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PubMed1973

Perfluorocarbons having a short dwell time in the liver.

Perfluorinated organic liquids are useful as high capacity oxygen and carbon dioxide solvents. After intravenous infusion most of these perfluorinated emulsions are deposited in the liver and spleen in a matter of days, where they remain for the lifetime of the animal. Hence, while they may be useful as isolated organ perfusion media their value as artificial blood is limited. A family of perfluorocarbons has now been discovered, which, although deposited in the liver after circulation in the blood, leave the liver to be excreted via the lungs and skin in a matter of days without apparent harmn to the animal.

Animals↗
PubMed2003

Modulation of T cell immunity by TCR/pMHC dwell time and activating/inhibitory receptor pairs on the antigen-presenting cell.

The molecular interactions occurring at the interface between the antigen presenting cell (APC) and the T lymphocyte play an important role in the immune surveillance against infectious agents and tumors, as well as in autoimmunity and transplant rejection. The significance of the APC-T cell interaction in immunity is underscored by the observation that deficiencies in the function of either one of these two cell types cause extreme susceptibility to infections and tumor growth. Furthermore, a disregulated APC-T cell interaction can initiate autoimmunity. Thus, antigen recognition by T cells must be tightly regulated in order to ensure protection against pathogens and tumors, avoiding activation of self-reactive T cells. Efficient T cell activation requires two simultaneous signals provided by the APC: Antigen (or signal 1) and co-stimulation (or signal 2). The specificity of antigen recognition by T cells (signal 1) is controlled exclusively by the T cell receptor (TCR), an extremely diverse heterodimeric protein composed of disulfide-bonded alpha and beta chains. While it is clear that the TCR recognizes antigens as small peptides bound to molecules of the Major Histocompatibility Complex (MHC), the molecular explanation for the specificity of antigen recognition by the betaalphaTCR is just beginning to be elucidated. In this review are described some of the advances made in the understanding of the molecular interactions that define the antigen-specificity of the TCR, and the current models for T cell activation by antigen on APCs are discussed.

Animals↗
PubMed1992

Significantly improved peripheral intravenous catheter performance in neonates: insertion ease, dwell time, complication rate, and costs.

A prospective, randomized, controlled study was performed in neonates in an intensive care nursery to compare the performance of a peripheral intravenous catheter made of Aquavene material (test catheter) with that of a conventional peripheral catheter made of Teflon material (control catheter). Aquavene is a newly developed biomaterial that softens and expands on contact with body fluids. A total of 105 catheters (50 test and 55 control) were inserted in 63 neonates. The median time to a catheter-related complication was 3.60 days for the test catheters and 1.75 days for the control catheters (p = 0.0007). Infiltration rate for the test catheters was 56% as compared with 78% for the control catheters (p = 0.03). The test catheters provided fewer catheter-related complications (p = 0.006), with 34% of the test catheters reaching end of therapy as compared with 9% of the control catheters (p = 0.004). On average, 1.8 test catheters were used per insertion versus 2.3 control catheters (p = 0.08). The test catheters were rated easier to insert (p = 0.05), with a shorter time required for insertion. Because of improved performance, cost savings were realized with the test catheters after the first day of therapy, even though the per unit cost of the test catheter was greater. These data indicate that the test catheter, made of Aquavene material, is superior to the Teflon catheter for peripheral intravenous therapy in neonates.

Biocompatible Materials↗
PubMed1989

Gating scheme for single GABA-activated Cl- channels determined from stability plots, dwell-time distributions, and adjacent-interval durations.

To study the gating of a GABA-activated Cl- channel, currents from single channels activated by 1.0 microM GABA were examined in patches of membrane excised from cultured chick cerebral neurons. The distributions of open and shut interval durations were each described by the sum of 3 exponential components, suggesting that the channel normally enters at least 3 open and 3 shut states. Five different 6-state gating schemes were found that could describe, all equally well, the observed distributions of open and shut interval durations. Plots of the mean duration of open intervals adjacent to shut intervals of specified durations revealed that, on the average, openings of brief duration were adjacent to closings of long duration. This observation indicated 2 or more independent transition pathways between the open and shut states. Examination of the distributions of open intervals adjacent to shut intervals of specified durations revealed that the time constants of the exponential components describing these conditional open-interval distributions were independent of the durations of the adjacent shut intervals. In contrast, the areas changed in a manner consistent with open states of briefer mean lifetimes typically making transitions to shut states of longer mean lifetimes. Four of the 5 gating schemes considered were rejected because they did not predict the relationship between adjacent intervals or because they predicted that the channel should switch between 2 gating modes with markedly different mean open and shut times, which was not a characteristic of the experimental data. The single remaining kinetic scheme could account for the observed kinetic properties of the GABA channel.

Animals↗
PubMedDate not supplied

Risks associated with 72- and 96-hour peripheral intravenous catheter dwell times.

BACKGROUND: The risk of complications in peripheral intravenous therapy is higher on the second day of therapy and may continue to increase with time, making routine restarts after 3 days a common practice. The objective of the study was to determine whether the risks of complications after a peripheral i.v. catheter restart after 72 hours are less than the risks of complications if the therapy is continued to 96 hours. METHODS: A retrospective chart review was completed for 722 patients in a community hospital with peripheral i.v. catheters for i.v. fluids or saline locks. Measurements collected were i.v. therapy start date, number of restarts, termination date, and reason for termination; the data were analyzed using risk models. RESULTS: There were 596 uncomplicated therapies. Complications prompted termination in 188 cases. The average duration of therapy was 1.8 days. The probability of complications was least in the first 24 hours, (0.074; standard deviation [SD], 0.013), and increased to 0.176 (SD, +/- 0.026) in the 24- to 48-hour period. The probability of a complication in the 48- to 72-hour period and the 72- to 96-hour period was 0.130 (SD, 0.026). A restarted catheter has a significantly higher risk of complication in its first 24 hours than does an initial catheter. CONCLUSIONS: From these results, the authors conclude that restarting catheters at 72 hours does not reduce the risk of complication in the next 24 hours when compared with simply continuing the therapy with the original catheter. Additional studies should be conducted to justify a policy of automatically restarting therapy after 72 hours.

Catheterization, Peripheral↗
PubMed1994

Optimization of interstitial volume implants.

For interstitial applications of high dose rate (HDR) afterloading brachytherapy, generally a single stepping iridium-192 source is used, enabling optimization of the dose distribution by optimization of the relative time (dwell time) that the source remains at a certain position (dwell position). We analysed the effects of geometric optimization in a regular volume implant, with strictly parallel catheters, and in an irregular volume implant, such as an implant for tumours of the base of the tongue characterized by a non-parallel geometry and varying catheter separations. In both examples the reference dose is specified at 85% of the mean central dose (as is done in the Paris system for dose specification) in the non-optimized as well as the optimized plan. The irradiated volume, the dose uniformity, and the choice of the reference dose of optimized and non-optimized dose distributions were compared. This was done by isodose plots for representative planes, volume dose histograms (distributed, contiguous, and natural), and dose non-uniformity ratios (DNRs). For the regular implant, optimization results in a 28% increase in the treated volume with a similar increase in the overdosed volumes. In order to keep the treated volume comparable with the non-optimized dose distribution, 90-95% of the mean central dose should be chosen as a reference dose or the range of active dwell positions should be shortened in case of optimization. In the case of the irregular volume implant at the base of the tongue, the method for dose specification should be kept unchanged after geometric optimization as the volume enclosed by the reference isodose does not increase. It is clear from the volume-dose histograms that there is a reduction of the overdosed volume due to optimization. This is accompanied by an increase in the uniformity index and a decrease of the DNR. In conclusion, geometric optimization appears to be an effective tool to improve the dose distribution of interstitial volume implants. Contiguous and natural volume dose histograms appear, apart from planar dose plots, valuable methods for evaluating the dose distribution of an implant.

Brachytherapy↗
PubMed2001

Optimization in high dose rate brachytherapy for utero-vaginal applications.

BACKGROUND AND PURPOSE: High dose rate (HDR) remote afterloading intracavitary brachytherapy is an effective treatment modality which has some advantages over low dose rate (LDR) techniques for gynaecological cancer. Optimization is one of the possibilities of modern brachytherapy techniques, especially the stepping source technology. The use of the term 'optimization' implies achieving the desired optimum dose distribution by changing some parameters of the treatment. The aim of this study was to theoretically evaluate the optimization possibilities by modifying dwell times and dwell positions of the uterine and vaginal sources. MATERIALS AND METHODS: Working on a virtual utero-vaginal model, the dose distribution variations in the rectum, bladder, mean point B reference points and volume parameters were investigated whilst giving a standard dose to point A in the Manchester system. In this model, the intrauterine tandem consisted of 27 dwell positions for 2.5 mm steps and 14 dwell positions for 5 mm steps. Vaginal colpostats consisted of five dwell positions each for 2.5 mm steps. Using a Nucletron Plato treatment planning system and a Microselectron Ir-192 HDR stepping source unit, the dwell times of the intrauterine (T(u)) and vaginal sources (T(v)) were modified at the ratios of (T(u)/T(v)) 1:1; 1:2; 1:3; 1:4; 1:0.50; 1:0.33; and 1:0.25 for the two different dwell positions, 2.5 and 5 mm steps, of the intrauterine tandem. RESULTS: All evaluated parameters decreased with increasing dwell time ratios of uterine tandem to vaginal colpostats, with the greatest fall in the percentage of rectum reference dose (D(R) %), 23 and 28% for 2.5 and 5 mm dwell positions respectively; in addition, the reference isodose volume decreased by 14 and 17% for 2.5 and 5 mm dwell positions, respectively. All evaluated parameters increased with decreasing dwell time ratios of uterine tandem to vaginal colpostats for both dwell positions. The DR% of 1:1-1:4 (T(u)/T(v)) weightings showed an increase from 40.6 to 58.3 (44%) for 2.5 mm and from 49.2 to 67.5 (37%) for 5 mm dwell positions. The volume was increased by 27 and 37% for 2.5 and 5 mm dwell positions respectively. CONCLUSION: Modern brachytherapy techniques enable the individualization of treatments by optimization procedures in gynaecological brachytherapy applications. By altering the dwell time and position, some important changes in reference points, volume and treatment time can be achieved, whilst maintaining a standard dose to point A.

Brachytherapy↗
PubMed1999

The effects of roll vs. pitch rotation in humans under orthostatic stress.

BACKGROUND: It has been known since 1953 that pre-exposure to less than +1 Gz will reduce subsequent +Gz-tolerance. With few exceptions, during operational flying, the transition from hypogravity to hypergravity involves roll as well as pitch rotation. We examined the effect of roll vs. pitch rotation while undergoing transition from hypogravity to +1 Gz on a tilt table. METHODS: Twelve subjects (28-47 yr old) were rotated at 45 degrees x s(-1) from head-up (HU) at 15 degrees relative to gravitational vertical to 135 degrees head-down (HD) and back to the HU position after different HD dwell times. HD dwell times were set at 7, 15, and 30 s. The subject was rotated about the interaural axis (pitch) and about the naso-occipital axis (roll). Both the HD dwell times and axes of rotation were randomized within and across subjects. BP and heart rate were recorded during the HU-HD-HU maneuver. RESULTS: Analysis of variance, repeated measure design revealed that the rate and magnitude of BP decrease induced by the HD to HU maneuver is significantly higher (p < 0.01) in roll than in pitch during all HD dwell times. The decrease of BP at 7s is significantly (p < 0.01) higher than at 15s and 30s. Heart rate increases significantly higher (p < 0.01) in pitch than in roll at 7s-dwell time. CONCLUSION: Our results suggest that the compensatory mechanism to orthostatic stress is more efficient in response to pitch than roll rotation. This is reflected from the findings that the mean magnitude of OH (orthostatic hypotension) and the rate of BP decrease induced by the HD-HU maneuver is significantly greater in roll rotation than pitch rotation. The mean HR increase post HD-HU rotation is significantly higher in the pitch than the roll rotation. The significant rate of BP decrease during HD-HU roll rotation could have important implications for maintaining G-tolerance and spatial orientation during subsequent exposure to hypergravity.

Adaptation, Physiological↗
PubMed2001

Scanned continuous wave CO2 laser resurfacing: a closer look at the different scanning modes.

BACKGROUND: The immediate effects of CO2 laser resurfacing include tissue ablation and residual thermal damage. These laser-tissue interactions are shaped by parameters including fluence, dwell time, and number of passes. OBJECTIVE: To assess the vaporization depth and residual thermal damage following use of the "superficial" or "deep" scanning modes of a 40 W continuous wave CO2 laser using both frozen and paraffin sections. METHODS: Fourteen subjects were divided into two groups for test treatments in the right preauricular area with two passes of the laser. The "superficial" mode parameters were 10 mm2 scan, 200 mm lens, power 36 W, scan time 0.24 seconds, dwell time 0.22 msec, and fluence 5.5 J/cm2. The "deep" mode settings were 9 mm2 scan, 200 mm lens, power 18 W, scan time 0.64 seconds, dwell time 0.28 msec, and fluence 7.0 J/cm2. The deep mode has a greater pattern density than the superficial mode and also has a double pattern of exposure. Biopsies encompassing equal areas of treated and untreated skin were taken immediately postoperatively and processed with both frozen and paraffin-embedded techniques. RESULTS: Vaporization depth was similar in both scanning modes and by both tissue-processing techniques. On frozen sections, residual thermal damage was 20% greater in the deep mode than the superficial mode, but this was not a statistically significant difference. There was no significant difference between the two modes in the depth of thermal injury on paraffin sections. CONCLUSION: In keeping with theoretical expectations, vaporization depth was similar in both treatment groups. No significant difference in residual thermal damage could be demonstrated between the two modes. However, the results on frozen sections suggest that residual thermal damage may be greater in the deep mode than in the superficial mode. In addition, frozen sections may be more sensitive than paraffin sections in the detection of residual thermal damage following laser resurfacing.

Acne Vulgaris↗
PubMed1995

Selectivity and gating properties of a cAMP-modulated, K(+)-selective channel from Drosophila larval muscle.

The selectivity and gating properties of cAMP-modulated, voltage-independent, K(+)-selective channel from Drosophila larval muscle were investigated using the patch-clamp technique. In symmetrical 115 mM K+ the channel displayed a linear current-voltage relation with slope conductance of 43 pS. Under biionic conditions (115 mM K+ pipette/115 mM X+ cytoplasmic) the permeability sequence was K+ > Rb+ > NH4+ >> Cs+,Na+. The channel was impermeable to Ca2+ (PCa/PK < 0.02). Under steady-state conditions and regardless [cAMP], open dwell times showed a double exponential distribution. [cAMP] did not affect the time constants of the two components of open times, or their relative amplitudes. Moreover, successive openings were correlated in open time. Closed dwell times were made of at least three exponential components. Fast application of cAMP to the cytoplasmic side of the channel induced a transient increase in open probability that relaxed to a lower value within seconds. This last result suggests that cAMP can activate and desensitize this cAMP-modulated, K(+)-selective channel.

Animals↗
PubMed2006

Limping of homodimeric kinesin motors.

Conventional kinesin, a homodimeric motor protein that transports cargo in various cells, walks limpingly along microtubule. Here, based on our previously proposed partially coordinated hand-over-hand model, we present a new mechanism for the limping behaviors of both wild-type and mutant kinesin homodimers. The limping is caused by different vertical forces acting on the heads in two successive steps during the processive movement of the dimer. From the model, various theoretical results, such as the dependences of the mean dwell time and dwell time ratio on the coiled-coil length and on the external load as well as the effect of vertical force on velocity, are in good agreement with previous experimental results. We predict that a high degree of limping will correlate strongly with a high sensitivity of ATP turnover rate to upwards force.

Animals↗