Translating an academic module into an online resource.

Blended learning, which combines face-to-face sessions with online work, is used to provide flexible learning and courses for students who are geographically dispersed. Canterbury Christ Church University recognised the importance of developing an academic module for dispensing opticians across the UK and the requirement to address the needs of an increasingly diverse population of students. Following interest in the module from the Association of British Dispensing Opticians, a decision was made to reformat the module into an online resource. This article describes some of the pedagogical processes involved in developing the online resource. Quantitative and qualitative data are analysed to identify challenges and successes. The importance of developing an educational biography to achieve depth of understanding and thought is acknowledged. The article concludes that some face-to-face interaction is still necessary, not least for helping to reduce students' anxiety.

A test of founder effect speciation using multiple loci in the auklets (Aethia spp.).

Whether speciation results more frequently from the genetic consequences of founder events or from gradual genetic divergence of large populations is a matter of debate. In this study, multiple analyses were applied to data from three loci (cytochrome b, alpha-enolase intron VIII, and MHC class II B) to test for founder effects associated with speciation in Aethia (Aves: Alcidae), a genus of seabirds thought to have undergone a rapid founder-induced radiation. Effective population sizes (N(e)) were derived from estimators of based on allelic diversity and the coalescent and from data on trans-species polymorphism. Results indicated that N(e) has been on the order of 10(5)-10(6) individuals throughout the evolutionary histories of least and crested auklets (A. pusilla and A. cristatella, respectively) and that N(e) of the ancestral species was at least 16,000 individuals. Computer simulations of MHC evolution indicated that a single-generation bottleneck at speciation could not have involved <85 individuals for each species. More moderate simulation scenarios indicated that population size could not have dropped below 2000 individuals at the time of species founding. Demographic history appears to have been stable for the auklets throughout the past several million years, and a founder effect associated with their speciation is unlikely.

Bone mineral content and collagen metabolites in children receiving steroid treatment for nephrotic syndrome.

UNLABELLED: Bone mineral density (BMD) and content (BMC) were measured in nine children treated with corticosteroids for nephrotic syndrome and in age-matched controls, using dual-energy X-ray absorptiometry (DEXA). The urinary excretion of cross-linked N-telopeptide (NTx) released from collagen type I as a specific marker of bone resorption was also measured. There were no significant differences in body size, BMD results or NTx urinary concentrations between patients and controls, nor could any significant differences be found when the six patients given a cumulative corticosteroid dose of >15 g were analysed separately. The lack of significant differences could be due to the small number of patients included in the study. But when the measured BMD and BMC were analysed according to methods that corrected for body size and puberty stage, values well within the normal range were found in patients as well as in controls. There was, however, a significant, negative correlation between the urinary excretion of NTx and the cumulative dose of corticosteroids. CONCLUSION: Despite treatment for long periods with high, cumulative doses of corticosteroids, the skeletons of the patients had a normal mineral content, which is encouraging for all those in need of steroids for nephrotic syndrome. A negative correlation between urinary collagen degradation products and the cumulative steroid dose might point to a reduced growth velocity in patients on high doses of steroids earlier than an effect on bone mineralization.

Relieving the pressure in the radiology department.

Interventional radiological procedures can be complex, requiring patients, many of whom already have compromised arterial circulation, to lie immobile for significant periods. X-ray table mattresses are designed to avoid radiation attenuation, which could degrade image quality or increase patient dose. Consequently, most mattresses do not have pressure redistribution properties. Skin changes, noted after lengthy radiological procedures, would appear to indicate that this unrelieved pressure places vulnerable patients at risk of sustaining pressure damage that could potentially initiate pressure ulcer development. This article examines the biomedical basis of pressure ulcer development, and discusses the suitability of alternative support devices for radiological examinations in an apparently under-researched environment.

Adverse reactions to contrast media.

Knowledge of the physiological effects of contrast media helps radiology nurses to prepare patients fully. Hypersensitive reactions can progress rapidly so immediate nursing interventions and medical assistance are required. Pre-assessment, psychological support, vigilance, integrated monitoring and decision-making are the most effective prophylaxis.

Urinary calcium excretion in Swedish children.

Urinary calcium excretion was measured in an unselected population of 153 healthy Swedish children aged 2-18 years. Urine was collected after an ordinary meal. Urinary calcium excretion was measured as the calcium/creatinine concentration ratio (UCa/Cr) and expressed in mmol/l per mmol/l. UCa/Cr was 0.44 +/- 0.379 (mean +/- SD). As the UCa/Cr in this childhood population was not distributed in a normal manner, the results are more correctly presented as the 50th (0.33) and 97th (1.5) centiles. There was a weak but significant correlation between UCa/Cr and age, with higher values in the lower age groups. There was no correlation between UCa/Cr and the anamnestic intake of cow's milk. Repeated samples from some children showed a coefficient of variation between days of 30-40%. The upper limits of normal UCa/Cr (97th centile = 1.5; +2 SD = 1.2) in this investigation were higher than what is considered normal by others. In spite of this, none of the children had a history of renal stone disease or any other symptoms of hypercalciuria. Renal stone disease is thought to be rare in Swedish children although the real incidence is not known. The diagnosis of hypercalciuria should be based on repeated samples from an individual with symptoms and related to age-related reference values from the same population group.

Mathematical modelling of retinal tear formation: implications for the use of heavy liquids.

When force is applied to detached retina it elevates, stretches, and becomes irreversibly deformed. Finally it tears, and the timing and location of tear formation are determined by the distribution of stress within the retina. This stress distribution is dependent upon the retinal contour. We have tested this using retinas of freshly enucleated bovine eyes. A suture was attached to isolated retinal tissue using butylacrylate (Histoacryl) glue and traction was applied to this suture so stretching the retina. We present a mathematical model of the in vitro data obtained, with predictions for local retinal internal tensions. We show that these are altered by the addition of hydrostatic forces due to the presence of heavy liquids. These findings have implications for epiretinal membrane dissection during surgery and for the use of heavy liquids during membrane peeling.

Mathematical modelling of the elastic properties of retina: a determination of Young's modulus.

The retina can be regarded as an elastic membrane or sheet which stretches and deforms when a force is applied to it. Isolated bovine retina was taken and a graded traction force applied to determine retinal profile as a function of force. The resulting profile can be modelled mathematically and the model then used to determine a value for the elastic constant. The value of the elastic constant obtained by this method is approximately 2 N/m. This value of the elastic constant, combined with the observed retinal thickness, yields a value of Young's modulus for retina of approximately 2 x 10(4) Pa, which is about 2 orders of magnitude weaker than typical rubber. This value can then be used in modelling retinal behaviour in vivo when forces are applied to detached retina.

Bradykinin, a new potential mediator of inflammation-induced bone resorption. Studies of the effects on mouse calvarial bones and articular cartilage in vitro.

The effect of bradykinin and desArg9-bradykinin on bone was studied in cultures of calvarial bones taken from 6-7-day-old mice. Bradykinin, at and above a 3-nM concentration, caused a dose-dependent stimulation of bone mineral mobilization and matrix degradation. Bradykinin-stimulated resorption was inhibited by calcitonin, an increased concentration of phosphate in the culture medium, hydrocortisone, dexamethasone, indomethacin, meclofenamic acid, naproxen, and 5, 8, 11, 14-eicosatetraenoic acid. The results suggest that bradykinin stimulates osteoclast-mediated bone resorption by a process that is dependent on endogenous prostaglandin production. The stimulatory effect of bradykinin, but not of parathyroid hormone and prostaglandin E2, was potentiated by the angiotensin-converting enzyme inhibitor, BPP5a. Treatment with carboxypeptidase B did not affect the capacity of the peptide to stimulate 45Ca release. DesArg9-bradykinin (1 mumole/liter) stimulated 45Ca release to the same degree as did bradykinin. Bradykinin (3 microM) did not affect the degradation of cartilage proteoglycans, as assessed by the release of 35S-sulfate from prelabeled calf articular cartilage in organ culture. These findings suggest that generation of bradykinin in inflammatory lesions of rheumatoid arthritis and periodontitis may contribute to the bone resorptive process seen in the joints and alveolar bone; however, bradykinin does not directly activate chondrocytes into a catabolic state.

Enhanced breakdown of bovine articular cartilage proteoglycans by conditioned synovial medium in vitro. The effect of glycosaminoglycan polysulfate.

The effect of glycosaminoglycan polysulfate (GAGPS, Arteparon) upon the breakdown of calf articular cartilage proteoglycans has been studied in vitro. GAGPS had no significant effect upon this breakdown when cartilage was cultured alone but significantly reduced the breakdown enhanced by conditioned medium from organ cultures of calf synovial membrane. Culturing the synovial membrane in the presence of GAGPS did not alter the capacity of conditioned medium to degrade cartilage proteoglycans.

The effect of continuous mechanical pressure upon the turnover of articular cartilage proteoglycans in vitro.

Fragments of calf articular cartilage maintained in organ culture were subjected to continuous mechanical pressure applied by means of lead weights of differing sizes. Increasing the pressure from approximately 7.5-30 kgfcm-2 proportionately decreased the breakdown of proteoglycans as measured by the release of [35S]sulphate from prelabeled cartilage. The difference was observed as early as 24 hours after culture. During the first 24 hours after removal of a 30 kgfcm-2 pressure the release of [35S]sulphate was slightly greater than that of the nonweight-bearing controls and then subsequently returned to the level of the controls. Application of a mechanical pressure of 30 kgfcm-2 to calf articular cartilage reduced the incorporation of [35S]sulphate to about half the level of the nonweight-bearing controls. A pressure of 15 kgfcm-2 had no significant effect upon [35S]sulphate incorporation. The production of lactate by the cartilage under the influence of 30 kgfcm-2 for 4 days was not significantly different from that of nonweight-bearing controls indicating the retained viability of the tissue. The present study indicates that proteoglycan metabolism of calf articular cartilage in vitro is capable of responding rapidly to variations in applied load. The potential importance of this finding in terms of the functional demands of articular cartilage is apparent, and it can be speculated that a failure of this adaptability of the chondrocytes is an important factor in the etiology of degenerative joint disease.

Enhanced breakdown of bovine articular cartilage proteoglycans by conditioned synovial medium in vitro: a possible role for prostaglandins.

Addition of conditioned medium derived from fragment cultures of synovium dissected from bovine knee joints (SM) to cultures of articular cartilage derived from the same animal resulted in a significant increase in breakdown of cartilage proteoglycans, measured as the release of [35S]sulphate from pre-labelled cartilage pieces. Culturing the synovium in the presence of indomethacin (indo-SM) at a concentration of 1.4 x 10(-5) mol/l reduced the breakdown-enhancing effect of the SM in some but not in all of the experiments. Addition of prostaglandins E1 or E2 (PGE1 or PGE2) (2.8 x 10(-7)-1.4 x 10(-5) mol/l) together with indo-SM resulted in a significant enhancement of breakdown of cartilage proteoglycans. PGA1, PGB1 and PGF2 alpha(less than 1.5 x 10(-5) mol/l) had, however, no effect in this system. Neither PGE1, PGE2 nor indomethacin at the concentrations mentioned above had any direct effect on breakdown of cartilage proteoglycans. No difference was found between the breakdown enhancing capacity of SM derived from synovium cultured in the presence of indo plus PGE1 or PGE2 (less than 4 x 10(-5) mol/l) and indo-SM. These findings are discussed in terms of cellular interactions.

Enhanced breakdown of bovine articular cartilage proteoglycans by conditioned synovial medium. The effect of serum and dextran sulphate.

Medium from cultured bovine synovial membrane when applied to articular cartilage from the same animal enhanced proteoglycan breakdown, as measured by the release of [35S]sulphate from prelabelled cartilage, principally by activating chondrocytes to secrete or activate their own enzymes. This effect persisted whether or not the synovium was cultured in medium containing fetal calf serum. The release of proteoglycans from cartilage was markedly enhanced when the synovium was cultured in the presence of dextran sulphate (200 micrograms/ml), while dextran sulphate had no effect upon cartilage alone or when added together with medium cultured in the absence of dextran sulphate. Since the release of the proteoglycan breakdown products from frozen and thawed cartilage was not stimulated by dextran sulphate, this agent appeared to be enhancing the indirect chondrocyte-mediated effect of synovial medium rather than the direct proteolytic enzyme-induced effect. A possible mechanism for the production of a substance responsible for the chondrocyte-mediated matrix degradation is proposed, involving monocyte-like or macrophage-like cells, either resident in the synovial tissue or derived from the circulation.

Enhanced breakdown of bovine articular cartilage proteoglycans by conditioned synovial medium in vitro. The effect of glucocorticoids and protein synthesis inhibitors.

Addition of conditioned synovial medium (SM) from cultured calf knee-joint synovium to cultures of articular cartilage from the same animal resulted in a significant increase in breakdown of cartilage proteoglycans. Culturing the synovium in the presence of glucocorticoids (hydrocortisone, dexamethasone, prednisolone) or protein synthesis inhibitors (cycloheximide or actinomycin D) reduced the breakdown effect. In contrast, enhancement of proteoglycan breakdown was observed when the cartilage was exposed to glucocorticoids in the presence of SM from synovium cultured without these drugs (control SM). The stimulatory effect on cartilage breakdown of control SM or control SM + glucocorticoids was markedly reduced in the presence of actinomycin D or cycloheximide. The authors conclude that glucocorticoids under certain conditions enhance cartilage degradation and therefore, although they exert the temporary anti-inflammatory effects, treatment of joint diseases with glucocorticoids may not be beneficial in the long-term.

The effect of diphenylhydantoin upon degradation of sulphated macromolecules in cat palatal mucosa in vitro.

The effect of diphenylhydantioin (DPH) upon the degradation of in vivo [35S]-sulphate-labelled proteoglycans was studied in cat palatal mucosa during organ culture. 8-week-old cats were injected intraperitoneally with [35S]-sulphate and 24 hours later the palatal mucosa was taken to organ culture. The release of radioactivity into the culture medium was taken as a measure of degradation of sulphated macromolecules, presumably proteoglycans, and the release of hydroxyproline as an indicator for collagen degradation. A parallel decrease in the release of radioactivity and in the release of hydroxyproline was observed when the culture was done in the presence of DPH (20 mg/l). Chromatography of the culture medium upon Sephadex G-25 revealed that the reduced release of radioactivity was due to a reduction of macromolecular degradation products leaving the amounts of free sulphate in the medium unchanged. The results were interpreted using a two compartment theory for proteoglycan degradation, extracellular breakdown of the protein core resulting in the production of macromolecular degradation products and intracellular lysosomal degradation resulting in free sulphate as the identifiable product. The results indicate that DPH inhibited the extracellular enzymatic degradation of proteoglycans without influencing their intracellular degradation.

The glycosaminoglycans of human articular cartilage: molecular weight distribution of chondroitin sulphate in different layers in the adult individual.

Articular cartilage from 3 human femoral heads was sectioned serially, at 200 micron thickness, parallel to the articular surface. The morphologically normal cartilage was compared with superficially fibrillated cartilage. Sections from 5 or 6 defined layers representing the cartilage bulk were pooled and the sodium salt of chondroitin sulphate was isolated from each layer. The molecular weight distribution of the chondroitin sulphate was determined by either Sephadex G-200 or Sephacryl S-200 gel chromatography. For the normal articular cartilage from the 3 individuals a reduction of the average molecular weight of the chondroitin sulphate from the articular surface to the cartilage-bone junction was observed. In the superfically fibrillated cartilage superficial layer chondroitin sulphate had a smaller average molecular weight than the corresponding normal cartilage of the same femoral head.

The glycosaminoglycans of human articular cartilage: concentration and distribution in different layers in the adult individual.

The articular cartilage from morphologically normal femoral heads from 7 humans, aged 50-85 years, was sectioned parallel to the surface firstly at 40 micron thickness and then serially at 200 micron thickness to the cartilage-bone junction. Pooled sections from separate layers were used for analysis of the glycosaminoglycans by Cetylpyridinum chloride and ECTEOLA-cellulose microcolumns. The total concentration of glycosaminoglycans per dry weight tissue showed an increase with distance from the articular surface. The increase was shown to be due, principally, to keratan sulphate, while the levels of hyaluronic acid and chondroitin sulphate showed a proportional decrease with depth. The 40 micron thick superficial layer contained a considerably lower concentration of both keratan sulphate and chondroitin sulphate than the rest of the cartilage. These superficial layer glycosaminoglycans, and particularly chondroitin sulphate, showed a more polydisperse distribution according to molecular weight/charge density than the corresponding glycosaminoglycans of the more deeply situated layers. In view of findings on bovine articular cartilage of different age-classes reported previously, these features of the superficial layer appear to represent the normal biochemical structure.

Chondroitin sulphate of calf knee-joint cartilage.

Chondroitin sulphate from different layers of calf knee-joint cartilage has been isolated and purified. Analysis for hexosamine, uronic acid, sulphate and relative proportions of the 4- and 6-isomers revealed no differences between the layers. However, an increase in the average molecular weight of the chondroitin sulphate was found to correspond with distance from the articular surface. In particular, the average molecular weight in the epiphyseal cartilage was significantly higher than that in the articular cartilage. The chondroitin sulphate of the 40-mu-mthick articular surface layer was found to have a higher molecular weight than the rest of the articular part of the cartilage and also to be more polydisperse. These results, regarding molecular size, are in agreement with the cetylpyridinium chloride cellulose microcolumn fractionation patterns.