I am an emeritus professor of ophthalmology with a special interest in microcirculation: https://glaucomaresearch.ch/en/ and http://www.flammer-syndrome.ch/en/
Journal of Ocular Pharmacology and Therapeutics, Dec 1, 2011
To determine the possibility of plasma citrate as a biomarker in patients with glaucoma. Twenty-o... more To determine the possibility of plasma citrate as a biomarker in patients with glaucoma. Twenty-one consecutive Caucasian patients with glaucoma and 21 sex- and age-matched controls were investigated. Plasma citrate, plasma creatinine, urine citrate, and urine creatinine were analyzed by ion chromatography. Mean (±standard deviation) concentrations and the calculated fractional citrate excretions were compared using the Mann-Whitney test. Sensitivity and specificity to detect glaucoma using plasma citrate levels were calculated. The mean plasma citrate (104.8±23.2 vs. 128.2±31.1 μmol/L; P=0.01) concentrations were significantly lower among the patients with glaucoma, whereas the mean urine citrate concentrations (1.7±0.9 vs. 2.8±1.9 μmol/L; P=0.07) were slightly lower. Mean plasma and mean urine creatinine concentrations showed no significant differences (plasma creatinine: 63.0±16.7 vs. 63.4±15.5 μmol/L; P=0.72; urine creatinine: 9.6±5.1 vs. 11.5±8.4 μmol/L; P=0.67). The calculated fractional citrate excretions were also not different with 12.1% versus 13.6% (P=0.37). Setting the cut-off limit at 110 μmol/L, the plasma citrate level evaluation would have a sensitivity of 66.7% and a specificity of 71.4% to detect glaucoma. In this masked study, plasma citrate levels were significantly decreased in Caucasian patients with glaucoma giving the possibility to use them eventually as a biomarker. The kidney function was normal in both groups, leaving the etiology of this hypocitraemia yet unexplained.
In glaucoma there is a loss of retinal ganglion cells. There is evidence that this loss can occur... more In glaucoma there is a loss of retinal ganglion cells. There is evidence that this loss can occur by apoptosis. The signal transduction leading to retinal ganglion cell apoptosis in glaucoma is not yet clear. The present study compares the gene expression in lymphocytes of normal tension glaucoma patients (NTG-patients) with the one of healthy controls. Subtractive hybridization was used to compare mRNA in lymphocytes of six vasospastic NTG-patients with six age and sex matched healthy subjects. Genes coding for p53-protein, NTP (neural thread protein) and 20 S proteasome subunit XAPC7 were overexpressed, whereas those coding for XPGC (Xeroderma pigmentosum gene), the survivin protein as well as one type of ABC transport protein were underexpressed. In comparison to healthy controls, patients with vasospastic NTG seem to over- as well as under-express certain genes in their lymphocytes.
Klinische Monatsblatter Fur Augenheilkunde, May 1, 2001
The aim of this study was to investigate the vasorelaxing properties of pinacidil (a potassium-ch... more The aim of this study was to investigate the vasorelaxing properties of pinacidil (a potassium-channel-opener) in isolated porcine ciliary arteries. Isometric contractions of isolated porcine ciliary arteries were measured with a myograph system. The vessels were first precontracted with the thromboxane A2 analog U 46619 (0.1 microM), and then exposed, in a cumulative manner, to increasing concentrations of pinacidil (1 nM-100 microM). Relaxations have been expressed in percent of the maximal contraction evoked by U 46619 (0.1 microM). Pinacidil showed a pronounced concentration-dependent relaxing effect in isolated porcine ciliary arteries. The difference between pinacidil and time-control experiments was significant (100 microM: 112 +/- 2% vs. 18 +/- 6%, P < 0.0001). The half-maximal concentration (pD50) value was 5.3 +/- 0.1 (-log M). The present study indicates that pinacidil has marked vasorelaxing properties in isolated porcine ciliary arteries.
ABSTRACT A variety of pathological processes at the level of the optic nerve head, such as papill... more ABSTRACT A variety of pathological processes at the level of the optic nerve head, such as papilledema, circulatory diseases, glaucoma, as well as certain inborn abnormalities, cause visual-field defects. The type of visual-field defect is dependent on the anatomic distribution of the nerve fibers involved and on the disease causing the optic nerve head damage. Therefore, the location and cause of the lesion determine the shape, extension, and depth of the visual-field defect.
<p>IOP = intraocular pressure</p><p>*Mann-Whitney U test</p><p><... more <p>IOP = intraocular pressure</p><p>*Mann-Whitney U test</p><p><sup>†</sup>Chi-square test</p><p><sup>‡</sup>Fisher’s exact test</p><p><sup>§</sup>Patients treated with more than one drug or fixed combination drugs were multiply counted according to the number of used drugs.</p><p>Data are represented as mean ± standard deviation unless otherwise noted.</p><p>Comparison of baseline characteristics between eyes of bilateral normal-tension glaucoma patients with unilateral optic disc hemorrhage (ODH group) and those of bilateral normal-tension glaucoma patients without an episode of optic disc hemorrhage (Non-ODH group).</p
Graefes Archive for Clinical and Experimental Ophthalmology, Mar 1, 1993
Perimetry is the standard examination in glaucoma, whereas contrast sensitivity is often proposed... more Perimetry is the standard examination in glaucoma, whereas contrast sensitivity is often proposed as a complementary test. This study investigates the extent to which the outcomes of the two tests correlate. One eye each of 44 glaucoma patients and 16 glaucoma suspects was tested with the Haag-Streit Visometer and the Octopus 201 perimeter (program G1). Contrast sensitivities correlated highest with the center of the visual field (Spearman&#39;s rho = 0.76; P &lt; 0.001) and slightly less with the mean sensitivity of the entire visual field (rho = 0.63; P &lt; 0.001). Mean contrast sensitivity correlated weakly with the square root of corrected loss variance (rho = -0.45; P &lt; 0.001) and short-term fluctuation (rho = -0.34; P &lt; 0.007). The two tests differed considerably only in very few patients. We recommend careful evaluation of the central area of glaucomatous visual fields whenever contrast sensitivity testing is not available.
72 patients (135 eyes) with visual field defects from various neurological disorders were examine... more 72 patients (135 eyes) with visual field defects from various neurological disorders were examined on the Octopus automated perimeter using both a quantitative and a semi-quantitative procedure. The semiquantitative strategy tests only whether the sensitivity is normal, relatively or absolutely disturbed. When it was used, normal values and absolute defects agreed in about 90% of the test locations with the quantitative measurements. Relative defects, however, were falsely negative (i.e. ‘normal’) or positive (i.e.‘absolute defect’) in more than 50% of the test locations with the semiquantitative procedure. Since in optic nerve and chiasmal lesions a frequent occurrence of relative defects must be expected, quantitative measurements should be performed in these disorders. In suprageniculate lesions, on the other hand, absolute defects often predominate. In most of these cases semiquantitative examinations, which are much more time saving, deliver sufficient information to the clinician.
Purpose: To quantify the gene expression levels of the ABC-proteins MDR1 (P-glycoprotein) and MRP... more Purpose: To quantify the gene expression levels of the ABC-proteins MDR1 (P-glycoprotein) and MRP (multidrug resistance-associated protein) isoforms in isolated mononuclear cells of vasospastic persons with increased Endothelin-1 plasma levels. Methods: Quantitative real-time RT-PCR was performed to determine the expression levels of the MDR1 (P-glycoprotein) gene and MRP1 to MRP5 genes as well as the expression of the ETA and ETB receptor in mononuclear cells derived from 11 vasospastic subjects compared to 10 healthy controls. Results: Mononuclear cells of vasospastic subjects showed a significant decrease in the expression of MDR1 (P-glycoprotein) gene (p=0.029), MRP2 gene (p=0.003), and MRP5 gene (p=0.013) when compared to healthy controls. These effects were poorly correlated with ET-1 plasma levels. No significant ETA and ETB receptor expression was observed in both groups. Conclusions: Vasospastic persons differ in their expression pattern of MDR proteins from healthy controls. This might be an indirect effect of elevated ET-1 levels.
<p>The distribution of the pressure in the (A) central retinal vein and (B) central retinal... more <p>The distribution of the pressure in the (A) central retinal vein and (B) central retinal artery measured by using contact lens ophthalmodynamometer in normal-tension glaucoma (NTG) patients with and without optic disc hemorrhage (ODH): (1) group A (eyes of bilateral NTG patients with ODH); (2) group B (fellow eyes with no ODH); (3) group C (randomly selected eyes of bilateral NTG patients without an episode of ODH).</p
A local cooling test produces a typical flow stop reaction in nailfold capillaries in 88% of pati... more A local cooling test produces a typical flow stop reaction in nailfold capillaries in 88% of patients with Raynaud's phenomenon, but only in 15% of healthy controls. A stop reaction occurred in 9 of 12 patients with Prinzmetal variant angina, exceeding significantly that in 2 of 12 matched control subjects. Also in patients with reversible visual disorders presumably due to vasospasm, the test resulted in a stop reaction in 16 of 25 cases exceeding that in control. In both of these patient groups the cooling test as well as the symptoms reacted favorably to nifedipine. Thus, the local cold exposure test appears to be useful for objective clinical examination not only of patients with Raynaud's phenomenon but also of patients with vasospastic syndromes such as variant angina and visual disorders.
Journal of Ocular Pharmacology and Therapeutics, Dec 1, 2011
To determine the possibility of plasma citrate as a biomarker in patients with glaucoma. Twenty-o... more To determine the possibility of plasma citrate as a biomarker in patients with glaucoma. Twenty-one consecutive Caucasian patients with glaucoma and 21 sex- and age-matched controls were investigated. Plasma citrate, plasma creatinine, urine citrate, and urine creatinine were analyzed by ion chromatography. Mean (±standard deviation) concentrations and the calculated fractional citrate excretions were compared using the Mann-Whitney test. Sensitivity and specificity to detect glaucoma using plasma citrate levels were calculated. The mean plasma citrate (104.8±23.2 vs. 128.2±31.1 μmol/L; P=0.01) concentrations were significantly lower among the patients with glaucoma, whereas the mean urine citrate concentrations (1.7±0.9 vs. 2.8±1.9 μmol/L; P=0.07) were slightly lower. Mean plasma and mean urine creatinine concentrations showed no significant differences (plasma creatinine: 63.0±16.7 vs. 63.4±15.5 μmol/L; P=0.72; urine creatinine: 9.6±5.1 vs. 11.5±8.4 μmol/L; P=0.67). The calculated fractional citrate excretions were also not different with 12.1% versus 13.6% (P=0.37). Setting the cut-off limit at 110 μmol/L, the plasma citrate level evaluation would have a sensitivity of 66.7% and a specificity of 71.4% to detect glaucoma. In this masked study, plasma citrate levels were significantly decreased in Caucasian patients with glaucoma giving the possibility to use them eventually as a biomarker. The kidney function was normal in both groups, leaving the etiology of this hypocitraemia yet unexplained.
In glaucoma there is a loss of retinal ganglion cells. There is evidence that this loss can occur... more In glaucoma there is a loss of retinal ganglion cells. There is evidence that this loss can occur by apoptosis. The signal transduction leading to retinal ganglion cell apoptosis in glaucoma is not yet clear. The present study compares the gene expression in lymphocytes of normal tension glaucoma patients (NTG-patients) with the one of healthy controls. Subtractive hybridization was used to compare mRNA in lymphocytes of six vasospastic NTG-patients with six age and sex matched healthy subjects. Genes coding for p53-protein, NTP (neural thread protein) and 20 S proteasome subunit XAPC7 were overexpressed, whereas those coding for XPGC (Xeroderma pigmentosum gene), the survivin protein as well as one type of ABC transport protein were underexpressed. In comparison to healthy controls, patients with vasospastic NTG seem to over- as well as under-express certain genes in their lymphocytes.
Klinische Monatsblatter Fur Augenheilkunde, May 1, 2001
The aim of this study was to investigate the vasorelaxing properties of pinacidil (a potassium-ch... more The aim of this study was to investigate the vasorelaxing properties of pinacidil (a potassium-channel-opener) in isolated porcine ciliary arteries. Isometric contractions of isolated porcine ciliary arteries were measured with a myograph system. The vessels were first precontracted with the thromboxane A2 analog U 46619 (0.1 microM), and then exposed, in a cumulative manner, to increasing concentrations of pinacidil (1 nM-100 microM). Relaxations have been expressed in percent of the maximal contraction evoked by U 46619 (0.1 microM). Pinacidil showed a pronounced concentration-dependent relaxing effect in isolated porcine ciliary arteries. The difference between pinacidil and time-control experiments was significant (100 microM: 112 +/- 2% vs. 18 +/- 6%, P &lt; 0.0001). The half-maximal concentration (pD50) value was 5.3 +/- 0.1 (-log M). The present study indicates that pinacidil has marked vasorelaxing properties in isolated porcine ciliary arteries.
ABSTRACT A variety of pathological processes at the level of the optic nerve head, such as papill... more ABSTRACT A variety of pathological processes at the level of the optic nerve head, such as papilledema, circulatory diseases, glaucoma, as well as certain inborn abnormalities, cause visual-field defects. The type of visual-field defect is dependent on the anatomic distribution of the nerve fibers involved and on the disease causing the optic nerve head damage. Therefore, the location and cause of the lesion determine the shape, extension, and depth of the visual-field defect.
<p>IOP = intraocular pressure</p><p>*Mann-Whitney U test</p><p><... more <p>IOP = intraocular pressure</p><p>*Mann-Whitney U test</p><p><sup>†</sup>Chi-square test</p><p><sup>‡</sup>Fisher’s exact test</p><p><sup>§</sup>Patients treated with more than one drug or fixed combination drugs were multiply counted according to the number of used drugs.</p><p>Data are represented as mean ± standard deviation unless otherwise noted.</p><p>Comparison of baseline characteristics between eyes of bilateral normal-tension glaucoma patients with unilateral optic disc hemorrhage (ODH group) and those of bilateral normal-tension glaucoma patients without an episode of optic disc hemorrhage (Non-ODH group).</p
Graefes Archive for Clinical and Experimental Ophthalmology, Mar 1, 1993
Perimetry is the standard examination in glaucoma, whereas contrast sensitivity is often proposed... more Perimetry is the standard examination in glaucoma, whereas contrast sensitivity is often proposed as a complementary test. This study investigates the extent to which the outcomes of the two tests correlate. One eye each of 44 glaucoma patients and 16 glaucoma suspects was tested with the Haag-Streit Visometer and the Octopus 201 perimeter (program G1). Contrast sensitivities correlated highest with the center of the visual field (Spearman&#39;s rho = 0.76; P &lt; 0.001) and slightly less with the mean sensitivity of the entire visual field (rho = 0.63; P &lt; 0.001). Mean contrast sensitivity correlated weakly with the square root of corrected loss variance (rho = -0.45; P &lt; 0.001) and short-term fluctuation (rho = -0.34; P &lt; 0.007). The two tests differed considerably only in very few patients. We recommend careful evaluation of the central area of glaucomatous visual fields whenever contrast sensitivity testing is not available.
72 patients (135 eyes) with visual field defects from various neurological disorders were examine... more 72 patients (135 eyes) with visual field defects from various neurological disorders were examined on the Octopus automated perimeter using both a quantitative and a semi-quantitative procedure. The semiquantitative strategy tests only whether the sensitivity is normal, relatively or absolutely disturbed. When it was used, normal values and absolute defects agreed in about 90% of the test locations with the quantitative measurements. Relative defects, however, were falsely negative (i.e. ‘normal’) or positive (i.e.‘absolute defect’) in more than 50% of the test locations with the semiquantitative procedure. Since in optic nerve and chiasmal lesions a frequent occurrence of relative defects must be expected, quantitative measurements should be performed in these disorders. In suprageniculate lesions, on the other hand, absolute defects often predominate. In most of these cases semiquantitative examinations, which are much more time saving, deliver sufficient information to the clinician.
Purpose: To quantify the gene expression levels of the ABC-proteins MDR1 (P-glycoprotein) and MRP... more Purpose: To quantify the gene expression levels of the ABC-proteins MDR1 (P-glycoprotein) and MRP (multidrug resistance-associated protein) isoforms in isolated mononuclear cells of vasospastic persons with increased Endothelin-1 plasma levels. Methods: Quantitative real-time RT-PCR was performed to determine the expression levels of the MDR1 (P-glycoprotein) gene and MRP1 to MRP5 genes as well as the expression of the ETA and ETB receptor in mononuclear cells derived from 11 vasospastic subjects compared to 10 healthy controls. Results: Mononuclear cells of vasospastic subjects showed a significant decrease in the expression of MDR1 (P-glycoprotein) gene (p=0.029), MRP2 gene (p=0.003), and MRP5 gene (p=0.013) when compared to healthy controls. These effects were poorly correlated with ET-1 plasma levels. No significant ETA and ETB receptor expression was observed in both groups. Conclusions: Vasospastic persons differ in their expression pattern of MDR proteins from healthy controls. This might be an indirect effect of elevated ET-1 levels.
<p>The distribution of the pressure in the (A) central retinal vein and (B) central retinal... more <p>The distribution of the pressure in the (A) central retinal vein and (B) central retinal artery measured by using contact lens ophthalmodynamometer in normal-tension glaucoma (NTG) patients with and without optic disc hemorrhage (ODH): (1) group A (eyes of bilateral NTG patients with ODH); (2) group B (fellow eyes with no ODH); (3) group C (randomly selected eyes of bilateral NTG patients without an episode of ODH).</p
A local cooling test produces a typical flow stop reaction in nailfold capillaries in 88% of pati... more A local cooling test produces a typical flow stop reaction in nailfold capillaries in 88% of patients with Raynaud's phenomenon, but only in 15% of healthy controls. A stop reaction occurred in 9 of 12 patients with Prinzmetal variant angina, exceeding significantly that in 2 of 12 matched control subjects. Also in patients with reversible visual disorders presumably due to vasospasm, the test resulted in a stop reaction in 16 of 25 cases exceeding that in control. In both of these patient groups the cooling test as well as the symptoms reacted favorably to nifedipine. Thus, the local cold exposure test appears to be useful for objective clinical examination not only of patients with Raynaud's phenomenon but also of patients with vasospastic syndromes such as variant angina and visual disorders.
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