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Biomedical subjects

C Bunce

Publications and source records attributed to C Bunce.

At least 19 recordsLinked to original sources

Retrospective analysis of risk factors for late presentation of chronic glaucoma.

BACKGROUND: Why some individuals present to the ophthalmologist in the early stages of chronic glaucoma but others present with very advanced visual field loss is a question which has received little attention. This study is an attempt to identify some basic characteristics of people who present with late glaucoma. METHODS: A retrospective case-control study by medical record review was employed. 100 cases and 100 controls were identified from the notes of patients presenting to Moorfields Eye Hospital glaucoma service between July 1993 and July 1995. Cases were defined as new patients presenting with absolute field loss within five degrees of fixation and a cup to disc ratio of greater than 0.8 in one or both eyes. Controls were new patients with no absolute field loss within 20 degrees in either eye, but otherwise typical glaucomatous field loss and a cup to disc ratio of greater than 0.5 or a difference of 0.2 or more between the discs. RESULTS: The ethnic origin, sex, referral source, presenting IOP, and age of the subjects studied were independently associated with late presentation. An African Caribbean patient is estimated to be four and a half times more likely to attend with advanced field loss than a white patient of similar age, sex, IOP, and referral source (adj OR: 4.55, 95% CI [1.57, 13.18]). A female patient is estimated to be one third (0.34, [0.15, 0.74]) as likely to attend late than a male patient of the similar age, IOP, ethnic origin, and referral source. A patient referred via any source other than an optometrist with the correct diagnosis is estimated to be greater than four times (4.32 [1.89, 9.88]) more likely to be a late attender than a patient of the same sex, ethnicity, and similar age but referred with a diagnosis of glaucoma. There was a trend of increasing odds of late presentation with increasing age (adj OR per 10 years, baseline 40-49 years 1.68 [1.22, 2.20]). A patient whose presenting IOP is 21-25 mm Hg is estimated to be a quarter (0.24, [0.09, 0.64]) as likely to attend with advanced field loss than a patient of the same ethnic origin, sex, age, referral source, but with presenting IOP of greater than 31 mm Hg. CONCLUSIONS: These data strongly suggest that certain subgroups of patients with glaucoma are likely to be at greater risk of presenting with advanced and irremediable field loss.

Adult

Reproducibility of fundus autofluorescence measurements obtained using a confocal scanning laser ophthalmoscope.

AIM: To evaluate the reproducibility of the background fundus autofluorescence measurements obtained using a confocal scanning laser ophthalmoscope. METHODS: 10 normal volunteers and 10 patients with retinal disease were included in the study. One eye per subject was chosen randomly. Five images of the same eye of each individual were obtained, after pupillary dilatation, by two investigators using a confocal scanning laser ophthalmoscope. Background fundus autofluorescence was measured at 7 degrees temporal to the fovea in normal volunteers and between 7 and 15 degrees temporal to the fovea in patients. Within session reproducibility of the measurements obtained by each investigator and interobserver reproducibility were evaluated. RESULTS: For investigator 1 the median values of fundus autofluorescence obtained were 31.9 units for normal volunteers and 27.3 units for patients. The median largest differences in readings in normal volunteers was 5.7 units (range 1.4-13.5 units) and in patients 4.2 units (1.5-15.1 units). For investigator 2 the median values of fundus autofluorescence obtained were 28.9 units for normal volunteers and 27.4 units for patients. The median largest difference in readings in normal volunteers was 3.6 units (2.7-11.7 units), and in patients 4.1 units (1.5-9.3 units). The median interobserver difference in readings in normal volunteers was 3.3 units and for patients 6.6 units. The median greatest interobserver difference in measurements obtained for normal volunteers was 8.8 units (8.4-23.0 units) and for patients 11.1 units (7.1-40.8 units). CONCLUSION: Within session reproducibility of the measurements of background fundus autofluorescence was satisfactory. Although interobserver reproducibility was moderate, the variability of the measurements of fundus autofluorescence between observers appears to be small when compared with variation in fundus autofluorescence with age and disease.

Adolescent

Detection of optic disc change with the Heidelberg retina tomograph before confirmed visual field change in ocular hypertensives converting to early glaucoma.

AIM: To determine whether analysis of sequential optic disc images obtained with the Heidelberg retina tomograph (HRT) is able to demonstrate optic disc change before the development of reproducible field defects in a group of ocular hypertensive (OHT) patients converting to early glaucoma. METHODS: Two groups were analysed: (1) 13 eyes of 13 OHT patients who subsequently developed reproducible field defects (converters); and (2) 13 eyes of 11 normal control subjects. Two sequential optic disc images were obtained using the HRT (median separation between images was 12 months for the converters and 13 months for the normals). The second image in the converter group was obtained before confirmed visual field loss. The optic disc variables were analysed both globally and segmentally using HRT software version 1.11. The Wilcoxon signed rank test was used to determine if there were any significant differences between the variables of the two image sets. RESULTS: Significant optic disc change was demonstrated in the group of converters: (1) global variables: the cup area increased by 9.7%, the C/D area ratio increased by 10.5%, and the rim area decreased by 6.9%; (2) segmental variables: the superonasal cup area increased by 11.0%, the superonasal C/D area ratio increased 11.7%, and the inferonasal cup volume increased by 28.4%. The temporal rim volume decreased by 15.6%, the inferotemporal rim volume decreased by 23.6%, and the rim area in the superonasal and superotemporal segments decreased by 6.6% and 6.9% respectively. CONCLUSION: Analysis of sequential optic disc images on the HRT allowed the detection of glaucomatous change before confirmed visual field change in a group of OHT patients converting to early glaucoma.

Aged

BD8 certification of visually impaired people.

BACKGROUND: There is debate as to the completeness of the blind and partial sight registers in England and Wales. The purpose of this study was to estimate the proportion of eligible visually impaired people attending the hospital eye service who have a BD8 certificate and to identify factors associated with not being certified. METHODS: Cross sectional survey of patients attending outpatients by medical record review analysed by multiple logistic regression. RESULTS: 51% (43%, 58%) of patients identified as eligible for registration did not have a BD8 certificate. The severity of visual impairment and the main diagnosis in terms of requirements for treatment, permanence of visual loss, and visual field loss were independently associated with non-certification. A partially sighted patient is estimated to be three times more likely to not have a BD8 certificate as a blind patient of similar diagnosis (adj OR: 3.4 (95% CI: 1.7, 6.8)). A patient whose impairment is due to abnormal visual fields is estimated to be greater than three times more likely to be non-certified than one with low visual acuity of similar severity and cause (adj OR: 3.6 (95% CI: 1.0, 12.7)). People whose impairment is potentially reversible are estimated to be eight times (8.3 (2.2, 31.4)) more likely not to have a certificate compared with people who had permanent non-treatable visual loss; and in those with permanent visual loss, a requirement for ongoing treatment was found to be associated with a lower odds of certification. CONCLUSIONS: These data strongly suggest that epidemiological data collected during registration are biased towards permanent, non-treatable causes of visual loss and those which affect central rather than peripheral vision. Certain subgroups of the visually impaired are likely to be at greater risk of non-certification. BD8 guidelines need to be simplified.

Aged

Brain natriuretic peptide: identification of a second natriuretic peptide in human aqueous humour.

AIMS/BACKGROUND: To measure aqueous humour levels of brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) in humans. To compare peptide levels in glaucomatous and control eyes to test the hypothesis that these peptides are increased in glaucoma. BNP and ANP are cyclic endopeptides whose principal biological effects are natriuresis and vasodilatation. Experimental glaucoma in animal models results in elevated aqueous ANP. Intravenous ANP administration in both animals and humans causes lowering of intraocular pressure (IOP). There are equivocal data to support a role for ANP in IOP regulation in human eyes. There are as yet no published data on BNP in human aqueous humour. METHOD: This was a case-control study. Cases were primary open angle, pseudoexfoliation, and mixed mechanism glaucoma eyes undergoing trabeculectomy. Controls were cataract extraction eyes. There were 47 trabeculectomy eyes (44 patients) and 47 cataract extraction eyes (46 patients) matched for age, sex, race, systemic medications, and type of anaesthetic. 100-200 microliters of aqueous humour were aspirated by paracentesis as the first step in the surgical procedure. Peptide levels were later measured by radioimmunoassay. RESULTS: The presence of BNP and ANP in human aqueous humour was confirmed. BNP was present in higher concentrations than ANP. BNP levels tended to be greater in control eyes--glaucoma median 56.5 (range 0-3526.5) pg/ml versus control median 65.16 (range 0-1788) pg/ml (Wilcoxon signed rank test p = 0.78). ANP levels tended to be greater in glaucoma eyes than in controls: glaucoma median 3 (range 0-68.5) pg/ml versus control median 0 (range 0-60) pg/ml (Wilcoxon signed rank test p = 0.82). ANP and BNP were log linearly related in both groups (r glaucoma group = 0.961, r control group = 0.894). CONCLUSION: This is the first report of BNP and ANP in human aqueous humour. Peptide levels did not differ significantly between glaucoma and cataract extraction eyes. A linear relation between log BNP and ANP was found. Further studies are required to clarify the role of these peptides in aqueous humour production and IOP regulation.

Adult

Sebaceous carcinoma of the eyelid: a clinicopathological study.

BACKGROUND: Sebaceous carcinoma of the eyelid is rare. The diagnosis might be difficult because of its ability to masquerade as other periocular lesions. Prognosis is still regarded as being poor compared with most other malignant eyelid tumours with a mortality second only to malignant melanoma. The present study retrospectively analyses clinical and histopathological findings and outcome in a series of patients with sebaceous carcinoma of the eyelid in Britain. METHODS: 43 patients with histologically confirmed sebaceous carcinoma treated at Moorfields Eye Hospital between 1976 and 1992 were subjected to retrospective analysis. Clinical data of all patients were reviewed from the charts; all surviving patients except four cases lost for follow up were re-examined. Histological specimens were reviewed in 41 cases. RESULTS: 23 females and 20 males, mean age 63 years (range 37-79), were treated. Primary therapy was surgery in 37 and radiotherapy in six cases. After a median follow up of 40 months (range 1-148) 30 patients were alive without recurrences, four patients had died from the tumour, and one was alive with local recurrence and distant metastases. Four patients had died of non-tumour related causes. Histologically, unfavourable outcome was correlated with poor tumour differentiation and extensive invasion. CONCLUSION: Early diagnosis and consequent surgical therapy of sebaceous carcinoma of the eyelid leads to a better outcome and higher survival rates than generally assumed. Even local recurrences can be treated successfully. However, sebaceous carcinoma remains a threatening disease, which leads to death in 9% and to mutilating exenteration in 23% of our patients.

Adenocarcinoma, Sebaceous

CD45RC isoforms define two types of CD4 memory T cells, one of which depends on persisting antigen.

The cellular basis of immunological memory remains a controversial area with respect to the identity of memory T cells and the role of persisting antigen. CD4 T cells are phenotypically divided by the expression of high and low molecular weight isoforms of CD45, surface markers that are frequently used to identify "naive" (CD45Rhigh) and "memory" (CD45Rlow) subsets. The latter subset responds rapidly in antigen recall assays but paradoxically has a short life span, a property that is difficult to reconcile with long-term memory. The present study examines these issues using a DTH (delayed-type hypersensitivity) model in which contact sensitivity to dinitrochlorobenzene (DNCB) was transferred to athymic nude rats by recirculating CD4 T cell subsets defined in the rat by the anti-CD45RC mAb OX22. As expected, CD45RC+ (but not RC-) CD4 T cells from normal unprimed rats transferred a DNCB-specific DTH response, whereas, 4 d after sensitization the CD45RC- (memory) subset alone contained the DNCB reactivity. However, when donor cells were collected from thymectomized rats sensitized two mo earlier, DNCB-specific responses were transferred by both CD45RC- and RC+ subsets suggesting that many of the latter had developed from cells with a memory phenotype. This was confirmed when CD45RC CD4 T cells from 4-d primed rats were parked in intermediate nude recipients and recovered 2 mo later. DNCB-specific activity was now found wholly within the CD45RC+ "revertant" subset; the CD45RC-CD4 T cell population was devoid of activity. Importantly, we found that the total switch-back from CD45RC- to RC+ could be prevented, apparently by persisting antigen. The results indicate that there are two functionally distinct categories of memory T cells: one, a short-lived CD45Rlow type which orchestrates the rapid kinetics, the other, a longer-lived CD45Rhigh revertant which ensures that immunological memory endures.

Animals

Lymphoproliferative disorders in IL-7 transgenic mice: expansion of immature B cells which retain macrophage potential.

Transgenic mice carrying the murine IL-7 gene under the MHC class II (E alpha) promoter are described which develop lymphoid tumours at a high incidence when maintained in conventional or specific pathogen-free environments. Cells obtained from the lesions were relatively monomorphic, expressed a variety of B cell associated markers (BP-1, B220, CD43) but lacked surface Ig. Some mice, showed expanded populations of cells phenotypically similar to the recently reported bipotent B/macrophage stem cell subset (AA4.1high, B220-, Ig-) which could be cloned and maintained in vitro. These cells expressed IL-7 receptors, proliferated in response to IL-7 and in most cases had germline configuration of the Ig heavy chain locus. Cell lines cloned from two such tumours generated macrophages spontaneously in culture, consistent with their bipotent B cell/macrophage phenotype. These results suggest that IL-7 plays a role in very early stages of B cell ontogeny prior to bona fide B cell commitment.

Animals

Analysis of enteropathy induced by tumour necrosis factor alpha.

Tumour necrosis factor (TNF)-alpha has been implicated in the pathogenesis of experimental and clinical enteropathy, but its exact role is unknown. We show here that a single dose of TNF-alpha causes significant small intestinal pathology in normal adult mice, which develops within 15 minutes, persists for up to 48 hours and is enhanced by interferon-gamma (IFN-gamma). The enteropathy consists of villus atrophy and crypt hyperplasia and is therefore similar to that found in immunologically mediated enteropathies such as graft-versus-host reaction (GvHR). TNF-alpha is also cytotoxic to an intestinal crypt cell line in vitro. Thus, a direct action of TNF-alpha on crypt cells may be involved in its enteropathic effects in vivo. Together, these findings indicate that TNF-alpha alone, or in concert with other cytokines, may be an important effector molecule in immunologically mediated intestinal pathology and may ultimately provide a target for specific immunotherapy for clinical enteropathies.

Animals