Rapid assessment of glycoprotein IIb/IIIa blockade with the platelet function analyzer (PFA-100) during percutaneous coronary intervention.

BACKGROUND: The platelet function analyzer PFA-100 (Dade Behring, Miami, Fla) evaluates platelet function by determining the time to occlusion of an aperture in a membrane coated with collagen and adenosine diphosphate or epinephrine as whole blood flows under shear stress conditions. Platelet aggregation causes aperture occlusion, and results are reported as closure time (CT). Interindividual variability is observed in the level of platelet inhibition achieved with use of the current abciximab dosing regimen (0.25-mg/kg bolus + 10-microg/min infusion for 12 hours). The relationships between specific levels of platelet inhibition and clinical efficacy and safety have not been fully established. METHODS AND RESULTS: We prospectively studied platelet function in 27 patients receiving abciximab during percutaneous coronary intervention. This evaluation included determinations of platelet-rich plasma aggregometry, receptor occupancy studies (D3 assay), and CT measurements at baseline and 10 minutes, 4 hours, 12 hours, and 24 hours after the bolus. All patients received abciximab, aspirin, and heparin; patients undergoing coronary stent implantation received aspirin and ticlopidine after the procedure. CT results were reported within 10 minutes after initiation of testing. For 96% of patients, CT was 300 seconds (maximum CT) immediately after abciximab bolus and remained so throughout the infusion. At 24 hours we observed variable recovery from platelet inhibition and in 72% of patients CT returned to normal (< or =130 seconds). CONCLUSIONS: Findings with the PFA-100 were similar to results observed with platelet aggregometry and receptor occupancy measurements. Most patients treated with abciximab exhibit normalized platelet function at 24 hours despite moderate levels of receptor occupancy, suggesting dissociation between occupancy and function.

Component stretching in fast and slow oblique saccades in the human.

We have studied the dynamics of human saccades along various cardinal (horizontal and vertical) and oblique directions in two different experimental paradigms yielding fast and slow saccades, respectively. We found that the saturation of vectorial peak velocity with amplitude, which is already well known from earlier studies on fast saccades, was equally pronounced in slow saccades. In both paradigms, the saturation level had a quite similar strong dependence on saccade direction. We found that the peak-velocity/amplitude relationships (main-sequences) of fast saccades in different directions were not simply scaled versions of one another. Whereas peak velocity in small saccades showed less anisotropy, different rates of saturation with amplitude in different directions (expressed in the angular constant parameter) caused the bundle of main-sequence curves to fan out at larger amplitudes. This property is reflected in a straight-line relationship between the angular constant and the asymptotic peak velocity parameters of the main-sequence. The possible contribution of neural control signals and plant properties is discussed. We also studied the main-sequences of oblique saccade components and found clear evidence for component stretching in both paradigms which increased as the saccade vector turned away from the cardinal direction under study. We conclude that the factors determining component stretching probably reside in the final pathway common for both saccade types. These experimental findings, revealing several common features in fast and slow saccades, were compared with quantitative predictions for the dynamics of oblique saccades, made from two existing two-dimensional models, predicting that the dynamic properties of components depend upon the direction of the saccade vector.

An analysis of curvature in fast and slow human saccades.

In order to study the cooperation of peripheral motor subsystems, the degree of curvature of human saccades along cardinal (right, up, left, down) and oblique directions was computed from an extensive set of experimental data. Our curvature measure allows comparison of fast and slow saccade trajectories elicited in different experimental conditions, independent of the speed of execution. Although we found clear and consistent subject-specific differences, the most common pattern in oblique visually-guided (i.e., fast) saccades reflected early dominance of the horizontal velocity signal as expressed in saccade trajectories curving away from the horizontal axis. Plots of curvature against direction yielded consistent idiosyncratic patterns with periodical increases and decreases in saccade curvature which were largely independent of saccade amplitude. At the cardinal axes, mean saccade curvature was generally less, but rarely entirely absent, and fitted smoothly into the curvature pattern of neighbouring quadrants. Memory-guided saccades, which have been shown earlier to be considerably slower than visually-guided saccades and to be more variable in their dynamic properties, showed a strikingly similar dependence of curvature on saccade direction, although some small but consistent differences were noticed. This finding suggests that saccade curvature is determined by mechanisms residing in the final common pathway for both saccade types. The curvature data were compared with quantitative predictions from three different models for the generation of oblique saccades. By quantifying the curvature of human saccades and thereby revealing the shortcomings of these models, the present paper documents new constraints with which future models of the saccadic system must comply and allows certain suggestions on how these might be developed.

Comparison of saccades evoked by visual stimulation and collicular electrical stimulation in the alert monkey.

In the alert monkey we have compared the properties of saccades elicited by a visual stimulus (V-saccades) with those generated by electrical stimulation in the superior colliculus (E-saccades). We found that whereas there exists a graded relation between E-saccade amplitude and current strength, E-saccade direction is remarkably independent of electrical stimulation parameters. At sufficiently high current strengths (about 20 microA), E-saccades are consistently directed toward the center of the movement field of nearby cells, except when stimulation is performed at sites near the collicular borders. Further interesting differences between the amplitude and direction behaviour were observed when the variability in E-saccade vectors, obtained with fixed stimulation parameters, was analyzed. In all cases, E-saccade amplitude scatter exceeds direction scatter, suggesting the possibility of a polar coordinate organization for the coding of saccade metrics. These data are compared with V-saccade scatter data, recently obtained in the human (Van Opstal and Van Gisbergen 1989c). Finally, an analysis of saccade dynamics shows that E-saccades can reach V-saccadic velocities at higher current strengths. However, at near-threshold current strengths, where E-saccade amplitude decreases, we found at most stimulation sites (22/37) that E-saccades are consistently slower than V-saccades of the same amplitude. Possible mechanisms underlying the collicular role in saccade generation are discussed.

A short-latency transition in saccade dynamics during square-wave tracking and its significance for the differentiation of visually-guided and predictive saccades.

Several recent studies indicate that saccades elicited in the absence of a visual target are slower than visually-guided movements of the same size. In addition, we have shown earlier that the slower saccades observed in two different paradigms had more asymmetrical (skewed) velocity profiles. Recently, it has been reported that predictive saccades are also slower. An interesting question, which arises if predictive and visually-guided saccades do have different velocity profiles, is whether the time when the transition occurs can be determined from their dynamic characteristics (peak velocity and skewness) and whether this transition latency can serve as a plausible criterion for distinguishing predictive and visually-guided saccades. To investigate this problem, visually-guided and predictive saccades were elicited by various experimental paradigms in six normal human subjects. Eye movements were measured using the double-magnetic induction method. We found that scatter plots of normalized peak velocity against latency showed an abrupt, small (10-20%) increase at a surprisingly short latency (about 30-70 ms). Furthermore, skewness of the saccadic velocity profile showed a significant drop at comparable latencies. There was a tight correlation between the peak velocity and skewness transition latencies of each subject. Considering the shape of the latency histograms in this and earlier studies, as well as other data, it appears unlikely that these very short transition latencies demarcate the distinction between predictive and fully visually-guided saccades. Instead, we suggest the possibility that the visual stimulus can speed up saccades at an earlier time than it can initiate and guide them. If this is the case, the very short transition latencies (mean: about 50 ms) probably represent the sum of afferent and efferent pure time delays in the system and do not include the time needed for the computation of saccade metrical properties.

A parametric analysis of human saccades in different experimental paradigms.

In this paper we report on human saccade dynamics in three different experimental paradigms: visual target, remembered target and anti-saccade task. We found that saccades to remembered targets and anti-saccades have strongly reduced peak velocities coupled with markedly increased durations. In addition we observed a considerable degree of asymmetry in the velocity profiles of these saccades. By using gamma functions to describe the shape of the velocity profiles a parameter characterizing the degree of asymmetry (skewness) was computed: it was found that skewness increases with saccade amplitude. Due to the large variability in saccade durations for any given amplitude in our data we could confirm the recent claim, based on pharmacologically induced slow saccades, that skewness is more tightly related to duration than to amplitude. The duration/skewness relationship appeared to be nearly invariant with saccade type. We conclude that the commonly used main-sequence description of saccades is incomplete and can be extended usefully by including skewness. The possible neural basis of the task-related differences in saccade properties and their implications for models of the saccadic system are discussed. It is suggested that the marked differences in dynamic properties among different saccade types may reflect processes in the visuomotor rather than in the motor system.

Resistance of Escherichia coli in faeces and the use of antimicrobial agents in the treatment of hospital patients.

Resistance of faecal Escherichia coli to ampicillin, tetracycline, sulphamethoxazole and gentamicin was studied in patients admitted to seven different departments in two hospitals. The resistance of ampicillin, tetracycline and sulphamethoxazole in the seven patient groups was 27-57%, 26-56% and 35-63%, respectively. Resistance to gentamicin was found in only one department. An E. coli flora predominantly resistant to ampicillin, tetracycline or sulphamethoxazole (greater than 50% of the E. coli strains in a faecal sample resistant) was found in 10-38%, 4-30% and 21-35% of the samples. A cross-sectional study focusing on the influence of the use of antimicrobial agents on the occurrence of resistant strains revealed a positive correlation between the annual turnover of broad-spectrum penicillins in various departments and the occurrence of predominantly ampicillin-resistant E. coli strains in these departments.

Faecal carriage of aerobic gram-negative bacilli and drug resistance of Escherichia coli in different age-groups in Dutch urban communities.

Faecal carriage rates for aerobic gram-negative bacilli and for antibiotic-resistant Escherichia coli were determined in samples of the Dutch urban population. Of the 741 people studied, 64 were under 1 year old (infants), 53 were 1-5 years old, and there were approximately 200 in each of the age-ranges 6-17 years, 18-49 years and 50-80 years. Carriage rates of E. coli were similar (87-93%) in all age groups, but Klebsiella and Enterobacter species were found more often in specimens from infants and young children than in those from older people. E. coli strains resistant to tetracycline, ampicillin, or sulphamethoxazole or to any one or more of them were detected in 42%, 26%, 46% and 66% respectively of the specimens found to contain E. coli. The corresponding figures for the finding of E. coli populations that were predominantly resistant to tetracycline, ampicillin or sulphamethoxazole were 12%, 6% and 20%. The frequency of resistance to any of these drugs was not related to age or sex of the subjects. All E. coli isolates were sensitive to gentamicin. Among the 577 subjects aged 6-80 years from whose samples E. coli was isolated were 19 who had taken antibacterial drugs in the previous 30 days and 11 who were involved in cattle farming; carriage rates for tetracycline-resistant and sulphonamide-resistant E. coli were significantly higher among these 30 than in the other 547.