their partners also needs to be clearly defined. Clearly, a better understanding of the epidemiology of this disorder, especially with regard to prevalence and risk factors, is necessary. The prevalence of PE appears to vary across socio-cultural and geographic populations. The elucidation of the etiology of PE and risk factors associated with PE has been difficult. However, several risk factors for PE exist that have strong support in the literature. Clearly, an improved and universal definition and understanding of PE and its epidemiology will improve the clinical management of PE and the success of future epidemiologic studies and clinical trials.

Urinary catheterization in care homes for older people: self-reported questionnaire audit of catheter management by care home staff.

A self-administered questionnaire was used to determine care home staff's reported knowledge of the urinary catheter care standards published by the National Institute for Clinical Excellence (NICE) and the Association of Continence Care, and to see whether this differed in homes with higher catheterization rates. Seven hundred and fifty out of 1438 (52%) nursing and care staff from 37 randomly selected care homes with high, medium and low catheterization rates responded. There was no difference in reported practice in care homes in the three health districts sampled or those with differing catheterization rates. Eighty-three percent of the nursing staff and 40% of the other care staff received formal catheter care training. However, at least 10% of all staff reported not washing their hands before handling a catheter, and delaying emptying a urine bag until it was full, rather than three-quarters full. Only 45% of nursing staff and 40% of other care staff encouraged residents to empty their own catheter bags. Routine use of catheter maintenance solutions or bladder washouts was reported by 50% of all staff. Nursing staff (29%) and other care staff (54%) took urine specimens from the catheter bag tap. Compliance with standards has improved greatly since an audit in 1998. However, some non-compliance remains. There is a need for ongoing local audit and formal training in urinary catheter care, particularly for non-qualified care staff. Education is needed to ensure local implementation of NICE guidance.

Yeast-derived sigma C protein-induced immunity against avian reovirus.

Avian reoviruses (ARVs) can result in disease and economic losses in the poultry industry. Vaccines against ARV may not provide full protection and can cause adverse reactions. The coding sequence of the sigma C protein from strain S1133 of avian reovirus was expressed in Schizasaccharomyces pombe. Sigma C protein expression was demonstrated by Western blotting, and the protein was evaluated for its ability to protect specific-pathogen-free (SPF) chickens against challenge with the virulent S1133 strain. Serologic and challenge-infection data showed the efficacy of the recombinant vaccine administered orally each week for 3 consecutive wk. Sigma C protein induced antibody, as determined by enzyme-linked immunosorbent assay. Percentage (%) protection induced by the low dose (125 microg purified yeast-expressed sigma C protein/chicken) or the high dose (250 microg purified yeast-expressed sigma C protein/chicken) was 64 and 91, respectively. The commercial vaccine administered once or twice provided 82% protection. Results supported the feasibility of a plant-derived vaccine for use in poultry immunization schemes.

Potential neuroprotective strategies for perinatal infection and inflammation.

Preterm born infants have high rates of brain injury, leading to motor and neurocognitive problems in later life. Infection and resulting inflammation of the fetus and newborn are highly associated with these disabilities. However, there are no established neuroprotective therapies. Microglial activation and expression of many cytokines play a key role in normal brain function and development, as well as being deleterious. Thus, treatment must achieve a delicate balance between possible beneficial and harmful effects. In this review, we discuss potential neuroprotective strategies targeting systemic infection or the resulting systemic and central inflammatory responses. We highlight the central importance of timing of treatment and the critical lack of studies of delayed treatment of infection/inflammation.

Comparison of methods for analysis of clinical [11C]raclopride studies.

Five different methods for the estimation of the binding potential, a measure of Bmax/Kd, of [11C]raclopride in human striatum were compared using data from a dose ranging study of the neuroleptic CP-88,059-01. Binding potential was estimated indirectly, from distribution volumes in striatum and cerebellum, using both single- and two-tissue compartment models with a metabolite-corrected plasma curve as input function. The two-tissue compartment model was also used for a direct estimate of the binding potential. In addition, a direct estimate was obtained from the reference tissue compartment model using the cerebellum as indirect input function. Finally, an estimate of binding potential was calculated from the ratio of striatum over cerebellum counts at late times after injection. The estimates of striatum binding potential from all methods, except the direct determination using a two-tissue compartment model with metabolite-corrected plasma input function, correlated with each other. Use of an average metabolite correction resulted in only a small reduction in accuracy in this series of normal subjects. The reference tissue model provided estimates of the binding potential with the same sensitivity for detecting changes as those methods that required a metabolite-corrected plasma input function. This indicates that for routine analysis of clinical [11C]raclopride studies, no arterial cannulation is required. The range of normal values was significantly less variable with the reference tissue method than when simple striatum-to-cerebellum ratios were used.

Intramuscular ziprasidone compared with intramuscular haloperidol in the treatment of acute psychosis. Ziprasidone I.M. Study Group.

BACKGROUND: This 7-day, randomized, open-label, multicenter, international study compared the efficacy and tolerability of intramuscular (i.m.) ziprasidone with haloperidol i.m. and the transition from i.m. to oral treatment in hospitalized patients with acute psychotic agitation (related to DSM-III-R diagnoses). METHOD: Patients received up to 3 days of flexible-dose ziprasidone i.m. (N = 90) or haloperidol i.m. (N = 42) followed by oral treatment to day 7. After an initial ziprasidone i.m. dose of 10 mg, subsequent i.m. doses of 5 to 20 mg could be given every 4 to 6 hours (maximum daily dose = 80 mg) if needed, followed by oral ziprasidone, 80-200 mg/day. Haloperidol i.m. doses of 2.5 to 10 mg were given on entry, followed by 2.5 to 10 mg i.m. every 4 to 6 hours (maximum daily dose = 40 mg) if needed, then by oral haloperidol, 10-80 mg/day. RESULTS: The mean reductions in Brief Psychiatric Rating Scale (BPRS) total, BPRS agitation items, and Clinical Global Impressions-Severity scale scores were statistically significantly greater (p < .05, p < .01, and p < .01, respectively) after ziprasidone i.m. treatment compared with haloperidol i.m. treatment. Further reductions in these scores also occurred in both groups following transition to oral treatment. Ziprasidone was associated with a lower incidence of movement disorders and a reduced requirement for anticholinergic medication during both i.m. and oral treatment compared with haloperidol. Movement disorder scale scores improved with ziprasidone i.m. and oral treatment, but deteriorated with haloperidol. Other adverse events were rare with both treatments. CONCLUSION: Ziprasidone i.m. was significantly more effective in reducing the symptoms of acute psychosis and was better tolerated than haloperidol i.m., particularly in movement disorders. The transition from ziprasidone i.m. to oral ziprasidone was effective and well tolerated.

Dose dependent occupancy of central dopamine D2 receptors by the novel neuroleptic CP-88,059-01: a study using positron emission tomography and 11C-raclopride.

Positron emission tomography (PET) and 11C-raclopride were used to measure the occupancy of central dopamine D2 receptors by a new neuroleptic, CP-88,059-1. In a double blind dose escalation study, seven healthy male subjects received a predose of between 2 mg and 60 mg CP-88,059-1, 5 h before PET scanning. One additional subject was assigned to placebo predose. Receptor occupancy was defined as the percentage reduction in binding potential compared with that seen in the subject predosed with placebo and with that seen in seven unmedicated normal volunteers previously studied. Binding of 11C-raclopride decreased in a dose dependent manner, and 85% dopamine D2 receptor occupancy was achieved with the highest dose of CP-88,059-1. The findings confirm that brain dopamine D2 receptors are blocked by CP-88,059-1 and suggest that an effective antipsychotic dose will be between 20 mg and 40 mg. The study high-lights the potential of positron emission tomography in the preclinical evaluation of new drugs.

The time course of binding to striatal dopamine D2 receptors by the neuroleptic ziprasidone (CP-88,059-01) determined by positron emission tomography.

Positron emission tomography (PET) and 11C-raclopride were used to assess the time course of binding to central dopamine D2 receptors by the novel neuroleptic ziprasidone. In a third party blind study, six healthy male control subjects received a predose of 40 mg ziprasidone and were scanned at an interval of between 4 and 36 h post-dose. One additional subject was assigned to placebo predose and was scanned at 4 h post-dose. Binding potential (BP) was compared with that seen in the subject predosed with placebo and with that seen in nine unmedicated normal volunteers. Subjects studied up to 12 h post-dose had BPs that were greater than 2 SD less than the mean BP, indicative of extensive D2 receptor binding by ziprasidone. With increasing time between dosing and PET scanning there was a curvilinear increase in BP, so that all studies performed at or after 18 h post-dose gave BPs in the normal range (mean +/- 2 SD). Elevated prolactin levels returned to within the normal range by 18 h post-dose. PET measures of binding potential correlated significantly with serum levels of ziprasidone at the time of scanning and less significantly with absolute prolactin levels at the same time.

Prevalence of urinary catheterization in UK nursing homes.

A postal questionnaire survey was undertaken in registered nursing homes in three different health districts in England: Gloucestershire, North Staffordshire and Leeds. Nursing homes may be registered as general nursing or mental health homes. If homes also have provision for residential beds these are defined as dual registered homes. Overall, 9% (438/4900) of residents, with an equal male:female split, had urinary catheters. There was no significant difference in the overall urinary catheterization rate in the three districts (P=0.9). There was a wide range of urinary catheterization prevalence between homes, with some homes of all three categories having no catheterized residents and several with a prevalence of over 40%. The wide range of prevalence may be due to differences in residents' underlying medical conditions or to differences in attitudes towards urinary catheterization by nursing home staff. Almost all homes (114/124, 92%) stated they had an infection control policy, but 31% (38/124) did not have a written policy on urinary catheter care. In view of the potential for morbidity, infection control policies should include a section on the care of urinary catheters and this should form part of the continuing training of nursing home staff.

Immunization of chickens with VP2 protein of infectious bursal disease virus expressed in Arabidopsis thaliana.

Transgenic plants represent a safe, effective, and inexpensive way to produce vaccines. The immunogenicity of VP2 protein of an infectious bursal disease (IBD) virus variant E isolate expressed in transgenic Arabidopsis thaliana was compared with a commercial vaccine in specific-pathogen-free broiler chickens. The VP2 coding sequence was isolated and integrated into A. thaliana genome by Agrobacterium tumefaciens-mediated transformation. Soluble VP2 expressed in transgenic plants was used to immunize chickens. Chickens receiving oral immunization with plant-derived VP2 at 1 and 3 wk of age had an antibody response using enzyme-linked immunosorbent assay and 80% protection against challenge infection at 4 wk. Chickens primed with a commercial vaccine at 1 wk followed by an oral booster with VP2 expressed in plants at 3 wk of age showed 90% protection. Chickens immunized with a commercial vaccine at 1 and 3 wk showed 78% protection. Results supported the efficacy of plant-produced VP2 as a vaccine against IBD.

Structure and functional relationships in human pur H.

1. The human pur H (ATIC) gene encoding a bifunctional protein, hPurH, which carries the penultimate and final enzymatic activities of the purine nucleotide synthesis pathway, AICARFT & IMPCH, has been cloned and sequenced. The gene product, hPurH has been overexpressed in E. coli, purified to homogeneity and crystallized. 2. The human pur H gene lies on chromosome 2, between band q34 and q35. There is at least one intron of 278 bp near the 5' end. 3. Truncation mutant studies demonstrate two non-overlapping functional domains in the protein arranged as indicated in Figure 5. The existence of a linker or interaction region between the catalytic domains remains to be established. 4. Cleland-type kinetic inhibition experiments indicate that the AICARFT reaction is of the ordered, sequential type with the reduced folate cofactor binding first. 5. The reaction has a broad pH optimum in the alkaline range, with a maximum at about pH 8.2. 6. Preliminary transient phase kinetic studies show the presence of a "burst" indicating that a late step in the reaction sequence is rate limiting. 7. A PurH crystal structure is that of a dimer, with a putative single binding site for the reduced folate cofactor formed using elements from each of the monomer subunits. Probable binding sites for AICAR and FAICAR can be identified on each monomer. 8. Equilibrium sedimentation studies show hPurH apoprotein to be a monomer:dimer equilibrium mixture with a kD of 0.55 uM. 9. The crystal structure has permitted identification of a number of candidate amino acid residues likely to be involved in catalysis and/or substrate binding. Among these, we have thus far completed studies on two, Lysine 265 and Histidine 266. These appear to be critically involved in the AICARFT reaction, although whether their role(s) are in catalysis or binding remains to be determined.

Quantification of rats' behavior during reinforcement periods.

What is treated as a single unit of reinforcement often involves what could be called a reinforcement period during which two or more acts of ingestion may occur, and each of these may have associated with it a series of responses, some reflexive, some learned, that lead up to ingestion. Food-tray presentation to a pigeon is an example of such a "reinforcement period." In order to quantify this behavior, a continuous-reinforcement schedule was used as the reinforcement period and was chained to a fixed-ratio schedule. Both fixed-ratio size and reinforcement-period duration were manipulated. Rats were used as subjects, food as reinforcement, and a lever press as the operant. Major findings included (a) a rapid decline in response rates during the first 15 to 20 seconds of the reinforcement periods, and (b) a strong positive relationship between these response rates and the size of the fixed ratio. Also revealed was a short scallop not normally found in fixed-ratio response patterns, whose length was a function of fixed-ratio size and reinforcement-period duration. It is suggested that rapidly fluctuating excitatory processes can account for many of these findings and that such processes are functionally significant in terms of behavioral compensation.

A double-blind placebo-controlled multicentre study of sertraline in the acute and continuation treatment of major depression.

In a double-blind multicentre study of outpatients with DSM-III-R major depressive disorder, 129 sertraline and 129 placebo patients were evaluated over a 6-week period. Sertraline exhibited a significantly greater (P < 0.001) antidepressant effect compared to placebo as measured by the HAM-D, MADRS, CGI-S and CGI-I. In the subset of patients with severe depression (baseline HAM-D >/= 25), sertraline was also significantly more effective than placebo (P < 0.05). Side effects were more commonly reported in sertraline (59%) compared to placebo (38%) patients; the most common being nausea, headache and insomnia. A subset of 107 patients (66 sertraline; 41 placebo) who were defined as responders (CGI-I of 1 or 2) after 6 weeks treatment were entered into a 20-week continuation phase. In this responder subset, there was continuing improvement in both groups of patients, but with no significant differences in mean HAM-D or MADRS between the groups. However, a higher number of sertraline patients were associated with a persistent pattern of improvement relative to placebo (P < 0.05). The incidence of side effects was similar in sertraline (52%) and placebo (49%) treated patients in the continuation period.

The Effect of Adhesive Strapping on Medial Longitudinal Arch Support before and after Exercise.

The purpose of this study was to compare the ability of two methods of adhesive strapping to provide support to the medial longitudinal arch (MLA) before and after a standardized exercise of 10 minutes of jogging. Ten females, 19 to 35 years of age, were subjects. To determine the position of the MLA, the height of the navicular tuberosity from the floor was measured bilaterally while each subject was standing. Measurements were taken for the following three conditions: barefoot (BARE), before exercise with arches taped (PREEX), and after exercise with arches taped (POSTEX). Methods for taping the MLA were: 1) LowDye and 2) double X. Results of a two-way, within-subjects ANOVA were significant for conditions (F = 45.3, p < 0.0001) and tape methods x conditions interaction (F = 3.6, p < 0.05) but not for tape methods. The Tukey test resulted in a significant difference (p < 0.05) between BARE and PREEX and PREEX and POSTEX but not between BARE and POSTEX. Results indicate that support of the MLA by adhesive strapping was significantly diminished after exercise. J Orthop Sports Phys Ther 1991;14(1):18-23.

Liver resections in Auckland 1998-2001: mortality, morbidity and blood product use.

AIMS: There has been a marked increase in the number of liver resections undertaken at Auckland Hospital since 1998. Low central venous pressure anaesthesia was routinely used for liver resection during this period. The aim of this study was to review this experience, with particular emphasis on the peri-operative outcomes of morbidity, mortality and blood product use. METHODS: All patients undergoing liver resection from January 1998 to May 2001 were included in the review. Standardised data were collated retrospectively from hospital records and transferred to an electronic database for analysis. RESULTS: Of 123 patients undergoing liver resection, 113 were elctive and ten were urgent operations. 65% had major resections and 10% had synchronous extrahepatic surgery. There were three post-operative deaths (mortality 2.4%) due to liver failure and sepsis. One or more complications occurred in 68 patients (morbidity 55%). 72% did not receive a blood transfusion during their hospital stay. Only two of 113 elective patients required a massive blood transfusion (ten or more units). CONCLUSIONS: Mortality in the study period was low but morbidity remains significant. Blood product use was low in elective patients. These results compare well with those of specialised hepatobiliary units internationally.

Accuracy and reliability of the i-STAT point-of-care device for the determination of haemoglobin concentration before and after major blood loss.

We investigated the accuracy of i-STAT(®) (Abbott Point of Care Inc., Princeton, NJ, USA) haemoglobin (Hb) measurement in surgical patients with an estimated blood loss of ≥25% of total blood volume. Blood tests for i-STAT(®) Hb, laboratory Hb (Sysmex XE-2100(™), Sysmex Corporation, Kobe, Japan) and total plasma proteins were obtained at the start of surgery (T=0) and when an estimated 25% total blood volume loss had occurred (T=1). Thirty-one patients were recruited. The coefficient of variation of the paired i-STAT(®) Hb estimates was 2.8% and 2.9% at T=0 and T=1, respectively. The mean difference between i-STAT(®) and laboratory Hb was -7.6 g/l (standard deviation 6.5) at T=0 and -5.1 g/l (standard deviation 12) at T=1. The mean total plasma protein difference (total plasma protein T=0 minus T=1) was 13.6 g/l (95% confidence interval 10.2 to 17.0). There was poor correlation between total plasma protein and bias in i-STAT(®) measurements. The i-STAT(®) Hb had an acceptable coefficient of variation, but the Hb levels were lower than those estimated by the laboratory. The standard deviation of i-STAT(®) Hb was greater after ≥25% estimated total blood volume loss. Clinicians should not use the i-STAT(®) Hb in isolation for clinical decision-making when considering blood transfusion in a situation of 25% or greater blood loss.