Effect of the levonorgestrel-releasing intrauterine system on the uterine artery pulsatility index in postmenopausal hormone replacement therapy

Previous studies have demonstrated a significant reduction of N-methyl-D-aspartate (NMDA) receptor binding in spinal cord sections from patients who died with amyotrophic lateral sclerosis (ALS) compared to that in control patients. The reduction in NMDA receptor binding in ALS could be increased toward control values by treatment with phorbol ester, suggesting a role for receptor protein phosphorylation in this disorder. In the present study we have evaluated the time course of recovery of [3H]MK-801 binding following phorbol ester treatment to assess protein phosphatase activity in spinal cord sections from ALS and control subjects. Phorbol ester-stimulated changes in [3H]MK-801 binding returned to untreated values significantly faster in ALS tissue compared to control and could not be blocked by the coapplication of the protein phosphatase inhibitors sodium vanadate or sodium beta-D-glycerol phosphate. Okadaic acid coapplication blocked recovery in both ALS and control tissue at a concentration range at which phosphatase 2B (calcineurin) would likely be inhibited. The results suggest that abnormal levels or activity of protein phosphatases, including calcineurin, may be involved in the abnormal levels of NMDA receptors in ALS and may play some role in the pathogenesis of the disease.     

Significance of a diastolic notch in the uterine artery flow velocity waveform induced by uterine embolisation in the pregnant ewe

OBJECTIVE: To determine whether water exposure causes middle ear contamination in patients with collar button tympanostomy tubes (TTs). METHOD AND DESIGN: An in vitro model of a human head that contained an auricle, external auditory canal, tympanic membrane with TT, middle ear, eustachian tube, and mastoid cavity was developed. Two electrodes connected to an external ohmmeter resided in the middle ear to detect water entry. The model was tested with 4 types of water exposure: showering, bathing, hair rinsing, and swimming. Statistical analysis was performed by the Fisher exact test. MAIN OUTCOME MEASURES: A positive test result corresponded to water entering the middle ear via the TT, confirmed by a resistance reading of zero on the ohmmeter. A negative test result indicated no change in the initial high resistance reading. RESULTS: No positive test results were obtained for showering (0 of 60 tests), hair rinsing (0 of 60 tests), or head submersion (12.7 cm) in clean tap water (0 of 60 tests). Ten positive test results were obtained for head submersion in soapy water (10 of 97 tests), which was statistically different from clean water (P< or =.007). Swimming pool depths of 30, 45, 60, and 75 cm elicited positive test results in 2 of 16, 3 of 18, 2 of 20, and 11 of 20 tests, respectively. A higher incidence of water entry into the middle ear occurred at depths of more than 60 cm (P< or =.001). No statistical difference between depths of 60 cm or less occurred (P= .88). CONCLUSIONS: Showering, hair rinsing, and head submersion in clean tap water do not promote water entry into the middle ear. Submersion in soapy water increases the probability of water contamination. Pool water infrequently enters the middle ear with head submersion, but the incidence increases with deeper swimming (>60 cm). These data provide further evidence that many water precautions frequently advised in patients with TTs are unnecessary.     

Increased anticardiolipin antibodies are positively related to the uterine artery pulsatility index in unexplained infertility

The objective of the study was to evaluate, in patients with unexplained infertilty, the possible relationship between anticardiolipin antibodies and indices of uterine artery Doppler measurements. A total of 46 infertile women participated in the study and underwent ovarian stimulation. Transvaginal ultrasonography and colour Doppler were performed on the day of embryo transfer and patients were divided on the basis of pulsatility index (PI): group I, PI <2.5; group II, PI 2.5-3.0; and group III, PI >3.0. On the same day that Doppler analysis took place, peripheral blood was obtained and circulating anticardiolipin antibodies were assayed. The response to ovarian stimulation was similar in the three studied groups. No significant differences in oestradiol and ultrasonographic parameters were observed between the groups. A significant increase in anticardiolipin antibodies was observed in those patients with higher resistance to flow at the level of the uterine artery. A significant relationship was found between the uterine artery PI and anticardiolipin immunoglobulin G class (F = 14.35; P = 0.001), and immunoglobulin M class (F = 5.88; P = 0.020). It is concluded that, in unexplained infertility, anticardiolipin antibodies may be involved in uterine vascular modifications and that Doppler flow analysis of uterine arteries may be an important tool in the assessment and management of ovarian stimulation.     

Hemodynamic factors affecting uterine artery Doppler waveform pulsatility in sheep

Quantitative analysis of vascular resistance from the Doppler time-velocity waveform relies on measuring arterial pulsatility. However, input pressure waveform pulsatility, impedance, and resistance have all been found to effect artery flow waveform pulsatility in circulatory mathematic models and in umbilical sheep preparations in vivo. The present study used an in vivo sheep preparation to determine that embolization of the uteroplacental circulation and maternal angiotensin II administration caused changes in the uterine Doppler time-velocity waveform pulsatility that were dependent on input pressure waveform pulsatility, fundamental impedance, and resistance changes. Uteroplacental vascular embolization increased vascular resistance and the uterine artery Doppler waveform resistive index; the mean component of flow (mean pressure/resistance) decreased. Decreased uterine artery Doppler resistive index occurred despite angiotensin II-induced vasoconstriction and increased vascular resistance because the pulse component of flow (pulse pressure/impedance) decreased.     

The direct effects of circulating lidocaine on uterine blood flow and foetal well-being in the pregnant ewe

We infused lidocaine intravenously into 13 pregnant ewes at a rate sufficient to maintain plasma levels between 2-4 mugm/ml, which are those commonly seen with regional anaesthesia. These levels did not change maternal blood pressure, pulse rate, cardiac output, stroke volume, total peripheral resistance, uterine blood flow or intra-amniotic pressure. Foetal blood pressure and pulse rate remained stable as did both maternal and foetal blood gases and acid-base values.     

The influence of premedication on heart rate variability

Analysis of heart rate variability has been used to study the effects of midazolam, morphine and clonidine on the autonomic nervous system, when administered to patients for premedication. Ninety-five patients were studied 60 min before and 60 min after premedication. Normal saline (n = 25), midazolam 0.08 mg.kg-1 (n = 24), morphine 0.15 mg.kg-1 (n = 23), or clonidine 2 micrograms.kg-1 (n = 23) were administered intramuscularly by random allocation. A Holter device was connected to the patient during the study period. Using power spectral analysis the low-frequency and high-frequency components were calculated from the Holter recordings. These are markers for sympathetic and parasympathetic activity respectively; the low- to high-frequency ratio was also calculated, a ratio of > 1 signifying sympathetic dominance. A significant reduction was noticed in both low-frequency and high-frequency power in the three premedicated groups, whereas no changes were observed in the normal saline group. In the case of midazolam, both the low and high frequencies were decreased but the low- to high-frequency ratio did not change significantly. Morphine and clonidine depressed the low-frequency component more than the high-frequency component and the low- to high-frequency ratio was decreased, suggesting parasympathetic dominance. We conclude that heart rate variability may be a useful tool for investigating the effect of drugs on the autonomic nervous system.     

Age-dependent influence on heart rate variability in salt-sensitive hypertensive subjects

OBJECTIVE: The known association between systemic arterial hypertension in its initial stages and increased sympathetic nervous system drive prompted us to evaluate the influence of age on autonomic nervous system function in subjects with salt-sensitive arterial hypertension. DESIGN: In a randomized study, autonomic nervous system function was assessed by power spectral analysis of heart-rate variability calculated with an autoregressive algorithm in salt-sensitive hypertensives and controls at baseline and under sympathetic stress (passive head-up tilt). For 1 week before the study, all subjects kept to a diet supplying 120 mEq sodium. Sodium sensitivity was assessed by measuring and comparing arterial pressures after a 7-day controlled dietary sodium intake of 20 mEq per day after a 7-day period on 220 mEq sodium/day. SETTING: Geriatric division at the I Medical Clinic of the University of Rome "La Sapienza". PARTICIPANTS: Sixty-five patients with salt-sensitive hypertension (age range 19 to 89 years) and 64 age-matched normotensive controls, divided for data comparison into three age-groups: < 44 years; 44 to 64 years; and > or = 65 years. MEASUREMENTS: With an autoregressive algorithm in a power spectral analysis of heart rate variability, we detected four spectral frequency-domains: total power (0.0033 to 0.40 Hz), high-frequency power (0.16 to 0.40 Hz), low-frequency power (0.04 to 0.15 HZ) and very-low-frequency power (0.0033 to 0.04 Hz). To determine sodium sensitivity, for 1 week before the study all subjects kept to a diet supplying 120 mEq sodium. Sodium sensitivity was assessed by measuring and comparing arterial pressures after a 7-day controlled dietary intake of 20 mEq per day and after a 7-day period of 220 mEq sodium/day. RESULTS: Results were expressed as natural logarithms of power and normalized units. The hypertensive patients of all ages had significantly lower total power of heart rate variability than the normotensive controls (P < .05). At baseline, the youngest hypertensives had lower natural logarithms and low-frequency normalized units than controls (P < .001). After tilt, only their low-frequency normalized units exceeded those of controls (P < .001). The middle-aged hypertensive group had higher low-frequency normalized units than controls at baseline (P < .05) and after tilt (P < .001). At baseline and after tilt, the oldest hypertensives had lower low-frequency natural logarithms than controls (P < .05) and normalized units equal to those of controls. But the hypertensives of all ages were less able than controls (P < .001) to increase low-frequency power after head-up tilt. In the less than 44-year-old hypertensives, diastolic pressure correlated significantly with low-frequency power of heart rate variability, expressed in normalized units, at baseline (P < .05) and after head-tilt (P < .05). A significant inverse correlation was found between age and the natural logarithm of low-frequency power at baseline (r = -.682, P < .001) and after tilt (r = -.800; P < .001). Also, a significant inverse correlation was found to exist in normotensive subjects between the natural logarithm of low-frequency at baseline (r = -.595; P < .001) and after tilt (r = -.391; P < .001). The two regression line coefficients for age correlated significantly (P < .001) with the natural logarithm of low-power frequency after tilt. CONCLUSION: Whereas sodium chloride-sensitive hypertension appears to be associated with sympathetic hyperactivity in young and middle-aged subjects, in older people it is not. Sympathetic activity diminishes with age, declining faster in hypertensive subjects.     

The effect of uterine contractions on intrapartum fetal heart rate analyzed by a computerized system

In vivo electro-transfection efficiency and manner of transferred gene expression were investigated by fluorescence microscopic image analysis. Green fluorescent protein (GFP) gene was used as the genetic marker. Electroporation was carried out on the liver of live rats by use of disk electrodes mounted in the tips of tweezers, which were directly pressed onto the surface of a liver lobe in situ. Electroporation with eight electric pulses of 50 ms in duration at 50 V gave a good efficiency of transfection as judged by the induced GFP expression. Bright fluorescence of GFP appeared as dots, which were scattered around the area damaged by electroporation. The transfection efficiency increased as the amount of injected DNA was increased. The results indicate that the amount of induced gene expression can be controlled. Estimation of the efficiency of electro-gene transfer using the fluorescence of GFP and digital analysis of microscopic images was useful to determine the optimum conditions for local gene therapy in tissues and organs.     

The effect of diazoxide on uterine blood flow in pregnant sheep

Diazoxide, a labor inhibiting agent, was administered intravenously at various rates to seven pregnant, near-term sheep to evaluate its effect on cardiovascular and uterine hemodynamics. Uterine blood flow was measured with electromagnetic flow transducers. Rapid administration of diazoxide resulted in a profound maternal tachycardia with hypotension, an increase in uterine vascular resistance, and a significant decrease in uterine blood flow. With slow infusion of the drug, the changes in heart rate and blood pressure were minimized, uterine vascular resistance was decreased, and uterine blood flow was maintained. Therefore, slow infusion appears to be the preferred method for inhibiting labor with diazoxide.     

Effect of the vascular endothelium on contractions induced by prostaglandin F2 alpha in isolated pregnant guinea pig uterine artery

The purpose of this study was to examine the influence of endothelium on prostaglandin F2 alpha-mediated contractions in pregnant guinea pig uterine artery. Consequently, the effects of prostaglandin F2 alpha on pregnant guinea pig uterine arterial rings with both intact and denuded endothelium were studied. In vessels with denuded endothelium prostaglandin F2 alpha (0.1-10 microM) induced contraction (pD2 = 6.17) with greater potency than in vessels with intact endothelium (pD2 = 5.68). NG-Monomethyl-L-arginine (10 microM) did not affect the concentration-response curve for prostaglandin F2 alpha, regardless of endothelial condition. In contrast, in both types of preparation, indomethacin (10 microM) increased the maximal response value obtained with prostaglandin F2 alpha, but this effect was significantly greater in preparations with intact than in those with denuded endothelium (128.3 versus 206.5%). Moreover, indomethacin shifted the concentration-response curve for prostaglandin F2 alpha to the left only in preparations with intact endothelium. The pKA values for prostaglandin F2 alpha itself did not differ between preparations: 5.41 and 5.52 for pregnant guinea pig uterine artery with and without endothelium, respectively. The receptor reserve expressed as KA/EC50 was significantly greater in rings with denuded (4.44) compared to those in rings with intact endothelium (1.86). We conclude that prostaglandin-F2 alpha-induced contraction in pregnant guinea pig uterine artery is modulated by the vascular endothelium. It is probable that cyclooxygenase products relating to vasodilatation and derived from endothelium mediate this effect, acting as a functional endogenous antagonist and thereby reducing the apparent efficacy and potency of prostaglandin F2 alpha.     

A maternal complex partial seizure in labor can affect fetal heart rate

We describe a 33-year-old woman who had a complex partial seizure during labor. Intrauterine pressure catheter and fetal heart monitoring during the seizure revealed a strong, prolonged uterine contraction and simultaneous significant fetal heart rate deceleration for 3.5 minutes. This patient demonstrates that complex partial seizures may result in uterine hyperactivity during labor, which may result in fetal hypoxia.     

Effect of flecainide on heart rate variability in subjects without coronary artery disease or congestive heart failure

Echocardiography has a role in the management of acute complications of penetrating cardiac trauma. We report the case of a 30-year-old man who sustained a stab wound to the chest. In this case a traumatic perforation of the ventricular septum and the anterior leaflet of the mitral valve caused by a knife occurred without pericardial effusion. The diagnosis was made by transthoracic echocardiography. The ability of transesophageal echocardiography to delineate the intracardiac injuries more precisely helped to guide the surgical procedure.     

Intraobserver variability of pulsatility index measurements in three fetal vessels in the first trimester

PURPOSE: The intraobserver repeatability of pulsatility index measurements in 3 fetal vessels in the early weeks of gestation was evaluated. METHODS: The pulsatility index was calculated from the flow velocity waveforms from 3 fetal vessels in a series of 58 uneventful, low-risk, singleton first-trimester pregnancies using transvaginal color Doppler sonography. The intraobserver repeatability was expressed as the intraclass correlation coefficient. Mean menstrual age at the time of the examination was 10.3 weeks (range, 7.6-13). RESULTS: Flow velocity waveforms from the umbilical artery, abdominal aorta, and middle cerebral artery were obtained in 100% (58/58), 98.3% (57/58), and 100% (34/34) of cases, respectively. The intraclass correlation coefficients for these vessels were 0.89, 0.79, and 0.93, respectively. CONCLUSIONS: The intraobserver repeatability was acceptable for all the vessels studied.     

The influence of prostaglandin F-2alpha on pregnenolone metabolism by the autotransplanted ovary of the ewe

Eight ewes each with an autotransplanted ovary received infusions of tritium-labelled pregnenolone (41 muCi/hr) for 8 hr into the artery supplying the ovary, together with prostaglandin (PG) F-2alpha (30 mug/hr) for 3 hr beginning 2 hr after the start of the pregnenolone infusion. All animals exhibited oestrus 2-3 days after the start of the experiment. During the PGF-2alpha infusion blood flow through the ovaries was increased by 13%, but subsequently returned to pre-infusion levels. Secretion rates of endogenous progesterone and 20alpha-hydroxypregn-4-en-3-one dropped rapidly 5 hr after the PGF-2alpha infusion had started from values of 250 mug/hr and 25 mug/hr to values below 60 mug/hr and 8 mug/hr, respectively. At this time the conversion of radioactive pregnenolone to progesterone was reduced by 50% of its initial value, but the secretion of endogenous pregnenolone and the formation of radioactive metabolites other than progesterone were not diminished. In 4 control animals, which received pregnenolone only, no changes in ovarian blood flow, steroid secretion rates, or in the conversion of labelled pregnenolone were observed. These results suggest a possible involvement of PGF-2alpha in the regulation of progesterone biosynthesis by an action on the 3beta-hydroxysteroid oxidoreductase-delta5(-4) isomerase enzyme system.     

Effect of androstenedione administration on the maternal hypothalamo-pituitary-adreno-placental axis in the pregnant rhesus monkey

To assess the interaction among androgens, placenta, and the hypothalamo-pituitary-adrenal axis we studied effects of androstenedione administered intravascularly to the pregnant monkey on maternal plasma CRH, ACTH, dehydroepiandrosterone sulfate (DHEAS), cortisol, and estradiol concentrations. Ten monkeys (128 +/- 3 days gestation; mean +/- SEM) were instrumented under general halothane anesthesia with maternal femoral artery and venous catheters and uterine electromyogram electrodes. At 137-144 days gestation, baseline maternal femoral artery samples for CRH, ACTH, DHEAS, cortisol, and estradiol measurements were taken at 1.5-h intervals for 7 h starting 2 h before darkness. On the following day, a continuous iv androstenedione infusion (0.3 mg/kg.min at 0.25 ml/h) in 10% intralipid was started at 0930 h in four monkeys; the other six animals received vehicle alone at the same rate starting at the same time. Maternal blood sampling was repeated 1 and 3 days after androstenedione or vehicle administration. Maternal plasma CRH, ACTH, DHEAS, cortisol, and estradiol levels were unaffected by intralipid. In contrast, androstenedione infusion produced a sustained increase in maternal plasma estradiol and a sustained fall in maternal plasma ACTH, but did not affect maternal plasma CRH, DHEAS, or cortisol concentrations. These results provide evidence for negative feedback regulation by androgens at the hypothalamo-pituitary-adrenal axis in the pregnant monkey. Lack of inhibition of maternal plasma CRH after androstenedione administration supports differential regulation of hypothalamic and placental CRH by androgens.