Immunogenicity and safety of a two-dose live attenuated varicella vaccine given to adults following autologous hematopoietic stem cell transplantation.

BACKGROUND: Immunogenicity and safety of varicella vaccine (Varilrix(™) [Oka-RIT]; GlaxoSmithKline Vaccines) in adults who had undergone autologous hematopoietic stem cell transplantation (HSCT) were assessed (September 2003 to September 2007; NCT00792623). METHODS: Two Oka-RIT doses were given at 4.5 and 6.5 months post transplantation. Humoral immune responses were assessed using an immunofluorescence assay (anti-varicella zoster virus [VZV] antibody; cutoff 1:4) after each vaccine dose. Solicited local (8 day) and general (43 day), unsolicited (until day 43) adverse events (AEs) after each vaccine dose and serious adverse events (SAEs) (until 17.5 months post dose 2) were recorded. RESULTS: Of 45 patients, 19 were included in the according to protocol cohort for immunogenicity; 15 patients had pre- and post-vaccination serum samples positive for anti-VZV antibodies. Vaccine responses (anti-VZV antibody titer ≥1:4 in seronegative patients, and ≥4-fold increase in anti-VZV antibody titer in seropositive patients) were elicited by only 2 patients 2 months post dose 1, and by a single patient 1.5 months post dose 2. Although no major safety signals were detected, any and Grade 3 solicited AEs that were causally related to vaccination were reported by 44.8% and 10.3% patients, respectively. During the 43-day follow-up period, 3 patients developed varicella-like rash (1 vaccine-type VZV). Beyond 43 days, herpes zoster was reported in 2 patients and wild-type varicella infection in 2 patients (1 was breakthrough infection). Four non-fatal SAEs were reported by patients and considered causally unrelated to vaccination. CONCLUSION: Oka-RIT was poorly immunogenic but safe when given to adults up to 6 months post autologous HSCT, and alternative strategies are required to prevent VZV-associated complications in these populations.

Evaluating the potential utility of three-dimensional printed models in preoperative planning and patient consent in gastrointestinal cancer surgery.

INTRODUCTION: The Future of Surgery report from the Royal College of Surgeons of England acknowledges the important role that three-dimensional imaging will play in support of personalised surgical interventions. One component of this is preoperative planning. We investigated surgeons' and patients' perceptions of this evolving technology. MATERIALS AND METHODS: Ethical approval was obtained. From a normal computed tomography scan, three-dimensional models of the stomach, pancreas and rectum were rendered and printed on an Ultimaker™ three-dimensional printer. Semi-structured interviews were performed with surgeons and patients to explore perceived model effectiveness and utility. Likert scales were used to grade responses (1 = strongly disagree; 10 = strongly agree) and qualitative responses recorded. RESULTS: A total of 26 surgeons (9 rectal, 9 oesophagogastric, 8 pancreatic) and 30 patients (median age 62 years, interquartile range, IQR, 68-72 years; 57% male) were recruited. Median surgeon scores were effectiveness for preoperative planning, 6 (IQR 3-7), authenticity, 5 (IQR 3-6), likability, 6 (IQR 4-7), promoting learning, 7 (IQR 5-8), utility, 6 (IQR 5-7) and helping patients, 7 (IQR 5-8). Median patient scores were usefulness to the surgeon, 8 (IQR 7-9), authenticity, 8 (IQR 6-8), likability, 8 (IQR 7-8), helping understanding of condition, 8 (IQR 8-9), helping understanding of surgery, 8 (IQR 7-9) and feeling uncomfortable, 1 (IQR 1-4). Median overall decisional conflict score (0 = no; 100 = high) was 22 (IQR 19-28) and decision effectiveness was 25 (IQR 19-30). DISCUSSION: Overall, patients and surgeons considered that three-dimensional printed models were effective and had potential utility in education and, to a lesser extent, preoperative planning. Patient decisional conflict and effectiveness scores were weighted towards certainty in decision making but had room for improvement, which three-dimensional models may help to facilitate.

Long-term outcomes in patients with schizophrenia treated with risperidone long-acting injection or oral antipsychotics in Spain: results from the electronic Schizophrenia Treatment Adherence Registry (e-STAR).

BACKGROUND: The electronic Schizophrenia Treatment Adherence Registry (e-STAR) is a prospective, observational study of patients with schizophrenia designed to evaluate long-term treatment outcomes in routine clinical practice. METHODS: Parameters were assessed at baseline and at 3 month intervals for 2 years in patients initiated on risperidone long-acting injection (RLAI) (n=1345) or a new oral antipsychotic (AP) (n=277; 35.7% and 36.5% on risperidone and olanzapine, respectively) in Spain. Hospitalization prior to therapy was assessed by a retrospective chart review. RESULTS: At 24 months, treatment retention (81.8% for RLAI versus 63.4% for oral APs, p<0.0001) and reduction in Clinical Global Impression Severity scores (-1.14 for RLAI versus -0.94 for APs, p=0.0165) were significantly higher with RLAI. Compared to the pre-switch period, RLAI patients had greater reductions in the number (reduction of 0.37 stays per patient versus 0.2, p<0.05) and days (18.74 versus 13.02, p<0.01) of hospitalizations at 24 months than oral AP patients. CONCLUSIONS: This 2 year, prospective, observational study showed that, compared to oral antipsychotics, RLAI was associated with better treatment retention, greater improvement in clinical symptoms and functioning, and greater reduction in hospital stays and days in hospital in patients with schizophrenia. Improved treatment adherence, increased efficacy and reduced hospitalization with RLAI offer the opportunity of substantial therapeutic improvement in schizophrenia.

Awareness of surgical expenditure amongst UK trainees and consultants: A questionnaire study.

INTRODUCTION: Limited knowledge of surgical device and service costs restricts a surgeon's ability to make cost efficient choices and contribute to the efficiency savings required by the NHS to reduce the financial deficit. This study aims to assess how aware surgeons are of surgical equipment and regularly used services. METHODS: A single sided hard copy questionnaire asking for the estimate cost of 24 surgical devices/services was handed out to individuals at two separate UK annual conferences. Items and services which are regularly used and/or clinically significant were selected and, where possible, alternatives to those items were included for comparison. Participants were also asked for their grade and specialty. An estimate was deemed correct if it was within 20% of the actual cost. Planned subgroup analyses for grade and specialty were performed. RESULTS: The 143 participants consisted of 23 (16%) consultants, 39 (27%) registrars, 33 (23%) SHOs and 48 (34%) foundation doctors. Of the 95 participants who were SHO grade or more senior, 67 (71%) work within general surgery. Across all items, only 9.6% of estimates were correct. There was no statistically significant difference between training levels (consultant 11.5%, registrar 10.1%, SHO 8.6%, foundation 8.9%; p = 0.253). Participants were significantly less successful in correctly estimating the cost of high value (>£150 [USD $198; EUR €175]) items (8.5% vs. 11.1%); p = 0.011, and the cost of devices as compared to the cost of services (7.4% vs. 15.0%); p = 0.001. CONCLUSION: Surgeons across all grades and specialties have poor knowledge of device and service costs. It is important that this improves in order to allow surgeons to make a meaningful contribution to NHS efficiency savings by making informed decisions about their use of devices and services.

Paradoxical expression of adenosine deaminase in T cells cultured from a patient with adenosine deaminase deficiency and combine immunodeficiency.

T lymphocytes cultured from a patient (T.D.) with adenosine deaminase (ADA) deficiency expressed ADA activity in the normal range, inconsistent with her severe immunodeficiency, metabolic abnormalities, and with the absence of ADA activity in her B lymphocytes and other nucleated hematopoietic cells. ADA from T.D. T cells had normal Km, heat stability, and sensitivity to ADA inhibitors. Examination of HLA phenotype and polymorphic DNA loci indicated that T.D. was neither chimeric nor a genetic mosaic. Amplified and subcloned ADA cDNA from ADA+ T.D. T cells was shown by allele-specific oligonucleotide hybridization to possess the same mutations (Arg101----Trp, Arg211----His) previously found in the ADA-T.D. B cell line GM 2606 (Akeson, A. L., D. A. Wiginton, M. R. Dusing, J. C. States, and J. J. Hutton. 1988. J. Biol. Chem. 263:16291-16296). Our findings suggest that one of these mutant alleles can be expressed selectively in IL-2-dependent T cells as stable, active enzyme. Cultured T cells from other patients with the Arg211----His mutation did not express significant ADA activity, while some B cell lines from a patient with an Arg101----Gln mutation have been found to express normal ADA activity. We speculate that Arg101 may be at a site that determines degradation of ADA by a protease that is under negative control by IL-2 in T cells, and is variably expressed in B cells. Il-2 might increase ADA expression in T cells of patients who possess mutations of Arg101.

A study on the primary and secondary nucleation of ice by power ultrasound.

Several different investigations have been carried out to study the primary and secondary nucleation of ice by sonocrystallisation. Firstly, the primary nucleation of discrete ice crystals in a supercooled sucrose solution has been observed. For increasing concentrations of sucrose solutions from 0 to 45 wt%, the nucleation temperature consistently occurs at a higher nucleation temperature in the presence of ultrasound. The nucleation temperature also increases as the power output and duty cycle of a commercial ultrasonic horn are increased. Snap shot images of the bubble clouds obtained from the ultrasonic horn also show that the number of bubbles appears to increase as the ultrasonic output is increased. This suggests that the nucleation of ice is related to the power output and number of cavitation bubbles. The effect of a single bubble on the sonocrystallisation of ice is discussed. High-speed movies (1120 fps) have shown that the crystallisation appears to occur in the immediate vicinity of the single bubble. In most cases, many crystals are observed and it is not known whether a single ice crystal is being fragmented by the bubble or whether many crystals are being initiated. The bubble appears to undergo a dancing regime, frequently splitting and rejoining and also emitting some small microbubbles. A study on the secondary nucleation of ice in sucrose solutions has been carried out using a unique ultrasonic cold stage device. Images taken using a microscope system show that the pre-existing ice dendrite crystals can be broken up into smaller fragments by an ultrasonic field. Cavitation bubbles appear to be important during the fragmentation process, possibly melting any ice crystals in their path. Flow patterns around cavitation bubbles have also been observed, and these may be responsible for the fragmentation of ice crystals.

Identification of important mechanical and acoustic parameters for the sensory quality of cocoa butter alternatives.

In this study, the correlation between sensory attributes and the mechanical and acoustic properties of cocoa butter alternatives was elucidated. Needle penetration, cone penetration and compression tests were used to characterise mechanical properties and acoustic properties were evaluated by simultaneous texture and sound analyses. Results were correlated with a descriptive sensory evaluation. A significant correlation was found between hardness (needle penetration) and sensory hardness evaluated upon biting (r=0.91, p<0.05) and between Hencky strain (compression test) and the sensory toughness (r=0.94, p<0.05). In contrast, no significant correlation was found between brittleness (cone penetration) and the sensory brittleness. The use of different mechanical methods shed light on a complex rheological behaviour of fat which demonstrates the importance of not simply relying on results from penetration tests when evaluating fat texture. For instance, a hard fat was perceived very differently depending on the degree of elasticity. A significant correlation was found between sound pressure level (simultaneous sound and texture analyses) and the sensory evaluation of the sound intensity upon breakage (r=0.96 and 0.97, p<0.05). Both hardness and elasticity were found to be of great importance for the intensity of the sound emission i.e. a hard texture with a low degree of flexibility (less elastic) is more likely to provide a rapid energy release upon breakage and thus a high intensity sound emission.

Placental-like alkaline phosphatase in malignant and benign ovarian tumors.

Alkaline phosphatase (ALP) components in extracts of seven malignant and eleven benign ovarian tumors were characterized using the criteria of electrophoretic mobility before and after neuraminidase treatment, heat stability, L-phenylalanine inhibition and reactivity against antiplacental ALP antiserum. Seven of the eighteen tumors had ALP components which most closely resembled the ALP isoenzyme normally found in placenta and were clearly distinguished from all other tissue ALPs. The proportion of tumors with the placental-like ALP in the malignant group (five out of seven) was significantly greater than the proportion in the benign group (two out of eleven). The fraction (78%) of the malignant tumors with the isozyme represents a larger percentage than has previously been found by examination of cancer patients' sera. The electrophoretic mobilities of the placental-like ALPs in the tumors were in no case identical to the mobilities of any of the six common placental ALP phenotypes. The tumor ALPs may thus be determined by rare variant alleles at the ALP locus, or alternatively, the enzyme molecules may have been subject to structural modification. At least two of these tumors contained an electrophoretically slow. heat-stable, leucine-sensitive ALP, which may correspond to what has been termed the D-variant of placental ALP found in some other tumors.

Ultrasonic analysis of edible fats and oils.

Low intensity ultrasound is a powerful analytical technique for investigating the physico-chemical properties of many biological and non-biological materials. In this article its application for the characterization of edible fats and oils is assessed. Ultrasound can be used to determine the dynamic rheology and composition of oils, the oil content and droplet size of emulsions and the solid fat content of partially crystalline emulsions. It is capable of rapid and precise measurements, is non-destructive and non-invasive, can be used on-line or off-line and is relatively inexpensive. Ultrasonic techniques will therefore prove a useful addition to the existing analytical techniques used to characterize fats and oils.

Acoustic emission monitoring from a lab scale high shear granulator--a novel approach.

A new approach to the monitoring of granulation processes using passive acoustics together with precise control over the granulation process has highlighted the importance of particle-particle and particle-bowl collisions in acoustic emission. The results have shown that repeatable acoustic results could be obtained but only when a spray nozzle water addition system was used. Acoustic emissions were recorded from a transducer attached to the bowl and an airborne transducer. It was found that the airborne transducer detected very little from the granulation and only experienced small changes throughout the process. The results from the bowl transducer showed that during granulation the frequency content of the acoustic emission shifted towards the lower frequencies. Results from the discrete element model indicate that when larger particles are used the number of collisions the particles experience reduces. This is a result of the volume conservation methodology used in this study, therefore larger particles results in less particles. These simulation results coupled with previous theoretical work on the frequency content of an impacting sphere explain why the frequency content of the acoustic emissions reduces during granule growth. The acoustic system used was also clearly able to identify when large over-wetted granules were present in the system, highlighting its benefit for detecting undesirable operational conditions. High-speed photography was used to study if visual changes in the granule properties could be linked with the changing acoustic emissions. The high speed photography was only possible towards the latter stages of the granulation process and it was found that larger granules produced a higher magnitude of acoustic emission across a broader frequency range.

Post-processing of polymer foam tissue scaffolds with high power ultrasound: a route to increased pore interconnectivity, pore size and fluid transport.

The aim of this work is to demonstrate that the structural and fluidic properties of polymer foam tissue scaffolds, post-fabrication but prior to the introduction of cells, can be engineered via exposure to high power ultrasound. Our analysis is supported by measurements of fluid uptake during insonification and imaging of the scaffold microstructure via X-ray computed tomography, scanning electron microscopy and acoustic microscopy. The ultrasonic treatment is performed with a frequency of 30 kHz, average intensities up to 80,000 Wm(-2) and exposure times up to 20 h. The treatment is found to increase the mean pore size by over 10%. More striking is the improvement in fluid uptake: for scaffolds with only 40% water uptake via standard immersion techniques, we can routinely achieve full saturation of the scaffold over approximately one hour of exposure. These desirable modifications occur with negligible loss of scaffold integrity and mass, and are optimized when the ultrasound treatment is coupled to a pre-wetting stage with ethanol. Our findings suggest that high power ultrasound is highly targeted towards flow obstructions in the scaffold architecture, thereby providing an efficient means to promote pore interconnectivity and fluid transport in thick foam tissue scaffolds.

Longitudinal acoustic properties of poly(lactic acid) and poly(lactic-co-glycolic acid).

Acoustics offers rich possibilities for characterizing and monitoring the biopolymer structures being employed in the field of biomedical engineering. Here we explore the rudimentary acoustic properties of two common biodegradable polymers: poly(lactic acid) and poly(lactic-co-glycolic acid). A pulse-echo technique is developed to reveal the bulk speed of sound, acoustic impedance and acoustic attenuation of small samples of the polymer across a pertinent temperature range of 0-70 °C. The glass transition appears markedly as both a discontinuity in the first derivative of the speed of sound and a sharp increase in the acoustic attenuation. We further extend our analysis to consider the role of ethanol, whose presence is observed to dramatically modify the acoustic properties and reduce the glass transition temperature of the polymers. Our results highlight the sensitivity of acoustic properties to a range of bulk properties, including visco-elasticity, molecular weight, co-polymer ratio, crystallinity and the presence of plasticizers.

Genetics of serum lipids and lipoproteins. A study of twins at birth and 3-5 years of age.

The genetic influence on serum lipid and lipoprotein values was estimated in 12 monozygotic (MZ) and 8 dizygotic (DZ) twins at birth and 3-5 years of age. The intrapair variances for total cholesterol and high density lipoprotein (HDL) cholesterol were smaller in MZ than DZ twins thus indicating a significant genetic influence.

Heterogeneity of alkaline phosphatases in different HeLa lines.

Alkaline phosphatase (ALP) components in 8 cell lines of HeLa were examined. Line to line heterogeneity in ALP expression was observed using the criteria of electrophoretic mobility before and after neuraminidase treatment, heat stability, L-phenylanine inhibition, and reactivity against antiplacental ALP antiserum. Six lines contained a placentallike ALP isozyme and varying amounts of a liverlike ALP isozyme. One line contained a liverlike ALP isozyme only. One line contained a new ALP form which was clearly distinguished from the placental, liver, bone, and intestinal ALPs. Thus, derepression of the placental ALP structural locus appeared to have occurred in 6 of the 8 lines. However, where expressed, the placentallike ALP varied electrophoretically from line to line, and in only one case was the mobility identical to that of a common placental ALP phenotype. This phenotypic heterogeneity of the ""derepressed'' placentallike ALP contrasts markedly with the phenotypic stability of other enzymes expressed in HeLa cells.

Electrophoresis of human l-glutamate dehydrogenase: tissue distribution and preliminary population survey.

A method for the starch gel electrophoresis of human L-glutamate dehydrogenase (GLUD) is described, as is the tissue distribution of GLUD detected by this method. Extracts of livers from 200 Whites were analyzed without demonstration of an electrophoretic variant. The molecular size was estimated to be 330,000 and the isoelectric point pH 4.83.