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Biomedical subjects

Josef Flammer

Publications and source records attributed to Josef Flammer.

At least 37 records · Page 2Linked to original sources
PubMed2004

Reduced thirst in patients with a vasospastic syndrome.

PURPOSE: To compare thirst, drinking behaviour, and endothelin-1 (ET-1) plasma levels between vasospastic and non-vasospastic subjects. METHODS: We compared 67 subjects with a primary vasospastic syndrome with 64 age- and sex-matched non-vasospastic control subjects. A detailed medical history was recorded, including a questionnaire containing queries about thirst and drinking behaviour, history of migraine or unspecific headache, history of episodes of low blood pressure, and smoking habits. Body mass index (BMI) was calculated and blood samples were drawn for ET-1 measurements. RESULTS: Subjects with a vasospastic syndrome reported a reduced desire to drink and a lower estimated quantity of daily fluid intake, more often forgot to drink, more often had both migraine and unspecific headache, more often had episodes of low blood pressure, and had an increased plasma level of ET-1. These features differed statistically significantly between the two groups. There was also a non-significant trend among vasospastic subjects to smoke less and to have a smaller BMI. CONCLUSION: A reduced desire to drink is found frequently among vasospastic subjects.

Adult↗
PubMed2004

Role of anions in nitric oxide-induced short-circuit current increase in isolated porcine ciliary processes.

PURPOSE: To investigate how nitric oxide (NO) modulates short-circuit current (Isc) in isolated porcine ciliary processes. METHODS: Isc changes (Ussing-type chamber) induced either by the NO donors SNP or SIN-1, or by the cGMP analogue 8-pCPT-cGMP were assessed. The effect of inhibitors of guanylate cyclase (10 microM ODQ, 100 microM LY83583), protein kinase G (30 microM Rp-8-pCPT-cGMP, 3 microM KT 5823), protein kinase A (1 microM KT 5720), or protein kinase C (1 microM Go6983) on SNP- or 8-pCPT-cGMP-induced Isc changes were investigated. The effect of inhibitors of anion channel (100 microM niflumic acid, 1 mM DIDS, and 1 mM 9-AC), K+-channel (10 mM TEA, 10 mM BaCl2), Na+-channel blockers (1 mM amiloride), Na+-K+-2Cl- cotransporter inhibitor (0.5 mM bumetanide), or carbonic anhydrase inhibitor (1 mM acetazolamide) was studied. In Cl(-)- or HCO3(-)-free Krebs-Ringer solution, the effect of SNP- or 8-pCPT-cGMP-induced Isc changes was accessed. RESULTS: SNP, SIN-1, or 8-pCPT-cGMP increased Isc with a change in the potential difference that became more negative toward the nonpigmented epithelium (aqueous) side. The Isc increase induced by SNP or SIN-1, but not by 8-pCPT-cGMP, was prevented by ODQ and LY83583. SNP- and 8-pCPT-cGMP-induced Isc increases were prevented by Rp-8-pCPT-cGMP or KT5823 (but not by KT5720 or Go6983), or by niflumic acid, DIDS, 9-AC, or acetazolamide (but not by TEA, BaCl2, amiloride, or bumetanide). The effect of SNP and 8-pCPT-cGMP was abolished in Cl(-)- and reduced in HCO3(-)-free solutions. CONCLUSIONS: NO activates a guanylate cyclase-cGMP-protein kinase G pathway that appears to stimulate stroma-to-aqueous anionic transport, possibly Cl-, in porcine ciliary epithelium.

Animals↗
PubMed2003

Vasospastic persons exhibit differential expression of ABC-transport proteins.

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.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2003

Sequence analysis and high-throughput immunohistochemical profiling of KIT (CD 117) expression in uveal melanoma using tissue microarrays.

We aimed to immunohistochemically examine the expression of KIT (CD 117) in human posterior uveal melanoma and to analyze KIT-positive tumors for gene mutations. Brought into a tissue microarray (TMA) format were 101 formalin-fixed, paraffin-embedded posterior uveal melanomas. Immunohistochemistry was performed using the polyclonal anti-CD117 antibody from Dako (A4502). In ten selected KIT-positive tumors, exons 2, 8, 9, 11, 13 and 17 were sequenced. Of the 101 cases, 89 (88%) could be evaluated on the TMAs. Immunohistochemistry for CD 117 was weakly positive in 5 cases (6%), moderately positive in 10 cases (12%) and strongly positive in 57 cases (69%). No KIT mutations were detected in the analyzed exons. In conclusion, human posterior uveal melanoma frequently expresses CD117 at high levels. Although KIT mutations could not be found, it appears justified to investigate the utility of imatinib mesylate in the treatment of these patients.

Adult↗
PubMed2003

Rate of progression of glaucoma correlates with retrobulbar circulation and intraocular pressure.

PURPOSE: To evaluate the correlation between progression rate of glaucomatous damage and retrobulbar blood flow in an institutional setting. DESIGN: Retrospective, observational case series. METHODS: Twenty open-angle glaucoma patients with at least five visual field examinations and progressive damage in at least one eye were included in the study. Mean +/- standard deviation follow-up time was 4.3 +/- 1.6 years. As an indicator of progression rate of visual field damage, the angle to a horizontal line of the slope of the regression line of the visual field index mean defect over time was calculated for one randomly selected eye per patient. The association between this angle and intraocular pressure, as well as retrobulbar color Doppler imaging measurements obtained at the beginning of the observation period, was analyzed by a multiple linear regression analysis in a stepwise forward approach. RESULTS: With a faster rate in progression of glaucomatous damage, a lower baseline end diastolic blood flow velocity in the central retinal artery (partial r = -.63; P <.0037) and a higher baseline intraocular pressure (partial r =.59; P <.0078) were noted (multiple r =.69; P <.0043). Rate of progression was not related to the extent of preexisting visual field damage. CONCLUSIONS: Independent of the extent of glaucomatous damage and intraocular pressure, the progression rate of glaucomatous visual field damage statistically correlates with retrobulbar hemodynamic variables.

Antihypertensive Agents↗
PubMed2003

Reduction of nitrite production by endothelin-1 in isolated porcine ciliary processes.

It has been postulated that endothelin-1 and nitric oxide (NO) could participate in the modulation of aqueous humor dynamic in the eye. This study investigates whether endothelin-1 can reduce the production of nitrite (a stable metabolite of NO) in isolated porcine ciliary processes. Nitrite production was measured (Griess reaction) in the medium surrounding isolated ciliary processes before and after exposure to different drugs. Results are expressed in percent of basal nitrite production. In a concentration-dependent manner (0.1 nM to 1 microM), endothelin-1 significantly decreased basal nitrite production (1 microM: 81.7+/-3.5%; P<0.001). This effect was prevented by the endothelin type A (ETA)-receptor antagonist BQ123 (1 microM: 95.6+/-4.3%; P<0.05), but not by the endothelin type B (ETB)-receptor antagonist BQ788 (1 microM: 83.3+/-4.4%; P=0.86) or by the prostaglandin F2alpha analog unoprostone (30 microM: 86.7+/-3.7%; P=0.74). The adenylcyclase activator forskolin significantly increased basal nitrite production (1 microM: 143.4+/-3.9%, P<0.001). This effect was prevented both by endothelin-1 (0.1 microM; 113.9+/-6.7%: P<0.01) or the nitric oxide synthase inhibitor L-NAME (0.5 mM: 103.3+/-8.4%: P<0.001). The inhibitory effect of endothelin-1 on forskolin-induced nitrite production was significantly reversed by BQ123 (1 microM: 132.4+/-5.1%; P<0.01), but not by BQ788 (1 microM: 112.7+/-4.1%; P=0.64) or unoprostone (30 microM: 109.3+/-4.8%; P=0.98). These results suggest that endothelin-1, through an ETA receptor activation, can reduce both basal and forskolin-induced nitrite production in isolated porcine ciliary processes.

Animals↗
PubMed2003

The effects of antiglaucoma and systemic medications on ocular blood flow.

Based on the body of evidence implicating ocular blood flow disturbances in the pathogenesis of glaucoma, there is great interest in the investigation of the effects of antiglaucoma drugs and systemic medications on the various ocular vascular beds. The primary aim of this article was to review the current data available on the effects of antiglaucoma drugs and systemic medications on ocular blood flow. We performed a literature search in November 2002, which consisted of a textword search in MEDLINE for the years 1968-2002. The results of this review suggest that there is a severe lack of well-designed long-term studies investigating the effects of antiglaucoma and systemic medications on ocular blood flow in glaucomatous patients. However, among the 136 articles dealing with the effect of antiglaucoma drugs on ocular blood flow, only 36 (26.5%) investigated the effects of medications on glaucoma patients. Among these 36 articles, only 3 (8.3%) were long-term studies, and only 16 (44.4%) were double-masked, randomized, prospective trials. Among the 33 articles describing the effects of systemic medications on ocular blood flow, only 11 (33.3%) investigated glaucoma patients, of which only one (9.1%) was a double-masked, randomized, prospective trial. Based on this preliminary data, we would intimate that few antiglaucoma medications have the potential to directly improve ocular blood flow. Unoprostone appears to have a reproducible antiendothelin-1 effect, betaxolol may exert a calcium-channel blocker action, apraclonidine consistently leads to anterior segment vasoconstriction, and carbonic anhydrase inhibitors seem to accelerate the retinal circulation. Longitudinal, prospective, randomized trials are needed to investigate the effects of vasoactive substances with no hypotensive effect on the progression of glaucoma.

Eye↗
PubMed2003

Vasoactive properties of bimatoprost in isolated porcine ciliary arteries.

BACKGROUND: To investigate the vasoactive effect of bimatoprost (Lumigan), a new topical ocular hypotensive agent, in isolated porcine ciliary arteries. MATERIAL AND METHODS: Arteries were placed in a myograph system to measure isometric forces. Quiescent vessels as well as vessels pre-contracted with either 10 nM endothelin-1 or 100 mM potassium chloride (KCl) were exposed, in a cumulative manner, to increasing concentrations (0.1 nM - 0.1 mM) of bimatoprost (dissolved in ethanol). In quiescent vessels, results were expressed in percent of 100 mM KCl-induced contraction. In endothelin-1-pre-contracted vessels, results were expressed in percent of the maximal contraction induced by endothelin-1. In KCl-pre-contracted vessels, results were expressed in percent of the plateau contraction reached 30 minutes after 100 mM KCl application. RESULTS: Bimatoprost induced a significant (p < 0.05 - 0.001) vasoconstriction at concentrations equal to or higher than 0.1 micro M in quiescent vessels (0.1 mM: 73 +/- 12 %). In KCl-pre-contracted vessels, at concentrations higher than 1 micro M, bimatoprost induced significant (p < 0.05 - 0.01) contractions (0.1 mM: 67 +/- 17 %). In endothelin-1-pre-contracted vessels, bimatoprost also induced significant (p < 0.05 - 0.001) contractions at concentrations above 10 micro M (0.1 mM: 17 +/- 8 %). CONCLUSIONS: The present study indicates that bimatoprost appears to have, in vitro, some vasoactive properties in porcine ciliary arteries. The question whether Lumigan has an influence on ocular blood flow needs to be further investigated.

Amides↗
PubMed2003

Transepithelial short circuit currents in human and porcine isolated ciliary bodies: effect of acetazolamide and epinephrine.

BACKGROUND: To investigate in human and porcine isolated ciliary bodies the effect of acetazolamide and epinephrine on ciliary transepithelial ionic currents (a parameter linked to aqueous humor production). MATERIAL AND METHODS: Isolated ciliary bodies were mounted in a Ussing-type chamber to measure transepithelial potential difference (PD) and short circuit current (Isc) before and after exposure to either 100 micro M acetazolamide or 10 micro M epinephrine. RESULTS: In humans (N = 27), baseline PD was 1184 +/- 100 micro V (negative on the non-pigmented epithelial [NPE] side) and Isc 19.9 +/- 1.5 micro A/cm 2. Acetazolamide (N = 7 - 8) decreased Isc (NPE side: 8.4 +/- 1.1 micro A/cm 2; pigmented epithelial [PE] side: 7.4 +/- 0.9 micro A/cm 2) while epinephrine (N = 6) increased Isc only on the NPE side (9.9 +/- 0.8 micro A/cm 2). In pigs, baseline PD was in some preparations negative (862 +/- 84 micro V, N = 18) and in others positive (814 +/- 81 micro V, N = 10) on the NPE side with Isc 15.6 +/- 1.6 micro A/cm 2 and 16.3 +/- 2.6 micro A/cm 2, respectively. In all preparations, acetazolamide (N = 6 - 7) decreased Isc (NPE side: 6.1 +/- 0.6 micro A/cm 2; PE side: 4.8 +/- 0.3 micro A/cm 2) while epinephrine (N = 8) increased it only on the NPE side (10.5 +/- 0.6 micro A/cm 2). CONCLUSIONS: To our knowledge, this is the first time that this methodology is applied to measure transepithelial ionic currents in isolated human and porcine ciliary bodies. This method could be used to test drugs modulating aqueous humor production.

Acetazolamide↗
PubMed2003

Absence of vasoactive properties of travoprost in isolated porcine ciliary arteries.

BACKGROUND: Ocular blood flow dysregulation is considered to be a risk factor associated with the optic neuropathy observed in glaucoma patients. The present study evaluates the vasoactive effect of the ocular hypotensive agent travoprost (Travatan) on isolated pig ciliary arteries. MATERIAL AND METHODS: Isometric forces were measured with a myograph system. Quiescent vessels were exposed in a cumulative manner to increasing concentrations (0.1 nM - 0.1 mM) of travoprost ([+]-fluprostenol). Vessels pre-contracted with 100 mM potassium chloride (KCl) or 10 nM endothelin-1 were also exposed in a similar manner to travoprost. Time-control experiments without travoprost were always run in parallel. In quiescent vessels, contractions were expressed in percent of 100 mM KCl-induced contractions. In vessels pre-contracted with endothelin-1, relaxations were expressed in percent of the maximal contraction induced by this peptide, while in those pre-contracted with KCl, relaxations were expressed in percent of the plateau-contraction reached 30 minutes after the application of this drug. RESULTS: In quiescent vessels, travoprost had no statistically significant vasoconstrictive effect. In KCl- or in endothelin-1 pre-contracted vessels, travoprost had no statistically significant vasorelaxing effect. CONCLUSIONS: Although the clinical relevance of the results of this study for patients treated with travoprost (Travatan) needs to be further investigated, travoprost appears to have no vasoconstrictive properties in isolated porcine ciliary arteries.

Animals↗
PubMed2003

Colour vision deficiencies in Alzheimer's disease.

OBJECTIVE: visual disorders are among the earliest symptoms of Alzheimer's disease. It is, however, still controversial as to whether Alzheimer's disease impairs colour vision. In this study, colour vision of Alzheimer's disease patients was tested using the Ishihara test and the PV-16 choice test. The latter test, primarily designed for children, was chosen in order to avoid problems due to cognitive decline. METHODS: 26 patients with mild to severe Alzheimer's disease (M:F=5:21; mean age: 80+/-9 years, range: 53-95 years) and 25 controls (M:F=5:20; mean age 80+/-10 years, range: 56-100 years) were rated after undergoing complete neuro-ophthalmologic examination. RESULTS: the Alzheimer's disease patients made significantly more unspecific errors in the Ishihara test (P=0.02) and in the PV-16 choice test (P=0.0008) than the controls. No relation between test performance and severity of Alzheimer's disease was found. CONCLUSIONS: Alzheimer's disease patients have an unspecific colour vision deficiency independent of the severity of the disease.

Aged↗
PubMed2003

Unilateral fungal and mycobacterial keratitis after simultaneous laser in situ keratomileusis.

PURPOSE: To report a case of unilateral fungal and mycobacterial keratitis after simultaneous laser in situ keratomileusis (LASIK). METHODS: Case report of a 37-year-old woman who developed corneal infiltrates located at the flap-stroma interface in her left eye 3 weeks after LASIK for myopia. The infiltration progressed despite topical antibiotic therapy; therefore, the flap was lifted and irrigated with antibiotic solution. Parallel corneal scrapings were taken. The patient's condition deteriorated, prompting a lamellar keratoplasty. RESULTS: Corneal scrapings demonstrated no growth. Microbiologic cultures of the corneal specimen were reported as negative, whereas histopathologic examination disclosed fungal filaments. Two months later, the patient presented corneal infiltrates of the left eye again. Because the situation worsened despite therapy, a penetrating keratoplasty was performed. Histopathologic examination of the host cornea revealed no pathogenic species; microbiologic cultures, however, demonstrated Mycobacterium chelonae. CONCLUSION: Fungi and M. chelonae are rare and insidious causes of infectious keratitis after LASIK. Our case emphasizes the possible difficulties in diagnosing and treating a combined or subsequent infection with both species.

Antifungal Agents↗
PubMed2003

Extraocular blood flow and endothelin-1 plasma levels in patients with multiple sclerosis.

In order to evaluate whether plasma levels of the potent vasoconstrictor endothelin-1 (ET-1) are increased in patients with multiple sclerosis (MS) and whether these patients exhibit an ET-1-mediated vascular dysregulation, ET-1 plasma levels were measured in 30 patients with MS. Blood flow velocities in the ophthalmic artery, central retinal artery, central retinal vein, short lateral posterior ciliary artery, and short medial posterior ciliary artery were assessed in parallel. ET-1 plasma levels were significantly increased in MS patients when compared to sex- and age-matched healthy controls (2.0 +/- 0.4 pg/ml, range 1.1-2.8 vs. 1.5 +/- 0.2 pg/ml, range 0.9-2.0; p < 0.001). Moreover, the patients exhibited significant alterations of extraocular blood flow. The role of ET-1 in the inflammatory process remains to be clarified.

Adult↗
PubMed2003

Choroidal vascular reaction to hand-grip stress in subjects with vasospasm and its relevance in glaucoma.

PURPOSE: To assess the impact of vascular dysregulation on choroidal blood flow response to the hand-grip test and the relevance of this response to glaucoma. METHODS: Eighty healthy volunteers underwent a hand-grip test while choroidal blood flow was measured by means of laser Doppler flowmetry. Blood pressure, heart rate, and intraocular pressure (IOP) were monitored. Choroidal blood flow changes were compared between subjects with a positive history of cold hands and control subjects by means of analysis of variance. The relationship of the vascular response to the level of IOP at which progressive damage occurred was analyzed in 21 patients with primary open-angle glaucoma who had progressive damage despite normal or normalized IOP. RESULTS: Blood pressure and heart rate increased and IOP decreased in response to a hand-grip test. Healthy subjects with a positive history of cold hands (n = 36) demonstrated a decrease in choroidal blood flow during the hand-grip test (mean +/- SD: 13.5 +/- 5.8, 12.2 +/- 6.8, and 13.4 +/- 6.9 AU, at baseline, during the test, and 3 minutes after release, respectively), whereas control subjects (n = 44) demonstrated an inverse (12.5 +/- 8.3, 13.7 +/- 9.4, and 11.9 +/- 7.1 AU, respectively) response pattern (P = 0.039). Glaucoma patients with a decrease of at least 10% in choroidal blood flow during the hand-grip test had lower IOP (14.67 +/- 3.83 and 13.50 +/- 2.59 mm Hg in the right and the left eyes, respectively) compared (P = 0.032) with those without such a decrease (16.54 +/- 3.85 and 16.92 +/- 2.95 mm Hg in the right and the left eyes, respectively). CONCLUSIONS: A hand-grip test elicits a different blood flow response in subjects with vasospasm compared with control subjects. Damage by glaucoma in patients with a decrease in choroidal blood flow during a hand-grip test may progress at a relatively lower IOP.

Adult↗
PubMed2003

Adrenomedullin-induced endothelium-dependent relaxation in porcine ciliary arteries.

PURPOSE: To investigate adrenomedullin-induced relaxation in isolated porcine ciliary arteries. METHODS: In a myograph system (isometric force measurement), precontracted vessels ( approximately 0.1 micro M U46619; thromboxane A(2) analogue or approximately 10 nM endothelin-1) were exposed, in a cumulative manner, to increasing concentrations of adrenomedullin (1 nM to 1 micro M) in the presence or absence of different drugs. Some experiments were conducted in vessels with nonfunctional (intentionally mechanically damaged) endothelium. RESULTS: Adrenomedullin evoked marked relaxation [maximum relaxation (Rel(max)): 85.5 +/- 3.0%; negative log M concentration inducing 50% of Rel(max) (pD(2)): 7.4 +/- 0.1] in comparison to time-controls (Rel(max): 19.2 +/-4.8%; P < 0.001). Relaxation was inhibited by 3 micro M CGRP[8-37] (CGRP(1) receptor antagonist; Rel(max): 27.2% +/- 5.3%; P < 0.001) but not by 3 micro M adrenomedullin[22-52] (presumed adrenomedullin receptor antagonist; P = 0.75). Adrenomedullin-induced relaxation was less pronounced in nonfunctional endothelium vessels (Rel(max): 67.6% +/- 3.1%; pD(2): 6.9 +/- 0.1; P < 0.01). In vessels with functional endothelium, relaxation was not significantly influenced by 0.1 mM N(G)-nitro-L-arginine methyl ester (L-NAME; a nitric oxide synthesis inhibitor), 10 micro M indomethacin (a cyclooxygenase inhibitor), or 10 micro M 17-octadecynoic acid (a cytochrome P(450) inhibitor). In contrast, relaxation was significantly inhibited by either 10 mM tetraethylammonium (nonselective potassium channel inhibitor; P < 0.01) or 50 nM apamin (small conductance potassium channel inhibitor), together with 50 nM charybdotoxin (large and intermediate potassium channel inhibitor; P < 0.01). In the presence of these potassium channel inhibitors, the amount of relaxation was not significantly different (P > 0.50) from that observed in vessels with nonfunctional endothelium. CONCLUSIONS: In isolated porcine ciliary arteries, adrenomedullin induces relaxation that involves CGRP(1) receptors and is in part endothelium dependent. Endothelium-dependent relaxation was blocked by some potassium channel inhibitors, suggesting the possible release of an endothelium-derived hyperpolarizing factor (EDHF).

Adrenomedullin↗