An online survey of the use of digital cameras by members of the British Association of Dermatologists.

The use of digital cameras by clinicians is increasing, and raises issues concerning patient consent and confidentiality. An online survey of members of the British Association of Dermatologists was conducted using an anonymous questionnaire. In total, 339 individuals completed the survey, a response rate of 37.6%. The survey shows that there are variations in the type of consent obtained by clinicians taking digital images of patients, and the methods used to store images are not always compliant with current UK legislation. Guidelines would help to improve and standardize the practice of clinicians who take digital images of patients.

A calibration method for lateral forces for use with colloidal probe force microscopy cantilevers.

A calibration method is described for colloidal probe cantilevers that enables friction force measurements obtained using lateral force microscopy (LFM) to be quantified. The method is an adaptation of the lever method of Feiler et al. [A. Feiler, P. Attard, and I. Larson, Rev. Sci. Instum. 71, 2746 (2000)] and uses the advantageous positioning of probe particles that are usually offset from the central axis of the cantilever. The main sources of error in the calibration method are assessed, in particular, the potential misalignment of the long axis of the cantilever that ideally should be perpendicular to the photodiode detector. When this is not taken into account, the misalignment is shown to have a significant effect on the cantilever torsional stiffness but not on the lateral photodiode sensitivity. Also, because the friction signal is affected by the topography of the substrate, the method presented is valid only against flat substrates. Two types of particles, 20 microm glass beads and UO3 agglomerates attached to silicon tapping mode cantilevers were used to test the method against substrates including glass, cleaved mica, and UO2 single crystals. Comparisons with the lateral compliance method of Cain et al. [R. G. Cain, S. Biggs, and N. W. Page, J. Colloid Interface Sci. 227, 55 (2000)] are also made.

The characterisation of rough particle contacts by atomic force microscopy.

An Atomic Force Microscopy (AFM) reverse imaging technique has been used to determine the contact zone topography of glass and UO3 particles in contact with flat mica substrates. A method is proposed that uses this topography to determine an effective asperity radius of curvature for the contacting particle. Application of the method has been found to be consistent with established contact mechanics models, for both glass and UO3 particle probes that present significantly different surface roughness. The method proposed is straightforward to apply and offers a greater insight into the influence of particle micro- and nano-roughness on adhesion. This is important for applications that rely on the control of granular flow such as pellet or tablet manufacture.

Automated quantitative volumetric breast ultrasound data-acquisition system.

This paper describes the development and initial testing of an automated ultrasound imaging technique to acquire quantitative volumetric breast data; the clinical application being breast cancer diagnosis and management. A novel mechanical scanner has been designed and constructed to constrain the breast tissue without compromising the image, to acquire images of the majority of the breast using a conventional B-mode scanner and to maintain patient comfort. An algorithm to improve upon simple depth-dependent amplification by compensating for tissue-dependent attenuation is applied to the images, making the grey-scale values represent local scattering properties more closely. Registration techniques have been developed to correct for geometric errors arising in the data set because of tissue movement and variations in speed of sound in the tissues. The data sets are reconstructed into volumes and viewed interactively. A pilot study of seven patients was performed and selected results are presented to illustrate lesion features. The automated scan reduces operator-dependence, provides clear information on the 3-D tissue boundaries and provides a full record for monitoring or surgical planning.

Metacarpal index and bone mineral density in healthy African-American women.

Bone mineral density (BMD) reference data of non-Caucasian women is scarce but greatly needed for African-American women. The objective of this study was to establish a metacarpal normative reference database for African-American women using digital X-ray radiogrammetry (DXR) and hand radiographs and compare these values to existing Caucasian data. Two hundred and fifty healthy African-American women between the ages of 20 and 79 years old, 14 of whom were excluded, were recruited to participate from four different clinical sites. The study population was recruited in approximately equal number into the following groups: 20-29, 30-39, 40-49, 50-59, 60-69 and 70-79 years of age. A radiograph was acquired of each subject's non-dominant hand. The radiographs were scanned and analyzed using radiogrammetric techniques, and the BMD, MCI (Metacarpal Index), bone width and cortical thickness were calculated. The regression curve that best fit the data was a second order polynomial. The BMD and MCI of young adult women (20-40 years of age) were used to calculate T-score parameters. The young reference BMD and MCI with their associated standard deviations were found to be 0.6045 g/cm2+/-0.0529 g/cm2 and 0.5096 and 0.0792, respectively. However, the MCI was found to be approximately 2.5% lower (-0.0118) compared to Caucasian women. The African-American metacarpal BMD was found to be 3.5% (0.0207 g/cm2) higher across all ages when compared to existing Caucasian reference data acquired in a similar way. The differences were found to be entirely due to larger bone size, cortical diameter and bone width in the African-American women.

Bone response to intermittent parathyroid hormone is altered in mice null for {beta}-Arrestin2.

Intermittent PTH administration increases bone turnover, resulting in net anabolic effects on bone. These effects are primarily mediated by intracellular cAMP signaling. However, the molecular mechanisms that regulate PTH activity in bone remain incompletely understood. beta-Arrestin2, a G protein-coupled receptor regulatory protein, inhibits PTH-stimulated cAMP accumulation in vitro. Using beta-arrestin2(-/-) (KO) and wild-type (WT) mice, we investigated the response to PTH in primary osteoblasts (POB) and the effects of intermittent PTH administration on bone mass and microarchitecture in vivo. Compared with that in WT mice, PTH-stimulated intracellular cAMP was increased and sustained in KO POB. Intermittent exposure of POB to PTH significantly decreased the ratio of osteoprotegerin (OPG) receptor activator of nuclear factor-kappaB ligand (RANKL) mRNA expression in KO POB, whereas it increased this ratio in WT POB. Total body bone mass and cortical and trabecular bone parameters were 5-10% lower in male KO mice compared with WT, and these differences were magnified upon in vivo administration of intermittent PTH (80 mug/kg.d) for 1 month. Thus, PTH significantly increased total body bone mineral content as well as vertebral trabecular bone volume and thickness in WT, but not KO mice. The anabolic response to PTH in cortical bone was also slightly more pronounced in WT than KO mice. Histomorphometry indicated that PTH prominently stimulated indexes of bone formation in both WT and KO mice, whereas it significantly increased indexes of bone resorption (i.e. osteoclast number and surface) in KO mice only. In conclusion, these results suggest that beta-arrestins may specify the activity of intermittent PTH on the skeleton by limiting PTH-induced osteoclastogenesis.

Astrocyte and endothelial cell expression of ADAM 17 (TACE) in adult human CNS.

ADAM 17, also known as TACE, is an important sheddase for a number of proteins, including tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-alpha (TGF-alpha), L-selectin, p75, and p55 TNF receptors, and interleukin-1 receptor II (IL-1RII). The presence of ADAM 17 mRNA in adult mouse and rat CNS was recently reported (Karkkainen et al. Mol Cell Neurosci 15:547-560, 2000). However, the cellular origin of ADAM 17 remains unknown. In this study, we have used an anti-ADAM 17 antibody in an immunohistochemical study of its distribution in human adult CNS tissue. Cells with astrocytic and endothelial morphology were ADAM 17-positive. This finding was further confirmed using double immunofluorescence with antibodies against GFAP and von Willebrand factor, which label astrocytes and endothelial cells, respectively. This study demonstrates that ADAM 17 is expressed by astrocytes and endothelial cells in normal brain tissue and may have a role in normal brain function.

Fibroblast growth factor-2 inhibits myelin production by oligodendrocytes in vivo.

Fibroblast growth factor-2 (FGF-2) controls in part the timely differentiation of oligodendrocytes into the myelin-producing cells of the CNS. However, although differentiated oligodendrocytes express FGF receptors (R), the effect of FGF-2 on myelin-producing oligodendrocytes in vivo was unknown. In the present study, we show that delivery of FGF-2 into the cerebrospinal fluid of anaesthetized rat pups, aged postnatal day (P) 6 to 9, induced a severe loss of myelin in the caudal anterior medullary velum (AMV). Furthermore, we show that the caudal AMV was myelinated at the time of treatment, so the effects of FGF-2 represent a loss of myelin and not delayed differentiation. This was confirmed by injection of platelet-derived growth factor-AA (PDGF-AA), a factor known to affect the differentiation of PDGF-alphaR expressing oligodendrocyte progenitors, but which did not induce myelin loss in the caudal AMV and did not affect differentiated oligodendrocytes, which do not express PDGF-alphaR. Compared to controls treated with saline or PDGF-AA, FGF-2 induced an accumulation of PLP protein and MBP mRNA within the somata of myelin-producing oligodendrocytes. The results indicate that FGF receptor signalling disrupts myelin production in differentiated oligodendrocytes in vivo and interrupted the transport of myelin-related gene products from the oligodendrocyte cell body to their myelin sheaths.

Investigations into an unknown organism on the martian meteorite Allan Hills 84001.

Examination of fracture surfaces near the fusion crust of the martian meteorite Allan Hills (ALH) 84001 have been conducted using scanning electron microscopy (SEM) and atomic force microscopy (AFM) and has revealed structures strongly resembling mycelium. These structures were compared with similar structures found in Antarctic cryptoendolithic communities. On morphology alone, we conclude that these features are not only terrestrial in origin but probably belong to a member of the Actinomycetales, which we consider was introduced during the Antarctic residency of this meteorite. If true, this is the first documented account of terrestrial microbial activity within a meteorite from the Antarctic blue ice fields. These structures, however, do not bear any resemblance to those postulated to be martian biota, although they are a probable source of the organic contaminants previously reported in this meteorite.

In vivo actions of fibroblast growth factor-2 and insulin-like growth factor-I on oligodendrocyte development and myelination in the central nervous system.

The in vivo effects of fibroblast growth factor-2 (FGF-2) and insulin-like growth factor-I (IGF-I) on oligodendrocytes and CNS myelination were determined in the postnatal rat anterior medullary velum (AMV) following injection of both cytokines into the cerebrospinal fluid. Either FGF-2, IGF-I, or saline were administered via the lateral ventricle, twice daily commencing at postnatal day (P) 6. At P9, AMV were immunohistochemically labeled with the Rip antibody, to enable analysis of the numbers of myelin sheaths and of promyelinating and myelinating oligodendrocytes; promyelinating oligodendrocytes are a recognisable immature phenotype which express myelin-related proteins prior to forming myelin sheaths. In parallel experiments, AMV were treated for Western blot analysis to determine relative changes in expression of the myelin proteins 2', 3'-cyclic nucleotide 3'-phosphohydrolase (CNP) and myelin oligodendrocyte glycoprotein (MOG), which, respectively, characterise early and late stages of myelin maturation. In FGF-2-treated AMV, the number of promyelinating oligodendrocytes increased by 87% compared to saline-injected controls. The numbers of myelinating oligodendrocytes and myelin sheaths were not decreased, but conspicuous unmyelinated gaps within fibre tracts were indications of retarded myelination following FGF-2 treatment. Western blot analysis demonstrated decreased expression of CNP and a near-total loss of MOG, confirming that FGF-2 decreased myelin maturation. In contrast, IGF-I had no effect on the number of promyelinating oligodendrocytes, but increased the numbers of myelinating oligodendrocytes and myelin sheaths by 100% and 93%, respectively. Western blot analysis showed that the amount of CNP was increased following IGF-I treatment, correlating with the greater number of oligodendrocytes, but that MOG expression was lower than in controls, suggesting that the increased number of myelin sheaths in IGF-I was not matched by increased myelin maturation. The results provide in vivo evidence that FGF-2 and IGF-I control the numbers of oligodendrocytes in the brain and, respectively, retard and promote myelination.

The epidemiology of osteoporosis. Practical implications for patient care.

The new definition of osteoporosis moves this disorder from a disease of fractures to a disease of fracture risks. Like blood lipids and blood pressure, bone mineral density is now viewed as a predictor of possible problems. Through careful history taking and physical examination, primary care physicians can identify patients in whom intervention is likely to prevent the anguish of broken bones and lost mobility. In this article, Drs Goddard and Kleerekoper discuss the new diagnostic criteria and what they mean for your patients.

Phospholipase A2 activating protein induces tumor regression.

There has been increasing interest in attempts to harness the body's normal inflammatory response mediated through the eicosanoid pathway to treat tumors. Accumulating data indicate that the growth of several different cancers is modulated by a group of pro-inflammatory bioactive lipids, the best known of which are the eicosanoids. Eicosanoid pathway constituents modulate cell function in several important ways, and an agent that activates PLA(2) and up-regulates LTB(4) levels could be expected to be an effective cytotoxic tumor agent, especially if it stimulated NK cells. PLAP is a 28-kDa polypeptide that is a member of the WD-repeat protein, G-protein-transducin superfamily. The pro-inflammatory properties of PLAP have been elucidated using a number of different approaches. PLAP has been found in inflamed tissues and synovial fluid from patients with rheumatoid arthritis. Based on knowledge of PLAP as a pro-inflammatory agent, its capacity to modulate the immune response and the role of the inflammatory and immune responses in immune surveillance, the role of PLAP in cancer therapy was explored. Significant tumor regression was observed 72 hours following a single treatment with PLAP in an animal air pouch model of glioma. PEG-PLAP treatment increased the life expectancy of animals with Lewis lung cancer, and in preliminary studies in MTVL breast tumors in mice, PLAP treatment resulted in a similar increase in life expectancy. These findings suggest that PLAP holds promise as a potential therapy for cancer, and warrants further study.

Atomic force microscopy imaging of fragments from the Martian meteorite ALH84001.

A combination of scanning electron microscopy (SEM) and environmental scanning electron microscopy (ESEM) techniques, as well as atomic force microscopy (AFM) methods has been used to study fragments of the Martian meteorite ALH84001. Images of the same areas on the meteorite were obtained prior to and following gold/palladium coating by mapping the surface of the fragment using ESEM coupled with energy-dispersive X-ray analysis. Viewing of the fragments demonstrated the presence of structures, previously described as nanofossils by McKay et al. (Search for past life on Mars--possible relic biogenic activity in martian meteorite ALH84001. Science, 1996, pp. 924-930) of NASA who used SEM imaging of gold-coated meteorite samples. Careful imaging of the fragments revealed that the observed structures were not an artefact introduced by the coating procedure.

Knowledge and experience of drug use amongst church affiliated young people.

A large and growing proportion of young people in the UK are using drugs. Research from the US suggests a protective effect of church affiliation or 'religiosity', but this has not been investigated in British young people. In the present study, the prevalence of drug use was estimated amongst 7666 church affiliated young people in the UK in 1995, using a self report questionnaire survey. In the 12-16 year old age group, 23.4% had been offered at least one of a list of drugs, and 9.7% had tried such drugs. In those aged 17-30 years the figures were 46.1% and 23.3%, respectively. These figures are perhaps slightly less than, those obtained in secular surveys. Those who gave more positive responses to questions on Christian commitment were less likely to have been offered any of the listed drugs, or to have used them, as compared with those who gave no such responses. A lifetime history of ever having smoked demonstrated a far stronger association, with smokers being 15-20 times more likely to have used one of the listed drugs.

Phospholipase A2-mediated inflammation induces regression of malignant gliomas.

An ideal form of cancer therapy is the harnessing of innate immunity to eradicate spontaneously arising clones of malignant cells. To date, attempts to develop effective immunotherapies have met with limited success. Prostaglandins and leukotrienes, collectively known as eicosanoids, are important mediators of immune and inflammatory responses. Harnessing these compounds could be a method to treat cancers. Eicosanoids are formed after cleavage of fatty acids from phospholipids by phospholipase enzymes. We have previously described, characterized and cloned a naturally occurring mammalian activator of phospholipase A2. Injection of a 24 amino acid peptide from this phospholipase A2 activating protein (PLAP), resulted in induction of an acute inflammatory response, and a concomitant regression of gliomas in rats. Administration of 500 micrograms of this protein resulted in a 50% decrease of the tumor mass within 72 h. Tumor regression coincided with a greater than twenty-fold increase in levels of prostaglandin E2(PGE2) and leukotriene B4(LTB4), and a marked infiltration of natural killer(NK) cells. These data suggest that activation of phospholipase A2 and modulation of the eicosanoid biosynthetic pathway may provide a novel therapeutic strategy for the successful treatment of malignant tumors of the nervous system.

Myocardial protection for acquired heart disease surgery: results of a national survey.

To study current myocardial protection practices, all 4,393 United States board-certified thoracic surgeons were surveyed in 1992. Of the 1,413 respondents (32% total response), 936 are in active practice dealing with acquired heart disease. Based on their frequency of cases, respondents perform approximately 32% of all acquired heart disease operations in the United States yearly and individually average 157 patients/year. For myocardial protection, 98% of respondents routinely use cardioplegic arrest. The primary method of cardioplegia delivery is antegrade 36%, retrograde 4%, and a combination of antegrade and retrograde 60%. The types of cardioplegic solutions used are blood 72%, crystalloid 22%, and oxygenated crystalloid 6%. Continuous warm blood cardioplegia is used by 10% of respondents, whereas most (75%) have adopted a skeptical "wait and see" attitude or have abandoned it (6%). Overall, most surgeons (78%) report that they are very satisfied with their present methods of myocardial protection, whereas only 2% are dissatisfied. Still, the three areas believed most important for future research are reperfusion injury (74%), acutely infarcting myocardium (61%), and metabolic enhancers in cardioplegia (58%).

Regulation of synovial cell growth. Coexpression of transforming growth factor beta and basic fibroblast growth factor by cultured synovial cells.

OBJECTIVE: To demonstrate expression of transforming growth factor beta (TGF beta) and basic fibroblast growth factor (bFGF) by cultured rheumatoid arthritis (RA) synovial cells and to investigate their role as synovial cell mitogens. METHODS: Polypeptide growth factors were detected and identified by immunocytochemical staining and Western blot analysis. Messenger RNA (mRNA) transcripts encoding TGF beta and bFGF were identified by polymerase chain reaction analysis. The influence of neutralizing growth factor monoclonal antibodies (MAb) on RA synovial cell growth was investigated. TGF beta bioactivity was determined by Mv1Lu assay. RESULTS: Lysates of RA, as compared with normal, synovial cells contained greater amounts of TGF beta and bFGF. Western blot analysis identified a single TGF beta band (MW approximately 25 kd) in each of the cell lysates examined. Western blot analysis using MAb DE6 identified a doublet of bFGF bands (MW approximately 18.0 kd) in normal synovial cell lysates and 4 bFGF bands (MW approximately 18.0, 22.0, 22.6, and 25.2 kd) in RA synovial cell lysates. RA and normal synovial cells expressed mRNA transcripts encoding TGF beta 1 but not TGF beta 2, and FGF-2 (basic FGF). Additional mRNA transcripts encoding FGF-5 and FGF-7 were expressed by RA, but not normal, synovial cells in culture. In contrast to MAb 1D11.16, which caused a dose-dependent decrease in RA synovial cell growth, MAb DG2 (up to 100 micrograms/ml) had no effect on cell growth. CONCLUSION: RA and normal synovial cells cultured in serum-free medium express TGF beta 1 and native bFGF. However, only RA synovial cells in culture express higher molecular weight isoforms of bFGF. TGF beta 1 appears to regulate synovial cell growth in vitro through an external autocrine loop. Despite expression of high-affinity bFGF receptors on cultured synovial cells, the mechanisms by which bFGF modulates synovial cell growth are unknown.