Dose-dependant acute or subacute disease caused by Burkholderia pseudomallei strain NCTC 13392 in a BALB/c aerosol model of infection.

AIMS: The goal of this study was to examine, for the first time, the virulence and pathogenicity of aerosolized Burkholderia pseudomallei, strain NCTC 13392, in BALB/c mice in order to develop an animal model for testing novel medical countermeasures (MCMs) for the treatment of human acute and subacute (a disease state between acute and chronic) melioidosis. METHODS AND RESULTS: BALB/c mice were exposed to varying doses of aerosolized bacteria. Acute disease was seen in animals exposed to a very-high dose (≥103  CFU per animal) and death occurred 3-4 days postchallenge (pc). Bacteria were detected in the lungs, liver, kidney and spleen. In contrast, animals exposed to a low dose (<10 CFU per animal) survived to the end of the study (day 30 pc) but developed weight loss, a bacterial tissue burden and increasing clinical signs of infection from day 20 pc onwards, mimicking a subacute form of the disease. Pathological changes in the tissues mirrored these findings. CONCLUSIONS: This proof of concept study has shown that B. pseudomallei strain NCTC 13392 is virulent and pathogenic in BALB/c mice, when delivered by aerosol. By varying the doses of aerosolized bacteria it was possible to mimic characteristics of both human acute and subacute melioidosis, at the same time, within the same study. SIGNIFICANCE AND IMPACT OF THE STUDY: Burkholderia pseudomallei, the aetiological agent of melioidosis, causes a serious and often fatal disease in humans and animals. Novel MCMs are urgently needed for both public health and biodefense purposes. The present model provides a useful tool for the assessment and evaluation of new MCMs (e.g. therapeutics and vaccines) and offers the potential for testing new treatments for both subacute to chronic and acute melioidosis prior to human clinical trials.

The future of UK healthcare: problems and potential solutions to a system in crisis.

The UK's Health System is in crisis, central funding no longer keeping pace with demand. Traditional responses-spending more, seeking efficiency savings or invoking market forces-are not solutions. The health of our nation demands urgent delivery of a radical new model, negotiated openly between public, policymakers and healthcare professionals. Such a model could focus on disease prevention, modifying health behaviour and implementing change in public policy in fields traditionally considered unrelated to health such as transport, food and advertising. The true cost-effectiveness of healthcare interventions must be balanced against the opportunity cost of their implementation, bolstering the central role of NICE in such decisions. Without such action, the prognosis for our healthcare system-and for the health of the individuals it serves-may be poor. Here, we explore such a new prescription for our national health.

Oral contraceptive pill use and the susceptibility to markers of exercise-induced muscle damage.

PURPOSE: Firstly, to establish whether oral contraceptive pill (OCP) users are more susceptible to muscle damage compared to non-users, and secondly, to establish whether differences can be attributed to differences in patella tendon properties. METHODS: Nine female OCP users and 9 female non-users participated in the investigation. Combining dynamometry, electromyography and ultrasonography, patella tendon properties and vastus lateralis architectural properties were measured pre and during the first of 6 sets of 12 maximal voluntary eccentric knee extensions. Serum oestrogen levels were measured on the 7th day of the pill cycle and the 14th day of menstrual cycle in OCP users and non-users, respectively. Maximal voluntary isometric knee extension torque loss, creatine kinase and muscle soreness were measured 48 h pre-damage, post-damage, and 48, 96 and 168 h post-damage. RESULTS: Oestrogen levels were significantly lower in OCP users compared to non-users (209 ± 115 and 433 ± 147 pg/ml, respectively, p = 0.004). Proposed determinants of muscle damage, patella tendon stiffness and maximal eccentric torque did not differ between OCP users and non-users. The change in creatine kinase from pre to peak was significantly higher in OCP users compared to non-users (962 ± 968 and 386 ± 474 Ul, respectively, p = 0.016). There were no other differences in markers of muscle damage. CONCLUSION: Although our findings suggest that, when compared to non-users, the OCP may augment the creatine kinase response following eccentric exercise, it does not increase the susceptibility to any other markers of muscle damage.

Sequence of pathogenic events in cynomolgus macaques infected with aerosolized monkeypox virus.

UNLABELLED: To evaluate new vaccines when human efficacy studies are not possible, the FDA's "Animal Rule" requires well-characterized models of infection. Thus, in the present study, the early pathogenic events of monkeypox infection in nonhuman primates, a surrogate for variola virus infection, were characterized. Cynomolgus macaques were exposed to aerosolized monkeypox virus (10(5) PFU). Clinical observations, viral loads, immune responses, and pathological changes were examined on days 2, 4, 6, 8, 10, and 12 postchallenge. Viral DNA (vDNA) was detected in the lungs on day 2 postchallenge, and viral antigen was detected, by immunostaining, in the epithelium of bronchi, bronchioles, and alveolar walls. Lesions comprised rare foci of dysplastic and sloughed cells in respiratory bronchioles. By day 4, vDNA was detected in the throat, tonsil, and spleen, and monkeypox antigen was detected in the lung, hilar and submandibular lymph nodes, spleen, and colon. Lung lesions comprised focal epithelial necrosis and inflammation. Body temperature peaked on day 6, pox lesions appeared on the skin, and lesions, with positive immunostaining, were present in the lung, tonsil, spleen, lymph nodes, and colon. By day 8, vDNA was present in 9/13 tissues. Blood concentrations of interleukin 1ra (IL-1ra), IL-6, and gamma interferon (IFN-γ) increased markedly. By day 10, circulating IgG antibody concentrations increased, and on day 12, animals showed early signs of recovery. These results define early events occurring in an inhalational macaque monkeypox infection model, supporting its use as a surrogate model for human smallpox. IMPORTANCE: Bioterrorism poses a major threat to public health, as the deliberate release of infectious agents, such smallpox or a related virus, monkeypox, would have catastrophic consequences. The development and testing of new medical countermeasures, e.g., vaccines, are thus priorities; however, tests for efficacy in humans cannot be performed because it would be unethical and field trials are not feasible. To overcome this, the FDA may grant marketing approval of a new product based upon the "Animal Rule," in which interventions are tested for efficacy in well-characterized animal models. Monkeypox virus infection of nonhuman primates (NHPs) presents a potential surrogate disease model for smallpox. Previously, the later stages of monkeypox infection were defined, but the early course of infection remains unstudied. Here, the early pathogenic events of inhalational monkeypox infection in NHPs were characterized, and the results support the use of this surrogate model for testing human smallpox interventions.

Bone health measured using quantitative ultrasonography in adult males with muscular dystrophy.

OBJECTIVES: To compare muscle and bone health markers in adult males (aged 20-59 yrs) with and without muscular dystrophy (MD). METHODS: Participants included 11 Fascioscapulohumeral (FSH), 11 Becker's (Be), 9 limb girdle (LG), 11 Duchenne (DMD), and 14 non-dystrophic controls (CTRL). Physical activity was assessed using Bone (BPAQ) and disability specific (PASIPD) questionnaires. Bone QUS provided T- and Z scores from the Distal Radius (DR) and Mid-shaft tibia (MST). Tibialis anterior cross sectional area (TAACSA) was measured using B-mode ultrasound. Grip strength was measured in all but DMD. RESULTS: Physical activity was lower in DMD, FSH and BeMD than CTRL (P<0.05), and lower in DMD than other MDs (P<0.01). T and Z scores were lower in DMD and Be than CTRL (DR, P<0.05); and lower in DMD than CTRL, LG, and FSH (MST, P<0.01). TAACSA and grip strength was 35-59% and 50-58% smaller in MD than CTRL, respectively (P<0.01). Within MD, BPAQ correlated with bone QUS measures (r=0.42-0.38, P<0.01). PASIPD correlated with grip strength (r=0.65, P<0.01) and TAACSA (r=0.46, P<0.01). CONCLUSION: Muscle size, strength, and bone health was lower in adult males with MD compared to adult males without MD, the extent of this is partially determined by physical activity.

Cardiovascular MRI predicts 5-year adverse clinical outcome in heart transplant recipients.

Imaging recommendations for the follow-up of heart transplant recipients (HTRs) lack evidence justifying their prognostic value. Cardiovascular magnetic resonance imaging (CMRI) can characterize heart structure and function and has prognostic value in many myocardial diseases. We hypothesized that CMRI evaluation of cardiac allografts would predict adverse events. We performed CMRI on 60 HTRs evaluating biventricular size, function and myocardial scar. We performed survival analysis to identify independent predictors of cardiovascular (CV) death or hospitalization. Participants had a mean age of 51 ± 14 years, mean graft age of 3.5 years (±4) and 75% are male. Median follow-up time was 4.9 years with 22 CV hospitalizations and 7 CV deaths. A multivariable survival analysis of imaging and clinical variables identified myocardial scar (hazard ratio [HR] of 10.7, p = 0.005), right ventricular end- diastolic volume index (RVEDVI; 1.1/mL/m(2) , p = 0.001), graft age (HR = 1.2/year, p = 0.004) and previous allograft rejection (HR = 4.4, p = 0.006) as predictive of time to CV death or hospitalization. CMRI-derived myocardial scar and RVEDVI are independently associated with CV outcomes in HTRs.

Climate-driven range shifts explain the distribution of extant gene pools and predict future loss of unique lineages in a marine brown alga.

The climate-driven dynamics of species ranges is a critical research question in evolutionary ecology. We ask whether present intraspecific diversity is determined by the imprint of past climate. This is an ongoing debate requiring interdisciplinary examination of population genetic pools and persistence patterns across global ranges. Previously, contrasting inferences and predictions have resulted from distinct genomic coverage and/or geographical information. We aim to describe and explain the causes of geographical contrasts in genetic diversity and their consequences for the future baseline of the global genetic pool, by comparing present geographical distribution of genetic diversity and differentiation with predictive species distribution modelling (SDM) during past extremes, present time and future climate scenarios for a brown alga, Fucus vesiculosus. SDM showed that both atmospheric and oceanic variables shape the global distribution of intertidal species, revealing regions of persistence, extinction and expansion during glacial and postglacial periods. These explained the distribution and structure of present genetic diversity, consisting of differentiated genetic pools with maximal diversity in areas of long-term persistence. Most of the present species range comprises postglacial expansion zones and, in contrast to highly dispersive marine organisms, expansions involved only local fronts, leaving distinct genetic pools at rear edges. Besides unravelling a complex phylogeographical history and showing congruence between genetic diversity and persistent distribution zones, supporting the hypothesis of niche conservatism, range shifts and loss of unique genetic diversity at the rear edge were predicted for future climate scenarios, impoverishing the global gene pool.

Mobility histories of 7th-9th century AD people buried at early medieval Bamburgh, Northumberland, England.

Early Medieval England is described historically as a time when people migrated from the Continent to English shores. This study tests the hypothesis that those buried in the Bowl Hole cemetery, Bamburgh, Northumberland were nonlocally born, because of its royal status. Ninety-one male and female adult, and nonadult, skeletons were studied. Isotope ratios of strontium ((87) Sr/(86) Sr) and oxygen (δ(18) O) were generated for 78 individuals (28 females, 27 males, five "adults," 18 nonadults). The mean Sr value for human enamel was 0.71044, standard deviation (sd) 0.001, and the mean O (δw) value is -5.9‰, sd 1.6‰. Additionally, animal tooth enamel (mean Sr value 0.710587, sd 0.001; mean O value -6.5‰, sd 1.5‰), local soil (mean Sr value 0.709184, sd 0.0006), snail shells (mean Sr value 0.708888, sd 0.0001), and soil samples from a 5 km transect heading inland (mean Sr value 0.709121, sd 0.0003), were analyzed for an indication of the isotopic composition of bioavailable Sr in the modern environment and to assess the impact of sea-spray; water samples from a well, local rivers, and standing water were analyzed for local δ(18) O values (mean O value -6.4‰, relative to VSMOW, sd 2.8‰). Over 50% of those buried at Bamburgh were nonlocal. All ages and both sexes produced "nonlocal" signatures; some suggested childhood origins in Scandinavia, the southern Mediterranean or North Africa. Stature and other indicators of health status indicated differences in quality of life between local and migrant groups. These differences did not extend to burial practices.

Quantification of risk of emergency caesarean during labour after one previous caesarean section.

In its 2007 guideline, the Royal College of Obstetricians and Gynaecologists (RCOG) recommends vaginal birth after caesarean (VBAC) as safer than repeat elective caesarean sections. However, this document does not give details of risk of emergency caesarean section for women accepting VBAC. An emergency caesarean is associated with increased maternal and neonatal morbidity, and women do consider the eventuality of emergency delivery when deciding mode of delivery. We sought to quantify this risk by designing a retrospective cohort study in a consultant-led unit. While higher than average rates of successful planned VBAC were achieved, the odds of emergency caesarean delivery were increased in women undergoing VBAC (OR 3.0, 95% CI 1.2-7.6, p = 0.03). Odds of requiring a Category 1 emergency caesarean were markedly raised. Our data adds to the VBAC literature by quantifying the risk of Category 1 or 2 emergency caesarean section for women entering labour who have delivered by caesarean section once previously, giving the odds of emergency caesarean section on entering labour compared with women without a scar. This gives further information to those counselling women about birth after caesarean section.

Exploring the Challenges of Frailty in Medical Education.

Frailty is common, and medical students and doctors across all specialties will look after patients with frailty. The General Medical Council requires UK medical schools to teach and assess on frailty, and national geriatric societies across the globe include frailty in their recommended undergraduate curricula. However, frailty in medical education is challenging; there is uncertainty around what frailty is in medical education, including how and when to teach it; controversies in mapping teaching and assessments to recommended curricula; patients with frailty can be challenging to include in teaching and assessments due to functional, sensory, and/or cognitive impairments; an individual with frailty is likely to present atypically, with less predictable recovery, introducing complexities into clinical reasoning that can be challenging for students; the term frailty is often negatively perceived, used colloquially and avoided in educational interactions. This commentary discusses these challenges around frailty in undergraduate medical education and serves to provoke discussion about why frailty is so challenging to teach and learn about, including recommendations for how frailty education could be improved.

Loss of a globally unique kelp forest from Oman.

Kelp forests are declining in many regions globally with climatic perturbations causing shifts to alternate communities and significant ecological and economic loss. Range edge populations are often at most risk and are often only sustained through localised areas of upwelling or on deeper reefs. Here we document the loss of kelp forests (Ecklonia radiata) from the Sultanate of Oman, the only confirmed northern hemisphere population of this species. Contemporary surveys failed to find any kelp in its only known historical northern hemisphere location, Sadah on the Dhofar coast. Genetic analyses of historical herbarium specimens from Oman confirmed the species to be E. radiata and revealed the lost population contained a common CO1 haplotype found across South Africa, Australia and New Zealand suggesting it once established through rapid colonisation throughout its range. However, the Omani population also contained a haplotype that is found nowhere else in the extant southern hemisphere distribution of E. radiata. The loss of the Oman population could be due to significant increases in the Arabian Sea temperature over the past 40 years punctuated by suppression of coastal upwelling. Climate-mediated warming is threatening the persistence of temperate species and precipitating loss of unique genetic diversity at lower latitudes.

Exploring the response of a key Mediterranean gorgonian to heat stress across biological and spatial scales.

Understanding the factors and processes that shape intra-specific sensitivity to heat stress is fundamental to better predicting the vulnerability of benthic species to climate change. Here, we investigate the response of a habitat-forming Mediterranean octocoral, the red gorgonian Paramuricea clavata (Risso, 1826) to thermal stress at multiple biological and geographical scales. Samples from eleven P. clavata populations inhabiting four localities separated by hundreds to more than 1500 km of coast and with contrasting thermal histories were exposed to a critical temperature threshold (25 °C) in a common garden experiment in aquaria. Ten of the 11 populations lacked thermotolerance to the experimental conditions provided (25 days at 25 °C), with 100% or almost 100% colony mortality by the end of the experiment. Furthermore, we found no significant association between local average thermal regimes nor recent thermal history (i.e., local water temperatures in the 3 months prior to the experiment) and population thermotolerance. Overall, our results suggest that local adaptation and/or acclimation to warmer conditions have a limited role in the response of P. clavata to thermal stress. The study also confirms the sensitivity of this species to warm temperatures across its distributional range and questions its adaptive capacity under ocean warming conditions. However, important inter-individual variation in thermotolerance was found within populations, particularly those exposed to the most severe prior marine heatwaves. These observations suggest that P. clavata could harbor adaptive potential to future warming acting on standing genetic variation (i.e., divergent selection) and/or environmentally-induced phenotypic variation (i.e., intra- and/or intergenerational plasticity).

Deletion of protein kinase Cδ in mice modulates stability of inflammatory genes and protects against cytokine-stimulated beta cell death in vitro and in vivo.

AIMS/HYPOTHESIS: Proinflammatory cytokines contribute to beta cell destruction in type 1 diabetes, but the mechanisms are incompletely understood. The aim of the current study was to address the role of the protein kinase C (PKC) isoform PKCδ, a diverse regulator of cell death, in cytokine-stimulated apoptosis in primary beta cells. METHODS: Islets isolated from wild-type or Prkcd(-/-) mice were treated with IL-1ß, TNF-α and IFNγ and assayed for apoptosis, nitric oxide (NO) generation and insulin secretion. Activation of signalling pathways, apoptosis and endoplasmic reticulum (ER) stress were determined by immunoblotting. Stabilisation of mRNA transcripts was measured by RT-PCR following transcriptional arrest. Mice were injected with multiple low doses of streptozotocin (MLD-STZ) and fasting blood glucose monitored. RESULTS: Deletion of Prkcd inhibited apoptosis and NO generation in islets stimulated ex vivo with cytokines. It also delayed the onset of hyperglycaemia in MLD-STZ-treated mice. Activation of ERK, p38, JNK, AKT1, the ER stress markers DDIT3 and phospho-EIF2α and the intrinsic apoptotic markers BCL2 and MCL1 was not different between genotypes. However, deletion of Prkcd destabilised mRNA transcripts for Nos2, and for multiple components of the toll-like receptor 2 (TLR2) signalling complex, which resulted in disrupted TLR2 signalling. CONCLUSIONS/INTERPRETATION: Loss of PKCδ partially protects against hyperglycaemia in the MLD-STZ model in vivo, and against cytokine-mediated apoptosis in vitro. This is accompanied by reduced NO generation and destabilisation of Nos2 and components of the TLR2 signalling pathway. The results highlight a mechanism for regulating proinflammatory gene expression in beta cells independently of transcription.

Evolution and diversification within the intertidal brown macroalgae Fucus spiralis/F. vesiculosus species complex in the North Atlantic.

We examined 733 individuals of Fucusspiralis from 21 locations and 1093 Fucusvesiculosus individuals from 37 locations throughout their northern hemisphere ranges using nuclear and mitochondrial markers. Three genetic entities of F. spiralis were recovered. In northern and sympatric populations, the presence of "F. spiralis Low" in the mid-intertidal and "F. spiralis High" in the high-intertidal was confirmed and both co-occurred with the sister species F. vesiculosus. The third and newly-discovered entity, "F. spiralis South", was present mainly in the southern range, where it did not co-occur with F. vesiculosus. The South entity diverged early in allopatry, then hybridized with F. vesiculosus in sympatry to produce F. spiralis Low. Ongoing parallel evolution of F. spiralis Low and F. spiralis High is most likely due to habitat preference/local selection and maintained by preferentially selfing reproductive strategies. Contemporary populations of F. spiralis throughout the North Atlantic stem from a glacial refugium around Brittany involving F. spiralis High; F. spiralis South was probably unaffected by glacial episodes. Exponential population expansion for F. vesiculosus began during the Cromer and/Holstein interglacial period (300,000-200,000 yrs BP). Following the last glacial maximum (30,000-22,000 yrs BP), a single mtDNA haplotype from a glacial refugium in SW Ireland colonized Scandinavia, the Central Atlantic islands, and the W Atlantic.

Relation between Epstein-Barr viral and cell membrane immunofluorescence in Burkitt tumor cells. IV. Differentiation between antibodies responsible for membrane and viral immunofluorescence.

Previous reports (1, 2) have established that the expression of certain distinctive membrane antigen(s) on the surface of Burkitt's lymphoma (BL) and infectious mononucleosis (IM) cells is dependent on the presence of Epstein-Barr virus (EBV) in the cell line. The investigations reported here provide evidence that antibodies directed against EBV antigens, as revealed by the immunofluorescence test on acetone-fixed smears (8), and the membrane reactive antibodies, although often present in the same serum, are nevertheless distinctly different. Absorption of Mutua serum, the standard reference serum for demonstrating membrane antigen(s) on BL and IM cells, with BL cells completely removed anti-membrane activity without significantly affecting the anti-EBV antibody titer. Furthermore, sera were found which contained one type of antibody but not the other. Sera with high anti-membrane but low anti-EBV activity were found among relatives of BL patients. These sera reacted with the membranes of EBV-carrying BL and IM cells in essentially the same way, i.e., against the same spectrum of target cells, as the EBV-positive Mutua serum. They were unable to block the membrane reactivity of FITC-conjugated Mutua serum, however. In some cases they showed weak but incomplete blocking. One such EBV-negative, membrane-positive BL relative serum (Robert) was conjugated with FITC and used for direct staining of BL and IM cells. Again, this conjugate reacted against the same target cell spectrum as a Mutua conjugate, but its reactivity was completely blocked by a number of Burkitt patients' sera, although unconjugated Robert serum did not block the Mutua-conjugate. A number of other membrane-positive BL relative sera also failed to block Mutua, but completely blocked the Robert conjugate. A number of Swedish and African control sera and an isoantiserum gave no blocking against Robert conjugate. It therefore appears that the Mutua conjugate contains at least two antibody specificities against the EBV-determined membrane antigens. One, but not the other, is shared with the antibody specificity present in Robert's serum and a number of other sera from relatives of BL patients.

Relation between Epstein-- Barr viral and cell membrane immunofluorescence in Burkitt tumor cells. II. Comparison of cells and sera from patients with Burkitt's lymphoma and infectious mononucleosis.

Blastoid cell cultures derived from leukocytes of patients in the acute stage of infectious mononucleosis (IM) and harboring Epstein-Barr (EB) virus in at least 1% of the cells were found to possess antigens in their membranes which presently are indistinguishable from those detected in Burkitt's lymphoma (BL) cells by the techniques employed. It was noted that, in the course of IM, antibodies are formed which react in indirect immunofluorescence tests with membrane antigens of live cells from Burkitt tumor lines as well as from IM leukocyte cultures, including an autochthonous line in the case of one patient. Sets of sera from IM patients were tested which included a serum collected weeks to years before onset of illness. In the majority of these the pre-IM serum failed to react in membrane immunofluorescence (MIF) tests with any of several Burkitt tumor cell lines employed, but in some cases the presera reacted with cells of some but not others of the lines. Possible explanations for these discrepant results have been discussed. The antibodies involved in the MIF test are evidently distinct from those responsible for the EBV and heterophile reactions. Maximal MIF activity is attained long after the other two antibodies have reached maximal titers and antibodies to EBV and membrane antigens seem to persist for years whereas the heterophile reaction turns negative within a few months.

Relation between Epstein-Barr viral and cell membrane immunofluorescence in Burkitt tumor cells. 3. Comparison of blocking of direct membrane immunofluorescence and anti-EBV reactivities of different sera.

Sera from patients with Burkitt's lymphoma (BL), infectious mononucleosis (IM), carcinoma of the postnasal space (Ca PNS), and various controls were investigated for antibodies against the Epstein-Barr virus (EBV) by immunofluorescence on acetone-fixed smears (5) and for antibodies against the distinctive antigenic sites expressed on the surface of viable lymphoblastoid cells within EBV-carrying culture lines (1). The latter were studied by the blocking of direct membrane staining with FITC-conjugated Mutua serum. This serum has been derived from a Burkitt's lymphoma patient in long-term regression after chemotherapy and is free from detectable isoantibodies. It has been used previously as a standard of reference to demonstrate the presence of the membrane antigen(s) on all lines derived from BL biopsies and leukocytes from IM patients. It was found that 102 of 279 (37%) of the sera tested had high anti-EBV titers (>==80) and high membrane-blocking (Bl > 0.5) activity, 124 of 279 (44%) of the sera were low in both tests, 22 of 279 (8%) had low EBV titers (<==80), in spite of a high blocking index, and 31 of 279 (11%) of the sera were low in blocking activity (<0.5), in spite of a high EBV titer. The two tests thus gave concordant results with 81% and discordant with 19% of the sera. The majority of sera from BL patients were high in both tests. IM sera also showed a relationship between the two antibody activities but, in general, both activities were lower than in BL cases. Ca PNS sera seemed to fall into two main groups: (a) high anti-EBV, high blocking or (b) low anti-EBV, low blocking. Control sera, including four isoantisera, showed predominantly low reactivities in both tests.

Relation between Epstein-Barr viral and cell membrane immunofluorescence of Burkitt tumor cells. I. Dependence of cell membrane immunofluorescence on presence of EB virus.

A comparison was made of the immunofluorescence tests for detection of cell membrane and Epstein-Barr virus antigens in cells from Burkitt tumor biopsies or continuous cultures derived therefrom. On the whole, cell membrane fluorescence in established lines appeared to depend not only upon the presence of EBV but to a considerable degree also upon the extent of the persistent viral infection. There was no constant relationship, however, between the results of the two tests and exceptions to the rule were noted. These observations indicate that different antigens are involved in the two tests. Biopsy cells in general and young cultures may reveal strong MIF activity but few, if any, EBV-positive cells. The reverse, the presence of relatively large numbers of EBV antigen-containing cells in the absence of significant MIF reactions, was also noted on occasion in a few established cultures. The possible interpretations of these findings have been discussed.

The effect of ultrasound on the setting reaction of zinc polycarboxylate cements.

The set of glass ionomer cement (GIC) is accelerated by application of ultrasound. Although GIC has somewhat displaced zinc polycarboxylate cement (ZPC) in dental applications the latter is still extensively used. Like GIC, it provides direct adhesion to tooth and can provide F release, but is more radiopaque and biocompatible than GIC. The aim of this study is to examine the effect of ultrasound on the setting of ZPC using Fourier transform infra red spectroscopy and any interaction with SnF(2) addition. ZPC with and without SnF(2) addition (+/-S) at luting (L) 2:1 P/L ratio and restorative (R) 4:1 P/L ratio consistencies. Ultrasound is applied to the cement using Piezon-Master 400, EMS, Switzerland at 60 s from start of mixing for 15 s. The ratios of absorbance peak height at 1,400 cm(-1) -COO(-) to that at 1,630 cm(-1) -COOH were measured and compared those obtained for the cement not treated with US. These values were taken at the elapsed time at which no further change in spectrum [ratio] was observed at room temperature [10-20 min]. The US results are taken at 2 or 3 min. No US: R/+S (1.09), R/-S (1.2), L/+S (1.07), L/-S (1.04); US: R/+S (1.50), R/-S (1.64), L/+S (1.38), L/-S (1.05). The results show all four ZPC formulations are very sensitive to ultrasound whether with or without SnF(2). Reducing US to 10 s produces lower initial ratios but these increase up to 10 min when very high ratios (>2) are obtained. Previous studies with restorative GICs found that 40-55 s US was needed to produce the effect found with 15 s on ZPCs. ZPC powder is more basic than GIC glass; this may account for ZPC's greater sensitivity to US. Ultrasound may provide a useful adjunct to the clinical use of ZPC both as luting agent and temporary restorative.

Kinetics of fluoride ion release from dental restorative glass ionomer cements: the influence of ultrasound, radiant heat and glass composition.

To compare the effect of ultrasonic setting with self curing on fluoride release from conventional and experimental dental glass ionomer cements. To compare hand mixed and capsule mixing and the effect of replacing some of the reactive glass with zirconia. In a novel material which advocated using radiant heat to cure it, to compare the effect of this with ultrasound. To evaluate the effect of ultrasound on a glass ionomer with fluoride in the water but not in the glass. 10 samples of each cement were ultrasonically set for 55 s; 10 controls self cured for 6 min. Each was placed in 10 ml of deionised water which was changed at 1, 3, 7, 14, 21, 28 days. The solution fluoride content was measured using a selective ion electrode. All ultrasound samples released more fluoride than the controls. Release patterns were similar; after a few days, cumulative fluoride was linear with respect to t(1/2). Slope and intercept of linear regression plots increased with ultrasound. With radiant heat the cement released less fluoride than controls. The effect of ultrasound on cement with F in water increased only slope not intercept. Zirconia addition enhances fluoride release although the cement fluorine content is reduced. Comparison of capsule and hand mixing showed no consistent effect on fluoride release. Ultrasound enhances fluoride release from GICs. As heat has an opposite effect the heat from ultrasound is not its only action. The lesser effect on cement with fluoride only in the water indicates that of ultrasound enhances fluoride release from glass.