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Comparison of three techniques on time to awakening, time to orientation and incidence of nausea and vomiting using alfentanil in balanced anesthesia in an outpatient surgical setting.

Maximizing patient safety and comfort while minimizing adverse sequelae are continuing anesthetic challenges. The purpose of this study was to examine three anesthetic techniques utilizing alfentanil with regard to time to awakening, time to orientation and incidence of nausea and vomiting. Surgical procedures were limited to knee arthroscopy, laparoscopy and dental extractions. Unpremedicated ASA I/II outpatients (n = 74) between the ages of 18 and 59 were randomly assigned to one of three groups: Group I: alfentanil + 67% N2O + 33% O2 Group II: alfentanil + 67% N2O + 33% O2 + droperidol 0.015 mg/kg Group III: alfentanil + 100% O2 + 0.7% isoflurane Anesthesia was induced with alfentanil 40 micrograms/kg, atracurium 0.4 mg/kg, thiamylal 4 mg/kg and 100% O2 and was maintained according to group assignment. The anesthetic was supplemented as clinically indicated with incremental boluses of alfentanil 10 micrograms/kg. Upon completion of surgery, muscle relaxation was reversed with edrophonium 0.75 mg/kg and atropine 0.015 mg/kg. Analyses indicated that the three groups were comparable in terms of potentially confounding variables including gender, race, surgical procedure, age, percent of ideal body weight, case length and dose of alfentanil in micrograms/kg/hr. Time to awakening was significantly shorter in the two N2O groups by approximately 1.5 minutes, as compared to the O2 and isoflurane group (p = .0060). Time to orientation was significantly shorter in the N2O groups by approximately 1.5 minutes also, as compared to the O2 and isoflurane group (p = .0142). The two N2O groups did not differ significantly in either measure. The incidence of vomiting in the postanesthesia recovery room (PARR) indicated a significant difference (p = .0317) among groups with vomiting occurring 45.8% of the time in Group I, 28.8% of the time in Group II and 8% of the time in Group III. Total emetic score (nausea and vomiting) in the PARR indicated a significant difference (p = .03) among groups with symptoms occurring 50% of the time in Group I, 28% of the time in Group II, and 16% of the time in Group III.

Alfentanil↗

Lower extremity fractures: relationship to reaction time and coordination time.

The purpose of this study was to examine the possible relationship between delayed reaction time and slow coordination time as a contributing factor to lower extremity fracture. A simple reaction time tester and hand coordination tester were used to assess the relative times of reaction and coordination. Subjects were also questioned concerning their daily activity levels. A definite relationship was observed to exist between the times recorded and lower extremity fractures: subjects with lower extremity fractures exhibited delayed reaction times and longer coordination times. Moreover, shorter reaction times and coordination times were seen in those subjects who reported higher activity levels. Statistical analysis was performed on selected data which show an association of fracture with reaction time.

Adolescent↗

Documentation of time expenditures of clinical dietitians: results of a statewide time study in Texas.

The purpose of this study was to establish a profile of the amount of time expended by clinical dietitians in providing nutrition services. One hundred twenty-seven dietitians in 49 hospitals in Texas collected time data according to nutrition care activity, diet order classification, care level, and diagnosis. Frequency, mean time, standard deviation, and percentage of time were computed for each of the variables. Data were analyzed to ascertain relationships among the variables. The dietitians expended 50.7% of their time performing client-related activities, 9.8% in administrative/managerial functions, 1.0% in professional activities, 5.1% in non-professional activities, 14.0% in delay activities, and 19.5% in transit time. The diet order classification that required the largest amount of the dietitians' time according to selected components of the nutrition care process was the calorie-controlled diabetic diet. Among the four nutrition care levels, dietitians expended the greatest percentages of time providing services for patients requiring intermediate (35.4%) and advanced intermediate care (30.4%). Dietitians expended more time providing client-related activities to patients diagnosed with diseases and disorders of the endocrine and excretory systems than to other patients. Mean times provide the clinical manager with documentation for determining staffing needs and costs of services.

Dietetics↗

Transit time, trailing time, and cerebral blood flow during brain activation: measurement using multislice, pulsed spin-labeling perfusion imaging.

Transit time and trailing time in pulsed spin-labeling perfusion imaging are likely to be modulated by local blood flow changes, such as those accompanying brain activation. The majority of transit/trailing time is due to the passage of the tagged blood bolus through the arteriole/capillary regions, because of lower blood flow velocity in these regions. Changes of transit/trailing time during activation could affect the quantification of CBF in functional neuroimaging studies, and are therefore important to characterize. In this work, the measurement of transit and trailing times and CBF during sensorimotor activation using multislice perfusion imaging with pulsed arterial spin-labeling is described. While CBF elevated dramatically ( thick similar80.7%) during the sensorimotor activation, sizable reductions of transit time ( thick similar0.11 sec) and trailing time ( thick similar0.26 sec) were observed. Transit and trailing times were dependent on the distances from the leading and trailing edges of the tagged blood bolus to the location of the imaging slices. The effects of transit/trailing time changes on CBF quantification during brain activation were analyzed by simulation studies. Significant errors can be caused in the estimation of CBF if such changes of transit/trailing time are not taken into account.

Brain↗

Pharmacokinetics of temazepam after day-time and night-time oral administration.

The pharmacokinetic disposition of temazepam was compared after a day-time and night-time dose in an open randomised crossover study. Twelve healthy male volunteers received a single oral dose of 20 mg temazepam in a soft gelatine capsule at 0900 h or 2200 h. Blood samples were taken immediately before dosing and at selected times over the 36-h period after each dose. The absorption of temazepam was slower after evening administration; the absorption half-life and time to reach maximal plasma concentration being 0.53 h and 1.67 h respectively, compared to 0.38 h and 1.02 h following morning administration. Considering distribution characteristics, evening administration produced a lower peak plasma temazepam concentration (362 ng/ml) compared with a day-time level of 510 ng/ml. Distribution half-life after night-time administration was increased compared with day-time administration (1.76 h vs 1.03 h). A significantly higher percentage of the drug, relative to Cmax, remained in the plasma at 8 and 24 h after evening dosing (39.3 and 15.4% compared to 24.7 and 11.2% following day-time administration). In spite of the half-lives of absorption, distribution and elimination all being longer after the evening dose, the overall bioavailability, as measured by the area under the curve (AUC) was comparable after the two times of administration. Similarly the difference in the mean residence time (MRT) of the two doses was within accepted limits. It is concluded that a chronopharmacokinetic effect was seen for temazepam; however it is unlikely to be of any clinical significance.

Administration, Oral↗

Asymptotic distributions of apparent open times and shut times in a single channel record allowing for the omission of brief events.

The openings and shuttings of individual ion channel molecules can be described by a Markov process with discrete states in continuous time. The predicted distributions of the durations of open times, shut times, bursts of openings, etc. are all described, in principle, by mixtures of exponential densities. In practice it is usually found that some of the open times, and the shut times, are too short to be detected reliably. If a fixed dead-time tau is assumed then it is possible to define, as an approximation to what is actually observed, an 'extended opening' or e-opening which starts with an opening of duration at least tau followed by any number of openings and shuttings, all the shut times being shorter than tau; the e-opening ends when a shut time longer than tau occurs. A similar definition is used for e-shut times. The probability densities, f(t), of these extended times have previously been obtained as expressions which become progressively more complicated, and numerically unstable to compute, as t-->infinity. In this paper we present, for the two-state model, an alternative representation as an infinite series of which a small number of terms gives a very accurate approximation of f (t) for large t. For the general model we present an asymptotic representation as a mixture of exponentials which is accurate for all except quite small values of t. Some simple model-independent corrections for missed events are discussed in relationship to the exact solutions.

Ion Channel Gating↗

Time-shift compensation of ultrasonic pulse focus degradation using least-mean-square error estimates of arrival time.

Focus degradation produced by abdominal wall has been compensated using a least-mean-square error estimate of arrival time. The compensation was performed on data from measurements of ultrasonic pulses from a curved transducer that emits a hemispheric wave and simulates a point source. The pulse waveforms were measured in a two-dimensional aperture after propagation through a water path and after propagation through 14 different specimens of human abdominal wall. Time histories of the virtual point source were reconstructed by removing the time delays produced by geometric path differences and also removing time shifts produced by propagation inhomogeneities in the case of compensation, finding the complex amplitudes of the Fourier harmonics across the aperture, calculating the Fraunhofer diffraction pattern of each harmonic, and summing the patterns. This process used a least-mean-square error solution for the relative delay expressed in terms of the arrival time differences between neighboring points and included an algorithm to determine arrival time differences when correlation based estimates were unsatisfactory due to dissimilarity of neighboring waveforms. Comparisons of reconstructed time histories in the image plane show that the -10-dB effective radius of the focus for reception through abdominal wall without compensation for inhomogeneities averaged 48% greater than the corresponding average effective radius for ideal waveforms, while time-shift compensation reduced the average -10-dB effective radius to a value that is only 4% greater than for reception of ideal waveforms. The comparisons also indicate that the average ratio of energy outside an ellipsoid defined by the -10-dB effective widths to the energy inside that ellipsoid is 1.81 for uncompensated tissue path data and that time-shift compensation reduced this average to 0.93, while the corresponding average for ideal waveforms was found to be 0.35. These results show that time-shift compensation yields a significant improvement over the uncompensated case although other factors must be considered to achieve an ideal diffraction limited focus.

Abdominal Muscles↗

Real-time nucleic acid sequence-based amplification is more convenient than real-time PCR for quantification of Plasmodium falciparum.

Determination of the number of malaria parasites by routine or even expert microscopy is not always sufficiently sensitive for detailed quantitative studies on the population dynamics of Plasmodium falciparum, such as intervention or vaccine trials. To circumvent this problem, two more sensitive assays, real-time quantitative nucleic acid sequence-based amplification (QT-NASBA) and real-time quantitative PCR (QT-PCR) were compared for quantification of P. falciparum parasites. QT-NASBA was adapted to molecular beacon real-time detection technology, which enables a reduction of the time of analysis and of contamination risk while retaining the specificity and sensitivity of the original assay. Both QT-NASBA and QT-PCR have a sensitivity of 20 parasites/ml of blood, but QT-PCR requires a complicated DNA extraction procedure and the use of 500 microl of venous blood to achieve this sensitivity, compared to 50 microl of finger prick blood for real-time QT-NASBA. Both techniques show a significant correlation to microscopic parasite counts, and the quantification results of the two real-time assays are significantly correlated for in vitro as well as in vivo samples. However, in comparison to real-time QT-PCR, the results of real-time QT-NASBA can be obtained 12 h earlier, with relatively easy RNA extraction and use of finger prick blood samples. The prospective development of multiplex QT-NASBA for detection of various P. falciparum developmental stages increases the value of QT-NASBA for malaria studies. Therefore, for studies requiring sensitive and accurate detection of P. falciparum parasites in large numbers of samples, the use of real-time QT-NASBA is preferred over that of real-time QT-PCR.

Animals↗

Tumor marker doubling time in patients with prostate cancer: determination of prostate-specific antigen and prostatic acid phosphatase doubling time.

To estimate the growth rate of prostate cancer, the doubling times of prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) were determined in 51 patients: 44 were refractory to endocrine therapy, and 7 were in an untreated state. Since an exponential increase in PSA and PAP was observed in all patients, the doubling time was calculated from a semilogarithmic plot of the respective markers. PSA doubling time was almost identical with that of PAP. The tumor marker doubling time in untreated patients was approximately 10 times greater than that in the patients who were refractory to endocrine therapy. In endocrine refractory patients, the tumor marker doubling time in patients who showed deterioration of bone lesions was less than that in patients with local regrowth and/or lymph node metastasis. The prognosis of endocrine refractory patients from the time showing tumor marker failure was examined. The group showing the longest time (> 80 days) had better prognosis than that shown by the other groups with shorter doubling times. It is concluded that the determination of tumor marker doubling time is of value for measuring the growth rates of prostate cancer, and for assessing prognosis after relapse.

Acid Phosphatase↗

Interval timing with gaps and distracters: evaluation of the ambiguity, switch, and time-sharing hypotheses.

Gaps and distracters were presented during the timed signal to examine whether the stop/reset mechanism is activated by (a) changes in the timed signal (switch hypothesis), (b) ITI-like events (ambiguity hypothesis), or (c) processes concurrent with the timing process (time-sharing hypothesis). While the switch and ambiguity hypotheses predict that rats should time through (ignore) distracters, the time-sharing hypothesis predicts that extraneous events (e.g., gaps and distracters) delay timing by causing working memory to decay in proportion to the events' salience. The authors found that response functions were displaced by both gaps and distracters, in accord with the time-sharing hypothesis. Computer simulations show that the time-sharing and memory-decay hypotheses can mechanistically address present data, and reflect different levels of the same model.

Analysis of Variance↗

Transient changes in the pattern of food intake following a simulated time-zone transition to the east across eight time zones.

Twelve healthy adults were studied, singly or in groups of up to four, in an Isolation Unit before (control days) and for 3 days after a simulated time-zone transition to the east across 8 time zones (the clock being changed from 15:00 to 23:00h). Subjects were free to choose how to pass their waking hours (though naps were forbidden), and to eat what and when they wanted. A wide selection of food was provided, though the subjects had to prepare it. Subjects completed food intake questionnaire on waking and at 3h intervals during the waking day. This questionnaire assessed the reasons for choosing not to eat a meal or, if a meal was eaten, the reasons for doing so, the type of meal chosen and the reasons for this choice, and subjective responses to the meal (hunger before, enjoyment during, and satiety afterwards). Subjects also recorded the incidence and degree of indigestion and jet lag at 3 h intervals after the time-zone transition. Following the time-zone transition, the subjects experienced significant amounts of jet lag and recorded a significant increase in the incidence of indigestion. They also showed significant changes in their pattern of food intake, but, whereas the patterns of food intake were no longer significantly different from control days by the third post-shift day, the symptoms of jet lag and indigestion were still present then. The distribution of daytime meals was significantly affected on the first post-shift day, with a redistribution of the times that the main, hot meals were eaten; these times indicated some influence of an unadjusted body clock. On this day also, the reasons for determining food intake continued to be dominated by hunger and appetite (hunger even increasing in the frequency with which it was cited), and the reason for not eating a meal, by a lack of hunger. On both control and post-shift days, there was a marked effect of meal type upon the responses to food intake, with cold food being rated least and large hot meals most when appetite before the meal, enjoyment during it, and satiety afterward were considered. However, evidence suggested that the degree to which larger hot meals were preferred to cold meals was significantly less marked after the time-zone transition. On control days, sleep was unbroken; whereas, after the time-zone transition, all subjects woke on at least one of the 3 nights studied. During the first post-shift night, about half of the subjects ate a meal, the reason given being that they were "hungry." On those occasions when subjects woke but did not eat a meal, the reason cited was because they "could not be bothered" as frequently as because they were "not hungry.". A simulated time-zone transition is associated with significant changes to the incidence of indigestion, pattern of food intake, and subjective responses to food. However, these changes are generally transient and are only weakly linked to the sensation of jet lag.

Adult↗

Response times seen as decompression times in Boolean concept use.

This paper reports a study of a multi-agent model of working memory (WM) in the context of Boolean concept learning. The model aims to assess the compressibility of information processed in WM. Concept complexity is described as a function of communication resources (i.e., the number of agents and the structure of communication between agents) required in WM to learn a target concept. This model has been successfully applied in measuring learning times for three-dimensional (3D) concepts (Mathy and Bradmetz in Curr Psychol Cognit 22(1):41-82, 2004). In this previous study, learning time was found to be a function of compression time. To assess the effect of decompression time, this paper presents an extended intra-conceptual study of response times for two- and 3D concepts. Response times are measured in recognition phases. The model explains why the time required to compress a sample of examples into a rule is directly linked to the time to decompress this rule when categorizing examples. Three experiments were conducted with 65, 49, and 84 undergraduate students who were given Boolean concept learning tasks in two and three dimensions (also called rule-based classification tasks). The results corroborate the metric of decompression given by the multi-agent model, especially when the model is parameterized following static serial processing of information. Also, this static serial model better fits the patterns of response times than an exemplar-based model.

Adolescent↗

Prostatic-specific antigen doubling times in patients with prostate cancer: a potentially useful reflection of tumor doubling time.

PURPOSE: This study was undertaken to investigate the relationship of prostatic specific antigen doubling time with disease progression in irradiated patients whose only sign of failure was an abnormal prostatic specific antigen. METHODS AND MATERIALS: Post irradiation patients whose only sign of failure was an elevated prostatic specific antigen were followed without treatment. The prostatic specific antigen doubling time was determined and compared to original characteristics of disease, time to elevation of prostatic specific antigen after treatment and time to a second sign of failure. RESULTS: The prostatic specific antigen doubling times varied from 1.2 months to 36 months. The original grade and stage correlated with the doubling time as did the intervals to elevation of prostatic specific antigen and to a second sign of failure. CONCLUSION: We recommended delaying intervention until the prostatic antigen doubling time can be calculated for patients with prostatic specific antigen elevation as the only sign of failure. Patients with short doubling times (< 9 months) can be promptly treated while those with longer doubling times (> 1 year) may have androgen suppression delayed avoiding the cost and morbidity of that treatment.

Humans↗

The decreased influence of overall treatment time on the response of human breast tumor xenografts following prolongation of the potential doubling time (Tpot).

PURPOSE: Repopulation during fractionated radiotherapy has been postulated to result in a significant loss in local control in rapidly proliferating tumors. Clinical data suggest that accelerated fractionation schedules can overcome the influence of repopulation by limiting the overall treatment time. Unfortunately, accelerated therapy frequently leads to increased acute reactions, which may become dose limiting. An alternative to accelerated fractionation would be to decrease the rate of repopulation during therapy. To test the potential efficacy of this alternative, we examined the effect of reducing tumor proliferation rate on the response of MCF-7 human breast carcinoma xenografts treated with a short vs. a long course of fractionated therapy. To reduce the proliferation rate, we deprived nude mice transplanted with MCF-7 xenografts of the growth-stimulating hormone estradiol (E2). We have previously reported that E2 deprivation increases the potential doubling time (Tpot) for MCF-7 xenografts from a mean of 2.6 days to 5.3 days (p < 0.001). METHODS AND MATERIALS: E2-stimulated and E2-deprived MCF-7 breast carcinoma xenografts were clamped hypoxically and irradiated with four fractions of 5 Gy each, using either a short (3-day) or long (9-day) treatment course. E2 stimulation was restored in all animals at the completion of irradiation. Radiation response was determined by regrowth time and regrowth delay of the irradiated tumors as compared to unirradiated controls. RESULTS: Prolongation of therapy in rapidly proliferating, E2-stimulated tumors (Tpot approximately 2.6 days) resulted in a significant decrease in regrowth time in two identical experiments. With results pooled for analysis, the regrowth times for the short and long treatments were 62 and 32 days, respectively (combined p < 0.001). The shorter regrowth times suggest that there was less overall tumor damage with the longer fractionated radiotherapy course. No significant difference in regrowth time was observed in the more slowly proliferating, E2-deprived tumors (Tpot approximately 5.3 days) treated with either the short or long regimen. Median regrowth times were 48 and 54.5 days for the short and long treatments, respectively (combined p = 0.14). Similar changes were observed in regrowth delay. CONCLUSIONS: Reduction in the rate of cell proliferation, induced by E2 deprivation in MCF-7 human breast xenografts during fractionated radiotherapy, resulted in a significantly decreased dependence on overall treatment time in comparison to the more rapidly proliferating E2-stimulated tumors. This model suggests that pharmacologically induced reduction in the rate of tumor cell proliferation during a course of fractionated radiotherapy may be a viable alternative to accelerated fractionation for the treatment of rapidly proliferating tumors.

Animals↗

Probing the role of tightly bound phosphoenolpyruvate in Escherichia coli 3-deoxy-d-manno-octulosonate 8-phosphate synthase catalysis using quantitative time-resolved electrospray ionization mass spectrometry in the millisecond time range.

Escherichia coli 3-deoxy-D-manno-octulosonate 8-phosphate (KDO8P) synthase catalyzes the condensation of phosphoenolpyruvate (PEP) and D-arabinose 5-phosphate (A5P) to produce KDO8P and inorganic phosphate. The enzyme is often isolated with varying amounts of tightly bound PEP substrate. To better understand the role of tightly bound PEP in E. coli KDO8P synthase catalysis, a combination of transient kinetic methodologies including rapid chemical quench and mass spectrometry techniques such as time-resolved electrospray ionization mass spectrometry (ESI-TOF MS) were used to study the enzyme purified both in the PEP-bound state and in the unbound state. Pre-steady state burst and single-turnover experiments using radiolabeled [1-(14)C] and [(32)P]A5P revealed significant kinetic differences between these enzyme preparations. The active sites concentrations for the bound and unbound states of the enzyme were almost the same (approximately 100%) and the product release for both states of the enzyme was rate limiting. However, the rate constant of product formation for the PEP-bound enzyme (125 s(-1)) was higher than that of the unbound enzyme (46 s(-1)). This was further confirmed by single-turnover experiments using radiolabeled [(32)P]A5P. Interestingly, when PEP was removed from the PEP-bound enzyme and external PEP was added before the kinetic experiments, both the pre-steady state burst and the single-turnover kinetic parameters were similar to those of the enzyme purified in the unbound state. The rate constants of product formation were determined as 44 s(-1) (burst experiment) and 48 s(-1) (single-turnover experiment). The reaction kinetics of the E. coli KDO8P synthase was also followed by time-resolved ESI mass spectrometry. To validate the suitability of this technique for conducting enzyme kinetics, the standard reaction of p-nitrophenyl acetate hydrolysis by chymotrypsin was analyzed by stopped-flow and time-resolved ESI-TOF MS. The rate constant of p-nitrophenol formation followed by stopped-flow spectrophotometry matched perfectly the rate constant of acetyl-chymotrypsin intermediate formation followed by time-resolved ESI-TOF MS (0.1 s(-1)). The catalytic properties of the PEP-bound and unbound states of the E. coli KDO8P synthase were then studied on a millisecond time scale. The changes in the intensity of E*PEP, E*KDO8P, and E*intermediate complexes as a function of time were quantified and the reaction kinetics were modeled using KinTekSim simulation software. An analysis of the reaction kinetics established the kinetic competence of the intermediate based upon the rate constants for substrate decay and product formation. The ability of time-resolved ESI-TOF MS to detect and monitor the kinetics for the reaction intermediate constitutes a significant advantage over the traditional rapid chemical quench technique. For all three states of the enzyme (PEP-bound, unbound, and PEP removed from the PEP-bound state) the rate constants obtained by time-resolved ESI-TOF MS matched the pre-steady state rates determined by rapid chemical quench. A comparison of reaction time courses for each state of the enzyme revealed that, in the case of PEP-bound enzyme, the enzymatic reaction reached completion faster than that for the unbound state. In summary, these studies led to the conclusion that bound PEP has an important role in catalysis, maintaining the enzyme in a conformational state optimal for catalytic activity, and established the kinetic competence of the reaction intermediate. This technique has broad applicability for the kinetic analysis of any enzyme system where the substrates, products, or intermediates are eluding the common detection techniques or as a method alternative to the widely used radioactivity assays.

Aldehyde-Lyases↗

Antithrombotic effect of YM-75466 is separated from its effect on bleeding time and coagulation time.

The antithrombotic effects of YM-75466 ([N-[4-[(1-acetimidoyl-4-piperidyl)oxy]phenyl]-N-[(7-amidino-2-nap hthyl)methyl]sulfamoyl]acetic acid monomethane sulfonate), a novel orally-active factor Xa inhibitor, and its effects on bleeding time and coagulation time were studied in rats and compared with those of warfarin. Both agents were orally administered. In the venous thrombosis model, YM-75466 and warfarin inhibited thrombus formation dose-dependently, with ID50 values of 3.3 and 0.56 mg/kg, respectively. Ex vivo study showed that both YM-75466 and warfarin prolonged prothrombin time dose-dependently, with doses, causing a two-fold prolongation of prothrombin time in the control group, of 89 and 0.38 mg/kg, respectively. In bleeding time studies, YM-75466 and warfarin prolonged bleeding time dose-dependently, with doses, causing a two-fold prolongation of bleeding time in the control group, of > 100 and 0.43 mg/kg, respectively. These results show that the antithrombotic effects of YM-75466 are markedly separate from its effects on bleeding time and coagulation time compared with warfarin.

Animals↗

On the time dependent diffusion of macromolecules through transient open junctions and their subendothelial spread. 2. Long time model for interaction between leakage sites.

In Part 1 of this study (Weinbaum et al., 1988) a short time model has been proposed to describe the initial time dependent leakage of macromolecules at short distances (5 microns or less) from the exit of a transient open junction which the authors have hypothesized as a characteristic feature of endothelial cells in the process of turnover (Weinbaum et al., 1985). This open junction pathway has also been proposed (Weinbaum et al., 1988) to be the primary ultrastructural correlate of the 20 nm diameter large pore suggested by Renkin et al. (1977) using the predictions of cylindrical pore theory. The short time model in (Weinbaum et al., 1988), however, has major limitations in that it neglects the interaction between leakage sites, macromolecular entry through other pathways, the finite thickness of the vessel wall and the curvature of the cell perimeter. The longer time model developed herein will attempt to describe each of these features and also present an improved model and analytic solution for the steady state flux and uptake. In the previous steady state model developed by Weinbaum et al. (1985) the effect of the resistance of the transient open junctions and the non-isotropic diffusion in the underlying tissue due to the internal elastic lamina (IEL) were both neglected. New solutions are first presented which describe the effect of these important model refinements on the steady state macromolecular permeability of the major arteries. Time dependent solutions are then presented to predict the transient longer time labeling following the introduction of tracer macromolecules of varying size. These solutions and the corresponding short time solutions in Weinbaum et al. (1988) are the first solutions to our knowledge to describe the difficult time-dependent boundary value problem to determine how the channel exit concentration and flux at a leaky junction vary with time. This is accomplished by casting the boundary value problem in the form of an integral equation for the unknown flux at the cleft exit and then solving this problem using a specially designed numerical technique. The theoretical predictions are used to interpret the behavior of the localized leaks to HRP and albumin that have been reported in Stemerman et al. (1986) and our own recent experiments (Lin et al., 1988).

Animals↗

Dynamics of time and information in dynamic time.

Time is intrinsically locally asynchronous, dynamic in itself, and self-organizing in having locally asynchronous time precipitate further asynchronous time while leaving behind globally synchronous time. The resulting global synchronism is skewed in locally asynchronous time, while being vertical to the effected globally synchronous time. Information is a dynamic attribute of time and can be represented as a skewed synchronism in locally asynchronous time. Information originates in the communication among asynchronous times of a local character.

Information Science↗