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Biomedical subjects

Toke Bek

Publications and source records attributed to Toke Bek.

At least 19 recordsLinked to original sources
PubMed2006

Visual prognosis after panretinal photocoagulation for proliferative diabetic retinopathy.

INTRODUCTION: Proliferative diabetic retinopathy is treated with panretinal photocoagulation, which improves the visual prognosis in this complication considerably. The visual acuity (VA) and grade of retinopathy before treatment are known indicators of the visual prognosis after treatment, but the prognostic value of other clinical background and treatment parameters is unknown. METHODS: The study reports predictors for visual outcome identified among retrospective clinical background data and treatment parameters from 4422 panretinal photocoagulation sessions for proliferative diabetic retinopathy in 1013 eyes of 601 patients performed at the Department of Ophthalmology, Arhus University Hospital between 1985 and 2002. RESULTS: High pretreatment VA and low age were strong positive predictors of post-treatment VA (p < 0.0001). However, diabetes type, diabetes duration and calendar year of treatment showed no influence on post-treatment VA (p = 0.7829, 0.1782, and 0.3747, respectively). The visual prognosis was inversely related to the number of treatment sessions (p = 0.0259) and the number of vitrectomies (OR = 2.66 [1.24; 5.69], p = 0.0117, for more than two operations). However, the visual prognosis was unrelated to any of the other parameters studied. CONCLUSIONS: Pretreatment VA, age and the number of panretinal photocoagulation treatment sessions and vitrectomies necessary to halt the disease are indicators of the visual prognosis after panretinal laser photocoagulation for proliferative diabetic retinopathy.

Adult↗
PubMed2005

Predominant rod photoreceptor degeneration in Leber congenital amaurosis.

PURPOSE: An unusual retinal vascular morphology in an enucleated eye from a patient with Leber congenital amaurosis (LCA) has been associated with a mutation in AIPL1. The AIPL1 protein is expressed in the pineal gland and retinal photoreceptors. In the retina, AIPL1 is expressed in both developing cone and rod photoreceptors, but it is restricted to rod photoreceptors in the adult human retina. Therefore, this study was conducted to determine the photoreceptor phenotype in this LCA patient to determine if photoreceptors were differentially affected. METHODS: Additional genetic screening was performed and the consequences of the H82Y amino acid substitution characterized in an in vitro assay of NUB1 modulation. The morphology of the photoreceptors was examined by light and electron microscopy. Immunohistochemistry and immunofluorescent confocal microscopy was performed using a range of retinal photoreceptor markers. RESULTS: Transfection of the H82Y mutant AIPL1 in SK-N-SH cells revealed a normal subcellular localization and solubility but resulted in an increased ability of AIPL1 to redistribute GFP-NUB1 to the cytoplasm and resolve NUB1 fragment inclusion formation. Morphologically, the LCA retina appeared to be cone-dominant with a single layer of cone-like cells remaining in the central retina. Photoreceptor outer segments were absent and the surviving residual inner segments were severely shortened. Severe degeneration of the LCA retina was associated with upregulation of glial fibrillary acidic protein (GFAP). No signal was detected for AIPL1, rhodopsin, or L/M and S cone opsins in the LCA retina. Double labeling with peanut agglutinin (PNA) and wheat germ agglutinin (WGA) supported a cone-dominant phenotype for the surviving photoreceptors in the LCA retina, as did double labeling for cone arrestin, and rod and cone recoverin. The cone arrestin signal was restricted to the residual photoreceptor inner segments and was not detected in the cell bodies, axons, or axon terminals of the surviving photoreceptors. Recoverin immunoreactivity was most intense in the residual photoreceptor inner segments. CONCLUSIONS: The phenotype in this patient suggests that although AIPL1 is required for the development of normal rod and cone photoreceptor function, it might only be essential for rod and not cone survival in the adult.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Mutation analysis of the WFS1 gene in seven Danish Wolfram syndrome families; four new mutations identified.

Wolfram syndrome (WS) is a neuro-degenerative autosomal recessive (AR) disorder (OMIM #222300) caused by mutations in the WFS1 gene on 4p16.1. More than 120 mutations have been identified in WFS1 associated with AR WS, as well as autosomal dominant nonsyndromic low-frequency sensorineural hearing loss (LFSNHL). WFS1 variants were identified in eight subjects from seven families with WS, leading to the identification of four novel mutations, Q194X (nonsense), H313Y (missense), L313fsX360 (duplication frame shift) and F883fsX951 (deletion frame shift), and four previously reported mutations, A133T and L543R (missense), V415del (in frame triple deletion) and F883fsX950 (deletion frame shift). A mutation was found in 11/14 disease chromosomes, two subjects were homozygous for one mutation, one subject was compound heterozygous for two nucleotide substitutions (missense), one subject was compound heterozygous for a duplication and a deletion (frame shift), and in three families only one mutation was detected (Q194X and H313Y). All affected individuals shared clinically early-onset diabetes mellitus and progressive optic atrophy with onset in the first and second decades, respectively. In contrast, diabetes insipidus was present in two subjects only. Various degrees and types of hearing impairment were diagnosed in six individuals and cataract was observed in five subjects.

Adolescent↗
PubMed2004

The age-dependent decrease in the myogenic response of retinal arterioles as studied with the Retinal Vessel Analyzer.

PURPOSE: To study the age-dependent change in myogenic response of retinal arterioles. METHODS: Fifty-one healthy volunteers with at least ten persons in each of the five age decades (I-V) between 20 and 69 years were subjected to diameter measurement of retinal arterioles using the Retinal Vessel Analyzer (RVA) during rest and during an increase in the systemic blood pressure when lifting hand weights. The transmural pressure in the retinal arterioles during the procedures was estimated from the blood pressure and the intraocular pressure and was compared to the accompanying diameter response. RESULTS: The retinal arteriolar diameter showed a significant decrease as a function of increasing weight for the two younger age groups below the age of 40 years (P=0.007, group I, and P=0.049, group II), compatible with perfect autoregulation, whereas no such change was observed in persons above this age (P=0.41, 0.053, 0.29 for groups III-V, respectively). CONCLUSION: Studies on autoregulation in retinal disease should consider the normal age-related decrease in diameter response of retinal arterioles when the blood pressure is changed.

Adult↗
PubMed2004

The prevalence of retinopathy in an unselected population of type 2 diabetes patients from Arhus County, Denmark.

PURPOSE: To determine the prevalence of diabetic retinopathy and the causes of visual impairment in an unselected population of type 2 diabetes patients, and to describe the risk factors for developing diabetic retinopathy in this population. METHODS: A total of 10 851 type 2 diabetes patients were identified in the county of Arhus. A representative sample of 378 patients underwent a routine ocular examination, including fundus photography. Blood pressure and serum haemoglobin A1c, total cholesterol, high density lipoprotein cholesterol, triglyceride and apolipoprotein a were measured. RESULTS: The prevalence of diabetic retinopathy in the type 2 diabetes population was 31.5%. In all, 2.9% had proliferative diabetic retinopathy and 5.3% had clinically significant macular oedema. Of the latter, 8/20 (40%) were newly identified and had not yet been laser-treated. There was a positive correlation between severity of retinopathy and duration of diabetes, HbA(1c), systolic blood pressure and treatment with insulin. None of the patients had social blindness (visual acuity < 0.1), but 15/378 (4.0%) had developed visual impairment (VA < 0.3). CONCLUSION: The prevalence of diabetic retinopathy and visual impairment in this unselected type 2 diabetes population was lower than anticipated from the existing literature, and causes other than diabetic retinopathy contributed significantly to the occurrence of visual loss. A substantial number of the patients with vision-threatening diabetic maculopathy had not been referred for timely photocoagulation treatment.

Aged↗
PubMed2004

The occurrence and causes of registered blindness in diabetes patients in Arhus County, Denmark.

PURPOSE: To report the occurrence of registered blindness among diabetes patients in Arhus County, Denmark during 1993-2002. METHODS: Data were obtained from a database of 7527 diabetes patients, which included all patients in the county who had been treated for or had experienced visual loss due to diabetic retinopathy since 1992. Of these, 1949 had type 1 diabetes and represented 90% of the type 1 diabetes patient population in the county, and 5459 had type 2 diabetes and represented 40% of the type 2 diabetes patient population in the county. RESULTS: The point prevalence of legal blindness was 0.6% for type 1 and 1.5% for type 2 diabetes patients at January 1st, 2003. In type 1 diabetes patients, the major cause of blindness was proliferative diabetic retinopathy (PDR) (66.2% of all blind eyes); in type 2 diabetes patients the major causes were age-related macular degeneration (21.9%), PDR (18.0%) and diabetic maculopathy (DMac) (18.5%). During 1993-2002 there was a significant decrease in the number of blind eyes secondary to PDR (p = 0.008) in type 1 diabetes patients, and a significant increase in the number of blind eyes secondary to DMac (p = 0.005) in type 2 diabetes patients. CONCLUSION: The major challenge in reducing diabetes-related blindness is related to the detection and treatment of an increased incidence of diabetic maculopathy in type 2 diabetes patients.

Adult↗
PubMed2004

TOSCA-Imaging--developing Internet based image processing software for screening and diagnosis of diabetic retinopathy.

The primary aim of TOSCA-Imaging, which was a part of the TOSCA Project financed by EU's Fifth Framework IST Programme, was to develop Internet based software and image data bases for screening and diagnosis of diabetic retinopathy and implementing it into a real life situation. The work consisted of: 1) Construction of an Internet based communication platform for transmitting and analyzing retinal images. 2) Implementation of routines for detecting the first microaneurysm (transition from normal to pathologic), detecting patients needing referral for treatment (presence of venous beading or hard exudates near the fovea), and for serial analysis (image alignment). 3) Construction of a reference image data base. A preliminary validation showed that decisions that depended on a precise detection of individual lesions, e.g. the detection of normality, had a sensitivity and specificity of around 80%, whereas decisions that depended on the detection of lesion patterns, e.g. clinically significant macular oedema, had a sensitivity and specificity of more than 95%. Validation of the reference image data base by double grading by two expert graders suggested a sensitivity and a specificity of just below 90% for any lesion and of more than 95% for predicting the overall retinopathy grade. TOSCA-Imaging has succeeded in its primary aim of developing Internet based software and implementing it into a real life situation, integrating work within image processing done in four different European countries (England, Germany, Ireland, and Denmark) to be accessed from one Internet web site.

Algorithms↗
PubMed2003

[Diagnostic value of the chromatic contents of fundus photography].

The optical properties of the human lens change with age and are affected by both ocular and systemic diseases. A usual change is a gradual diffuse browning or sclerosis of the lens nucleus. This nuclear sclerosis leads to selective absorption of short wave (blue) light when broad band (white) light is sent into the eye. During fundus photography a light is flashed in front of the eye which enters the pupil and is reflected from the retina to be recorded on film. The light from the flash will pass twice through the optics of the eye where the short wave lengths will be absorbed. A new method has succeeded in describing the correlation between age and the selective absorption of blue light in the ocular lens. Preliminary studies using this method have shown that the ocular lens displays increased "ageing" in diabetic patients which is probably related to the cumulative exposition to hyperglycemia. The advantages of the method are that it uses clinical data already available in patients with retinal diseases and that it is fast, inexpensive, and non-invasive to carry out. The method is another example of the eye as a significant viewer to the study of generalized diseases and their systemic complications.

Age Factors↗
PubMed2003

Characterization of vasomotion in porcine retinal arterioles.

PURPOSE: To characterize vasomotion in porcine retinal arterioles in vitro using isobaric (pressure myograph) and isometric (wire myograph) methods. METHODS: Pressure myograph: 208 small porcine retinal arterioles (outer diameter 68 +/- 4 microm) were studied under isobaric conditions in a double-barrelled pipette system. Diameter changes of the arterioles were registered by video recordings. Wire myograph: 60 large porcine retinal arterioles (inner diameter 147 +/- 1.6 microm) were studied under isometric conditions in a small vessel myograph for force measurements. RESULTS: The rates of success in initiating vasomotion were 7.2% using the pressure myograph and 43% using the wire myograph (p < 0.001). The small vessels studied under isobaric conditions oscillated with a frequency of 0.014 Hz and the episodes lasted 6.0 +/- 1.0 min, whereas the large vessels under isometric conditions oscillated with a significantly faster frequency of 0.043 Hz and lasted 32.1 +/- 4.9 min (p = 0.026). CONCLUSION: Retinal vasomotion can be studied in vitro using both pressure myograph and wire myograph techniques. The wire myograph is superior to the pressure myograph in initiating and maintaining vasomotion in vitro.

Animals↗
PubMed2003

Myogenic response in isolated porcine retinal arterioles.

PURPOSE: To study the myogenic response in large and small porcine retinal arterioles and the effects of blockade of L-type voltage gated calcium channels on the myogenic response. METHODS: Eleven large (outer diameter 137.7 +/- 4.5 micro m) and fourteen small (77.3 +/- 3.7 micro m) isolated porcine retinal arterioles were studied for myogenic response while mounted between two double-barrelled pipette systems. The intraluminal pressure was varied from 0 to 140 cm H( 2)O (0-103 mmHg) and the diameter changes of the arterioles were registered. The pressure-diameter relation was determined for arterioles in calcium-containing and calcium free solutions and during inhibition of the L-type voltage gated calcium channels with nifedipine. RESULTS: Both large and small retinal arterioles showed a decrease in diameter as the intraluminal pressure was increased, but no significant difference was found between large and small arterioles (p = 0.39). Blockade of voltage gated calcium channels significantly abolished the myogenic response (p = 0.010 and p = 0.005, large and small arterioles respectively). CONCLUSIONS: The results indicate that myogenic responses are present throughout the retinal arteriolar system and that L-type voltage gated calcium channels are involved in transforming the stretch of retinal vascular smooth muscle cells induced by an increase in intraluminal pressure into a contraction.

Animals↗
PubMed2003

Increased serum IGF-I during pregnancy is associated with progression of diabetic retinopathy.

The IGF system has been associated with development and progression of diabetic retinopathy. We examined whether a simple measurement of the IGF system (serum total IGF-I) correlated with progression of diabetic retinopathy in pregnancy in type 1 diabetes. A prospective observational study was performed in 103 pregnant women with type 1 diabetes. Serum IGF-I was measured in maternal serum from week 14, every fourth week until week 30, and every second week until delivery. Twenty-four-hour blood pressure was measured with a portable oscillometry monitor. The women had visual acuity testing and fundus photography before pregnancy, once in each trimester, and 4 months after birth. Each eye was assigned an overall retinopathy grade on a scale from 1 to 6 independently by two experienced graders. During pregnancy, serum IGF-I increased with increasing gestational age until a plateau was reached in week 32. Progression of retinopathy was significantly associated with a higher level of IGF-I (P < 0.01). Serum IGF-I increased with increasing progression of retinopathy. Change of retinopathy was significantly associated with level of IGF-I (P < 0.01). During pregnancy, serum IGF-I increased with increasing birth weight until a plateau was reached in week 32. Birth weight was significantly associated with a higher level of serum IGF-I (P < 0.01).

Adult↗
PubMed2003

Dual blockade with candesartan cilexetil and lisinopril in hypertensive patients with diabetes mellitus: rationale and design.

BACKGROUND: Blood pressure (BP) reduction is the key to risk reduction of cardiovascular disease or renal failure in hypertensive patients with diabetes mellitus. Inhibition of the renin-angiotensin system by an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin II receptor blocker (ARB) provides efficient BP reduction and renal protection in hypertensive diabetes patients. But, despite this, the recommended BP levels can be difficult to achieve and dual blockade therapy might be a possible way of obtaining efficient BP reduction in hypertensive patients with diabetes. Dual blockade treatment is based on a principle of obtaining the broadest and most efficient blockade of angiotensin II, by using the combination of an ACE-inhibitor and an ARB. METHODS: The Candesartan And Lisinopril Microalbuminuria (CALM II) study is a one centre, one observer, double-blind, randomised, active-controlled, parallel-group study, investigating the efficacy and tolerability of candesartan cilexetil in combination with lisinopril, compared with the maximum recommended dose of lisinopril in hypertensive patients with diabetes mellitus. The study design consists of two treatment arms with either 16 mg candesartan cilexetil or 20 mg lisinopril added to concomitant treatment with 20 mg lisinopril. It comprises 80 patients with a minimum of 35 patients in each group and statistical power of 90% to detect a difference in systolic BP reduction of 6.5 mmHg. CONCLUSION: The CALM II study aims to investigate the effects of dual blockade on systolic BP, albuminuria, left ventricular mass and function, and retinopathy in hypertensive patients with diabetes mellitus.

Antihypertensive Agents↗
PubMed2002

Pulse pressure and diurnal blood pressure variation: association with micro- and macrovascular complications in type 2 diabetes.

BACKGROUND: In nondiabetic subjects pulse pressure (PP) is an independent predictor of cardiovascular disease and microalbuminuria. Reduced circadian blood pressure (BP) variation is a potential risk factor for the development of diabetic complications. We investigated the association between retinopathy, nephropathy, macrovascular disease, PP, and diurnal BP variation in a group of type 2 diabetic patients. METHODS: In 80 type 2 diabetic patients we performed 24-h ambulatory BP (AMBP) and fundus photographs. Urinary albumin excretion was evaluated by urinary albumin/creatinine ratio. Presence or absence of macrovascular disease was assessed by an independent physician. RESULTS: Forty-nine patients had no detectable retinal changes (grade 1), 13 had grade 2 retinopathy, and 18 had more advanced retinopathy (grades 3-6). Compared to patients without retinopathy (grade 1), patients with grades 2 and 3-6 had higher PP and blunted diurnal BP variation: night PP 55 +/- 10 mm Hg, 64 +/- 10 mm Hg, 61 +/- 15 mm Hg, P < .05 and systolic night/day ratio 89.3% +/- 7%, 94.6% +/- 8%, and 92.0% +/- 6%, P < .05 (grade 1, 2, and 3-6, respectively). Comparing nephropathy groups (45 normo-, 19 micro-, and 15 macroalbuminuric patients) results were similar: night PP 54 +/- 9 mm Hg, 57 +/- 10 mm Hg, and 70 +/- 15 mm Hg, P < .001 and systolic night/day ratio 88.9% +/- 7%, 92.0% +/- 7%, and 94.9% +/- 7%, P < .02. Likewise, compared to patients without macrovascular disease (n = 55), patients with this complication (n = 25) had higher AMBP values: night PP 57 +/- 12 mm Hg v 63 +/- 11 mm Hg, P < .05 and systolic night/day ratio 89.2% +/- 6% v 94.1% +/- 9%, P < .01. CONCLUSIONS: Increased PP and blunted diurnal BP variation are hemodynamic abnormalities associated with micro- and macrovascular complications in type 2 diabetes.

Albuminuria↗
PubMed2002

A clinicopathological study of venous loops and reduplications in diabetic retinopathy.

PURPOSE: To study possible causes of the gradual venous occlusion that precedes the formation of venous loops and reduplications in diabetic retinopathy using histopathological techniques. METHODS: Casts of the retinal vascular system from six eyes of five diabetic patients were used to identify venous loops and reduplications. Subsequently the lesions were studied by immunohistochemistry using antibodies against cellular and non-cellular components previously shown to be disturbed in the diabetic retina. RESULTS: In all eyes the venous abnormalities identified on the casts were accompanied by abnormal wall partitions dividing the venous lumen. These partitions consisted of a double layer of flat cells displaying immunoreactivity to von Willebrand factor and actin (endothelial cells), but not to glial fibrillary acid protein or S-100 protein (glial cells), CD3, CD20, CD68, or neutrophil elastase (leucocytes). Neutrophile granulocytes adhering to the walls of larger retinal venules were unrelated to the venous partition and to capillary occlusion in the adjacent retinal areas. CONCLUSIONS: Venous loops and reduplications are associated with partitions of the larger retinal venules consisting of a double layer of endothelial cells anchored to a thin basement membrane. An elucidation of the factors distinguishing this endothelial cell proliferation from preretinal new vessel formation may be important for understanding the pathophysiology of proliferative diabetic retinopathy.

Actins↗
PubMed2002

The relationship between age and colour content in fundus images.

INTRODUCTION: The morphological appearance of the ocular fundus is one of the key parameters used in the diagnosis and management of retinal disease. However, optical imperfections in the refractive media result in blurring, low luminance and contrast, and changes in the colour composition of the image which can be seen as an increasing yellowish appearance with age. The introduction of a method for quantifying this age-related change in colour content may help in diagnosing and grading pathological changes in the eye lens which are secondary to ocular and systemic diseases. METHODS: A total of 102 digitized fundus images from 102 healthy subjects (mean age = 50.4 years, range 7.0-94.3 years) were used to build a model for estimating the age of the subject from the colour content of the images. RESULTS: Estimation of age from the fundus images could be done within approximately 16 years. This variation could be reduced considerably by analysis of repeated photographs from the same examination. CONCLUSION: The colour content of fundus images can be used to estimate the ages of healthy subjects. Furthermore, when the colour content of fundus images deviates from that expected according to subject age, this may indicate causes other than age of increased light absorption in the lens, such as cumulative exposure to hyperglycaemia in diabetic patients. This could potentially be used to identify patients with undiagnosed type 2 diabetes in the general population and help to establish their risk of developing late diabetic complications as the cumulative exposure to hyperglycaemia is unknown at the time of diagnosis of the disease.

Adolescent↗
PubMed2002

Adenosine relaxation in small retinal arterioles requires functional Na-K pumps and K(ATP) channels.

PURPOSE: To study the effect of Na-K pump and K(ATP) channel inhibition on the diameter and the adenosine-induced vasodilation of small retinal arterioles. METHODS: Thirty isolated porcine arterioles with a diameter of approximately 70 microm were mounted in a double-barrelled pipette system placed in an organ bath, and diameter changes were studied under isobaric no-flow conditions. After an equilibration period, the arterioles were incubated with the Na-K pump inhibitors ouabain and low K(+) medium or the K(ATP) channel inhibitor glibenclamide, and spontaneous diameter changes were studied. Subsequently, the arterioles were precontracted and the adenosine concentration response curve was measured with and without the presence of inhibitors. RESULTS: Inhibition of the Na-K pump elicited a significant decrease in the spontaneous diameter of the vessels (P = 0.047), whereas no change in the spontaneous diameter was induced by inhibition of the K(ATP) channels (P = 0.754). Inhibition of the Na-K pump with ouabain or with low K(+) medium, as well as inhibition of the K(ATP) channels with glibenclamide, both diminished the adenosine induced vasodilation (P = 0.003, P = 0.01, and P = 0.003, respectively). CONCLUSION: The adenosine-induced vasodilation of small retinal arterioles involves the K(ATP) channels and the Na-K pump. Changes in the metabolism of adenosine as well as the activity of the K(ATP) channels or the Na-K pump can be expected to influence the retinal blood flow.

Adenosine↗