Diabetic retinal screening in the UK.
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Biomedical subjects
Publications and source records attributed to C Davey.
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PURPOSE: This paper reports a study which attempted to examine the influence of a varied assessment programme on student motivation to learn in an undergraduate therapy degree course. METHODS: In March 1997 a questionnaire was distributed to 98 third-year occupational therapy and physiotherapy students at the Southampton University School of Occupational Therapy and Physiotherapy. Using closed and open questions the questionnaire required the students to consider all the assessments they had taken in their 3 years of study and provide information about which type of assessment they found most motivating for their learning, and why. RESULTS AND CONCLUSIONS: The results revealed that students found a wide range of assessments motivating. There was some satisfaction with the mix and range of assessments. Three assessments emerged as the most motivating for student learning: Clinical/fieldwork II and III and Methods of inquiry III. In addition, four factors associated with assessment appeared to influence student motivation: perceived relevance and content of the assessment, enthusiastic lecturers and group influences. These factors need to be explored in more detail but in order to do so, educators need to be prepared to engage in an open dialogue with students about the learning climate that is created within higher education.
This paper discusses some of the technical aspects of converting a laboratory idea into a commercial product. The example used is the development of the Aber Instruments Biomass Monitor, which is now used worldwide in industry for the pitching of yeast in breweries and for biomass measurements in the pharmaceutical industry. Although the issues raised will relate to instrumentation in a production environment, many of the themes will be equally applicable to medical instruments.
Diabetic retinopathy remains the most common cause of blindness in people of working age but the provision of high quality eye screening for diabetic patients is still erratic in many health districts in the UK. National consensus guidelines recommend comprehensive population coverage, high sensitivity (>80%), high specificity (>95%), agreed clinical criteria, referral procedures and centralized data collection to facilitate audit. This study looks at the effectiveness of implementing a prompted recall programme for retinal screening in an inner-city district of North London. The scheme uses trained, accredited optometrists to screen patients with diabetes who are looked after in the community by their general practitioner. During the first 17 months of the scheme, 63 optometrists attended training and gained accreditation. Of the 666 patients recruited, 645 were scheduled for screening and 536 (83%) attended. Fourteen per cent of patients screened were found to have background retinopathy and 2.3% sight-threatening eye disease. In two audits, carried out 15 months apart in a random sample of GP practices, the incidence of recorded dilated fundoscopy increased from 48% at baseline to 56%, an increase of 8% (95% CIs 2%-14%). For referable eye disease, the sensitivity of this screening technique was 100%, the specificity 94% (95% CIs 90%-98%), the positive predictive value 79% (95% CIs 72%-86%) and the negative predictive value 100%. The administrative cost per case screened was Pound Sterling 12.60 (excluding clinical costs and any additional optometry payment).
We present the case of a young lady with unilateral pars planitis and associated cystoid macular oedema in whom visual symptoms fluctuated regularly during successive menstrual cycles. To date no such presentation of central macular oedema has been reported in the literature.
A domain, previously termed RE1, exists within the herpes simplex virus type 1 genome potentially influencing expression of immediate early genes and the latency associated transcripts. This domain consists of 10 tandem copies of a CT-rich sequence. We demonstrate that this domain binds multiple host-cell factors that may allow RE1 to act either as a transcriptional regulator and/or to affect nucleosomal and DNA structure in the latent genome.
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One of the mechanisms proposed to explain how CpG methylation effects gene repression invokes a DNA methylation-determined chromatin structure. Previous work implied that this DNA modification does not influence nucleosome formation in vitro, thus current models propose that certain non-histone proteins or a preferential affinity by linker histones for methylated DNA may mediate changes in chromatin structure. We have reinvestigated whether CpG methylation alters the chromatin structure of reconstitutes comprising only core histones and DNA. We find that DNA methylation prevents the histone octamer from interacting with an otherwise high affinity positioning sequence in the promoter region of the chicken adult beta-globin gene. This exclusion is attributed to methylation-determined changes in DNA structure within a triplet of CpG dinucleotides. In the affected nucleosome, this sequence motif is located 1.5 helical turns from the dyad axis and is oriented towards the histone core. These findings establish that DNA methylation does have the capacity to modulate chromatin structure directly, at its most fundamental level. Furthermore, our observations strongly suggest that a very limited number of nucleotides can make a decisive contribution to the translational positioning of nucleosomes.
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Our experience with this resident has had a significant impact on our approach to wound management. We no longer accept normal saline as the only option for wound cleansing. Instead, we approach wound cleansing systematically using the wound cleansing model outlined in Figure 1. If healing is not apparent, we critically review the situation and consider the bacterial status of the wound, the phase of wound healing, and the effects of wound cleansing versus wound disinfection on both the bacteria and the cells responsible for wound repair. In infected wounds or those colonized with a high bacterial count, careful attention is given to eradicating bacterial contamination. We carefully weigh the benefits of wound disinfection (eradication of bacterial contamination) against wound cleansing and the potential harm to the resident (delayed wound healing and unnecessary discomfort). If the benefits of wound disinfection outweigh the potential harm to the resident, we choose wound disinfection and monitor its effectiveness on a daily basis. When bacterial contamination has been eradicated and the wound is clean, we resume wound cleansing with normal saline.
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OBJECTIVES: Despite life-long maintenance therapy, cytomegalovirus (CMV) retinitis frequently progresses in patients with AIDS. Virological markers that could clarify pathogenesis and identify risk factors for progression are required. DESIGN AND METHODS: We prospectively recruited 45 patients with CMV retinitis. Blood and urine samples were collected before and after induction therapy, and on a monthly basis thereafter during routine medical and ophthalmological assessment, and at any time retinitis progressed. CMV load was measured by quantitative-competitive polymerase chain reaction (PCR). RESULTS: The median time to first progression of retinitis was 78 days and to death was 8.7 months. Eighty-five per cent of patients who were PCR-positive at diagnosis of retinitis became PCR-negative after 21 days of ganciclovir induction therapy. Six patients who remained PCR-positive after 21 days of treatment had a significantly higher CMV load at presentation (P = 0.005), and a shorter time to first progression of retinitis of 40 days. High CMV loads in blood at presentation were associated with a shorter time to progression (P = 0.16; relative hazard, 1.57) and a significantly shorter time to death (P = 0.004; relative hazard, 1.76). This significant relationship with survival remained after adjustment for potential confounding variables (CD4 count, age, method of drug administration). CONCLUSIONS: We conclude that CMV load in the blood of AIDS patients is an important factor in the pathogenesis of retinitis, and quantification of CMV could be used to both select patients for controlled clinical trials and to optimize individual anti-CMV induction therapy.
Positioned nucleosomes contribute to both the structure and the function of the chromatin fiber and can play a decisive role in controlling gene expression. We have mapped, at high resolution, the translational positions adopted by limiting amounts of core histone octamers reconstituted onto 4.4 kb of DNA comprising the entire chicken adult beta-globin gene, its enhancer, and flanking sequences. The octamer displays extensive variation in its affinity for different positioning sites, the range exhibited being about 2 orders of magnitude greater than that of the initial binding of the octamer. Strong positioning sites are located 5' and 3' of the globin gene and in the second intron but are absent from the coding regions. These sites exhibit a periodicity (approximately 200 bp) similar to the average spacing of nucleosomes on the inactive beta-globin gene in vivo, which could indicate their involvement in packaging the gene into higher-order chromatin structure. Overlapping, alternative octamer positioning sites commonly exhibit spacings of 20 and 40 bp, but not of 10 bp. These short-range periodicities could reflect features of the core particle structure contributing to the pronounced sequence-dependent manner in which the core histone octamer interacts with DNA.
A 3-A-resolution X-ray crystal structure of canine myeloperoxidase has previously revealed the overall structure of the molecule, including the polypeptide backbone conformation, but did not provide an unambiguous structure for the covalently bound heme. A higher resolution (2.28 A) X-ray crystal structure of human myeloperoxidase has now shown that the heme is a novel derivative of protoporphyrin IX in which three ring substituents form covalent bonds with amino acid side chains in the protein. Modified methyl groups on pyrrole rings A and C form ester linkages with glutamate 242 and aspartate 94, while a covalent bond between the vinyl group on ring A and the sulfur atom of methionine 243 results in a sulfonium ion linkage. The heme tetrapyrrole ring also shows considerable distortion from the planar conformation seen in most heme-containing proteins. The observed bending appears to result from these covalent bonds between diametrically opposed pyrrole rings A and C and the protein. Sequence comparisons suggest that the two ester linkages to the heme may also occur in other homologous mammalian peroxidases, but that the sulfonium ion linkage may be a unique feature of myeloperoxidase.
We have developed two new techniques to assess the positions adopted by core histone octamers when reconstituted onto DNA. These, together with a previously described technique, were applied to mapping binding sites on plasmid DNAs containing either the human zeta-globin or chicken beta-globin gene promoters. Each of the approaches enabled the sites occupied by histone octamers to be measured at high resolution and, in qualitative terms, revealed the same pattern of multiple, overlapping sites. Monomer extension, one of the novel techniques, can be used to reveal binding sites over extensive stretches of a single reconstitute (approximately 1000 bp). We found the distribution of histone octamer binding sites to be largely independent of the conditions employed for reconstitution, the topology of the DNA substrate and prolonged incubation under various post-reconstitution conditions. These properties, and features of the binding site maps that we derived, suggest that histone octamer positioning on these DNAs is predominantly a characteristic of the DNA sequence itself and, by implication, that nucleosome-nucleosome interactions and the formation of nucleosome arrays are of minor influence. Some of the techniques provide quantitative information concerning the relative binding strengths of the core histone octamer for different positioning sequences. In this context, it is notable that the majority of potential binding sites compete very poorly for the histone octamer, demonstrating that under the conditions pertinent to our analysis, the range of binding strengths exhibited by the octamer for particular DNA sequences is extensive, and greater than that observed when competitive binding has been studied by methods that do not reflect precise positioning.
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Congenital hypertrophy of retinal pigment epithelium (CHRPE) has been shown to be a frequent extracolonic manifestation of adenomatous polyposis coli (APC). The presence of CHRPE in patients with adenomatous polyps from families with cancer family syndrome suggests possible involvement of the APC gene locus in syndromes associated with less florid polyp formation than seen in APC. It also emphasises that caution must be exercised in using the presence of CHRPE clinically as a marker for APC in isolated at-risk individuals.