Bat rabies in the United Kingdom.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
Alan Smith
Publications and source records attributed to Alan Smith.
Honey bees navigate according to a map-like spatial memory.
By using harmonic radar, we report the complete flight paths of displaced bees. Test bees forage at a feeder or are recruited by a waggle dance indicating the feeder. The flights are recorded after the bees are captured when leaving the hive or the feeder and are released at an unexpected release site. A sequence of behavioral routines become apparent: (i) initial straight flights in which they fly the course that they were on when captured (foraging bees) or that they learned during dance communication (recruited bees); (ii) slow search flights with frequent changes of direction in which they attempt to "get their bearings"; and (iii) straight and rapid flights directed either to the hive or first to the feeding station and then to the hive. These straight homing flights start at locations all around the hive and at distances far out of the visual catchment area around the hive or the feeding station. Two essential criteria of a map-like spatial memory are met by these results: bees can set course at any arbitrary location in their familiar area, and they can choose between at least two goals. This finding suggests a rich, map-like organization of spatial memory in navigating honey bees.
Animals↗
Intranasal delivery of recombinant human growth hormone (somatropin) in sheep using chitosan-based powder formulations.
The effectiveness of chitosan in promoting the intranasal bioavailability of recombinant human growth hormone (hGH) has been evaluated. hGH was formulated with chitosan to produce a powder blend (Formulation A) and granules (Formulation B) for intranasal administration. The in vivo pharmacokinetic performance of the formulations was evaluated in a group of six sheep in a randomised crossover study. A subcutaneous injection of hGH solution was administered as a control. The intranasal and subcutaneous doses of hGH were 0.3 and 0.03 mg/kg, respectively. The intranasal formulations appeared to be well tolerated. Mean bioavailabilities of hGH from Formulations A and B were 14 and 15%, respectively relative to subcutaneous injection. It is concluded that chitosan-based intranasal powder formulations may provide a practical means for non-injectable delivery of hGH and, potentially, other therapeutic protein molecules.
Administration, Intranasal↗
The three-phase model of cardiac arrest as applied to ventricular fibrillation in a large, urban emergency medical services system.
BACKGROUND: Cardiac arrest is responsible for significant morbidity and mortality, with consistently poor outcomes despite the rapid availability of prehospital personnel for defibrillation attempts in patients with ventricular fibrillation (VF). Recent evidence suggests a period of cardiopulmonary resuscitation (CPR) prior to defibrillation attempts may improve outcomes in patients with moderate time since collapse (4-10 min). OBJECTIVES: To determine cardiac arrest outcomes in our community and explore the relationship between time since collapse, performance of bystander CPR, and survival. METHODS: Non-traumatic cardiac arrest data were collected prospectively over an 18-month period. Patients were excluded for: age <18 years, a "Do Not Attempt Resuscitation" (DNAR) directive, determination of a non-cardiac etiology for arrest, and an initially recorded rhythm other than VF. Patients were stratified by time since collapse (<4, 4-10, > 10 min, and unknown) and compared with regard to survival and neurological outcome. In addition, patients with and without bystander CPR were compared with regard to survival. RESULTS: : A total of 1141 adult non-traumatic cardiac arrest victims were identified over the 18-month study period. This included 272 patients with VF as the initially recorded rhythm. Of these, 185 had a suspected cardiac etiology for the arrest; survival to hospital discharge was 15% in this group, with 82% of these having a good outcome or only moderate disability. Survival was highest among patients with time since collapse of less than 4 min and decreased with increasing time since collapse. There were no survivors among patients with time since collapse greater than 10 min. Among patients with time since collapse of 4 min or longer, survival was significantly higher with the performance of bystander CPR; there was no survival advantage to bystander CPR among patients with time since collapse less than 4 min. CONCLUSIONS: The performance of bystander CPR prior to defibrillation by EMS personnel is associated with improved survival among patients with time since collapse longer than 4 min but not less than 4 min. These data are consistent with the three-phase model of cardiac arrest.
Aged↗
Effect of chitosan on the intranasal absorption of salmon calcitonin in sheep.
The effects of a chitosan-based delivery system on the pharmacokinetics of intranasally administered salmon calcitonin (sCT) were investigated in a sheep model. In particular, the feasibility of producing a formulation with a comparable or improved bioavailability and/or less variability than the currently marketed nasal product (Miacalcin nasal spray, Novartis Pharmaceuticals) was assessed. A comparator (control) formulation comprising sCT solution was also tested. Sheep (n=6) were dosed intranasally according to a randomized crossover design. The intranasal sCT dose was 1100 IU (equivalent to approximately 17 IU kg-1). After completion of the nasal dosing legs, five of the sheep received 300 IU sCT (equivalent to approximately 5 IU kg-1) by subcutaneous injection to estimate relative bioavailability. After intranasal or subcutaneous dosing, serial blood samples were taken and plasma separated by centrifugation before measuring sCT concentrations by ELISA. Pharmacokinetic (non-compartmental) and statistical (analysis of variance or non-parametric alternative) analyses were performed. No systemic or local adverse effects were observed following intranasal or subcutaneous administration of sCT. The mean relative bioavailability of sCT from the chitosan solution was improved twofold compared with Miacalcin nasal spray and threefold compared with sCT control solution. Inter-animal variability in sCT absorption appeared to be lower with use of the chitosan-based solution compared with the control solution or commercial product. Based on the reported sheep data, a chitosan delivery system could offer the potential to significantly improve the intranasal absorption of sCT and reduce the variability in absorption. In the clinical setting, this may allow relatively lower doses of the drug to be given intranasally and/or lead to improvements in the efficacy or quality of intranasal therapy.
Adjuvants, Pharmaceutic↗
TARGIT technology: coated starch capsules for site-specific drug delivery into the lower gastrointestinal tract.
TARGIT technology (West Pharmaceutical Services) is designed for site-specific delivery of drugs in the gastrointestinal (GI) tract and, in particular, targeted release into the colonic region. A key area of application is the delivery of therapeutic agents for local treatment of lower GI diseases. The technology is based on the application of pH-sensitive coatings onto injection-moulded starch capsules. An extensive body of clinical data has been generated showing reliable in vivo performance of the capsules. In gamma-scintigraphy studies around 90% of TARGIT capsules (n = 84) delivered their contents to the target site of the terminal ileum and colon. TARGIT-based products are in active clinical development for the treatment of conditions including inflammatory bowel diseases.
Administration, Oral↗
New diagnoses of HTLV infection in England and Wales: 2002-2004.
Human T cell lymphotropic viruses (HTLV) are retroviruses transmitted through breastfeeding, sexual contact, blood transfusion and injecting drug use. HTLV is endemic in the Caribbean, and parts of Africa, Japan and South America, with isolated foci in other areas. Infection is life long. Fewer than 5% of those infected progress to one of the HTLV-related diseases, but these are debilitating and often fatal. In England and Wales, laboratory and clinical reports of new HTLV diagnoses are routinely collected, including infections identified by the blood service since the introduction of anti-HTLV testing in August 2002. Between 2002 and 2004, 273 individuals were diagnosed with HTLV: 102 (37%) were male and 169 female (sex was not reported for two). Median ages at diagnosis were 54 and 50 years respectively. Clinical reports were received for 78% (212/273) individuals. Where reported, 58% (116/199) of individuals were of black Caribbean ethnicity and 29% (57/199) white; 87% (128/147) were probably infected heterosexually or through mother-to-child transmission; 45% (66/146) were probably infected in the Caribbean and 40% (59/146) in the United Kingdom. An appreciable number of HTLV infections continue to be diagnosed within England and Wales, with increases in 2002-2003 because of anti-HTLV testing of blood donations. While most infections diagnosed are directly associated with the Caribbean, transmission of HTLV infection is occurring within England and Wales. Specialist care services for HTLV-infected individuals and their families have improved in recent years, but prevention remains limited.
Comparative Study↗
Challenging intolerance.
Social identity is multilayered and complex. Schools, communities, and nations can implement structures and approaches that help youth to understand one another and respect differences.
Cultural Diversity↗
Community-wide vaccination with the heptavalent pneumococcal conjugate significantly alters the microbiology of acute otitis media.
BACKGROUND: Community-wide use of conjugated heptavalent pneumococcal vaccine (PCV7) in children <2 years of age could affect the microbiology of acute otitis media (AOM) in vaccinees, particularly for penicillin-nonsusceptible Streptococcus pneumoniae (PNSP). SETTING: Since Summer 2000, 94% of young children cared for by this 7-clinician, pediatric practice in rural central Kentucky received 3 or 4 doses of PCV7 in the first 18 months of life. OBJECTIVE: To determine changes in microbiology of AOM before and after community-wide routine implementation of PCV7. METHODS: Among children 7-24 months old with severe or refractory AOM, we compared 336 AOM isolates from 1992-1998 with 83 AOM isolates from 2000-2003 in children who had received 3 or 4 doses of PCV7. RESULTS: Comparing each cohort (1992-1998 versus 2000-2003), the proportion of S. pneumoniae decreased from 48% to 31% (P = 0.009; relative risk, 0.754; 95% confidence interval, 0.628-0.906), and nontypable Haemophilus influenzae increased from 41% to 56% (P = 0.01; relative risk, 1.87; 95% confidence interval, 1.15-3.04; beta-lactamase-positive, 56% versus 64%, not significant). The proportions of intermediate PNSP and resistant PNSP, respectively, were 16% and 9% versus 13% and 6% pre- and post-PCV7, respectively. Vaccine and vaccine-related serotypes, respectively, comprised 70% and 8% versus 36% and 32% of S. pneumoniae strains (P = 0.003). Post-PCV7, Gram-negative bacteria and beta-lactamase-producing organisms accounted for two-thirds and one-half of all AOM isolates, respectively. DISCUSSION: The overall proportion of S. pneumoniae isolates and vaccine serotypes in AOM were significantly reduced by community-wide use of PCV7 vaccine in our practice. The proportion of Gram-negative bacteria became 2-fold more frequent than S. pneumoniae in AOM in PCV7-vaccinated young children where PCV7 uptake was community-wide and supply was adequate.
Acute Disease↗
Correlation of SEC/MALLS with ultracentrifuge and viscometric data for chitosans.
Attempts have been made to correlate estimates of molecular weight for a group of cationic polysaccharides known as chitosans between the highly popular technique of size-exclusion chromatography coupled to multi-angle laser light scattering, "SEC-MALLS", and the less convenient but more established technique of sedimentation equilibrium in the analytical ultracentrifuge. Four pharmaceutical grade chitosans of various molecular weights and degrees of acetylation (4-30%) were chosen. Better correlation than previous was achieved, although some batch variability was observed. Despite the broad spectrum in degree of acetylation, a log s degrees(20,w) versus log Mw scaling plot appeared to fit a straight line with power-law exponent b=0.25 +/- 0.04, i.e. between the limits of rod (0.15) and coil (0.4-0.5), although this may be the average of a lower b value at low Mw and higher b at high Mw. With regard to viscosity, a logeta versus logMw scaling plot appeared to also fit a straight line with power-law exponent a=0.96 +/- 0.10, again between the coil (0.5-0.7) and rod (1.8) limits.
Centrifugation, Density Gradient↗
The toxicity of textile reactive azo dyes after hydrolysis and decolourisation.
The toxicity of C.I. Reactive Black 5 and three Procion dyes, as found in textile effluents, was determined using the bioluminescent bacterium Vibrio fischeri. Hydrolysed Reactive Black had a slightly greater toxicity than the parent form (EC(50) 11.4+/-3.68 and 27.5+/-4.01 mg l(-1), respectively). A baffled bioreactor with anaerobic and aerobic compartments was used to decolourise hydrolysed Reactive Black 5 in a synthetic effluent. Decolourisation of hydrolysed Reactive Black resulted in an increased toxicity (EC(50) 0.2+/-0.03 mg l(-1)). Toxicity was not detectable when decolourised Reactive Black 5 was metabolised under aerobic conditions. No genotoxicity was detected after the decolourisation of either the parent or the hydrolysed reactive dyes, either in vitro or in the bioreactor. The toxicity and genotoxicity of decolourised C.I. Acid Orange 7 was due to the production of 1-amino-2-naphthol (EC(50) 0.1+/-0.03 mg l(-1)).
Anaerobiosis↗
Augmentation of umbilical cord blood (UCB) transplantation with ex vivo-expanded UCB cells: results of a phase 1 trial using the AastromReplicell System.
Allogeneic stem cell transplantation with umbilical cord blood (UCB) cells is limited by the cell dose a single unit provides recipients. Ex vivo expansion is one strategy to increase the number of cells available for transplantation. Aastrom Biosciences developed an automated continuous perfusion culture device for expansion of hematopoietic stem cells (HSCs). Cells are expanded in media supplemented with fetal bovine serum, horse serum, PIXY321, flt-3 ligand, and erythropoietin. We performed a phase 1 trial augmenting conventional UCB transplants with ex vivo-expanded cells. The 28 patients were enrolled on the trial between October 8, 1997 and September 30, 1998. UCB cells were expanded in the device, then administered as a boost to the conventional graft on posttransplantation day 12. While expansion of total cells and colony-forming units (CFUs) occurred in all cases, the magnitude of expansion varied considerably. The median fold increase was 2.4 (range, 1.0-8.5) in nucleated cells, 82 (range, 4.6-266.4) in CFU granulocyte-macrophages, and 0.5 (range, 0.09-2.45) in CD34+ lineage negative (lin-) cells. CD3+ cells did not expand under these conditions. Clinical-scale ex vivo expansion of UCB is feasible, and the administration of ex vivo-expanded cells is well tolerated. Augmentation of UCB transplants with ex vivo-expanded cells did not alter the time to myeloid, erythroid, or platelet engraftment in 21 evaluable patients. Recipients of ex vivo-expanded cells continue to have durable engraftment with a median follow-up of 47 months (range, 41-51 months). A randomized phase 2 study will determine whether augmenting UCB transplants with ex vivo-expanded UCB cells is beneficial.
Adolescent↗
Isolation and characterisation of tilapia beta-actin promoter and comparison of its activity with carp beta-actin promoter.
The regulatory sequence including proximal promoter, untranslated exon 1 and intron 1 of the beta-actin gene from tilapia (Oreochromis niloticus) has been isolated and spliced to a beta-galactosidase reporter gene to test its activity. Comparisons of promoter activity have been carried out with three different constructs: (1) 1.6 kb tilapia beta-actin regulatory sequence, (2) 1.5 kb carp beta-actin regulatory sequence, and (3) 4.7 kb carp beta-actin regulatory sequence. Although the 1.6 kb tilapia beta-actin regulatory sequence gave slightly different expression patterns in tilapia embryos assayed by in situ X-gal staining, no difference was observed in expression level when the tilapia sequence was compared with the 4.7 kb carp beta-actin regulatory sequence by quantitative assay. In comparison with the 1.5 kb carp beta-actin regulatory sequence, the 1.6 kb tilapia beta-actin regulatory sequence gave higher expression levels in tilapia embryos, while a reverse result was observed in zebrafish embryos. In cell transfection experiments, the 1.6 kb tilapia beta-actin regulatory sequence showed three to four times better activity in blue gill cells than either the 4.7 kb carp beta-actin or the 1.5 kb carp beta-actin regulatory sequences. The 1.6 kb tilapia beta-actin regulatory sequence also drove higher reporter gene activity in somatic cells of tilapia than did the 4.7 kb carp beta-actin regulatory sequence following direct injection of constructs into muscle. Therefore, taken together, the data demonstrate that the tilapia beta-actin promoter can be used as an efficient regulatory sequence to produce autotransgenic tilapia.
Actins↗
Flavonoid effects on normal and leukemic cells.
Quercetin and flavopiridol, both flavonoids which influence oxidative milieu, proliferation, and apoptosis of various cell types, were examined for their effects on acute myelogenous leukemic cells and normal progenitors. Both quercetin and flavopiridol inhibited the growth and viability of various acute myelogenous leukemia (AML) cell lines and AML blasts isolated afresh from patients with AML of various subtypes. The effects on inhibition of proliferation and decreased viability were also significant in normal CD34+ cells isolated from normal marrow donors. In certain AML cases, the effects of flavopiridol appeared to be mediated through activation of caspase 3, offering one possible mechanism for the apoptosis evident after exposure to flavopiridol as measured by annexin V expression. These flavonoid compounds might find use in various therapeutic settings in AML.
Adult↗
Nuclear waste transportation: case studies of identifying stakeholder risk information needs.
The U.S. Department of Energy (DOE) is responsible for the cleanup of our nation's nuclear legacy, involving complex decisions about how and where to dispose of nuclear waste and how to transport it to its ultimate disposal site. It is widely recognized that a broad range of stakeholders and tribes should be involved in this kind of decision. All too frequently, however, stakeholders and tribes are only invited to participate by commenting on processes and activities that are near completion; they are not included in the problem formulation stages. Moreover, it is often assumed that high levels of complexity and uncertainty prevent meaningful participation by these groups. Considering the types of information that stakeholders and tribes need to be able to participate in the full life cycle of decision making is critical for improving participation and transparency of decision making. Toward this objective, the Consortium for Risk Evaluation with Stakeholder Participation (CRESP) participated in three public processes relating to nuclear waste transportation and disposal in 1997-1998. First, CRESP organized focus groups to identify concerns about nuclear waste transportation. Second, CRESP conducted exit surveys at regional public workshops held by DOE to get input from stakeholders on intersite waste transfer issues. Third, CRESP developed visual tools to synthesize technical information and allow stakeholders and tribes with varying levels of knowledge about nuclear waste to participate in meaningful discussion. In this article we share the results of the CRESP findings, discuss common themes arising from these interactions, and comment on special considerations needed to facilitate stakeholder and tribal participation in similar decision-making processes.
Communication↗
Allogeneic mesenchymal stem cells regenerate bone in a critical-sized canine segmental defect.
BACKGROUND: Mesenchymal stem cells from adult bone marrow are multipotent cells capable of forming bone, cartilage, and other connective tissues. In a previous study, we demonstrated that autologous mesenchymal stem cells could repair a critical-sized bone defect in the dog. The objective of this study was to determine whether the use of allogeneic mesenchymal stem cells could heal a critical-sized bone defect in the femoral diaphysis in dogs without the use of immunosuppressive therapy. METHODS: A critical-sized segmental bone defect, 21 mm in length, was created in the mid-portion of the femoral diaphysis of twelve adult dogs that weighed between 22 and 25 kg. Each defect was treated with allogeneic mesenchymal stem cells loaded onto a hollow ceramic cylinder consisting of hydroxyapatite-tricalcium phosphate. A complete mismatch between donor stem cells and recipient dogs was identified by dog leukocyte antigen typing prior to implantation. The healing response was evaluated histologically and radiographically at four, eight, and sixteen weeks after implantation. The radiographic and histological results at sixteen weeks were compared with the historical data for the control defects, which included defects that had been treated with a cylinder loaded with autologous mesenchymal stem cells, defects treated with a cylinder without mesenchymal stem cells, and defects that had been left untreated (empty). The systemic immune response was evaluated by the analysis of recipient serum for production of antibodies against allogeneic cells. RESULTS: For defects treated with allogeneic mesenchymal stem cell implants, no adverse host response could be detected at any time-point. Histologically, no lymphocytic infiltration occurred and no antibodies against allogeneic cells were detected. Histologically, by eight weeks, a callus spanned the length of the defect, and lamellar bone filled the pores of the implant at the host bone-implant interface. Fluorescently labeled allogeneic cells were also detected. At sixteen weeks, new bone had formed throughout the implant. These results were consistent with those seen in implants loaded with autologous cells. Implants loaded with allogeneic or autologous stem cells had significantly greater amounts of bone within the available pore space than did cell-free implants at sixteen weeks (p < 0.05). CONCLUSIONS: The results of this study demonstrated that allogeneic mesenchymal stem cells loaded on hydroxyapatite-tricalcium phosphate implants enhanced the repair of a critical-sized segmental defect in the canine femur without the use of immunosuppressive therapy. No adverse immune response was detected in this model.
Animals↗
Pneumococcal serotypes from acute otitis media in rural Kentucky.
OBJECTIVE: Acute otitis media (AOM) accounts for most infections caused by, but few data are available regarding the incidence of pneumococcal serotypes recovered from children with AOM in the United States. METHODS: Between January 1992 and March 1998, 777 middle ear pathogens from AOM were obtained from 701 patients by tympanocentesis (84.6%) or by culture of otorrhea (15.4%) from spontaneous perforation or draining tubes. The ambulatory patient population was mostly white and cared for by a sole private pediatric practice in rural Kentucky. RESULTS: Penicillin-nonsusceptible (penicillin MIC > or = 0.1 microg/ml) (PNSP) isolates accounted for 18% [6% resistant PNSP (rPNSP) and 12% intermediate resistant PNSP], and penicillin-susceptible strains accounted for 35% of the pathogens recovered from children with culture-proved AOM. Comparing the frequency of isolates between 1992 and 1993 with those between 1994 and 1998, overall rates of PNSP strains remained remarkably stable (32.2% 37.3%), but intermediate resistant PNSP strains doubled from 14% to 27% ( < 0.01), whereas rPNSP strains fell by one-third. Serotypes 19F (34%), 23F (30%), 6B (26%) and 14 (8%) accounted for nearly all rPNSP isolates. Two cross-reactive serotypes (6A and 19A) not included in the available pneumococcal conjugate vaccine comprised 8.4 and 15% of all serotypes and PNSP serotypes, respectively. Nearly all PNSP strains recovered in children < or =24 months are included in the vaccine serogroups. CONCLUSION: Depending on rates of efficacy and serotype cross-protection, the current pneumococcal conjugate vaccine could potentially protect against most PNSP strains in all ages, particularly in those < or =24 months.
Age Factors↗
Intracellular accumulation of human immunodeficiency virus protease inhibitors.
Intracellular accumulation of the protease inhibitors (PIs) saquinavir (SQV), ritonavir (RTV), and indinavir (IDV) was determined in 50 human immunodeficiency virus-positive patients. Following extraction, PIs were quantified by mass spectrometry. Paired plasma and intracellular samples were collected over a full dosing interval from patients (13 on SQV, 6 on RTV, 8 on IDV, 16 on SQV plus RTV, 7 on IDV plus RTV) with a plasma viral load of <400 copies/ml. Data were expressed as intracellular/plasma drug concentration ratios. A hierarchy of intracellular accumulation was demonstrated by the following medians: 9.45 for SQV > 1.00 for RTV > 0.51 for IDV. Coadministration of RTV did not boost ratios of SQV or IDV within the cell or in plasma, although absolute plasma and intracellular SQV concentrations were increased by RTV. Seven individuals receiving SQV in hard-gel capsule form (median, 32 months) had higher intracellular/plasma drug ratios than all other patients receiving SQV (median, 17.62 versus 4.83; P = 0.04), despite consistently low plasma SQV concentrations. How this occurs may provide insight into the mechanisms that limit adequate drug penetration into sanctuary sites.
Adolescent↗