Effect of asthma and six-months high-intensity interval training on heart rate variability during exercise in adolescents.

Little is known regarding the influence of asthma and exercise, and their interaction, on heart rate variability (HRV) in adolescents. Thirty-one adolescents with asthma (13.7±0.9 years; 21.9±3.9 kg·m-2; 19 boys, 12 girls) and thirty-three healthy adolescents (13.8±0.9 years; 20.3±3.2 kg·m-2; 16 boys, 17 girls) completed an incremental ramp test and three heavy-intensity constant-work-rate cycle tests. Thirteen adolescents (7 boys, 6 girls; 6 asthma, 7 control) completed six-months high-intensity interval training (HIIT) and were compared to age- and sex-matched controls. Standard time-domain, frequency-domain and non-linear indices of HRV were derived at baseline, three- and six-months. Asthma did not influence HRV at baseline or following HIIT. Total power, low frequency and normalised low frequency power, and sympathovagal balance increased at three-months in HIIT, subsequently declining towards baseline at six-months. Normalised high frequency power was reduced at three-months in both groups, which was sustained at six-months. No effects of HIIT were observed in the time-domain nor in the non-linear indices. HRV was not influenced by asthma, potentially because such derangements are a function of disease progression, severity or duration. HIIT may be associated with a short-term shift towards greater sympathetic predominance during exercise, perhaps caused by physiological overload and fatigue.

A prospective study of Rivaroxaban for central venous catheter associated upper extremity deep vein thrombosis in cancer patients (Catheter 2).

INTRODUCTION: Patients with cancer are at increased risk of thrombosis, particularly those with central venous catheter (CVC) placement, which may predispose to the development of upper extremity deep vein thrombosis (UEDVT). Standard treatment includes low molecular weight heparin (LMWH) or LMWH bridged to warfarin. The direct oral anticoagulants (DOACs) have become standard of care for uncomplicated venous thromboembolism (VTE), but research in patients with cancer is ongoing. OBJECTIVES: To assess rivaroxaban monotherapy in patients with cancer who develop UEDVT due to CVC for preservation of line function, and safety outcomes of VTE recurrence, bleeding risk and death. MATERIALS AND METHODS: Patients ≥18years of age with active malignancy and symptomatic proximal UEDVT with or without pulmonary embolism (PE), associated with a CVC, were eligible. Treatment included rivaroxaban 15mg oral twice daily for 3weeks, followed by 20mg oral daily for 9weeks. Patients were followed clinically for 12weeks to assess for line function, recurrent VTE and bleeding. RESULTS: Seventy patients (47 women) were included, with mean age 54.1years. The most common malignancy was breast cancer (41%). Preservation of line function was 100% at 12weeks. The risk of recurrent VTE at 12weeks was 1.43%, with one episode of fatal PE. 9 patients (12.9%) experienced 11 total bleeding episodes. CONCLUSIONS: Rivaroxaban showed promise in treating CVC-UEDVT in cancer patients, resulting in preserved line function. However, bleeding rates and a fatal pulmonary embolism on treatment are concerning safety outcomes necessitating further study before rivaroxaban can be recommended.

Perceptions of asthma and exercise in adolescents with and without asthma.

OBJECTIVE: To elicit the views of adolescents, with and without asthma, about exercise and asthma, and the perceived benefits of and barriers to participation. The adolescent views elicited would subsequently inform the design of a high-intensity exercise intervention to improve asthma control. METHODS: Fifty-four adolescents (age 13.1 ± 0.9 years; 26 with asthma) participated in twelve semi-structured group interviews. Questions were structured around knowledge, attitudes and beliefs towards asthma and its impact on exercise participation and lifestyle. The interviews were transcribed verbatim, thematically analysed and presented via diagrams of emergent themes. Ethical approval was granted by the institutional research ethics committee. RESULTS: Fear of an asthma attack emerged as the main barrier to exercise, with many adolescents with asthma withdrawing from exercise as a coping strategy; many healthy adolescents perceived this withdrawal as laziness or an excuse. Despite this, the majority (81%) of adolescents with asthma reported exercise to be their most enjoyable activity. Adolescents suggested incorporating mixed activities, such as team games (e.g., rounders, football, netball), for future interventions to ensure adherence. CONCLUSIONS: Whilst exercise is important in the management of asthma, the tendency of those with asthma to withdraw from exercise to avoid adverse events could be addressed through a games-based high-intensity exercise intervention. Furthermore, educating all adolescents on asthma could simultaneously reduce stigmatisation and enhance exercise engagement.

An experimental evaluation of the Agility MLC for motion-compensated VMAT delivery.

An algorithm for dynamic multileaf-collimator (dMLC) tracking of a target performing a known a priori, rigid-body motion during volumetric modulated arc therapy (VMAT), has been experimentally validated and applied to investigate the potential of the Agility (Elekta AB, Stockholm, Sweden) multileaf-collimator (MLC) for use in motion-compensated VMAT delivery. For five VMAT patients, dosimetric measurements were performed using the Delta(4) radiation detector (ScandiDos, Uppsala, Sweden) and the accuracy of dMLC tracking was evaluated using a gamma-analysis, with threshold levels of 3% for dose and 3 mm for distance-to-agreement. For a motion trajectory with components in two orthogonal directions, the mean gamma-analysis pass rate without tracking was found to be 58.0%, 59.0% and 60.9% and was increased to 89.1%, 88.3% and 93.1% with MLC tracking, for time periods of motion of 4 s, 6 s and 10 s respectively. Simulations were performed to compare the efficiency of the Agility MLC with the MLCi MLC when used for motion-compensated VMAT delivery for the same treatment plans and motion trajectories. Delivery time increases from a static-tumour to dMLC-tracking VMAT delivery were observed in the range 0%­20% for the Agility, and 0%­57% with the MLCi, indicating that the increased leaf speed of the Agility MLC is beneficial for MLC tracking during lung radiotherapy.

An experimental comparison of conventional two-bank and novel four-bank dynamic MLC tracking.

The AccuLeaf mMLC featuring four multileaf-collimator (MLC) banks has been used for the first time for an experimental comparison of conventional two-bank with novel four-bank dynamic MLC tracking of a two-dimensional sinusoidal respiratory motion. This comparison was performed for a square aperture, and for three conformal treatment apertures from clinical radiotherapy lung cancer patients. The system latency of this prototype tracking system was evaluated and found to be 1.0 s and the frequency at which MLC positions could be updated, 1 Hz, and therefore accurate MLC tracking of irregular patient motion would be difficult with the system in its current form. The MLC leaf velocity required for two-bank-MLC and four-bank-MLC tracking was evaluated for the apertures studied and a substantial decrease was found in the maximum MLC velocity required when four-banks were used for tracking rather than two. A dosimetric comparison of the two techniques was also performed and minimal difference was found between two-bank-MLC and four-bank-MLC tracking. The use of four MLC banks for dynamic MLC tracking is shown to be potentially advantageous for increasing the delivery efficiency compared with two-bank-MLC tracking where difficulties are encountered if large leaf shifts are required to track motion perpendicular to the direction of leaf travel.

Fetal thoracoamniotic shunting for large macrocystic congenital cystic adenomatoid malformations of the lung.

OBJECTIVE: To evaluate fetal thoracoamniotic shunting for isolated large macrocystic congenital cystic adenomatoid malformations (CCAM) of the lung. METHODS: This was a retrospective study of 11 fetuses with macrocystic CCAM who underwent thoracoamniotic shunting. This procedure was offered if fetal hydrops or signs of evolving hydrops (such as ascites or polyhydramnios) were present, or when there were very large lesions or lesions rapidly increasing in size. If there were multiple large cysts within the lesion, a single shunt was used, aiming to traverse several cysts. RESULTS: Shunts were inserted at a mean gestational age of 24.6 (range, 17-32) weeks. Marked mediastinal shift was present in all cases. Six fetuses were hydropic and, of the remaining five, one had severe polyhydramnios, three had lesions that were rapidly increasing in size and one had a very large lesion at initial presentation. In total, four cases had polyhydramnios. Shunting one cyst always decompressed the entire lesion and hydrops and/or polyhydramnios resolved in all surviving fetuses. One hydropic fetus that underwent the procedure at 17 weeks died 1 day later. The shunt dislodged in one case and the lesion did not re-expand. No mother went into labor or had ruptured membranes before 35.6 weeks. Mean gestational age at delivery was 38.2 weeks (n = 10). All pregnancies were delivered vaginally, with no maternal complications. All newborns had uneventful lobectomies, and pathology confirmed CCAM in all cases. CONCLUSION: Fetal thoracoamniotic shunting for large macrocystic CCAM is associated with favorable outcome in most cases, and should be considered in severe cases even before hydrops develops.

MLC tracking for Elekta VMAT: a modelling study.

A model has been developed to simulate volumetric modulated arc therapy (VMAT) delivery for Elekta control systems. The model was experimentally validated for static-tumour VMAT delivery and has been applied to the investigation of motion compensation with dynamic multileaf collimator (dMLC) delivery tracking for a series of VMAT lung treatment plans at various control point spacings for five patients. The relative increase in treatment time with dMLC tracking was calculated for four 1D rigid-body motion trajectories, and the effect of the control point spacing, the MLC leaf speed and an increased number of dose levels on the dMLC tracking delivery time evaluated. It has been observed that a faster leaf speed is advantageous for motion trajectories with shorter time periods and larger amplitudes. The accuracy of dMLC tracking was found to increase with a decreased control point spacing and is dependent on the amplitude and time period of the motion trajectory of the target. dMLC tracking is shown to be a promising emerging technology which can confer advantage over breath-hold motion-compensation techniques which more drastically reduce the efficiency of VMAT and are more invasive for the patient.

Fetal sensory-elicited body movements differ in breech compared to cephalic position.

Behavior was examined in 28 near term fetuses in the breech versus cephalic position. Breech fetuses had fewer body movements to a vibroacoustic stimulus and more to an airborne sound. These findings raise the possibility of differential perceptual experience before birth.

Prion diseases and the gastrointestinal tract.

The gastrointestinal (GI) tract plays a central role in the pathogenesis of transmissible spongiform encephalopathies. These are human and animal diseases that include bovine spongiform encephalopathy, scrapie and Creutzfeldt-Jakob disease. They are uniformly fatal neurological diseases, which are characterized by ataxia and vacuolation in the central nervous system. Although they are known to be caused by the conversion of normal cellular prion protein to its infectious conformational isoform (PrPsc) the process by which this isoform is propagated and transported to the brain remains poorly understood. M cells, dendritic cells and possibly enteroendocrine cells are important in the movement of infectious prions across the GI epithelium. From there, PrPsc propagation requires B lymphocytes, dendritic cells and follicular dendritic cells of Peyer's patches. The early accumulation of the disease-causing agent in the plexuses of the enteric nervous system supports the contention that the autonomic nervous system is important in disease transmission. This is further supported by the presence of PrPsc in the ganglia of the parasympathetic and sympathetic nerves that innervate the GI tract. Additionally, the lymphoreticular system has been implicated as the route of transmission from the gut to the brain. Although normal cellular prion protein is found in the enteric nervous system, its role has not been characterized. Further research is required to understand how the cellular components of the gut wall interact to propagate and transmit infectious prions to develop potential therapies that may prevent the progression of transmissible spongiform encephalopathies.

Oral versus vaginal misoprostol for induction of labor: a double-blind randomized controlled trial.

OBJECTIVE: To determine the efficacy of oral misoprostol (50 microg) administered every 3 hours compared to vaginal misoprostol (50 microg) administered every 6 hours for induction of labor. STUDY DESIGN: In this double-blind randomized trial, 126 women received misoprostol (50 microg) either orally every 3 hours or vaginally every 6 hours for induction of labor. Outcomes included time from induction to delivery, oxytocin augmentation, incidence of hyperstimulation and tachysystole, mode of delivery, and neonatal outcomes. RESULTS: Median time to delivery was shorter in those women who were receiving vaginal misoprostol (vaginal 14.3 hours vs oral 23.1 hours; P =.0004) and more women in the oral group required oxytocin augmentation of labor (73% vs 42%) (RR, 1.98; 95% CI, 1.29 to 3.06). The incidence of hyperstimulation was similar between the groups, but there was an increased incidence of tachysystole in the vaginal group (26.5% vs 9.7%)(RR, 2.74; 95% CI, 1.16 to 6.51). There was no difference between the groups with respect to mode of delivery or neonatal outcome. CONCLUSION: Vaginal misoprostol administered every 6 hours is more effective for induction of labor than oral misoprostol administered every 3 hours. The higher rates of tachysystole with use of vaginal misoprostol in the current study warrant further investigation.

A comparison of oral and vaginal misoprostol for induction of labour at term: a randomised trial.

OBJECTIVE: To compare the efficacy of oral with vaginal misoprostol for induction of labour at term. DESIGN: Randomised trial. SETTING: Tertiary Care hospital. PARTICIPANTS: One hundred and sixty-seven women requiring induction of labour. METHODS: The women were randomised to receive 50 microg of misoprostol orally or vaginally every 6 h until the cervix was favourable for amniotomy, spontaneous rupture of membranes, or active labour occurred. Sample size was calculated with a two-tailed alpha of 0.05 and a power of 95% to detect a 5 h difference in induction-to-delivery time. Student's t test was used for comparison of normally distributed continuous variables and the Mann-Whitney U test was used for non-Gaussian distributed continuous variables. Fisher' s exact and chi2 tests were used for comparison of categorical variables. The main outcome measure was induction to delivery time. RESULTS: The median induction to delivery time was significantly shorter with vaginal misoprostol (15.7 h range 4.3-55.7), compared with oral misoprostol (23.0 h range 3.2-141.7, P = 0.0013). The median number of doses was also significantly less in the vaginal misoprostol group, 1 (range 1-3), compared with the oral group, 2 (range 1-8), (P < 0.0001). The significant differences in outcome held true when nulliparous and multiparous women were analysed separately. There were no differences between the two routes of administration with respect to rates of hyperstimulation or neonatal asphyxia. There were more caesarean sections in the vaginal misoprostol group, but the difference was not statistically significant. CONCLUSIONS: Compared with oral misoprostol, vaginal misoprostol for induction of labour at term results in a shorter induction-to-delivery time, with fewer doses required per patient. Vaginal misoprostol may be associated with higher rates of caesarean section than oral misoprostol.

Effects of human pregnancy on cardiac autonomic function above and below the ventilatory threshold.

This study examined the effects of human pregnancy on heart rate variability (HRV), spontaneous baroreflex (SBR) sensitivity, and plasma catecholamines at rest and during exercise. Subjects were 14 healthy, physically active pregnant women (PG; mean gestational age = 33.9 +/- 1.0 wk). Results were compared with an age-matched nonpregnant control group (NPG; n = 14) with similar characteristics. The electrocardiographic R-wave-R-wave interval and systolic blood pressure (via finger plethysmograph) were measured on a beat-to-beat basis at rest and during upright cycling at 60 and 110% of the ventilatory threshold (T(vent)). Parasympathetic nervous system (PNS) modulation (as reflected by HRV high-frequency/total power and SBR slope) was significantly reduced at rest in the PG vs. the NPG. During exercise, PNS modulation decreased significantly in both groups, but the magnitude of PNS withdrawal from rest to 110% T(vent) was smaller in the PG vs. NPG. Sympathetic nervous system (SNS) modulation (reflected by the low-frequency power-to-high-frequency power ratio) increased above resting values at 60 and 110% T(vent) in the NPG. SNS modulation at 110% T(vent) was significantly lower in the PG compared with the NPG. Plasma norepinephrine and epinephrine levels were also lower at 110% T(vent) in the PG. It was concluded that healthy pregnant women exhibit lower PNS modulation at rest and blunted SNS modulation during exercise above T(vent) in late gestation.

Maximal exercise testing in late gestation: maternal responses.

OBJECTIVE: To study the effects of human pregnancy on metabolic and respiratory responses to maximal cycle ergometer testing and to test the hypothesis that the respiratory exchange ratio at maximal exercise and peak postexercise lactate concentration are lower in the pregnant compared with the nonpregnant state and that these effects are associated with lower excess postexercise oxygen consumption during pregnancy. METHODS: The pregnant (n = 14, mean gestational age 34.7 +/- 0.4 weeks) and nonpregnant control group (n = 14) included healthy, physically active women. Groups were matched for age, height, parity, prepregnant body mass and body mass index (BMI), and aerobic fitness. Breath-by-breath gas exchange was measured at rest, during exercise, and 15 minutes after exercise. The minimum sample size to detect a statistically significant result for a reasonable difference (0.25 L/min) in the ventilatory threshold was calculated to be ten subjects per group; thus, 14 was considered adequate. RESULTS: Maximal oxygen uptake, the ventilatory threshold, the point of respiratory compensation, and calculated work efficiency did not differ significantly between groups. However, the respiratory exchange ratio at maximal exercise, peak postexercise lactate, and excess postexercise oxygen consumption were significantly lower in the pregnant group. Peak lactate was significantly correlated with the respiratory exchange ratio and excess postexercise oxygen consumption. CONCLUSION: The capacity for weight-supported work is preserved in late gestation, and work efficiency is unchanged. However, carbohydrate utilization might be blunted at high levels of exertion. Blunted respiratory responses were attributed to reduced lactate production and/or dilution of lactate in an expanded blood volume.

Maximal exercise testing in late gestation: fetal responses.

OBJECTIVE: To determine the fetal response to and safety of maximal maternal exercise in the third trimester. METHODS: Twenty-three active women with uncomplicated pregnancies (singleton gestations) underwent maximal exercise testing in late gestation using a progressive maximal cycle ergometer protocol. Fetal heart rate (FHR) responses were monitored and classified using National Institute of Child Health and Human Development guidelines. Statistical analyses involved use of the Student t test, repeated measures analysis of variance with Tukey-Kramer multiple comparisons posttest, and the chi(2) test. RESULTS: There was an increase in baseline FHR in the 20-minute posttest period compared with the 20-minute pretest period. There were significantly fewer accelerations in the second posttest 10-minute segment compared with the second pretest 10-minute segment. Variability was reduced in both posttest periods compared with the first 10-minute pretest period. Time to reactivity increased after testing. Mild tachycardia was noted in two tracings and bradycardia occurred in a fetus with previously undiagnosed growth restriction. There were no abnormal neonatal outcomes. CONCLUSION: Maximal exercise testing in late gestation led to minimal changes in FHR. Fetal bradycardiac responses were not seen in appropriate for gestational age fetuses, suggesting that brief maximal maternal exertion for research or diagnostic purposes is safe in this group.

Unilateral thalamic infarction and vertical gaze palsy: cause or coincidence?

Although vertical gaze palsy (VGP) is commonly associated with lesions of the rostral mesencephalon, there is some evidence that VGP may also be caused by a unilateral thalamic lesion. The case of a 68-year-old man with persistent upward gaze palsy after a unilateral thalamic infarction, demonstrated on computed tomography and magnetic resonance imaging scans, is presented. Subsequent high-resolution magnetic resonance scanning, however, showed involvement of the rostral mesencephalon as well. The authors suggest that in previous patients with VGP ascribed to a unilateral thalamic infarction, a coexisting mesencephalic involvement may have been missed because of inappropriate imaging techniques. Strong evidence of unilateral thalamic infarction as a cause of VGP is still lacking.

Fetal responses to maternal strength conditioning exercises in late gestation.

Cardiovascular responses to strength conditioning exercises were examined in 12 healthy pregnant women and their unborn fetuses during the third trimester. A group of 12 healthy nonpregnant women of similar ages, parity, body height, and pre-pregnant body mass was also studied. Maternal heart rate and blood pressure and fetal heart rate (FHR) responses were measured in both the supine (30 degrees tilt) and seated postures during handgrip (HG), single-leg extension (SL), and double-leg extension (DL) exercise. Subjects performed 3 sets of 10 reps at 50, 70, and 90% of their 10-repetition maximum (10-RM) for each exercise in both postures. Pregnant subjects exhibited higher heart rates but similar blood pressure responses to control subjects under all experimental conditions. Significant increases were observed for the frequency of FHR accelerations (0.10 to 0.27/min) from rest to DL in the sitting posture at 90% RM. Moderate fetal bradycardia was observed occasionally in the tilted supine posture at rest and both during (SL, DL) and following (HG, SL, DL) exercise, suggesting that this posture should be avoided in late gestation. The results support the safety of moderate strength conditioning exercises in healthy pregnancy.