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Biomedical subjects

P M Dodson

Publications and source records attributed to P M Dodson.

At least 19 recordsLinked to original sources
PubMed2003

The platelet glycoprotein Ia/IIa gene polymorphism C807T/G873A: a novel risk factor for retinal vein occlusion.

Retinal vein occlusion (RVO) is associated with hyperhomocysteinaemia and the antiphospholipid syndrome-disorders known to contribute to both arterial and venous thrombosis. In both of these conditions and RVO, platelet activation occurs. Aspirin, not warfarin, is the most effective antithrombotic agent in RVO and, taken together, these observations suggest an important role for platelets in this common ocular thrombotic condition. Platelet glycoprotein Ia/IIa (GpIa/IIa) is an adhesion molecule mediating platelet-collagen interactions and is key to the initiation of thrombosis. Recently, the cellular density of this molecule was shown to be determined by two silent, linked polymorphisms (C807T/G873A) within the GpIa/IIa gene. There is evidence that some of the resulting genotypes are associated with thrombo-embolic disease. This study therefore aimed to establish the prevalence of the GpIa/IIa polymorphisms and the three commonest hereditary thrombophilic disorders (prothrombin gene G20210A (PT) mutation, Factor V Leiden (FVL), and the thermolabile methylene tetrahydrofolate reductase C677T (MTHFR) mutation) in patients with RVO and normal controls. The GpIa/IIa polymorphisms and thrombophilic abnormalities were all identified using the polymerase chain reaction.Our results show that the frequency of the GpIa/IIa polymorphisms was similar in our normal control population to previously published series. Patients with RVO, however, had only a 10% (4/40) frequency of the lowest risk subtype (CC/GG) compared to 37.5% (15/40) in the control group-P 0.0039. The incidence of the PT, FVL, and MTHFR thrombophilic mutations was not different between the two groups, but interestingly none of the 7/40 RVO cases with a PT, FVL, or MTHFR mutation had the low-risk GpIa/IIa genotype while all but one of the controls did-P<0.05. Thus, 17.5% of RVO patients harboured more than one prothrombotic abnormality. The principal difference between the RVO and control group was the very high incidence of the intermediate-risk GpIa/IIa subtype (CT/GA)-82.5 vs 50%, P&<0.05. These results suggest a major role for GpIa/IIa polymorphisms in the pathogenesis of RVO.

Adult↗
PubMed2002

The role of serum lipids in exudative diabetic maculopathy: is there a place for lipid lowering therapy?

Diabetic maculopathy is a common complication of diabetes mellitus, characterised by macular oedema and frequently accompanied by lipid exudation. It is the major cause of loss of vision from diabetic retinopathy. There is some evidence to implicate serum lipids in exudative maculopathy; cross-sectional studies suggest that higher serum lipid levels are found in patients with macular exudates, and prospective studies have shown an increased risk of exudative maculopathy if baseline cholesterol is higher. The treatment for diabetic maculopathy is laser photocoagulation of the pigment epithelium. With the advent of systemic lipid lowering therapy over the last decade, there may be potential for medical therapy also. There is some anecdotal evidence of the effect of lipid lowering agents (particularly statins) in reducing exudate, and a number of studies have shown that lipid lowering therapy may reduce macular exudates, but numbers in these trials are small. A randomised controlled trial is now required to investigate whether the use of systemic lipid lowering therapy is of benefit in patients with exudative maculopathy, even in the absence of dyslipidaemia.

Diabetic Retinopathy↗
PubMed2002

Hypertension and diabetes.

Hypertension is common in people with diabetes with an estimated prevalence using the new criteria (> or = 140/90) at 70%. The recent large randomized controlled studies in diabetic subjects has clearly shown the benefit of blood pressure lowering with reduction in cardiovascular endpoints and microvascular disease. ACE inhibitors, calcium antagonists, thiazide diuretics and beta-blocking agents have been the agents validated by the trials. The challenge now is to implement antihypertensive therapy to achieve tight blood pressure targets (< or = 140/80), usually requiring dual or even triple therapeutic regimens.

Antihypertensive Agents↗
PubMed2001

MHC class II region, CTLA4 gene, and ophthalmopathy in patients with Graves' disease.

Up to half of patients with Graves' hyperthyroidism have signs of thyroid associated ophthalmopathy, but the factors that cause this disorder are unknown. We investigated two major genetic susceptibility loci for Graves' disease in ophthalmopathy; the MHC class II region and the cytotoxic T lymphocyte antigen-4 (CTLA4) gene. Allelic frequencies of these genes in patients with Graves' disease who did and did not have concurrent thyroid-associated ophthalmopathy did not differ, and are, therefore, unlikely to contribute to its development.

Abatacept↗
PubMed2000

Plasma total homocysteine and retinal vascular disease.

PURPOSE: Hyperhomocysteinaemia has been linked to macrovascular disease. Our aim was to investigate whether there is a relationship between fasting plasma total homocysteine levels and retinal vascular disease. METHODS: We measured the homocysteine levels in 70 patients with arterial or venous retinal vessel occlusion and compared them with the levels in 85 controls without evidence of ischaemic heart disease. Homocysteine levels were determined by high-performance liquid chromatography with electrochemical detection and compared after logarithmic transformation. RESULTS: Homocysteine levels were found by univariate analysis (unpaired two-tailed t-test) to be significantly higher in the group with retinal artery occlusion than the group with retinal vein occlusion (p = 0.045) and in both groups compared with controls (18.4 and 13.8 vs 9.5 mumol/l; p = 0.0002 and < 0.0001, respectively). The controls, however, were significantly younger than the subjects (51.5 +/- 15.4 vs 66.2 +/- 11.9 years; p < 0.0001), but analysis of the results by age revealed significant differences between the groups and controls for the seventh decade (vein occlusions, p = 0.05) and for the eighth decade (artery occlusions, p = 0.037). Subgroup analysis of the retinal vessel occlusion group revealed significant differences in mean blood pressure between those with branch retinal vein occlusions (175/100 mmHg) and both those with central retinal vein occlusions (155/88 mmHg) and those with retinal artery occlusions (157/86 mmHg). Both vein occlusion subgroups also differed significantly with regard to homocysteine levels, branch < central (12.2 +/- 1.3 vs 15.0 +/- 1.6 mumol/l, p = 0.03). Multiple linear regression analysis revealed significant relationships between homocysteine levels and the presence of retinal vessel occlusion (p = 0.0002), serum creatinine (p = 0.001) and age (p = 0.003), but not gender. CONCLUSIONS: We conclude that homocysteine may be a risk factor for retinal vascular disease and could be simply and cheaply treated with folate and vitamins B6 and B12.

Adult↗
PubMed2000

Nine year follow-up study of morbidity and mortality in retinal vein occlusion.

PURPOSE: The aim of this study was to conduct a detailed retrospective follow-up of a large cohort of patients with retinal vein occlusion (RVO), examining morbidity and mortality, to investigate a possible relationship between RVO, large vessel disease and stroke, and to determine whether recurrence of RVO was influenced by treatment of associated medical conditions. METHODS: A follow-up study was undertaken in 1994 of all patients (n = 588) who presented to the medical ophthalmology clinics of the Birmingham and Midland Eye Hospital between 1982 and 1989 with a definitive diagnosis of RVO. RESULTS: Follow-up data were obtained on 549 patients (93%). Results showed that recurrence of RVO in the same or fellow eye was decreased by more than half in the follow-up group (3.3%) when compared with the known recurrence rate at initial presentation (8.8%). Comparison of the deceased with the survivors showed that the deceased patients were significantly older (mean age 70.2 vs 63.4 years). The prevalence of rubeosis iridis and smoking were statistically significantly increased when comparing the deceased with the survivors (p < 0.016 and p < 0.008 respectively). The deceased had a higher prevalence of diabetes (15.8% vs 10.1%), and there was a trend towards increased clinically evident macrovascular disease in those patients who had died (23.2% vs 19.5%). Neither hypertension nor hyperlipidaemia predicted death, as the prevalence rates of the two conditions were similar in survivors and those who had died (60.0% vs 60.6% and 48.4% vs 53.3%). The percentage of patients taking antiplatelet drug therapy was not different in the two groups (36.8% vs 38.3%). Analysis of the causes of death of the RVO population (n = 95) compared with the causes of death in the West Midlands population as a whole, showed that the percentage of deaths from myocardial infarction in the RVO population was significantly higher (23.1% vs 14.4%, p < 0.05). There was no statistical difference between the populations for ischaemic heart disease and stroke, although there was a trend for increased mortality from stroke (19% vs 13.5%). CONCLUSION: These data suggest a relationship between RVO, mortality and increased cardiovascular risk factors (smoking, diabetes and macrovascular disease), and support the possibility of an association between RVO and stroke. They also support the potential value of medical treatment of underlying medical conditions in preventing recurrence of RVO.

Adult↗
PubMed1999

Pigmentary retinal dystrophy and the syndrome of maternally inherited diabetes and deafness caused by the mitochondrial DNA 3243 tRNA(Leu) A to G mutation.

OBJECTIVE: To study the association of retinal disease and the syndrome of maternally inherited diabetes and deafness caused by an A to G mutation in the tRNA leucine gene at base pair 3243 (A3243G) of the mitochondrial genome. DESIGN: Observational study of a genetically defined subject group. PARTICIPANTS: Thirteen subjects with the mitochondrial DNA A3243G mutation from seven different pedigrees with maternally inherited diabetes and deafness. INTERVENTION: Assessment of visual symptoms and visual acuity, dilated indirect ophthalmoscopy, retinal photography, and retinal electrophysiology. MAIN OUTCOME MEASURES: Loss of vision, funduscopic evidence of pigmentary retinal disease or diabetic retinopathy, and electrophysiologic evidence of defective functioning of the retinal pigment epithelium/photoreceptor complex. RESULTS: Funduscopic examination revealed abnormalities of retinal pigmentation in ten subjects (77%). Defects included speckled and patchy hyperpigmentation at the posterior pole of the fundus, particularly in the macular area, and varying degrees of loss of retinal pigmentation. Three subjects (23%) had visual symptoms, which included night blindness, visual loss, and photophobia. Electrophysiologic studies revealed impaired electro-oculogram responses in four of nine subjects with defects of retinal pigmentation (44%), two of whom also had much reduced scotopic and, to a lesser extent, flicker electroretinogram b wave potentials. Two subjects had diabetic retinopathy, including one with retinal depigmentation and impaired electro-oculogram activity. Both subjects with diabetic retinopathy had unilateral reduced electroretinogram responses, especially oscillatory potentials. CONCLUSIONS: Abnormalities of retinal pigmentation are common in subjects with maternally inherited diabetes and deafness caused by the mitochondrial DNA A3243G mutation. Visual symptoms, in particular loss of visual acuity, appear to be infrequent. The combination of deficits in the electro-oculogram and scotopic and flicker electroretinograms suggests that the retinal dystrophy includes defective functioning of retinal pigment epithelial cells and of both rod and cone photoreceptors. The pigmentary retinopathy does not prevent diabetic retinopathy; a single subject had funduscopic and electrophysiologic evidence of both diseases. Current evidence suggests that the mitochondrial DNA A3243G mutation accounts for 0.5% to 2.8% of diabetes. Most ophthalmic and diabetic clinics are therefore likely to contain such patients, who may benefit from identification of the genetic defect causing their disease and from genetic counseling.

Adenine↗
PubMed1999

The development of Graves' disease and the CTLA-4 gene on chromosome 2q33.

Case-control studies suggest that the CTLA-4 gene may be a susceptibility locus for Graves' disease. The previously reported A/G polymorphism at position 49 in exon 1 of the CTLA-4 gene was, therefore, investigated in a case-control (n = 743) and family-based (n = 179) dataset of white Caucasian subjects with Graves' disease. The relationship between CTLA-4 genotype and severity of thyroid dysfunction at diagnosis was also investigated. An increase in frequency of the G (alanine) allele was seen in Graves' patients compared with control subjects (42% vs. 31.5%, respectively; corrected P<0.0002; odds ratio = 1.58), and a significant difference in the distribution of GG, GA, and AA genotypes was observed between the groups (chi2 = 21.7; corrected P<0.00003). Increased transmission of the G allele was seen from heterozygous parents to affected offspring compared to unaffected offspring (chi2 = 5.7; P = 0.025). Circulating free T4 concentrations at diagnosis were significantly associated with CTLA-4 genotype (F = 3.26; P = 0.04). These results support the hypothesis that CTLA-4 may play a role in regulating self-tolerance by the immune system and in the pathogenesis of autoimmune disorders such as Graves' disease.

Abatacept↗
PubMed1998

Pupillary dilatation and driving in diabetic patients.

Diabetic patients routinely have their pupils dilated for fundoscopy as part of the annual review. To assess the ability of diabetic patients to drive after pupillary dilatation we studied 61 diabetic patients (18 IDDM, 43 NIDDM), mean age 54.98 years, before and 1 h after pupillary dilatation with 1% tropicamide. Binocular visual acuity (BVA) and contrast sensitivity were checked without glare, with glare, and with glare and sunglasses. Glare was introduced using a 60 W bulb in all 61 patients and with a 500 W bulb in 37 of these patients. Prior to dilatation all 61 patients had a BVA of 6/9 or better. A significant reduction in BVA was found post-dilatation (p = 0.005) and 4 out of the 61 patients (6.56%) had a post-dilatation BVA of less than 6/9. The 60 W glare source caused a significant reduction in BVA pre-dilatation (p < 0.05), but not the 500 W glare. With glare, post-dilatation BVA reduced further, resulting in 6 and 7 patients having a BVA of less than 6/9 with the 60 W and 500 W glare source, respectively. The addition of sunglasses with glare did not improve the BVA. No patient with a BVA of 6/5 pre-dilatation reduced to less than 6/9 post-dilatation. No significant change in contrast sensitivity was found in any of the test conditions. We conclude that patients who meet the visual legal requirements to drive (BVA < or = 6/9) prior to dilatation may not fulfil them post-dilatation. This has important clinical implications and the time course of the phenomenon requires exploration. Meanwhile, patients need to be warned not to drive after pupillary dilatation when they attend for annual fundoscopic examination, certainly for at least two hours.

Adult↗
PubMed1998

Linkage disequilibrium between the human leukocyte antigen class II region of the major histocompatibility complex and Graves' disease: replication using a population case control and family-based study.

Early case control studies found association of the DRB1 allele, DR3, with Graves' disease (GD). Recent reports, claim the DQA1 allele, DQA1*0501, to be the primary susceptibility determinant within the human leukocyte antigen (HLA) class II region. We typed 228 GD patients, 364 controls, and 98 families (parents, GD, and unaffected sibling) at the DRB1, DQB1, and DQA1 loci. The case control study showed an increased frequency in GD, compared to controls, of DRB1*0304 (47% vs. 24%; pc < 1.4 x 10(-5)), DQB1*02 (58% vs. 46%; pc < 0.035), DQB1*0301/4 (42% vs. 28%; pc < 3.5 x 10(-3)) and DQA1*0501 (67%, vs. 39%; pc < 7 x 10(-6)). The DRB1*0304-DQB1*02-DQA1*0501 haplotype was increased in GD (47%) vs. controls (24%; pc < 1.8 x 10(-5); odds ratio = 2.72). No independent association of these alleles was observed. Preferential transmission of DRB1*0304-DQB1*02-DQA1*0501 from parents heterozygous for the haplotype to GD siblings (72%) was seen in the families (chi2 = 11.95; 1 d.f.; P = 0.0005). Lack of preferential transmission to unaffected siblings (53%; chi2 = 0.19; 1 d.f.; P = NS) excluded segregation distortion. These results show that linkage disequilibrium between GD and the HLA class II region is due to the extended haplotype DRB1*0304-DQB1*02-DQA1*0501.

Alleles↗
PubMed1997

Sex hormone preparations and retinal vein occlusion.

Retinal vein occlusion (RVO) is most commonly seen in middle-aged or older patients and is associated with underlying cardiovascular risk factors. It is much less common in younger patients. Use of the oral contraceptive pill (OCP) is known to be a risk factor for cardiovascular and cerebrovascular disease. There have previously been a few isolated case reports of patients sustaining an RVO whilst taking the OCP. The aim of this study was to investigate patients sustaining an RVO whilst taking the OCP or hormone replacement therapy (HRT). From a large series of 588 patients, we found 11 with an RVO associated with sex hormone preparations. Of these, 6 had taken the OCP and 5 were HRT users. From this large group there were only 9 female patients aged under 35 years who sustained an RVO. Of these, 6 were associated with use of the OCP. All patients were investigated for recognised medical risk factors for RVO. None of these factors were identified in the patients who had used the OCP. Of the patients taking HRT, 4 of the 5 had other potential risk factors. From our large series, the prevalence of RVO in female patients under 35 years taking the OCP was 66%. There is a 30% uptake of the OCP in the general population. These data support the view that RVO is a contraindication to the use of the OCP. Additionally, it would appear (albeit from limited data) that patients who sustain RVO may continue with their HRT, as HRT is not a major single risk factor for RVO.

Adult↗
PubMed1997

Diabetic eye disease: a natural history study.

In previous studies on diabetic retinopathy it has not been possible to relate risk factors to reduced vision because of the influence of vision-preserving treatment. Demographic data, cardiovascular risk factors and ocular features from the diabetic population of the Seychelles are described. Diabetic retinopathy in this population had not been modified by laser treatment. The population described consists of entirely type 2, maturity onset diabetics. Using a multivariate logistic regression model, the risk factors were deduced for three outcome variables: (1) reduced vision, defined as 6/36 or worse in both eyes; (2) the presence of diabetic retinopathy; and (3) the presence of maculopathy, preproliferative and proliferative retinopathy, grouped as severe retinopathy. Insulin treatment was associated with all outcome variables, duration from diagnosis of diabetes with retinopathy of all forms, and increasing age with reduced vision and severe retinopathy. Hypertensive diabetic patients were twice as likely to have reduced vision as compared with non-hypertensive diabetic individuals.

Adult↗