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M Korth

Publications and source records attributed to M Korth.

At least 37 records · Page 2Linked to original sources

Motion-Evoked pattern visual evoked potentials in glaucoma.

PURPOSE: To evaluate motion-evoked brain potentials for glaucoma diagnosis. PATIENTS AND METHODS: Stripe patterns were presented in Maxwellian view under different stimulus conditions not combined in a factorial design. Spatial frequencies of 0.33 and 0.88 cycles/degree, with speeds of 10 and 5.9 degrees/second and contrasts of 0.04 and 0.93 were used. A 32 degrees whole field and a peripheral 32 degrees-27 degrees annular stimulus were used. Duration of motion was 200 milliseconds, and the interstimulus interval was 1,800 milliseconds. Recordings were obtained from Oz and P3. Thirty-four healthy patients, 12 glaucoma suspects, and 26 patients with open-angle glaucoma were tested. RESULTS: Normal response amplitudes decrease with age only under low contrast conditions, whereas response peak times increase under most conditions. Normal responses are much larger at P3 than at Oz, whereas in open-angle glaucoma, much less difference is seen. In these patients, the response amplitude at P3 is significantly reduced under all conditions, whereas a delay in peak time is less pronounced. A small but significant negative correlation (r = -0.44, P < 0.05) between response amplitude and mean perimetric defect was observed only with the annular stimulation. At a specificity of 90%, a sensitivity of approximately 76.7% for the low contrast and low spatial frequency condition was observed. CONCLUSIONS: Motion-evoked responses recorded at P3 are altered in open-angle glaucoma and thus can be useful as an additional test in glaucoma diagnosis.

Adult↗

Visual evoked potentials under luminance contrast and color contrast stimulation in glaucoma diagnosis.

PURPOSE: To evaluate the diagnostic value of visual evoked potential (VEP) assessment with luminance-contrast and color-contrast stimulation in the detection of glaucoma. PATIENTS AND METHODS: The study included 59 patients (96 eyes) with glaucomatous changes of the optic disc and visual field defects and 58 control eyes of 29 healthy patients. Four types of pattern VEP stimulation (0.9 cycle/degree) were performed in all patients: achromatic, alternating sine-wave stripe pattern: 6 reversals per second, contrast of 10% (activation of predominantly the magnocellular pathway); isoluminant, red-green stripe pattern: 83.3 milliseconds onset, 83.3 milliseconds offset, contrast of 30% and 80% (activation of predominantly the parvocellular pathway); and blue grating with yellow background adaptation: 200 milliseconds onset, 500 milliseconds offset (activation of the blue-sensitive pathway). RESULTS: The glaucoma group and the control group differed significantly (P < 0.01) in the peak times of all chromatic VEP responses and to a lesser degree in the achromatic VEP. Considering the amplitudes, only the low-contrast red-green stimulus showed a statistically significant reduction in glaucoma. At a predefined specificity of 90%, in separating patients with glaucoma from healthy control subjects, the peak time of the blue-yellow VEP had a high sensitivity (90%), whereas the sensitivity of the achromatic VEP was low (31%). The red-green VEP showed a sensitivity of 73% using low contrast and 71% using high contrast. In a paired correlation analysis with visual field defects, all stimulations showed significant (P < 0.05) results. Correlation coefficients were highest (R = 0.79, P < 0.01) for the peak time of the blue-yellow VEP. CONCLUSIONS: VEP measurements with presumable stimulation of single neuronal pathways can detect glaucomatous optic nerve damage in a considerable fraction of patients with visual field loss. Occipital responses to chromatic stimulation seem to be more sensitive to glaucoma damages than do responses to achromatic pattern reversal stimulation.

Chronic Disease↗

BK(Ca) channel activation by membrane-associated cGMP kinase may contribute to uterine quiescence in pregnancy.

We investigated the influence of pregnancy on large-conductance calcium-activated potassium channel (BK(Ca)) activity (NP(o)) and on channel expression in membranes of isolated human myometrial smooth muscle cells. NP(o) in inside-out patches was higher in pregnant myometria (PM) compared with nonpregnant myometria (NPM), and the half-maximal activation potential was shifted by 39 mV to more negative potentials. This effect was not due to an enhanced BK(Ca) channel expression. In the presence of cAMP kinase (PKA) or cGMP kinase (PKG), NP(o) increased in patches from PM but decreased in those from NPM. Western blot analysis and use of a specific PKG inhibitor (1 microM KT-5823) verified the existence of a partially active membrane-associated PKG. Inhibition of PKA by 100 nM PKI, the inhibitory peptide of PKA, had no effect on NP(o). 8-p-Chlorophenylthio-cGMP (8-pCPT-cGMP) hyperpolarized cells from PM. This effect was abolished by iberiotoxin, a specific blocker of BK(Ca) channels. It is concluded that an endogenous, membrane-bound PKG in myometrial cells specifically enhances BK(Ca) channel activity during pregnancy and thus may contribute to uterine quiescence during pregnancy.

Alkaloids↗

Multivariate approach for quantification of morphologic and functional damage in glaucoma.

PURPOSE: To determine the usefulness of confirmatory factor analysis in examination of morphometric, electrophysiological, and psychophysical quantitative methods that measure the extent of global glaucomatous damage without referring to a preselected gold standard. METHODS: In a cross-sectional clinical study, 406 eyes of 203 glaucoma patients and 200 eyes of 100 normal control subjects 18 to 70 years old underwent optic disc morphometry, automated perimetry, measurement of temporal contrast sensitivity by a full-field flicker test, blue-on-yellow visually evoked potential (VEP), and black-and-white pattern-reversal electroretinogram (ERG). Diagnosis of glaucoma was based on a qualitative classification of the optic nerve head and retinal nerve fiber layer independent of intraocular pressure and visual field. Confirmatory factor analysis was performed in the patient group as a whole and in a subgroup showing moderate to advanced glaucomatous optic nerve head damage. RESULTS: The confirmatory factor analysis models explained the data satisfactorily (P > 0.18, all patients; P > 0.34, subgroup). Global glaucomatous damage was quantified best by the mean defect of automated perimetry (r = 0.81; r = 0.87), followed by the area of the neuroretinal rim (r = 0.64; r = 0.73), the full-field flicker test (r = 0.59; r = 0.65), the pattern-reversal ERG amplitude (r = 0.54; r = 0.55), and the VEP peak time (r = 0.55; r = 0.54). CONCLUSIONS: Confirmatory factor analysis allows quantification of the validity of established and new procedures that measure global glaucomatous damage using cross-sectional data. The results are not dependent on the preselection of a specific gold standard. Psychophysical testing and morphometry quantified glaucomatous damage best, compared with electrophysiological procedures.

Adolescent↗

Effects of mitoxantrone on excitation-contraction coupling in guinea pig ventricular myocytes.

The mechanisms of the inotropic effect of mitoxantrone (MTO), a synthetic dihydroxyanthracenedione derivative with antineoplastic activity, was investigated in guinea pig ventricular myocytes using whole-cell patch-clamp methods combined with fura-2 fluorescence and cell-edge tracking techniques. In right ventricular papillary muscles, 30 microM MTO increased isometric force of contraction as well as action potential duration (APD) in a time-dependent manner. The force of contraction was increased approximately 3-fold within 4 h. This positive inotropic effect was accompanied by a prolongation of time to peak force and relaxation time. In current-clamped single myocytes treated with 30 microM MTO for 30 min, an increase of cell shortening by 77% and a prolongation of APD by 19% was observed. Peak amplitude of the intracellular Ca(2+) transients was also increased by 10%. The contribution of APD prolongation to the enhancement of cell shortening induced by MTO was assessed by clamping control myocytes with action potentials of various duration. Prolongation of APD(90) (ADP measured at 90% of repolarization) by 24% led to an increase of cell shortening by 13%. When the cells were clamped by an action potential with constant APD, MTO still caused an increase of cell shortening by 59% within 30 min. No increase of the peak intracellular Ca(2+) transients, however, was observed under this condition. We conclude that both the APD prolongation and a direct interaction with the contractile proteins contributed to the positive inotropic effect of MTO.

Action Potentials↗

The full-field flicker test in glaucomas: influence of intraocular pressure and pattern of visual field losses.

BACKGROUND: The purpose of this study was to evaluate how temporal contrast sensitivity (TCS) determined with full-field flicker stimuli is influenced by intraocular pressure and whether TCS is reduced in glaucoma patients with diffuse perimetric losses as well as in patients with localized visual field deficits. METHODS: TCS was determined with sinusoidally flickering light (37.1 Hz) in a full-field bowl. Perimetric mean defect (MD) and cumulative defect curves (Octopus G1) were used to distinguish between patients with localized and diffuse field deficits. Normal subjects (296), low-tension glaucoma patients (98) and open-angle glaucoma patients with previously elevated intraocular pressure (541) were classified into five subgroups taking into account the depth of their visual field losses. RESULTS: No significant correlation between full-field flicker sensitivity and prevailing intraocular pressure was found in normals (Y=1.36+0.006 X) or in patients (Y=0.95-0.0002 X). Analyses of validity at a predefined specificity of 90% reveal a reduction of TCS in patients with early (MD<5 dB) diffuse perimetric losses (sensitivity 69%) as well as in those showing localized visual field defects (sensitivity 65%). Sensitivity was 87% in patients with diffuse perimetric defects (MD 5-10 dB), 93% in a group of patients with both types of losses, and 100% in advanced glaucomas (MD>20 dB). The lack of TCS is similar in open-angle glaucomas and in field-loss-matched normal-tension glaucoma patients. CONCLUSIONS: Significantly reduced TCS in patients with early diffuse perimetric losses as well as in those showing localized visual field defects indicates that localized damages can be associated with general deterioration of the ability to perceive flickering stimuli. Thus, this flicker test can be performed in a full-field bowl with no need for fixation. Considering its other clinical qualities (photopic conditions, low influence of prevailing intraocular pressure and media opacity) the test may be a useful, convenient supplementary procedure in glaucoma screening.

Chronic Disease↗

Effects of mitoxantrone on action potential and membrane currents in isolated cardiac myocytes.

1. The effects of mitoxantrone (MTO), an anticancer drug, on the membrane electrical properties of cardiac myocytes were investigated using the whole-cell clamp technique. 2. In isolated guinea-pig ventricular myocytes, 30 microM MTO induced a time-dependent prolongation of action potential duration (APD) which was occasionally accompanied by early afterdepolarizations. APD prolongation was preserved in the presence of 10 microM tetrodotoxin and showed reverse rate-dependence. 3. Both the inward rectifier K+ current (I(KI)) and the delayed rectifier K+ current (I(K)) of guinea-pig ventricular myocytes were significantly depressed by 30 microM MTO. The rapidly activating component of I(k) (I(Kr)) seemed to be preferentially blocked by MTO. The transient outward current was not affected by MTO in rat ventricular myocytes. 4. Thirty microM MTO had no direct effect on the L-type Ca2+ current (I(Ca(L))), but reversed the inhibitory effect of 1 microM carbamylcholine but not the A1-adenosine receptor agonist (-)-N6-phenylisopropyladenosine (1 microM) on I(Ca(L)) enhanced by 50 nM isoprenaline in guinea-pig ventricular myocytes. In guinea-pig atrial mycotyes, 30 microM MTO inhibited by 93% the muscarinic receptor gated K+ current (I(K,ACh)) evoked by 1 microM carbamylcholine, whereas I(K,ACh) elicited by 100 microM GTPgammaS, a nonhydrolysable GTP analogue, was only decreased by 12%. 5. The specific binding of [3H]QNB, a muscarinic receptor ligand, to human atrial membranes was concentration-dependently displaced by MTO (1-1000 microM). 6. In conclusion, MTO blocks cardiac muscarinic receptors and prolongs APD by inhibition of I(KI) and I(Kr). The occasionally observed early afterdepolarizations may signify a potential cardiac hazard of the drug.

Action Potentials↗

Temporal contrast sensitivity with peripheral and central stimulation in glaucoma diagnosis.

AIMS: To evaluate temporal contrast sensitivity with full field, peripheral, and central stimulation and to determine the most sensitive corresponding retinal area for glaucoma damage. METHODS: Temporal contrast sensitivity was determined either with a full field, a peripheral annular area from 30 degrees to 90 degrees, or a central area from 0 degree to 30 degrees at a frequency of 37.1 Hz. 232 eyes of 232 subjects were included. They were classified into four groups: eyes with ocular hypertension (OHT, n = 54), "preperimetric" glaucomas (n = 73) with glaucomatous optic disc abnormalities but no visual field loss, "perimetric" glaucomas (n = 53) with visual field loss, and 52 normals. RESULTS: In all four groups, temporal contrast sensitivity was almost equal with full field and peripheral, but significantly higher than with central stimulation (p < 0.001). With regard to the diagnostic power of the three different stimulus areas, OHTs and glaucomas were found to be best discriminated from normals by peripheral stimulation. CONCLUSIONS: According to these results, temporal contrast sensitivity seems to be determined by peripheral retinal areas. As the diagnostic power of the three different stimulus areas was best with the peripheral stimulation, this condition should be used for early glaucoma diagnosis.

Adult↗

Defective smooth muscle regulation in cGMP kinase I-deficient mice.

Regulation of smooth muscle contractility is essential for many important biological processes such as tissue perfusion, cardiovascular haemostasis and gastrointestinal motility. While an increase in calcium initiates smooth muscle contraction, relaxation can be induced by cGMP or cAMP. cGMP-dependent protein kinase I (cGKI) has been suggested as a major mediator of the relaxant effects of both nucleotides. To study the biological role of cGKI and its postulated cross-activation by cAMP, we inactivated the gene coding for cGKI in mice. Loss of cGKI abolishes nitric oxide (NO)/cGMP-dependent relaxation of smooth muscle, resulting in severe vascular and intestinal dysfunctions. However, cGKI-deficient smooth muscle responded normally to cAMP, indicating that cAMP and cGMP signal via independent pathways, with cGKI being the specific mediator of the NO/cGMP effects in murine smooth muscle.

Animals↗

Regulation of stably expressed and native BK channels from human myometrium by cGMP- and cAMP-dependent protein kinase.

The cloned BK channel alpha subunit from human myometrium was stably expressed in Chinese hamster ovary cells, either alone (CHOalpha cells) or in combination with the auxiliary beta subunit (CHOalpha+beta cells). We studied basic channel properties and the effects of cGMP- and cAMP-dependent protein kinases on the BK channel activity. Coexpression of alpha and beta subunits enhanced the Ca2+ and voltage sensitivity of the BK channel, and decreased the inhibitory potency of iberiotoxin. Blocking and stimulating effects on BK channel activity by charybdotoxin and nitric oxide, respectively, were independent of the beta subunit. The cGMP kinase Ialpha and cAMP kinase failed to affect BK channel activity in CHOalpha and CHOalpha+beta cells at different [Ca2+]i and voltages. In contrast, BK channels in freshly isolated myometrial cells from postmenopausal women responded to cAMP kinase and cGMP kinase with a fourfold and twofold decrease in their open probability (NPo), respectively. These effects could be reversed by alkaline phosphatase and remained unaffected by the phosphatase inhibitor okadaic acid (100 nM). In 28% of myometrial cells, however, cAMP and cGMP kinases increased NPo 2-fold and 3.5-fold, respectively. This stimulation was enhanced rather than reversed by alkaline phosphatase and was abolished by 100 nM okadaic acid. The results suggest that in stably transfected CHO cells the expressed BK channel is not regulated by cAMP kinase and cGMP kinase. However, in native myometrial cells stimulatory and inhibitory regulation of BK channels by cAMP kinase and cGMP kinase was observed, suggesting that channel regulation by the protein kinases requires factors that are not provided by CHO cells. Alternatively, failure of regulation may have been due to the primary structure of the myometrial BK channel protein used in this study.

Animals↗

[Glaucoma and pregnancy--review of the literature with a case report].

BACKGROUND: Intraocular pressure usually decreases during pregnancy. Pregnancy-related physiological changes do not seem to cause progression of glaucoma. PATIENT AND METHODS: The literature regarding glaucoma, ocular hypertension and pregnancy indexed in Medline is reviewed. In addition, we report on a 35-year-old patient with ocular hypertension and a known glaucoma family history, who was thoroughly examined before, during and after pregnancy (visual fields, optic disc measurements, 24-hours tension profile, sense physiology ["Erlanger flicker-test", pattern-reversal-ERG, blue-yellow-VEP], ocular perfusion). RESULTS: Visual fields and optic disc measurements did not become worse during pregnancy. Also the other sensory parameters ("Erlanger flicker-test", pattern-reversal-ERG, blue-yellow-VEP) did not deteriorate. Intraocular pressure was reduced by 7 mm Hg during and 2 months after pregnancy. Systolic and diastolic blood velocity of the ophthalmic artery measured by dopplersonography was increased by 60% during pregnancy. CONCLUSIONS: According to present knowledge pregnancy is associated with decreased intraocular pressure and does not seem to constitute a risk factor for progression of ocular hypertension or primary open angle glaucoma. Whether antiglaucomatous drug therapy during pregnancy is necessary awaits further evaluation.

Adult↗

Frequency dependence in the action of the class III antiarrhythmic drug dofetilide is modulated by altering L-type calcium current and digitalis glucoside.

We investigated how modulation of L-type calcium current affects the class II antiarrhythmic effect of dofetilide. Action-potential duration (APD) was determined in guinea pig papillary muscle by microelectrode techniques at different stimulation frequencies (0.5-3 Hz). The APD-prolonging effect (deltaAPD) of 10 nM dofetilide was reversed frequency dependent; it was 51 +/- 6 ms at 0.5 Hz and lower at 3 Hz, 21 +/- 3 ms. Either 10 microM diltiazem or 0.1 microM Bay K 8644 (BayK) was added to decrease or increase L-type calcium currents. In the presence of dofetilide + diltiazem, deltaAPD was reduced to 32 +/- 4 ms at 0.5 Hz but not affected at 3 Hz. Conversely, dofetilide + BayK further prolonged deltaAPD to 78 +/- 10 ms at 0.5 Hz but not at 3 Hz. When 10 microM dihydroouabain, a digitalis glucoside, was added to dofetilide, deltaAPD was more pronounced at 0.5 Hz and reduced at 3 Hz. We conclude that the reversed frequency-dependent effect of dofetilide on APD can be modulated by altering L-type calcium currents. With reduced calcium current, the frequency profile is less reversed and more favorable. The similarity of BayK and dihydroouabain in aggravating the reversed frequency-dependent effect of dofetilide is in line with a contribution of intracellular calcium to this reversed rate-dependent profile in the guinea pig ventricle.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

A multivariate sensory model in glaucoma diagnosis.

PURPOSE: To evaluate whether the combination of two psychophysical and two electrophysiological procedures improves diagnostic validity compared with single procedures. METHODS: In a clinical study, 73 patients with glaucoma from the University Eye Hospital in Erlangen and 122 healthy control subjects from the university staff, ranging in age from 19 to 62 years, underwent measurement of temporal contrast sensitivity using a full-field flicker test, spatiotemporal contrast sensitivity, blue-on-yellow visual evoked potential (VEP), and a black-and-white, pattern-reversal electroretinogram. Diagnostic reference criteria included applanation tonometry, optic disc morphometry, and automated perimetry. Sensitivity was determined univariately with a fixed specificity of 80% and in a multivariate approach using logistic regression analysis. The classification rate was estimated using the leaving-one-out method. The correlation with intraocular pressure, visual field defects, and optic nerve defects was determined. RESULTS: Contrast sensitivity measurements and the blue-on-yellow pattern-onset VEP showed comparable sensitivity (85%, 84%, and 85%) with 80% specificity, and a pattern-reversal electroretinogram showed lower sensitivity (64%). The first three methods contributed independent information to a diagnostic score. This score improved sensitivity to 94%, with a specificity of 89%. All procedures moderately correlated with the neuroretinal rim area of the optic disc (r=0.32-0.46). The psychophysical tests showed a higher correlation with visual field defects (r > 0.5) than the electrophysiological tests (r < 0.3). CONCLUSIONS: The multivariate approach substantially increased the diagnostic validity compared with single procedures. This was probably because the diagnostic procedures under investigation tested different aspects of visual function.

Adult↗

Large-field S-cone flicker test.

BACKGROUND: Disturbances of blue color vision and of temporal contrast sensitivity can indicate early damage in glaucoma. For the present study a quick and easy test was devised which examines both functions at one time by testing the temporal contrast sensitivity of a blue flickering light on an intense yellow background. METHODS: Large coextensive background and test fields (85 degrees) are used, making fixation uncritical. Detailed experiments were made in two normal subjects to derive spectral sensitivity curves from flicker-fusion frequency (FFF) versus intensity functions and to obtain complete temporal contrast-sensitivity (De Lange) curves under different levels of adaptation and test lights. After selection of appropriate luminances and one stimulation frequency from these experiments, test-retest variability was studied in four subjects in five repetitions. In addition, normal values were collected from 22 subjects. RESULTS: Spectral sensitivities for two levels of FFF (15 Hz and 44 Hz) agree with Stiles' pi 1 at the low and with pi 4 at the high FFF. Temporal contrast-sensitivity curves show a low-frequency section with peak sensitivity at 1 Hz and a high-frequency section with a peak at around 4 Hz. From the basic experiments the following conditions for the clinical examination were selected: Background luminance 2600 cd/m2, test luminance at 451 nm 0.8 cd/m2, stimulation frequency 4 Hz. The test-retest variability showed an acceptable intraclass correlation co-efficient (0.6). CONCLUSIONS: The present experiments carried out with a very large stimulus led to meaningful results which are in rather good agreement with results reported in the literature on small-field stimuli. The blue-on-yellow flicker test carried out under the conditions mentioned above is a quick and easy test which could be helpful in improving early glaucoma diagnosis.

Adaptation, Ocular↗

[Value of blue-on-yellow VEP for early diagnosis in suspected glaucoma. Biostatistical considerations and results].

BACKGROUND: In the Erlangen glaucoma study, the blue-on-yellow VEP was shown to be able to discriminate between controls and manifest glaucoma patients. SCIENTIFIC QUESTIONS AND AIMS: In our investigation, we assessed the validity of the blue-on-yellow VEP for early diagnosis of glaucoma. With this aim, we compared different subgroups of glaucoma suspects. The main issue of the investigation was the biostatistical aspects of early diagnosis of glaucoma. MATERIAL, METHODS AND RESULTS: Within a group of patients who were suspected of having ocular hypertensive glaucoma without visual field loss we compared 109 patients with optic disc damage [preperimetric (PPM) 47 +/- 11 years] and 91 patients without optic disc damage [ocular hypertension (OHT) 45 +/- 10 years]. We evaluated the N 1-amplitude and the peak latency of the blue-on-yellow VEP. The peak latency was significantly longer in the PPM group (first examination: OHT 118 +/- 9.5 ms, PPM 122.0 +/- 10.5 ms; second examination: 119.1 +/- 7.4/121.9 +/- 11.0 ms; third examination: 118.5 +/- 9.1/122.4 +/- 10.9 ms). The amplitude was reduced in the PPM group (P = 0.08). The differences between the two groups only allowed limited individual separation: (sensitivity of 42% for advanced optic disc damage with 80% specificity among OHT patients). CONCLUSIONS: The reduced sensitivity of a diagnostic procedure within a group of glaucoma suspect patients compared with patients with manifest glaucoma might be explained by: (1) possible misclassifications of patients and (2) a smaller degree of loss of visual function in the early stages of the disease.

Adult↗

The full-field flicker test in early diagnosis of chronic open-angle glaucoma.

PURPOSE: To evaluate whether the full-field flicker test, a psychophysical test employing full-field flickering stimuli to measure temporal contrast sensitivity, can detect glaucomatous optic nerve damage in patients with increased intraocular pressure and glaucomatous optic disk abnormalities but normal visual fields. METHODS: Temporal contrast sensitivity was determined with a sinusoidally flickering light (frequency, 37.1 Hz) of constant mean photopic luminance (10 cd/m2) presented in a full-field bowl of 58-cm diameter. The prospective study included three groups of individuals: the "preperimetric" glaucoma group of 80 patients with increased intraocular pressure, glaucomatous optic disk abnormalities, and normal visual fields; the "perimetric" glaucoma group of 56 glaucomatous patients with increased intraocular pressure and glaucomatous changes of the optic disk and visual field; and the control group of 96 normal subjects. RESULTS: Temporal contrast sensitivity was significantly (P < .001) lower in the two glaucoma groups than in the control group. In the preperimetric glaucoma group, 34% of the patients (27/ 80) were recognized by the full-field flicker test at a specificity of 99%. For all study subjects, temporal contrast sensitivity decreased significantly (P < .001) with decreasing neuroretinal rim area, enlarging peripapillary atrophy, and diminishing retinal nerve fiber layer visibility. CONCLUSIONS: The full-field flicker test can detect glaucomatous optic nerve damage in patients with increased intraocular pressure, glaucomatous optic disk abnormalities, and normal visual fields. Considering its feasibility, simplicity, quick performance, and low costs, the full-field flicker test may be helpful in clinics and in screening examinations as a supplement to glaucoma diagnosis.

Adult↗

The effect of stimulus size on human cortical potentials evoked by chromatic patterns.

The effect of stimulus size on the pattern onset-offset visual evoked potential elicited with stimuli of two different wavelengths is studied under intensive yellow adaptation: (1) The onset response obtained with a 460 nm pattern is of negative polarity (N1) and saturates in amplitude with a stimulus radius of 7 deg. The onset response obtained with a 550 nm pattern is of positive polarity and continues to increase up to the maximum size (32.2 deg). (2) The peak time of N1 (460 nm) decreases with increasing stimulus size, that of P1 (550 nm) remains constant. These results are discussed as reflecting either varying retinal and brain anatomy, or cone activity, color-opponent activity, or luminance contrast activity.

Adaptation, Physiological↗

Differential effect of beta-adrenergic stimulation on the frequency-dependent electrophysiologic actions of the new class III antiarrhythmics dofetilide, ambasilide, and chromanol 293B.

INTRODUCTION: Blockade of the rapid delayed rectifier potassium current (IKr) as an important mechanism for current Class III antiarrhythmics is less effective in action potential prolongation during beta-adrenergic activation. We hypothesized that blockade of the increased slow IK (IKs) current during beta-adrenergic stimulation could improve action potential prolongation and tested this hypothesis by comparison of three different IK blockers: dofetilide, a selective blocker of IKr; ambasilide, a nonselective blocker of IK; and chromanol 293B, a selective blocker of IKs. METHODS AND RESULTS: Transmembrane action potential duration was determined in guinea pig papillary muscles. After equilibration with the potassium channel blockers (dofetilide 10 nM, ambasilide 10 microM, chromanol 293B 10 microM), isoproterenol (10 and 100 nM) was added. The action potential prolonging effect of dofetilide was reduced in the presence of increasing concentrations of isoproterenol whereas the effect of ambasilide was much less reduced. In contrast, the effect of chromanol 293B clearly was increased in the presence of both concentrations of isoproterenol. No afterdepolarizations were observed after application of isoproterenol in control. Following isoproterenol, but not before, dofetilide and chromanol 293B induced early afterdepolarizations in 20% and 17% of the papillary muscles, whereas ambasilide and chromanol 293B induced delayed afterdepolarizations in 27% and 33%, respectively. CONCLUSION: In contrast to dofetilide, the Class III effect of ambasilide is less reduced and the effect of chromanol 293B is enhanced during beta-adrenergic stimulation. Our data support the hypothesis that IKs blockade improves the efficacy of antiarrhythmics in action potential prolongation during beta-adrenergic activation; however, this effect may increase the risk of afterdepolarizations.

Action Potentials↗