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Biomedical subjects

J Flammer

Publications and source records attributed to J Flammer.

At least 91 records · Page 5Linked to original sources

Physiology of perfusion as it relates to the optic nerve head.

Blood flow in the optic nerve has been demonstrated to be autoregulated, and, thus, within certain limits, to be independent of the local perfusion pressure. As in the brain, a close coupling of neuronal activity and optic nerve head blood flow has been demonstrated. A number of regulatory systems and factors participate in the regulation of vascular tone in various organs, including the optic nerve. Metabolic and myogenic mechanisms keep local perfusion constant or adapted to the local metabolic needs. Such mechanisms seem to be involved in the regulation of optic nerve blood flow as well. In contrast, neuronal blood flow regulation is of minor importance in the optic nerve. Many of the regulatory modalities induce a response of vascular smooth muscle cells through stimulation of factors produced by the endothelial cell layer. Indeed, endothelial factors are of utmost importance in the regulation of optic nerve blood flow. The facts that there is a basal formation of nitric oxide, which leads to an active dilation of the ocular vasculature, and that endothelin-1 decreases blood flow to the anterior optic nerve in a dose-dependent manner suggest that alterations in these regulatory mechanisms might be relevant for optic nerve blood flow alterations as they relate to glaucomatous optic neuropathy. It is hoped that a detailed knowledge of blood flow regulation in the optic nerve might initiate new treatment modalities in optic neuropathies that are hemodynamic and vascular in nature.

Animals↗

Modulation of Heidelberg Retinal Flowmeter parameter flow at the papilla of healthy subjects: effect of carbogen, oxygen, high intraocular pressure, and beta-blockers.

The Heidelberg Retina Flowmeter (HRF) is intended to assess ocular blood flow by scanning laser doppler flowmetry. In the retina and possibly in the optic nerve head, carbogen increases blood flow, whereas pure oxygen or high intraocular pressure (IOP) decrease it. This study addresses whether at the papilla of healthy volunteers, the HRF parameter flow, is modulated by breathing 5% carbogen (5% carbon dioxide + 95% oxygen) for 7 minutes, breathing 100% oxygen for 7 minutes, increasing IOP to 50 mm Hg with a suction cup, or decreasing IOP with a single topical ocular instillation of the beta-blockers 0.5% betaxolol (betoptic) or 0.5% timolol (timoptic). At the papilla (20 degrees x 5 degrees, 256 X 64 pixels), values of HRF parameter, flow (50 X 50) pixels, increased after carbogen (N = 5, P < 0.05), but decreased after oxygen (N = 5, P < 0.05) or IOP increase (N = 5, P < 0.01). Although IOP values were significantly reduced by betaxolol (N = 9, P < 0.05) and timolol (N = 9, P < 0.01), HRF values were only significantly decreased (N = 9, P < 0.05) after timolol. In conclusion, at the papilla of healthy volunteers, a positive correlation exists between changes in values of the HRF-parameter, flow, and stimuli considered to modulate retinal and ONH blood flow. Furthermore, although of unkown clinical relevance, it appears that in contrast to betaxolol, values of the HRF parameter, flow, at the papilla of healthy volunteers are significantly decreased after a single instillation of timolol.

Administration, Inhalation↗

Potential role of nitric oxide and endothelin in the pathogenesis of glaucoma.

Glaucoma is an optic nerve head neuropathy in which retinal ganglion cells are lost. A clear association exists between glaucoma and different risk factors, such as high intraocular pressure (IOP) or blood-flow dysregulation. Nitric oxide (NO) and endothelin, two recently identified cellular mediators, appear to be involved in the regulation of IOP as well as in the modulation of ocular blood flow. To some extent, NO is also involved in apoptosis, a mechanism of cell death that can lead to retinal ganglion cell loss in glaucoma. This article provides a short and simplified overview of the biochemistry of NO and endothelin and highlights the potential role of these two mediators in certain important aspects related to the pathogenesis of glaucoma.

Apoptosis↗

Fludrocortisone in the treatment of systemic hypotension in primary open-angle glaucoma patients.

BACKGROUND: Fludrocortisone is a potent mineralocorticoid, which has no known direct vasoactive properties, and is the first-line drug for treatment of orthostatic hypotension. The present study evaluated the systemic hemodynamic effects of fludrocortisone treatment in glaucoma patients. PATIENTS AND METHODS: A retrospective analysis of the charts of glaucoma patients of the University Eye-Clinic Basel was performed. Twenty-two patients with open-angle glaucoma under treatment with fludrocortisone were selected. The selected patients had one 24-h blood pressure recording immediately prior to treatment with fludrocortisone and one recording at least 2 months after starting the treatment. Parallel to blood pressure recordings, diurnal intraocular tension curve recordings and visual field testings were carried out. In addition, twelve patients also had nail-fold video-capillaroscopy. RESULTS: IOP and visual fields remained stable. The average values for all systemic blood-pressure readings showed an improvement in the follow-up compared to primary examination. Mean (+/- SD) night-to-day ratio ('nocturnal dips') of systolic, diastolic and mean arterial blood pressure decreased from 13.6 +/- 4.3%, 16.9 +/- 5.2% and 15.9 +/- 3.5%, respectively, to 9.9 +/- 5.9% (p = 0.01), 13.2 +/- 4.3% (p = 0.044) and 11.7 +/- 3.9% (p = 0.0004). Baseline capillary blood-flow velocity increased and capillary blood-flow standstill time after cold provocation decreased significantly under fludrocortisone therapy. CONCLUSION: Hemodynamic parameters show a tendency towards improvement in a magnitude which might be of clinical relevance.

Blood Flow Velocity↗

[Dermatitis and conjunctivitis after contact with Euphorbia myrsinites (wolf's milk extract)--a case report].

BACKGROUND: Fresh sap of euphorbiaceae leads to a toxic burn of the skin and the eyes. Since years the sap of euphorbiaceae has been used in the treatment of different kinds of verrucas. PATIENTS: After contact with the sap of Euphorbia myrsinites three children developed a toxic dermatitis. In addition, the youngest girl showed a conjunctivitis and an occlusion of the right eye. Phorbolesters are considered to be responsible for the toxicity of the euphorbiaceae. All three children have resulted in a restitutio ad integrum. CONCLUSION: This case report is demonstrating the danger of toxic burn of this kind of plant.

Administration, Topical↗

Localization of nitric oxide synthase isoforms in porcine ocular tissues.

PURPOSE: To determine by immunohistochemistry the distribution of different nitric oxide synthases (NOS) isoforms in the porcine eye. METHODS: By light microscopy (immunofluorescence), porcine ocular tissues were investigated using monoclonal antibodies against neuronal NOS (nNOS; NOS I), endothelial NOS (ecNOS; NOS III), and macrophage NOS (macNOS; NOS II). RESULTS: Specific nNOS immunoreactivity was detected along the apical cytoplasmic portions of the non-pigmented and pigmented ciliary epithelial cells, in the endothelial lining of the corneoscleral meshwork and the uveal cords of the iridocorneal angle tissue, as well as in the photoreceptor layer of the sensory retina. Immunoreactivity for ecNOS was confined to the vascular endothelium of the vessels of the conjunctiva, iris, ciliary body, retina, choroid and optic nerve. A mild immunostaining for macNOS was present in the cytoplasm of some non-pigmented ciliary epithelial cells. CONCLUSIONS: The predominant localization of nNOS in ciliary epithelial and trabecular endothelial cells suggests a possible involvement of nNOS in both the production and outflow of aqueous humor in porcine eyes.

Animals↗

Is corneal temperature correlated with blood-flow velocity in the ophthalmic artery?

PURPOSE: To evaluate the correlation of blood-flow velocities in the ophthalmic artery and corneal temperature in normal subjects and glaucoma patients. METHODS: Corneal temperature was measured on both eyes by means of the THI-500 non-contact infrared thermometer in 18 healthy volunteers and in 18 age and sex matched open-angle glaucoma patients. In these subjects, blood flow velocity was assessed by means of color Doppler imaging (CDI) in both ophthalmic arteries. Peak systolic velocity (PSV), end diastolic velocity (EDV), and resistivity index (RI = [(PSV-EDV)/ PSV]) were computed. RESULTS: Corneal temperature values correlated positively with the ipsilateral values of EDV (R(2) = 0.13, p = 0.028, and R(2) = 0.16, p = 0.017 in the left and the right eyes respectively) and negatively with the ipsilateral values of RI (R(2) = 0.11, p = 0.046 and R(2 ) = 0.11, p = 0.044 in the left and the right eyes respectively) in the ophthalmic artery. In addition, the interocular difference in corneal temperature values were significantly correlated positively with the difference in EDV(R( 2) = 0.30, p = 0. 0005) and negatively with the difference in RI (R( 2) = 0.20; p: 0. 0056). All regression models were statistically comparable between normals and glaucoma patients, as well as between right eyes and left eyes. PSV did not contribute to corneal temperature. CONCLUSIONS: The present study suggests that retrobulbar hemodynamics influence corneal temperature, and that this relationship is comparable in normal subjects and glaucoma patients.

Adult↗

Relationship between blood flow velocities in retrobulbar vessels and laser Doppler flowmetry at the optic disk in glaucoma patients.

The relationship between blood flow velocities in retrobulbar vessels and blood flow at the optic nerve in glaucoma patients was assessed in a prospective study. The Heidelberg retina flowmeter (HRF) was used to assess optic nerve head blood flow in 13 open-angle glaucoma patients. In the same patients, color Doppler imaging (CDI) measurements were obtained from the ophthalmic artery, the central retinal artery and the posterior ciliary arteries. Using data for one randomly selected eye per subject, correlations between HRF recordings and CDI measurements were evaluated by means of Spearman's rank correlation factor. All three HRF parameters correlated with CDI measurements obtained from retrobulbar vessels. The most marked correlations were those of the HRF parameter 'volume' with the end-diastolic velocity in the ophthalmic artery and the medial posterior ciliary artery (R = 0.79, p = 0.0012 and R = 0.81, p = 0.0007, respectively), and the peak systolic velocity in the lateral posterior ciliary artery (R = 0.82, p = 0.0006). The present study suggests that glaucoma patients with altered blood flow in retrobulbar vessels are likely to show an alteration in optic nerve blood flow as measured with the HRF.

Aged↗

Asymmetry in intraocular pressure and retinal nerve fiber layer thickness in normal-tension glaucoma.

The etiology of glaucoma is most probably multifactorial. This study intended to investigate the asymmetry in intraocular pressure (IOP) and that in retinal nerve fiber layer (RNFL) thickness in normal-tension glaucoma patients. Two diurnal tension curves, obtained within 3 months and counting at least five IOP readings each, including an early morning IOP measurement upon awaking, were obtained in 15 normal-tension glaucoma patients. None of the patients received IOP-lowering therapy. IOP asymmetry was present in at least three readings and was always in the same direction. The optic nerve was imaged in both eyes in each patient by means of confocal scanning laser ophthalmoscopy (Heidelberg Retina Tomograph). The interocular difference in RNFL thickness and the RNFL cross-sectional area were correlated with the interocular difference in IOP by means of Spearman's rank correlation factor. Nine female and 6 male normal-tension glaucoma patients (mean +/- SD age was 62. 4 +/- 16.9 years) were included in this study. Interocular IOP asymmetry varied between 0.30 and 4 mm Hg. Strong negative correlations were found between interocular asymmetry in IOP and interocular asymmetry in RNFL thickness asymmetry (R = -0.652, p = 0. 0083) and interocular asymmetry in RNFL cross-sectional area (R = -0. 702, p = 0.0034). The present results demonstrate for the first time a more marked thinning of the neuroretinal nerve fiber layer in the eye with the higher IOP in normal-tension glaucoma patients.

Chronic Disease↗

Variability in the measurement of corneal temperature using a noncontact infrared thermometer.

PURPOSE: To assess the variability of corneal temperature and the reproducibility of its measurement by means of a noncontact infrared thermometer in healthy subjects. METHODS: The THI-500 noncontact infrared thermometer (Tasco Japan, Osaka, Japan) was used for the measurement of corneal temperature. The reproducibility of corneal temperature measurements was assessed for 5 consecutive temperature readings obtained within 45 min or within 5 days. In addition, the interocular difference in corneal temperature and the diurnal temperature changes of the cornea were assessed. For each experiment, 10 healthy subjects were recruited. RESULTS: The reliability of 5 consecutive corneal temperature measurements obtained within 45 min and within 5 days was 97.92 and 85.35%, respectively. Interocular differences in corneal temperature were not statistically significant (p = 0.70). Average corneal temperature varied significantly during the day (p < 0.0001), with lower corneal temperature readings during the morning hours compared to those obtained during the afternoon. CONCLUSION: The assessment of corneal temperature by means of noncontact infrared thermometry is highly reproducible. Corneal temperature varies throughout the day, and this variation is independent of variations in environmental temperature.

Adult↗

Body mass index in glaucoma.

PURPOSE: To compare body mass index (BMI) of patients with open-angle glaucoma or normal-tension glaucoma with BMI in control subjects. METHODS: BMI was calculated for 288 control subjects, 42 patients with open-angle glaucoma with treated intraocular pressure (IOP) higher than 21 mmHg, 87 patients with open-angle glaucoma with progression of glaucomatous damage despite IOP less than 21 mmHg, and 57 patients with normal-tension glaucoma. RESULTS: There was no statistical difference in BMI between patients with glaucoma and control subjects. If anything, there was a tendency for patients with glaucoma to have a lower BMI than control subjects. CONCLUSION: These data show that obesity seems not to be a risk factor for glaucoma.

Aged↗

Effect of Ox-LDL on endothelium-dependent response in pig ciliary artery: prevention by an ET(A) antagonist.

PURPOSE: To investigate whether oxidized low-density lipoprotein (Ox-LDL) affects endothelium-dependent responses in isolated porcine ciliary arteries. METHODS: In a myograph system for isometric force measurements, quiescent vessels were incubated with 50 microg/ml, 100 microg/ml, or 200 microg/ml Ox-LDL; 100 microg/ml native LDL (n-LDL); 1 microM of the ET(A)- endothelin receptor antagonist BQ 123; 100 microg/ml Ox-LDL coadministered with 1 microM BQ 123; or 100 microg/ml Ox-LDL coadministered with 50 microM of the protein synthesis inhibitor cycloheximide. Vessels with nonfunctional endothelium (intentionally and mechanically damaged) were also exposed to 100 microg/ml Ox-LDL. Two hours later, vessels were washed, precontracted with the thromboxane A2 analog U 46619 (approximately 0.1 microM), and exposed to bradykinin (0.1 nM to 3 microM), an endothelium-dependent relaxing agent. RESULTS: In quiescent vessels, Ox-LDL evoked delayed contractions. In contrast, no contractions were observed after exposure to n-LDL, BQ 123, Ox-LDL with BQ 123, or Ox-LDL with cycloheximide. In vessels with nonfunctional endothelium, Ox-LDL did not evoke contraction. Bradykinin-induced relaxations were inhibited in a dose-dependent manner by Ox-LDL, but not by n-LDL, BQ 123 alone, Ox-LDL with BQ 123, or Ox-LDL with cycloheximide. CONCLUSIONS: In porcine ciliary arteries, Ox-LDL affects endothelium-dependent responses through the activation of ET(A)- endothelin receptors. As Ox-LDL can accumulate in atherosclerotic plaques, such a mechanism might be involved in the occlusion of the ophthalmic circulation observed in patients with hypercholesterolemia and atherosclerosis.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Vascular dysregulation: a principal risk factor for glaucomatous damage?

Both intraocular pressure (IOP) and vascular factors appear to play an important role in the pathogenesis of glaucomatous optic neuropathy (GON). Arteriosclerosis and its risk factors are of minor importance, whereas vasospastic syndrome clearly is associated with GON. A vascular endotheliopathy seems to be involved in the diathetic hyperresponsiveness to stimuli, such as coldness or emotional stress. This in turn leads to a compromised autoregulation, and thereby renders the eye more sensitive to IOP or to a decrease in blood pressure. A variation in ocular perfusion may lead to an increase in free oxygen radicals. This may finally lead to apoptosis.

Animals↗

Isoproterenol, forskolin, and cAMP-induced nitric oxide production in pig ciliary processes.

PURPOSE: To investigate whether isoproterenol and forskolin, two adenylylcyclase activators, or 8-bromo-cAMP, an adenosine 3',5'-cyclic monophosphate (cAMP) analog, increase nitric oxide (NO) production in isolated porcine ciliary processes. METHODS: Nitrite (an NO metabolite) was measured (Griess reaction) before and 2 hours after exposure to 0.1 to 100 microM isoproterenol (a beta-adrenoreceptor agonist), 0.01 to 100 microM forskolin, or 0.1 to 1000 microM 8-bromo-cAMP. Some experiments were conducted in the presence of 0.5 mM N(G)-nitro-L-arginine methyl ester (L-NAME; a nitric oxide synthase [NOS] inhibitor), 10 microM propranolol (a beta-adrenoreceptor antagonist), or 1 microM KT 5720 (a cAMP-dependent protein kinase inhibitor). cAMP production was also measured (by immunoassay). RESULTS: Nitrite production was increased by isoproterenol (maximum, 10 microM: 164%; P < 0.001), forskolin (maximum, 10 microM: 254%; P < 0.001), and 8-bromo-cAMP (maximum, 100 microM: 184%; P < 0.001), an effect prevented by L-NAME (P < 0.05-0.001). Propranolol inhibited only isoproterenol-induced (10 microM) nitrite production (P < 0.05), whereas KT 5720 (P < 0.05) inhibited isoproterenol- (10 microM) and 8-bromo-cAMP-induced (10 microM) nitrite production. Furthermore, cAMP production evoked by isoproterenol (10 microM, P < 0.05) but not by forskolin (10 microM, P < 0.001) was inhibited by propranolol (P < 0.05). CONCLUSIONS: In isolated porcine ciliary processes, drugs activating adenylylcyclase or mimicking cAMP increase the production of NO by a mechanism that appears to involve both a cAMP-dependent protein kinase and NOS.

8-Bromo Cyclic Adenosine Monophosphate↗

Modulation of endothelin-1-induced contractions by magnesium/calcium in porcine ciliary arteries.

BACKGROUND: The present study was performed to investigate the influence of extracellular magnesium on changes in contractile tone induced by endothelin-1, and on relaxations to bradykinin in isolated porcine ciliary arteries. METHODS: Vessels were studied in a myograph system for measurement of isometric forces. Concentration-response curves (10(-10)-10(-7) M) to endothelin-1 were constructed in the presence of different concentrations (0, 1.2, 2, 10 mM) of magnesium (MgSO4). Endothelin-1-precontracted vessels (approximately 10(-8) M) were exposed to magnesium (10(-5)-10(-2) M) in the presence or absence of either the inhibitor of nitric oxide formation L-NAME (approximately 10(-4) M), or different concentrations of calcium (2.5, 5, 10 mM). In endothelin-1-precontracted vessels (10(-8) M), relaxations to bradykinin (10(-10)-10(-6) M) were conducted in the presence of different concentrations of magnesium (0, 1.2, 10 mM). RESULTS: Contractions to endothelin-1 were reduced only in the presence of 10 mM magnesium. (1.2 mM vs 10 mM, P = 0.001). In endothelin-1-precontracted vessels, magnesium evoked complete concentration-dependent relaxations (pD2 = 3.1 +/- 0.1), which were shifted to the right by increasing extracellular concentrations of calcium (2.5 vs 5 mM, P < 0.05). L-NAME had no influence on magnesium-induced relaxations. Relaxations to bradykinin remained unaffected by changes in extracellular magnesium concentrations. CONCLUSIONS: In a mechanism which appears to be compatible with a calcium-antagonist effect, magnesium strongly modulates changes in contractile tone evoked by endothelin-1, but has no effect on bradykinin-induced relaxations.

Animals↗