J Atiea

Bio: J Atiea is an academic researcher from University of Wales. The author has contributed to research in topics: Insulin & Renal function. The author has an hindex of 8, co-authored 11 publications receiving 286 citations.

Possible new method to improve detection of diabetic retinopathy: Polaroid non-mydriatic retinal photography.

Abstract: Two retinal cameras (Canon CR2 45NM and CR3 45NM) have recently become available and are capable of producing an instant colour photography of a 45 degree field of retina, including the macula and optic disc, without dilatation of the pupils being necessary. The ability of each camera to detect diabetic retinopathy was compared with that of doctors in diabetic clinics using ophthalmoscopy during busy clinic hours. The CR3 was found to be considerably superior to the CR2 in terms of quality of photograph because it can use a smaller pupil. Overall, the detection rate of the camera was more than four times higher than that of ophthalmoscopy through undilated pupils and more than twice as high as that of ophthalmoscopy through dilated pupils. Lesions missed by ophthalmoscopy but detected by the camera included soft exudates and circinate rings of hard exudates, sometimes encroaching on the macula. Though various aspects of this system of screening for diabetic retinopathy, in particular its ability to detect new retinal vessels, have not yet been assessed, the system may prove beneficial in the detection and monitoring of diabetic retinopathy.

Renal response to intravenous somatostatin in insulin-dependent diabetic patients and normal subjects.

Abstract: The acute effects of iv somatostatin (SRIH; 100 micrograms/h) on the urinary flow (Uvol), effective renal plasma flow (RPF), and glomerular filtration rate (GFR) were compared with those of a control infusion of 0.15 M NaCl in nine insulin-dependent diabetic (IDD) patients of less than 10 yr disease duration and six normal subjects (NS). RPF and GFR were measured using a standard primed constant isotope infusion of [125I]iodohippurate and [51Cr]chromium EDTA. Uvol, RPF, and GFR were measured during 20-min clearance periods. During the NaCl infusion mean Uvol, RPF, and GFR were 14.1 +/- 0.2 (+/- SEM), 708 +/- 4, and 150 +/- 1 mL/min in the IDD group and 12.7 +/- 0.4, 568 +/- 5, and 110 +/- 2 mL/min in the NS group, respectively. In the IDD patients Uvol, RPF, and GFR decreased from 16.6 +/- 1.8, 670 +/- 30, 146 +/- 4 mL/min pre-SRIH to 9.2 +/- 1 (P less than 0.001), 553 +/- 25 (P less than 0.001), and 130 +/- 5 (P less than 0.001) mL/min, respectively, at 120 min during the SRIH infusion. Similarly, in the NS group mean Uvol, RPF, and GFR were 14.2 +/- 0.6, 552 +/- 15, and 112 +/- 5 mL/min pre-SRIH and decreased to 7.4 +/- 0.6 (P less than 0.001), 422 +/- 7 (P less than 0.001), and 93 +/- 3 (P less than 0.001) mL/min, respectively, after 120 min of the SRIH infusion. SRIH, therefore, had a profound effect on renal function in both IDD patients and NS, resulting in a reduction in RPF, GFR, and, as a consequence, Uvol.

Effect of somatostatin on renal function

Abstract: Somatostatin has profound effects on both splanchnic and portal vascular beds. The effects of intravenous somatostatin (100 micrograms/h) on urinary volume, effective renal plasma flow, and glomerular filtration rate were compared with the effects of a control infusion of physiological saline in six normal subjects. Renal plasma flow and glomerular filtration rate were measured by primed constant isotope infusions of iodine-125 iodohippurate and chromium-51 edetic acid. Urinary volume, renal plasma flow, and glomerular filtration rate were measured during 20 minute clearance periods. During the control infusion urinary volume, renal plasma flow, and glomerular filtration rate remained essentially unchanged at 254 (SEM 3) ml/20 min, 568 (5) ml/min/1.73 m2, and 110 (2) ml/min/1.73 m2 respectively. From similar basal values the infusion of somatostatin led to a rapid decrease in all three variables. After 120 minutes of infusion of somatostatin urinary volume, renal plasma flow, and glomerular filtration rate were reduced to 148 (17) ml/20 min (p less than 0.01), 422 (7) ml/min/1.73 m2 (p less than 0.001), and 93 (3) ml/min/1.73 m2 (p less than 0.05) respectively. This effect on renal function should be borne in mind whenever somatostatin is used.

Recombinant DNA derived monomeric insulin analogue: comparison with soluble human insulin in normal subjects.

Abstract: OBJECTIVE--To compare the rate of absorption from subcutaneous tissue and the resulting hypoglycaemic effect of iodine-125 labelled soluble human insulin and a monomeric insulin analogue derived by recombinant DNA technology. DESIGN--Single blind randomised comparison of equimolar doses of 125I labelled soluble human insulin and insulin analogue. SETTING--Study in normal people at a diabetes research unit and a university department of medical physics. SUBJECTS--Seven healthy male volunteers aged 20-39 not receiving any other drugs. INTERVENTIONS--After an overnight fast and a basal period of one hour two doses (0.05 and 0.1 U/kg) of 125I labelled soluble human insulin and insulin analogue were injected subcutaneously into the anterior abdominal wall on four separate days. END POINT--To find a fast acting insulin for meal related requirements in insulin dependent diabetics. MEASUREMENTS and main results--Residual radioactivity at the injection site was measured continuously for the first two hours after injection of the 125I labelled preparations and thereafter for five minutes simultaneously with blood sampling. Frequent venous blood samples were obtained over six hours for determination of plasma immunoreactive insulin, insulin analogue, glucose, and glucagon values. Time to 50% of initial radioactivity at the injection site for the insulin analogue compared with soluble insulin was 61 v 135 minutes (p less than 0.05) with 0.05 U/kg and 67 v 145 minutes (p less than 0.001) with 0.1 U/kg. Concentrations in plasma increased faster after the insulin analogue compared with soluble insulin, resulting in higher plasma concentrations between 10 and 150 minutes (0.001 less than p less than 0.05) after 0.05 U/kg and between 40 and 360 minutes (0.001 less than p less than 0.05) after 0.1 U/kg. The hypoglycaemic response to insulin analogue was a plasma glucose nadir at 60 minutes with both doses compared with 90 and 120 minutes with soluble insulin at 0.5 and 0.1 U/kg respectively. The response of glucagon substantiated the earlier and more dramatic hypoglycaemic effect with the insulin analogue. CONCLUSIONS--The much faster absorption from subcutaneous tissue of the disubstituted monomeric insulin analogue compared with soluble insulin suggests that the analogue may be a potential candidate for rapid insulin delivery after subcutaneous bolus injection.

Roles of circadian rhythmicity and sleep in human glucose regulation

Abstract: I. Introduction II. Characteristics and Causal Mechanisms of 24-h Rhythms of Glucose Regulation in Normal Young Subjects A. 24-h variations in glucose tolerance B. Causal mechanisms III. Alterations of 24-h Rhythms of Glucose Regulation in Normal Aging A. Daytime variations in glucose tolerance B. Nighttime variations in glucose tolerance C. Respective roles of sleep and time of day D. Significance and clinical implications IV. Diurnal Variations of Glucose Regulation in Obesity A. Daytime variations in glucose tolerance B. Nighttime variations in glucose tolerance C. Significance and clinical implications V. Alterations in 24-h Rhythmicity of Glucose Regulation in Non-Insulin-Dependent Diabetes Mellitus (NIDDM) A. Alterations in daytime variations in glucose tolerance B. Alterations in nighttime variations in glucose levels during fasting C. Significance and clinical implications VI. Alterations in 24-h Rhythmicity of Glucose Regulation in Insulin-Dependent Diabetes Mellitus (IDDM) A. Alterations in dayt...

Automatic detection of diabetic retinopathy using an artificial neural network : a screening tool

Abstract: AIMS: To determine if neural networks can detect diabetic features in fundus images and compare the network against an ophthalmologist screening a set of fundus images. METHODS: 147 diabetic and 32 normal images were captured from a fundus camera, stored on computer, and analysed using a back propagation neural network. The network was trained to recognise features in the retinal image. The effects of digital filtering techniques and different network variables were assessed. 200 diabetic and 101 normal images were then randomised and used to evaluate the network's performance for the detection of diabetic retinopathy against an ophthalmologist. RESULTS: Detection rates for the recognition of vessels, exudates, and haemorrhages were 91.7%, 93.1%, and 73.8% respectively. When compared with the results of the ophthalmologist, the network achieved a sensitivity of 88.4% and a specificity of 83.5% for the detection of diabetic retinopathy. CONCLUSIONS: Detection of vessels, exudates, and haemorrhages was possible, with success rates dependent upon preprocessing and the number of images used in training. When compared with the ophthalmologist, the network achieved good accuracy for the detection of diabetic retinopathy. The system could be used as an aid to the screening of diabetic patients for retinopathy.

Monomeric insulins and their experimental and clinical implications.

Abstract: Due to the inherent pharmacokinetic properties of available insulins, normoglycemia is rarely, if ever, achieved in insulin-dependent diabetic patients without compromising their quality of life. Subcutaneous insulin absorption is influenced by many factors, among which the associated state of insulin (hexameric) in pharmaceutical formulation may be of importance. This review describes the development of a series of human insulin analogues with reduced tendency to self-association that, because of more rapid absorption, are better suited to meal-related therapy. DNA technology has made it possible to prepare insulins that remain dimeric or even monomeric at high concentration by introducing one or a few amino acid substitutions into human insulin. These analogues were characterized and used for elucidating the mechanisms involved in subcutaneous absorption and were investigated in preliminary clinical studies. Their relative receptor binding and in vitro potency (free-fat cell assay), ranging from 0.05 to 600% relative to human insulin, were strongly correlated (r = 0.97). In vivo, most of the analogues exhibited approximately 100% activity, explainable by a dominating receptor-mediated clearance. This was confirmed by clamp studies in which correlation between receptor binding and clearance was observed. Thus, an analogue with reduced binding and clearance gives higher circulating concentrations, counterbalancing the reduced potency at the cellular level. Absorption studies in pigs revealed a strong inverse correlation (r = 0.96) between the rate of subcutaneous absorption and the mean association state of the insulin analogues. These studies also demonstrated that monomeric insulins were absorbed three times faster than human insulin. In healthy subjects, rates of disappearance from subcutis were two to three times faster for dimeric and monomeric analogues than for human insulin. Concomitantly, a more rapid rise in plasma insulin concentration and an earlier hypoglycemic response with the analogues were observed. The monomeric insulin had no lag phase and followed a monoexponential course throughout the absorption process. In contrast, two phases in rate of absorption were identified for the dimer and three for the normal hexameric human insulin. The initial lag phase and the subsequent accelerated absorption of soluble insulin can now be explained by the associated state of native insulin in pharmaceutical formulation and its progressive dissociation into smaller units during the absorption process. In the light of these results, the effects of insulin concentration, injected volume, temperature, and massage on the absorption process are now also understood.(ABSTRACT TRUNCATED AT 400 WORDS)

Sensitivity and specificity of photography and direct ophthalmoscopy in screening for sight threatening eye disease: the Liverpool diabetic eye study

Abstract: Abstrac Objective: To evaluate different methods for community based screening for sight threatening diabetic eye disease. Design: Prospective study. Setting: Mobile screening unit visiting inner city community clinics; hospital assessment clinic (tertiary centre). Subjects: 395 diabetic patients registered with four general practices in an inner city location. Interventions: Community based photography with mydriasis and direct ophthalmoscopy through dilated pupils by an experienced ophthalmologist, both compared with reference standard of slit lamp biomicroscopy by a consultant specialist in medical retinal disease. Main outcome measures: Sensitivity and specificity of screening method and prevalence of sight threatening diabetic eye disease (moderate preproliferative retinopathy, circinate maculopathy, exudate within 1 disc diameter of fixation, other diabetes related eye disease). Results: 358 subjects underwent photography, 326 attended hospital clinic for ophthalmoscopy, and six were ungradable on photographs and biomicroscopy, leaving 320 for analysis. Of these 295 (91%) attended clinic within four months of photography. Sensitivity of detection of eye disease by photography was 89% (95% confidence interval 80% to 98%), significantly better than for direct ophthalmoscopy (65% (51% to 79%)). Analysis of patients with false negative results indicated possible improvement of photographic sensitivity to 93% by addition of stereoscopic macular pair photographs. Specificity of detection of sight threatening eye disease was 86% (82% to 90%) for photography and 97% (95% to 99%) for direct ophthalmoscopy. Conclusions: Since high sensitivity is essential for an effective screening programme, a photographic method should be considered as preferred option in national, community based screening programmes. Even in the hands of an experienced ophthalmologist, direct ophthalmoscopy is limited by weaknesses inherent to the instrument.