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Biomedical subjects

M Korth

Publications and source records attributed to M Korth.

At least 73 records · Page 4Linked to original sources

[Blue-sensitive VEP test in diagnosis of glaucoma].

BACKGROUND: Glaucomatous eye diseases can be associated in many cases with a disturbance of blue-color vision. Also visual evoked potentials (VEPs) can be altered in glaucoma. In the present study both tests were combined in order to increase the sensitivity of the method, i.e. the pattern VEP was examined under conditions isolating the blue-sensitive part of the visual pathway. METHOD: 34 normals, 14 patients with ocular hypertension (OHT), 15 patients with a so called pre-perimetric primary open-angle glaucoma (PPOAG), and 32 patients with primary open-angle glaucoma (POAG) were examined by presenting in the onset-offset mode blue stripe patterns 1. without an adaptive background light (blue- "black" pattern = BB) and 2. with an intensive yellow adaptation light (blue-on-yellow pattern = BY) suppressing the red- and green-sensitive cones. Amplitudes and peak times of the onset response were evaluated. RESULTS: BB responses are of positive, BY responses of negative polarity (inion-ear). In normals the latter responses are significantly larger and have a significantly longer peak time. While in the patients groups the BB responses were not significantly altered, the BY responses were significantly reduced only in POAG. The peak time was significantly delayed in both PPOAGs and POAGs. The BY peak time proved to be most significant: Sensitivity 87.1%, specificity 82.4%. CONCLUSION: The recording of the VEP with blue stimuli presented under selective yellow adaptation is a sensitive test for early glaucoma diagnosis.

Adult↗

Intracellular sodium activity and its regulation in guinea-pig atrial myocardium.

1. Intracellular Na+ activity (aNai) and membrane resting potential were studied in quiescent guinea-pig atrial and papillary muscles by means of Na(+)-sensitive and conventional microelectrodes. The effects of the cardioactive steroid dihydroouabain (DHO) on aiNa, force of contraction and sarcolemmal Na+, K(+)-ATPase activity were also investigated. 2. In thirty atria and twenty-two papillary muscles, aNai amounted to 8.0 +/- 0.2 and 4.7 +/- 0.3 mM, respectively (mean +/- S.E.M.). When both tissues were from the same animal, with the same ion-sensitive microelectrode mean aNai values of 7.9 +/- 0.2 and 5.1 +/- 0.5 mM (P < 0.01) were obtained from eight atrial and eight papillary muscles, respectively. 3. Membrane resting potentials (Em) were significantly (P < 0.001) more negative in the papillary muscles (-83.5 +/- 0.7 mV; n = 8) than in the atrium (-78.1 +/- 0.5 mV; n = 8). Deviation of Em from EK (determined by K(+)-sensitive microelectrodes) was 3.0 +/- 0.2 mV in ventricular (P < 0.05) and 6.1 +/- 0.3 mV in atrial preparations (P < 0.05). 4. Inhibition of the Na+ pump by DHO increased aNai of the atrium within 10 min by 0.6 +/- 0.1 (n = 7), 1.3 +/- 0.1 (n = 5) and 3.2 +/- 0.2 mM (n = 5) at 5, 10 and 30 microM, respectively. In the papillary muscle, 10 microM DHO was without effect while aNai rose by 1.0 +/- 0.1 (n = 5) and 2.9 +/- 0.2 mM (n = 6) at 30 and 120 microM DHO. 5. Consistent with the aNai measurements, the potency of DHO to increase force of the isometric contraction was three times higher in atrium than in papillary muscle (stimulation frequency 0.2 Hz). 6. Hydrolytic activity of sarcolemmal Na+,K(+)-ATPase isolated from atria amounted to only one third of that detected in ventricles (0.07 +/- 0.01, n = 6, versus 0.2 +/- 0.01 mumol phosphate released min-1 (g tissue)-1, n = 5). The inhibitory potencies of DHO on sarcolemmal Na+,K(+)-ATPase preparations were found to be identical in the enzymes from either tissue. 7. It is concluded that a lower Na+ pump density is responsible for the higher aNai and for the lower resting membrane potential in atrial as compared to ventricular cells. The regulation of cellular Na+ homeostasis in atrial muscle appears to be closer to the limits of its capacity than in ventricle, explaining the higher sensitivity of the atrium to interventions which impede Na+ pump activity.

Animals↗

Clinical electrophysiology relevant for early glaucoma diagnosis.

This review reports findings of the recent literature about electrophysiologic techniques that are used in glaucoma diagnosis and research. Included in this review are results obtained by recording electrical responses from the eye (electroretinograms) and from the brain (visual evoked potentials). Studies concerned the electroretinogram evoked by patterned stimuli that originates in the proximal retina and with flash-evoked responses that originate from the proximal retina, such as oscillatory potentials and scotopic threshold responses, from middle layers of the retina (B wave), and from the outer retina (A waves and C waves). Regarding the pattern electroretinogram, the authors agree on its usefulness in the diagnosis of glaucoma. However, the optimal stimulus conditions (temporal and spatial frequency, retinal location, contrast, and color), which component of the response to evaluate, and the value of the pattern electroretinogram in follow-up treatment are debatable. Flash-evoked components of the electroretinogram that have been considered in the past to be of low value in diagnosis of glaucoma now seem to be more important. New developments in visual evoked potentials techniques, such as photostress methods, contrast sensitivity measurements, ramp stimulation, and selective adaptation for isolating blue-cone activity seem to be promising in further increasing the diagnostic value of visual evoked potential measurements.

Electrophysiology↗

[Blue-sensitive mechanisms in pattern ERG and VEP].

Pattern onset-offset ERGs and VEPs in response to square-wave stripe patterns of different wavelengths and spatial frequencies under chromatic yellow adaptation (two-channel Maxwellian view) were studied in three subjects. One channel provided a steady homogeneous adapting field of 570 nm, while the other channel, containing the patterns, was superimposed on the adapting field (33 degrees). The spectral sensitivity curve of the ERG had a prominent peak in the blue (460 nm) and a shoulder in the red and green (above 500 nm). For wavelengths below 500 nm the shape of the psychophysically determined sensitivity curve to the onset and offset of the pattern was in close agreement with the electroretinal sensitivity curves determined for a low-amplitude criterion. With almost all wavelengths there were two components in the same VEP response at the same time: a slow negative wave with maximum sensitivity at 460 nm and an earlier fast positive component with maximum sensitivity in the red-green region. When the spatial frequency of a 460 nm test pattern was varied under yellow adaptation the onset response in the ERG showed only very slight spatial tuning. In the onset response of the VEP, however, the slow component showed prominent spatial tuning (around 2 c/deg) under the same conditions.

Adult↗

Alterations of saccadic eye movements in myotonic dystrophy.

Saccadic eye movements were examined by means of infrared reflection oculography in 8 patients having myotonic dystrophy and in 65 control subjects. In 7 patients typical alterations of the saccades could be observed. In comparison with the normal controls the saccades were significantly hypometric, of longer duration, of lower peak velocity, and showed a typical pattern of velocity and acceleration.

Adult↗

The different contributions of local luminance decreases and increases to the pattern electroretinogram (PERG).

The typical pattern-onset-offset stimulus (stimulus A) consisting of local luminance increases and decreases was broken down into stimuli presenting only local luminance increases (stimulus B) or only local luminance decreases (stimulus C). With stimulus B the onset ERGs are luminance responses. With stimulus C the onset ERGs are pattern-related responses showing a spatial band-pass function. With stimulus A the response is a linear addition of responses to stimuli B and C. The simultaneously recorded VEP is a pattern-related response with all three stimuli (A-C).

Contrast Sensitivity↗

Intracellular Na+ activity and positive inotropic effect of sulmazole in guinea pig ventricular myocardium. Comparison with a cardioactive steroid.

Recent studies suggest that inhibition of Na+,K(+)-ATPase may contribute to the positive inotropic action of the imidazopyridine sulmazole. Therefore, we investigated the effect of sulmazole and its stereoisomers and for comparison the effect of the cardioactive steroid dihydroouabain (DHO) on intracellular Na+ activity by means of Na(+)-sensitive microelectrodes. In the resting papillary muscle of the guinea pig, (+/-)-sulmazole increased intracellular Na+ activity (aiNa) within 15-20 minutes by 0.5 +/- 0.1 (n = 3), 1.3 +/- 0.1 (n = 7), 2.7 +/- 0.2 (n = 6), and 4.9 +/- 0.5 (n = 6) mM at 60, 100, 300, and 1,000 microM, respectively. (+)-Sulmazole was more effective than the racemate; aiNa was increased by 1.2 +/- 0.3, 2.1 +/- 0.3, and 4.0 +/- 0.2 mM at 60, 100, and 300 microM, respectively (n = 2 for each concentration). In the contracting papillary muscle (0.2 Hz), (+)- and (+/-)-sulmazole (600 and 1,000 microM) produced a maximum positive inotropic effect that exceeded that of DHO by 11% and 8%, respectively. As an inotropic agent, (+)-sulmazole was almost twice as potent as the racemate. The maximum direct inotropic effect of (-)-sulmazole (1,000 microM) amounted to only 14% of the DHO maximum and was, in contrast to the racemate and (+)-sulmazole, antagonized by 3 microM carbachol. (-)-Sulmazole did not affect aiNa.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Muscarinic receptor stimulation and cyclic AMP-dependent effects in guinea-pig ventricular myocardium.

1. The effect of carbachol on force of contraction, contraction duration, intracellular Na+ activity and cyclic AMP content was studied in papillary muscles of the guinea-pig exposed to isoprenaline or the phosphodiesterase inhibitor 3-isobutyl, 1-methyl xanthine (IBMX). The preparations were obtained from reserpine-pretreated animals and were electrically driven at a frequency of 0.2 Hz. 2. Isoprenaline (10 nM) and IBMX (100 microM) produced comparable positive inotropic effects of 9.8 and 9.7 mN, respectively. Carbachol (3 microM) attenuated the inotropic effects by 82% (isoprenaline) and by 79% (IBMX). The shortening of contraction duration which accompanied the positive inotropic effect of isoprenaline (by 14.9%) and of IBMX (by 22.4%) was not significantly affected by 3 microM carbachol. 3. The positive inotropic effect of 10 nM isoprenaline and of 100 microM IBMX was accompanied by an increase in cellular cyclic AMP content of 58 and 114%, respectively. Carbachol (3 microM) failed to reduce significantly the elevated cyclic AMP content of muscles exposed to either isoprenaline or IBMX. 4. In the quiescent papillary muscle, isoprenaline (10 nM) and IBMX (100 microM) reduced the intracellular Na+ activity by 28 and 17%, respectively. This decline was not influenced by the additional application of 3 microM carbachol. 5. The results demonstrate that muscarinic antagonism in guinea-pig ventricular myocardium exposed to cyclic AMP-elevating drugs is restricted to force of contraction. The underlying mechanism does not apparently involve the cytosolic signal molecule cyclic AMP.

1-Methyl-3-isobutylxanthine↗

Spatial heterogeneity of intracellular Ca2+ concentration in nonbeating guinea pig ventricular myocytes.

The spatial distribution of intracellular Ca2+ concentration was determined by fluorescent digital imaging microscopy in fura-2-loaded quiescent cardiac myocytes isolated from guinea pig ventricle. Fluorescent ratio images revealed discrete as well as clustered bright fluorescent spots ("hot spots"), which occupied approximately 20-50% of an individual cell's area. The fluorescent intensity and the area of the hot spots were increased by agents that deplete Ca2+ in the sarcoplasmic reticulum, namely, ryanodine (20-40 nM) and caffeine (5-15 mM). However, when cells were exposed to agents that deplete mitochondrial Ca2+, such as the protonophore, carbonyl cyanide m-chlorophenyl-hydrazone (CCCP, 100-300 nM), or the inhibitor of electron transport, antimycin A (4-40 nM), the fluorescent intensity and the area of the hot spots were reduced. These results indicate that the spatial distribution of intracellular Ca2+ concentration in the ventricular myocytes of guinea pig is quite heterogeneous. The ability of CCCP and antimycin A, but not of caffeine and ryanodine, to reduce the fluorescent intensity in the hot spots implies that Ca2+ compartmentation in the mitochondria is largely responsible for the intracellular Ca2+ heterogeneity seen in the present study.

Animals↗

[Luminance contrast and color contrast evoked pattern electroretinogram in normal eyes and in eyes with glaucoma].

Pattern-onset ERGs obtained with color contrast (red-green, blue-yellow) and luminance contrast (green "black") square-wave-stripe patterns (spatial frequency 0.3 c/deg, 32 degree field) were studied in larger groups of normal and glaucomatous (chronic open-angle glaucoma) eyes. Colored stimuli were generated in a two-channel Maxwellian-view system using grating monochromators. In producing isoluminant lights of different colors, the peak latency of the response was used as a criterion. Luminance-contrast responses always have significantly smaller amplitude and shorter peak latency than color-contrast responses. This can be explained by the smaller number and shorter latency of the non-color-coded phasic anglion cells and by the larger number and longer latency of the color-coded tonic cells. Glaucomatous eyes respond with significantly smaller amplitudes at all contrast conditions tested; however, this response reduction is most pronounced with red-green patterns. Peak latencies are not significantly altered in glaucomatous eyes. Since red-green patterns are most appropriate in showing glaucoma damage in the pattern ERG, the largest absolute losses seem to occur among the large red-green antagonistic group of ganglion cells.

Aged↗

Differences between pattern onset and pattern reversal retinal responses.

The pattern-evoked electroretinogram was recorded to pattern onset-offset and pattern reversal stimuli in two color-normal subjects with either luminance contrast of black-red (600 nm) and black-green (526 nm) square-wave stripe patterns or color contrast red-green patterns. The size of the onset response shows a spatial tuning with luminance contrast patterns and only a simple low-pass filter function with color contrast patterns. The peak latency of the response to luminance contrast increases with increasing spatial frequency but stays constant with color contrast patterns. The size of the reversal responses, however, shows only a low-pass filter function under both contrast conditions. The peak latency to luminance contrast shows a slight increase and to color contrast it remains constant with increasing spatial frequency. The differences noted under the various stimulus conditions must take into account the possible effects of different luminance modulation depths of onset and reversal stimuli, the modulation transfer function of the eye, and the activity of luminance-antagonistic and color-antagonistic receptive fields.

Color Perception↗

The pattern-evoked electroretinogram (PERG): age-related alterations and changes in glaucoma.

Pattern-onset electroretinograms (PERGs) were studied in 147 normal subjects of different ages (14-79 years) and in 110 eyes of 65 patients with glaucoma or ocular hypertension. The responses showed an increase (P less than 0.001) in peak latency with increasing age and a decrease (P less than 0.001) in amplitude which approximately parallels the loss of ganglion cells estimated by other authors. Many glaucoma eyes showed a loss of the normally present spatial tuning. In the age group above 50 years 50% of the onset responses were significantly diminished and the peak latencies were not significantly different. A negative correlation (P less than 0.001) was found between the size of the PERG and the cup/disc ratio and a positive correlation (P less than 0.001) with the area of the neuroretinal rim of the optic disc. The PERG decreased (P less than 0.01) with increasing visual field losses.

Adolescent↗

Spatial and spatiotemporal contrast sensitivity of normal and glaucoma eyes.

The spatial contrast sensitivity (CS) to static patterns was tested in the central retina of 156 normal subjects. It showed a decrease above 50 years of age at all spatial frequencies tested which was slightly more pronounced in females than in males. The spatial CS was also studied in 32 glaucoma eyes: Small reductions were found only in the group below 50 but not in eyes of patients above 50. The spatiotemporal CS to phase-reversing patterns was tested in four retinal quadrants of 99 normal subjects. It showed no age dependence in males whereas in females it decreased significantly beyond 50 years at all spatial frequencies tested. The spatiotemporal CS was studied also in 21 glaucoma eyes: Strong losses were again noted only in patients below 50. Spatiotemporal CS losses and perimetric losses were also compared in the four quadrants: For both measures the severest losses were found in the lower nasal and the mildest in the upper temporal quadrant. The spatiotemporal CS test of the peripheral retina seems to be a more powerful tool in glaucoma research than the spatial CS test of the central retina; however, effects of age and gender have to be considered.

Adult↗

Electrical responses of the human eye to changes in saturation of the stimulating light.

Previous studies on color vision using the electroretinogram or the evoked potential have concentrated only on brightness and hue but not on the saturation of color. In the present investigation patterns of alternate stripes of a highly saturated color and a totally desaturated color (= white) of equal brightness were presented in the pattern-reversal mode. It can be demonstrated that the reading obtained is in agreement with psychophysical saturation scale data of earlier investigators.

Color↗

Stimulation of muscarinic receptors raises free intracellular Ca2+ concentration in rat ventricular myocytes.

The effect of carbachol on free intracellular calcium concentration, ([Ca2+]i) and on intracellular hydrogen concentration (pHi) was determined from fluorescence signals obtained from rat ventricular myocytes. Application of carbachol (300 mumol/l) to quin2-loaded myocytes bathed in 2 mmol/l Ca2+-containing solution caused [Ca2+]i to increase within 7-10 minutes from 182 +/- 9 to 212 +/- 11 nmol/l (n = 4). Carbachol acted via stimulation of muscarinic receptors because atropine (1 mumol/l) either prevented or abolished the increase in [Ca2+]i. Carbachol also produced a positive inotropic effect in rat papillary muscles contracting isometrically at a frequency of 0.5 Hz and enhanced contracture in resting preparations in the presence of high extracellular Ca2+ concentration ([Ca2+]o) (20 mmol/l). The effect of carbachol on [Ca2+]i was dependent on [Ca2+]o. In the presence of 10 mmol/l [Ca2+]o, the increase in [Ca2+]i was about two times that elicited by carbachol when bath [Ca2+]o was 2 mmol/l. Reduction of [Ca2+]o to 50 mumol/l abolished the carbachol effect but did not prevent caffeine-induced Ca2+ release. The carbachol-induced rise in [Ca2+]i remained unchanged in the presence of either 10 mmol/l caffeine or 1 mumol/l ryanodine. In the absence of extracellular Na+ concentration [( Na+]o), carbachol no longer produced an increase in [Ca2+]i of cardiomyocytes and failed to enhance Na+-withdrawal contracture of the rat papillary muscle. In contrast to the effect on [Ca2+]i, carbachol did not produce any change in pHi as determined from fluorescence signals obtained from rat ventricular myocytes loaded with 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Differential effects of (-)-norepinephrine and of (+/-)-isoproterenol on cardiac contraction, an uptake phenomenon.

Concentration-dependent inotropic effects of (-)-norepinephrine and of (+/-)-isoproterenol were compared in isometrically contracting guinea pig papillary muscles stimulated at a frequency of 0.2 Hz. (-)-Norepinephrine (0.1-100 mumol/l) elicited a positive inotropic effect that was not antagonized by carbachol, failed to produce a positive inotropic staircase after resumption of stimulation and shortened relaxation time in a concentration-dependent fashion.(+/-)-Isoproterenol had a dual action: at low and moderately effective concentrations (1-30 nmol/l), the positive inotropic effect was antagonized by carbachol, a positive inotropic staircase was elicited and time to peak force was shortened. At (+/-)-isoproterenol concentrations exceeding an EC80 for the positive inotropic effect (greater than 30 nmol/l), relaxation time became shorter, staircase and carbachol-induced antagonism became less pronounced until at 300 nmol/l inotropic effects of (+/-)-isoproterenol resembled closely those of (-)-norepinephrine. Cyclic AMP derivatives and the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine mimicked (+/-)-isoproterenol in their inotropic actions. Impairment of neuronal uptake caused (-)-norepinephrine 1) to produce (+/-)-isoproterenol-like effects on the isometric contraction, 2) to induce a positive inotropic staircase and 3) to become sensitive to carbachol-induced antagonism. The results are compatible with the concept that neuronal uptake produces a distribution of (-)-norepinephrine within the papillary muscle which allows predominantly high concentrations of (-)-norepinephrine to become effective in the receptor compartment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗