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Biomedical subjects

K Donner

Publications and source records attributed to K Donner.

At least 19 recordsLinked to original sources
PubMed1992

Influence of loperamide and loperamide oxide on the anal sphincter. A manometric study.

The objective of this study was to investigate the effects of the opioid loperamide and its recently synthesized pharmacologically inactive prodrug loperamide oxide on the anal sphincter. In a double-blind, placebo-controlled crossover study, anorectal manometry was performed in 12 healthy volunteers five hours after oral bolus application of 10 mg of loperamide, loperamide oxide, or placebo. Loperamide significantly increased the threshold volumes for minimal perception and urgency to defecate (P less than 0.05) and raised the volume required to abolish recovery of the rectoanal inhibitory reflex (P less than 0.05). These findings suggest that loperamide has a specific continence-improving action on the anal sphincter. However, anal resting pressure and maximal squeeze pressure were unaffected in our study and do not seem to be responsible for this effect. The effects under loperamide oxide showed a similar tendency but were without statistical significance.

Adult↗
PubMed1992

Noise and the absolute thresholds of cone and rod vision.

Literature data on light detection by cone and rod vision at absolute threshold are analysed in order (1) to decide whether the threshold performance of dark-adapted cone vision can, like that of rod vision, be consistently explained as limited by noise from a "dark light"; (2) to obtain comparable estimates of the dark noise and dark light of (foveal) cones and (peripheral) rods. The dark noise was estimated by a maximum-likelihood procedure from frequency-of-seeing data and compared with the dark light derived from increment-threshold functions. In both cone and rod vision, the estimated dark noise coincides with Poisson fluctuations of the estimated dark light if 17% (best estimate) of lambda max-quanta incident at the cornea produce excitations. At that fraction of quanta exciting, dark lights are equivalent to 112 isomerisations per sec in each foveal cone and 0.011 isomerisations per sec in each rod. It is concluded that (1) the threshold performance of dark-adapted cone as well as rod vision can be consistently described as noise-limited, but not by postulating a multi-quantum coincidence requirement for single receptors; (2) the underlying intrinsic activity in both the cone and the rod system is light-like as regards correspondence between noise effect and background adaptation effect. One possibility is that this activity is largely composed of events identical to the single-photon response, originating in the visual pigment, in cones as well as in rods.

Dark Adaptation↗
PubMed1992

On the relation between ERG waves and retinal function: inverted rod photoresponses from the frog retina.

In rod mass receptor photoresponses recorded across the isolated frog retina, a paradoxical cornea-positive wave may precede the response of normal polarity. We present a model which shows that the light-induced decrease in rod current can give rise to inverted or biphasic ERG signals if the distal part (tip) of the rod outer segment responds more slowly and/or less sensitively than the proximal part (base). The condition is that current entering at the tip is represented with greater weight in the ERG. The model reproduces recorded ERG waveforms well. It further predicts that if there is a light-insensitive conductance in the tip membrane, ERG photoresponses may be non-recordable although current photoresponses are only slightly reduced. The model reveals a type of complexity in the relation between mass potentials and underlying physiological processes which has not previously received attention.

Animals↗
PubMed1992

Intraindividual variability of anorectal manometry parameters.

The present study investigates the intraindividual day-to-day variability of anorectal manometry parameters. Manometric studies were performed in twelve healthy volunteers on three different days. A low compliance capillary perfusion system was used. The values measured on day 1 and day 2, as well as those on day 2 and day 3, showed no significant (p greater than 0.05) differences for any parameter in Wilcoxon's test. Mean percentage of differences as a measure for intraindividual day-to-day variation was relatively low for anal resting (mean: 13.5%) and maximal squeeze (17.5%) pressure. However, it was high for the threshold volumes for minimal perception (71.8%) and urgency to defecate (38.5%) during rectal balloon distention as well as for the minimal volume required to abolish recovery of the rectoanal inhibitory reflex (41.2%). We conclude that anal resting pressure and maximal squeeze pressure both are the most stable anorectal manometry parameters in man, at least over a period of a few days.

Adult↗
PubMed1990

Sulfhydryl binding reagents increase the conductivity of the light-sensitive channel and inhibit phototransduction in retinal rods.

The mechanisms by which sulfhydryl (SH-) binding reagents modulate the light-sensitive conductance of retinal rods were investigated by current recording from single rods, by patch clamp recording from the plasma membrane of the rod outer segment (ROS), and by biochemical study of their effects on the light-induced hydrolysis of cyclic GMP. The electrophysiology, as well as measurements of the reagents' ability to traverse the ROS plasma membrane, was done on amphibian (Rana and Ambystoma) rods, and the biochemistry on bovine rods. The main SH-reagents used were N-ethyl-maleimide (NEM) and iodoacetamide (IAA). Both transiently increased rod current, but part of the large current could not be turned off by light. After a few minutes' exposure, NEM, but not IAA, caused a continuous decay of the rod's light sensitivity. In patch-clamp recordings from the ROS plasma membrane, the reagents increased conductivity both in the presence and absence of cGMP, consistent with the observation that the drug-induced current increase in intact rods involved both light-sensitive and light-insensitive components. In vitro, NEM was found to be a powerful inhibitor of cGMP hydrolysis, which can explain the gradual loss of light sensitivity in the rod and could initially contribute to the increased dark current via elevated cGMP levels. Thus, SH-reagents act both by modifying the light-sensitive channel and by inhibiting phototransduction inside the rod.

Ambystoma↗
PubMed1990

Weber and noise adaptation in the retina of the toad Bufo marinus.

Responses to flashes and steps of light were recorded intracellularly from rods and horizontal cells, and extracellularly from ganglion cells, in toad eyecups which were either dark adapted or exposed to various levels of background light. The average background intensities needed to depress the dark-adapted flash sensitivity by half in the three cell types, determined under identical conditions, were 0.9 Rh*s-1 (rods), 0.8 Rh*s-1 (horizontal cells), and 0.17 Rh*s-1 (ganglion cells), where Rh* denotes one isomerization per rod. Thus, there is a range (approximately 0.7 log units) of weak backgrounds where the sensitivity (response amplitude/Rh*) of rods is not significantly affected, but where that of ganglion cells (1/threshold) is substantially reduced, which implies that the gain of the transmission from rods to the ganglion cell output is decreased. In this range, the ganglion cell threshold rises approximately as the square root of background intensity (i.e. in proportion to the quantal noise from the background), while the maintained rate of discharge stays constant. The threshold response of the cell will then signal light deviations (from a mean level) of constant statistical significance. We propose that this type of ganglion cell desensitization under dim backgrounds is due to a post-receptoral gain control driven by quantal fluctuations, and term it noise adaptation in contrast to the Weber adaptation (desensitization proportional to the mean background intensity) of rods, horizontal cells, and ganglion cells at higher background intensities.

Action Potentials↗
PubMed1990

Rod phototransduction modulated by bicarbonate in the frog retina: roles of carbonic anhydrase and bicarbonate exchange.

1. Effects on rod phototransduction following manipulation of retinal CO2-HCO3- and H+ fluxes were studied in dark-adapted retinas of the frog and the tiger salamander. 2. Rod photoresponses to brief flashes of light were recorded from the isolated sensory retina as electroretinogram mass receptor potentials and from isolated rods by the suction-pipette technique. The experimental treatments were: (1) varying [CO2] + [HCO3-] in the perfusion fluid: (2) applying acetazolamide (AAA), which inhibits the enzyme carbonic anhydrase (CA); and (3) applying 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS) which blocks exchange mechanisms transporting HCO3- across cell membranes. 3. The concentration of the internal transmitter of the rods, cyclic GMP, was biochemically determined from the rod outer segment layer of retinas that had been incubated in the same solutions as were used for perfusion in the electrophysiological experiments. 4. The introduction of 6 mM-sodium bicarbonate to replace half the buffer of a nominally CO2-HCO3(-)-free (12 mM-phosphate or HEPES, [Na+] constant) Ringer solution doubled the cyclic GMP concentration in the rod outer segment layer and increased the saturating response amplitude and the relative sensitivity of rods in the intact retina. 5. The introduction of 0.5 mM-AAA into bicarbonate-containing Ringer solution accelerated the growth of saturated responses and sensitivity. Incubation of the retina in AAA-bicarbonate Ringer solution elevated the concentration of cyclic GMP ninefold compared with the phosphate control. 6. No effects of switching to bicarbonate-AAA Ringer solution were observed in the photocurrent of isolated rods drawn into suction pipettes with only the outer segment protruding into the perfusion fluid. The target of AAA is probably the CA-containing Müller cell. 7. The introduction of DIDS into the perfusate (at normal pH 7.5) set off a continuous decay of photoresponses which finally abolished light sensitivity completely. The decay proceeded regardless of whether bicarbonate and AAA were present or not. 8. Rods that had lost their photosensitivity in DIDS recovered almost fully when the pH of the DIDS perfusate was raised to 8.5. They also recovered when DIDS was washed out with bicarbonate Ringer solution at constant pH (7.5). 9. It is proposed that all our treatments ultimately modulate the intracellular pH of the rods which is determined by the relative rates of H+ leakage and HCO3- transport into the cells.(ABSTRACT TRUNCATED AT 400 WORDS)

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1990

The frequency of isomerization-like 'dark' events in rhodopsin and porphyropsin rods of the bull-frog retina.

1. The dark current and responses to dim flashes were recorded with the suction pipette technique from single rods in pieces of bull-frog retina taken from either the dorsal porphyropsin or the ventral rhodopsin field. 2. The composition of visual pigment in the rods was determined by microspectrophotometry. Rods from the dorsal pieces contained 70-88% porphyropsin523 mixed with rhodopsin502. The ventral rods contained almost pure rhodopsin, any possible admixture of porphyropsin being below the level of detectability (less than 5%). 3. In most cells, the responses to dim flashes were well fitted by a four-stage linear filter model, with no systematic differences in the response kinetics of porphyropsin and rhodopsin rods. The amplitude of saturated responses varied between 8 and 55 pA and that of responses to single isomerizations between 0.4 and 3.5 pA. 4. In porphyropsin rods, discrete events similar to the response to one photoisomerization were clearly seen in complete darkness. The dark current amplitude histogram was fitted by a convolution of the probability densities for the Gaussian continuous noise component and the averaged dim-flash response waveform. This allows estimation of the frequency and amplitude of discrete events and the standard deviation of the continuous component. The mean frequency of discrete dark events thus obtained from six porphyropsin cells was 0.057 rod-1 s-1 at 18 degrees C. 5. In rhodopsin rods, the dark current amplitude histogram appeared completely symmetrical, indicating that the frequency of discrete events must be lower than 0.005 rod-1 s-1 (except in one rod where it was 0.006 events rod-1 s-1). Per molecule of rhodopsin, the events are then at least 5 times rarer than reported for toad rhodopsin rods at the same temperature. 6. The low rate of isomerization-like 'dark' events in bull-frog rhodopsin rods shows, firstly, that results cannot be generalized across species even for rhodopsins which appear spectrally identical. Secondly, it suggests that these events need not (in an evolutionary sense) constitute an irreducible noise factor which must set the ultimate limit to the sensitivity of dark-adapted vision. 7. The difference between porphyropsin and rhodopsin rods shows that, given (presumably) the same opsin, the pigment utilizing retinal2 and absorbing maximally at longer wavelengths produces more noise. The signal/noise ratio attained in the photoreceptor may be an important factor in the natural selection of visual pigments.

Animals↗
PubMed1990

[Functional diagnosis of early arthroses of the extremities].

Patient history and clinical examination are important for the diagnosis of degenerative joint disease. Here the typical statements of a patient suffering from early osteoarthritis are described and, as far as possible, explained. The joint in question must be systematically examined. Furthermore, the neighboring joints and soft-tissue structures, i.e., muscles, tendons etc., should be examined and evaluated with respect to their importance in hindering the functional chain. The neuroreflectory mechanisms involved herein are described.

Humans↗
PubMed1989

Visual latency and brightness: an interpretation based on the responses of rods and ganglion cells in the frog retina.

Rod and cone photoresponses in a variety of species have been accurately described with linear multistage filter models. In this study, the response latency and initial coding of intensity at two higher levels of visual processing are related to such photoreceptor responses. One level is the retinal output (spiking discharges from frog ganglion cells, based on experimental data reported here), the other is the perceptual level in humans (psychophysical latency and brightness functions, based on data from the literature). Photoreceptor responses are described with the "independent activation" model of Baylor et al. (1974). The intensity dependence of the early ganglion cell discharge, its latency and initial impulse frequency, is shown to follow from such a waveform, assuming that 1) latency L = l + D, where l is the time it takes for the rod response linearly summed over the ganglion cell's receptive field to reach a criterion amplitude, and D is a constant delay; and 2) the initial frequency (below saturation) is proportional to the steepness of rise of the summed rod response at time l. It is shown that the intensity dependences of 1) human visual latency and 2) brightness sensation, including effects of stimulus area and duration, are accounted for by the same model. The predicted functions are not power functions of intensity, but approximate such over wide ranges. Thus, a large body of psychophysical data is explained simply by the waveform of photoreceptor responses.

Action Potentials↗
PubMed1988

Low retinal noise in animals with low body temperature allows high visual sensitivity.

The weakest pulse of light a human can detect sends about 100 photons through the pupil and produces 10-20 rhodopsin isomerizations in a small retinal area. It has been postulated that we cannot see single photons because of a retinal noise arising from randomly occurring thermal isomerizations. Direct recordings have since demonstrated the existence of electrical 'dark' rod events indistinguishable from photoisomerization signals. Their mean rate of occurrence is roughly consistent with the 'dark light' in psychophysical threshold experiments, and their thermal parameters justify an identification with thermal isomerizations. In the retina of amphibians, a small proportion of sensitive ganglion cells have a performance-limiting noise that is low enough to be well accounted for by these events. Here we study the performance of dark-adapted toads and frogs and show that the performance limit of visually guided behaviour is also set by thermal isomerizations. As visual sensitivity limited by thermal events should rise when the temperature falls, poikilothermous vertebrates living at low temperatures should then reach light sensitivities unattainable by mammals and birds with optical factors equal. Comparison of different species at different temperatures shows a correlation between absolute threshold intensities and estimated thermal isomerization rates in the retina.

Animals↗
PubMed1988

The dilated urinary tract in children. Prospective analysis with correlation of radiological, isotope, pressure perfusion and surgical findings.

Moderate and even severe dilatation of the urinary tract in the absence of vesicoureteric reflux may remain stable or show spontaneous resolution. Two such cases are described. Twenty-five children with dilated urinary systems were studied to correlate the radiological, isotope, pressure perfusion and surgical findings. A positive Whitaker test correlated well with the surgical findings and post-operative improvement in renal function in all patients with pelviureteric junction (PUJ) and vesicoureteric junction (VUJ) obstruction. High flow rates of 8.6 and 12 ml are required even in neonates and infants in order to demonstrate obstruction by Whitaker testing.

Adolescent↗
PubMed1988

Temperature-dependence of rod photoresponses from the aspartate-treated retina of the frog (Rana temporaria).

The effects of temperature changes on rod photoresponses were studied by recording the aspartate-isolated mass receptor potential in the dark-adapted retina of the frog Rana temporaria. The amplitude of saturating responses, indicating the magnitude of the dark current, increased linearly with temperature in the measured range 6-26 degrees C, extrapolating to zero dark current at 0 degrees C. Sensitivity was maximal around 18 degrees C but the decrease towards lower temperatures was shallow. The results show that rod phototransduction in the frog Rana temporaria is adapted to lower temperatures than in the tropical toad Bufo marinus. Responses to dim flashes were, approximately up to peak, well fitted by the same 'independent activation' model with four delay stages as have been found to best describe current responses from single toad rods. The kinetics (reciprocal time-to-peak) showed Arrhenius-type temperature-dependence with apparent activation energy 12.4 kcal mol-1 and Q10 = 2.1.

Adaptation, Physiological↗
PubMed1987

Surround control of center adaptation in the receptive fields of frog retinal ganglion cells.

The sensitivity and intensity-response [R(log I)] functions of the receptive field center were determined by extracellular recording from frog retinal ganglion cells. The object was to study the steady-state adapting effects of peripheral background patterns: steady annuli and spinning "windmills" of light. Steady annular backgrounds could not be shown to directly effect any change of center responsiveness, only an enhancement of late response components attributable to depression of surround sensitivity. Movement of a windmill pattern shifted R(log I) functions to higher log intensities and decreased the maximal number of spikes in the response, but did not depress the saturation level of the impulse frequency. Its action thus resembled direct light-adaptation of the center.

Action Potentials↗
PubMed1987

Transient sensitivity reduction and biphasic photoresponses observed when frog retinal rods are oxidized.

1. Rod photoresponses and the effects of oxidation have been studied by recording either the transretinal voltage in aspartate-treated retinas or the outer segment current of single rods. 2. Oxidizing conditions transiently decreased, reducing conditions increased sensitivity. 3. Biphasic photoresponses were seen when the level of oxidation was rising and also in some other sensitivity-depressing conditions. 4. A model is proposed which explains the biphasic responses in terms of sensitivity differences between the tip and the base of the rod outer segment.

Animals↗
PubMed1987

Adaptation-related changes in the spatial and temporal summation of frog retinal ganglion cells.

The spatial and temporal summation of light by the receptive field centre of frog retinal ganglion cells were studied by extracellular recording in the eyecup preparation. The purpose was to quantify how summation changes with the state of light and dark adaptation and to clarify whether changes are due to the transition between rod and cone vision. Spatial summation was found to decrease by 30-50% as the cell was light-adapted to a threshold some 4 log units above the dark-adapted one. Temporal summation for threshold responses fell as the power -0.17 of the intensity of an adapting steady background. Neither change was bound to the rod-cone transition but occurred in the ranges of both receptor types; at equal sensitivities the summation of both receptor systems was matched.

Adaptation, Ocular↗
PubMed1987

Ganglion cell performance at absolute threshold in toad retina: effects of dark events in rods.

1. The performance of ganglion cells in detecting flashes of light near the absolute threshold was studied in an isolated eye-cup preparation of toad retina. Retinal ganglion cells, through which all visual information from the rods must flow to the brain, are in a key position for evaluating the still unproven hypothesis that the absolute light sensitivity is limited by rod noise (Barlow, 1956). 2. The dark-adapted threshold intensity for these cells, which were selected on the basis of their high sensitivity, averaged 0.029 Rh* flash-1 (range 0.008-0.062), where Rh* signifies one photoisomerization per rod. On average, 46 photoisomerizations were needed per receptive field per flash to evoke a threshold response (range 16-84). 3. In the threshold region, frequency of responses versus mean flash intensity was determined. Threshold performance could be described by theoretical frequency of response curves, allowing intrinsic noise to be estimated in terms of an equivalent rate of photoisomerization-like (dark) events. In two completely characterized cells the rate of dark events corresponded to 0.03 and 0.06 Rh*DS-1, where Rh*D signifies one dark event per rod. 4. Threshold elevations produced by dim backgrounds were studied. The results of these experiments are consistent with a dark event rate equivalent to 0.046 Rh*DS-1, or 0.037 Rh*DS-1 after correcting for a probable decrease in summation time. 5. The rate of actual dark events (0.028 Rh*DS-1, 20 degrees C) measured in Bufo rods (Baylor, Lamb & Yau, 1980) is close to the equivalent rates determined here. Thus, for the ganglion cells signalling the dimmest lights, the dark events in rods appear to be the most significant intrinsic retinal noise source limiting detection.

Action Potentials↗