基于生物医学信号控制用于起搏器依赖的高频电刀系统

传统的高频电刀系统由术者随机启动,对依赖起搏器的患者,如在起搏器警觉期启动,电刀干扰信号将抑制起搏脉冲而危及生命,因此术前必须将起搏器程控为固定频率模式工作,但可能导致竞争心律,甚至诱发心律失常,而在心电图R波后的心室不应期发生的干扰信号将触发起搏器的噪音反转功能,不抑制起搏脉冲,提示将R波作为电刀的启动信号可应用于起搏器依赖的患者。该系统拟采用美国亚德诺半导体公司(ADI)的ADuC847微控芯片,将经无源线性网络屏蔽电刀干扰信号采集到的心电信号进行模数转换处理后输送给R波识别电路,通过单稳态触发电路同步触发启动电刀,制备一种基于体表心电图R波控制的,在起搏器心室通道不应期启动并触发起搏器噪音反转,不需要程控起搏器工作模式即可用于起搏器依赖患者的高频电刀系统。     

Behavior of central venous blood temperature in short duration and repeated stress--possibilities for temperature controlled frequency-adapted pacemaker stimulation

Although an exercise-induced increase in blood temperature has been well-known for some time, there was still some doubt whether the change in central venous blood temperature with short-lasting and repetitive physical exercise can be measured and utilized by a temperature controlled pacing system. We studied the central venous blood temperature with short-lasting and repetitive exercise in ten healthy young volunteers and in ten pacemaker patients. The blood temperature was measured intracardially while they walked upstairs. A height of 20 m was covered within 100 +/- 5 s. An oxygen uptake of 27 ml/min/kg was calculated for this level of exercise. After walking upstairs once, the volunteers had an increase in central venous blood temperature of 0.3 degrees C and the pacemaker patients of 0.37 degrees C. After walking upstairs three times, the volunteers had an overall rise in blood temperature of 0.67 degrees C and the pacemaker patients of 0.86 degrees C. Thus, the central venous blood temperature shows a pronounced, measurable increase with short-lasting exercise as well. However, the rises in blood temperature accumulate with repetitive exercise, as the duration of exercise (100 s) when walking upstairs once is not sufficient for a new level of temperature to be reached according to the level of exercise. Thus, a temperature controlled pacing system should take these complex changes into consideration.     

A new test for pacemaker leads: Capacitance measurement

A device has been developed which permits in man the measurement of the capacitance of a chronically implanted pacemaker lead at the moment of battery replacement. A large increase in capacitance suggests important body fluid penetration into the lead. This can be due to an insulation defect (caused by a suture or a guide wire during implantation) or to a degeneration of the insulation material or to the lead-design. This fluid penetration should be avoided since it can be responsible for some electro-chemical reactions.Calculated values for the capacitance of a system consisting of an inner and an outer conductor, with two media in between, agree rather well with measured values.It is suggested that the measurement of the capacitance of a pacemaker lead is an additional tool for the evaluation of chronically implanted pacemaker leads. This method can also be of interest for the quality control of pacemaker leads.     

A microprocessor controlled timing device for cardiac electrical stimulation.

A microcomputer controlled device for delivering precisely timed stimuli to cardiac chambers is described. Stimulation patterns are determined by software, rather than hardware design, resulting in enhanced flexibility. Additionally, by providing timing inputs to conventional laboratory stimulators, this instrument can convert these limited use devices into ones capable of generating complex cardiac stimulation patterns at moderate cost.     

Principle of the activity-controlled rate-adaptive cardiac pacemaker: analysis of stress and environment-induced mechanical effects on the human body

Rate-adaptive pacemakers are increasingly becoming part of clinical routine, the most widespread systems being activity-controlled. In order to shed more light on the foundations of mechanical forces which can possibly be utilized for controlling rate-adaptive systems, we conducted tests on six healthy volunteers and six pacemaker patients. With the aid of three orthogonal wide-band linear acceleration pick-ups attached to the body, the mechanical signals were recorded from the three axes during different activities. Along with standardized exercise on bicycle and treadmill ergometers, we tested the influence of household activities and interference influences. The results were analyzed in terms of the amplitude and frequency content of the signals. For walking activities we found a signal amplitude increasing in largely linear fashion with the walking speed, the signal amplitudes being approximately twice as high on the vertical axis as on the other two axes. Exercise on the bicycle ergometer produced mechanical signals of clearly lower amplitude than comparable walking activities. The Fast-Fourier analysis showed amplitude peaks in the low frequency range of 1 to 4 Hz for all forms of physiological exercise, while interference influences showed amplitude peaks mainly in the range above 8 Hz. The use of an acceleration pickup and a corresponding low pass filter might be a way of reducing the effect of nonphysiological interference influences on an activity-controlled pacemaker system. A sensor measuring in the horizontal axis appears to be the most favorable compromise for the various types of exercise. However, due to the considerable difference in signal amplitude for different types of exercise of the same intensity, an activity-controlled pacemaker system cannot entirely meet metabolic conditions and requirements.     

Luteinzing hormone activity in menotropins optimizes folliculogenesis and treatment in controlled ovarian stimulation

Although the role that LH plays in folliculogenesis is still controversial, recent evidence points toward facilitatory actions of LH activity in ovulation induction. Thus, we compared the response to either highly purified FSH (75 IU FSH/ampoule; group A, 25 subjects) or human menopausal gonadotropin (75 IU FSH and 75 IU LH/ampoule; group B, 25 subjects) in normoovulatory GnRH agonist-suppressed women, candidates for intrauterine insemination. A fixed regimen of 2 daily ampoules of highly purified FSH or human menopausal gonadotropin was administered in the initial 14 days of treatment; menotropin dose adjustments were allowed thereafter. Treatment was monitored with daily blood samples for the measurement of LH, FSH, 17beta-estradiol (E(2)), progesterone, testosterone, hCG, inhibin A, and inhibin B, and transvaginal pelvic ultrasound was performed at 2-day intervals. Although preovulatory E(2) levels were similar, both the duration of treatment (16.1 +/- 0.8 vs. 12.6 +/- 0.5 days; P< 0.005) and the per cycle menotropin dose (33.6 +/- 2.4 vs. 23.6 +/- 1.1 ampoules; P < 0.005) were lower in group B. In the initial 14 treatment days the area under the curve of FSH, progesterone, testosterone, inhibin A, and inhibin B did not differ between the 2 groups, whereas LH, hCG, and E(2) areas under the curve were higher in group B. The occurrence of small follicles (<10 mm) and the inhibin B/A ratio in the late follicular phase were significantly reduced in group B. A nonsignificant trend toward a higher multiple gestation rate was present in group A (60% vs. 17%). We conclude that ovulation induction with LH activity-containing menotropins is associated with 1) shorter treatment duration, 2) lower menotropin consumption, and 3) reduced development of small ovarian follicles. These features can be exploited to develop regimens that optimize treatment outcome, lower costs, and reduce occurrence of complications such as multiple gestation and ovarian hyperstimulation.     

A new method for the determination of arylesterase activity in human serum using simulated body fluid

Arylesterase activity (EC 3.1.1.2), one of the three functions of the paraoxonase enzyme (PON1), is thought to protect low-density lipoproteins (LDL) and high-density lipoprotein (HDL) from oxidation and to facilitate reverse cholesterol transport. The Eckerson et al. method, which employs Tris/HCl buffer, has been extensively used and could be considered as the reference method, although it shows relatively low precision and reproducibility. Using simulated body fluid (SBF), which simulates blood electrolyte composition, a significant improvement in arylesterase activity determination was achieved. Modifications of SBF bicarbonate and chloride concentrations did not result in further improvements. To validate this method arylesterase activity was measured using SBF and Tris/HCl in 23 subjects with increased cardiovascular disease risk. Precision was significantly higher using SBF than with Tris/HCl. Data from both methods do not significantly differ in samples with arylesterase activity > or = 30.6 U/L using SBF, but do differ significantly when very low activity samples (< 30.6 U/L) were included. Differences suggest that the Tris/HCl buffer gives misleading activity results, especially in very low activity samples. For the first time, results suggest that SBF can successfully be used instead of Tris/HCl in arylesterase activity determination.     

Effects of volume and frequency of mechanical ventilation on respiratory activity in humans

This study evaluated the interaction between respiratory chemical drive and non-chemical factors related to the frequency and level of thoracic displacement during mechanical ventilation in shaping respiratory activity. Ten normal subjects were artificially hyperventilated with a positive-pressure mechanical respirator to a baseline end-tidal PCO2 of approximately 30 Torr. Thereafter, in separate trials, the end-tidal PCO2 was increased by (a) progressively raising the concentration of CO2 in the inspired gas (FICO2) while holding tidal volume (VT) and breathing frequency (f) constant, (b) lowering f while holding VT and FICO2 constant, and (c) lowering VT while maintaining a constant f and FICO2. Initially, as the PCO2 rose above baseline levels with increases in FICO2, there was no change in inspiratory muscle activity, as measured by the peak inspiratory airway pressure, until the PCO2 reached 40 Torr. This PCO2 threshold for a change in respiratory activity was significantly reduced when the tidal volume or frequency of mechanical ventilation was lowered. These results suggest that non-chemical drives related to the frequency and level of thoracic displacement interact with chemical stimuli in shaping respiratory activity.     

A randomized controlled trial of adaptive ventilation for Cheyne-Stokes breathing in heart failure

Heart failure is associated with Cheyne-Stokes breathing, which fragments patients' sleep. Correction of respiratory disturbance may reduce sleep fragmentation and excessive daytime sleepiness. This randomized prospective parallel trial assesses whether nocturnal-assist servoventilation improves daytime sleepiness compared with the control. A total of 30 subjects (29 male) with Cheyne-Stokes breathing (mean apnea-hypopnea index 19.8 [SD 2.6] and stable symptomatic chronic heart failure (New York Heart Association Class II-IV) were treated with 1 month's therapeutic (n = 15) or subtherapeutic adaptive servoventilation. Daytime sleepiness (Osler test) was measured before and after the trial with change in measured sleepiness the primary endpoint. Secondary endpoints included brain natriuretic peptide levels and catecholamine excretion. Active treatment reduced excessive daytime sleepiness; the mean Osler change was +7.9 minutes (SEM 2.9), when compared with the control, the change was -1.0 minutes (SEM, 1.7), and the difference was 8.9 minutes (95% confidence interval, 1.9-15.9 minutes; p = 0.014, unpaired t test). Significant falls occurred in plasma brain natriuretic peptide and urinary metadrenaline excretion. We conclude that adaptive servoventilation produces an improvement in excessive daytime sleepiness in patients with Cheyne-Stokes breathing and chronic heart failure. This study suggests improvements in neurohormonal activation with this treatment.     

Effects of muscarinic receptor stimulation on Ca2+ transient, cAMP production and pacemaker frequency of rabbit sinoatrial node cells

We investigated the contribution of the intracellular calcium (Ca _i ²⁺ ) transient to acetylcholine (ACh)-mediated reduction of pacemaker frequency and cAMP content in rabbit sinoatrial nodal (SAN) cells. Action potentials (whole cell perforated patch clamp) and Ca _i ²⁺ transients (Indo-1 fluorescence) were recorded from single isolated rabbit SAN cells, whereas intracellular cAMP content was measured in SAN cell suspensions using a cAMP assay (LANCE^®). Our data show that the Ca _i ²⁺ transient, like the hyperpolarization-activated “funny current” (I _f) and the ACh-sensitive potassium current (I _K,ACh), is an important determinant of ACh-mediated pacemaker slowing. When I _f and I _K,ACh were both inhibited, by cesium (2 mM) and tertiapin (100 nM), respectively, 1 μM ACh was still able to reduce pacemaker frequency by 72%. In these I _f and I _K,ACh-inhibited SAN cells, good correlations were found between the ACh-mediated change in interbeat interval and the ACh-mediated change in Ca _i ²⁺ transient decay (r ² = 0.98) and slow diastolic Ca _i ²⁺ rise (r ² = 0.73). Inhibition of the Ca _i ²⁺ transient by ryanodine (3 μM) or BAPTA-AM (5 μM) facilitated ACh-mediated pacemaker slowing. Furthermore, ACh depressed the Ca _i ²⁺ transient and reduced the sarcoplasmic reticulum (SR) Ca²⁺ content, all in a concentration-dependent fashion. At 1 μM ACh, the spontaneous activity and Ca _i ²⁺ transient were abolished, but completely recovered when cAMP production was stimulated by forskolin (10 μM) and I _K,ACh was inhibited by tertiapin (100 nM). Also, inhibition of the Ca _i ²⁺ transient by ryanodine (3 μM) or BAPTA-AM (25 μM) exaggerated the ACh-mediated inhibition of cAMP content, indicating that Ca _i ²⁺ affects cAMP production in SAN cells. In conclusion, muscarinic receptor stimulation inhibits the Ca _i ²⁺ transient via a cAMP-dependent signaling pathway. Inhibition of the Ca _i ²⁺ transient contributes to pacemaker slowing and inhibits Ca _i ²⁺ -stimulated cAMP production. Thus, we provide functional evidence for the contribution of the Ca _i ²⁺ transient to ACh-induced inhibition of pacemaker activity and cAMP content in rabbit SAN cells.     

Pregnancy confirmed after controlled ovarian stimulation for infertility: A case report

Rational:Induction of ovarian stimulation by use of the gonadotropin-releasing hormone agonist (GnRHa) long protocol in the luteal phase is a common practice and results in stable pregnancy and live births; it is often used in patients with normal ovarian function. Some patients with normal ovulation may be pregnant before ovulation induction, which can be easily confirmed by asking the patient about cessation of menstruation. However, some pregnancy complications may cause vaginal bleeding along with normal menstrual blood loss; in such a situation, hormone levels can often mirror that seen in pituitary down-regulation and the value of β-HCG may be less than 5 mIU/mL. Under these conditions, the physician might start the cycle of ovarian stimulation. During ovarian stimulation, the increase in β-HCG can cause premature luteinization and follicle maturation disorder, and poor embryo quality, which can easily be overlooked. In this study, we report a case of pregnancy at the end of controlled ovarian stimulation induced by GnRHa long protocol in the luteal phase, followed by follicle maturation disorder and poor embryo quality. This case provided a reference and served as a cautionary note that could perhaps obviate occurrence of similar cases.Patient concerns:A 30-year-old woman with a diagnosis of unexplained infertility was scheduled for in vitro fertilization embryo culture (IVF) at our clinic. Pregnancy was confirmed at the end of controlled ovarian stimulation, which was followed by follicular maturation disorder and poor embryo quality.Diagnosis:The patient with a diagnosis of unexplained infertility was scheduled for IVF at our clinic.Interventions:Oocyte retrieval was still arranged for her after confirmation of pregnancy. As per the β-HCG level and the trans-vaginal ultrasound examination findings, we considered 2 possibilities: an adverse intrauterine pregnancy or extra-uterine pregnancy. Therefore, we decided to terminate the pregnancy; hence, 50 mg/d of mifepristone was given for 2 days, combined with 200 μg misoprostol.Outcomes:Elevated β-HCG level had an adverse effect on maturation and fertilization of oocytes, and even embryo quality.Conclusion:Once pregnancy is confirmed, ovulation induction should be terminated as soon as possible.     

Prerequisites for pacemaker electrodes for individual programming of a low stimulation impulse (comparison of an Elgiloy and a steroid-dependent pacemaker electrode)

The individual programming of cardiac pacemakers to pulse amplitudes of 2.5 volts and less reduces unnecessary energy consumption by the pacing impulse. In order not to impair the safety margin, electrodes must reveal a low chronic pacing threshold associated with a small standard deviation. For 3 months after implantation we investigated these conditions in 10 patients with a steroid-eluting lead and in 10 patients with a conventional elgiloy lead. During the study period patients with a steroid-eluting lead had a significantly lower pacing threshold. Twelve weeks after implantation all steroid-patients had 0.8 volts pacing threshold at 0.5 ms pulse width. In contrast to the conventional lead the steroid-eluting lead had a significantly lower impedance. Since voltage enters squared into the energy consumption formula, patients with a steroid-eluting lead needed significantly less energy for an effective stimulation of the myocardium 4 and 12 weeks after implantation. R-wave amplitude was not different in both groups. Our investigation demonstrates that immediately after implantation all patients with a steroid-eluting lead can be programmed at 2.5 volts pulse voltage or individually even lower. The saved energy results either in an extended pulse generator longevity or allows the implantation of a smaller pulse generator with a reduced battery capacity.     

A new methodology for controlled particle inhalation by small rodents

In order to investigate the deposition, retention, and clearance mechanisms implicated in particle inhalation under standardized conditions, we developed a continuous negative-pressure ventilation system, whereby the breathing pattern in small rodents could be controlled during exposure to aerosols. Using an on-line open-flow set-up, 19 anesthetized, intubated, and paralyzed Syrian golden hamsters, individually contained within a whole-body box, were artificially ventilated under the said continuous negative-pressure conditions, 1 of 5 different combinations of breathing frequency and tidal volume being established. The animals were then exposed to aerosols containing 6-micron diameter polystyrene spheres, and the deposition of particles in the conducting airways was monitored photometrically. During exposure, the level of respiration (mean lung inflation) was stabilized by means of a negative-pressure vent. Breathing frequency and tidal volume, as well as the compliance of the system, remained virtually unchanged during the course of a single experiment, and in each case, a reproducible deposition of particles was achieved. Our findings indicate that tidal volume, but not breathing frequency, has a marked influence on the particle deposition ratio. Breathing frequency exerts opposing and counterbalancing effects on this latter parameter by enhancing the impaction of particles on the one hand, and by decreasing sedimentation on the other.     

A new selective estrogen receptor modulator with potent uterine antagonist activity, agonist activity in bone, and minimal ovarian stimulation

The use of selective estrogen receptor modulators for the treatment of estrogen-dependent diseases in premenopausal women has been hindered by undesirable ovarian stimulation and associated risks of ovarian cysts. We have identified a selective estrogen receptor modulator compound (LY2066948) that is a strong estrogen antagonist in the uterus yet has minimal effects on the ovaries of rats. LY2066948 binds with high affinity to both estrogen receptors and has potent estrogen antagonist activity in human uterine and breast cancer cells. Oral administration of LY2066948 to immature rats blocked uterine weight gain induced by ethynyl estradiol with an ED50 of 0.07 mg/kg. Studies in mature rats demonstrated that LY2066948 decreases uterine weight by 51% after 35 d treatment, confirming potent uterine antagonist activity over several estrous cycles. This strong uterine response contrasted with the minimal effects on the ovaries: serum estradiol levels remained within the normal range, whereas histologic evaluation showed granulosa cell hyperplasia in few of the rats. Bone studies demonstrated that LY2066948 prevented ovariectomy-induced bone loss and treatment of ovary-intact rats caused no bone loss, confirming estrogen receptor agonist skeletal effects. Collectively, these data show that LY2066948 exhibits a tissue-specific profile consistent with strong antagonist activity in the uterus, agonist activity in bone, and minimal effects in the ovaries.     

The effects of body position, controlled breathing and exercise on the heart rate variability parameters in healthy subjects

The behavior of temporal and spectral parameters of the heart rate variability was determined during 5 different maneuvers in order to characterize the level of sympathetic-vagal activity. The discriminating capacity of two spectral parameter estimation schemes were compared, and the respiratory influence was evaluated. One hundred and ten records of instantaneous heart rate and respiratory amplitude were analyzed, both in temporal and spectral perspectives. The records were obtained from 22 healthy subjects, under a five-stage protocol: supine, controlled breathing, standing, exercise, and recovery. A discriminating and characteristic behavior was found among the maneuvers, specifically for the dispersion parameters, low and intermediate partial components. The two integration-normalization procedures used in the estimation of the spectral components showed similarities, producing a functional interpretation independent of the selected procedure. The division of the low frequency component in two separate bands, allowed an improved discriminating capacity. The respiration had an important influence in the controlled breathing maneuver while being lower in the rest of the stages. In conclusion, the maneuvers determined a typical behavior of the dispersion and spectral parameters (low and intermediate partial components) of the heart rate variability, showing adequate distinctive levels in the sympathetic-vagal activity for each maneuver.     

Androgen dependent stimulation of aromatase activity in genital skin fibroblasts from normals and patients with androgen insensitivity

OBJECTIVE: To measure the effect of androgens or aromatase activity as an index of androgen responsiveness in patients with androgen insensitivity. DESIGN: Genital skin fibroblasts were established in culture using primary skin explants obtained from normal males at the time of circumcision and from androgen insensitive patients who had surgery either for gonadectomy (complete androgen insensitivity syndrome) or for reconstruction of the external genitalia (partial androgen insensitivity syndrome). PATIENTS: Foreskin samples were obtained at the time of circumcision in 27 normal males. Scrotal or labia majora skin was obtained at the time of surgery from 14 patients with the complete and 22 with the partial forms of the androgen insensitivity syndrome. MEASUREMENTS: Basal and stimulated levels of aromatase activity were measured in genital skin fibroblasts following preincubation with natural and synthetic, nonmetabolizable androgens. RESULTS: Following a 48-hour preincubation with testosterone or dihydrotestosterone, there was a five to six-fold stimulation of aromatase activity in normal fibroblasts. Mibolerone, a synthetic androgen, produced similar results. The stimulatory effect was blocked by anti-androgens. Seven patients with partial androgen insensitivity, of whom four were either receptor deficient or showed a qualitative defect in androgen binding, had reduced mibolerone induced stimulation of aromatase activity. All ten patients with receptor negative complete androgen insensitivity had an absent response. There was no aromatase induction in a further three patients with complete androgen insensitivity who were receptor positive. Two siblings in the latter group had an exon deletion encoding for part of the DNA binding domain of the androgen receptor. CONCLUSIONS: Androgens stimulate aromatase activity in genital skin fibroblasts from normals. The response is mediated via the androgen receptor and can be decreased or absent in patients with the androgen insensitivity syndrome. This may be a useful in-vitro marker of androgen responsiveness in such patients.     

Method for the direct comparison of the frequency behavior in QT- and activity-controlled pacemaker systems

A non-invasive method of testing the suitability of an activity-controlled pacemaker system in patients with VVT-programmable systems is presented. The QT-time controlled TX-pacemaker of a 36-year-old patient was programmed into the VVT-mode. Then the activity-controlled pacemaker (Activitrax) was fixed epicutaneously above the pectoral muscles and two stimulation electrodes were applied above the implanted pacer and the tip of the implanted probe. Thus the external could be made to trigger the implanted system. The frequency profile was recorded with identical loads with QT and/or activity control. For both the frequency-adapted pacemaker systems, the direct comparison yields characteristic frequency profiles: a quick frequency increase and decrease of both Activitrax and load, but a delayed frequency profile of the QT-controlled pacer. Different frequency maxima are rendered by the two pacemakers as a function of the load.