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Tumour blood flow changes induced by application of electric pulses.

The effect of electric pulses on tumour blood flow was investigated in the murine fibrosarcoma SA-1. After the application of short intense electric pulses, relative tumour perfusion was measured using an 86RbC1 extraction technique. A significant reduction of tumour perfusion (approximately 30% of control) was observed within 1 h following the application of eight electric pulses to the tumour. Thereafter, tumour blood flow slowly recovered, almost reaching the pretreatment level by 24 h. No change in perfusion was induced in the untreated contralateral normal leg muscle. A similar pattern of blood flow reduction was induced when a second set of electric pulses was applied to the tumour following a 24 h interval. The degree of tumour blood flow reduction was dependent upon the number of electric pulses applied, at 1040 V, and less effect was observed if less than eight pulses were applied. A modification of the amplitude of the electric pulses resulted in changes in the direction of tumour blood flow response. Tumour blood flow increased following pulses in the range between 80 and 560 V and decreased at amplitudes higher than 640 V. These results demonstrate that the local application of electric pulses to solid tumours can modify tumour blood flow. Pulses of increased amplitude resulted in the progressive reduction of tumour blood flow with a corresponding increase in tumour cytotoxicity as measured by growth delay. Tumour blood flow reduction by electric pulses could have potential in exploiting modalities mediated by tumour hypoxia, e.g. activation of bioreductive agents.

Animals↗

Implications of pulsed chemical exposures for aquatic life criteria and wastewater permit limits.

Subacute effects of pulsed copper, zinc, or ammonia exposures were examined, including a range of pulse concentrations, durations, frequencies, and recovery times between pulses, using short-term chronic Pimephales promelas and 21-d Daphnia magna tests. Sublethal effects were rarely observed independent of mortality. Effects were observed only at concentrations near the species continuous exposure 48 h LC50 for each chemical. Daphnia often rebounded from temporary reproduction effects, meeting or exceeding control responses by the end of the test. Effects of 24 h ammonia or copper pulses were diminished soon after the pulse was removed, while 24 h zinc pulses caused continued effects for several days following removal of the pulse, indicating a slower uptake and/or depuration rate for zinc. D. magna exhibited less mortality as copper pulses were spaced further apart, while fish were equally or more affected with longer recovery times between copper pulses, indicative of different adaptation mechanisms between the two species. Responses were not predictable based on either average concentration or a combination of duration and concentration. Chronic water quality criteria and effluent permit limits, expressed as a 4- or 30-d average concentration, respectively, may not be appropriate for protecting against effects of pulsed exposures, depending on the frequency, magnitude, and duration of pulses, as well as the recovery period between events.

Ammonia↗

Safety and efficiency of pulse charge multiplication for chronic ventricular output programming.

Fifty-one patients with Intermedics pacemakers and different chronic (> or = 12 months) ventricular lead models were investigated. Ventricular charge thresholds (microC) were measured telemetrically at 1.0, 2.0, 2.5, and 3.5 V, respectively. Then pulse duration was increased until charge per pulse (microC) was twice the threshold value in patients not being pacemaker dependent (n = 39) and three times the threshold in pacemaker dependent patients (n = 12), thus giving a 2:1 or 3:1 safety factor in terms of charge ("safety charge"). At safety charge settings, the battery current was measured telemetrically for all four pulse amplitudes (PA) in VVI mode at 70 beats/min. For safety purposes, only pulse amplitudes were considered that fulfilled two conditions: (1) pulse duration threshold (PDT) < or = 0.30 ms at PA and (2) PDT < or = 1.00 ms at a pulse amplitude of (PA-0.5 V). The combination of pulse amplitude and pulse duration that yielded the safety charge at the lowest battery current was defined as optimized ventricular output (Copt). It was found at 1.0 V in 27 patients and at 2.0 V in 24 patients. The safety pulse duration (SPD) that yielded a 2:1 safety charge in patients who were not pacemaker dependent was 0.32 +/- 0.12 ms for both, 1.0 V (n = 23) and 2.0 V (n = 16), respectively. In pacemaker dependent patients, the SPD for the 3:1 safety charge was 0.61 +/- 0.25 ms (at 1.0 V, n = 4) and 0.47 +/- 0.11 ms (at 2.0 V, n = 8), respectively. The safety factor for conversion of PDT into SPD was 3.15 (range 3.00-3.38) for pacemaker dependent patients and 2.04 (range 2.00-2.43) for patients who were not pacemaker dependent, respectively. Charge thresholds measured at study entrance, after 24 hours, and again after 6 months showed a median variation of 14% and a maximum individual variation of 55%. On day 0 and 180, 24-hour Holter recordings were obtained from all patients and revealed constant ventricular capture at output settings Copt. When the output was changed from a fixed setting (2.5 V at 0.50 ms) to Copt, the battery current decreased by 17.5% (P < 0.0001). In conclusion, pacing thresholds in patients with chronic ventricular leads are stable enough to permit programming battery-saving low output settings, if pacemakers are followed on a regular basis. Titration of a 2:1 safety charge (a 3:1 safety charge in pacemaker dependent patients) by prolongation of pulse duration is safe, provided that pulse amplitude is chosen carefully. Using this approach, current consumption can significantly be reduced without jeopardizing patient's life.

Aged↗

Experimental and clinical study of a holmium: YAG laser with adjustable pulse duration.

BACKGROUND: The holmium:YAG laser is used for treatment of urolithiasis, transurethral laser ablation for benign prostate hypertrophy and bladder tumor. The pulse duration was fixed in the previous Ho:YAG laser systems. We have evaluated more practical pulse durations to disintegrate the stone. The SPHINX Ho40 (Heraeus Corporation) can change the pulse duration freely in the range from 150 microsec. to 800 microsec. MATERIALS AND METHODS: 1) We measured the total energy to perforate through stone models at three different pulse durations (150, 300, 600 microsec.). 2) We experimented with the energy of each single pulse and the power of the shock wave. 3) We observed thermogenesis during the lithotripsy for each pulse duration. 4) Disintegration effects of Ho:YAG are compared with other lithotripsy systems in clinical cases. RESULTS: 1) It was possible that the smallest amount of the total energy went through the fragment at the pulse duration 150 microsec. 2) The maximum amount of energy of the wave is higher when the pulse duration is short. Although the amount of energy was 12.6 V, the amounts of energy at 800 microsec decreased with a pulse duration 150 microsec. to 6.46 V which was about 40 % 3) The highest temperatures achieved when the irradiation of laser was started and finished were compared. The shorter the pulse duration was, the higher was the peak power. The shock wave was also more effective to disintegrate stones on using short pulse durations. 4) The individual clinical success rates are Ho:YAG (85.1 %), Alexandrite (80.6 %) and Lithoclast (74.5 %).

Holmium↗

Optimal control theory for a target state distributed in time: optimizing the probe-pulse signal of a pump-probe-scheme.

Optimal control theory (OCT) is formulated for the case of a two-color pump-probe experiment. The approach allows to calculate the pump-pulse shape in such a way that the probe-pulse absorption signal is maximized. Since the latter quantity is given by the time-averaged expectation value of a time dependent operator (the probe-pulse field-strength times the dipole operator) a version of OCT has to be used where the target state is distributed in time. The method is applied to a molecular three-level system with the pump-pulse driving the transition from the electronic ground state into the first-excited electronic state and the probe-pulse connecting the first-excited state with a higher lying electronic state. Depending on the probe-pulse duration, the vibrational wave packet becomes localized or at least highly concentrated in the Franck-Condon window for the transition into the higher-excited state. The dependence on the probe-pulse duration and on the delay time between the optimized pump-pulse and the probe-pulse is discussed in detail. The whole study demonstrates the feasibility of laser pulse induced temporal wave packet localization and the use of spectroscopic quantities as target states in experiments on femtosecond laser pulse control.

Journal Article↗

A long-lived fusogenic state is induced in erythrocyte ghosts by electric pulses.

Treatment of erythrocyte ghosts in random positions in a suspension with membrane fusion-inducing direct current electric field pulses causes the membranes to become fusogenic. Significant fusion yields are observed if the membranes are dielectrophoretically aligned into membrane-membrane contact with a weak alternating electric field as much as 5 min after the application of the pulses. This demonstrates that a long-lived membrane structural alteration is involved in this fusion mechanism. Other experiments indicate that the areas on the membrane which become fusogenic after treatment with the pulses may be very highly localized. The locations of these fusogenic areas coincide with where the trans-membrane electric field strength was greatest during the pulse. The fusogenic membrane alteration, or components thereof, in these areas laterally diffuses very slowly or not at all, or, to be fusogenic, must be present at concentrations in the membrane above a certain threshold. The loss of soluble 0.9-3-nm-diameter fluorescent probes from resealed cytoplasmic compartments of randomly positioned erythrocyte ghosts occurs through electric field pulse-induced pores only during a pulse but not between pulses or after a train of pulses if the probe diameter is 1.2 nm or greater. For a given pulse treatment of membranes in random positions in suspensions, an increase in ionic strength of the medium results in (a) a decrease in loss during the pulse, (b) no difference in loss between pulses, and (c) an increase in fusion yield when membrane-membrane contact is established. The latter two results (b and c) are incompatible with a fusion mechanism that proposes a simple relationship between electric field-induced pores and fusion.

Cell Communication↗

Independent populations of primed F1 guinea pig T lymphocytes respond to antigen-pulsed parental peritoneal exudate cells.

Thymus-dependent (T) lymphocytes from (2 x 13)F1 hybrid guinea pigs immunized to ovalbumin (OVA) in complete Freund's adjuvant can be stimulated to proliferate in vitro by antigen-pulsed peritoneal exudate cells (PECs) derived from either strain 2 or strain 13 donors. In this communication, we show that the population of primed F1 T lymphocytes which can be activated by antigen-pulsed strain 2 PECs is largely independent of the population of cells that can be activated by antigen-pulsed strain 13 PECs. This was demonstrated by both positive and negative selection procedures. In the former, T lymphocytes from OVA-primed (2 x 13)F1 donors were enriched by initial culture with OVA-pulsed strain 2 or strain 13 PECs for 1 wk. Cells selected by culture with OVA-pulsed strain 2 PECs responded well to OVA-pulsed strain 2 PECs and poorly to OVA-pulsed strain 13 PECs. If positive selection had been carried out with OVA-pulsed strain 13 PECs, the selected F1 T cells responded well to OVA-pulsed 13 PECs and poorly to OVA-pulsed 2 PECs. Negative selection was achieved by short term culture with antigen-pulsed PECs and by eliminating proliferating cells by treatment with bromodeoxyuridine and light. This procedure demonstrated that the population of primed F1 T lymphocytes which are responsive to OVA or to purified protein derivative of tuberculin can be divided into subpopulations uniquely responsive to antigen on either strain 2 or strain 13 PECs. Evidence was presented to indicate that this selective responsiveness was not the result of the action of alloantigen-specific suppressor cells. The results are considered in terms of current concepts of the genetic and molecular regulation of the interaction of PECs and T lymphocytes.

Animals↗

Control of cavitation activity by different shockwave pulsing regimes.

The aim of the study was to control the number of inertial cavitation bubbles in the focal area of an electromagnetic lithotripter in water independently of peak intensity, averaged intensity or pressure waveform. To achieve this, the shockwave pulses were applied in double pulse sequences, which were administered at a fixed pulse repetition frequency (PRF) of 0.33 Hz. The two pulses of a double pulse were separated by a variable short pulse separation time (PST) ranging from 200 micros to 1500 ms. The number and size of the cavitation bubbles were monitored by scattered laser light and stroboscopic photographs. We found that the number of inertial cavitation bubbles as a measure of cavitation dose was substantially influenced by variation of the PST, while the pressure pulse waveform, averaged acoustic intensity and bubble size were kept constant. The second pulse of each double pulse generated more cavitation bubbles than the first. At 14 kV capacitor voltage, the total number of cavitation bubbles generated by the double pulses increased with shorter PST down to approximately 400 micros, the cavitation lifespan. The results can be explained by cavitation nuclei generated by the violently imploding inertial cavitation bubbles. This method of pulse administration and cavitation monitoring could be useful to establish a cavitation dose-effect relationship independently of other acoustic parameters.

Dose-Response Relationship, Radiation↗

Modulation of luteinizing hormone pulse amplitude by the frequency of luteinizing hormone-releasing hormone stimulation and by testosterone in castrated, hypothalamic-lesioned male rats.

The frequency of spontaneous luteinizing hormone (LH) pulses is thought to be a direct result of the frequency of luteinizing hormone-releasing hormone (LHRH) pulses from the hypothalamus. By contrast, the amplitude of spontaneous LH pulses may be controlled by several factors other than the amplitude of LHRH pulses. We tested two hypotheses: 1) that LH pulse amplitude is determined in part by the frequency of LHRH pulses of constant magnitude, and 2) that testosterone (T) exerts a direct feedback effect on the pituitary gland to regulate LH pulse amplitude. Gonadal feedback was eliminated by castrating adult male rats (n = 20). Endogenous LHRH secretion was eliminated by lesioning the medial basal hypothalamus. Serum LH levels (0.19 +/- 0.04 ng/ml RP-2, mean +/- SEM) and T levels (0.15 +/- 0.02 ng/ml), measured several weeks after hypothalamic lesioning, confirmed the hypogonadotropic hypogonadal state of the animals. During a 8-h period, unanesthetized, unrestrained animals were injected with 40-ng pulses of LHRH via catheters into the jugular vein, and blood samples for LH measurement were drawn at 10-min intervals. The LHRH pulse interval was 20 min during the first 4 h in all animals. The pulse interval was doubled to 40 min in half of the animals (n = 10) during the next 4 hours; in the other 10 animals, the pulse interval was maintained constant at 20 min throughout the study. Within both of these groups, one-half of the animals (n = 5) were infused with T to achieve a physiological level of T in serum (2.46 +/- 0.36 ng/ml at 4 h), while the other half received vehicle.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Role of gonadotropin-releasing hormone pulse frequency in differential regulation of gonadotropins in the gilt.

We tested the hypothesis that different GnRH pulse frequencies will affect serum LH and FSH differently. Ovariectomized gilts (n = 6), immunized against GnRH, were given 200-ng pulses of GnRH agonist (GnRH-A) every 180 min for 3 days (pretreatment), followed by GnRH-A pulses every 30, 60, or 180 min for 3 days (treatment) in a Latin rectangle design. Mean gonadotropin concentrations did not change over time when GnRH pulses were administered every 180 min. Initiation of high GnRH-A pulse frequency (30 min) caused a robust increase in serum LH to 265% of the pretreatment level (p < or = 0.007) and a more moderate increase in serum FSH to 127% of pretreatment level (p < or = 0.02). After 66 h of frequent pulsing, desensitization had occurred and serum LH concentrations were similar to pretreatment concentrations, but serum FSH had decreased to 53% of pretreatment levels (p < or = 0.0008). After 72 h of treatment, 5 micrograms GnRH-A was infused to estimate residual releasable pools of LH and FSH, and the amounts of LH and FSH released were negatively correlated with GnRH-A pulse frequency. The results of this study imply that the LH surge is terminated because the pituitary gland becomes incapable of responding to an otherwise adequate stimulus, and not because of exhaustion of releasable LH pools. Our results confirm that in the pig the response to altered GnRH-A pulse frequency differs between LH and FSH. High GnRH pulse frequency is more effective in acutely releasing LH than FSH. Low pulse frequency of GnRH supports FSH synthesis and release, but is not as effective in increasing LH concentrations, while high GnRH pulse frequency inhibits FSH synthesis and release.

Activity Cycles↗

Predictors of pulse oximetry data failure.

BACKGROUND: Pulse oximeters have been reported to fail to record data in 1.12-2.50% of cases in which anesthesia records were handwritten. There is reason to believe that these may be underestimates. Computerized anesthesia records may provide insight into the true incidence of pulse oximetry data failures and factors that are associated with such failures. METHODS: The current study reviewed case files of 9,203 computerized anesthesia records. Pulse oximetry data failure was defined as the presence of at least one continuous gap in data > or = 10 min in duration in a case. A multivariate logistic regression model was used to identify predictors of pulse oximetry data failure, and a modified case-control method was used to determine whether extremes of blood pressure and hypothermia during the procedure were associated with pulse oximetry data failure. RESULTS: The overall incidence of cases that had at least one continuous gap of > or = 10 min in pulse oximetry data was 9.18%. The independent preoperative predictors of pulse oximetry data failure were ASA physical status 3,4, or 5 and orthopedic, vascular, and cardiac surgery. Intraoperative hypothermia, hypotension, hypertension, and duration of procedure were also independent risk factors for pulse oximetry data failure. CONCLUSIONS: Pulse oximetry data failure rates based on review of computerized records were markedly greater than those previously reported. Physical status, type of surgery, and intraoperative variables were risk factors for pulse oximetry data failure. Regulations and expectations regarding pulse oximetry monitoring should reflect the limitations of the technology.

Humans↗

Corneal epithelial injury thresholds for multiple-pulse exposures to Tm:YAG laser radiation at 2.02 microm.

Corneal epithelial damage thresholds for exposures to sequences of pulses of 2.02 microm infrared radiation produced by a Tm:YAG laser were investigated. Thresholds were determined for sequences of pulses at frequencies of 1, 10, 20, and 100 Hz. The duration of the individual pulses was 0.300 s at 1 Hz, 0.025 s at 10 and 20 Hz, and 0.005 s at 100 Hz. Threshold damage is correlated by an empirical power law of the form H(th) = CN(-alpha), in which H(th) is the threshold radiant exposure per pulse, and N is the number of pulses. The constant C differs depending on the pulse repetition frequency and individual pulse duration. The exponent alpha has values between 0.22 and 0.29. For some Tm:YAG exposures the empirical power law underestimates the damage threshold for small numbers of pulses. An empirical critical temperature model in which the critical damage temperature has a weak dependence on the duration of the single pulses or the entire train of pulses also correlates injury thresholds for both single and multiple pulses.

Animals↗

Hepatitis B virus (HBV) antigen-pulsed monocyte-derived dendritic cells from HBV-associated hepatocellular carcinoma patients significantly enhance specific T cell responses in vitro.

To investigate whether hepatitis B virus (HBV) antigen-pulsed monocyte-derived dendritic cells (MoDC) could mount a T cell response in hepatocellular carcinoma (HCC) patients associated with chronic HBV infection, peripheral blood mononuclear cells (PBMCs) from 36 HBV-associated HCC patients were induced into MoDC and pulsed with hepatitis B core antigen (HBcAg) and hepatitis B surface antigen (HBsAg), alone and in combination. Co-stimulatory molecules CD80, CD86 and CD40, as well as human leucocyte antigens D-related (HLA-DR) were found to express at the highest level on MoDC pulsed with HBcAg or HBsAg + HBcAg, at a median level on MoDC pulsed with HBcAg or HBsAg alone, and at the lowest level on non-antigen-pulsed MoDC. Interleukin (IL)-10 and IL-12 cytokines were released by antigen-pulsed MoDC at increased levels in the order: no-antigen < HBsAg < HBcAg < HBcAg + HBsAg. MoDC pulsed with HBcAg or HBsAg + HBcAg also had the strongest ability to stimulate autologous T cell proliferation and intracellular interferon (IFN)-gamma production. HBcAg- or HBsAg + HBcAg-pulsed MoDC could also induce HBV core peptide-specific CD8(+) T cell proliferation determined by tetramer staining. In addition, the antigen-pulsed MoDC were found to have a stronger capacity to produce IL-12 and induce T cell response in vitro for patients with higher alanine transaminase (ALT) levels than those with lower ALT levels, indicating that antigen pulse could substantially reverse the impaired function of MoDC in primary HCC patients with active chronic hepatitis B. In conclusion, HBV antigen-pulsed MoDC from HCC patients with chronic hepatitis B could induce HBV-specific T cell response in vitro.

Adult↗

Effects of changing gonadotrophin-releasing hormone pulse frequency on gonadotrophin secretion in men.

To investigate the effects of alterations in GnRH pulse frequency on gonadotrophin secretion, we administered low dose GnRH pulses (25 ng/kg) at hourly or 2-hourly frequencies to eight normal men. All subjects received GnRH pulses i.v. every 2 h for 88 h. Following this, exogenous GnRH was discontinued in four normal men (Group A, GnRH withdrawal), and the frequency of GnRH injections was increased to one pulse every hour for 24 h in the other four normal men (Group B, hourly GnRH). Blood samples were obtained every 20 min for LH and FSH and every 12 h for testosterone (T) and oestradiol (E2). Plasma LH increased in all subjects during injection of GnRH pulses every 2h. Withdrawal of GnRH pulses in Group A men was accompanied by a fall in mean LH, reductions in LH pulse amplitude (means +/- SEM: control 6.5 +/- 1.0; GnRH withdrawal 4.0 +/- 0.5 mIU/ml) and pulse frequency (control 5.5 +/- 0.2; GnRH withdrawal 3.5 +/- 0.7 pulses/12 h), and an increase in plasma E2 (control 122 +/- 15; GnRH withdrawal 340 +/- 37 pmol/l). Gonadotrophin responses to GnRH (25 ng/kg) were normal when tested 32 h after GnRH withdrawal. Injection of hourly GnRH pulses in Group B men was accompanied by a time-dependent change in mean LH, which transiently rose, then fell, and subsequently rose to a plateau during the second 12 h period of hourly GnRH. The final rise in LH was accompanied by an increase in LH frequency to 11.8 +/- 0.3 pulses/12 h. These data suggest that: (1) increases in gonadal steroids decrease LH secretion by reducing the amplitude and frequency of endogenous GnRH pulses; and (2) the normal adult male pituitary requires approximately 12 h to initiate a sustained increase in LH secretion in response to a doubling in GnRH pulse frequency.

Adult↗

Stimulation-evoked release of [3H]-noradrenaline by 1, 10 or 100 pulses and its modification through presynaptic alpha 2-adrenoceptors.

1 Mice isolated vasa deferentia were loaded with 1-[7,8-3H]-noradrenaline and subsequently field stimulated with 1, 10 or 100 pulses (2 ms pulse width, 1 Hz). The tritium overflow was separated into [3H]-noradrenaline and its 3H-metabolites. 2 The resting release of tritium contained about 7% [3H]-noradrenaline, 33% [3H]-3, 4-dihydroxyphenylglycol ([3H]-DOPEG) and 60% 3H-non-catechols with usually less than 1% [3H]-dihydroxymandelic acid ([3H]-DOMA). The proportion of the tritium as [3H]-noradrenaline increased with stimulation train length to 35% with 100 pulses; this increase in [3H]-noradrenaline was associated with falls in [3H]-DOPEG and 3H-non-catechols. Generally the proportional increase in [3H]-noradrenaline on stimulation was about 10 x total tritium when compared with the resting release. 3 The fractional release of [3H]-noradrenaline per pulse was independent of train length, averaging about 6 x 10(-6). This was reduced by the alpha 2-adrenoceptor agonist clonidine (0.3 - 30 nM) with an IC50 of 4.8 nM (10 pulses at 1 Hz). 4 The alpha 2-adrenoceptor antagonist, yohimbine (10 - 100 nM), did not alter the fractional release of [3H]-noradrenaline elicited by 1 pulse. The antagonist did not change the amount or composition of the resting or evoked tritium overflow. However, yohimbine (1 - 100 nM) increased the fractional release of [3H]-noradrenaline per pulse for trains of 10 or 100 pulses (1 Hz) in a concentration-dependent fashion. An increase above controls was significant only with 100 pulses and yohimbine, 30 nM. 5 The results show that the release of noradrenaline during trains of pulses in the mouse vas deferens can be regulated through presynaptic alpha 2-adrenoceptors. There was no evidence of inhibition by noradrenaline of its own release following a single pulse.

Animals↗

Overexposure analysis of pulsed distributed feedback laser source.

The goal of this study is to assess the risk of overexposure, when DFB dye laser is used for medical treatment in pulsed mode operation. Results of experimental study showing an unexpected rise of energy in pulses of distributed feedback dye laser (DFDL) output due to temperature phase gratings in dye cell during passively Q switched and mode-locked operation is reported. This unintended increase in the number of pulses, pulse duration, per pulse energy may cause side effects, when used for selective photothermolysis. To probe this phenomenon the most commonly used Rh6G dye was excited with 10-20 pulses of second harmonic of a passively Q switched and mode-locked Nd:yttrium-aluminum-garnet(YAG) laser. The outputs of DFDL and Nd:YAG laser were recorded by an Imacon-675 streak camera. The peak of DFDL output pulses was found delayed proportionally from the peak of the Nd:YAG pulses by more than an interpulse period of excitation laser. A computer program was used to simulate the experimentally measured results to estimate the thermal decay constants and energy retained by medium. The delay between peaks of Nd:YAG (input) and DFDL (output) pulses was found to vary from 10 to 14 ns for various cavity lengths. It was interesting to note that for smaller inter-pulse periods the effect of gradual gain buildup satisfied the threshold conditions for some of the pulses that otherwise cannot lase. This may lead to unintended increase in energy fluence causing overexposure-induced bio effects.

Feedback↗

Ion recombination correction for very high dose-per-pulse high-energy electron beams.

The parallel-plate ionization chamber is the recommended tool for the absorbed dose measurement in pulsed high-energy electron beams. Typically, the electron beams used in radiotherapy have a dose-per-pulse value less then 0.1 cGy/pulse. In this range the factor to correct the response of an ionization chamber for the lack of complete charge collection due to ion recombination (ksat) can be properly evaluated with the standard "two voltage" method proposed by the international dosimetric reports. Very high dose-per-pulse electron beams are employed in some special Linac dedicated to the Intra-Operatory-Radiation-Therapy (IORT). The high dose-per-pulse values (3-13 cGy/pulse) characterizing the IORT electron beams allow to deliver the therapeutic dose (10-20 Gy) in less than a minute. This considerably reduces the IORT procedure time, but some dosimetric problems arise because the standard method to evaluate ksat overestimates its value by 20%. Moreover, if the dose-per-pulse value >1 cGy/pulse, the dependence of ksat on the dose-per-pulse value cannot be neglected for relative dosimetry. In this work the dependence of ksat on the dose-per-pulse value is derived, based on the general equation that describes the ion recombination in the Boag theory. A new equation for ksat, depending on known or measurable quantities, is presented. The new ksat equation is experimentally tested by comparing the absorbed doses to water measured with parallel-plate ionization chambers (Roos and Markus) to that measured using dose-per-pulse independent dosimeters, such as radiochromic films and chemical Fricke dosimeters. These measurements are performed in the high dose-per-pulse (3-13 cGy/pulse) electron beams of the IORT dedicated Linac Hitesys Novac7 (Aprilia-Latina, Italy). The dose measurements made using the parallel-plate chambers and those made using the dose-per-pulse independent dosimeters are in good agreement (<3%). This demonstrates the possibility of using the parallel-plate ionization chambers also for the very high dose-per-pulse (> 1 cGy/pulse) electron-beam dosimetry.

Algorithms↗

Performance of LH pulse-detection algorithms at rapid rates of venous sampling in humans.

To assess the influence of the sampling rate on the quantitative characterization of pulsatile luteinizing hormone (LH) release, we withdrew blood at 4-min intervals for 8 h in five men and at 1-min intervals for 2 h in six other men. For comparative purposes, significant LH pulses were enumerated by three independent, computerized pulse-detection algorithms currently available. Our results indicate that, although the absolute number of LH pulses detected was influenced by the particular algorithm used and the estimate of intra-assay variance, all three analyses yielded increased pulse-frequency estimates at more intensive rates of venous sampling. Moreover, using a fourth, modified pulse-detection algorithm intended to maximize recognition of true-positive LH pulses while minimizing both false-positive and false-negative pulses, we observed that venous sampling at 4- and 1-min intervals exposed 4- and 12-fold more LH pulses, respectively, than could be discerned at conventional sampling rates. At rapid rates of venous sampling, the pattern of LH pulses comprised high-frequency, low-amplitude LH pulsations superimposed on lower-frequency LH peaks. This pattern suggests that the pituitary gland is responsive to high rates of intermittent neural stimulation. Moreover, these observed profiles are consistent with rapid initial rates of LH disappearance and/or distribution that we could demonstrate after intravenous bolus injections of purified LH in hypogonadotropic volunteers. In conclusion, we have compared results from three different pulse-detection algorithms at various rates of venous sampling and demonstrated a critical influence of sampling rate on apparent LH pulse frequency in humans.

Adult↗