Biomedical subjects

Toke Bek

Publications and source records attributed to Toke Bek.

26 records · Page 2Linked to original sources

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↗

PubMed2002

Macular edema reflects generalized vascular hyperpermeability in type 2 diabetic patients with retinopathy.

OBJECTIVE: Diabetic maculopathy (DMa) is the most prevalent sight-threatening type of retinopathy in type 2 diabetes and a leading cause of visual loss in the western world. The disease is characterized by hyperpermeability of retinal blood vessels and subsequent formation of hard exudates and macular edema, the degree of which can be estimated by measurement of retinal thickness. We examined associations between retinal thickness as evaluated by optical coherence tomography scanning (OCT), glomerular leakage as evaluated by urinary albumin excretion rate (UAE), and general vascular leakage as evaluated by the transcapillary escape rate of albumin (TER(alb)) in type 2 diabetic patients with and without DMa. RESEARCH DESIGN AND METHODS: In 20 type 2 diabetic patients with DMa and 20 type 2 diabetic patients without retinopathy matched for age, sex, and duration of diabetes, we performed OCT, fundus photography, fluorescein angiography, and 24-h ambulatory blood pressure measurement. UAE was determined by radioimmunoassay. TER(alb) was determined as the initial disappearance of intravenously injected (125)I-labeled human serum albumin. RESULTS: Patients with diabetic maculopathy had higher HbA(1c) (8.5 +/- 1.5 vs. 7.4 +/- 1.2%, P < 0.05) and higher total cholesterol (5.8 +/- 0.7 vs. 5.2 +/- 0.9 mmol/l, P < 0.05) than patients without retinopathy. UAE was higher in the DMa group than in the group with no retinopathy (9.3 x// 3.1 vs. 3.9 x// 1.9 micro g/min, P < 0.01). There was no difference in TER(alb) between the two groups (6.0 +/- 1.6 vs. 6.6 +/- 1.5%, NS). In the group with DMa, OCT, TER(alb), and UAE correlated significantly (OCT versus TER(alb): r = 0.55, P < 0.05; OCT versus UAE: r = 0.58, P < 0.01; UAE versus TER(alb): r = 0.81, P < 0.01). Conversely, there were no correlations between these three parameters in the group without retinopathy. CONCLUSIONS: Macular edema seems to reflect a generalized vascular leakage in type 2 diabetic patients.

Albuminuria↗

PubMed2002

Bradykinin relaxation in small porcine retinal arterioles.

PURPOSE: To study changes in the spontaneous diameter of small retinal arterioles and bradykinin (BK)-induced vasodilation during inhibition of the synthesis of nitric oxide (NO), prostaglandins (PGs), and cytochrome P450 2C8/9-dependent endothelial-derived hyperpolarizing factor (EDHF). METHODS: Forty-eight isolated porcine arterioles with a diameter of approximately 70 microm were mounted in a double-barreled pipette system placed in an organ bath, and diameter changes were studied under isobaric conditions. After an equilibration period, the arterioles were incubated with inhibitors of the synthesis of NO, PGs, or cytochrome P450 2C8/9-dependent EDHF, and spontaneous diameter changes were studied. Subsequently, the arterioles were precontracted, and the diameter was assessed after addition of BK in cumulative concentrations. RESULTS: Inhibition of NOS elicited a significant decrease in the spontaneous diameter of the vessels (P = 0.028), whereas no change in the spontaneous diameter was induced by inhibition of PG or cytochrome P450 2C8/9 dependent EDHF synthesis (P = 0.35 and P = 0.75, respectively). The vasodilating effect of BK was decreased by inhibition of NO (P = 0.002) but not by inhibition of prostaglandin or cytochrome P450 2C8/9-dependent EDHF synthesis (P = 0.82 and P = 0.94, respectively). CONCLUSIONS: The results suggest the presence of a spontaneous release of NO, which keeps the retinal microcirculation dilated under normal conditions. The finding of BK-induced relaxation being dependent on the NO synthase (NOS), but not on PGs or cytochrome P450 2C8/9-dependent EDHF may be of importance for understanding the microcirculatory effects of pharmacologic compounds affecting the BK metabolism, such as angiotensin-converting enzyme (ACE) inhibitors.

Animals↗

PubMed2002

Using a model of the colour content in retinal fundus images to screen for sight threatening diabetic retinopathy.

The aim of the study was to assess the potential use of a model of the colour content in retinal fundus images to screen for sight threatening retinopathy in diabetes. Diabetic retinopathy is the most frequent cause of blindness in the population of working age in industrialised countries, but efficient therapies do exist, and accurate and early diagnosis, and correct treatment can prevent blindness in more than 50% of all cases. However, up to 50% of cases of type 2 diabetes, which comprises 85-90% of all patients, are undiagnosed, with an average delay of 10 years between the onset of the condition and diagnosis. In an other study we have described how there is a linear relation between age and the colour composition of retinal images from non-diabetic subjects. In the present study this relation was compared to the colour composition of retinal images from diabetes patients. We found that for the patients in the present study there is a significant difference in the colour composition between normal subjects and diabetic subjects with retinopathy. Although the number of patients in our study is too small to allow any conclusion, we suggest that this difference potentially may be used as the basis for a simple screening method for sight threatening retinopathy in unrecognised diabetes, or potentially may help estimating the risk of developing diabetic late complications in newly diagnosed type 2 diabetes.

Adolescent↗