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PubMed2003

Developing expertise - the contribution of paediatric accident and emergency nurses to the care of children, and the implications for their continuing professional development.

AIM: The purpose of this paper is to explore the contribution of paediatric accident and emergency nurses to the care of children. METHOD: Using a case study approach, the paper focuses on the experiences of three nurses working in this setting, obtained through working alongside the nurses and discussing and observing their experiences. FINDINGS: It became apparent that the nurses were regarded as "experts" in the care of children in this setting. The nurses themselves however, did not share this perception. Their experiences are analysed with reference to literature on expertise, focussing specifically on published accounts of children's nurses' experiences, and research which has explored the concept of expertise within the context of accident and emergency work. The implications for continuing professional development needs are discussed within the context of recent government reports, which make recommendations in respect of access and delivery of on-going professional education. To this end it is advocated that a multi-professional approach is adopted, with children's nurses sharing learning and thus access to, courses customarily provided to adults nurses working in this setting.

Child↗

PubMed1998

Stromelysin-1 (MMP-3) and stromelysin-2 (MMP-10) expression in developing human bone: potential roles in skeletal development.

Stromelysin, a member of the matrix metalloproteinase family, demonstrates wide substrate specificity with the ability to degrade proteoglycan, fibronectin, laminin, casein, and the nonhelical region of collagen. The two forms of stromelysin (SL), types 1 (MMP-3) and 2 (MMP-10), share 82% sequence homology, but exhibit differences in cellular synthesis and inducibility by cytokines and growth factors in vitro. However, the distribution of the two isoforms in bone has not been reported. We investigated the presence of SL-1 and SL-2 in human osteophytic and neonatal rib bone using immunohistochemistry and, combined with a new method of in situ zymography, determined the activity of the immunolocalized stromelysins. Latent SL-1 was strongly expressed in the extracellular matrix in fibrous tissue surrounding areas of endochondral ossification in osteophytes, and adjacent to the periosteum of fetal rib bone. Active SL-1 expression was detected in osteocytes and the matrix surrounding osteocytic lacunae. SL-2 showed intense cell-associated staining at sites of resorption in areas of endochondral ossification and in resorptive cells at the chondro-osseous junction, which correlated with enzyme activity detected by zymography. Within the rib, active SL-2 expression was localized in chondrocytes of the growth plate, whereas only occasional SL-1 signal was evident. Vascular areas showed strong SL-2 staining with some proteolytic activity. SL-2, but not SL-1, was strongly expressed in osteoclasts and most mononuclear cells within the marrow. At sites of bone formation both isoforms were expressed by osteoblasts with SL-1 also present in osteoid. These results demonstrate, for the first time, the differential expression of SL-1 and SL-2 in developing human bone, indicating specific roles for the two isoforms. In situ zymography demonstrates that SL-2 is produced in an active form with associated degradation, whereas SL-1, in a matrix-bound proenzyme form, may act as a reservoir for later activation.

Glycoproteins↗

PubMed2000

Infant vocabulary development assessed with a British communicative development inventory.

Communicative Development Inventories (CDIs) were collected from 669 British children aged between 1;0 and 2;1. Comprehension and production scores in each age group are calculated. This provides norming data for the British infant population. The influence of socioeconomic group on vocabulary scores is considered and shown not to have a significant effect. The data from British infants is compared to data from American infants (Fenson, Dale, Reznick, Bates, Thal & Pethick, 1994). It is found that British infants have lower scores on both comprehension and production than American infants of the same age.

Child Language↗

PubMedDate not supplied

Development of a streptavidin-anti-carcinoembryonic antigen antibody, radiolabeled biotin pretargeting method for radioimmunotherapy of colorectal cancer. Reagent development.

With pretargeting, radioisotope delivery to tumor is decoupled from the long antibody localization process, and this can increase tumor:blood ratios dramatically. Several reagents were prepared for each step of a "two-step" pretargeting method, and their properties were investigated. For pretargeting tumor, streptavidin-monoclonal antibody (StAv-mab) conjugates were prepared by cross-linking sulfo-SMCC-derivatized streptavidin to a free thiol (SH) group on MN-14 [a high-affinity anti-carcinoembryonic antigen (CEA) mab]. Thiolated mabs were generated either by reaction of 2-iminothiolane (2-IT) with mab lysine residues or by reduction of mab disulfide bonds with (2-mercaptoethyl)amine (MEA). Both procedures gave protein-protein conjugates isolated in relatively low yields (20-25%) after preparative size-exclusion (SE) chromatography purification with conservative peak collection. Both StAv-MN-14 conjugates retained their ability to bind to CEA, to an anti-idiotypic antibody to MN-14 (WI2), and to biotin, as demonstrated by SE-HPLC. Two clearing agents, WI2 mab and a biotin-human serum albumin (biotin-HSA) conjugate, were developed to remove excess circulating StAv-MN-14 conjugates in animals. Both clearing proteins were also modified with galactose residues, introduced using an activated thioimidate derivative, to produce clearing agents which would clear rapidly and clear primary mab rapidly. At least 14 galactose residues on WI2 were required to reduce blood levels to 5.9 +/- 0.7% ID/g in 1 h. Faster blood clearance (0.7 +/- 0.2% ID/g) was observed in 1 h using 44 galactose units per WI2. For the delivery of radioisotope to tumor, several biotinylated conjugates consisting of biotin, a linker, and a chelate were prepared. Conjugates showed good in vitro and in vivo stability when D-amino acid peptides were used as linkers, biotin-peptide-DOTA-indium-111 had a slightly longer blood circulation time (0.09 +/- 0.02% ID/g in 1 h) than biotin-peptide-DTPA-indium-111 (0.05 +/- 0.03% ID/g in 1 h) in nude mice. A longer circulation time with the neutral DOTA complex might allow higher tumor uptake.

Animals↗

PubMedDate not supplied

Development and qualification of a novel virus removal filter for cell culture applications.

Commercial bioreactors employing mammalian cell cultures to express biological or pharmaceutical products can become contaminated with adventitious viruses. The high expense of such a contamination can be reduced by passing all gases and fluids feeding the bioreactor through virus inactivation or removal steps, which act as viral barriers around the bioreactor. A novel virus barrier filter has been developed for removing viruses from serum-free cell culture media. This filter removes the 20 nm minute virus of mice by >3 log reduction value (LRV), the 28 nm bacteriophage PhiX174 by >4.5 LRV, the mycoplasma Acholeplasma laidlawii by > or =8.8 LRV, and the bacteria Brevundimonas diminuta by > or =9.2 LRV. Robust removal occurs primarily by size exclusion as demonstrated over a wide range of feedstocks and operating conditions. The filtered media are indistinguishable from unfiltered media in growth of cells to high densities, maintenance of cell viability, and productivity in expressing protein product. Insulin and transferrin show high passage through the filter. The virus barrier filter can be autoclaved. The relatively high membrane permeability enables the use of a moderate filtration area.

Acholeplasma laidlawii↗

PubMed2005

Synthesis of haptens for development of antibodies to alkylphenols and evaluation and optimization of a selected antibody for ELISA development.

The development of an enzyme-linked immunosorbent assay (ELISA) based on polyclonal antibodies for a class of endocrine disrupting compounds, 4-nonylphenol, is described. The parent molecule was derivatized at the ortho position of the free phenolic hydroxyl group to obtain the hapten, NP1, and it was conjugated with keyhole limpet hemocyanin, which was used as an immunogen. Four antisera were generated and screened against three coating antigens. The most sensitive ELISA from the screening tests (antiserum NP03As, 1/1000, and coating antigen NP1-BSA, 1 microg/mL) was further optimized and characterized. The influence of various physicochemical factors (organic solvent, pH, ion strength) was investigated. Methanol as the additive organic solvent was found to be the best organic solvent for the ELISA, with optimal sensitivity observed at a concentration of 5%. The ELISA parameters were changed at more acidic or basic pH values, whereas higher ionic strengths strongly suppressed the I(50) value and the maximum absorbance. The most sensitive ELISA for 4-nonylphenol exhibited an I(50) value of 38.6 +/- 5.5 microg/L, with a dynamic range from 12 to 350 microg/L, and the lower limit of detection was 7.7 +/- 1.3 microg/L. The optimized ELISA displayed no significant cross-reaction against the parent compounds, nonylphenol ethoxylates, degradation products, carboxylates, and bisphenol A, except in 4-octylphenol.

Antibodies↗

PubMed2001

Development of a pharmacophore model for histamine H3 receptor antagonists, using the newly developed molecular modeling program SLATE.

New molecular modeling tools were developed to construct a qualitative pharmacophore model for histamine H3 receptor antagonists. The program SLATE superposes ligands assuming optimum hydrogen bond geometry. One or two ligands are allowed to flex in the procedure, thereby enabling the determination of the bioactive conformation of flexible H3 antagonists. In the derived model, four hydrogen-bonding site points and two hydrophobic pockets available for binding antagonists are revealed. The model results in a better understanding of the structure-activity relationships of H3 antagonists. To validate the model, a series of new antagonists was synthesized. The compounds were designed to interact with all four hydrogen-bonding site points and the two hydrophobic pockets simultaneously. These ligands have high H3 receptor affinity, thereby illustrating how the model can be used in the design of new classes of H3 antagonists.

Animals↗

PubMed1976

Study on sex-organ development. Oestrogen-receptor translocation in the developing chick Müllerian duct.

After oestradiol administration in vivo, 87-95% of the initial concentration of oestradiol receptor in the cytoplasm of the embryonic-chick Müllerian-duct cell was translocated into the nucleus. The process of translocation depends on the amount of oestardiol administered in vivo. At 6 h after oestradiol administration in vivo, about 30% replenishment of the initial content of the cytosol receptor was observed in the cytoplasm. The Müllerian-duct nuclei, after exposure to non-radioactive oestradiol, exhibit saturable exchange with [3H]oestradiol in vitro. The exchange of oestradiol is temperature- and time-dependent. The optimal temperature and time for exchange are 37-41 degrees C and 2h respectively. The [3H]oestradiol-receptor complex extracted from the exchanged nuclei is present in 5-6S form, and its isoelectric point is 6.8. The number of nuclear oestradiol-binding sites of the developing Müllerian duct are 1.66, 2.22, 2.63, and 2.50 pmol/mg of DNA respectively for embryos of 10, 12, 15 and 18 days. The dissociation constants of the nuclear oestradiol receptor of the four observed developmental stages range from 3.0 to 3.1 nM.

Animals↗

PubMedDate not supplied

Avian thyroid development in chemically contaminated environments: is there evidence of alterations in thyroid function and development?

Poor reproductive success, developmental abnormalities, and behavioral alterations in fish-eating birds in some Great Lakes areas have led to more than 35 years of toxicological studies and residue monitoring of herring gull (Larus argentatus) populations. Polyhalogenated aromatic hydrocarbons (PHAHs), especially polychlorinated biphenyls (PCBs), are widespread contaminants in the Great Lakes ecosystem. The introduction of regulations and elimination of point sources since the 1970s have resulted in decreased PHAHs in fish-eating bird eggs and tissues. PCB exposure is associated with thyroid disruption (hypothyroidism) in mammals, but much less is known of PCB effects on avian thyroid function. Our 1998-2000 studies of herring gulls from the Great Lakes show that both pipping embryos and prefledglings from highly contaminated sites have marked depletion of thyroid gland hormone stores compared with similarly aged gulls at the reference sites. However, organismal hypothyroidism was not apparent in many embryo and chick collections where severe depletion of thyroid gland hormone was observed. Adults, sampled at two high PCB sites and a low PCB site in the Great Lakes and the maritime reference colony in 2001, showed no differences in organismal thyroid status across sites, but gulls from the high sites had enlarged thyroid glands and depressed thyroid gland hormone stores. Here we discuss the evidence that ecological exposure to PHAHs are responsible for thyroid deficiencies in gulls and that during development these deficiencies lead to developmental abnormalities in young gulls from highly contaminated Great Lakes sites.

Animals↗

PubMed2001

[Development of a questionnaire for assessing motivational conditions for prediction of therapy cooperation of LVA insured patients during inpatient medical rehabilitation--initial results of scale development].

Medical staff working in rehabilitation often criticize their in-patients' lack of motivation to cooperate in therapy. Consequently, very often the aims of the therapy would not be reached. That, again, causes expenses that could be avoided and it also causes frustration on both sides. On the basis of Schwarzer's Health Action Process Approach (HAPA) we designed a questionnaire on motivation to predict the degree of the in-patients' cooperation in therapy during rehabilitation. The results presented here are based on an interim analysis of 508 questionnaires answered by LVA insurees (Landesversicherungsanstalten, wage earners' pension insurance funds) who had applied for rehabilitation in a clinic. The applicants suffered from illness of the back and spine as well as degenerative illness of the joints. A first examination of the scales Specific Outcome Expectancies, Specific Self-efficacy and Intention of the questionnaire showed very good statistical results as well as correlations between these variables that correspond to HAPA. It also turned out that there is a direct connection between the scores of the motivation variables (e.g. Specific Self-efficacy) and that of cooperation in therapy. These initial test results indicate a generic character of the instruments used in this research project. They also point out starting points for interventions to increase motivation that are to be developed.

Adult↗

PubMed1980

Contribution to the development of the heart. Part 1: normal development.

The formation of the relief of cardiac septa occurs in connexion with the development of shape of the external cardiac wall. Changes in the form of the external cardiac wall precede changes in the internal cardiac wall. The originally straight tubular heart is angulated at typical sites during cardiac looping. At the site of angulations the primary circular cross-section is deformed to an oval and is thereby narrowed. This deformation causes a growth of the endocardial and subendocardial tissue along the long sides of the oval to form protrusions into the cardiac lumen. These protrusions represent the anlagen of the fibrous cardiac septa. The site of origin of the fibrous septa is directly dependent on the direction of primary deformation. Origin and site of the ventricular septum results from the locally different directions and patterns of growth in the right and left ventricle. The anlagen of the cardiac septa are not isolated formations, but rather represent a continuous system of protrusions. Depending on the position and form of its components, their free edges grow towards each other and fuse wherever they meet.

Animals↗

PubMed1981

Contribution to the development of the heart. Part III: The aortic arch complex. Normal development and morphogenesis of congenital malformation.

The present paper reports our study of the developmental transformation of the aortic arch complex. A system of interarterial septa in the region of the embryonic aortic arch complex is demonstrated by means of microdissection and scanning electron microscopy. Local differences in growth of the dorsal and ventral free edges of these interarterial septa define, together with the commonly known obliteration of arterial segments, the arrangement of the origin of the great arteries. On the basis of this interarterial septal system a concept of disturbed interarterial septal growth, complemental to the long-established mechanism of obliteration, is introduced for interpretation of the formal genesis of malformations of the great arteries and their branches arising from the heart. The following pathogenetic mechanisms are suggested to contribute to the development of malformations in the aortic arch complex: 1. Increase or decrease of the number of interarterial septa 2. Excessive or reduced septal growth or deviating growth directions 3. Origin of septa in abnormal positions 4. Abnormal blending of the free edges of interarterial septa 5. Abnormal connection with the truncus septa 6. Abnormal processes of obliteration.

Animals↗

PubMedDate not supplied

[Relations between development of the apophyses of the ilial crest (Risser's sign) and development of the hand skeleton in girls with scoliosis].

The maturation of the iliac apophysis (Risser sign) and of the bones of the hand and wrist of 34 girls with scoliosis with 46 pairs of data were analyzed to get information upon their predictive value for further growth and development of the scoliotic curve. A strong correlation was found between the Risser sign and the maturation of the hand and wrist (r = 0.74, p less than 0.005). The prognostic value of the Risser sign (r = -0.57) for further height gain is superior to chronological age only (r = -0.52), the maturation of the hand and wrist (r = -0.62) however is superior to the Risser sign. It can be assumed that this also holds for their prognostic value for the progression of the scoliotic curve. We feel that in the clinician routine for girls with scoliosis the determination of the skeletal maturity from X-rays of the hand is sufficient and with its probably unavoidable irradiation risks to the gonads the determination of the Risser sign should be abandoned.

Adolescent↗

PubMed2002

Maternal stress and T-cell differentiation of the developing immune system: possible implications for the development of asthma and atopy.

The constant increase in asthma and atopy prevalences--despite improved treatment and knowledge of many aspects of the diseases--has raised growing concern. Accumulating evidence suggests that these increases in atopic diseases are largely attributable to environmental and lifestyle factors, and the lack of systemic childhood infections has in many studies emerged as a major factor. In addition to current high standards of hygiene and the lack or scarcity of such infections, another factor characteristic of our present-day lives could be involved. This review briefly outlines the possibility that prolonged maternal stress associated with sustained excessive cortisol secretion could affect the developing immune system--especially T(H)1/T(H)2 cell differentiation--and further increase the susceptibility to asthma and atopy in genetically predisposed individuals. This hypothesis is critically evaluated in the light of current knowledge.

Antigens, Differentiation, T-Lymphocyte↗

PubMed2003

Critical roles for IFN-beta in lymphoid development, myelopoiesis, and tumor development: links to tumor necrosis factor alpha.

We have generated mice null for IFN-beta and report the diverse consequences of IFN-beta for both the innate and adaptive arms of immunity. Despite no abnormalities in the proportional balance of CD4 and CD8 T cell populations in the peripheral blood, thymus, and spleen of IFN-beta-/- mice, activated lymph node and splenic T lymphocytes exhibit enhanced T cell proliferation and decreased tumor necrosis factor alpha production, relative to IFN-beta+/+ mice. Notably, constitutive and induced expression of tumor necrosis factor alpha is reduced in the spleen and bone marrow (BM) macrophages, respectively, of IFN-beta-/- mice. We also observe an altered splenic architecture in IFN-beta-/- mice and a reduction in resident macrophages. We identify a potential defect in B cell maturation in IFN-beta-/- mice, associated with a decrease in B220+ve/high/CD43-ve BM-derived cells and a reduction in BP-1, IgM, and CD23 expression. Circulating IgM-, Mac-1-, and Gr-1-positive cells are also substantially decreased in IFN-beta-/- mice. The decrease in the numbers of circulating macrophages and granulocytes likely reflects defective maturation of primitive BM hematopoiesis in mice, shown by the reduction of colony-forming units, granulocyte-macrophage. We proceeded to evaluate the in vivo growth of malignant cells in the IFN-beta-/- background and give evidence that Lewis lung carcinoma-specific tumor growth is more aggressive in IFN-beta-/- mice. Taken altogether, our data suggest that, in addition to the direct growth-inhibitory effects on tumor cells, IFN-beta is required during different stages of maturation in the development of the immune system.

Animals↗

PubMed2002

Development and evolution of lateral line placodes in amphibians I. Development.

Lateral line placodes are specialized regions of the ectoderm that give rise to the receptor organs of the lateral line system as well as to the sensory neurons innervating them. The development of lateral line placodes has been studied in amphibians since the early 1900s. This paper reviews these older studies and tries to integrate them with more recent findings. Lateral line placodes are probably induced in a multistep process from a panplacodal area surrounding the neural plate. The time schedule of these inductive processes has begun to be unravelled, but little is known yet about their molecular basis. Subsequent pattern formation, morphogenesis and differentiation of lateral line placodes proceeds in most respects relatively autonomously: Onset and polarity of migration of lateral line primordia, the type, spacing, size and number of receptor organs formed, as well as the patterned differentiation of different cell types occur normally even in ectopic locations. Only the pathways for migration of lateral line primordia depend on external cues. Thus, lateral line placodes act as integrated and relatively context-insensitive developmental modules.

Journal Article↗

PubMed2006

The development of a stable, coated pellet formulation of a water-sensitive drug, a case study: development of a stable core formulation.

A development program has been carried out to provide a stable extrusion/spheronisation pellet formulation for a highly water-soluble drug, sitagliptin, which undergoes a change in physical form on processing and is subject to hydrolytic decomposition. A conventional extrusion/spheronization formulation resulted in significant degradation of the drug. The inclusion of glyceryl monostearate into the formulation was found to reduce the water levels required to such a level that there was no significant degradation of the drug during processing to form pellets. The use of a ram extruder to screen formulations with small quantities minimizes the need for the drug in the formulation-screening process, and the results from this method of extrusion were found to be translatable to the use of a screen extruder, which allowed scale-up of the process.

Chemistry, Pharmaceutical↗

PubMed2002

Developing appropriate community-based postgraduate training in a developing country.

The School of Medical Sciences, KNUST, established in 1975, indicated its educational orientation to a community-based and community-oriented system using the problem-based learning approach. Falling victim to the phenomenon of brain-drain, the School developed a postgraduate medical curriculum which takes into account the needs and demands of national governments and communities for quality specialist care and equitable distribution of existing health facilities. There is an innovative community-based fourth year for obstetrics and gynaecology, ophthalmology, otorhinolaryngology, paediatrics, surgery and medicine. After attainment of the Part I Examination, residents are sent to Ulm, Maastricht, Britain and the United States for clinical attachments for a period of 3 to 6 months before returning to sit for their Final Part II for the Fellowship of the West African College of Surgeons or Physicians (FWACS, FWACP). By ensuring that the Final Examinations take place after the elective attachment, none of the new breed of specialists so far produced has been lost to the Western world. The strengths and weaknesses of the programme are discussed.

Journal Article↗