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Biomedical subjects

S Allen

Publications and source records attributed to S Allen.

At least 19 recordsLinked to original sources
PubMed2006

Evidence that the canonical Wnt signalling pathway regulates deer antler regeneration.

Wnt signalling regulates many developmental processes, including the fate specification, polarity, migration, and proliferation of cranial neural crest. The canonical Wnt pathway has also been shown to play an important role in bone physiology and there is evidence for its recapitulation during organ regeneration in lower vertebrates. This study explores the role of the Wnt signalling pathway in deer antlers, frontal bone appendages that are the only mammalian organs capable of regeneration. Immunocytochemistry was used to map the distribution of the activated form of beta-catenin ((a)betaCAT). A low level of (a)betaCAT staining was detected in chondrocytes and in osteoblasts at sites of endochondral bone formation. However, (a)betaCAT was localised in cellular periosteum and in osteoblasts in intramembranous bone, where it co-localised with osteocalcin. The most intense (a)betaCAT staining was in dividing undifferentiated cells in the mesenchymal growth zone. Antler progenitor cells (APCs) were cultured from this region and when the canonical Wnt pathway was inhibited at the level of Lef/TCF by epigallocatechin gallate (EGCG), the cell number decreased. TUNEL staining revealed that this was as a result of increased apoptosis. Activation of the pathway by lithium chloride (LiCl) had no effect on cell number but inhibited alkaline phosphate activity (ALP), a marker of APC differentiation, whereas EGCG increased ALP activity. This study demonstrates that beta-catenin plays an important role in the regulation of antler progenitor cell survival and cell fate. It also provides evidence that beta-catenin's function in regulating bone formation by osteoblasts may be site-specific.

Animals↗
PubMed2006

Interleukin 18 and human immunodeficiency virus type I infection in adolescents and adults.

Interleukin (IL)-18, a proinflammatory cytokine, has been recognized recently as an important factor in both treated and untreated patients with human immunodeficiency virus type 1 (HIV-1) infection. Consistent with all earlier reports, our quantification of serum IL-18 concentrations in 88 HIV-1 seropositive, North American adolescents (14-18 years old) revealed a positive correlation with cell-free HIV-1 viral load at two separate visits (Spearman's r = 0.31 and 0.50, respectively, P < 0.01 for both), along with a negative correlation with CD4+ T cell counts (r = -0.31 and -0.35, P < 0.01 for both). In additional analyses of 66 adults (21-58 years old) from Zambia, HIV-1 seroconversion was associated uniformly with elevated IL-18 production (P < 0.0001). These epidemiological relationships were independent of other population-related characteristics, including age, gender and ethnicity. In neither study population could serum IL-18 concentrations be associated with the IL-18 gene (IL18) promoter genotypes defined by five major single nucleotide polymorphisms. Collectively, these findings suggest that circulating IL-18 rather than the IL18 genotype may provide a useful biomarker for HIV-1-related events or outcomes.

ADP-ribosyl Cyclase 1↗
PubMed2006

Tranquilliser use as a risk factor for falls in hospital patients.

This study looked at associations of tranquilliser use and falls risk in a hospital population of confused and nonconfused patients. In a prospective observational study in a rehabilitation hospital for elderly patients, we followed 1025 consecutive patients. The number of fallers, recurrent fallers and total falls was recorded. Confused patients (p < 0.0001) and patients on tranquillisers (p = 0.001) were significantly more likely to fall than nonconfused patients and patients off tranquillisers. Confused patients on tranquillisers were significantly more likely to have recurrent falls (p = 0.026) when compared with confused patients off tranquillisers. The risk was apparent from admission, persisting throughout the first 30 days of stay. This was not noted for nonconfused patients. We identified a stratification of risk for falls with nonsignificant trends for confused and nonconfused patients on tranquillisers to be fallers and to have more falls compared with patients off tranquillisers. These data are associational and do not necessarily imply causality. There is however no evidence to recommend the routine withdrawal of tranquillisers from all patients. Any future research needs to include confused patients.

Accidental Falls↗
PubMed2006

The Practical Approach to Lung Health in South Africa (PALSA) intervention: respiratory guideline implementation for nurse trainers.

AIM: This paper describes the design, facilitation and preliminary assessment of a 1-week cascade training programme for nurse trainers in preparation for implementation of the Practical Approach to Lung Health in South Africa (PALSA) intervention, tested within the context of a pragmatic cluster randomized controlled trial in the Free State province. PALSA combines evidence-based syndromic guidelines on the management of respiratory disease in adults with group educational outreach to nurse practitioners. BACKGROUND: Evidence-based strategies to facilitate the implementation of primary care guidelines in low- to middle-income countries are limited. In South Africa, where the burden of respiratory diseases is high and growing, documentation and evaluation of training programmes in chronic conditions for health professionals is limited. METHOD: The PALSA training design aimed for coherence between the content of the guidelines and the facilitation process that underpins adult learning. Content facilitation involved the use of key management principles (key messages) highlighted in nurse-centred guidelines manual and supplemented by illustrated material and reminders. Process facilitation entailed reflective and experiential learning, role-playing and non-judgemental feedback. DISCUSSION AND RESULTS: Preliminary feedback showed an increase in trainers' self-awareness and self-confidence. Process and content facilitators agreed that the integrated training approach was balanced. All participants found that the training was motivational, minimally prescriptive, highly nurse-centred and offered personal growth. CONCLUSION: In addition to tailored guideline recommendations, training programmes should consider individual learning styles and adult learning processes.

Education, Nursing, Continuing↗
PubMed2006

Validity and reliability of active shape models for the estimation of Cobb angles in adolescent idiopathic scoliosis.

Choosing the most suitable treatment for scoliosis relies heavily on accurate and reproducible Cobb angle measurement from successive radiographs. The objective is to reduce variability of Cobb angle measurement by reducing user intervention and bias. Custom software to automate Cobb angle measurement from posteroanterior radiographs was developed using active shape models. Validity and reliability of the automated system against a manual and semi-automated measurement method was conducted by two examiners each performing measurements on 3 occasions from a test set (N=22). A training set (N=47) of radiographs representative of curves seen in a scoliosis clinic was used to train the software to recognize vertebrae from T4 to L4. Images with a maximum Cobb angle between 20 degrees and 50 degrees, excluding surgical cases, were selected for training and test sets. Automated Cobb angles were calculated using best-fit slopes of the detected vertebrae endplates. Intra-class correlation coefficient (ICC) and standard error of measurement (SEM) showed high intra-examiner (ICC > 0.90, SEM 2-3 degrees) and inter-examiner (ICC > 0.82, SEM 2-4 degrees), but poor inter-method reliability (ICC=0.30, SEM 8-9 degrees). The automated method underestimated large curves. The reliability improved (ICC = 0.70, SEM 4-5 degrees) with exclusion of the 4 largest curves (>40 degrees) in the test set. The automated method was reliable for moderate sized curves, but did not properly detect vertebrae in larger curves. Optimization of constraints on scaling, rotation, translation, and iteration may improve reliability with larger curves.

Adolescent↗
PubMed2005

Thermodynamic behaviour and the effect of temperature on the removal of dyes from aqueous solution using modified diatomite: a kinetic study.

The effect of solution temperature and the determination of the thermodynamic parameters of adsorption of methylene blue (MB), Cibacron Reactive black C-NN (RB) and Cibacron Reactive golden yellow MI-2RN (RY) onto manganese-oxides-modified diatomite (MOMD), such as activation energy, E, enthalpy of activation, DeltaH*, entropy of activation, DeltaS*, and free energy of activation, DeltaG*, on the adsorption rates is important in understanding the adsorption mechanism. The rate and the transport/kinetic processes of dye adsorption onto the adsorbents were described by applying various kinetic adsorption models. This would lead to a better understanding of the mechanisms controlling the adsorption rate. The pseudo-second-order model was the best choice among all the kinetic models to describe the adsorption behaviour of RB onto MOMD, suggesting that the adsorption mechanism might be a chemisorption process. The activation energies, E, for RB, RY and MB were -6.74, 56.65 and 99.80 kJ/mol, respectively. The negative value of the activation energy suggested that the rise in the solution temperature did not favour RB adsorption onto MOMD. Moreover, the activation energy of the diffusion process, E', for RB, RY and MB increased as MB > RY >> RB. It means that the RB molecules are much faster moving and a lower energy is needed to diffuse into MOMD than RY and MB molecules. E', the activation energy for adsorption into pores, of RY is higher than E, indicating that the rate-limiting step of RY adsorption onto MOMD might be diffusion controlled, while the activation energy of the diffusion process, E', of MB is slightly lower than E, suggesting that the rate-limiting step is a combination of chemical and diffusion adsorption.

Journal Article↗
PubMed2005

A comparative study of the sensitivity of the 3-induction and 9-induction Buehler test procedures for assessing skin sensitisation potential.

Assessment of skin sensitization potential is a mandatory requirement for the registration or notification of most types of chemicals and products. Until recently, two methods using the guinea pig as test model were the most widely accepted; the guinea pig maximisation test and the Buehler test. In the case of agrochemical formulations, which constitute the final end use product in contact with operators, industry and also some regulatory authorities consider the Buehler method more appropriate as the methodology is more relevant to likely exposure in the field. However, certain European regulatory authorities have become concerned about the sensitivity of the Buehler test for this purpose and have requested that a modified method is used in which additional applications of test materials are used during the induction phase of the protocol (a total of 9 rather than the normal 3). This study was designed to assess whether this modification was justified. Six reference substances (formaldehyde, alpha-hexylcinnamaldehyde, fragrance mix, thimerosal, mercaptobenzothiazole and phthalic anhydride); all mild to moderate skin sensitizing chemicals, were assessed in a study, which compared the use of 3 and 9 induction applications. The results of this study demonstrated that, although most of these sensitisers were detected by both protocols, the modified method (9 induction applications) was no more sensitive than the standard method (3 induction applications). As the modified protocol is also potentially more stressful to the animals, it is concluded that the use of additional induction applications in the Buehler test cannot be justified from either a scientific or an animal welfare perspective.

Allergens↗
PubMed2005

Deer antlers: a zoological curiosity or the key to understanding organ regeneration in mammals?

Many organisms are able to regenerate lost or damaged body parts that are structural and functional replicates of the original. Eventually these become fully integrated into pre-existing tissues. However, with the exception of deer, mammals have lost this ability. Each spring deer shed antlers that were used for fighting and display during the previous mating season. Their loss is triggered by a fall in circulating testosterone levels, a hormonal change that is linked to an increase in day length. A complex 'blastema-like' structure or 'antler-bud' then forms; however, unlike the regenerative process in the newt, most evidence (albeit indirect) suggests that this does not involve reversal of the differentiated state but is stem cell based. The subsequent re-growth of antlers during the spring and summer months is spectacular and represents one of the fastest rates of organogenesis in the animal kingdom. Longitudinal growth involves endochondral ossification in the tip of each antler branch and bone growth around the antler shaft is by intramembranous ossification. As androgen concentrations rise in late summer, longitudinal growth stops, the skin (velvet) covering the antler is lost and antlers are 'polished' in preparation for the mating season. Although the timing of the antler growth cycle is clearly closely linked to circulating testosterone, oestrogen may be a key cellular regulator, as it is in the skeleton of other male mammals. We still know very little about the molecular machinery required for antler regeneration, although there is evidence that developmental signalling pathways with pleiotropic functions are important and that novel 'antler-specific' molecules may not exist. Identifying these pathways and factors, deciphering their interactions and how they are regulated by environmental cues could have an important impact on human health if this knowledge is applied to the engineering of new human tissues and organs.

Androgens↗
PubMed2005

The relationship of falls to injury among hospital in-patients.

The need to reduce falls is driven by the need to reduce injury. If patients at risk of injury can be distinguished from the patients at risk of falls, there is the potential for a more effective fall risk management policy by targeting injury prevention measures. We conducted a prospective observational study, with blinded endpoint evaluation of 825 consecutive patients admitted to geriatric rehabilitation wards. We identified 150 fallers (18.2%) contributing 243 falls. Fifty-six patients sustained an injury contributing 73 (30.0%) injurious falls. Only five (6.8%) falls resulted in injury of major severity. We identified no significant differences in demographics between injurious and non-injurious falls. A logistic regression analyses of the independent risk factors of suffering an injurious fall were a history of falls (p=0.036), confusion (p=0.001) and an unsafe gait (p=0.03). However, we identified no significant differences in clinical characteristics between patients suffering injurious and non-injurious falls. None of the characteristics studied can identify patients prone to injury after a fall. Injury is largely unpredictable, and more research is needed to determine how injury can be prevented in patients at risk of falls.

Accidental Falls↗
PubMed2004

Exploring the mechanisms regulating regeneration of deer antlers.

Deer antlers are the only mammalian appendages capable of repeated rounds of regeneration; every year they are shed and regrow from a blastema into large branched structures of cartilage and bone that are used for fighting and display. Longitudinal growth is by a process of modified endochondral ossification and in some species this can exceed 2 cm per day, representing the fastest rate of organ growth in the animal kingdom. However, despite their value as a unique model of mammalian regeneration the underlying mechanisms remain poorly understood. We review what is currently known about the local and systemic regulation of antler regeneration and some of the many unsolved questions of antler physiology are discussed. Molecules that we have identified as having potentially important local roles in antlers include parathyroid hormone-related peptide and retinoic acid (RA). Both are present in the blastema and in the rapidly growing antler where they regulate the differentiation of chondrocytes, osteoblasts and osteoclasts in vitro. Recent studies have shown that blockade of RA signalling can alter cellular differentiation in the blastema in vivo. The trigger that regulates the expression of these local signals is likely to be changing levels of sex steroids because the process of antler regeneration is linked to the reproductive cycle. The natural assumption has been that the most important hormone is testosterone, however, at a cellular level oestrogen may be a more significant regulator. Our data suggest that exogenous oestrogen acts as a 'brake', inhibiting the proliferation of progenitor cells in the antler tip while stimulating their differentiation, thus inhibiting continued growth. Deciphering the mechanism(s) by which sex steroids regulate cell-cycle progression and cellular differentiation in antlers may help to address why regeneration is limited in other mammalian tissues.

Animals↗
PubMed2004

Recapitulation of the parathyroid hormone-related peptide-Indian hedgehog pathway in the regenerating deer antler.

Parathyroid hormone (PTH)-related peptide (PTHrP) and the PTH/PTHrP receptor (PPR) play an essential role in controlling growth plate development. The aim of the present study was to use the deer antler as a model to determine whether PTHrP and PPR may also have a function in regulating cartilage and bone regeneration in an adult mammal. Antlers are the only mammalian appendages that are able to undergo repeated cycles of regeneration, and their growth from a blastema involves a modified endochondral process. Immunohistochemistry was used to establish sites of localization of PTHrP and PPR in antlers at different stages of development. The pattern of Indian Hedgehog (IHH) and transforming growth factor-beta1 (TGF beta1) distribution was also investigated, because PTHrP expression in the developing limb is regulated by IHH and during embryonic growth plate formation TGF beta1 acts upstream of PTHrP to regulate the rate of chondrocyte differentiation. In the antler blastema (<10 days of development), PTHrP, PPR, and TGF beta1 were localized in epidermis, dermis, regenerating epithelium, and in mesenchymal cells but IHH expression was not detected. In the rapidly growing antler (weeks 4-8 of development), PTHrP, PPR, and TGF beta1 were localized in skin, perichondrium, undifferentiated mesenchyme, recently differentiated chondrocytes, and in perivascular cells in cartilage but not in fully differentiated hyperytrophic chondrocytes. IHH was restricted to recently differentiated chondrocytes and to perivascular cells in cartilage. In mineralized cartilage and bone, PTHrP, PPR, IHH, and TGF beta1 were immunolocalized in perivascular cells and differentiated osteoblasts. PTHrP and PPR were also present in the periosteum. TGF beta1 in vitro stimulated PTHrP synthesis by cells from blastema, perichondrium, and cartilage. The findings of this study suggest that molecules which regulate embryonic skeletal development and postnatal epiphyseal growth may also control blastema formation, chondrogenesis, and bone formation in the regenerating deer antler. This finding is further evidence that developmental signaling pathways are recapitulated during adult mammalian bone regeneration.

Animals↗
PubMed2004

Evaluation of body weight as a predictive factor for transvenous ventricular defibrillation characteristics.

AIMS: To investigate the correlation between body weight and defibrillation threshold (DFT) for transvenous lead systems using a porcine model. METHODS AND RESULTS: Twenty-eight pigs were anaesthetised and DFTs assessed in single and dual coil configurations using a four-reversal binary search method. DFT was correlated with body weight in the RV --> Can and RV --> SVC + Can configurations. A Pearson correlation coefficient and a two-sided p-value were calculated. A positive correlation exists between body weight and DFT in RV --> Can (r=0.66, p<0.000) and RV --> SVC + Can (r=0.44, p=0.018). CONCLUSION: There is a significant correlation between body weight and DFT in swine. This tends to be greater in the two-electrode than in the three-electrode configuration. With these and previous human observations, one may predict a higher DFT in heavy individuals and make appropriate procedural adjustments.

Animals↗
PubMed2004

Proteomic analysis of voided urine after prostatic massage from patients with prostate cancer: a pilot study.

OBJECTIVES: Serum prostate-specific antigen measurements are widely used for the early detection of prostate cancer but lack specificity, thus warranting the search for additional biomarkers. METHODS: Two-dimensional gel electrophoresis followed by matrix-assisted laser desorption ionization-time of flight-mass spectroscopy (MALDI-TOF-MS) analysis was used to investigate the protein profiles of voided urine after prostatic massage from 6 patients with histologically confirmed prostate cancer and 6 age-matched patients with benign prostatic hyperplasia. RESULTS: The median number of protein spots per gel was lower in the urine from the patients with cancer (median 143 spots, range 118 to 163) than in the urine from those with benign prostatic hyperplasia (median 154 spots, range 142 to 209), although the difference was not statistically significant. MALDI-TOF-MS analysis identified six commonly expressed proteins: alpha-enolase, isocitrate dehydrogenase, beta-2-microglobulin, alpha-1-microglobulin, complex-forming glycoprotein HC, and PRO2044. Of the five protein spots seen in a subset of patients with cancer, one was identified as calgranulin B/MRP-14. Immunohistochemical staining of prostatic tissue showed greater expression of calgranulin B/MRP-14 in 2 of 7 well-differentiated, 1 of 12 moderately differentiated, and 0 of 8 poorly differentiated tumors relative to adjacent benign tissue; expression of calgranulin A/MRP-8, a heterodermic binding partner of calgranulin B/MRP-14, was absent. CONCLUSIONS: The role of urinary calgranulin B/MRP-14 as a potential novel marker for prostate cancer needs additional investigation.

Aged↗
PubMed2004

Direct atomic force microscopy observations of monovalent ion induced binding of DNA to mica.

Multivalent ions in solution are known to mediate attraction between two like-charged molecules. Such attraction has proved useful in atomic force microscopy (AFM) where DNA may be immobilized to a mica surface facilitating direct imaging in liquid. Theories of DNA immobilization suggest that either 'salt bridging' or fluctuation in the positions of counter ions about both the mica surface and DNA backbone secure DNA to the mica substrate. Whilst both theoretical and experimental evidence suggest that immobilization is possible in the presence of divalent ions, very few studies identify that such immobilization is possible with monovalent ions. Here we present direct AFM evidence of DNA immobilized to mica in the presence of only monovalent ions. Our data depict E. coli plasmid pBR322 adsorbed onto the negatively charged mica both after short (10 min) and long (24 h) incubation periods. These data suggest the need to re-explore current theories of like-charge attraction to include the possibility of monovalent interactions. We suggest that this DNA immobilization strategy may offer the potential to image natural processes with limited immobilization forces and hence enable maximum conformational freedom of the immobilized biomolecule.

Aluminum Silicates↗
PubMed2004

Detection of severe protein-energy malnutrition by nurses in The Gambia.

AIM: To test whether nurses can use the WHO integrated management of childhood illness (IMCI) nutrition algorithm to identify reliably severe protein-energy malnutrition in children. METHODS: Nurses were trained to identify severe protein-energy malnutrition using IMCI training materials. They identified visible severe wasting and bipedal oedema, and categorised weight-for-age using a growth chart, in consecutive children attending outpatient clinics. Their findings were compared with weight for height Z (WHZ) score, bipedal oedema assessed by a trained observer, and weight-for-age Z score. RESULTS: A total of 352 children were recruited, of whom 34 (9.7%) were severely wasted (WHZ score <-3) and 18 (5.1%) had bipedal oedema. In the detection of severe wasting, the nurses' assessments showed 56% sensitivity, 95% specificity, and 56% positive predictive value (PPV), and for bipedal oedema 22%, 99%, and 57% respectively. Overall, the nurses identified only half of 50 children with severe wasting and/or bipedal oedema and wrongly identified a further 13 children as severely malnourished. Plotting weight for age by the nurses showed 62% sensitivity, 99% specificity, and 89% PPV for the detection of children with very low weight. CONCLUSIONS: Severe malnutrition was both under-diagnosed and wrongly diagnosed by nurses trained in the use of the IMCI nutrition algorithm in a clinic setting in The Gambia. These guidelines for health workers and the training materials, particularly with respect to calculation of age, need further development to improve the detection of malnourished children.

Algorithms↗
PubMed2003

Electrostatic interactions observed when imaging proteins with the atomic force microscope.

The atomic force microscope (AFM) is now an established and valuable tool for the study of biological macromolecules in aqueous environments. In this paper we form a patterned boundary via the microcontact printing of individually isolated proteins, covalently attached to a solid support. We use this boundary to investigate electrostatic interactions that can occur between an AFM tip and a protein surface during imaging in solution. The observed height variations of the protein film are found to be a combination of not only structural considerations and thickness of the protein film, but also the repulsive contribution from electrostatic interactions between the AFM tip and the sample. These variations in measured heights of the protein surface can be described by Derjaguin, Landau, Verway, Overbeek (DLVO) theory. Our experimental results show that height measurements can be manipulated either negatively or positively by adjusting the pH and concentration of the electrolyte buffer that is utilised.

Algorithms↗