A measure of heart rate variability is sensitive to orthostatic challenge in women with chronic fatigue syndrome

The use of symptoms generated by head up tilt (HUT) is not a useful tool in identifying chronic fatigue syndrome (CFS). We investigated whether heart rate variability (HRV) assessed early during HUT might be useful. A sample of 46 female subjects (24 with CFS and 22 sedentary, age-matched healthy controls; CON) who had exhibited no difference in time to syncope during tilt was examined for HRV responses to 10 min of 70 degrees HUT after 5 min of baseline in the supine position. HRV data were analyzed by the method of coarse graining spectral analysis. Variables compared between groups included mean and standard deviation (SD(RRI)) of RR intervals (RRI), amplitudes of low- (A(LF); 0.04-0.15 Hz) and high-frequency (A(HF); >0.15 Hz) harmonic as well as aperiodic, fractal (A(FR); 1/f(beta)) spectral components, the spectral exponent beta, and the difference in these values between baseline and HUT for each subject. In the supine baseline, only mean RRI was significantly (P < 0.01) lower in CFS than in CON. During HUT, however, mean RRI (P < 0.01), SD(RRI) (P < 0.01), A(HF) (P < 0.05), and A(FR) (P < 0.01) were significantly lower in CFS than in CON. When the difference in values between baseline and HUT for each subject was examined, only the difference for A(FR) (deltaA(FR)) was significantly (P < 0.01) lower in CFS than in CON, suggesting that A(FR)is a disease-specific response of HRV to HUT. When a cut-off level was set to deltaA(FR) = -2.7 msec, the sensitivity and the specificity in differentiating CFS from controls were 90% and 72%, respectively. The data suggest that a decrease in aperiodic fractal component of HRV in response to HUT can be used to differentiate patients with CFS from CON.     

Physiological responses of aged men to head-up tilt during heat exposure

The effects of age on cardiovascular and thermoregulatory responses to passive tilting were investigated using six old (61-73 yr) and 10 young (21-39 yr) unacclimatized men. Experiments were carried out at 26 degrees C and after exposure to 40 degrees C and 40% relative humidity for 105 min. Continuous measurements of esophageal (Tes) and mean skin (Tsk) temperatures and heart rate (HR) were recorded. Other variables studied included blood pressure (BP), forearm blood flow (FBF), and cardiac output (CO), which were measured at 4- to 5-min intervals. Measurements were made in the supine position and after 70 degrees head-up tilt for 15 min. Cardioacceleration during the tilt test was greater in the young men than in the old. Other cardiovascular responses of the old men to orthostatism were qualitatively similar to that of the young except for FBF and forearm vascular conductance. The old men did not show significant changes in FBF during tilting, suggesting a deterioration in the sympathetic nervous reflex in the aged. However, other circulatory adaptations seemed to overcome this deficiency resulting in orthostatic tolerance similar to that of the young. During head-up tilt at 26 and 40 degrees C, Tes of both age groups increased. This may reflect a decrease in conductive heat transfer presumably due to diminished blood flow to the periphery.     

Heart rate variability and cardiac reflexes in small for gestational age infants.

To assess the influence of intrauterine growth retardation and postnatal development on heart rate variability (HRV) and cardiac reflexes, we studied 27 healthy small for gestational age (SGA) and 23 appropriate for gestational age (AGA) infants during a nap study. Resting HRV was assessed by point dispersion of Poincaré plots for overall (SDRR) and instantaneous beat-to-beat variability (SDDeltaRR) and the ratio (SDRR/SDDeltaRR). Heart rate reflex and arousal responses to a 60 degrees head-up tilt were determined. All tests/measures were repeated twice in quiet and active sleep and in prone and supine sleep positions at 1 and 3 mo of age. SGA infants exhibited higher resting sympathetic tone [SDRR/SDDeltaRR: 1.9 (95% confidence interval: 1.7, 2.0) and 1.7 (95% confidence interval: 1.5, 1.8) in SGA and AGA, respectively; P=0.046] and a tendency for a smaller tachycardic reflex response to the tilt [Deltaheart rate: 24 beats/min (95% confidence interval: 20, 28) and 30 (95% confidence interval: 25, 34)] in SGA and AGA, respectively; P=0.06]. HRV indexes were reduced in the prone compared with supine position (P<0.0001), but reflex tilt responses were unchanged with position. SGA/AGA differences were independent of sleep position. Gestational age weight status did not influence the likelihood of arousal, but prone sleeping per se reduced the odds 2.5-fold. The findings suggest reduced autonomic activity and cardiac reflexes in SGA infants. The finding that the sympathetic component of the control of HRV was higher in SGA infants could link with findings in adulthood of an association between being born SGA and a higher risk of cardiovascular disease.     

Identification and Prediction of Diabetic Sensorimotor Polyneuropathy Using Individual and Simple Combinations of Nerve Conduction Study Parameters

Objective

Evaluation of diabetic sensorimotor polyneuropathy (DSP) is hindered by the need for complex nerve conduction study (NCS) protocols and lack of predictive biomarkers. We aimed to determine the performance of single and simple combinations of NCS parameters for identification and future prediction of DSP.

Materials and Methods

406 participants (61 with type 1 diabetes and 345 with type 2 diabetes) with a broad spectrum of neuropathy, from none to severe, underwent NCS to determine presence or absence of DSP for cross-sectional (concurrent validity) analysis. The 109 participants without baseline DSP were re-evaluated for its future onset (predictive validity). Performance of NCS parameters was compared by area under the receiver operating characteristic curve (AROC).

Results

At baseline there were 246 (60%) Prevalent Cases. After 3.9 years mean follow-up, 25 (23%) of the 109 Prevalent Controls that were followed became Incident DSP Cases. Threshold values for peroneal conduction velocity and sural amplitude potential best identified Prevalent Cases (AROC 0.90 and 0.83, sensitivity 80 and 83%, specificity 89 and 72%, respectively). Baseline tibial F-wave latency, peroneal conduction velocity and the sum of three lower limb nerve conduction velocities (sural, peroneal, and tibial) best predicted 4-year incidence (AROC 0.79, 0.79, and 0.85; sensitivity 79, 70, and 81%; specificity 63, 74 and 77%, respectively).

Discussion

Individual NCS parameters or their simple combinations are valid measures for identification and future prediction of DSP. Further research into the predictive roles of tibial F-wave latencies, peroneal conduction velocity, and sum of conduction velocities as markers of incipient nerve injury is needed to risk-stratify individuals for clinical and research protocols.     

Sexual development in early- and late-maturing Bos indicus and Bos indicus x Bos taurus crossbred bulls in Brazil

Two experiments were conducted to evaluate sexual development in early- and late-maturing Nelore (Bos indicus) and Canchim (3/8 Bos indicus x 5/8 Bos taurus crossbred) bulls and to determine predictors of sexual precocity, and pubertal and maturity status. In Experiment 1, 12 Nelore bulls where examined from 300 to 900 days of age. Puberty was characterized by an ejaculate containing > or =50 million sperm with > or =10% motile sperm, and maturity by an ejaculate containing > or =70% morphologically normal sperm. In Experiment 2, 28 Canchim bulls where examined from 295 to 488 days of age and puberty was characterized by an ejaculate containing > or =30% motile sperm. In both experiments, bulls were classified as early- or late-maturing based on age at puberty. Early-maturing bulls were younger (P < 0.05) than late-maturing bulls at puberty (527 days versus 673 days in Experiment 1 and 360 days versus 461 days in Experiment 2) and at maturity (660 days versus 768 days in Experiment 1). In general, early-maturing bulls were heavier and had greater scrotal circumference (SC), testes, and testicular vascular cone diameter than late-maturing bulls during the experimental period. Scrotal circumference adjusted for 365 days of age was a good predictor of sexual precocity; minimum yearling SC of 19 and 24 cm for Nelore and Canchim bulls, respectively, had the best predictive values. Early-maturing bulls were lighter and had smaller SC at puberty than late-maturing bulls; therefore, sexual precocity was not related to the attainment of a threshold body weight or testicular size earlier, but to lower thresholds in early-maturing bulls. When predictors of pubertal status were evaluated, SC had the best sensitivity/specificity relationship in Nelore bulls, and high sensitivity and specificity in Canchim bulls. When predictors of sexual maturity were evaluated in Nelore bulls, age, weight, and SC had similar sensitivity, specificity, and predictive values. At puberty, approximately 60% of the sperm present in the ejaculate were morphologically defective. Changes in semen quality after puberty in Nelore bulls were characterized by increased motility and proportion of morphologically normal sperm, with a decrease in the proportion of major sperm defects. In conclusion, early-maturing bulls were more developed in the pre-pubertal period and attained puberty at earlier stages of body and testicular development than late-maturing bulls. Yearling SC could be used to select bulls for sexual precocity and SC was the best predictor of pubertal status. Age, weight, and SC were equally good predictors of sexual maturity in B. indicus bulls.     

Assessment of parasympathetic reactivation after exercise

The objective of this study was to evaluate whether heart rate variability (HRV) can be used as an index of parasympathetic reactivation after exercise. Heart rate recovery after exercise has recently been shown to have prognostic significance and has been postulated to be related to abnormal recovery of parasympathetic tone. Ten normal subjects [5 men and 5 women; age 33 +/- 5 yr (mean +/- SE)] exercised to their maximum capacity, and 12 subjects (10 men and 2 women; age 61 +/- 10 yr) with coronary artery disease exercised for 16 min on two separate occasions, once in the absence of atropine and once with atropine (0.04 mg/kg) administered during exercise. The root mean square residual (RMS), which measures the deviation of the R-R intervals from a straight line, as well as the standard deviation (SD) and the root mean square successive difference of the R-R intervals (MSSD), were measured on successive 15-, 30-, and 60-s segments of a 5-min ECG obtained immediately after exercise. In recovery, the R-R interval was shorter with atropine (P < 0.0001). Without atropine, HRV, as measured by the MSSD and RMS, increased early in recovery from 4.1 +/- 0.4 and 3.7 +/- 0.4 ms in the first 15 s to 7.2 +/- 1.0 and 7.4 +/- 0.9 ms after 1 min, respectively (P < 0.0001). RMS (range 1.7-2.1 ms) and MSSD were less with atropine (P < 0.0001). RMS remained flat throughout recovery, whereas MSSD showed some decline over time from 3.0 to 2.2 ms (P < 0.002). RMS and MSSD were both directly related (r(2) = 0.47 and 0.56, respectively; P < 0.0001) to parasympathetic effect, defined as the difference in R-R interval without and with atropine. In conclusion, RMS and MSSD are parameters of HRV that can be used in the postexercise recovery period as indexes of parasympathetic reactivation after exercise. These tools may improve our understanding of parasympathetic reactivation after exercise and the prognostic significance of heart rate recovery.     

Calf blood flow during prolonged tilt in idiopathic dilated cardiomyopathy and after cardiac transplantation

In severe congestive heart failure (CHF), abnormal reflex control of calf blood flow during brief head-up tilt that appears to normalize after transplantation (HTX) may be present during prolonged observation also. Therefore, we studied the effect of prolonged (30 min) 50 degrees head-up tilt on calf skeletal muscle blood flow measured by the local (133)Xe washout method in CHF and after HTX and in patients with the presence vs. absence of native right atrium (+PNA and -PNA, respectively). During brief head-up tilt, skeletal muscle blood flow increased 13 +/- 42% in 9 severe CHF patients in contrast to a -28 +/- 22% decrease (P < 0.01) in 11 control subjects, -24 +/- 30% decrease in 15 moderate CHF patients (P < 0.05), -25 +/- 14% decrease in 12 patients with recent HTX (P < 0.01), and -21 +/- 24% decrease in 8 patients with distant HTX (P = 0.06). However, during sustained tilt, blood flow declined to similar levels of that in the other groups in severe CHF. HTX -PNA vs. +PNA showed blunted skeletal muscle vasomotor control (P < 0.05) and a higher systolic blood pressure (139 +/- 14 vs. 125 +/- 15 mmHg, P < 0.05) and heart rate (92 +/- 10 vs. 83 +/- 8 beats/min, P < 0.05). Thus paradox vasodilatation of calf skeletal muscle in severe CHF is present only during brief but not prolonged tilt. This may be one explanation of the rare presence of orthostatic intolerance in CHF and implies only a minor possible role for the abnormality in edema pathogenesis. Removal of all right atrium in HTX has an important hemodynamic impact that may possibly affect later clinical outcome.     

Age dependency of cardiovascular autonomic responses to head-up tilt in healthy subjects.

In elderly subjects, heart rate responses to postural change are attenuated, whereas their vascular responses are augmented. Altered strategy in maintaining blood pressure homeostasis during upright position may result from various cardiovascular changes, including age-related cardiovascular autonomic dysfunction. This exploratory study was conducted to evaluate impact of age on cardiovascular autonomic responses to head-up tilt (HUT) in healthy subjects covering a wide age range. The study population consisted of 63 healthy, normal-weight, nonsmoking subjects aged 23-77 yr. Five-minute electrocardiogram and finger blood pressure recordings were performed in the supine position and in the upright position 5 min after 70 degrees HUT. Stroke volume was assessed from noninvasive blood pressure signals by the arterial pulse contour method. Heart rate variability (HRV) and systolic blood pressure variability (SBPV) were analyzed by using spectral analysis, and baroreflex sensitivity (BRS) was assessed by using sequence and cross-spectral methods. Cardiovascular autonomic activation during HUT consisted of decreases in HRV and BRS and an increase in SBPV. These changes became attenuated with aging. Age correlated significantly with amplitude of HUT-stimulated response of the high-frequency component (r = -0.61, P < 0.001) and the ratio of low-frequency to high-frequency power of HRV (r = -0.31, P < 0.05) and indexes of BRS (local BRS: r = -0.62, P < 0.001; cross-spectral baroreflex sensitivity in the low-frequency range: r = -0.38, P < 0.01). Blood pressure in the upright position was maintained well irrespective of age. However, the HUT-induced increase in heart rate was more pronounced in the younger subjects, whereas the increase in peripheral resistance was predominantly observed in the older subjects. Thus it is likely that whereas the dynamic capacity of cardiac autonomic regulation decreases, vascular responses related to vasoactive mechanisms and vascular sympathetic regulation become augmented with increasing age.     

Influence of the presence of a mature female on puberty attainment in gilts

At 90 days of age, 40 Large White gilts were assigned to one of two treatments. At 155 days, a mature female which was left intact (Treatment I) or ovariectomized (Treatment O) was placed in each pen of five experimental gilts. From 180 days, estrus was checked daily with the back pressure test, and the occurrence of ovulation was detected by measuring the concentration of plasma progesterone at weekly intervals. From 240 days, a mature boar was introduced, for 5 minutes daily, into each pen during estrus detection. Gilts were slaughtered within 12 days after ovulation or at 270 days of age if they were not cyclic earlier. The percentage of gilts reaching puberty before 225 days of age was significantly higher in Treatment I (7 19 ) than in Treatment O (0 19 ) even though the average age at puberty was similar (I, 231 +/- 24 days; O, 243 +/- 12 days; mean +/- SD). Age at puberty and the number of days between mature female introduction and puberty differred significantly between the pens of gilts in Treatment O but not in Treatment I. Ovarian weights, ovulation rate and percentage of gilts with silent estrus were similar in the two treatments. Thus, the occurrence of pubertal estrus may be influenced by contact with an older, cyclic female or with other contemporary females raised in the same pen.     

Comparison of cardiovascular response to passive tilt in young and elderly men

To test the hypothesis that altered hemodynamic responses to postural changes are associated with aging, cardiovascular responses to head-up tilt (HUT) and head-down tilt (HDT) were examined in 12 healthy young (average age, 24.6 +/- 1.7 years) and 12 healthy elderly (average age, 68.6 +/- 2.2 years) men. Subjects were passively tilted from supine to 30 degrees, 60 degrees, and 90 degrees HUT and HDT. Responses to these perturbations were determined 5 min after tilting with measures of heart rate (HR), blood pressure (SBP, DBP), and echocardiographically determined left ventricular diameter in systole and diastole (LVIDs, LVIDd). In HUT there were no significant age effects. In both young and elderly, SBP decreased significantly (p less than 0.05), and DBP and HR increased significantly. Ejection fraction (EF), mean arterial blood pressure (MABP), and rate-pressure product (RPP) were unchanged in both groups. In HDT, the hemodynamic responses of the young and elderly were in opposite directions and significant age effects were found for SBP, DBP, HR, LVIDs, EF, MABP, and RPP. In HDT, the young appear to increase cardiac output primarily due to an increase in EF and end-diastolic volume (LVIDd), while HR is unchanged and SBP is decreased. MABP is unchanged, suggesting a small decrease in total peripheral resistance. The elderly may increase cardiac output slightly, owing to an increase in LVIDd with no change in EF, and a large increase in HR. Afterload increased markedly, therefore attenuating any increase in cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS)     

全身运动质量评估联合颅脑超声对脑损伤高危儿运动发育结局的预测价值

摘要 目的：研究全身运动（GMs）质量评估和颅脑超声（CUS）在脑损伤高危儿运动发育结局中的预测价值。方法：选取2019年10月至2021年6月入住徐州医科大学附属医院新生儿重症监护室（NICU）具有脑损伤高危因素的早产儿605例,建立随访档案。入院24h、3d、7d内各做一次CUS检查,异常者每周复查1次直至出院,记录最异常结果。矫正胎龄36～40周行扭动运动GMs质量评估,矫正3～6月龄行不安运动GMs质量评估。矫正12月龄通过Gesell发育量表和小儿脑瘫诊断分型标准明确运动发育结局,分析GMs质量评估、CUS对不良运动发育结局和脑瘫的预测效度。结果：最终获得完整随访资料的脑损伤高危儿为536例,随访至12月龄的运动发育结局为运动发育正常424例,运动发育迟缓105例,脑瘫7例。扭动运动GMs质量评估对运动发育结局预测的敏感性为56.25%、特异性为82.78%;不安运动GMs质量评估对运动发育结局预测的敏感性为73.21%、特异性为98.82%;CUS对运动发育结局预测的敏感性为54.46%、特异性为94.34%。扭动运动GMs质量评估联合CUS对运动发育结局预测的敏感性为81.25%、特异性为81.13%;不安运动GMs质量评估联合CUS对运动发育结局预测的敏感性为84.82%、特异性为96.46%。GMs质量评估和CUS对脑瘫预测的敏感性和阴性预测值均为100.00%;联合应用GMs质量评估和CUS可明显提高对不良运动结局的敏感性及阳性预测值。结论：CUS对脑损伤高危儿的不良运动发育结局尤其是脑瘫具有良好的预测价值,GMs质量评估联合CUS可明显提升对脑损伤高危儿不良运动发育结局的早期预测价值。     

Two molecular forms of plasma adrenomedullin during tilt test in healthy subjects.

There is accumulating evidence suggesting that adrenomedullin (AM) may participate in the regulation of circulatory homeostasis and pathophysiology of cardiovascular disease. A recent study revealed that two molecular forms of AM, an active form of mature AM (AM-m) and an intermediate inactive form of glycine-extended AM (AM-Gly), circulate in human plasma. The object of the present study was to evaluate the effect of orthostasis on a time course of two molecular forms of plasma AM and to compare them with the behavior of other vasoactive hormones. Twelve healthy male volunteers were studied. The experimental protocol consisted of 20 min of supine rest, tilting at 70 degrees for 20 min, and then 20 min of supine rest. Blood pressure and heart rate were measured every minute. Blood samples were obtained before, at 2 and 18 min during the tilt test, and 2 and 18 min after the test for the measurements of vasoacting hormones and hematocrit. Blood pressure and heart rate were slightly increased earlier during tilting and then remained elevated until the end of the test. The increase in heart rate and blood pressure returned to normal levels early after the tilt test. Plasma epinephrine and norepinephrine significantly increased during the tilt test. These hormones returned to normal levels 18 min after the test. The plasma renin activity, antidiuretic hormone and dopamine were also increased by the end of the tilt test, whereas plasma atrial natriuretic peptide was significantly decreased after the tilt test. Hematocrit increased slightly in the early phase of the tilt test and was further increased by the end of the test. In contrast, plasma AM-Gly or AM-m did not change during the tilt test or the recovery period. Nitric oxide metabolites did not change, either. There were no significant relationships between plasma catecholamines and AM. Plasma brain natriuretic peptide did not change during the tilt test or the recovery period, either. These results suggest that the two molecular forms of AM, AM-m and AM-Gly in plasma, did not respond to the short term tilting stress. These findings may support the hypothesis that plasma AM is secreted in a constitutive manner from the vascular wall.     

Autonomic cardiovascular and respiratory control during prolonged spaceflights aboard the International Space Station.

Impaired autonomic control represents a cardiovascular risk factor during long-term spaceflight. Little has been reported on blood pressure (BP), heart rate (HR), and heart rate variability (HRV) during and after prolonged spaceflight. We tested the hypothesis that cardiovascular control remains stable during prolonged spaceflight. Electrocardiography, photoplethysmography, and respiratory frequency (RF) were assessed in eight male cosmonauts (age 41-50 yr, body-mass index of 22-28 kg/m2) during long-term missions (flight lengths of 162-196 days). Recordings were made 60 and 30 days before the flight, every 4 wk during flight, and on days 3 and 6 postflight during spontaneous and controlled respiration. Orthostatic testing was performed pre- and postflight. RF and BP decreased during spaceflight (P < 0.05). Mean HR and HRV in the low- and high-frequency bands did not change during spaceflight. However, the individual responses were different and correlated with preflight values. Pulse-wave transit time decreased during spaceflight (P < 0.05). HRV reached during controlled respiration (6 breaths/min) decreased in six and increased in one cosmonaut during flight. The most pronounced changes in HR, BP, and HRV occurred after landing. The decreases in BP and RF combined with stable HR and HRV during flight suggest functional adaptation rather than pathological changes. Pulse-wave transit time shortening in our study is surprising and may reflect cardiac output redistribution in space. The decrease in HRV during controlled respiration (6 breaths/min) indicates reduced parasympathetic reserve, which may contribute to postflight disturbances.     

Voluntarily Produced Increases in Heart Rate Variability Modulate Autonomic Effects of Endotoxin Induced Systemic Inflammation: An Exploratory Study

Exposure of healthy people to lipopolysaccharide (LPS; endotoxin) produces a pro-inflammatory response, subjective symptoms, and decreased heart rate variability (HRV). Given the efficacy of HRV biofeedback (BF) for treating asthma, the large autonomic effects of HRV BF, and the link between vagus nerve activity and inflammation, we hypothesized that HRV BF would dampen the acute manifestations of systemic inflammation induced by LPS challenge. Healthy participants age 18-40 were randomly assigned to four-one-hour training sessions of either HRV BF (n = 6) or a control 15/min paced breathing condition (n = 5) prior to acute experimentally induced LPS exposure. Participants were coached to do the procedures for 10 min each at five hourly time points after LPS injection, and then 2 h later. Subjective symptoms, HRV parameters, and plasma cytokine levels were measured at each time point, 2 h afterward, and the following morning. Participants were able to perform the procedures both during four pre-exposure training sessions and while experiencing LPS-induced symptoms. The HRV BF group showed significant attenuation of the LPS-induced decline in HRV for the 6 h following LPS exposure, suggesting that HRV BF decreased autonomic dysfunction produced by LPS-induced inflammation. HRV BF also reduced symptoms of headache and eye sensitivity to light, but did not affect LPS-induced levels of pro-inflammatory cytokines or symptoms of nausea, muscle aches, or feverishness. Further evaluation of HRV BF appears to be warranted among patients with inflammatory conditions.     

Chronic leptin infusion advances, and immunoneutralization of leptin postpones puberty onset in normally fed and feed restricted female rats

Does leptin play a vital role in initiating puberty in female rats and can it overrule a nutrionally imposed (i.e. a 30% feed restriction, FR) delay in puberty onset? Prepubertal female rats were chronically infused for 14 days with leptin (icv or sc) or leptin-antiserum (icv) while puberty onset was monitored by means of scoring the moment of vaginal opening (VO). Median VO age was higher (35 days versus 27 days) in FR animals but leptin levels at VO were significantly decreased (1.44 +/- 0.17 ng/ml versus 2.79 +/- 0.31 ng/ml). Centrally (icv) and peripherally (sc) infused leptin (1 microg/day) advanced VO age compared to FR controls (30 days versus 35 days and 31 days versus 41 days, respectively). Congruently, centrally (icv) administered leptin-antiserum (0.6 microg/day) delayed puberty onset. In normally fed rats median VO age was only marginally advanced (26 days versus 27 days) but only if leptin was applied centrally. The effects of FR on puberty onset are counteracted or even normalized by the infusion of leptin, whereas immunoneutralization of central leptin postpones puberty onset. We therefore conclude that central leptin is crucial for initiating puberty in female rats.     

Decrease in cardiac output and muscle sympathetic activity during vasovagal syncope

The importance of cardiac output (CO) to blood pressure level during vasovagal syncope is unknown. We measured thermodilution CO, mean blood pressure (MBP), and leg muscle mean sympathetic nerve activity (MSNA) each minute during 60 degrees head-up tilt in 26 patients with recurrent syncope. Eight patients tolerated tilt (TT) for 45 min (mean age 60 +/- 5 yr) and 15 patients developed syncope during tilt (TS) (mean age 58 +/- 4 yr, mean tilt time 15.4 +/- 2 min). In TT patients, CO decreased during the first minute of tilt (from 3.2 +/- 0.2 to 2.5 +/- 0.3 l x min(-1) x m(-2), P = 0.001) and thereafter remained stable between 2.5 +/- 0.3 (P = 0.001) and 2.4 +/- 0.2 l x min(-1) x m(-2) (P = 0.004) at 5 and 45 min, respectively. In TS patients, CO decreased during the first minute (from 3.3 +/- 0.2 to 2.7 +/- 0.1 l x min(-1) x m(-2), P = 0.02) and was stable until 7 min before syncope, falling to 2.0 +/- 0.2 at syncope (P = 0.001). Regression slopes for CO versus time during tilt were -0.01 min(-1) in TT versus -0.1 l x min(-1) x m(-2) x min(-1) in TS (P = 0.001). However, MBP was more closely correlated to total peripheral resistance (R = 0.56, P = 0.001) and MSNA (R = 0.58, P = 0.001) than CO (R = 0.32, P = 0.001). In vasovagal reactions, a progressive decline in CO may contribute to hypotension some minutes before syncope occurs.     

The relationship between secretory patterns of gonadotrophic hormones and the attainment of puberty in bull and heifer calves born early or late during the spring calving season

It was suggested that an early increase in gonadotrophin secretion in calves aged between 6 and 24 weeks might be critical for initiating developmental changes culminating in puberty. An early rise in luteinizing hormone (LH) release appears to be caused by an increase in LH pulse frequency in bull calves and by an increase in LH pulse amplitude in heifer calves. Previously we have found differences in the characteristics of the LH rise between prepubertal beef calves born in spring or fall; however, age at puberty was not affected by season of birth. Here we report the LH/FSH secretory patterns in prepubertal bull and heifer calves (Hereford x Charolais), born in March or April, respectively (i.e., early or late during the spring calving season; six animals of each sex born at each time). The bull calves of both groups reached puberty (defined as an attainment of scrotal circumference of >or=28 cm) at 43.2+/-1.3 weeks of age (P>0.05). Age at puberty for March- and April-born heifer calves (defined as the age at which serum progesterone concentrations first exceeded 0.4 ng/ml) averaged 56.0+/-1.4 weeks (P>0.05). Based on blood samples taken weekly from birth to 26 weeks of age, and then every other week until puberty, bull calves born in March exceeded April-born bull calves in mean serum LH concentrations at 6, 10 and 12 weeks of age (P<0.05). Mean FSH concentrations were greater (P<0.05) in March-born compared to April-born bull calves from 34 to 32 weeks before puberty. Mean serum LH (at 40, 42 and 56 weeks) and FSH concentrations (at 2, 10, 20, 22-26, 30 and 56 weeks of age) were greater (P<0.05) in heifer calves born in April than March. On the basis of frequent blood sampling (every 12 min for 10 h), heifer calves born in April exceeded March-born animals in mean LH and FSH concentrations, at 5 and 25 weeks, and LH pulse frequency, at 5, 10 and 25 weeks of age (P<0.05). None of the parameters of LH secretion (i.e., mean concentrations of LH, LH pulse frequency and amplitude based on frequent blood collection) differed between March- and April-born bull calves in this study (P>0.05). In summary, March-born bull calves had greater mean serum LH and FSH concentrations prior to 24 weeks of age than April-born calves. April-born heifer calves had greater mean serum concentrations of LH and FSH but this difference was not confined to the early postnatal period. Although there were significant differences in absolute amounts of LH secreted, there were no differences in the frequency of LH secretory pulses amongst March- and April-born bull calves and no differences in LH pulse amplitude in heifer calves born in March or April. As these particular parameters of LH secretion, as well as age at puberty, are not affected by the time or season of birth, they may be primary hormonal cues governing sexual development in bulls and heifers, respectively.     

Causes of precocious puberty in children referred for evaluation in hospital conditions

INTRODUCTION: Symptoms of precocious puberty (PP) in children always arouse anxiety in their parents. Many children with PP are being hospitalized for the detailed diagnostic work-up. The aim of our study was to analyze the frequency of the variants of PP in children referred to our department. MATERIAL: Retrospective analysis of 119 children (103 girls and 16 boys) referred for hospitalization in the years 2003-2005 due to signs of precocious puberty was performed. RESULTS: Premature thelarche, benign variant of puberty, was diagnosed in 62 (53%) girls, in the mean age of 3.39 (+/- 2.33) years. Their mean height was within 0.7 +/- 1.1 SD. Premature pubarche was diagnosed 30 (25%) children--22 girls and 8 boys in the mean age was 7.24 (+/- 0.81) years. Their mean height was 1.3 +/- 1.0 SD and was significantly higher than normal (p < 0.0001). Premature menarche was diagnosed in 8 (7%) girls in the mean age 4.81 +/-2.26 years. Mean height in this group was normal for age (0.9+/-0.8 SD). PP was diagnosed in 19 (16%) children (11 girls and 8 boys) in the mean age 5.91 +/- 1.63 years. Mean height in this group was 1.6 +/- 0.7 SD, and was significantly higher than the mean for age (p<0.0005). GnRH-dependent type was present in 15 children, diagnosed as idiopathic in 9 girls and 1 boy. In 5 children (4 boys and 1 girl) pathology of central nervous system was found. In 4 children GnRH-independent precocious puberty was diagnosed--in 3 caused by congenital adrenal hyperplasia and in 1 boy by tumour of testis (leydigioma). CONCLUSIONS: Girls with precocious thelarche without growth acceleration present the benign variant of puberty and need clinical follow up only. Boys with clinical signs of precocious puberty should be carefully evaluated to rule out the organic cause.     

Regulation of rat hepatic cytochrome P-450: age-dependent expression, hormonal imprinting, and xenobiotic inducibility of sex-specific isoenzymes

The influence of age, sex, and hormonal status on the expression of eight rat hepatic cytochrome P-450 (P-450) isoenzymes was evaluated by both catalytic and immunochemical methods. The male specificity of P-450 2c(male)/UT-A, the major microsomal steroid 16 alpha-hydroxylase of uninduced rat liver [Waxman, D.J. (1984) J. Biol. Chem. 259, 15481-15490], was shown to reflect its greater than or equal to 30-fold induction at puberty in male but not in female rats. The female specificity of P-450 2d(female)/UT-I was shown to reflect its developmental induction in females. P-450 PB-2a/PCN-E was shown to mediate greater than or equal to 85% of microsomal steroid 6 beta-hydroxylase activity; the male specificity of this P-450 largely reflects its developmental suppression in female rats. Neonatal gonadectomy and hormonal replacement experiments established that neonatal androgen "imprints" or programs the male rat for developmental induction of P-450 2c(male)/UT-A, for maintenance of P-450 PB-2a/PCN-E, and for suppression of P-450 2d(female)/UT-I, all of which occur in male rats at puberty. By contrast, the expressed levels of P-450 isoenzymes PB-1/PB-C, 3/UT-F, PB-4/PB-B, ISF-G, and beta NF-B were mostly unaffected by the rats' age, sex, and hormonal status. Studies on the sex specificity of P-450 induction established that the response of these latter five isoenzymes to the P-450 inducers phenobarbital, beta-naphthoflavone, pregnenolone-16 alpha-carbonitrile, and isosafrole is qualitatively and quantitatively equivalent in females as in males.     

Neonatal Gram Negative and Candida Sepsis Survival and Neurodevelopmental Outcome at the Corrected Age of 24 Months

Objectives

To evaluate the long term neurodevelopmental outcome of premature infants exposed to either gram- negative sepsis (GNS) or neonatal Candida sepsis (NCS), and to compare their outcome with premature infants without sepsis.

Methods

Historical cohort study in a population of infants born at <30 weeks gestation and admitted to the Neonatal Intensive Care Unit (NICU) of the Academic Medical Center in Amsterdam during the period 1997–2007. Outcome of infants exposed to GNS or NCS and 120 randomly chosen uncomplicated controls (UC) from the same NICU were compared. Clinical data during hospitalization and neurodevelopmental outcome data (clinical neurological status; Bayley –test results and vision/hearing test results) at the corrected age of 24 months were collected. An association model with sepsis as the central determinant of either good or adverse outcome (death or severe developmental delay) was made, corrected for confounders using multiple logistic regression analysis.

Results

Of 1362 patients, 55 suffered from GNS and 29 suffered from NCS; cumulative incidence 4.2% and 2.2%, respectively. During the follow-up period the mortality rate was 34% for both GNS and NCS and 5% for UC. The adjusted Odds Ratio (OR) [95% CI] for adverse outcome in the GNS group compared to the NCS group was 1.4 [0.4–4.9]. The adjusted ORs [95% CI] for adverse outcome in the GNS and NCS groups compared to the UC group were 4.8 [1.5–15.9] and 3.2 [0.7–14.7], respectively.

Conclusions

We found no statistically significant difference in outcome at the corrected age of 24 months between neonatal GNS and NCS cases. Suffering from either gram –negative or Candida sepsis increased the odds for adverse outcome compared with an uncomplicated neonatal period.