Search PubMed⌕ Search

Biomedical subjects

J M Gibson

Publications and source records attributed to J M Gibson.

At least 19 recordsLinked to original sources

Quantitative analysis of multi-spectral fundus images.

We have developed a new technique for extracting histological parameters from multi-spectral images of the ocular fundus. The new method uses a Monte Carlo simulation of the reflectance of the fundus to model how the spectral reflectance of the tissue varies with differing tissue histology. The model is parameterised by the concentrations of the five main absorbers found in the fundus: retinal haemoglobins, choroidal haemoglobins, choroidal melanin, RPE melanin and macular pigment. These parameters are shown to give rise to distinct variations in the tissue colouration. We use the results of the Monte Carlo simulations to construct an inverse model which maps tissue colouration onto the model parameters. This allows the concentration and distribution of the five main absorbers to be determined from suitable multi-spectral images. We propose the use of "image quotients" to allow this information to be extracted from uncalibrated image data. The filters used to acquire the images are selected to ensure a one-to-one mapping between model parameters and image quotients. To recover five model parameters uniquely, images must be acquired in six distinct spectral bands. Theoretical investigations suggest that retinal haemoglobins and macular pigment can be recovered with RMS errors of less than 10%. We present parametric maps showing the variation of these parameters across the posterior pole of the fundus. The results are in agreement with known tissue histology for normal healthy subjects. We also present an early result which suggests that, with further development, the technique could be used to successfully detect retinal haemorrhages.

Algorithms↗

Insulin-like growth factor binding protein-2 (IGFBP-2) is a marker for the metabolic syndrome.

AIMS/HYPOTHESIS: IGFs and their binding proteins are increasingly recognised as important in understanding the pathogenesis of cardiovascular disease. Low IGFBP-1, particularly coupled with low IGF-I, is associated with increased cardiovascular risk. In relation to structural and regulatory parallels between IGFBP-1 and - 2 we have now examined the hypothesis that IGFBP-2 may be a marker for cardiovascular risk. METHODS: Fasting IGFBP-2, IGFBP-1, IGFBP-3, IGF-I, IGF-II, insulin, C-peptide, glucose, lipids, NEFAs, and HbA1c were measured in a cohort of 163 patients with type 2 diabetes. Individuals were categorised according to the presence or absence of the metabolic syndrome. RESULTS: Patients with the metabolic syndrome had a lower IGFBP-2 concentration. Low circulating IGFBP-2 was associated with elevated fasting glucose (rho = - 0.23, p = 0.003). IGFBP-2 correlated negatively with triglycerides (rho = - 0.19, p = 0.01) and LDL-cholesterol (rho = - 0.20, p = 0.01), and positively with insulin sensitivity (HOMA-S) (rho = 0.26, p = 0.02). Multivariate logistic regression demonstrated that low IGFBP-2 was independently associated with an increased risk of the metabolic syndrome (OR 0.31 [95 % CI 0.11 - 0.90]; p = 0.03). IGFBP-3 did not differ according to the presence or absence of metabolic syndrome. CONCLUSION/INTERPRETATION: Low IGFBP-2 is associated with multiple cardiovascular risk factors similarly to IGFBP-1. Such associations were not apparent for IGFBP-3. Lack of marked prandial regulation of IGFBP-2, in contradistinction to IGFBP-1, may make IGFBP-2 a more robust biomarker for identification of insulin-resistant individuals at high cardiovascular risk in epidemiological studies.

Biomarkers↗

GAD antibodies in probands and their relatives in a cohort clinically selected for Type 2 diabetes.

AIMS: A subset of patients who present as if they have Type 2 diabetes have positive pancreatic autoantibodies, and have been referred to as having latent autoimmune diabetes in adults (LADA). We assessed the prevalence and clinical characteristics of patients with glutamic acid decarboxylase antibodies (GADA) in a cohort clinically selected for Type 2 diabetes and determined the presence of diabetes and GADA in their first-degree relatives. METHODS: GADA were measured in 2059 subjects, not known to be related, and clinically selected as having Type 2 diabetes for genetic studies. Clinical characteristics were compared in GADA positive and GADA negative subjects. Diabetes and GAD antibody status were compared in 208 first-degree relatives of GADA positive and GADA negative probands. RESULTS: Of the subjects, 136 (7%) were GADA positive. Compared with the GADA negative subjects, they were slimmer (P < 0.001), diagnosed at a younger age (P = 0.011) and progressed to insulin faster (P < 0.001). Thirty-three per cent of GADA positive subjects had a first-degree relative with diabetes compared with 42% of GADA negative subjects (P = 0.034). The overall prevalence of GADA was similar in the first-degree relatives of GADA positive and GADA negative probands (4 v 5%), and 19 of 22 (86%) diabetic relatives of GADA positive probands were GADA negative. CONCLUSION: Despite clinically selecting a Type 2 diabetes cohort, 7% were GADA positive with an altered phenotype. These GADA positive patients had a strong family history of non-autoimmune diabetes. This suggests that, in this subgroup of patients, autoimmune pancreatic beta-cell destruction occurs on a background of Type 2 diabetes genetic susceptibility.

Adult↗

Marked differences in the IGF system that are associated with migration in comparable populations of Gujaratis living in Sandwell, UK, and Gujarat, India.

AIMS/HYPOTHESES: We previously reported independent links between the IGF system and the development of impaired glucose tolerance and cardiovascular risk. This study tests the hypothesis that the lifestyle change which accompanies population migration, with attendant increases in cardiovascular risk, is reflected by changes in the IGF system. MATERIALS AND METHODS: We compared a specific Gujarati community in Sandwell, UK (n=205), with people still resident in the same villages of origin near Navsari, India (n=246). We performed anthropometry and measured fasting plasma insulin, IGF-I, insulin-like growth factor binding protein (IGFBP)-1 and IGFBP-3. RESULTS: Daily calorie intake, BMI and WHR were significantly higher in UK Gujaratis than in Indian Gujaratis. IGFBP-1 was significantly lower in UK migrants (mean 29.5 [95% CI 25.9-33.0] vs 56.5 [50.6-62.5] microg/l; F=48.4, p<0.001). Conversely, fasting insulin, IGFBP-3 and IGF-I were all higher in UK Gujaratis (mean IGF-I 145.9 [138.1-153.6]ng/ml in UK Gujaratis and 100.9 [94.6-107.3] ng/ml in Navsari Gujaratis; F=76.6, p<0.001). These differences were still apparent when adjustment was made for BMI by location for IGF-I (F=57.4, p<0.001) and IGFBP-3 (F=5.7, p=0.02), but were no longer apparent for IGFBP-1 and insulin. At the population level, the decrease in IGFBP-1 for a given increase in insulin was significantly smaller in UK Gujaratis, suggesting greater hepatic insulin resistance in this group. CONCLUSIONS/INTERPRETATION: Environmental factors have profound effects on circulating IGF system components and on the relationship between IGFBP-1, IGF-I and related metabolic variables. This may have long-term implications for the development of worsening glucose tolerance and cardiovascular disease.

Blood Glucose↗

Is measurement of blood pressure worthwhile in the diabetic eye clinic?

PURPOSE: The UK Prospective Diabetic Study has confirmed the importance of blood pressure (BP) as a major risk factor for diabetic retinopathy (DR). We wanted to investigate whether measuring the BP in the diabetic eye clinic could identify new hypertensive patients and monitor control in existing ones. PATIENTS AND METHODS: We compared BP in patients attending the diabetic eye clinic with home blood pressure measurement (HBPM) and ambulatory BP measurement (ABPM). In all, 106 patients attending a diabetic eye clinic were selected at random from clinic attendees. BP measurement (on an Omron 705 CP) was performed in the eye clinic and also compared to HBPM three times per day with an Omron 705 CP machine, and was compared to diabetic clinic measurements. In addition, 11 randomly chosen patients had 24 h ABPM to validate the above techniques. RESULTS: In all, 106 patients (70 male and 36 female) were recruited for the study, of which 71 were known to be hypertensive on antihypertensive medication. Of the total, 75 patients (70.8%) had BP > 140/85 in the eye clinic, of which 51 (68%) were known to be hypertensive on treatment and this was confirmed in 46 (90%) on HBPM. A total of, 24 patients (22.6%) were newly diagnosed as hypertensive in the eye clinic, which was confirmed by HBPM in 22 patients (92%). The mean BP of the measurements performed in the eye clinic was significantly higher than that carried out in the diabetic clinic (P < 0.01). Tropicamide 1% and phenylephrine 2.5% eye drop instillation had no effect on BP. In 11 randomly chosen patients, 24 h ABPM validated both diabetic eye clinic and home BP measurements. CONCLUSION: Attendance at the diabetic eye clinic is an important chance to detect both new patients with systemic hypertension and those with inadequate BP control. Ophthalmologists should be encouraged to measure BP in their diabetic patients attending diabetic eye clinics, as it is an important risk factor for DR. On the basis of our findings, good BP control is a goal yet to be achieved in diabetic patients with retinopathy.

Adult↗

Low sex hormone binding globulin is a potential marker for the metabolic syndrome in different ethnic groups.

Hepatic sex-hormone binding globulin (SHBG) production is down-regulated by insulin and low levels reflect insulin resistance. Because insulin resistance is closely related to the development of cardiovascular disease in different ethnic groups we examined ethnic variation in SHBG across populations with different baseline cardiovascular risk and metabolic syndrome prevalence. Participants were population-based, of European (n = 142), Pakistani (n = 130), and African-Caribbean (AfC) origin (n = 193). SHBG, fasting lipids, and glucose concentrations plus insulin sensitivity (HOMA-S) were determined. Age adjusted SHBG was significantly lower in both Pakistani men and women. Circulating SHBG levels were lower in those with impaired vs. normal glucose homeostasis. SHBG correlated positively with HOMA-S (rho = 0.28, p < 0.001), and negatively with WHR (rho = - 0.38, p < 0.001), BMI (r = - 0.30, p < 0.001), and diastolic blood pressure (rho = - 0.14, p < 0.01) across all ethnic groups. In multivariate logistic regression analysis a low SHBG increased the likelihood of the metabolic syndrome (odds ratio [OR] = 0.42 [0.21 - 0.82], p = 0.01) as did higher fasting NEFA (OR 1.47 [1.04 - 2.08], p = 0.03), low IGFBP-1 concentrations (OR 0.6 [0.44 - 0.81], p = 0.001), age (OR 1.05 [1.02 - 1.09], p = 0.003), and Pakistani ethnicity (p = 0.001) in a model which also contained gender, lnCRP, IGF-I, and IGF-II. As ethnic differences in SHBG level closely parallel differences in insulin resistance. Its measurement may be useful in identifying individuals at particular risk of the metabolic syndrome, for early intervention.

Biomarkers↗

Dietary intake and the insulin-like growth factor system: effects of migration in two related populations in India and Britain with markedly different dietary intake.

BACKGROUND: The insulin-like growth factor (IGF) system is implicated in the pathogenesis of diabetes and cardiovascular disease. OBJECTIVE: We report the effects of total energy intake on the IGF system in two populations with markedly different dietary macronutrient intake and cardiovascular event rate. DESIGN, SUBJECTS AND SETTING: Dietary macronutrient intake was measured in a specific Gujarati migrant community in Sandwell, UK (n=205) compared with people still resident in the same villages of origin in India (n=246). Fasting IGF-I, IGF-binding protein (IGFBP)-1 and IGFBP-3, insulin and glucose (0 and 2-hour) were measured. RESULTS: Total energy and total fat intake were higher in UK migrants, as were IGFBP-3 and IGF-I (mean (95% confidence interval): 145.9 (138.1-153.6) vs. 100.9 (94.6-107.3) ng ml(-1); F=76.6, P<0.001). IGFBP-1 was lower in UK migrants (29.5 (25.9-33.0) vs. 56.5 (50.6-62.5) microg l(-1); F=48.4, P<0.001). At both sites, IGF-I correlated positively with total energy (Spearman's rho=0.45, P<0.001) and total fat (rho=0.44, P<0.001) as did IGFBP-3 with total energy (rho=0.21, P<0.05) and fat (rho=0.26, P<0.001). Conversely, in Indian Gujaratis, IGFBP-1 fell with increasing total energy (rho=-0.27, P<0.001) and fat intake (rho=-0.26, P<0.01) but not in UK Gujaratis. Multiple linear regression modelling showed that increasing quartiles of fat intake were associated with higher IGF-I (beta=0.42, P=0.007) independent of age, body mass index, plasma insulin, fatty acids and 2-hour glucose. CONCLUSION: In these genetically similar groups, migration to the UK and adoption of a different diet is associated with marked changes in the IGF system, suggesting that environmental factors profoundly modulate serum concentrations and actions of IGFs.

Blood Glucose↗

PINK1 (PARK6) associated Parkinson disease in Ireland.

Mutations in the PINK1 gene have recently been shown to cause autosomal recessive Parkinson disease (PD). The authors assessed the prevalence of PINK1 gene mutations in 290 well-characterized early- and late-onset PD patients from Ireland. In a 51-year-old PD patient with a family history of PD, the authors identified a novel heterozygous mutation (R147H) in exon 2 of the PINK1 gene. Overall, these data indicate that PINK1 mutations are a rare cause of PD in Ireland.

Adolescent↗

Does cardiovascular therapy affect the onset and recurrence of preretinal and vitreous haemorrhage in diabetic eye disease?

AIMS: To review the role of cardiovascular disease and therapy in the onset and recurrence of preretinal/vitreous haemorrhage in diabetic patients. METHODS: Retrospective case note analysis of diabetic patients with vitreous haemorrhage from the Diabetic Eye Clinic at Birmingham Heartlands Hospital. RESULTS: In total, 54 patients (mean age 57.1, 37 males, 20 type I vs 34 type II diabetic patients) were included. The mean (SD) duration of diagnosed diabetes at first vitreous haemorrhage was significantly longer, 21.9 (7.6) years for type I and 14.8 (9.3) years for type II diabetic patients (P < 0.01, unpaired t-test, two-tailed).Aspirin administration was not associated with a significantly later onset of vitreous haemorrhage. Four episodes were associated with ACE-inhibitor cough. There was a trend towards HMGCoA reductase inhibitor (statin) use being associated with a delayed onset of vitreous haemorrhage: 21.4 years until vitreous haemorrhage (treatment group) vs 16.2 years (nontreatment group) (P = 0.09, two-tailed, unpaired t-test, not statistically significant). During follow-up 56 recurrences occurred, making a total of 110 episodes of vitreous haemorrhage in 79 eyes of 54 patients. The mean (range) follow-up post haemorrhage was 1067 (77-3842) days, with an average of 1.02 recurrences. Age, gender, diabetes type (I or II) or control, presence of hypertension or hypercholesterolaemia, and macrovascular complications were not associated with a significant effect on the 1-year recurrence rate. Aspirin (and other antiplatelet or anticoagulant agents) and ACE- inhibitors appeared to neither increase nor decrease the 1-year recurrence rate. However, statin use was significantly associated with a reduction in recurrence (Fisher exact P < 0.05; two-tailed) with an odds ratio (95% CI) of 0.25 (0.1-0.95). CONCLUSION: In this retrospective analysis, the onset of preretinal/vitreous haemorrhage was not found to be accelerated by gender, hypertension, hypercholesterolaemia, evidence of macrovascular disease, or HbA1c. Neither aspirin nor ACE-inhibitor administration accelerated the onset or recurrence of first vitreous haemorrhage. Statins may have a protective role, both delaying and reducing the recurrence of haemorrhage.

Adult↗

Educational outreach in diabetes to encourage practice nurses to use primary care hypertension and hyperlipidaemia guidelines (EDEN): a randomized controlled trial.

OBJECTIVE: To determine the effectiveness of specialist nurse delivered education in primary care to improve control of hypertension and hyperlipidaemia in patients with diabetes. DESIGN AND SETTING: Practice-level randomized controlled trial, Salford, England. SUBJECTS: From 44 practices, 10 303 subjects presenting in general practice with raised blood pressure (= 140/80 mmHg), raised total cholesterol (= 5.0 mmol/l) or both. INTERVENTIONS: Practices were randomized to receive either the intervention for hyperlipidaemia or for hypertension; practices acted as control for the intervention not received. Specialist nurses arranged a schedule of visits with general practitioners and general practice nurses, reminding them of diabetes protocols and clinical targets. They provided educational materials and protocols used in secondary care for nurse and doctor interventions including stepping up pharmacotherapy when necessary. Practices received a list of patients in their practice who were poorly controlled at their last annual review; new and recalled patients were targeted. OUTCOME MEASURES: At subsequent annual review, blood pressure and total cholesterol values were obtained from the Salford electronic diabetes register for patients from participating practices. RESULTS: Overall, specialist nurse-led educational outreach to primary care was associated with no improvement in patients achieving target after 1 year-odds ratio (OR): 1.03 (95% CI 0.95-1.11; P = 0.52). Similar results were achieved with hyperlipidaemia OR: 1.04 (95% CI 0.88-1.23; P = 0.62) and hypertension OR: 1.01 (95% CI 0.80-1.27; P = 0.93). CONCLUSION: This study provides evidence that the use of specialist nurses to perform educational outreach to improve target adherence to patients with diabetes in primary care is not effective.

Blood Pressure↗

Evaluation of a bedside blood ketone sensor: the effects of acidosis, hyperglycaemia and acetoacetate on sensor performance.

AIMS: To assess the performance of a handheld bedside ketone sensor in the face of likely metabolic disturbances in diabetic ketoacidosis, namely: pH, glucose and acetoacetate. METHODS: The effects of pH (7.44-6.83), glucose (5-50 mmol/l) and acetoacetate (0-5 mmol/l) were examined in venous blood to investigate the accuracy of betahydroxybutyrate measurement (0-5 mmol/l) by a handheld ketone sensor. Sensor results were compared with a reference method. Linear regression models were fitted to the difference between the methods with the concentration of metabolite as the explanatory factor. RESULTS: Decreasing pH and increasing glucose had no effect on the accuracy of the handheld ketone sensor; the gradients of the fitted lines were -0.14 and -0.003, respectively. The 95% confidence intervals were -0.7-0.4 and -0.01-0.004, respectively (P = 0.59 and 0.4, respectively). In the acetoacetate study, a positive relationship between the sensor and reference method results was found, the gradient was 0.09. The 95% confidence interval was 0.05-0.14 (P < or = 0.001), indicating that high concentrations of acetoacetate interfere with the sensor performance. CONCLUSIONS: Acidosis and hyperglycaemia have minimal effects on the sensor performance. However, high concentrations of acetoacetate result in some overestimation of betahydroxybutyrate. This bedside ketone sensor provides useful data over a broad range of conditions likely to be encountered during moderate to severe diabetic ketoacidosis.

Acetoacetates↗

A protocol for improved glycaemic control following corticosteroid therapy in diabetic pregnancies.

AIMS: Diabetic pregnancies have an increased risk of respiratory distress syndrome (RDS) and preterm delivery. Antenatal corticosteroids can prevent RDS but induce acute severe hyperglycaemia. We have developed a protocol which prevents hyperglycaemia and can be used easily by ward staff. METHODS: Intramuscular dexamethasone is given in two doses 12 h apart. Subcutaneous insulin and diet are continued but from the first dexamethasone dose until 12 h after the second, supplementary intravenous insulin is infused according to hourly blood glucose measurements. The protocol incorporates four graded sliding scales. The initial scale is selected according to the patient's current subcutaneous insulin dose and advanced if the blood glucose is > or = 10.1 mmol/l for 2 consecutive hours. RESULTS: In a 10-month period eight (three gestational, five pre-gestational) women received antenatal corticosteroids from a total of 37 diabetic pregnancies. The median amount of supplementary intravenous insulin required was 74 U (range 32-88 U); the median glucose values achieved were 5.8-8.9 mmol/l. Seventy-five percent of glucose measurements were within an acceptable range of 4-10 mmol/l. Only one baby developed RDS. DISCUSSION: Large amounts of supplementary intravenous insulin are needed to achieve even moderate glycaemic control. This protocol enables routine ward staff to manage this successfully.

Clinical Protocols↗

The influence of dietary intake on the insulin-like growth factor (IGF) system across three ethnic groups: a population-based study.

OBJECTIVE: The insulin-like growth factor (IGF) system has been implicated in the aetiopathogenesis of cancer, cardiovascular disease and diabetes. Since dietary factors and ethnicity are considered contributory to the development of these diseases, we examined the IGF system in relation to nutritional intake by ethnic group. DESIGN, SUBJECTS AND SETTING: Dietary intake in 257 subjects of White European, African-Caribbean and Pakistani ethnic origin living in Manchester, UK was assessed using ethnic-group-specific food-frequency questionnaires to assess habitual nutrient intake over the previous 12 months. Fasting IGF-I, IGF-II and IGF-binding protein-1 (IGFBP-1) concentrations were determined and their relationship to specific dietary constituents was analysed. RESULTS: Analysis by quintiles of nutrient intake showed a significant increase in circulating IGF-I concentration with increasing dietary fat intake (F for trend=3.9, ), saturated fat intake and for protein intake There was also a significant increase in IGF-II by quintiles of dietary protein intake There was a trend for increasing IGF-I with increasing energy intake. The relationships between circulating concentration of IGFBP-1, an acute regulator of IGF action, and fat/protein intake were opposite to those for IGF-I and IGF-II. Multiple linear regression modelling showed that people of Pakistani origin and older subjects had lower levels of IGF-I (Pakistani origin vs. others, ) (age, for both). There was an independent inverse relationship between IGF-I and dietary carbohydrate intake CONCLUSIONS: This study provides evidence for a dietary contribution to regulation of the IGF system, although the effects of ethnicity on circulating IGF levels remain dominant. We propose that the IGF system's influences on cancer risk in specific ethnic groups are potentially modifiable by dietary intervention.

Adult↗

Superficial siderosis of the central nervous system many years after neurosurgical procedures.

Recurrent haemorrhage into the subarachnoid space causes superficial siderosis, which clinically manifests as cerebellar ataxia, sensorineural hearing loss, and myelopathy. Two patients developed clinical, radiological, and biochemical evidence of superficial siderosis many years after surgery. One had two posterior fossa operations, a left temporal craniectomy, and radiotherapy for a presumed brain tumour before developing clinical evidence of superficial sidersosis 37 years later. The other had small bilateral subdural collections from recurrent shunt revisions following posterior fossa surgery for a Chiari malformation, and then developed deafness and ataxia. The first patient currently has the longest recorded delay between presumed subarachnoid bleeding and clinical manifestations of superficial siderosis. Both patients provide further evidence that superficial siderosis of the central nervous system, a progressive neurodegenerative vascular condition, may be a delayed complication of neurosurgical procedures.

Adult↗