Septicaemia and septic arthritis in a neonatal calf caused by Lactococcus lactis.
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Animals↗
Biomedical subjects
A Stephenson
Publications and source records attributed to A Stephenson.
Teaching professional development in medical schools.
Doctors must increasingly be aware of what they should be, as well as what they should know. Professionalism, including a value system that supports the compassionate care of patients, is a means of encapsulating and prioritising these competing responsibilities. Accordingly, in this article, we assume that professionalism is an essential aspect of medical practice that needs to be taught to those entering medicine. We first describe critiques of professionalism and current challenges to it, in practice and in medical education. We then assess the current efforts of curriculum reform to incorporate professionalism and the methods used to teach it. Adopting and assessing such approaches to ensure that they are effective is of central importance in the education of future clinicians.
Clinical Competence↗
Metals in tissues of European otters (Lutra lutra) from Denmark, Great Britain and Ireland.
Samples of livers of European otters from Denmark, Great Britain and Ireland were analyzed for manganese, chromium, zinc, copper, nickel and cobalt. Concentrations were generally significantly higher in samples from Great Britain. It was considered that this reflected the catchment geology from where the specimens originated.
Animals↗
Superior epithelial arcuate lesions with soft contact lens wear.
BACKGROUND: Superior epithelial arcuate lesions (SEALs) are an infrequent and often asymptomatic complication of conventional soft contact lens wear. The characteristic arcuate pattern of the full-thickness corneal epithelial lesion usually occurs in the area covered by the upper eyelid, within 2 to 3 mm of the superior limbus in the 10- and 2-o'clock region. METHODS: Literature on SEALs and recent clinical records from clinical trials using two types of prototype high Dk soft contact lenses were reviewed to gain greater insights into the etiology of SEALs. RESULTS AND CONCLUSIONS: The reported low incidence of SEALs is partly because SEALs are not usually symptomatic. The etiology of SEALs is multifactorial. Our current hypothesis is that SEALs are produced by mechanical chaffing at the peripheral cornea. This chaffing occurs as a result of inward pressure of the upper lid, in an area where the peripheral corneal topography and lens design, rigidity, and surface characteristics combine to create excessive "frictional" pressure and abrasive shear force on the epithelial surface. Patient characteristics such as gender, age, and specific corneal and lid topographies also appear to influence the occurrence of SEALs. Prototype silicone hydrogel lenses are made from higher modulus materials with surfaces that seem to differ subtly in wettability in some patients. The prevalence of SEALs may well increase with the first generations of these lenses.
Clinical Trials as Topic↗
Effect of endotoxin on oleic acid lung injury does not depend on priming.
Recent studies have demonstrated significant synergistic physiological and biochemical effects between low-dose endotoxin (Etx) administration and oleic acid (OA)-induced canine lung injury. To evaluate whether this interaction depends on Etx priming of some key cell population, we compared the effects of giving low-dose Etx both after as well as before inducing lung injury with OA. In addition to hemodynamic and blood-gas measurements, positron emission tomographic imaging was used to measure edema accumulation and intrapulmonary blood flow distribution. Biochemical measurements of the stable metabolites of prostacyclin and thromboxane were obtained as well as measurements of isoprostanes and reactive sulfhydryls as evidence for possible concomitant oxidant production. We found that the physiological and biochemical effects of low-dose Etx developed 30-45 min after its administration, regardless of whether Etx was administered before or after OA. No increase in either isoprostane or reactive sulfhydryl production after Etx and/or OA was detected. These data suggest that the synergistic effect of low-dose Etx and OA-induced lung injury is not due to a priming effect of Etx.
Animals↗
Student learning centres in the community: a review of an organisation model.
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Community Health Centers↗
The relationship of genotype to cognitive outcome in galactosaemia.
AIMS: To evaluate the cognitive outcome of a cohort of children with galactosaemia in relation to genotype. METHODS: The cohort was drawn from children notified to the British Paediatric Surveillance Unit galactosaemia study which ran from 1988 to 1990. Cognitive outcome was assessed using the Wechsler Intelligence Scale for Children or the Wechsler Preschool and Primary Scale of Intelligence. Parents completed a questionnaire detailing educational status, and the attending paediatrician returned a questionnaire regarding age at diagnosis and biochemical outcome over the previous two years. RESULTS: A total of 45 children were genotyped: 30 were homoallelic for the Q188R mutation, the remainder being heteroallelic for Q188R with K285N (n = 4), L195P (n = 4), or other mutations (n = 7). Psychometric evaluation was available in 34 cases: mean full scale IQ was 79, verbal quotient 79, and performance quotient 82. Genotype was not related to galactose-1-phosphate (Gal-1-P) concentrations. However, children homoallelic for the Q188R mutation had significantly lower IQ scores than those who were heteroallelic (73. 6 v 94.8). This difference was independent of social and demographic influences and Gal-1-P concentrations over the previous two years. CONCLUSIONS: In children with galactosaemia, cognitive outcome appears to relate to genotype rather than metabolic control, as reflected by Gal-1-P concentrations. The value of measuring Gal-1-P concentrations routinely once successfully established on a galactosaemia diet is questionable as concentrations do not appear to affect outcome. In the UK population, homozygosity for the Q188R mutation is invariably associated with a poor outcome, and there is evidence that variability in neurocognitive outcome is at least part dependent on allelic heterogeneity.
Child↗
Single-handed practices--their contribution to an undergraduate teaching network in the first year of the new curriculum.
OBJECTIVES: The new curriculum at King's College School of Medicine and Dentistry, which commenced in September 1996, requires all medical undergraduates to have a general practice placement throughout the 5 years of their medical education. DESIGN: This paper discusses recruitment, training and support of teaching practices for the new curriculum, reviews the distribution of single-handed general practices in the network and, via a selection of monitoring and evaluation procedures, discusses the implications of a policy which is inclusive of single-handed practices. The findings relate to the experience of the first semester of the first year of the new curriculum. It also examines the contributions that single-handed practices have made to the teaching network and the kind of support needed, if single-handed practices are to continue to contribute to the King's teaching network. SETTING: King's College School of Medicine and Dentistry. SUBJECTS: Medical undergraduates. RESULTS: The findings of this paper revealed that over a third of general practice provision is via single-handed practices in South-east London. Within the undergraduate teaching network, 10% of practices are single-handed. Students are welcomed and receive a learning experience comparable to those students in larger practices. Attendance at training events has proved difficult for some of these tutors, but the extra input from the department, in order to address this deficit, has not been onerous. Indeed, single-handed practices have not been unique with regard to difficulties in attendance at training events. CONCLUSIONS: The study concludes that single-handed practices can make satisfactory provision for undergraduates in the new curriculum and there is no evidence from this study to suggest otherwise.
Curriculum↗
De novo reverse transcription of HTLV-1 following cell-to-cell transmission of infection.
Analogous to transmission of human T-cell leukemia virus type 1 (HTLV-1) in vivo, an in vitro cell-to-cell infection model was established by coculturing MT-2 cells as virus donors and HUT78 cells as recipients. At a donor:recipient ratio of 1:2, cell fusion occurred and a new round of HTLV-1 genome replication was initiated in the cocultured cells. Newly synthesized unintegrated viral DNA was detected by Southern blot within 4-8 h and then increased between 8 and 48 h following cell mixing. The most dominant species of unintegrated viral DNA was 3.7 kb in size which hybridized to a full-length HTLV-1 DNA probe but not to a Kpnl viral DNA fragment that is absent from a defective proviral genome that has been previously identified in MT-2 cells. Northern blot analysis showed large amounts of viral RNA in the virus donor cells and in the cocultured cells, with a 3.4-kb species being the most abundant. This 3.4-kb RNA gave a pattern identical to that of the 3.7-kb unintegrated viral DNA in hybridization studies using the two probes. It seems likely that the unspliced RNA transcript from the defective proviral genome in MT-2 cells was effectively reverse transcribed upon initiation of cell-to-cell viral transmission to susceptible HUT78 cells. Despite active de novo reverse transcription, however, viral RNA levels remained unchanged following cell-to-cell transmission of HTLV-1 infection and no viral antigen production could be attributed to the newly initiated round of viral genome replication. As an abortive infection model this simple cell-to-cell infection system warrants more detailed study as it has the potential to provide reliable information regarding the early events in HTLV-1 transmission and infection.
Cell Line↗
Assembly of GABAA receptors composed of alpha1 and beta2 subunits in both cultured neurons and fibroblasts.
GABAA receptors are believed to be pentameric hetero-oligomers, which can be constructed from six subunits (alpha, beta, gamma, delta, epsilon, and rho) with multiple members, generating a large potential for receptor heterogeneity. The mechanisms used by neurons to control the assembly of these receptors, however, remain unresolved. Using Semliki Forest virus expression we have analyzed the assembly of 9E10 epitope-tagged receptors comprising alpha1 and beta2 subunits in baby hamster kidney cells and cultured superior cervical ganglia neurons. Homomeric subunits were retained within the endoplasmic reticulum, whereas heteromeric receptors were able to access the cell surface in both cell types. Sucrose density gradient fractionation demonstrated that the homomeric subunits were incapable of oligomerization, exhibiting 5 S sedimentation coefficients. Pulse-chase analysis revealed that homomers were degraded, with half-lives of approximately 2 hr for both the alpha1((9E10)) and beta2((9E10)) subunits. Oligomerization of the alpha1((9E10)) and beta2((9E10)) subunits was evident, as demonstrated by the formation of a stable 9 S complex, but this process seemed inefficient. Interestingly the appearance of cell surface receptors was slow, lagging up to 6 hr after the formation of the 9 S receptor complex. Using metabolic labeling a ratio of alpha1((9E10)):beta2((9E10)) of 1:1 was found in this 9 S fraction. Together the results suggest that GABAA receptor assembly occurs by similar mechanisms in both cell types, with retention in the endoplasmic reticulum featuring as a major control mechanism to prevent unassembled receptor subunits accessing the cell surface.
Animals↗
Medical education. Early learning centres.
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Clinical Clerkship↗
Family physicians' knowledge of malignant melanoma.
BACKGROUND: The incidence and mortality of melanoma have been increasing during the past two decades. Melanoma is relatively easy to detect and, when diagnosed early, is curable. OBJECTIVE: Our purpose was to assess the baseline knowledge of malignant melanoma among family practitioners and to identify their preferred method of learning new information about the skin. METHODS: The design was a randomized survey by mailed questionnaire. RESULTS: More than 50% of physicians stated they lacked confidence in being able to recognize melanoma. Family physicians were well informed on factors affecting prognosis, but knowledge deficits were identified on history, physical examination, and risk factors. The most effective method of learning new information about the skin was hands-on teaching demonstration. CONCLUSION: Many family physicians are not confident in their ability to recognize melanoma, and knowledge deficits were identified. In addition, some important risk factors were not well recognized. Thus, those at highest risk may not be receiving education on early detection that may help decrease the incidence and mortality of melanoma.
Adult↗
Loricrin mutation in Vohwinkel's keratoderma is unique to the variant with ichthyosis.
A mutation in the glycine-rich cornified envelope protein loricrin has recently been reported in Vohwinkel's keratoderma (honeycomb keratoderma with pseudoainhum), in a pedigree amongst whom ichthyosis was also a feature. We have studied two further families with Vohwinkel's keratoderma for evidence ofloricrin mutations. Our first family (VK1) also had ichthyosis but not deafness. In lesional and nonlesional skin, granular and transitional cell layers were increased. In immunoelectron-microscopic studies cornified envelopes were abnormally thin and were labeled densely by anti-involucrin antibodies, but only sparsely by antiloricrin antibodies; however, abnormal intranuclear granules seen in granular and cornified layer cells were labeled by antibodies to both C- and N-terminal loricrin. Microsatellite markers in VK1 supported linkage to the loricrin locus in the epidermal differentiation complex at 1q21 (Zmax = 2.48). The loricrin gene was sequenced, identifying a heterozygous mutation as previously reported: a G insertion producing a frameshift after codon 231 and an abnormal C-terminal peptide lacking residues necessary for cross-linking. In our second family (VK2), affected members had sensorineural deafness but not ichthyosis. Immunoelectron-microscopic studies showed normal loricrin distribution, and assuming complete penetrance, linkage to 1q21 was excluded. Vohwinkel's keratoderma is thus clinically and genetically heterogeneous. Only the variant with ichthyosis appears to be due to loricrin mutation. As the arginine-rich domain in C-terminal loricrin caused by the frameshift contains several potential bipartite nuclear localization signals, we suggest that the intranuclear accumulation of loricrin in VK1 is due to these motifs, and may be unique to insertional mutation.
Adolescent↗
Sequence variation at the phenylalanine hydroxylase gene in the British Isles.
Using mutation and haplotype analysis, we have examined the phenylalanine hydroxylase gene in the phenylketonuria populations of four geographical areas of the British Isles: the west of Scotland, southern Wales, and southwestern and southeastern England. The enormous genetic diversity of this locus within the British Isles is demonstrated in the large number of different mutations characterized and in the variety of genetic backgrounds on which individual mutations are found. Allele frequencies of the more common mutations exhibited significant nonrandom distribution in a north/south differentiation. Differences between the west of Scotland and southwestern England may be related to different events in the recent and past histories of their respective populations. Similarities between southern Wales and southeastern England are likely to reflect the heterogeneity that is seen in and around two large capital cities. Finally, comparison with more recently colonized areas of the world corroborates the genealogical origin by range expansion of several mutations.
Alleles↗
Teaching medical students about long-term illness.
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Ambulatory Care↗
Reduced expression of HLA-B35 in schizophrenia.
The frequencies of HLA class I (HLA-A, B, C) and class II (HLA-DR, DQ) antigens were measured in 107 unrelated schizophrenic subjects and the results compared with 264 controls from south-east Scotland and a second control group of 133 individuals from north-east England. The expression of HLA-B35 was significantly reduced in the schizophrenic population compared to both control populations and these differences remained significant after correction for multiple testing. Linkage of schizophrenia and the major histocompatibility complex region of chromosome 6p was, however, excluded in a group of 17 families multiply affected with schizophrenia. Linkage was also excluded with several red cell antigens, red cell enzymes and plasma proteins. A negative association between the frequency of an HLA antigen and schizophrenia suggests that immune mechanisms may contribute to the aetiology of the disease in some subjects.
Adolescent↗
Confirmation of the 2p locus for the mild autosomal recessive limb-girdle muscular dystrophy gene (LGMD2B) in three families allows refinement of the candidate region.
The mild autosomal recessive limb-girdle muscular dystrophies (LGMD) are a heterogeneous group of muscle diseases. The first gene to be mapped and associated with this phenotype was a locus on 15q based on linkage analysis in families from a French geographic isolate. These results have been confirmed in other populations, but it was shown that there is genetic heterogeneity for this form of LGMD. Recently, a second locus has been mapped to chromosome 2p. The confirmation of the mapping of this second locus in LGMD families from different populations is of utmost importance for the positional cloning of this gene (HGMW-approved symbol LGMD2B). In this publication, haplotypes generated from five chromosome 2 markers from all of the known large families linked to chromosome 2p are reported together with the recombinants that show the current most likely location of the LGMD 2B gene.
Chromosome Mapping↗
GABAA receptor subunits have differential distributions in the rat retina: in situ hybridization and immunohistochemistry.
The distributions of nine different subunits of the gamma-aminobutyric acidA (GABAA) receptor (alpha 1, alpha 2, alpha 3, alpha 5; beta 1, beta 2, beta 3; gamma 2; delta) were investigated in the rat retina using immunocytochemistry and in situ hybridization. With the exception of the alpha 5 subunit, all subunits could be localized. Each subunit was expressed in characteristic strata within the inner plexiform layer (IPL). Some subunits (e.g., gamma 2) showed a ubiquitous distribution, while others (e.g., delta) were restricted to narrow sublayers. Double labeling experiments using different combinations of the subunit-specific antibodies revealed colocalizations of subunits within individual neurons. Additionally, GABAA receptor subunits were mapped to distinct populations of retinal neurons by coapplication of defined immunocytochemical markers and subunit-specific antibodies. Cholinergic amacrine cells were found to express the alpha 2, beta 1, beta 2/3 and delta subunits, while dopaminergic amacrine cells express the alpha 2, alpha 3 and gamma 2 subunits. Dissociated rod bipolar cells express the alpha 1 and gamma 2 subunits. In summary, this study provides evidence for the existence of multiple GABAA receptor subtypes in the retina. The distinct stratification pattern of the subunits in the IPL suggests that different functional circuits involve specific subtypes of GABAA receptors.
Animals↗