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Biomedical subjects

A J Dickinson

Publications and source records attributed to A J Dickinson.

At least 19 recordsLinked to original sources
PubMed2006

Orbital lymphatics: do they exist?

INTRODUCTION: Although the lymphatic system was first described almost 400 years ago, it is only in very recent years that researchers have been able to identify lymphatic channels with reasonable accuracy. Through advances in molecular biology and the development of endothelial cell markers the long held view that the human orbit is devoid of lymphatics has now been challenged. DISCUSSION: This review discusses the current evidence on this topic, which confirms the presence of orbital lymphatics in lachrymal gland and optic nerve sheath.

Biomarkers↗
PubMed2006

A questionnaire survey on the management of Graves' orbitopathy in Europe.

OBJECTIVE: To determine management patterns among clinicians who treat patients with Graves' orbitopathy (GO) in Europe. DESIGN AND METHODS: Questionnaire survey including a case scenario of members of professional organisations representing endocrinologists, ophthalmologists and nuclear medicine physicians. RESULTS: A multidisciplinary approach to manage GO was valued by 96.3% of responders, although 31.5% did not participate or refer to a multidisciplinary team and 21.5% of patients with GO treated by responders were not managed in a multidisciplinary setting. Access to surgery for sight-threatening GO was available only within weeks or months according to 59.5% of responders. Reluctance to refer urgently to an ophthalmologist was noted by 32.7% of responders despite the presence of suspected optic neuropathy. The use of steroids was not influenced by the age of the patient, but fewer responders chose to use steroids in a diabetic patient (72.1 vs 90.5%, P<0.001). Development of cushingoid features resulted in a reduction in steroid use (90.5 vs 36.5%, P<0.001) and increase in the use of orbital irradiation (from 23.8% to 40.4%, P<0.05) and surgical decompression (from 20.9 to 52.9%, P<0.001). More ophthalmologists chose surgical decompression for patients with threatened vision due to optic neuropathy, who were intolerant to steroids than other specialists (70.3 vs 41.8%, P<0.01). CONCLUSION: Deficiencies in the management of patients with GO in Europe were identified by this survey. Further training of clinicians, easier access of patients to specialist multidisciplinary centres and the publication of practice guidelines may help improve the management of this condition in Europe.

Decompression, Surgical↗
PubMed2004

Ten years' experience of retrograde balloon dilatation of pelvi-ureteric junction obstruction.

OBJECTIVE: To analyse the long-term success of retrograde balloon dilatation (RBD) of pelvi-ureteric junction obstruction (PUJO). PATIENTS AND METHODS: The records of 58 adult patients (mean age 48 years, range 18-94) who had RBD between 1990 and 2001 were reviewed retrospectively. All symptomatic patients were included and assessed by dynamic renography. Success was judged as a symptomatic and/or functional improvement. Recurrence of symptoms was recorded and any evidence of deterioration of function despite improved symptoms. Complications were also recorded. RESULTS: In all, 44 (76%) patients were asymptomatic after RBD. There was no relationship between symptomatic change and renographic improvement; some patients who were rendered pain-free had either no improvement or even deterioration in their split renal function. Conversely, some patients who had a demonstrable improvement in their renal function continued to be symptomatic. However, a long-term follow-up (mean 6.1 years) of nine patients who were symptomatically improved showed good maintenance of split renal function. CONCLUSION: RBD is an effective treatment for PUJO and its success is maintained in the long term.

Adolescent↗
PubMed2004

The use of porous polyethylene (Medpor) lower eyelid spacers in lid heightening and stabilisation.

BACKGROUND/AIMS: The management of lower eyelid retraction can be challenging, and established techniques to correct it are not always successful. Previous reports have suggested a role for the ultrathin high density porous polyethylene lower eyelid spacer (Medpor LES) in such patients. The authors report the experience of three surgeons implanting Medpor LES over 1 year, and ascertain whether such implants are a safe and effective alternative to autogenous spacers. METHODS: A prospective, interventional, non-comparative case series of consecutive patients. Surgical indications for Medpor LES were noted. Preoperative and postoperative lower marginal reflex distance (L-MRD), vertical palpebral aperture (PA), lagophthalmos, and scleral show inferior to the limbus (LSS) were recorded, together with major and minor complications. RESULTS: 32 patients (35 eyelids) had a Medpor LES inserted, 22/32 under local anaesthetic, and nine with adjunctive procedures. Mean follow up was 22 months (range 15-28 months). The Medpor LES was effective in reducing the palpebral aperture (p<0.001) and lagophthalmos (p = 0.04) and raising the lower eyelid height by reducing both L-MRD (p = 0.006) and LSS (p<0.001). However there were major complications in 7/32 patients and minor complications in 8/32, most requiring further surgery. Final outcome was good in 24/35 eyelids and satisfactory in 5/35. CONCLUSIONS: Despite a good or satisfactory final outcome in the majority of patients, the value of this technique is limited by complications, and should be reserved for those unsuitable for safer techniques.

Adult↗
PubMed2003

CTLA4 gene and Graves' disease: association of Graves' disease with the CTLA4 exon 1 and intron 1 polymorphisms, but not with the promoter polymorphism.

OBJECTIVE: Recent studies have shown that Graves' disease (GD) is linked to and associated with alleles of the cytotoxic T lymphocyte antigen-4 (CTLA4) locus. However, the true pathogenic polymorphism(s) at this locus remains uncertain. Moreover, the association studies of the promoter CTLA4(-318)C/T polymorphism in white GD populations have produced conflicting results. Therefore, we have analysed three CTLA4 single nucleotide polymorphisms, including promoter CTLA4(-318)C/T, exon 1 CTLA4(49)A/G and intron 1 CTLA4(1822)C/T in our GD cohort from the UK. PATIENTS AND METHODS: We studied 301 white patients with GD and 349 healthy ethnically matched local controls. Amongst GD probands, 129 had significant thyroid-associated orbitopathy (TAO; NOSPECS class III or worse). The CTLA4(-318)C/T, CTLA4(49)A/G and CTLA4(1822)C/T polymorphisms were genotyped by using the restriction enzymes MseI, Bst71I and HaeIII, respectively. RESULTS: We found no association between GD and alleles of CTLA4(-318)C/T. GD was found to be associated with the G allele of CTLA4(49)A/G[P = 5.9 x 10(-6), odds ratio (OR) 1.65] and the T allele of CTLA4(1822)C/T (P = 7.7 x 10(-6), OR 1.64). The frequencies of these alleles were significantly higher in GD probands with significant TAO than in those without TAO (G allele: P = 0.001, OR 1.68; T allele: P = 0.001, OR 1.70). CONCLUSIONS: The promoter CTLA4(-318)C/T polymorphism is not in linkage disequilibrium with the pathogenic polymorphism(s) at the CTLA4 locus. The alleles of both the exon 1 CTLA4(49)A/G and the intron 1 CTLA4(1822)C/T polymorphisms are associated with GD, which is stronger in patients with TAO.

Abatacept↗
PubMed2001

Controversies in the clinical evaluation of active thyroid-associated orbitopathy: use of a detailed protocol with comparative photographs for objective assessment.

Despite many learned publications over recent decades, the assessment of active thyroid-associated orbitopathy (TAO) remains difficult and controversial. There are no biochemical, immunological or imaging investigations which can identify active disease reliably, and clinical assessment is still of paramount importance. We therefore review the strengths and weaknesses of all methods of clinical assessment. A new atlas for clinical assessment of soft tissue signs has been developed, and its reproducibility assessed. It details a suggested protocol that could help standardize descriptions of TAO and allow more objective assessment of its activity and severity. This is relevant to general endocrinologists, who have a crucial role in the identification of patients who require ophthalmological assessment. Certain aspects are more relevant to ophthalmologists and endocrinologists who have a special clinical and research interest in TAO. Unless a reproducible system of assessment is devised and widely adopted, it will remain difficult to interpret research meaningfully, particularly if results appear to contradict.

Clinical Protocols↗
PubMed2000

Development of embryonic cells containing serotonin, catecholamines, and FMRFamide-related peptides in Aplysia californica.

This study demonstrates the presence of a relatively extensive but previously unrecognized nervous system in embryonic stages of the opisthobranch mollusc Aplysia californica. During the trochophore stage, two pairs of cells were observed to be reactive to antibodies raised against the neuropeptides FMRFamide and EFLRIamide. These cells were located in the posterior region of the embryo, and their anterior projections terminated under the apical tuft. As the embryos developed into veliger stages, serotonin-like immunoreactive (LIR) cells appeared in the apical organ and were later observed to innervate the velum. Also, aldehyde-induced fluorescence indicative of catecholamines was present in cells in the foot, oral, and possibly apical regions during late embryonic veliger stages. Just before the embryo hatches as a free-swimming veliger, additional FMRFamide-LIR and catecholamine-containing cells appeared in regions that correspond to the ganglia of what will become the adult central nervous system (CNS). Neurons and connectives that will contribute to the adult CNS appear to develop along the pathways that are pioneered by the earliest posterior FMRFamide-LIR cells. These observations are consistent with the hypothesis that, besides their presumed roles in the control of embryonic behaviors, some elements may also guide the development of the CNS. Embryonic nervous systems that develop prior to and outside of the adult CNS have also been reported in pulmonate and prosobranch species of molluscs. Therefore, the demonstration of early developing neurons and their transmitter phenotypes in A. californica presents new opportunities for a better understanding of the ontogeny and phylogeny of both behavioral and neuronal function in this important model species.

Amino Acid Sequence↗
PubMed1998

Mohs' surgery of periocular basal cell carcinoma using formalin-fixed sections and delayed closure.

Mohs' surgery of periocular basal cell carcinoma (BCC) ensures a high cure rate with maximal preservation of normal tissue. The formalin-fixed paraffin-embedded tissue technique allows Mohs' surgery to be performed using routine pathology facilities and permits the efficient use of operating room personnel and theatre time. The inevitable delay between excision and closure may potentially result in a poor functional and cosmetic outcome, particularly around the eye. We prospectively studied all patients with periocular BCC treated with this technique at our unit between 1985 and 1996. One hundred and twenty-three periocular BCCs in 120 patients were treated. Microscopic clearance was achieved in all cases. Closure was performed on average 5 days after the initial excisional stage. Closing procedures included direct closure, flaps and grafts. Significant complications affecting outcome were noted in only two patients. Eighty-eight per cent of patients assessed had a functional and cosmetic result regarded as excellent, good or adequate. Mohs' surgery of periocular BCC using formalin-fixed paraffin-embedded tissue and delayed closure results in a satisfactory functional and cosmetic outcome and offers a viable alternative to the frozen section fresh tissue technique.

Adult↗
PubMed1997

Prevalence of age-related maculopathy at two points in time in an elderly British population.

UNLABELLED: As the demography of Western society changes, the population prevalence of diseases such as age-related macular degeneration (AMD) is expected to rise. Despite this, there remains a paucity of quality data concerning the population prevalence of AMD, the commonest cause of blindness in the elderly. PURPOSE: To report the prevalence of AMD at two points in time in an elderly population. METHOD: A geographically defined random population sample of elderly people was defined in 1980, and studied in 1982-4. In 1990, a cohort of survivors was identified. Participants underwent full ophthalmic examination with fundus photography using the same camera on each occasion. Photographs were randomly encoded and graded by two independent masked observers using the Wisconsin Age-related Maculopathy Grading System. Disagreements were resolved by consensus. RESULTS: Eighty-eight survivors participated in the follow-up examinations. Of these, 82 subjects had gradable retinal photographs for both examination points in at least one eye. There were 158 pairs of images (initial and subsequent) available for analysis. The mean age was 80 years (range 77-90 years) at the initial examination, and 87 years (range 84-97 years) at the subsequent examination; 70.7% of subjects were female. Prevalence rates for the initial examination were: drusen 72.8%, drusen confluence 37.3%, degeneration of the retinal pigment epithelium (RPE) 51.3%, increased pigment 22.2%, exudative AMD 1.9% and geographic atrophy 1.9%. Rates at second examination were: drusen 62.7% drusen confluence 41.8%, RPE degeneration 72.8%, increased pigment 16.5%, exudative AMD 3.8% and geographic atrophy 3.2%. CONCLUSION: This 'double' prevalence study provides detailed data on AMD lesions at two points in time in a population-based group of elderly people.

Age Distribution↗
PubMed1997

Seven year follow-up of age-related maculopathy in an elderly British population.

UNLABELLED: Despite age-related macular degeneration (AMD) being the commonest cause of blindness amongst the elderly in Western society, the incidence of new lesions is poorly documented and the natural history of existing disease remains ill understood. PURPOSE: To document in an elderly population the incidence of new AMD lesions and the progression of pre-existing AMD over time. METHOD: Baseline ophthalmic examinations were performed on a geographically defined random population sample of elderly people in 1982-4, and retinal photographs taken. The present study re-examined and re-photographed survivors after approximately 7 years using the same fundus camera. Photographs were randomly encoded, and independently graded for AMD features by two masked observers using the Wisconsin AMD grading system. Disagreements were resolved by review to reach a consensus. RESULTS: Eighty-two of the 88 participating survivors had photographs of gradable quality on both occasions in at least one eye. Mean age at follow-up was 87 years (range 84-97 years) and 70.7% of subjects were female. Paired photographs were available on 158 eyes, and showed important differences in drusen type, drusen area and characteristics of the retinal pigment epithelium (RPE) between initial and subsequent examinations. The 7 year incidence (and regression) of lesions was: drusen 30.6% (20.0%), RPE degeneration 54.5% (8.8%), increased pigment 11.6% (64.7%), subretinal haemorrhage 1.3%, subretinal scar/fibrin 1.3% and geographic study 1.3%. CONCLUSION: These unique population-based results provide new insight into the natural history of AMD in an elderly population.

Aged↗
PubMed1997

The Wisconsin Age-related Macular Degeneration grading system: performance in an independent centre.

INTRODUCTION: Age-related Macular Degeneration (AMD) is the commonest cause of blindness in developed nations. Despite this, the epidemiology of AMD is poorly understood. A need for the documentation of AMD prevalence and incidence at a population level has stimulated the development of a comprehensive, observer-based, photographic grading method for AMD in Wisconsin. AIM: To independently assess the performance of the Wisconsin method by self-taught graders outside its centre of inception. METHOD: The inter-observer variability and confidence limits for detection of change were assessed for two self-taught graders (ophthalmologists). Self teaching was achieved exclusively from documentation and photographs provided by the system developers in Wisconsin. 295 retinal photographs of elderly people were independently assessed for 13 features by each of the two graders. RESULTS: Weighted and unweighted kappa statistics, % exact and one step apart agreement, and confidence limits for detection of change were calculated for the graded features on a "by eye' basis, and where appropriate, on a "by retinal subfield' basis. Levels of agreement for weighted kappa were moderate to substantial for most features. 95% and 90% confidence limits for significant change beyond measurement error were determined in terms of scale increments. CONCLUSION: We conclude that the Wisconsin AMD grading system can be independently learnt from documentation and photographs alone, and that an acceptable level of performance is attainable by self-taught graders.

Aged↗
PubMed1996

Expression of the angiogenic factor thymidine phosphorylase/platelet-derived endothelial cell growth factor in primary bladder cancers.

Thymidine phosphorylase (TP), also known as platelet-derived endothelial cell growth factor, has been implicated in bladder cancer angiogenesis. To examine its role more clearly, we have quantified and localized its expression using Western analysis and immunohistochemistry in a series of 105 bladder cancers. We have also assessed the relationship between TP expression and other tumor parameters including quantitative angiogenesis, p53 status, ploidy, and survival. By Western analysis, TP expression was 5-fold higher in tumors than in normal bladder samples (P < 0.02). Expression was 15-fold higher in invasive tumors than in normal bladder (P < 0.001) and 8-fold higher than in superficial tumors (P < 0.005). Immunohistochemistry of the tumors showed TP was present in the neoplastic epithelium in 27% of the tumors, in the inflammatory cells in 72% of the tumors, in stromal cells in 30% of the tumors, and in tumor-associated endothelium in 11% of the tumors. Expression by Western blotting and immunohistochemistry was significantly up-regulated in tumors compared with normal bladder (P < 0.05). Tumor cell TP expression correlated with tumor grade (P < 0.02), but there was no correlation between tumor cell TP expression and tumor stage (P = 0.46), ploidy (P = 0.52), p53 expression (P = 0.9), tumor vascularity (P = 0.8), relapse-free survival (P = 0.57), or overall survival (P = 0.94). TP protein is expressed in bladder cancers, and expression is associated with an aggressive phenotype. Because TP can activate a number of cytotoxic agents, it provides a potential therapeutic target in bladder cancer.

Adult↗
PubMed1996

A retrospective study of the investigation and management of muscle-invasive bladder cancer in the South West Region.

OBJECTIVE: To evaluate the present management of muscle-invasive bladder cancer in the South West Region and to assess the workload resulting from the rationalization of treatment in specific centres. METHODS: A retrospective survey was undertaken in all the hospitals in the South West Region, to assess the management of all patients presenting with muscle-invasive bladder cancer in the years 1989 and 1993. Data were collected from histopathology records and hospital in-patients' notes. The optimum standard of assessment and treatment were defined by a panel of specialists in urological tumours. The management of patients was compared against these defined standards. RESULTS: A total of 186 and 199 patients in 1989 and 1993, respectively, were evaluated. When comparing their assessment against the defined standard, only 69% of patients in 1989 and 58% in 1993 had an intravenous urogram, with 7% and 4%, respectively, having no upper tract imaging (the remainder undergoing ultrasonography). Evidence from an examination under anaesthetic (EUA) was found for 80% of patients in 1989 and 84% of patients in 1993. Only 23% of patients in 1989 and 36% in 1993 were staged by either computed tomography or magnetic resonance imaging. In both 1989 and 1993, 54% of patients had definitive treatment, 31% had an endoscopic follow-up only and 15% had no treatment; there were no differences in age or co-morbidity among these groups. The median time elapsed between referral and diagnosis was 59 days (1989) and 52 days (1993), and the median delay to definitive treatment was 114 and 96 days, respectively. CONCLUSION: There was insufficient upper tract imaging, poor clinical staging in the EUA and too few investigations for staging. The low rate of definitive treatment may be a consequence of the delays in management, allowing the tumour to progress, and suggesting the need for a more rapid assessment of haematuria.

Adult↗