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PubMed1995

Endogenous opioid peptides control the amplitude and shape of gonadotropin-releasing hormone pulses in the ewe.

This study was designed to test the hypothesis that endogenous opioid peptides (EOP) mediate the negative feedback action of estradiol on GnRH pulse size in breeding season ewes. If this hypothesis is correct, one would predict that an EOP antagonist should increase GnRH pulse size in estradiol-treated ovariectomized (OVX+E), but not in OVX, ewes. We, therefore, examined the effects of naloxone on GnRH pulse profiles in the hypophyseal portal blood of OVX and OVX+E ewes (n = 6/group). Samples were collected every 10 min for 6 h before, 6 h during, and 4 h after naloxone infusion. Estradiol treatment decreased GnRH pulse size and increased GnRH pulse frequency. Naloxone treatment had no effect on GnRH pulse frequency, but significantly increased GnRH pulse size. However, this stimulatory action of naloxone on GnRH pulse size was evident in both OVX and OVX+E ewes. These results are thus not consistent with the hypothesis that EOP mediate the negative feedback action of estradiol. Interestingly, naloxone not only increased GnRH pulse amplitude, but also prolonged the duration of GnRH release during a pulse. To obtain a more precise characterization of the effects of naloxone on the dynamics of GnRH release, pulse profiles in six OVX ewes were examined in hypophyseal portal blood sampled every minute for 4 h before and 4 h during naloxone infusion. Naloxone again increased both the amplitude and duration of GnRH pulses. The increase in GnRH pulse duration was caused by a prolongation of both the plateau and declining phases of the GnRH pulse. In addition to these effects on GnRH release during a pulse, naloxone increased the amount of GnRH collected between pulses in both experiments. The stimulatory effects of naloxone on GnRH release in OVX ewes indicate that the role of EOP in the control of GnRH is not limited to mediating the feedback actions of steroids. In particular, the dramatic effects of naloxone on GnRH pulse shape and interpulse GnRH levels raise the possibility that EOP play an important role in synchronizing the activity of the GnRH neurons involved in episodic GnRH secretion.

Animals↗
PubMed2005

Comparisons between oral pulse alfacalcidol therapy and daily therapy in maintenance hemodialysis patients with secondary hyperparathyroidism: a randomized, controlled, and multicenter study.

OBJECTIVE: To investigate the efficacy and safety of 1alpha-(OH)-D3 high-dose pulse therapy or daily low-dose therapy in secondary hyperthyroidism in maintenance hemodialysis patients in China. METHODS: Maintenance hemodialysis patients of both gender with intact parathyroid hormone (iPTH) level above 200 pg/mL were randomly divided into a pulse group and a daily group. They were treated for 20 weeks, with 2 microg oral Alfacalcidol twice weekly or thrice weekly in the pulse group, and 0.5 microg oral Alfacalcidol per day in the daily group. The therapeutic end point was parathyroid hormone level < 200 pg/ mL. The iPTH levels during the study were monitored, and parameters representative of calcium and phosphate metabolism and side effects were also observed. RESULTS: One hundred and fifty-eight patients were initially enrolled, 91 in the pulse therapy group and 67 in the daily therapy group. There was no significant difference in age, hemodialysis duration, proportion of diabetic nephropathy and systemic diseases, proportion of patients who had received active vitamin D therapy previously, mean initial iPTH level (pulse group 570.47 +/- 295.86 pg/mL; daily group 498.33 +/- 207.84 pg/mL), serum calcium, serum phosphate, alkaline phosphatase (AKP), and albumin between two groups. In the pulse therapy group there were more patients with iPTH levels of 500 to approximately 1,000 pg/mL and > 1,000 pg/mL, so stratified analysis according to iPTH level was used. In therapeutic end point, iPTH levels in both groups were significantly lower compared with those before therapy (pulse group 261.29 +/- 234.97 pg/mL, P < .01; daily group 262.17 +/- 274.82 pg/mL, P < .01). After 4 weeks, the ratio of reaching end point in the pulse group was 35.2%, which was significantly higher than that (19.4%) in the daily group (P < .05). More obvious change was seen in the 200 to approximately 500 pg/mL subgroup by stratified analysis (P < .05), whereas there was no significant difference between the 500 to approximately 1,000 pg/mL and > 1,000 pg/mL subgroup (P > .05). At therapeutic end point, the total ratio of reaching end point did not differ between the two groups, and there were no obvious differences between each subgroup. In the iPTH 200 to approximately 500 pg/mL subgroup, mean iPTH%/week in the pulse group was significantly higher than that in the daily group, and no obvious difference was seen in other subgroups. AKP levels decreased significantly in both groups at therapeutic end point (pulse group 98.42 +/- 54.52 vs. 74.21 +/- 30.68 IU/L, P < .01; daily group 103.3 +/- 68.04 vs. 75.40 +/- 34.12 IU/L, P < .01). On the 4th week, AKP level in pulse group (82.39 +/- 35.23 IU/L) was significantly lower than the initial level (98.42 +/- 54.52 IU/L, P < .05), whereas in the daily group there was no difference between each week. The mean serum calcium, phosphate, and [Ca2+] x [P3+] levels in both groups did not change greatly. Nine patients in the pulse group (9.9%) and 8 patients in the daily group (11.9%) suffered hypercalcemia at least once. Persistent hypercalcemia occurred in 8 patients in the pulse group (8.8%) and 9 patients in the daily group (13.4%), but the difference in proportion did not show statistical significance. The serum phosphate in the daily group was higher after the therapy (1.74 +/- 0.36 vs. 1.89 +/- 0.36 mmol/L, P < .05), whereas that in the pulse group remained unchanged. At therapeutic end point, [Ca2+] x [P3+] level in the daily group was higher than that before the therapy (48.04 +/- 11.71 vs. 55.46 +/- 12.66, P < .05), whereas in the pulse group there was no significant difference. Side effects for both groups were minimal and well tolerated. CONCLUSIONS: Alfacalcidol [1alpha-(OH)-D3] has good and safe effects on secondary hyperparathyroidism in maintenance hemodialysis patients. The efficacy and early effects of pulse therapy are superior to those of daily therapy in moderate hyperparathyroidism patients.

Administration, Oral↗
PubMed2001

Paired-pulse repetitive transcranial magnetic stimulation of the human motor cortex.

In nine healthy humans we modulated corticospinal excitability by using conditioning-test paired-pulse transcranial magnetic stimulation in a repetitive mode (rTMS), and we compared its effect to conventional single-pulse rTMS. We applied 80 single pulses or 80 paired pulses to the motor cortex at frequencies ranging from 0.17 to 5 Hz. The conditioning-test intervals were 2, 5, or 10 ms. Motor evoked potential (MEP) amplitudes from the abductor digiti minimi (ADM) as target muscle and extensor carpi radialis (ECR) indicated the excitability changes during and after rTMS. During paired-pulse rTMS at a facilitatory conditioning-test interval of 10 ms, we observed a facilitation of MEPs at 1, 2, and 5 Hz. A similar facilitation was found during single-pulse rTMS, when stimulus intensity was adjusted to evoke MEPs of comparable size. Using an inhibitory conditioning-test interval of 2 ms, paired-pulse rTMS at frequencies of 1 and 2 Hz caused no change in MEP size during the train. However, paired-pulse rTMS at 5 Hz caused a strong enhancement of MEP size, indicating a loss of paired-pulse inhibition during the rTMS train. Since no facilitatory effect was observed during single-pulse rTMS with an adjusted stimulus intensity, the MEP enhancement during 5 Hz rTMS was specific for "inhibitory" paired-pulse rTMS. After 5 Hz rTMS MEPs were facilitated for 1 min, and this effect was not substantially different between paired-pulse rTMS and single-pulse rTMS. The correlation between ADM and ECR was most pronounced at 5 Hz rTMS. We conclude that paired-pulse rTMS is a suitable tool to study changes in corticospinal excitability during the course of rTMS. In addition, our data suggest that short trains of paired-pulse rTMS are not superior to single-pulse rTMS in inducing lasting inhibition or facilitation.

Adult↗
PubMed2004

Electroporation of subcutaneous mouse tumors by rectangular and trapezium high voltage pulses.

The artificial electrotransfer of bioactive agents such as drugs, peptides or therapeutical nucleic acids and oligonucleotides by membrane electroporation (MEP) into single cells and tissue cells requires knowledge of the optimum ranges of the voltage, pulse duration and frequency of the applied pulses. For clinical use, the classical electroporators appear to necessitate some tissue specific presetting of the pulse parameters at the high voltage generator, before the actual therapeutic pulsing is applied. The optimum pulse parameters may be derived from the kinetic normal mode analysis of the current relaxations due to a voltage step (rectangular pulse). Here, the novel method of trapezium test pulses is proposed to rapidly assess the current (I)/voltage (U) characteristics (IUC). The analysis yields practical values for the voltage U(app) between a given electrode distance and pulse duration t(E) of rectangular high voltage (HV) pulses, to be preset for an effective in vivo electroporation of mouse subcutaneous tumors, clamped between two planar plate electrodes of stainless steel. The IUC of the trapezium pulse compares well with the IUC of rectangular pulses of increasing amplitudes. The trapezium pulse phase (s) of constant voltage and 3 ms duration, following the rising ramp phase (r), yields a current relaxation which is similar to the current relaxation during a rectangular pulse of similar duration. The fit of the current relaxation of the trapezium phase (s) to an exponential function and the IUC can be used to estimate the maximum current at a given voltage. The IUC of the falling edge (phase f) of the trapezium pulse serves to estimate the minimum voltage for the exploration of the long-lived electroporation membrane states with consecutive low-voltage (LV) pulses of longer duration, to eventually enhance electrophoretic uptake of ionic substances, initiated by the preceding HV pulses.

Animals↗
PubMedDate not supplied

A prototype device for standardized calibration of pulse oximeters II.

OBJECTIVE: There is no commonly accepted in vivo calibration method for pulse oximeters available up to now. On the basis of a prototype device for the calibration of pulse oximeters which was introduced recently, a second approach based on the same concept was tackled in order to design a reliable method for standardized calibration of pulse oximeters. METHODS: An extensive clinical database of time-resolved optical transmission spectra of patient fingers is used to simulate the behavior of patients. A device which is capable of playing back these spectroscopic data to pulse oximeters, and a database where the oxygen status measured with the reference method (Co-Oximetry) is stored, are the main parts of the concept. The playback device has an artificial finger as interface to the pulse oximeters and serves to collect light from the pulse oximeter for analysis and to playback simulated light to the pulse oximeter. The light intensity emitted by two LEDs which illuminates the pulse oximeter detector is controlled via a computer in such a way that it is the same as if the pulse oximeter light had passed the finger. The pulse oximeter display during the data playback can thus be compared to the true SaO2 of the patient. The device is tested with 4 pulse oximeters based on 100 patient spectra. RESULTS: For the four pulse oximeters used in this investigation, an Agilent Technologies CMS monitor (formerly Hewlett-Packard), an Ivy 2000 with Masimo Set technology and Nellcor N-3000 and N-395, there is good correlation between SPO2 and SaO2, and mean and standard deviation of in vivo SpO2-SaO2 and playback SpO2-SaO2 are in good agreement. For two instruments, Nellcor N3000 and Agilent CMS Monitor, a quantitative comparison between the in vivo and in vitro SpO, results was derived. A mean of the deviation playback vs. in vivo SpO2 is less than 0.5% SpO2. The error limits are comparable with the calibration error of the conventional calibration routine. The device is also capable of data playback even in situations with rapid desaturation changes, as displayed in Figure 2. For the other tested pulse oximeters the results are comparable. CONCLUSIONS: Compared to the first prototype the current version is simpler and less expensive in production. Many of previously existing problems are solved and the applicability to a large variety of pulse oximeters and sensors is given. The novel concept for the calibration of pulse oximeters is a tool for assessing the performance of pulse oximeters.

Calibration↗
PubMed1987

Effects of gonadotropin-releasing hormone pulse-frequency modulation on luteinizing hormone, follicle-stimulating hormone and testosterone secretion in hypothalamo/pituitary-disconnected rams.

The effects of changes in pulse frequency of exogenously infused gonadotropin-releasing hormone (GnRH) were investigated in 6 adult surgically hypothalamo/pituitary-disconnected (HPD) gonadal-intact rams. Ten-minute sampling in 16 normal animals prior to HPD showed endogenous luteinizing hormone (LH) pulses occurring every 2.3 h with a mean pulse amplitude of 1.11 +/- 0.06 (SEM) ng/ml. Mean testosterone and follicle-stimulating hormone (FSH) concentrations were 3.0 +/- 0.14 ng/ml and 0.85 +/- 0.10 ng/ml, respectively. Before HPD, increasing single doses of GnRH (50-500 ng) elicited a dose-dependent rise of LH, 50 ng producing a response of similar amplitude to those of spontaneous LH pulses. The effects of varying the pulse frequency of a 100-ng GnRH dose weekly was investigated in 6 HPD animals; the pulse intervals explored were those at 1, 2, and 4 h. The pulsatile GnRH treatment was commenced 2-6 days after HPD when plasma testosterone concentrations were in the castrate range (less than 0.5 ng/ml) in all animals. Pulsatile LH and testosterone secretion was reestablished in all animals in the first 7 days by 2-h GnRH pulses, but the maximal pulse amplitudes of both hormones were only 50 and 62%, respectively, of endogenous pulses in the pre-HPD state. The plasma FSH pattern was nonpulsatile and FSH concentrations gradually increased in the first 7 days, although not to the pre-HPD range. Increasing GnRH pulse frequency from 2- to 1-hour immediately increased the LH baseline and pulse amplitude. As testosterone concentrations increased, the LH responses declined in a reciprocal fashion between Days 2 and 7. FSH concentration decreased gradually over the 7 days at the 1-h pulse frequency. Slowing the GnRH pulse to a 4-h frequency produced a progressive fall in testosterone concentrations, even though LH baselines were unchanged and LH pulse amplitudes increased transiently. FSH concentrations were unaltered during the 4-h regime. These results show that 1) the pulsatile pattern of LH and testosterone secretion in HPD rams can be reestablished by exogenous GnRH, 2) the magnitude of LH, FSH, and testosterone secretion were not fully restored to pre-HPD levels by the GnRH dose of 100 ng per pulse, and 3) changes in GnRH pulse frequency alone can influence both gonadotropin and testosterone secretion in the HPD model.

Animals↗
PubMed1991

Double-pulse calcium channel current facilitation in adult rat sympathetic neurones.

1. Double-pulse facilitation of Ca2+ channel currents in enzymatically dispersed adult rat superior cervical ganglion neurones was investigated using the whole-cell variant of the patch-clamp technique. Voltage-clamp recordings were performed at room temperature (21-24 degrees C) in solutions designed to isolate Ca2+ channel currents. 2. Ba2+ currents, elicited by a 0 mV test pulse, were increased in amplitude when preceded by a 40 ms pulse to voltages greater than 0 mV. The magnitude of facilitation was dependent on pre-pulse voltage and reached a maximum of 50% (i.e. 1.5 x the current amplitude elicited without a pre-pulse) at a pre-pulse voltage of +80 mV. Half-maximal facilitation occurred at about +25 mV. A small decrease (-6%) in test pulse amplitude was present at pre-pulse voltages between -40 and 0 mV. The magnitude of facilitation was also dependent on test pulse voltage. Facilitation was greatest between test pulse voltages of -10 and 0 mV. 3. Facilitation slowly decreased during prolonged (1 h) dialysis of the neurone even though the Ba2+ current amplitude was well maintained. 4. Increasing the pre-pulse duration over the range 0-120 ms produced an exponential increase in facilitation with a time constant of 17.3 ms. Conversely, lengthening the interpulse duration over the range 5-915 ms, while maintaining a constant pre-pulse amplitude and duration, resulted in an exponential decrease in facilitation with a time constant of 197 ms. 5. At a test potential of 0 mV, the decay of the facilitated Ba2+ current component was fitted to a double exponential function with time constants of about 25 and 150 ms. The time constants had little pre-pulse voltage dependence between +30 to +80 mV. 6. The initial rising phase of both the control and facilitated Ba2+ current were reasonably well described by a single exponential (tau rise) after a delay of 300 microseconds. The tau rise versus test pulse potential relationship was 'bell shaped' over the test pulse voltage of -20 to +30 mV reaching a maximum near -5 mV. tau rise was similar for control and facilitated currents except at potentials greater than +10 mV where the rise of the facilitated current was accelerated. 7. Control and facilitated activation curves, as derived from tail current amplitudes, were described by the sum of two Boltzmann functions. A facilitating pre-pulse produced an increase in the proportion of the current contributed by the component activated at more hyperpolarized test potentials.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

Long term superfusion of rat anterior pituitary cells: effects of repeated pulses of gonadotropin-releasing hormone at different doses, durations, and frequencies.

We investigated the temporal release of LH by rat pituitary cells superfused with repeated pulses of GnRH at different doses (amplitudes), frequencies, and pulse durations. Anterior pituitary (AP) cells prepared from ovariectomized rats were cultured on bio-beads and then placed in columns and superfused. The cells were stimulated intermittently for 24 h with synthetic GnRH given as pulses of 6-, 10-, or 15-min duration at frequencies of one pulse per 30, 60, or 90 min. In the first experiment we tested the temporal response of cells exposed to different doses of GnRH. At all doses, the first pulse of GnRH stimulated greater LH release than subsequent pulses. The response to subsequent pulses varied with dose. At low doses (1 and 5 X 10(-10)M) of GnRH, the AP cells stabilized and released similar amounts of LH in response to each sequential identical GnRH pulse for up to 24 h. In contrast, at high doses (10(-8) and 10(-6)M) of GnRH, the AP cells gradually released less LH with each pulse. During the initial pulses, the dose-response curves of LH release were linear between doses of 5 X 10(-10) to 1 X 10(-6) M GnRH. Thereafter, the maximum response was diminished, and the slope of the dose-response curve was reduced. In subsequent experiments we found that the decline in responsiveness with time was not due to either degradation of GnRH in the medium or loss of cell viability. The low responsiveness to high GnRH pulses at the end of the superfusion period could be overcome temporarily by further increasing the dose of GnRH. In the presence of high doses, changing GnRH pulse frequency from one 6-min pulse per h to one 6-min pulse per 1.5 h or changing duration from one repeated 10-min pulse per h to one repeated 6-min pulse per h had no detectable effect on the temporal pattern of LH release. These results suggest that, similar to constant infusion, pulsatile delivery of GnRH at high doses to AP cells can induce cell refractoriness to GnRH. This loss of responsiveness probably involves factors in addition to depletion of GnRH receptors and the releasable LH pool. In contrast, pulsatile delivery of low doses of GnRH appears to maintain LH release at a relatively constant level for up to 24 h.

Animals↗
PubMed1992

Pulse repetition rate and duration affect the responses of bat auditory cortical neurons.

Under free field stimulation conditions, we studied the effect of pulse repetition rate and duration on the responses of auditory cortical neurons of the big brown bat, Eptesicus fuscus. The best frequency (BF) and minimum threshold (MT) of each recorded neuron were first determined with a 4 ms pulse delivered from a specific point of the bat's frontal auditory space at which the neuron had maximal spatial sensitivity. Then a 4 ms pulse was delivered repetitively at different rates with an intensity in 10 dB increments above the neuron's MT and its number of impulses and response latency to each combination of repetition rate and intensity were recorded. From the series of isorepetition rate-intensity functions, we identified the neuron's best intensity (BI) which elicited a maximal number of impulses. By using a 4 ms BF and BI pulse delivered at a wide range of repetition rates, we then determined the neuron's best repetition rate (BRR) to which the neuron discharged maximally. The effect of pulse duration on the neuron's responses was subsequently studied by recording its number of impulses and latency to a BF, BI and BRR pulse delivered at a wide range of durations. A neuron's best duration (BD) to which the neuron discharged maximally was also identified. We found that cortical neurons sequentially isolated with an orthogonally penetrated electrode have comparable BFs, MTs and latencies. In addition, high BF neurons tend to have higher MTs and shorter latencies than low BF neurons. Most intensity-rate functions of cortical neurons were nonmonotonic but they can be affected by pulse repetition rate. Under repetitive single pulse stimulation, all cortical neurons show low pass characteristic to pulse repetition rate such that their number of impulses reduced drastically with increasing pulse repetition rate regardless of pulse intensity. The BRRs of most cortical neurons studied are between 1 and 3 pulses/s and their BDs are between 0.5 and 10 ms. Response latencies of cortical neurons generally shortened to a plateau level with increasing pulse intensity. In contrast, they increased with pulse repetition rate and varied in different manner with pulse duration. Nevertheless, a cortical neuron generally responds with a shortest latency to a pulse delivered at its BF, BI, BRR and BD. Thus in auditory signal processing, a neuron's responses to a wide combination of pulse intensity, duration and repetition rate enhance its versatility in signal detection. Its maximal response to a specific combination of signal duration, repetition rate and intensity provides a neural basis for fine analysis of signal features.

Acoustic Stimulation↗
PubMed1996

Effect of pulse duration on bubble formation and laser-induced pressure waves during holmium laser ablation.

BACKGROUND AND OBJECTIVE: One concern during laser ablation of tissue is the mechanical injury that may be induced in tissue in the vicinity of the ablation site. This injury is primarily due to rapid bubble expansion and collapse or due to laser-induced pressure waves. In this study, the effect of laser pulse duration on the thermodynamics of bubble formation and accompanying acoustic pressure wave generation has been investigated. STUDY DESIGN/MATERIALS AND METHODS: Q-switched holmium:YAG laser pulses (pulse duration 500 ns, pulse energy 14 mJ) and free-running holmium:YAG laser pulses (pulse duration 100-1,100 microseconds, pulse energy 200 mJ) were delivered in water and tissue phantoms via a 200- and 400-microns fiber, respectively. The tissue phantoms consisted of polyacrylamide gels with varying mechanical strengths. Bubble formation was recorded with a fast flash photography setup, while acoustic transients were measured with a needle hydrophone. RESULTS: It was observed that, as the pulse length was increased the bubble shape changed from almost spherical for Q-switched pulses to a more elongated cylinder shape for longer pulse durations. The bubble expansion velocity was larger for shorter pulse durations. Only the Q-switched pulse induced a measurable thermo-elastic expansion wave. All pulses that induced bubble formation generated pressure waves upon collapse of the bubble in gels as well as in water. However, the magnitude of the pressure wave depended strongly on the size and geometry of the induced bubble. CONCLUSION: The magnitude of the collapse pressure wave decreased as laser pulse duration increased. Hence it may be possible to reduce collateral mechanical tissue damage by stretching the holmium laser pulse.

Acoustics↗
PubMed1998

Bubble formation as primary interaction mechanism in retinal laser exposure with 200-ns laser pulses.

BACKGROUND AND OBJECTIVE: Retinal laser photocoagulation is generally performed by laser pulses of a few hundred milliseconds. The tissue interaction mechanism is a pure thermal interaction mechanism. As pulse duration gets shorter, different, non-thermal interaction mechanisms start to appear. The time domain for a change of tissue interaction mechanism seems to be in the ns and micros range. The goal of this study was to characterize the tissue interaction mechanism with 200-ns laser pulses, which approximate the thermal relaxation time of single melanin granules. MATERIALS AND METHODS: The retinas of 19 eyes of 10 rabbits were irradiated by 10 and 500 repetitive laser pulses (wavelength, 532 nm; repetition rate, 500 Hz; pulse duration, 200 ns; per pulse energy, 0-120 microJ; retinal spot size, 100 microm). The effects were evaluated by fluorescein angiography, ophthalmoscopy and by theoretical thermal calculations. Light microscopy and transmission electron microscopy were additionally performed on lesions irradiated by 500 pulses. RESULTS: Single pulse threshold energies for angiographic visibility were 3.5 microJ (10 pulses) and 2.1 microJ (500 pulses), for ophthalmoscopic visibility 9.0 microJ (10 pulses) vs. 8.6 microJ (500 pulses). At energy levels above ophthalmoscopic visibility macroscopically visible bubble formation inside the retina could be observed. This occurred at energy levels of 35 microJ (10 pulses) vs. 17 microJ (500 pulses). Microscopic evaluation of lesions irradiated with 500 pulses and energies at the angiographic threshold showed a damage primarily to the RPE. Additional outer segment damage of the photoreceptors could be found. A gap between damaged RPE cells and the outer segments could be repeatedly found as well as damaged RPE cells, which were detached from intact Bruch's membrane. Temperature calculation shows that temperatures above 100 degrees C may exist around single melanin granules. CONCLUSION: The studies suggest that RPE damage may occur by bubble formation around single melanin granules.

Animals↗
PubMed1986

Pulsed laser damage thresholds and laser treatment energy parameters, in vivo, of human aphakic intraocular membranes.

Energy and power density damage thresholds were determined for the perforation of human aphakic pupillary membranes and intraocular lens implants, in vivo, at the focal point of Neodymium-YAG ophthalmic laser systems, at 1,064 nm, which produced Q-switched nanosecond pulses (TEMoo, pulse duration; 20 ns) and mode-locked pulse trains (TEMoo, 9-11 pulses, pulse duration; 30 ps, entire pulse train delivered in 50-70 ns). Pulse energies bracketing the damage thresholds and focal diameter were tabulated. The energy density and power density thresholds for perforation of the pupillary membranes (hereafter referred to as perforation threshold) were slightly lower and power density damage thresholds higher for shorter duration pulses, eg--66 J/cm2 (2,200 GW/cm2) with the picosecond pulse trains vs 80 J/cm2 (2.7 GW/cm2) with the nanosecond pulses and were similar in pseudophakics and aphakics; 78 J/cm2 for pseudophakics vs 83 J/cm2 aphakics, both treated with single nanosecond Nd-YAG pulses, and 68 J/cm2 for pseudophakic vs 66 J/cm2 for aphakic patients treated with picosecond Nd-YAG laser pulse trains. The number of laser pulses and pulse energies required for successful discussion of the pupillary membranes depended not only on the pulse parameters but also on the characteristics of the membrane, such as thickness, nonuniformity, capsular haze, or capsular haze combined with fibrosis.

Aphakia, Postcataract↗
PubMed1991

"Real time" measurement of endogenous dopamine release during short trains of pulses in slices of rat neostriatum and nucleus accumbens: role of autoinhibition.

Release of endogenous dopamine elicited in slices of rat neostriatum or nucleus accumbens by a single electric pulse or by trains of 4 or 10 pulses was examined using fast cyclic voltammetry. Single electric pulses gave rise to a marked and transient increase in the extracellular concentration of dopamine in the neostriatum (by 0.43 mumol/l) and nucleus accumbens (by 0.39 mumol/l). The overflow elicited by subsequent pulses delivered at a frequency of 0.2 Hz caused separate but much smaller peaks of dopamine concentration, whereas the overflow elicited by subsequent pulses delivered at 1 Hz caused only a shoulder in the descending limb of the peak due to pulse 1. Four pulses at 5 Hz produced a monophasic response that was higher than the single pulse-evoked peak. Nomifensine 1 mumol/l greatly increased and prolonged the evoked overflow of dopamine. In the absence of nomifensine, metoclopramide 0.3 mumol/l did not change the response to a single pulse or 4 pulses delivered at 0.2 Hz but increased the response to 4 or 10 pulses at 1 Hz and to 4 pulses at 5 Hz. In the presence of nomifensine, metoclopramide increased the response to a single pulse as well as, to a greater extent, the response to 4 pulses at 0.2 Hz and 4 pulses at 1 Hz. Sulpiride 1 mumol/l produced effects similar to those of metoclopramide in the neostriatum in the presence of nomifensine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1999

Comparison of the effects of short, high-voltage and long, medium-voltage pulses on skin electrical and transport properties.

High-voltage pulses have been shown to increase rates of transport across skin by several orders of magnitude on a time scale of minutes to seconds. Two main pulse protocols have been employed to promote transport: the intermittent application of short ( approximately 1 ms) high-voltage (approximately 100 V across skin) pulses and a few applications of long (=100 ms) medium-voltage (>30 V across skin) pulses. In order to better evaluate the benefits of each protocol for transdermal drug delivery, we compared these two protocols in vitro in terms of changes in skin electrical properties and transport of sulforhodamine, a fluorescent polar molecule of 607 g/mol and a charge of -1. Whereas both protocols induced similar alterations and recovery processes of skin electrical resistance, long pulses of medium-voltage appeared to be more efficient in transporting molecules across skin. Skin resistance decreased by three (short pulses) and two (long pulses) orders of magnitude, followed by incomplete recovery in both cases. For the same total transported charge, long pulses induced faster and greater molecular transport across skin than short pulses. In addition, a greater fraction of the aqueous pathways created by the electric field was involved in molecular transport when using long pulse protocols. Transport was concentrated in localized transport regions (LTRs) for both protocols but LTRs created by long pulses were an order of magnitude larger than those formed by short pulses and the short pulses created an order of magnitude more LTRs. Overall, this study is consistent with the creation of fewer, but larger aqueous pathways by long, medium-voltage pulses in comparison to short, high-voltage pulses.

Adult↗
PubMed1998

Accuracy of two pulse oximeters at low arterial hemoglobin-oxygen saturation.

OBJECTIVE: To evaluate the performance of two pulse oximeters in the measurement of arterial hemoglobin saturation in hypoxemic children. DESIGN: Prospective, repeated-measures observational study. SETTING: A 16-bed pediatric intensive care unit in a children's tertiary hospital. PATIENTS: Sixty-six patients with arterial saturation of <90%. INTERVENTIONS: Three arterial blood samples were taken from each subject during a 48-hr period. Pulse oximeter measurements of arterial saturation were compared with arterial saturation determined by cooximetry. MEASUREMENTS AND MAIN RESULTS: Arterial saturation was measured using one or both pulse oximeters (SpO2) and compared with the arterial hemoglobin saturation determined by cooximetry (SaO2). Sixty-two subjects were studied, using the Ohmeda pulse oximeter giving 185 data points (78 with saturations <75% [defined by the average of pulse oximeter and cooximeter]); 53 subjects were studied, using the Hewlett-Packard pulse oximeter yielding 155 data points (60 with saturations <75%). SpO2 ranged from 24% to 94%. Bias and precision of the Ohmeda pulse oximeter were -2.8% and 4.8% >75% and -0.8% and 8.0% <75%. Bias and precision of the Hewlett-Packard pulse oximeter were -0.5% and 5.1% >75% and 0.4% and 4.6% <75%. Intrapatient regression coefficient (r) for the differences between pulse oximeter and cooximeter was 0.58 for the Ohmeda and 0.59 for the Hewlett-Packard. Regression coefficients for predicting change in cooximeter value given a change in the Ohmeda pulse oximeter were 0.59 and 0.71 <75% and >75%, respectively. Similar coefficients for the Hewlett-Packard pulse oximeter were 0.50 and 0.70, respectively. CONCLUSION: The performance of the Ohmeda pulse oximeter deteriorated below an SpO2 of 75%. The Hewlett-Packard pulse oximeter performed consistently above and below an SpO2 of 75%. The ability of both pulse oximeters to reliably predict change in SaO2 based on change in pulse oximetry was limited. We recommend measurement of PaO2 or SaO2 for important clinical decisions.

Child↗
PubMed2002

Thresholds for retinal injury from multiple near-infrared ultrashort laser pulses.

Multiple-pulse lasers are routinely used in the laboratory for research, manufacturing, medical procedures, and in military applications. In order to provide a safe work environment for personnel using these lasers, safety standards have been established and have been in use for many years. These safety standards have addressed laser pulses of nanosecond duration and longer. Recently, safety standards have been updated to address laser pulses as short as 100 femtoseconds in duration. In order to tie these "ultrashort" laser pulses to hazard trends in currently established standards for multiple-pulse exposures with repetition rates less than several kilohertz, this experiment was conducted. Reported herein are minimum visible lesion thresholds in the paramacula of the primate retina using an 800-nm wavelength laser with 1,000 pulses per second, at 130 femtoseconds (fs) pulse duration. The minimum visible lesion (MVL) thresholds were determined at 1 h and 24 h post exposure for 1, 10, 100, 1,000, and 10,000 pulses and are compared with thresholds reported by other researchers. These new data are evaluated relative to the current safety standards for retinal exposure limits as a function of the number of pulses for femtosecond-pulse duration. Data from this study show that the retinal ED50 thresholds/pulse in the paramacula decrease by almost a factor of four as the number of pulses goes from one to ten and then decrease very little for an increase of three decades more in the number of pulses. The MVL-ED50 at the threshold decreased from 0.55 microJ for a single pulse to 0.15 microJ/pulse for 10 pulses and then only to 0.11 microJ/pulse for 10,000 pulses.

Animals↗
PubMed2007

Effects of 532 nm pulsed-KTP laser parameters on vessel ablation in the avian chorioallantoic membrane: implications for vocal fold mucosa.

OBJECTIVES: Selective vascular ablation (photoangiolysis) using pulsed lasers that target hemoglobin is an effective treatment strategy for many vocal fold lesions. However, vessel rupture with extravasation of blood reduces selectivity for vessels, which is frequently observed with the 0.45-ms, 585-nm pulsed dye laser. Previous studies have shown that vessel rupture is the result of vaporization of blood, an event that varies with laser pulse width and pulse fluence (energy per unit area). Clinical observations using a 532-nm wavelength pulsed potassium-titanyl-phosphate (KTP) laser revealed less laser-induced hemorrhage than the pulsed dye laser. This study investigated settings for the pulsed KTP laser to achieve selective vessel destruction without rupture using the avian chorioallantoic membrane under conditions similar to flexible laryngoscopic delivery of the laser in clinical practice. STUDY DESIGN: The chick chorioallantoic membrane offers convenient access to many small blood vessels similar in size to those targeted in human vocal fold. Using a 532-nm pulsed KTP laser, pulse width, pulse energy, and working distance from the optical delivery fiber were varied to assess influence on the ability to achieve vessel coagulation without vessel wall rupture. METHODS: Third-order vessels (n = 135) were irradiated: Energy (471-550 mJ), pulse width (10, 15, 30 ms), and fiber-to-tissue distance (1 mm, 3 mm) were varied systematically. RESULTS: Selective vessel destruction without vessel wall rupture was more often achieved by increasing pulse width, increasing the fiber-to-tissue distance, and decreasing energy. Vessel destruction without rupture was consistently achieved using 15- or 30-ms pulses with a fiber-to-tissue distance of 3 mm (pulse fluence of 13-16 J/cm). CONCLUSIONS: This study substantiates our clinical observation that a 532-nm pulsed KTP laser was effective for ablating microcirculation while minimizing vessel wall rupture and hemorrhage.

Animals↗
PubMed1980

The refurbished pulse generator.

With the advent of long-life lithium pulse generators, normally functioning pulse generators with a potential life of more than five years have been removed from patients and become available for re-implantation. Although pulse generator refurbishing is widely employed, the practice has not been accepted in the United States. At The Royal Melbourne Hospital, all lithium pulse generators removed because of patient death or other causes were washed in a quaternary ammonium compound and soaked in formaldehyde. Pulse generators were than electronically tested and, if within specification, were made available for re-implantation. Pulse generators were then washed under sterile conditions in distilled water and gas-sterilized with ethylene oxide. Between 1975 and 1978 (48 months), 600 pulse generators were implanted and 93 pulse generators removed. There were 56 deaths, 22 cases of pre-erosion, erosion, or infection and 15 elective removals either due to lead problems or impending power source depletion. Eight-three (89%) pulse generators were refurbished (14% of total implants). This included 12 pulse generators refurbished on two occasions. Ten pulse generators were returned to manufacturers, seven because of impending power source depletion, two with suspected electronic faults, and one with a damaged case. Two complications occurred in patients with refurbished pulse generators. An infective process present with the previous pulse generator spread to a new pocket. The other pulse generator was removed 35 months post second implantation because of impending power source depletion. Primary infection or unusual tissue reactions did not occur. Pulse generator refurbishing as described was found to be a safe and economic procedure.

Electric Power Supplies↗