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Effects of cochlear-implant pulse rate and inter-channel timing on channel interactions and thresholds.

Interactions among the multiple channels of a cochlear prosthesis limit the number of channels of information that can be transmitted to the brain. This study explored the influence on channel interactions of electrical pulse rates and temporal offsets between channels. Anesthetized guinea pigs were implanted with 2-channel scala-tympani electrode arrays, and spike activity was recorded from the auditory cortex. Channel interactions were quantified as the reduction of the threshold for pulse-train stimulation of the apical channel by sub-threshold stimulation of the basal channel. Pulse rates were 254 or 4069 pulses per second (pps) per channel. Maximum threshold reductions averaged 9.6 dB when channels were stimulated simultaneously. Among nonsimultaneous conditions, threshold reductions at the 254-pps rate were entirely eliminated by a 1966-micros inter-channel offset. When offsets were only 41 to 123 micros, however, maximum threshold shifts averaged 3.1 dB, which was comparable to the dynamic ranges of cortical neurons in this experimental preparation. Threshold reductions at 4069 pps averaged up to 1.3 dB greater than at 254 pps, which raises some concern in regard to high-pulse-rate speech processors. Thresholds for various paired-pulse stimuli, pulse rates, and pulse-train durations were measured to test possible mechanisms of temporal integration.

Analysis of Variance↗

Source-to-sensation level ratio of transmitted biosonar pulses in an echolocating false killer whale.

Transmitted biosonar pulses, and the brain auditory evoked potentials (AEPs) associated with those pulses, were synchronously recorded in a false killer whale Pseudorca crassidens trained to accept suction-cup EEG electrodes and to detect targets by echolocation. AEP amplitude was investigated as a function of the transmitted biosonar pulse source level. For that, a few thousand of the individual AEP records were sorted according to the spontaneously varied amplitude of synchronously recorded biosonar pulses. In each of the sorting bins (in 5-dB steps) AEP records were averaged to extract AEP from noise; AEP amplitude was plotted as a function of the biosonar pulse source level. For comparison, AEPs were recorded to external (in free field) sound pulses of a waveform and spectrum similar to those of the biosonar pulses; amplitude of these AEPs was plotted as a function of sound pressure level. A comparison of these two functions has shown that, depending on the presence or absence of a target, the sensitivity of the whale's hearing to its own transmitted biosonar pulses was 30 to 45 dB lower than might be expected in a free acoustic field.

Acoustics↗

Temporal integration of trains of tone pulses by normal and by cochlearly impaired listeners.

Two experiments investigated the temporal integration of trains of tone pulses by normal and by cochlearly impaired listeners. In the first experiment, thresholds were measured for a single 5-ms, 4-kHz tone pulse, and for ten such tone pulses as a function of interpulse interval (delta t). For normal listeners, temporal integration, defined as the threshold difference between one and ten pulses, was about 8 dB for delta t less than 20 ms, and about 5 dB at longer delta t's. For impaired listeners, temporal integration was only about 2-3 dB across the range of delta t's (5-160 ms) studied. A second experiment measured psychometric functions (log d' versus log signal power) for a single pulse and for ten pulses with delta t's of 5 ms and 80 ms. The normal listeners' functions had slopes close to unity in all three conditions, with a few exceptions. The impaired listeners' functions had slopes close to unity for ten pulses with delta t = 5 ms, but had slopes significantly greater than unity for delta t = 80 ms, and for a single pulse. At delta t = 80 ms, the increase in d' relative to the condition with a single tone was similar (a factor of square root of 10) for both impaired and normal listeners, but the threshold difference was smaller for the impaired listeners due to their steeper psychometric functions. For impaired listeners, then, temporal integration at delta t = 80 ms was normal in terms of a change in d' but abnormal when measured as a threshold difference.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Stimulation↗

Pulsing electromagnetic fields induce cellular transcription.

Weak, pulsing electromagnetic fields can modify biological processes. The hypothesis that responses to such induced currents depend on pulse characteristics was evaluated by using transcription as the target process. Two pulses in clinical use, the repetitive single pulse and the repetitive pulse train, were tested. These pulses produced different results from each other and from controls when transcription in dipteran salivary gland cells was monitored with tritiated uridine in transcription autoradiography, cytological nick translation, and analysis of isolated RNA fractions. The single pulse increased the specific activity of messenger RNA after 15 and 45 minutes of exposure. The pulse train increased specific activity only after 45 minutes of exposure.

Animals↗

Pharmacodynamics of pulse dosing versus standard dosing: in vitro metronidazole activity against Bacteroides fragilis and Bacteroides thetaiotaomicron.

Pulse dosing is a novel approach to dosing that produces escalating antibiotic levels early in the dosing interval followed by a prolonged dose-free period. Antibiotic is frontloaded by means of four sequential bolus injections, after which antibiotic levels are allowed to diminish until the next dose. This study compares standard thrice-daily dosing and pulse dosing of metronidazole against Bacteroides spp. in an in vitro model. Two American Type Culture Collection Bacteroides fragilis isolates (metronidazole MIC for each organism = 1 mg/liter) were exposed to metronidazole for 48 or 96 h. Human pharmacokinetics were simulated for an oral 500-mg dose given every 8 h (maximum concentration of drug [C(max)] = 12 mg/liter; half-life = 8 h; area under the curve [AUC] = 294 mg . h/liter) and for pulse dosing. Pulses, each producing an increase in metronidazole concentration of 9 mg/liter, were administered at times 0, 2, 4, and 6 h of each 24-h cycle, with a targeted half-life of 8 h (AUC = 347 mg . h/liter). A metronidazole-resistant B. fragilis strain (metronidazole MIC = 32 mg/liter) was exposed to both dosing regimens and, additionally, to a regimen of 1,500 mg administered once daily (C(max) = 36 mg/liter; AUC = 364 mg . h/liter). Furthermore, regimens against one B. fragilis isolate and one B. thetaiotaomicron isolate corresponding to one-fourth and one-eighth of the thrice-daily and pulse dosing regimens, mimicking peak metronidazole concentrations achieved in abscesses, were simulated in 48-h experiments (metronidazole MIC = 1 mg/liter). Time-kill curves were generated for each experiment and analyzed for bactericidal activity, defined as a bacterial burden reduction >/= 3 log(10) CFU/ml. The results of paired (Wilcoxon matched-pair signed-rank test) and nonpaired (Mann-Whitney test) statistical analyses conducted on time to 3 log(10) kill data and area under the kill curve data from each of the thrice-daily dosing experiments versus each of the pulse dosing experiments were considered not significant for a given isolate-dosing regimen combination. The thrice-daily dosing, pulse dosing, and once-daily dosing regimens all exhibited bactericidal activity. Metronidazole administered in standard or pulse dosing fashion was highly active against both susceptible and resistant strains of Bacteroides spp.

Anti-Bacterial Agents↗

Minimizing false-positive errors in hormonal pulse detection.

To explore the problem of type I (false-positive) statistical errors associated with enumerating endocrine pulses, we used the analysis of immunoactive luteinizing hormone (LH) pulses as a paradigm. In this system, the distribution of measurement error was found to approximate a Gaussian pattern. Moreover, the choice of a fixed threshold criterion to identify a hormone pulse (as generally undertaken to date) was shown to yield significantly different false-positive error rates under different experimental conditions. Therefore, we developed a technique to minimize the detection of false-positive signals and to maintain an essentially uniform error rate among different experimental groups. This simple technique requires that the pulse-detection threshold be adjusted in relation to the degree of intra-assay measurement error present. Our method should facilitate the valid comparison of endocrine pulse frequencies in normal physiological states vs. those associated with hormonal deficiency when measurement error is typically greater. In addition, this approach will aid in a more meaningful assessment of pulse concordance between two or more different hormonal species (i.e., in different assays) and will assist in comparisons of pulse properties quantitated in different laboratories. In summary, rates of false-positive pulse detection using conventional fixed-threshold criteria are materially influenced by even small differences in within-assay variance. We present a technique to minimize this type I statistical error and to maintain an essentially uniform error rate among different experimental groups.

False Positive Reactions↗

Effect of voltage and charge of electrical ablation pulses on canine myocardium.

Multiple paired lesions produced by a train of high-voltage low-charge rectangular pulses (20 A, 30 microsecond) and a train of low-voltage high-charge rectangular pulses (2 A, 300 microsecond) were made to the left ventricular epicardium of 23 dogs to determine the relative influence of voltage and charge delivery on injury of canine myocardium. Both pulsing methods contained equal amounts of energy (15 J) delivered over equal periods of time (100 ms), and both pulsing methods were nonarcing and therefore nonbarotraumatic. The volume of cardiac tissue injury resulting from both types of pulses was then evaluated from planimetered serial histological sections after 1, 10, and 30 days. Over the 30-day period, lesion size progressively decreased to 56% of its original value for the high-voltage low-charge pulse. In contrast, lesion size from the low-voltage high-charge pulse remained relatively constant, decreasing only 12% of its original value. These results indicate that when energy delivery is held constant, voltage, not charge, is the dominant mediator of cell injury. Also, cells subjected to high voltages appear to recover partially over time with significantly less constancy of tissue injury than that seen with low-voltage high-charge pulses.

Animals↗

A molecular explanation for the long-term suppression of circadian rhythms by a single light pulse.

With the use of a molecular model for circadian rhythms in Drosophila based on transcriptional regulation, we show how a single, critical pulse of light can permanently suppress circadian rhythmicity, whereas a second light pulse can restore the abolished rhythm. The phenomena occur via the pulsatile induction of either protein degradation or gene expression in conditions in which a stable steady state coexists with stable circadian oscillations of the limit cycle type. The model indicates that suppression by a light pulse can only be accounted for by assuming that the biochemical effects of such a pulse much outlast its actual duration. We determine the characteristics of critical pulses suppressing the oscillations as a function of the phase at which the rhythm is perturbed. The model predicts how the amplitude and duration of the biochemical changes induced by critical pulses vary with this phase. The results provide a molecular, dynamic explanation for the long-term suppression of circadian rhythms observed in a variety of organisms in response to a single light pulse and for the subsequent restoration of the rhythms by a second light pulse.

Animals↗

Change of transmitter release kinetics during facilitation revealed by prolonged test pulses at the inhibitor of the crayfish opener muscle.

A presynaptic voltage-control method was used to study synaptic facilitation at the inhibitory neuromuscular synapse of the crayfish opener muscle. The expression of the F2 component of facilitation, monitored 150 ms after a conditioning stimulus, was examined by systematically changing the duration of the presynaptic test pulse. (Test pulses in all experiments were depolarized to 0 mV.) Control and facilitated inhibitory postsynaptic potentials (IPSPs) exhibited identical time courses when test pulse duration was brief (approximately 2 ms). When the duration of the test pulse was increased beyond 2 ms, the transmitter release time course shifted to an earlier point in time during facilitation. Meanwhile, the increase in total transmitter release, measured from inhibitory postsynaptic conductance (IPSG) area (total release), became less pronounced with increasing duration of the test pulse. With a 20-ms test pulse, facilitation did not cause any detectable change in total release but the half-maximal point of the facilitated IPSG shifted by 3 ms (release shift). This change in release kinetics was not associated with a decrease in minimal synaptic delay. Furthermore, the relationship between total release and presynaptic pulse duration suggested that the transmitter release activated by a 20-ms pulse can be defined as a distinct component of continuous transmitter release (early component). The facilitation process accelerated the release kinetics of the early component but did not modify its total transmitter content. To test the hypothesis that the release shift is indeed mediated by the same mechanism that increases IPSP amplitude during facilitation, we investigated the correlation between the release shift and IPSP amplitude change. The two parameters were significantly correlated when the magnitude of facilitation was changed 1) during the decay of facilitation and 2) by varying the strength of the conditioning stimulus. The experimental approach reported here provides two new physiological parameters, release shift and total release, for the analysis of synaptic facilitation.

Animals↗

Electrical activity of the pulse generator of gonadotropin-releasing hormone in 26-month-old female rats.

To know whether age-related changes occur in the activity of the pulse generator of gonadotropin-releasing hormone (GnRH), old (26 months) and young (3 months) female rats were examined by recording multiunit activity (MUA) in the median eminence region of the hypothalamus, concurrently with blood samplings through an intra-atrial cannula at 6-min intervals to determine serum luteinizing hormone (LH) concentrations. We have regarded the MUA showing intermittent increases (volleys) at 20-30 min intervals, followed by LH pulses, as the electrical activity of the GnRH pulse generator. We were successful in recording MUA in 18 (26%) of 69 old ovariectomized rats and in 8 (32%) of 25 young ovariectomized rats. The overall mean (+/-SE) of the interval between MUA volleys in old ovariectomized rats was 35.1 +/- 2.0 min (n = 18), which was significantly longer than that of 22.5 +/- 1.5 min (n = 8) in young ovariectomized rats. The mean interval between LH pulses in old ovariectomized rats was 32.2 +/- 3.6 (n = 10), also being significantly longer than that of 23.3 +/- 1.0 (n = 8) in young ovariectomized rats. Further, the LH pulse amplitude in old rats (0. 95 +/- 0.07 ng/ml) was significantly smaller than in young rats (3. 40 +/- 0.36 ng/ml). The present study also confirmed that the increase in serum LH after intravenous injection of 50 ng GnRH was much smaller in old ovariectomized rats. These results show that the electrical activity of the GnRH pulse generator is certainly reduced with age. Taken together with findings suggesting an age-dependent decrease in stimulated transmitter release, attenuation in both frequency and amplitude of GnRH pulses as well as in pituitary responsiveness to GnRH pulses may account for the decreased pulsatile LH secretion observed in aging rats.

Aging↗

Evaluation of fragmentation with single or multiple pulse setting of Lithoclast for renal calculi during percutaneous nephrolithotripsy and its impact on clearance.

OBJECTIVES: To evaluate the impact of single or multiple pulse settings of Lithoclast to fragment renal calculi, and its effect on fragment size and clearance. MATERIAL AND METHODS: In a prospective study 153 patients, who had been treated over a period of 35 months for renal stone disease by percutaneous nephrolithotomy, were evaluated. In 69 cases the single and in 84 cases the multiple pulse modes were used to fragment the stone intracorporeally using the pneumatic lithoclast. The 2 groups were similar with regard to patient characteristics, stone location and size. RESULTS: Most stones were staghorn. The lithoclast was effective with good fragmentation in all cases. The mean operating and fluoroscopy times in the single and multiple pulse mode were 124.1 and 5.8, and 141.2 and 7.4 min, respectively (both differences statistically significant, p < 0.001). Immediate postoperatively residual stone fragments were seen in 16 cases with the single and 35 cases with the multiple pulse mode setting (difference statistically significant, p < 0.05). Relook procedures were required in 14 cases with the single and 22 cases with the multiple pulse setting (difference not statistically significant). No specific complication was seen related to the use of either of the two modes. On follow-up 1 patient in the multiple pulse setting developed stone recurrence after 19 months. CONCLUSIONS: The single pulse mode was associated with controlled fragmentation of the stone, formation of larger fragments which were easier to pick up, less stone scatter, shorter operating time and less exposure to fluoroscopy. The single pulse mode was also associated with statistically less chances of postoperative residual fragments.

Adult↗

Dendritic cells transduced with tumor-associated antigen gene elicit potent therapeutic antitumor immunity: comparison with immunodominant peptide-pulsed DCs.

Several studies have shown that vaccine therapy using dendritic cells (DCs) pulsed with specific tumor antigen peptides can effectively induce antitumor immunity. Peptide-pulsed DC therapy is reported to be effective against melanoma, while it is still not sufficient to show the antitumor therapeutic effect against epithelial solid tumors such as gastrointestinal malignancies. Recently, it has been reported that vaccine therapy using DCs transduced with a surrogate tumor antigen gene can elicit a potent therapeutic antitumor immunity. In this study, we investigated the efficacy of vaccine therapy using DCs transduced with the natural tumor antigen in comparison with peptide-pulsed DCs. DCs derived from murine bone marrow were adenovirally transduced with murine endogenous tumor antigen gp70 gene, which is expressed in CT26 cells, or DCs were pulsed with the immunodominant peptide AH-1 derived from gp70. We compared these two cancer vaccines in terms of induction of antigen-specific cytotoxic T lymphocyte (CTL) responses, CD4+ T cell response against tumor cells, migratory capacity of DCs and therapeutic immunity in vivo. The cytotoxic activity of splenocytes against CT26 and Meth-A pulsed with AH-1 in mice immunized with gp70 gene-transduced DCs was higher than that with AH-1-pulsed DCs. CD4+ T cells induced from mice immunized with gp70 gene-transduced DCs produced higher levels of IFN-gamma by stimulation with CT26 than those from mice immunized with AH-1-pulsed DCs (p < 0.0001), and it was suggested that DCs transduced with tumor-associated antigen (TAA) gene induced tumor-specific CD4+ T cells, and those CD4+ T cells played a critical role in the priming phase of the CD8+ T cell response for the induction of CD8+ CTL. Furthermore, DCs adenovirally transduced with TAA gene showed an enhancement of expression of CC chemokine receptor 7 and improved the migratory capacity to draining lymph nodes. In subcutaneous models, the vaccination using gp70 gene-transduced DCs provided a remarkably higher therapeutic efficacy than that using AH-1-pulsed DCs. These results suggested that vaccine therapy using DCs adenovirally transduced with TAA gene can elicit potent antitumor immunity, and may be useful for clinical application.

Adenocarcinoma↗

Central pulse pressure and atherosclerotic alterations of coronary arteries.

Central pulse pressure is more likely to reflect the haemodynamic conditions to which the heart and coronary arteries are subjected than is peripheral pulse. We reviewed the data currently available on the correlations between central pulse pressure and both the presence and extent of coronary artery disease, as well as clinical outcomes. Five clinical studies have reported an association between central pulse pressure and the presence of coronary artery disease documented by coronary angiography. Four studies, including three of the previous ones, also found a correlation between central pulse pressure and the extent of coronary artery disease. In one of these studies, however, the correlation was present only in men, whereas no link was found between pulse pressure and coronary artery disease in women. After coronary angioplasty, increased central pulse pressure has been found correlated with the occurrence of restenosis after balloon angioplasty, but not after stent implantation. Finally, the ASCOT-CAFE trial found a positive correlation between pulse pressure and the occurrence of cardiovascular events, confirming the prognostic significance of this parameter.

Angioplasty, Balloon, Coronary↗

Internal cardiac defibrillation in man: pronounced improvement with sequential pulse delivery to two different lead orientations.

Wider applicability of an implantable automatic defibrillator depends on achieving internal cardiac defibrillation consistently with the lowest possible energy. In animal studies, we have found that the cardiac defibrillation threshold could be reduced when sequential shocks separated in time and spacially arranged were delivered to the heart. We compared internal cardiac defibrillation using a single pulse shock delivered through an intravascular catheter with this new method for internal cardiac defibrillation in patients undergoing cardiac surgery for the correction of arrhythmias. For the single pulse shock and the first pulse of the sequential pulse shock, current was passed through an intravascular catheter with the catheter cathode at the apex of the right ventricle and the anode at the superior vena cava-atrial junction region. The second pulse of the sequential pulse countershock was delivered between the catheter cathode in the right ventricular apex and an oval plaque electrode secured on the laterobasal left ventricular epicardium as anode. With the single pulse alone for shock delivery, 12 patients could be defibrillated with an average of 20.1 +/- 16.8 J, with a corresponding leading-edge peak voltage and current of 836 +/- 319 V and 9.4 +/- 4.5 A, respectively. However, two of the patients could not be defibrillated with energies below 50 J. With the sequential pulse shock delivery, a significant reduction in all values were recorded. Mean total energy for defibrillation averaged 7.7 +/- 6.0 J. Leading-edge peak voltage and current from the catheter averaged 430 +/- 148 V and 5.0 +/- 2.8 A, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effects of varying electrode configuration with catheter-mediated defibrillator pulses at the coronary sinus orifice in dogs.

We compared two methods of delivering single damped sine-wave defibrillator pulses to the coronary sinus orifice in 20 dogs. Ten dogs had "unipolar" (coronary sinus to precordial disc) and 10 had "bipolar" (coronary sinus proximal to coronary sinus distal electrode) discharges. Delivered voltage, current, and energy were recorded during each pulse. Electrophysiologic testing was done before and 4 weeks after the procedure. Histologic examination of the atrioventricular groove was done at 1 mm serial sections. For the unipolar configuration a 200 J defibrillator pulse resulted in a peak voltage of 3370 +/- 125 V, a peak current of 21 +/- 4 A, and a delivered energy of 253 +/- 29 J as compared with 3010 +/- 99 V, 70 +/- 4 A, and 144 +/- 18 J, respectively, for the bipolar configuration (p less than .001). Three dogs (two with bipolar, one with unipolar pulses) had gross coronary sinus rupture and died from acute pericardial tamponade. In addition, irrespective of electrode configuration, all dogs showed microscopic rupture of the coronary sinus internal elastic membrane. Transmural atrial scarring occurred in all 10 dogs that received a unipolar pulse but in only two dogs that received a bipolar pulse (p = .0004). Unlike the atrium, injury to the left ventricle was limited in both groups. Similarly, injury to the periannular myocardium was inconsistent and not transmural in either group. No significant electrophysiologic changes were observed. With the present technique, unipolar rather than bipolar catheter-mediated defibrillator pulses result in transmural atrial injury that might prevent accessory pathway conduction. Regardless of electrode configuration, high-energy defibrillator pulses consistently cause some degree of coronary sinus rupture, most likely related to a barotraumatic mechanism.

Animals↗

Genome-wide linkage analysis for loci affecting pulse pressure: the Family Blood Pressure Program.

Pulse pressure, the difference between systolic and diastolic blood pressure, is an independent risk factor for cardiovascular disease. Increased pulse pressure reflects reduced compliance of arteries and is a marker of atherosclerosis. To locate genes that affect pulse pressure, a genome-wide linkage scan for quantitative trait loci influencing pulse pressure was performed using variance components methods as implemented in sequential oligogenic linkage analysis routines. The analysis sample included 10 798 participants in 3320 families who were recruited as part of the Family Blood Pressure Program and were phenotyped with an oscillometric blood pressure measurement device using a consistent protocol across centers. Pulse pressure was adjusted for the effects of sex, age, age2, age-by-sex interaction, age2-by-sex interaction, body mass index, and field center to remove sources of variation other than the genetic effects related to pulse pressure. Significant linkage was observed on chromosome 18 (logarithm of odds [LOD]=3.2) in a combined racial sample, chromosome 20 (LOD=4.4), and 17 (LOD=3.6) in Hispanics, chromosome 21 (LOD=4.3) in whites, chromosome 19 (LOD=3.1) in a combined sample of blacks and whites, and chromosome 7 (logarithm of odds [LOD]=3.1) in blacks from the GenNet Network. Our genome scan shows significant evidence for linkage for pulse pressure in multiple areas of the genome, supporting previous published linkage studies. The identification of these loci for pulse pressure and the apparent congruence with other blood pressure phenotypes provide increased support that these regions contain genes influencing blood pressure phenotypes.

Adult↗

Pulse pressure and cardiovascular mortality in normotensive and hypertensive subjects.

There is now increasing evidence that high pulse pressure, which is an indicator of large artery stiffness, is an independent risk factor for cardiovascular mortality, especially coronary mortality, in different populations. We have recently shown in a large French population that in male subjects aged 40 to 69 years, increased pulse pressure was a strong predictor of cardiovascular mortality, especially coronary mortality. In the present report, we analyzed the effect of pulse pressure in men and women of the same cohort after classifying them as normotensive (systolic blood pressure [SBP] <140 mm Hg and DBP <90 mm Hg) or hypertensive (SBP >/=160 mm Hg or DBP >/=95 mm Hg). After adjustment for age, mean blood pressure, and other risk factors, the relative risk (95% confidence limits) for cardiovascular mortality for an increase of 10 mm Hg of pulse pressure was 1.20 (1.01 to 1.44) in normotensives and 1.09 (1.03 to 1.14) in hypertensives. Cardiovascular and coronary death rates were similar in the group of normotensive men with a pulse pressure >50 mm Hg and in the group of hypertensive men with a pulse pressure <45 mm Hg. No association between cardiovascular mortality and pulse pressure was observed in either normotensive or hypertensive women (0.85 [0.60 to 1.21] and 1.0 [0. 91 to 1.11], respectively). Low mortality rates could explain this observation in normotensive but not in hypertensive women, in whom cardiovascular mortality rates were relatively high. Because a high pulse pressure in men is an independent predictor of cardiovascular mortality in both hypertensives and in those considered as having normal blood pressure, this parameter could aid in evaluating cardiovascular risk.

Adult↗

Episodic luteinizing hormone secretion in man. Pulse analysis, clinical interpretation, physiologic mechanisms.

The demonstration that luteinizing hormone (LH) release from the pituitary is episodic rather than constant raises fundamental questions regarding the physiologic control of pulsatile LH secretion and its possible alteration in patients with gonadal disorders. To evaluate this mode of LH secretion, quantitative means of analyzing LH pulse amplitude, frequency, shape, and area were established and utilized to study normal subjects and patients with disorders of gonadotropin secretion. Similar patterns of LH secretion were observed in normal men, in women during the follicular phase of the menstrual cycle, and in patients with hyper- and hypogonadotropism, hirsuitism, and amenorrhea (mean pulse amplitude 39-179% from nadir to peak, frequency 2.7-3.9 secretory spikes/6 h). These observations suggested that the pattern of LH secretion is similar in both normal individuals and in those with a variety of pathologic conditions. By contrast, the pattern of pulsatile secretion appeared to differ in the following conditions. LH pulses of higher amplitude (333+/-170%) and lower frequency (1.6+/-0.24 SEM/6 h) characterized the secretory patterns of women during the luteal phase of the menstrual cycle, suggesting that gonadal steroids may modulate LH pulses. LH pulses of low amplitude (26+/-2.1%) and frequency (1.3+/-0.36/6 h) were observed in women with anorexia nervosa. Either integrated LH levels or a mean LH level determined from multiple samples provided a more accurate reflection of gonadotropin secretion than the use of single LH measurements. With multiple sampling over 6 h, it was possible to reduce the 95% confidence limit of LH estimates from +/-50-90 to +/-12%. This allowed normal subjects to be distinguished from patients with low or moderately elevated LH levels in whom gonadotropin levels in single samples were often in the "normal range."Several aspects of the physiologic control of pulsatile LH secretion were studied. The concordance of follicle-stimulating hormone (FSH) with LH pulses progressively increased as LH pulse height increased (P < 0.01) suggesting possible hypothalamic mediation of gonadotropin pulses. Measurement of the "apparent half-life" of LH after secretory spikes revealed half times of 34-233 min. It is likely that this variability was attributable to at least two phenomena: (a) constant low level LH secretion that continued after certain secretory episodes but not others; (b) variable mixing of newly secreted LH into at least two pools. The alpha adrenergic-blocking agents, chlorpromazine and phentolamine, failed to block LH secretory spikes at doses sufficient to result in a 30 mm drop in systolic blood pressure in normal men.

Adult↗