Malathion-induced epidemic hysteria in an elementary school. More than 100 people, including firefighters, police officers, paramedics, nurses and physicians responded to reports that students at an elementary school had been exposed to an unknown and possibly toxic substance; 296 students were transported to eight hospital emergency departments. None were diagnosed as acutely ill. The substance was subsequently identified as approximately 22 ml of malathion, diluted in 15 L of water and applied by means of a hand-held sprayer approximately 100 m from the school. The odor apparently drifted to the school in 19 to 24 km/h winds. The episode was determined to be epidemic hysteria, possibly triggered by the malathion odor, but perpetuated by the stress of the emergency response. Hallmarks of epidemic hysteria are discussed, and recommendations for dealing with similar events are offered.


Oak (Quercus incana) leaf poisoning in cattle. Oak poisoning occurred in crossbred cattle due to eating immature tender oak (Quercus incana) leaves. Mortality was 70%. The animals exhibited anorexia, severe constipation and brisket edema. The feces were hard, pelleted and coated with blood and mucous. Significant reductions in blood hemoglobin and mean corpuscular hemoglobin, and significant elevations in serum bilirubin were observed. Serum urea nitrogen and creatinine were greatly increased. There was bilirubinuria, proteinuria, hypoproteinemia and hypocalcemia, and greatly increased activities of serum aspartate aminotransferase, lactate dehydrogenase and alkaline phosphatase. The levels of tannins and condensed tannins were 97.7 mg tannic acid equivalent and 5.8 mg catechin equivalent/g of dry leaves. There was extensive nephro- and hepatotoxicity in the affected cattle due to hydrolysable tannins and simple phenols in the oak leaves.


Paraquat poisoning in children: survival of three cases. Five children with paraquat poisoning are presented. Three were diagnosed early, treated and survived; the other 2 arrived 1-2 days after paraquat ingestion and died subsequently from respiratory failure due to pulmonary fibrosis.


Toxicology consultation fees to health care facilities: a successful revenue generating program for poison centers. Poison information center funding is a continuous problem and is growing more critical as cost containment effects the health care industry. Although a limited number of poison centers are partially funded by governmental agencies, general poison center operational support is derived from a variety of sources, and there is significant pressure upon centers to identify alternative funding sources. Affiliated members of our member hospital treatment network have provided one revenue source, but not all hospitals within our service region have subscribed. Furthermore, hospitals outside of our service region have utilized the service without any financial responsibility despite recommendations to use their local center. Therefore, to provide an incentive for local hospitals to subscribe to the service and to dissuade hospitals from outside of the region from using the service, we implemented a toxicology consultative fee for service on all calls emanating from non-member hospitals. In just 19 mo, recruitment of 16 new member hospitals has generated $65,150 additional revenue. Non-member hospitals electing not to affiliate but to remunerate for toxicology consultations (226 cases) have generated $20,400 (98% collection rate). A startling 95% reduction in calls from hospital outside of region has resulted since this fiduciary initiative began. New revenue totaling $85,550 has been generated by establishment of a toxicology consultation fee, and our staff is now able to dedicate priceless time and resources to the poison information needs of the residents of our region.


The poison center as a reservoir for antidotes for veterinary poisoning emergencies. Animal poisonings account for a significant number of the cases responded to by poison centers. The majority of consultations involve small animals and do not necessitate the use of large amounts of pharmacologic antagonists, such as atropine to treat anticholinesterase pesticide poisonings. However, large animals such as cattle present unique management problems, since phenomenal amounts of antidotes may be needed to treat a herd of cattle, creating a significant economic impact. The most challenging dilemma is providing 24-h availability and a means of acquisition of sufficient quantities of antidotes to reduce the economic impact of large-animal poisonings. In conjunction with a state veterinary medical association, a RPIC serves as a depot for the storage and distribution of emergency veterinary antidotes. Sufficient quantities of atropine, methylene blue, calcium EDTA, sodium nitrite and thiosulfate, and activated charcoal are available via the RPIC to treat a herd of 200 cattle. The antidotes are available only for emergency treatment and with a veterinary prescription. The 24-h nature of the poison center makes it an ideal location to serve the needs of veterinarians.


Imprint coding on solid medication forms: problems in interpretation. Currently, the FDA is planning to mandate imprinting on all solid medication forms. Regardless of the system it employs, identifying the manufacturer accurately and quickly is critical. Our data demonstrate that the current use of "logotypes" falls far short of minimally acceptable accuracy. We urge use of clear identifiers and that the proposed system be tested in the field prior to its implementation.


In vivo evaluation of the adsorptive capacity of activated charcoal for camphor. Camphor, a cyclic terpene, is the toxic ingredient in many over-the-counter (OTC) products. Early seizure activity due to camphor ingestion often contraindicates the use of traditional decontamination therapies in favor of oral activated charcoal use. No research data supports the affinity of activated charcoal for camphor. This study was conducted to evaluate the effectiveness of activated charcoal in preventing camphor absorption in a rat model. Camphor 40% in cottonseed oil (1 g/kg) was administered to 100 male Sprague-Dawley rats via oral gavage. Aqueous activated charcoal suspension (2 g/kg) was administered to the study group of 50 rats. Serum camphor concentrations were determined by gas chromatography at defined intervals over 10 h. No mortality occurred in either the control or activated charcoal-treated group. Area-under-the-curve bioavailability comparisons of each group revealed no significant differences (activated charcoal 421 micrograms x h/ml vs camphor 409 micrograms x h/ml). The absorption rate constants (Ka) and T 1/2 and elimination rate constants (Ke) and T 1/2 of each group were nearly identical and similar to those reported for humans. These preliminary data indicate the need for careful evaluation of the efficacy of oral activated charcoal administration as the sole means of preventing the absorption of camphor.


The administration of desferrioxamine to paraquat-intoxicated rats. We investigated the effect of desferrioxamine, an effective iron chelator, on animal survival and on plasma vitamin E levels after administration of paraquat doses close to the LD50. Male Sprague-Dawley rats received 20 mg paraquat/kg followed by 300 mg desferrioxamine/kg/d given ip over 2 d at 3 equal intervals. The results suggested that desferrioxamine prevented the paraquat-induced depletion of vitamin E, but did not improve the mortality due to paraquat. In ancillary in vitro experiments with a paraquat-based free radical system, where glutathione reductase and NADPH were used as sources of enzymic activity for the redox cycling of paraquat, desferrioxamine effectively prevented the formation of hydroxyl radicals, as determined by deoxyribose degradation.


Response of brown hisex chicks to low levels of Jatropha curcas, Ricinus communis or their mixture. Feeding Jatropha curcas seed at 0.5% of the basic diet for 2 w was not lethal to chicks. In chicks fed 0.5% Ricinus communis seed or a mixture of 0.5% J curcas + 0.5% R communis for 2 w, there was dullness, poor growth, locomotor disturbance and death. Pathological changes were correlated with alterations in clinical chemistry and hematology.


Effects of bracken fern (Pteridium aquilinum L Kuhn) feeding during the development of female rats and their offspring. Bracken fern (Pteridium aquilinum L Kuhn), is widely food in many parts of the world; the toxic effects have been demonstrated on many species of animals, and both carcinogenicity and enzootic hematuria has been studied. We investigated the effects of feeding bracken fern on the development of female rats and their offspring. The plant was fed as 30% of the normal diet on an ad libitum basis. Bracken fern did not modify the weight gain of the female rats during development, nor affect estrus cycle duration or milk production, the plant did reduce female fertility and weight gain during pregnancy. It also adversely affected physical and neurobehavioral development in the offspring.


Toxicological interactions of Abrus precatorius and Cassia senna in the diet of Lohmann broiler chicks. The combination of 0.5% Abrus precatorius seed and 2% Cassia senna fruit in the diet of Lohmann broiler chicks caused severe lesions, reduced weight gain, inefficient feed utilization and anemia. Organ lesions correlated with changes in clinical chemistry and hematology. Tissue recovery was not complete 2 w following withdrawal of the test diet. Feeding 0.5% Abrus or 2% Senna diets alone produced decreased growth and tissue lesions that did not return to normal 2 w following return to normal rations.


Abnormalities of smooth pursuit and saccadic control in schizophrenia and affective disorders. Smooth pursuit abnormalities have been reported in patients with schizophrenia and their first-degree relatives, suggesting that abnormal tracking may serve as a biological marker for schizophrenia. Recent studies in schizophrenic patients have found reduced pursuit gain, low initial acceleration and abnormal gain-corrective saccade interactions. Impaired saccadic initiation has been noted in anti-saccade tasks and in predictive saccade generation, as has saccadic hypometria. While abnormalities have been found in affective disorder patients, studies of their first-degree relatives suggest that abnormalities during pursuit are more closely associated with schizophrenia. Identification of specific defects allows informed speculation about their neural substrates and suggests possible relationships between the ocular motor defects and other cognitive and perceptual abnormalities associated with the major psychiatric disorders.


The perception of globally coherent motion. How do human observers perceive a coherent pattern of motion from a disparate set of local motion measures? Our research has examined how ambiguous motion signals along straight contours are spatially integrated to obtain a globally coherent perception of motion. Observers viewed displays containing a large number of apertures, with each aperture containing one or more contours whose orientations and velocities could be independently specified. The total pattern of the contour trajectories across the individual apertures was manipulated to produce globally coherent motions, such as rotations, expansions, or translations. For displays containing only straight contours extending to the circumferences of the apertures, observers' reports of global motion direction were biased whenever the sampling of contour orientations was asymmetric relative to the direction of motion. Performance was improved by the presence of identifiable features, such as line ends or crossings, whose trajectories could be tracked over time. The reports of our observers were consistent with a pooling process involving a vector average of measures of the component of velocity normal to contour orientation, rather than with the predictions of the intersection-of-constraints analysis in velocity space.


Visual memory for vernier offsets.

Visual memory for vernier offsets. Human ability to perceive and remember precise spatial relationships was investigated in a vernier acuity task. An initial ("standard") vernier stimulus with a variable offset was presented for 100 msec. After a delay of 1, 4, or 8 sec, another vernier target (the "variable" stimulus) followed, also for 100 msec. Observers compared the offsets of the two stimuli with each other. For very small offsets, discrimination between smaller and larger offsets was very precise, in the hyperacuity range. Thresholds increased linearly with the spatial offset of the standard stimulus, suggesting that the precision of the mechanism solving this spatial task scales with offset size. Control experiments suggested that this effect was not due to variations in retinal eccentricity. Thresholds also increased with increasing delay between the presentations of the two stimuli. By varying the delay, we directly measured the fading of the spatial memory trace.


The effects of common movement and spatial separation on position- and motion-based judgements of relative movement. When common movement is superimposed on relative movement (changes in separation between two dots), relative movement thresholds increase nonlinearly as a function of initial dot separation. For large separation (greater than 2.0 deg), thresholds increase gradually with increased separation. It is shown that this reflects judgments based on perceived relative motion. For small separations (less than 2.0 deg), thresholds increase sharply with increased separation. It is shown that this reflects judgments based on perceived changes in relative position. Evidence is presented that superimposed common movement reduces sensitivity to relative movement by reducing sensitivity to relative motion. This provides a "window", in the range of small dot separations, for relative movement judgements to be based on the perception of changes in relative position, even though motion is perceived for individual dots.


Sustained and transient properties of chromatic and luminance systems. Reaction times were measured to 450 and 650 mm test increments to examine the temporal behavior of the chromatic and luminance systems. A response-terminated random foreperiod paradigm was employed. Stimuli consisted of chromatic test increments upon backgrounds of varying spatial structure. Conditions were chosen which may preferentially favor the reaction time response being mediated by the chromatic or luminance systems. The temporal properties of the chromatic and luminance systems were demonstrated by the shape of the estimated hazard functions of the reaction time distributions. When the white background was spatially coincident with the test field, the hazard functions showed a relatively small peak. As white sectors were added to the annulus surround (introducing spatial transients between test and background fields), however, the hazard functions became more and more peaked. The hazard functions of the luminance system were estimated by assuming that the chromatic and luminance systems function in parallel. We concluded from the results that the chromatic system may be characterized as a quasi-sustained mechanism and the luminance system as a transient mechanism.


Visual suppression of torsional vestibular nystagmus in rhesus monkeys. Juvenile rhesus monkeys, placed on a motorized turntable, were rotated at constant velocity and then decelerated about an Earth-vertical axis. The animals were implanted with dual search coils to measure eye movements in three dimensions. By changing the monkey's body position (upright, ear-down, supine), postrotatory nystagmus was elicited in the horizontal, vertical, or torsional direction. Peak slow phase eye velocity and time constant of velocity decay were compared between decelerations in the dark and in the light. In all nystagmus directions, illumination reduced the time constant (Tc) to values around 5 sec. Peak velocity (Vp) was markedly attenuated in the horizontal and vertical directions (around 50%), but the effect of light on Vp in the torsional direction was small (less than 20%). These findings were independent of the velocity step size. Our hypothesis is that the two dynamic components of optokinetic nystagmus, as they interact with postrotatory nystagmus during visual suppression, differ in their dimensionality: the early component (fast component, direct pathway, pursuit system) is mainly activated in the horizontal and vertical directions, while the late component (slow component, indirect pathway, optokinetic system) effectively operates in all three dimensions.


Is the visual field temporally homogeneous? We asked the question "is the visual field temporally homogeneous when the well known spatial inhomogeneity is taken into account?" Our results show that the visual field exhibits inhomogeneity for stimuli of low spatial frequency for which the spatial inhomogeneity is minimal. This inhomogeneity takes the form of a reduction in sensitivity for stimuli of low temporal frequency in the periphery and an enhancement of sensitivity for stimuli of high temporal frequency in the periphery. The low temporal frequency loss in the periphery is post-receptoral and must involve a selective loss of sensitivity of the low pass filter. The enhanced high frequency sensitivity may be post-receptoral or purely receptoral. The consequence of such an inhomogeneity for subsequent stages of visual processing is discussed.


The coding of spatial position by the human visual system: effects of spatial scale and contrast. In this study we investigate the nature of the computations that underlie the encoding of spatial position by the human visual system. Specifically, we explore the relationship between alignment accuracy and spatial scale on the one hand, and between alignment accuracy and contrast on the other. We do this for stimuli where local luminance, local contrast, and orientation cues do not underlie performance. The results suggest that spatial localisation is independent of spatial scale and weakly dependent on contrast. We present subsequent models based on the properties of some classes of visual cortical neurones, namely multiplicative noise and contrast energy detection of complex cells, which describe the form of these relationships.


Extraocular muscle forces in alert monkey. We describe an extraocular muscle (EOM) force transducer that provides low-noise signals from an alert animal for several months, is implanted without disinserting the muscle, and is well-tolerated by the body, and present results obtained with the device. The transducer can be used to study orbital statics and dynamics, and oculomotor control signals undiminished by orbital low-pass filtering and antagonistic pairing of muscles. It may provide an index of effective EOM innervation, useful in studies of orbital tissue healing and plasticity, and oculomotor (OM) signal adaptation. During horizontal saccades transducers implanted in the lateral rectus (LR) and medial rectus (MR) of a monkey trained to fixate revealed an agonist muscle tension waveform corresponding to the "pulse-slide-step" pattern of saccadic innervation, and an antagonist waveform that was similar within a scale factor. We never observed transient increases in antagonist force at the ends of saccades (active braking) or at the beginnings. Onset of saccadic force in LR preceded that in MR by 1.6 msec for abducting saccades, and lagged that in MR by 1.1 msec for adducting saccades. During vertical saccades, transient force changes were found in LR and MR, which were likely due, at least in part, to globe translation. LR and MR forces during fixation tended to be largest with the eye about 10 degrees in elevation, and smallest in depression, indicating that effective total innervation was a function of vertical gaze, or that there was variation in the elastic component of muscle force related to orbital geometry, with LR and MR innervation independent of vertical gaze. An exponential decrease in fixation force, having a time constant of about 10 days, was observed after implantation. This may have reflected adaptive muscle lengthening or post-surgical healing.


Visual remapping in infantile nystagmus. The possibility that patients with idiopathic infantile nystagmus achieve spatial constancy by visual remapping was investigated by comparing subjective localization of flashed test targets to their absolute position in space and to their absolute position on the retina. Nystagmats first viewed a screen-stationary reference target that was followed by a test flash. A computer used eye movement feedback to precisely control the test flash position on the retina. All six nystagmats detected test flashes throughout their nystagmus cycle. For three nystagmats test flashes (total N = 48) were delivered to the same retinal locus that were, at different times, to the right and left of the reference target. More than two-thirds of such crossover stimuli were correctly located in space: when only those stimuli at least 0.5 deg from the reference were considered, two of three subjects correctly located all stimuli. Taken together these results argue that our subjects could see throughout the nystagmus cycle and shifted their visual map in synchrony with their nystagmus as an explicit means of avoiding oscillopsia.


Visual segmentation of a heterochromatic field into center/surround components. The process of visual segmentation was studied by quantitatively estimating the apparent difference (i.e. the perceptual contrast) between two segments of a heterochromatic field. A chromatic test bar (Munsell 5R 6/6, 5BG 6/6, 5Y 6/6, or 5PB 6/6) was centered in an achromatic surround (Munsell N6) and the luminance contrast between the test bar and surround was varied between 0 and 39%. At equiluminance (0% luminance contrast) the chromatic border between center and surround was vague and perceptual contrast was minimal. When luminance contrast was increased slightly (5-15%) the border between center and surround was more distinct and perceptual contrast was almost two times greater than predicted by a model that combines spatial differences in chromaticity and luminance as orthogonal vectors. A luminance border may enhance perceptual contrast by increasing the salience of the center/surround hue difference. A vector model is consistent with perceptual contrast only at relatively high luminance contrasts, where hue differences play a relatively minor role in visual segmentation.


The effects of colour adaptation and stimulus size on white perception as a function of eccentricity in man. We studied how much desaturating complementary colour had to be added to blue, green or red after homochromatic adaptation of short duration in order to perceive white or grey at eccentricities of 0-15 deg in the nasal visual field. The CIE 1931 (x,y) chromaticity coordinates corresponding to achromatic perception were subtracted from the chromaticity coordinates of blue, green and red in order to obtain the threshold differences (dx, dy) in chromaticity coordinates. When the stimulus size was constant at all visual field locations, the absolute values of dx and dy decreased with increasing eccentricity, which means that the desaturation threshold for white or grey perception was higher at the fovea than in the periphery. However, when the stimulus size was M-scaled magnifying its size with increasing eccentricity in inverse proportion to the lowest local sampling density of the human retina (cones and ganglion cells at eccentricities 0-10 and above 10 deg, respectively), dx and dy with blue became independent of visual field location except for the very centre of the fovea. However, M-scaling was unsuccessful with green and red. Although M-scaling with green reduced the change in dx and dy as a function of eccentricity, it had no effect on dx and dy with red colour.


Lateral motion bias associated with reading direction. We found that when Americans view ambiguous lateral long-range apparent motion, they exhibit a robust bias to experience leftward movement. In successive experiments, right-handers and left-handers, and left-side drivers from Japan equally manifested this leftward bias. However, bilingual viewers whose first language reads from right to left exhibited no lateral bias. Furthermore, the bilingual sample produced a significant correlation between exposure to English and extent of leftward motion bias. The findings provide strong evidence that reading habits can influence directionality in motion perception.


Spatial frequency tuning of facilitation by masks. The spatial frequency tuning of facilitation by masks is derived for a 2 c/deg test grating, counterphased at 8.8 Hz, from the contrasts at which masks of different spatial frequencies facilitate maximally. This tuning function has a bandwidth at half height of roughly 1.5 octaves, much broader than has been estimated previously from tuning functions determined at a constant contrast for each mask. We show also that best facilitation more than doubles sensitivity for tests of 4 c/deg and below, and that the magnitude of the facilitation effect declines at higher spatial frequencies.


Barn owls have symmetrical accommodation in both eyes, but independent pupillary responses to light. We have studied accommodation behaviour in the barn owl (Tyto alba). By defocussing one eye with various spectacle lenses and recording the refractive state in both eyes continuously during pecking, we found that the owls' accommodation was symmetrical in both eyes, with no regard to the power of the lens used. Even with no visual input to one eye, the amount of accommodation was always identical in both eyes. On the other hand, pupillary responses to light were independent. This finding differs from an earlier observation in the chicken, where both accommodation and pupillary responses were found to be independent. The result is discussed with regard to current knowledge on the central pathways for control of accommodation and pupillary responses in birds.


Infant temporal contrast sensitivity at low temporal frequencies. The data on infant temporal contrast sensitivity functions (TCSFs) are scarce and contradictory. Earlier studies suggest that critical flicker frequency (CFF) is adultlike at 2-3 months postnatal (Regal, D. M., 1981 Vision Research, 21, 549-555), while contrast sensitivity at low temporal frequencies remains poor. If both of these findings are true, then infant TCSFs are much flatter than those of adults. In the present study, we have re-investigated 2-month-olds' contrast thresholds at low temporal frequencies. To match the conditions of Regal's CFF study, test fields were embedded in a luminance-matched surround. As in previous studies, low contrast sensitivities were found. Models of infants' flat TCSFs are discussed.


Temporal contrast sensitivity in human infants. Temporal contrast sensitivity was measured in 1.5- and 3-month-old infants using the FPL procedure. Stimuli were 0.1 c/deg counterphase-flickering sinewave gratings. Temporal rates ranged from 1 to 20 Hz. Because the spatial sinewave underwent phase shifts of 180 degrees, the target could not be seen unless the observer was able to resolve it temporally. Adults were tested with the same temporal stimuli using a 2-alternative forced-choice procedure and a spatial frequency of 0.5 c/deg. Adult temporal CSFs were bandpass with peak sensitivity at 10 Hz. Infant temporal CSFs were lowpass at 1.5 months and bandpass at 3 months. The infants' contrast sensitivity was over a log-unit lower than adults'. Unlike spatial CSFs, infant sensitivity was closest to adult sensitivity at the highest flicker rate.


Control of interocular suppression as a function of differential image blur. This experiment studied normal adults, normal children, and corrected strabismics with alternating fixation, evaluating their ability to detect information presented to one eye under viewing conditions which might affect their eye preference. An apparatus was used which allowed unconstrained, binocular viewing of a video monitor, but in which the image seen by one eye was blurred while that seen by the other eye was in sharp focus. Under these viewing conditions, subjects were asked to identify a sharply focused letter which was shown briefly to the eye which was seeing the blurred background image or to the one which was watching the well-focused image. The question was whether there would be general suppression of the eye that was shown a degraded background, causing a reduction in its ability to process other information being presented. The results indicate no performance penalty for children, a mild decrement in recognition accuracy for normal adults, and a severe deficit in the ability of corrected strabismics to attend to the eye which views a blurred image. These results suggest that the loss of binocular vision that accompanies childhood strabismus is not a result of an inherent sensitivity to blurring, insofar as such vulnerability is reflected by these acute testing conditions.


Recovering heading for visually-guided navigation. We present a model for recovering the direction of heading of an observer who is moving relative to a scene that may contain self-moving objects. The model builds upon an algorithm proposed by Rieger and Lawton, based on earlier work by Longuet-Higgins and Prazdny. The algorithm uses velocity differences computed in regions of high depth variation to locate the focus of expansion, which indicates the observer's heading direction. We relate the behavior of the model to psychophysical observations regarding the ability of human observers to judge heading direction, and show how the model copes with self-moving objects in the environment.


Responses of cat horizontal cells to sinusoidal gratings. The spatiotemporal properties of cat horizontal (H-) cells were studied by recording the intracellular responses in the optically intact, in vivo, eye to sinusoidal gratings at a photopic mean illumination level. In order to investigate the linearity of spatial summation a "null test" was performed in which the responses to contrast reversal gratings were measured at different positions of the grating relative to the receptive field. Spatial and temporal transfer functions were measured using drifting sinusoidal gratings of variable spatial and temporal frequencies. The amplitudes of cat H-cell responses to contrast reversal gratings modulated with a square wave time-course showed a sinusoidal dependence on spatial phase. When zero crossings of the grating were lined up with the receptive field center, as defined by the maximum of the measured line weighting function, contrast reversal produced no response modulation. This result did not depend on the spatial frequency of the grating or the temporal frequency of contrast modulation over substantial ranges. The response waveform was found not to depend on the spatial phase of the grating. The spatial transfer function of cat H-cells has low-pass characteristics with a cut-off frequency in the range of about 0.4-1.5 c/deg. The shape of the spatial transfer function was roughly the same for temporal frequencies ranging from 3 to 10 Hz. The temporal transfer function exhibited band-pass characteristics with a maximum response amplitude at 3-6 Hz. The amplitude fall-off for low and high temporal frequencies was independent of the spatial frequency of the grating. The results obtained with sine gratings were found not to agree with the receptive field profiles measured with narrow slits flashed at different positions in the receptive field.


[Clinical manifestations of insulin resistance. The hormonal-metabolic syndrome X (5H), its prevalence and impact on cardiovascular morbidity and mortality. I]. Insulin resistance (prereceptor, receptor, postreceptor) is a complex phenomenon. It penetrates into the clinical picture via hyperinsulinism as impaired glucose tolerance, or NIDDM, as hyperlipoproteinaemia, arterial hypertension and hirsutism in women (syndrome 5H) associated with the polycystic ovary syndrome or the HAIR-AN syndrome. Based on a group of their 480 patients with NIDDM, 108 women with hirsutism, 320 patients with myocardial infarction and the results of the national cardiovascular programme the authors estimate the prevalence of the 5H syndrome as follows: in the general population 5-10%, in patients with arterial hypertension 15-30%, in NDDM 65-90%, in hirsutic women 10-20% and in patients with myocardial infarction 30-50%. These figures could be, however, substantially higher if as the criterion the IRI response was taken or that of C-peptide in OGTT or the results of the hyperinsulinaemic euglycaemic clamp. The clinical 5H syndrome is a phenomenon of latent insulin resistance perceived late by doctors and patients.


[Hyperinsulinism as a major etiopathogenic link with arterial hypertension, hyperlipoproteinemia and hirsutism. II]. The authors analyze mechanism by which hyperinsulinism causes NIDDM, hypertension, hyperlipoproteinaemia and hirsutism (5H syndrome). They demonstrate on a group of their 100 patients with NIDDM and arterial hypertension that, as compared with matched pairs without arterial hypertension, they have significantly higher levels of C-peptide and less favourable parameters of dyslipoproteinaemia. Hirsutism occurs in 10-15% of the adult female population, but in 18.4% women with NIDDM. However, in a group of 48 hirsutic women with NIDDM they did not find, as compared with matched pairs (i.e. women with NIDDM of analogous age, BMI and BP) significantly higher C-peptide and lipid levels. According to the authors congenital insulin resistance modified by numerous endogenous and exogenous factors is eventually manifested in the phenotype, in particular via hyperinsulinism as NIDDM, hypertension, associated with dyslipoproteinaemia and obesity which then, as the main risk factors, condition a high cardiovascular morbidity and mortality. Although hirsutism and the polycystic ovary syndrome are associated with hyperinsulinism, their interrelation is probably less close and thus has not such a negative impact on national health.


[Diagnosis of syndrome X using comprehensive analysis of the electrical field of the heart]. The authors describe the clinical picture and results of some auxiliary examinations in 18 patients with the X syndrome, i.e. with angina pectoris with a normal angiographic finding on the coronary arteries. For the diagnosis of ischemic cardiac changes, which are an integral part of this syndrome, the authors used a complex analysis of the electric cardiac field by means of a Cardiac 128.1 apparatus (manufactured by ZPA-Cakovice). In patients with the X syndrome they observed a significant reduction of some potential and integral values, as compared with an equally sized group of healthy subjects. On maps of the electric manifestation of cardiac activity on the chest surface ischemic changes were revealed on the antrior and lower cardiac wall but also in its lateral and posterior wall. These changes were older and were found in the subendocardial layer or concurrently in another area of the heart with affection of the subepicardial layer. Minor non-transmural fibroses, most frequently on the septum, in some instances spreading to the anterior and lower cardiac wall, were a surprising finding. At present it is not possible to differentiate merely by analysis of the electric cardiac field the X syndrome and ischemic heart disease. This should be made possible by further comparative studies. The present paper is the first description of ischemic and fibrous cardiac changes in X syndrome diagnosed by a complex analysis of the electric cardiac field in the professional literature published in Czechoslovakia and other countries.


[Initial experience with adenosine triphosphate in supraventricular arrhythmia]. The author presents data from the literature pertaining to the possible use of adenine nucleosides in recent years. The main action of adenosine or adenosine triphosphate is focused above all on influencing supraventricular tachycardia which developed as a result of the reentry mechanism. Based on his own observation, the author presents his initial experience with adenosine triphosphate (ATP, Spofa) in different indications: interference with supraventricular tachycardia with slim QRS complexes, interference of tachycardia with wide QRS complexes, termination of atrial flutter in digitalis intoxication and finally induction of an electrocardiographic tracing of latent ventricular preexcitation of the Wolf-Parkinson-White syndrome type.


[Immunogenetic study in hypertrophic cardiomyopathy]. Results of assessment of HLA antigens in hypertrophic cardiomyopathies in the world literature are very controversial. Work dealing with this problem in sufficiently large groups of patients is lacking, i.e. work which takes into account different functional and morphological forms of the disease. The authors made therefore a detailed investigation of 60 class 1 and 2 antigens in 117 patients with this disease. Values of the relative risk and chi 2 test revealed a number of possible associations. After correction for the number of examined antigens a significantly higher prevalence was proved only in HLA-B21 in patients with the obstructive form and in patients with advanced myocardial hypertrophy (thickness of more than 30 mm). Examination of HLA antigens can have in the mentioned cases a certain importance during comprehensive examinations of not quite typical forms of the disease. Carriership of antigen B21 is associated with an increased risk of serious cardiological disease, manifested already in young age.


[Patients after thyroid gland surgery from the aspect of the endocrinologist]. The authors examined 85 patients after a mean interval of 2.5 years following thyroidectomy. They focused attention on evaluation of the functional state using as criteria the TSH and TRH test. Simultaneously they examined by ultrasonography the volume of the remainder of the thyroid gland. In 8 patients operated on account of carcinoma the average volume of the thyroid gland was 1.3 ml. Five patients were hypothyroid despite permanent substitution. Of 77 patients operated on account of benign goitre evident hypothyroidism was found in 29 (37.7%) and latent hypothyroidism in 14 (18.2%). The volume of the remainder of the thyroid gland in these patients was on average smaller than 4 ml, while in patients who were euthyroid after thyroidectomy the mean volume of the remaining thyroid was more than 4.5 ml.


[Ultrasonography in subacute thyroiditis]. The authors draw attention to the altered ultrasonographic (USG) picture of the thyroid gland with subacute inflammation (SAT). A typical finding in the first to third stage of the disease are irregular different sized hypoechogenic to almost echo-void foci with normal parenchyma in between. The finding is normal only in the fourth stage of the disease. In 22 patients before 1987 the USG finding of the thyroid gland was evaluated. In 17 the examination revealed the assumed SAT which was confirmed in 15 patients. Seven patients were at that time hypothyroid. The USG finding was evaluated again in 1990. Ten patients, 2.8 years after the acute stage of SAT had a normal USG finding and were euthyroid. Five patients, not more than one year after the acute stage of SAT had still a pathological USG finding. Four of them were hypothyroid. Based on USG examination it is possible to identify before the cytotogical examination at first ill defined hypothyroidism or hypothyroidism as SAT in stage 1 to 3.


[Personal experience with treatment of autoimmune thrombocytopenia using intravenous IgG]. An immunoglobulin preparation for i.v. administration, Ivega (Imuna) was administered to 14 patients, 0.4 g/kg on five consecutive days, but also in lower doses. In all investigated patients a rapid onset of the therapeutic effect was observed--regression of haemorrhage and in 11 a concurrent rise of thrombocytes from a mean value of 20.10(9)/l to mean values of 130.10(9)/l with a maximum between the 6th and 14th day after administration. The tolerance of treatment was satisfactory and no side-effects were observed.


[Systemic lupus erythematosus after thymectomy in myasthenia gravis]. The authors describe a case of systemic lupus erythematosus in a 33-year-old female patient who developed the disease 12 years after thymectomy on account of myasthenia gravis. The activity of systemic lupus erythematosus was controlled by pulsed treatment with methyl prednisolone followed by long-term oral glucocorticoid and immunosuppressive therapy. The authors discuss the risk of systemic lupus erythematosus after thymectomy on account of myasthenia gravis with regard to the HLA haplotype.


[A fistula between the aorta and esophagus--an uncommon sequela of dissection of the thoracic aorta]. In a patient with repeated dissection of the ascendent aorta where the first episode was resolved surgically by an intraluminal prosthesis the authors describe the rare consequence of the development of a new dissection manifested by an aorto-oesophageal fistula. In the described case an inoperable episode was involved which fully confirmed the clinical validity of the pathognomic Chiari triad.


[Tumor microembolization in the lungs--a cause of marked dyspnea, syncope, hemolytic syndrome and disorders of hemocoagulation]. The authors describe the course of the disease in a 28-year-old woman who suffered two years following surgery of breast cancer from rapidly deteriorating dyspnoea, syncopes and laboratory manifestations of global respiratory insufficiency. The finding on auscultation of the lungs was normal, pulmonary angiography did not reveal signs of serious pulmonary embolization. The patient died after ten days in hospital despite comprehensive therapy and artificial ventilation. Necropsy revealed multiple microembolizations of tumourous cells into the pulmonary vessels as the main causes of the disease. Concurrently infiltration of the bone marrow by tumourous cells was revealed. The course of the disease was complicated by impaired haemocoagulation as a result of microangiopathic haemolytic anaemia and disseminated intravascular coagulation during the passage of erythrocytes through the pathologically altered pulmonary capillaries and impaired liver function.


[Circulating heparin-like anticoagulant--2 cases of successful therapy]. In the circulation of patients with severe haemorrhagic conditions in rare instances an anticoagulant of heparin nature can be detected, the exact origin of which has not been elucidated so far. These patients can be treated by protamine sulphate. The authors present their own observations in two women where the circulating anticoagulant of heparin nature was detected during a haemorrhagic condition after spontaneous rupture of an enlarged spleen and in scleroderma with organ affection. In both instances treatment was successful.


The use of head-up tilt table testing in the evaluation of unexplained syncope. Head-up tilt table testing was performed in 50 patients for evaluation of syncope. A positive test occurred in 29 patients (58 percent). Of these 29 patients, 15 were categorized as vasovagal; 11 as orthostatic hypotension; and three as chronotropic incompetence. Isoproterenol facilitated the occurrence of a positive test in 13 patients. Medications were used to treat 15 of the 29 patients having a positive test result. Syncope recurred in two patients over a 9 +/- 5 month follow-up period. In patients having unexplained syncope, head-up tilt table testing may provide a diagnosis and can be used to assess therapy. Earlier use of this testing modality in selected patients may obviate more expensive testing.


Pyomyositis in a diabetic host.

Pyomyositis in a diabetic host. A case of pyomyositis in a diabetic host is presented. Pyomyositis is occurring more often and clinicians must be aware of this entity, especially in the immunocompromised host. The reasons for more frequent and severe infections in the diabetic patient are outlined.


[Economic aspects of therapy for lipid metabolism disorders]. The primary and secondary prevention of cardiovascular diseases and, therefore, the therapy of hyperlipidemia is essential in strategies to lower morbidity and mortality from coronary heart disease (CHD), the most relevant atherosclerosis-associated disease. These programs imply not only a medical but also an economic challenge to our health system. That is why all therapeutic measures have to be evaluated regarding their cost-effectiveness. A cost-effectiveness profile was calculated for all the therapies of hyperlipidemia (nutritional therapy, dietetic nutritionals, drugs and LDL-apheresis) with respect to the following parameters: total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides. The daily costs of all interventional measures are compared to the success rate, whereby an index of daily therapy costs and 1% change per lipid parameter was calculated. Nutritional therapy is by far the cheapest, and LDL-apheresis the most expensive but also the most effective and reliable therapeutic measure. It has to be considered, however, that dietary intervention can be very successful in overnutrition while in rare cases of severe homozygous familial hypercholesterolemia there is no therapeutic alternative to LDL-apheresis. Life-style modifications, such as changing nutritional habits, may contribute towards reducing or removing one or more risk factor(s) (e.g. malnutrition is associated with overweight, hyperlipoproteinemia (HLP), hyperinsulinemia (syndrome X), hyperfibrinogenemia and hypertension). But neither health politicians nor the population seem to be conscious of the fact that life-style changes help to reduce medical expenditure. Considering the fact that nearly every medical service is getting more and more expensive, the need to introduce financial regulations is evident.(ABSTRACT TRUNCATED AT 250 WORDS)


Alterations of antioxidant tissue defense enzymes and related metabolic parameters in streptozotocin-diabetic rats--effects of iodine treatment. This study reports on the effect of streptozotocin (STZ) induced diabetes on water soluble-SH and -SS, as well as on hepatic glutathione peroxidase (GSH-Px), catalase and superoxide dismutase (SOD) activity and on malondialdehyde (MDA) content. In addition, we determined serum concentrations of glucose, cholesterol, triglycerides and thyroxine, and thyroid weight. To elucidate the possible impact of exogenous iodine on impaired free radical tissue defense mechanisms STZ-diabetic rats were exposed to iodine brine providing for a daily iodide uptake of about 300 micrograms/kg body weight. STZ-exposure caused a decline in thyroid weight (p less than 0.01) and in total serum thyroxine (p less than 0.001), as well as a fall in hepatic catalase (CAT) activity (p less than 0.01) versus control group. Impairment of catalase activity was related to serum glucose level (r = -0.569, p less than 0.01), while hepatic MDA was positively related to serum glucose (r = + 0.5, p less than 0.01). No protective effects of iodine brine were seen with regard to impairment by STZ of antioxidant enzyme status. We conclude that impairment by STZ of antioxidant enzymes may contribute to STZ-dependent experimental diabetes.


[Alcoholic ketoacidosis--3 episodes in one patient]. 3 episodes of alcoholic ketoacidosis were observed in one female patient over a period of 19 months. The clinical picture consisted of vomiting, dehydration, hyperventilation and abdominal pain. Predominant laboratory findings were acidosis (pH less than 7) and hyperglycaemia, with blood glucose values of 354, 330 and 147 mg/dl. This disorder is an important cause of metabolic acidosis, but especially in the German literature there are only rare reports on this issue. The picture of ketoacidosis in mostly chronically malnourished alcoholics reflects not only the complex abnormalities of acid-base balance caused by excessive cumulation of ketoacids, but also the related severe depletion of electrolytes and extracellular volume. Adequate acute therapy (as for diabetic ketoacidosis) and thorough follow-up treatment of any concurrent conditions result in rapid reversal of the syndrome in most cases. Since there are few reports of repeated episodes in one patient, an overview of this disorder is presented concerning management and differential diagnosis of the basis of our case report.


[Gliadin IgA antibodies in diagnosis of celiac disease in childhood]. An enzyme immunoassay kit for the determination of anti-gliadin-IgA antibodies in serum has been evaluated in the diagnosis of coeliac disease in childhood. 84 patients, 22 of them with coeliac disease according to ESPGAN's criteria were tested between 1978 and 1989 and the results have been correlated with the findings on small intestine biopsy and the clinical features. The sensitivity of the test was 95.5% and the specificity was 87.0% on initial diagnosis. On a gluten-free diet reduced antibody levels were seen in all patients. During gluten challenge 11 of 13 children showed an increase in anti-gliadin-IgA concentration. Of the remaining 2 without antibody elevation IgA deficiency became manifest in one patient, the other had a nearly normal mucosa on small intestine biopsy. Provided that IgA deficiency is ruled out and the gluten intake is sufficient the test seems to be useful for screening and might replace biopsy after gluten challenge in cases of increasing antibody levels.


Therapeutic drug monitoring and pharmacokinetic dose prediction methods. Therapeutic drug monitoring is recommended in suspected drug overdosage, in cases of therapeutic failure, in the establishment of regimens in patients with altered pharmacokinetics and in patients with unknown previous medications. Pharmacokinetic dose prediction methods have been developed allowing individual dosage adaptation. As examples, the three-point method of Sawchuk and the Bayesian technique are described. Drug concentrations could be predicted with sufficient accuracy by use of the three-point method in critically ill patients treated with aminoglycosides or flucytosine. Bayesian forecasting proved to be useful in predicting the nocturnal concentration curves in patients with asthma treated with a sustained-release preparation of theophylline for once-daily dosage. The efficiency of drug treatment can be considerably improved by monitoring serum drug concentrations and individualizing dosage using pharmacokinetic methods.


Clinical relevance of the determination of antiepileptic drugs in serum. Opinions on the clinical relevance of the determination of antiepileptic drugs in serum are very divergent. Specially the value of routine determinations has not been clarified up to now. At present the determination of antiepileptic drugs is indicated in the following situations: resistance to therapy including suspected irregular intake, adjustment of the serum level into the therapeutic range to prevent under- or overdosage, suspected intoxication (particularly during combined therapy), dosage monitoring when changes in the dosage-serum level relationship might occur, combined therapy, dosage reduction in the absence of seizures, determination of a baseline level in patients with good anticonvulsant control, legal indications, therapy research.


Therapeutic drug monitoring for the 1990s: meeting the laboratory needs of a changing environment. The need for monitoring serum and plasma concentrations for therapeutic drugs given to hospitalized and outpatients will continue to growth during the next few years, both in terms of the number of tests ordered each year and the number of different drugs that are monitored. The clinical laboratory will play an important role in implementing and maintaining accurate, cost-effective drug monitoring and treatment programs. To meet changing needs, further development and evaluation of automated analytical assays will be necessary.


Analyses of the pattern of therapeutic drug monitoring in a university hospital laboratory. Suitability and performance of the CEDIA assays. New homogeneous enzyme immunoassays (CEDIA assays) for therapeutic drug monitoring were evaluated on Boehringer Mannheim/Hitachi 704. A fluorescence polarization immunoassay and HPLC were chosen as comparison methods. A good correlation of patient data was observed for both methods (slopes 1.033-1.167). Imprecision within-run and between-day as well as the recovery in control samples of an external quality control survey were excellent and comparable to the routine method. In order to optimize the use of the CEDIA assays also for parameters which are less frequently requested, a parameter-setting for the batch-analyzer COBAS Fara was worked out. Performance of the CEDIA assays on random access analyzers is discussed with regard to the background of a laboratory for clinical chemistry in a University Hospital.


Liquid chromatographic analysis of phenobarbital, phenytoin, and theophylline. Sera from the routine of therapeutic drug monitoring were assayed for phenobarbital, phenytoin, and theophylline with three different methods: fluorescence polarization immunoassay as the standard procedure, the new CEDIA assays within a multicenter evaluation and HPLC which is known to yield results with a high specificity. CVs for between-day imprecision ranged from 2.6-8.6%, depending on the concentration of the drugs. There was a tendency to lower CVs for the HPLC procedure. Accuracy was verified with commercial control materials and spiked sera and proved to be satisfactory for all three methods and parameters. The linear range was approx. twice as wide for the HPLC compared with the other methods. The method comparisons were quite favorable. Deviations occurred mainly in the subtherapeutic concentration range.


Results of the multicenter evaluation of the CEDIA Theophylline assay. We report on the results of the multicenter evaluation of the CEDIA Theophylline assay on Boehringer Mannheim/Hitachi analyzers in 15 clinical laboratories in Europe and U.S.A. Main items of investigation were imprecision, recovery of control sera, interlaboratory survey and method comparisons using patient samples. Imprecision was found to be comparable to other routine methods. An advantage of the CEDIA assay can be seen in the good interlaboratory transferability of results. The new test has been shown to measure very accurately particularly by comparison with HPLC procedures revealing highly correspondent results. The reagent can be used up to one month using multiple recalibration. Due to its high practicability and reliability the CEDIA Theophylline assay can be recommended as a very suitable routine method for therapeutic drug monitoring on random access analyzers like Boehringer Mannheim/Hitachi analysis systems.


Results of the multicenter evaluation of the CEDIA Phenytoin assay. Thirteen clinical evaluation sites in Europe and U.S.A. investigated the CEDIA Phenytoin assay on Boehringer Mannheim/Hitachi analyzers with respect to imprecision, recovery of control sera, interlaboratory survey, linearity and method comparisons using patient samples. The linear dose-response relationship up to 40 micrograms/mL was confirmed by all participants. Imprecision at therapeutic analyte concentrations equalled that of other routine methods. Recovery of controls was found in a +/- 6% range for target values assigned by the CEDIA assay. The good interlaboratory transferability of the CEDIA assay was confirmed with control material and human samples. The reconstituted reagent can be used up to one month using weekly recalibration. In method comparison studies good correlations to other routine methods were obtained. Results in analyte-free human sera did not deviate systematically from the zero-point. Thus, the accuracy in patient sera has been shown for the CEDIA Phenytoin assay.


Results of the multicenter evaluation of the CEDIA Phenobarbital assay. The CEDIA Phenobarbital assay has been evaluated in twelve clinical laboratories in Europe and U.S.A. on Boehringer Mannheim/Hitachi analysis systems. The evaluation focused on the analysis of imprecision and accuracy. Within-run and between-day coefficients of variations of the new assay were comparable to those of established routine methods. As demonstrated in an interlaboratory survey study with controls and human sera, results obtained in different laboratories showed a good agreement. The CEDIA Phenobarbital assay measured very accurately, as particularly confirmed by comparison with HPLC. It can be recommended as a reliable and practicable test for monitoring of phenobarbital on Boehringer Mannheim/Hitachi analyzers used in routine clinical chemistry.


Practical aspects of monitoring cardiac drugs in the blood. Various factors known to affect digoxin blood values are discussed in the present review. A reduction as well as an increase in digoxin levels may be due to the method employed, to errors in the preanalytical phase, to peculiarities of the patient, to diseases or to the administration of drugs. Increased digoxin concentrations above the therapeutic range are much more common than manifestations of digoxin intoxication. However, geriatric patients are specially sensitive to intoxication. Attention has to be paid to digoxin-like immunoreactive factors (DLIF) being synthesized under certain physiologic and pathophysiologic conditions which cause falsely elevated values in digoxin-immunoassays. The determination of digoxin levels is indicated in suspected intoxication or hypersensitivity to digoxin, in patients with pacemakers or those receiving certain drugs, in old people and in patients suffering from any concomitant disease. The time of blood collection has to be carefully controlled in order to determine digoxin concentrations of diagnostic value, the physical activity of the patient being a main influencing factor.


CEDIA--homogeneous immunoassays for the 1990s and beyond. New homogeneous enzyme immunoassays have been developed for cortisol, digoxin, digitoxin, theophylline, phenytoin, and phenobarbital using the cloned enzyme donor immunoassay technology. As applied to Boehringer Mannheim/Hitachi analysis systems these methods provide rapid, accurate and precise quantification of analytes, with minimal interferences from endogenous serum constituents and low cross-reactivities to structurally-related hormonal precursors, drug metabolites and natural compounds. Additional significant features of the new assays are linear standard curves and two-point calibration. The six CEDIA assays join the two currently available CEDIA assays for determination of the thyroid parameters T4 and T Uptake. Additional new therapeutic drug and anemia monitoring assays are under development, demonstrating the versatility of the cloned enzyme donor immunoassay technology. These tests, in concert with Boehringer Mannheim/Hitachi analyzers, provide a high throughput, random access immunoassay system. The menu of available assays should continue to increase during the 1990s, providing efficient automation while allowing consolidation of testing on a limited number of instrument systems.


Improving the specificity of digoxin immunoassays. The overall reliability of measuring digoxin in serum improved significantly with the discovery and application of immunoassays. However, because of the low concentration of digoxin being measured, its narrow therapeutic range in serum, and the presence of endogenous digoxin-like immunoreactive factors (DLIF), developing assays for measuring digoxin still pose formidable challenges. In this presentation, recent developments in the characterization of DLIF from bovine adrenal cortex and human serum are described. Data accumulated to date suggest there is one principal endogenous molecular factor (DLIF) in humans that cross-reacts with anti-digoxin antibodies. This factor exists at sufficiently high concentrations in some patients to interfere with measurements of digoxin by most digoxin immunoassays. All digoxin immunoassays should be tested to interference from this endogenous factor. Various techniques for reducing DLIF cross-reactivity are reviewed. The isolation and purification of DLIF now provides new approaches for selecting specific anti-digoxin antibodies used in developing more accurate digoxin immunoassays.


Endogenous digoxin-like immunoreactive factors (DLIF) as measured by the CEDIA digoxin assay and a fluorescence polarization immunoassay. The sensitivity of a new homogeneous enzyme immunoassay for the determination of digoxin (CEDIA Digoxin assay) and a fluorescence polarization immunoassay (FPIA) to interference by digoxin-like immunoreactive factors (DLIF) was studied in sera from pregnant women, newborns, patients undergoing hemodialysis and patients with renal insufficiency, but without hemodialysis. None of the patients had been treated with digoxin or digitoxin. Cross-reactivity of DLIF in the CEDIA assay was generally lower than in the FPIA. Data on the distribution DLIF of values and method comparisons showed that sera of the four patient groups reacted in a completely different way in both assays, suggesting that the nature of DLIF in the four groups is not identical. Addition of digoxin to sera of patients not treated with this drug resulted in a reduction of the apparent DLIF concentration in the CEDIA assay and the FPIA. This shows that DLIF interference may be less pronounced in sera of patients undergoing digoxin therapy compared to untreated persons. Although the CEDIA assay is less sensitive to DLIF interference than the FPIA, further efforts are needed to reduce the extent of this interference.


Evaluation of the CEDIA digoxin assay on Boehringer Mannheim/Hitachi 717 analyzer. Some aspects of a new homogeneous enzyme immunoassay for the determination of digoxin have been evaluated, as part of a multicenter project. The CEDIA Digoxin assay is based on the use of two beta-galactosidase fragments (EC 3.2.1.23) produced by recombinant DNA techniques, one of them linked to digoxin. These two fragments couple to form the complete active enzyme, if not hindered by anti-digoxin antibodies. Digoxin in serum competes for antibody binding. The procedure can easily be automated and does not require special equipment. The imprecision of the method was studied at three different concentration levels (0.56, 1.29 and 2.77 ng/mL of digoxin). Within-run coefficients of variation were 8.01%, 5.57% and 3.30%, respectively, the corresponding between-day CVs being 17.4%, 8.41% and 4.89%. The procedure was found to be linear up to 4.4 ng/mL. Reagents were stable for at least four weeks. Results obtained by the CEDIA Digoxin assay compared well with those obtained by fluorescence polarization immunoassay.


Results of the multicenter evaluation of a novel homogeneous immunoassay for digoxin based on the cloned enzyme donor immunoassay technology. A new CEDIA assay for the measurement of digoxin in serum on random access analyzers was evaluated by twelve laboratories in Europe and the United States. Studies on the analytical range, reproducibility, calibration stability, recovery in controls, interlaboratory comparability, comparability with routine methods, and the effect of various interfering factors have been performed and the results are presented in this paper. The analytical performance was comparable to that of routine methods provided the manual pipetting step for pre-incubation was performed with accurate pipettes. A major advantage of the CEDIA Digoxin assay in terms of convenience is the simple two-point calibration procedure. Moreover, digoxin can be determined within 15 minutes after receiving the samples on random access analyzers like Boehringer Mannheim/Hitachi analysis systems. Thus, the CEDIA Digoxin assay represents an attractive alternative to the measurement of digoxin on dedicated immunochemical assay systems.


Results of the multicenter evaluation of a homogeneous immunoassay for digitoxin based on the cloned enzyme donor immunoassay technology. We evaluated a CEDIA assay for the determination of digitoxin in serum on random access analyzers. The multicenter evaluation included studies on the analytical range, calibration stability and reproducibility of the new assay. Moreover, recovery in controls, transferability of results obtained in different laboratories, comparability with routine methods, and the effect of various interfering factors have been analyzed. Summarized the analytical performance was comparable to that of routine methods. The CEDIA Digitoxin assay represents an attractive alternative to established digitoxin immunoassays because it can be performed on random access analyzers, thus permitting the simultaneous determination of digitoxin and other serum analytes without sample splitting.


An evaluation of a non-isotopic homogeneous enzyme immunoassay (CEDIA assay) for cortisol and its clinical utility. Serum cortisol is one of the more frequently requested steroid hormone assays. Its use is important in evaluating diseases of the adrenal cortex and pituitary. We briefly review the biochemistry of cortisol synthesis, the pathophysiology resulting from adrenal and pituitary abnormalities and the more specific immunochemical procedures which have replaced colorimetric chemical assays for cortisol. We also report our results on the evaluation of the analytical performance of the non-isotopic homogeneous CEDIA Cortisol assay and compare the advantages of this assay to state-of-the-art immunoassays.


Results of the multicenter evaluation of the CEDIA cortisol assay. The present paper describes the multicenter evaluation of the CEDIA Cortisol test for total cortisol. The observed linearity of the test was between 1.2 and 50 micrograms/dL cortisol. The limit of detection was calculated as 1.2/dL. Imprecision studies covering the diagnostically relevant range (5-20 micrograms/dL cortisol) yielded coefficients of variation between 1.7-8.9% (within-run) and 2.7-10.5% (between-day). An interlaboratory survey using 41 human samples and three control sera demonstrated that the new CEDIA Cortisol assay has a good interlaboratory transferability. Method comparison studies between the CEDIA Cortisol test and EIA, FIA, FPIA, and various RIAs yielded an acceptable level of agreement and concordant results in most cases. Low cross-reactivity of the antibody used in the new cortisol assay was observed with precursors or metabolites of cortisol. Especially, dexamethasone did not cross-react. However, prednisolone, 6-methylprednisone, and corticosterone showed cross-reactivities. No limitation by endogenous interferences was observed. The CEDIA Cortisol assay permits the precise, fast and sufficiently specific determination of cortisol. Furthermore, it offers the advantages of a non-radioactive assay and can be performed conveniently on Boehringer Mannheim/Hitachi analyzers in combination with routine clinical chemistry.


Economic aspects of therapeutic drug monitoring. In the last two decades two major trends heavily influenced the situation of the clinical laboratories. Cost saving issues have become more and more significant and an exploding number of tests has to be performed by a limited number of technicians. The latter task is facilitated by the use of automated analyzers. The CEDIA assays for therapeutic drug monitoring (TDM) can be performed on Boehringer Mannheim/Hitachi systems used for routine clinical chemistry. This means that now it is possible to determine all parameters of clinical chemistry, proteins, and TDM without sample splitting on one analyzer, resulting in saving of manual workload and costs.


[Differential diagnosis of peptic ulcer]. Although new pathogenetic findings of peptic ulcers have been detected, there still remain some open questions. Accurate anamnestic evaluation will find out risk factors as cigarette-smoking, stress and therapy with nonsteroidal antiinflammatory drugs (NSAIDs), and will be helpful in differential diagnosis. Endoscopy is the diagnostic means of choice, and enables to easy helicobacter pylori detection. Since some gastric ulcers are actually carcinomas, it is absolutely necessary to obtain multiple biopsies. The Zollinger-Ellison syndrome and symptoms of other rare diseases of the upper intestine are discussed.


[Helicobacter pylori. New apsects in the pathogenesis of peptic ulcer disease]. Antral gastritis and peptic ulcer disease are closely related to gastric Helicobacter pylori (HP) infection. HP possesses several pathogenic features which point to a causal role of HP in the development of gastroduodenal lesions. It is now generally accepted that HP causes type B gastritis, while its role in the pathogenesis of peptic ulcers is still unsolved. According to the classical ulcer concept, peptic ulceration is the result of an imbalance between protective mucosal mechanisms and aggressive digestive factors. The identification of HP does not disprove this concept, however, HP has to be added as a major pathogenic factor.


[Methodology and clinical significance of intragastric long-term pH measurement]. Intragastric long-term pH-metry is a suitable method of assessing gastric acidity under conditions of real life. The pH-metry system consists of three components: pH electrode, solid state recorder, and data analyzing system. Combined glass electrodes are recommended for gastric pH studies. Up to now, there are no generally accepted normal values in gastric pH-metry and thus data analyzing is not uniformly standardized. Intragastric pH-metry is the method of choice for monitoring of antisecretory treatment. This method enables the recognition of non-responders and improves dosing of antisecretory drugs. The prognostic value of gastric pH-metry in the assessment of acid-related diseases, if any, has still to be defined.


[Current therapy of ulcer disease].

[Current therapy of ulcer disease]. It is generally accepted that ulcer pathogenesis is mainly mediated by an imbalance between aggressive factors as gastric acid and pepsin, and obviously genetically determined defects in protection mechanisms of the gastric and duodenal mucosa. Since at present it is not possible to substitute these defects properly by pharmacological measures, the modern ulcer therapy aims to a distinct acid reduction as the main and most successful therapeutic principle. Recent studies show a direct correlation between the effectiveness and the acid reducing potency of a given anti-ulcer drug, assessed by pH above 3 over time. By long term treatment using H2-blockers and most recently the ATPase inhibitor Omeprazole it is now possible to reduce drastically the relapse rates of gastrointestinal ulcers and to improve significantly quality of life. An effective prophylaxis in duodenal ulcer can also be achieved by combination therapy with bismuth plus antibiotics or with omeprazole plus antibiotics. Even ulcers induced by nonsteroidal-antirheumatic drugs or acetylsalicylate can be adequately treated and prevented by acid reducing drugs. The present article includes pathophysiological and pharmacological backgrounds of medical ulcer therapy as well as guidelines for indication and mode of application of the different antiulcer drugs concerning short and long term treatment.


[Complications of peptic ulcer].

[Complications of peptic ulcer]. The complication rate of peptic ulcer disease is 2 to 5% a year. Hemorrhage occurs four times more often than perforation and penetration. High age and the use of nonsteroidal antiinflammatory drugs (NSAID) are the most important risk factors. The incidence of rebleeding is twice as high after a first complication. About 15 to 30% of bleeding patients die because of this complication. Endoscopy is the means of choice in diagnosis and primary therapy. Gastric retention and vomiting of stale food are typical symptoms of gastric outlet obstruction.


[Surgical treatment of stomach and duodenal ulcer]. Despite lots of innovation in conservative treatment, surgery has established in ulcer therapy. Elective surgery shows a very low mortality rate whereas that of emergency operations is approximately ten times that high. If one intends to improve the currently insufficient results of ulcer treatment, this is only possible by decreasing the number of emergency operations which for many years remains on a nearly unchanged level, in favour of elective surgery. This especially is true for patients on high risk regarding an ulcer complication. Most important complications are recurrent phases within short time and poor compliance. A further complication is any critical factor in general which leads to the assumption that an appearing ulcer complication may most likely not be survived. Critical factors mainly are advanced age and attendant cases of illness. It may be expected that the still high mortality of this benign disease can be considerably reduced by applying the formula "more elective--less emergency surgery".


[Abortion in the penal code].

[Abortion in the penal code]. Before discussing the change of legal norms it is necessary to know the actual law. The paper shows the West-German penal code and it's application in respect of the pregnant women, the physician and third persons.


[Legal protection of the fetus in West Germany]. No German legislation specifically addresses legal protection to the unborn child. Abortion which is synonymous with killing an unborn child remains a crime respective if prosecution is carried out or not. The German Supreme Court produced guidelines in 1975 concerning the unborn child's protection which indicate that the life of the unborn should be afforded the same legal protection as that of a living being. But jurisdiction, new legal drafts or the public debate alone are not able to reduce the number of abortions.


The effect of alcohol consumption on body weight among Wisconsin adults. It is a common perception that alcohol use increases body weight. In fact, people are often advised to reduce their drinking if they wish to lose weight. To assess the relationship between alcohol use and body weight, we analyzed data from 5,496 Wisconsin men and women. We compared weights of drinkers and non-drinkers and adjusted for potential confounders. For women, there was a strong inverse relationship between drinking and weight. Women who drank any alcohol weighed an average of 2.6 kg (5.6 lbs) less than women who did not drink (p less than .0001). This association was found for all types of alcoholic beverages. No difference in weight was found overall between drinking and non-drinking men, although men who drank wine weighed significantly less (1.8 kg, p less than .05) than non-drinkers. These results, combined with other recent studies, suggest that alcohol use does not lead to increased weight among Wisconsin adults, and may be associated with lower weight among women.


[Long-term follow-up of Crohn disease].

[Long-term follow-up of Crohn disease]. 184 patients diagnosed with Crohn's disease were observed for an average of 5 years and evaluated for clinical pattern and course of disease. The male/female ratio was almost equal (90 m. vs. 94 f.). The peak of disease manifestation was between years 18-32. Familial clustering of inflammatory bowel disease was observed in 2.2%. The pattern of anatomic involvement was ileocolic in 53%, colon in 24%, small bowel in 20% and other locations in 3%. 34% of patients were afflicted with at least one extraintestinal manifestation, 34% developed fistulae. Fistula formation was seen more often in colon involvement than small bowel involvement (69% vs. 32%). 48% of the patients were operated at least once. 3 patients died during the observation period, 2 of them with sepsis. Evolution of carcinoma was not observed. Some of our results are in accordance with the literature, some distinct observations (e.g. low familial clustering) underline the theory of a multifactorial pathogenesis in Crohn's disease.


Percutaneous transhepatic dissolution of gallbladder stones. The method of percutaneous transhepatic dissolution with methyl tert-butyl ether (MTBE) has been used at the Zagreb Clinical Hospital Department of Medicine since 1989. From December 1989 until December 1991, 69 patients, 51 (74%) females and 18 (26%) males, with symptomatic and cholesterol gallbladder stones were hospitalised at the Department. All patients preferred percutaneous transhepatic dissolution to surgical treatment of gallbladder stones. The gallbladder was successfully punctured and the catheter placed into the gallbladder lumen in 63 (91%) patients, whereas complete dissolution was achieved in 59 (85.5%) patients. In 21 (33.9%) of these 59 patients, after completed dissolution computer-processed roentgenograms and ultrasonic scan of the gallbladder revealed residual particles of debris sized up to 2 mm. Six patients in whom puncture, i.e. the placement of the catheter into the lumen was unsuccessful, were electively operated on the following day without any complications. The mean duration of hospitalisation for 63 patients was 4.5 days.


[Surgical therapy of acute cholecystitis--advantages of early operation]. 229 patients with an acute cholecystitis were operated on at the Surgical University Hospital of Ulm between 3/1982 and 6/1990. 42.3% of the patients were older than 70 years, the mean age being 64.3 years. 51.5% suffered from a complicated form of the disease. Intercurrent diseases were preoperatively found in 76%. Intraoperative complications of a technical nature occurred in 3.1%. The overall postoperative morbidity rate was 54%, with 9.4% of local problems, and showed a clear dependency on age and the number of preexisting risk factors. 31% had to undergo reoperation. The overall mortality rate was 2.6%, with a 0% mortality for patients under 65 years. The number of preexisting risk factors clearly correlated the period of hospitalisation, which was 16.1 days on average. In symptomatic gallstone diseases an early elective cholecystectomy should be strongly considered, especially in aged and multimorbid patients.


Plasma and tissue alterations of peptide YY and enteroglucagon in rats after colectomy. Peptide YY (PYY) and enteroglucagon are produced by endocrine cells of the colonic mucosa. PYY inhibits upper gastrointestinal motility, and enteroglucagon is trophic for small bowel mucosa. Adaptive increase in the production and release of these peptides may improve functional results after colorectal resections. We hypothesized that if segments of the colon were resected, then production and release of PYY and enteroglucagon would increase in the remaining segments of bowel. Animals which underwent colonic transections and partial resections had transient elevations of PYY up to 250 +/- 80 pmol/L, which dropped to control group levels in the second week following surgery. Rats with an abdominal colectomy had significantly greater PYY levels than all other groups from the third (208 +/- 30 pmol/L) to the thirty-eighth (100 +/- 16 pmol/L) week of the study. Circulating levels of enteroglucagon were elevated to 156 +/- 35 pmol/L in rats with a right hemicolectomy during the first week following surgery. Enteroglucagon levels did not significantly vary in the other groups studied. Both tissue PYY (413 +/- 33 pmol/gram) and tissue enteroglucagon (171 +/- 17 pmol/gram) were significantly elevated in the rectums of the rats with an abdominal colectomy, as compared to all other groups. The elevated tissue levels may thus account for the ability to maintain elevated plasma PYY. Double immunogold labeling of endocrine cells in the colorectal tissue for PYY and enteroglucagon revealed both peptides within the same endocrine cells and secretory granules. These studies support the hypothesis that circulating levels of PYY are elevated after major colonic resections and suggest that L-type endocrine cells may participate in adaptive responses which improve intestinal function following colonic surgery.


[Endosonography in gastroenterology--an intermediate evaluation]. Endoscopic ultrasonography has widened the diagnostic spectrum of gastrointestinal disorders in two respects: For the first time it became possible to visualize the gastrointestinal wall with its layer structure. EUS was shown to be highly accurate in the local staging of gastrointestinal tumors (T and N stage). The clinical relevance of endosonography derives from stage-dependent treatment protocols selecting patients for different forms of tumor therapy. The second advantage of endosonography is a high-resolution imaging of the pancreas enabling the detection of small lesions (e.g. endocrine tumors). Endoscopic ultrasonography is furthermore the most reliable method for local staging of pancreatic and ampullary carcinoma. The role of endosonography in benign gastroenterological disorders is less well established. With the increasing use of laparoscopic surgery endosonography may become even more important in the future.


Biological and clinical aspects of autoimmune inner ear disease. The clinical presentation, diagnosis, and management of autoimmune inner ear disease are reviewed. Recent studies indicating an autoimmune etiology and pathogenesis are discussed, along with a comparative analysis of several promising new animal models. Further studies to define the natural history, pathogenesis, and diagnosis of the disease are suggested.


Use of Xenopus laevis frog egg extract in diagnosing human male unexplained infertility. Approximately one in six married couples find themselves involuntarily infertile. This ratio translates to between two and four million U.S. couples. Although numerous tests are available for diagnosing infertility problems, 5-10 percent of all couples who seek medical treatment are diagnosed with unexplained infertility. Several tests are presently available for diagnosing male infertility; however, none of the present procedures test for activation of the sperm nucleus following entry into the fertilized egg, a series of events critical for the entry of the zygote into the developmental program. We have developed an in vitro human sperm activation assay, using Xenopus laevis frog egg extract. When normal human sperm is permeabilized and then mixed with frog egg extract, the sperm nuclei decondense, synthesize DNA, and recondense during a three-hour time course. We have tested this assay's utility in diagnosing previously unexplained infertility. We found that 20 percent of the male infertility patients produced sperm that responded abnormally in the assay (95 percent confidence interval, 4-48 percent; n = 15), while sperm samples from 15 fertile males showed no abnormal responses (p = 0.0112). These preliminary results indicate that the human sperm activation assay may be a useful tool for diagnosing some cases of human infertility.


[Endoscopic sonography of the anorectum in inflammatory rectal diseases]. 213 patients, classified in 3 groups, were examined in a prospective trial using endorectal ultrasound. 80 patients (group A) had no anorectal disease, the endorectal ultrasound showed normal structures of the anorectum and the perirectal tissue. 80 patients (group B) suffered from Crohn's disease, 30 of them had no clinical signs, the rest of this group (50 patients) felt pain in the anal/perianal region. 83 patients (group C) had perianal abscesses or fistulas, Crohn's disease could be excluded. In all 64 perianal fistulas and 66 perianal abscesses were diagnosed. The results of the rectal-proctological examination were compared with endorectal ultrasound. 100% of the perianal abscesses could be recognized using endosonography. The digital-proctological examination revealed only 57% of perianal abscesses and 48% of perianal fistulas; the supralevatory abscesses couldn't be detected proctologically at all. By endorectal ultrasonography we obtained useful informations about localization and extension of the inflammatory process. From a therapeutic and prognostic view the endorectal ultrasound is a simple, practicable and useful method to investigate perianal and anorectal diseases.


[Intestinal regulation of pancreatic enzyme secretion: stimulatory and inhibitory mechanisms]. How exocrine pancreatic secretion is regulated is only partly known. It is assumed that interaction of several neural and hormonal mechanisms is involved. In man, the intestinal component of these control mechanisms is very important while extra-intestinal mechanisms (such as the cephalic and the gastric phase) play lesser roles. Regulation of pancreatic secretion by the intestine is composed of three main mechanisms. 1. The proximal intestinal (duodenal) phase of the secretory response to a meal is elicited by nutrients within the proximal intestinal lumen. It is mediated mainly by interactions between cholinergic reflexes and release of the peptide hormone cholecystokinin (CCK). Recent data suggest that part of the action of CCK is not exerted directly on the acinar cellular level, but rather by modulation of cholinergic inputs. 2. The distal intestinal (ileal) phase is elicited by contact of the distal intestinal mucosa with nutrients that pass through the ileal lumen due to physiological malabsorption. The ileum (in contrast to the duodenum) induces net-inhibition of pancreatic secretion. The mediation is unknown, candidate mediators are PYY and GLP-1. 3. Intestinal feedback-regulation of pancreatic secretion in humans is controlled by intraluminal protease activity; this mechanism is not covered in the present paper.


Cheyne-Stokes respiration in congestive heart failure. Cheyne-Stokes respiration is an abnormal breathing pattern which commonly occurs in patients with decompensated congestive heart failure and neurologic diseases, in whom periods of tachypnea and hyperpnea alternate with periods of apnea. In the majority of these patients, the ventilatory patterns may not be recognized, and the clinical features are generally dominated by the underlying disease process. Cheyne-Stokes respiration may, however, have profound effects on the cardiopulmonary system, causing oxygen desaturation, cardiac arrhythmias, and changes in mental status. Treatment of Cheyne-Stokes respiration in congestive heart failure with supplemental oxygen or nasal continuous positive airway pressure, in addition to conventional therapy, may improve the overall cardiac function and perhaps the patient's prognosis.


[Cholesterol lowering and life expectancy: a critical evaluation]. Numerous studies have confirmed a positive correlation between serum cholesterol levels and the occurrence of coronary artery disease. Lowering cholesterol by 1% is accompanied by a reduction of coronary events by 2%. The rate of fatal coronary events is not significantly influenced. Coronary angiography demonstrated only a mild average reduction of coronary lesions after cholesterol-lowering therapy. This might be explained by the low lipid content of a coronary plaque (5-15%). The majority of intervention trials revealed an increase of the extracardiac mortality in treatment groups. Thus, up to the present, it remains unproven that cholesterol-lowering therapy leads to an increase in life expectancy.


[Relationship between lipid metabolism disorders and age of first manifestations of coronary heart disease]. In 509 male patients, age less than 45 years, with angiographically documented coronary artery disease (CHD) we found (in contrast to age-matched controls: 459 participants of the PROCAM study) an increased amount of total cholesterol (259 vs. 221 mg/dl), LDL-cholesterol (185 vs. 142 mg/dl), Apo-B (138 vs. 118 mg/dl), lipoprotein(a) (12 vs. 5 mg/dl) and uric acid (6.4 vs. 5.8 mg/dl); HDL-cholesterol (40.5 vs. 46.8 mg/dl), Apo-A-I (122 vs. 143 mg/dl) and Apo-A-II (38 vs. 43 mg/dl) were significantly lower. These differences in lipid-metabolism between CHD-patients and controls in the younger group were essentially more pronounced than in older individuals of a group of 423 male patients over the age of 45 years who suffered from CHD and 545 age-matched PRO-CAM participants. Among the extent of the disorder in lipid metabolism, the apolipoprotein E-polymorphism, and the age of onset of CHD there exists a significant correlation which proves the special importance to therapeutically influence disorders of lipid metabolism especially in younger patients.


[Modulation of vascular tone of normal and arteriosclerotic arteries by leukocytes]. Leukocytes, in particular mononuclear cells, play a central role in the pathogenesis of arteriosclerosis. The arteriosclerotic vessel wall is chemotactic for circulating leukocytes. Activated leukocytes are known to release a variety of vasoactive substances. Thus, activation of leukocytes in diseased arteries is not only an epiphenomenon of an inflammatory process, but instead may contribute to arteriosclerosis-associated complications such as vasoconstriction/vasospasm and thrombotic vessel occlusion. Influence of leukocytes on vascular tone appears to be complex and may be modulated by the presence of intact endothelium and additional blood constituents such as platelets. In vitro, mononuclear and polymorphonuclear leukocytes both relax and contract isolated arteries according to experimental conditions and leukocyte isolation protocols. In vivo, activation of leukocytes by chemotactic peptides f-met-leu-phe or complement C5a produces pronounced vasoconstriction. Mediators of these leukocyte-induced vascular responses are partially characterized and consist of nitric oxide (or EDRF-like factor), superoxide anions, thromboxane A2, peptidoleukotrienes, and an unknown contractile factor. In addition, leukocytes may indirectly modulate vascular tone by cleavage of angiotensin II from angiotensinogen or angiotensin I, and by inhibiting or stimulating platelet aggregation. Thus, leukocytes and their products may have several pathways to modulate vascular tone. Abnormal interactions between endothelium-platelet-leukocytes with vascular tone may play an important role in the pathogenesis of vascular complications in patients with coronary artery disease.


[Anti-arrhythmia and pro-arrhythmia effects of oral cibenzoline therapy in sustained ventricular tachycardia]. The efficacy and safety of the new class-I antiarrhythmic drug cibenzoline was assessed in 12 patients with spontaneous and inducible ventricular tachycardia. Programmed ventricular stimulation, 24-h ambulatory electrocardiogram (ECG), and continuous ECG monitoring were performed without antiarrhythmic drugs and after oral administration of 254 +/- 80 mg of the substance. Oral cibenzoline suppressed the induction of tachycardia in only one patient. Induction of tachycardia was more difficult in two patients, unchanged in four patients, and easier in two patients. Cycle length of induced tachycardia and QT-interval corrected for frequency were not changed significantly; effective refractory period of the right ventricle was prolonged. Twenty-four hours of ambulatory monitoring during cibenzoline treatment (n = 9) showed no significant increase in the frequency of ventricular premature complexes. However, spontaneous sustained ventricular tachycardia developed in three patients after initiation of cibenzoline treatment. In two patients, termination of induced ventricular tachycardia was significantly more difficult under cibenzoline; several DC-shocks were required to terminate the tachycardia. Thus, the use of oral cibenzoline in patients with sustained spontaneous and inducible ventricular tachycardias showed a low antiarrhythmic efficacy at programmed stimulation and a high incidence of spontaneous ventricular tachycardia.


[Value of a provocation test with diprafenone in patients with bifascicular block]. The significance of provocative tests in patients with bifascicular block is not established. We studied 14 patients with bifascicular block, syncope and documented episodes of high degree AV-block. 1.5 mg/kg Diprafenon was given after a period of at last 12 hours 1:1 AV-conduction. Electrophysiologic evaluation was performed before and after diprafenon. AV-block III could be provoked in 1 of 14 patients with Diprafenon. Therefore a total AV block occurred in 7% of patients. The low sensitivity of provocative test with Diprafenon even in patients with documented high degree AV-block prevents its application in clinical practice.


[Left ventricular catheter ablation of the AV conduction system with radiofrequency electric current]. We report on a 32-year-old female patient with a history of recurrent atrial fibrillation and rapid ventricular response (up to 240 beats/min) resistant to multiple drug therapy. In this patient, we successfully performed a radiofrequency catheter ablation of the atrioventricular (AV) junction from the left ventricle, after radiofrequency energy application in His-position above the tricuspid valve was unsuccessful. This technique offers an-alternative treatment in patients in whom the conventional right-sided catheter ablation of the AV junction proves ineffective.


[Effects of endurance training on left ventricular filling dynamics: a study using stress Doppler echocardiography]. To evaluate the impact of endurance training on left-ventricular (LV) filling dynamics Doppler mitral flow was derived in 23 amateur endurance-trained athletes (AT) aged 31 (24-39) years with a personal marathon record greater than or equal to 200 min, and in 20 ultra-endurance athletes (UEA) aged 38 (28-42) years with a personal marathon record less than 200 min during bicycle exercise in supine position. Twenty-two untrained healthy volunteers (UT) aged 27 (24-30) years served as control. In particular, atrial filling fraction (AFF) as the relative share of atrial contribution to LV filling was measured. At rest AFF was significantly higher in UT (29%) as compared to AT (25%) and UEA (25%). During exercise (150 watt) atrial fraction increased significantly more in UT (37%) as compared to AT (34%) and UEA (29%) (p less than 0.01). At this point of measurement UEA had significantly lower values for AFF than AT (p less than 0.001). Two min post exercise atrial filling fraction already reached baseline values in UEA (24%) and AT (26%), while it remained significantly elevated in UT as compared to baseline values (38%, p less than 0.001). Ten min post exercise atrial filling fraction showed still elevated values in UT (32%), but decreased under baseline values in UEA (23%). No differences in heart rate between the two athlete groups at all times of measurement were observed. Thus, while atrial filling fraction rose in all study groups during exercise, it returned earlier to baseline values in athletes than in untrained subjects. This indicates a better cardiac adaptation to physical stress and a better diastolic performance during exercise in endurance-trained athletes, being even more pronounced in ultra-endurance athletes.


[The quality of life of the elderly in Germany]. The quality of life of the elderly in Germany is described in respect to selected aspects of objective living conditions and subjectively perceived quality of life. On the background of a general trend to an "aging society" a new situation has arisen for the elderly in unified Germany. The analyses depend on representative data from official statistics and the social sciences and they are concerned with demographic characteristics, distribution of wealth, and indicators of well-being. The conclusion is that, on the whole, the elderly cannot be regarded as a social problem; moreover, the challenge is to correct social inequality among the elderly people.


[The development of needs and income security in the elderly--some general comments]. The development of the requirement of private persons (by households) is discussed by micro-economic models, legal regulations, and cross-section-data, and is represented in stylized figures. These hypothetical longitudinal profiles are compared to those of income. The analysis supplies evidence of increasing requirement and decreasing income during retirement.


[Monetary security for the aged--concepts of political distribution goals and income-related effects of pension security systems]. This contribution discusses some theoretical aspects related to the question of whether, and in what way, a uniform social security target has been defined for the monetary old-age protection in the Federal Republic of Germany, and to what extent different pension schemes fulfill this target. The analysis leads to the conclusion that only a "target range", and not a defined value, has been developed for the indicator "individual replacement rate". The investigation into the effects of old-age pension schemes on income shows that, even after benefit cuts, public sector employees, on the whole, are better protected than employees in the private sector. A future, detailed empirical analysis would have to investigate individual social groups.


[From foreign worker to pensioner--selected aspects of financial security and social care of elderly foreigners in Germany]. There is evidence that many older migrants of foreign nationality remain permanently in the Federal Republic of Germany. Therefore the question of their social protection after retirement arises. This contribution discusses the financial protection via statutory pensions and social assistance, as well as the care provided by their families or on an inpatient or outpatient basis. Deficits in social protection of older immigrants are evident, which should be investigated more thoroughly and dealt with by social policy.


Benign breast disease in Papua New Guinea. In this study 302 biopsy-confirmed benign breast lesions in Papua New Guinean (Melanesian) women during a ten-year period were reviewed. Inflammatory breast disease was the most frequent type. Chronic mastitis, chronic suppurative mastitis and abscesses formed 32% of benign breast lesions and 71% of the group of mastitides. 10 cases of tuberculous mastitis were recorded. Fibrocystic disease was observed at a lower age (31.9 +/- 8.2 years) than has been reported from Black United States and West Indian populations. The high frequency of mastitis is an important finding. This is most likely to be associated with lactation. Proper hygiene during breastfeeding and the judicious use of antibiotics should reduce this high frequency. Education of women about these matters should form part of health education programs in Papua New Guinea.