Nonlinear heart rate dynamics: circadian profile and influence of age and gender.

Heart rate variability (HRV) is used as a marker of autonomic modulation of heart rate. Nonlinear HRV parameters providing information about the scaling behaviour or the complexity of the cardiac system were included. In addition, the chaotic behaviour was quantified by means of the recently developed numerical noise titration technique. 24h Holter recordings of a large healthy population (N=276, 141 males, 18-71 years of age) were available. The goal was to investigate the influence of gender, age and day-night variation on these nonlinear HRV parameters. Numerical titration yielded similar information as other nonlinear HRV parameters do. However, it does not require long and cleaned data and therefore applicable on short (5min) noisy time series. A higher nonlinear behaviour was observed during the night (NLdr; day: 50.8±19.6%, night: 59.1±19.5%; P<0.001) while nonlinear heart rate fluctuations decline with increasing age (NLdr; Pearson correlation coefficient r between -0.260 and -0.319 dependent on gender and day or night, all P<0.01). A clear circadian profile could be found for almost every parameter, showing in particular which changes occur during the transition phases of waking up and going to sleep. Our results support the involvement of the autonomic nervous system in the generation of nonlinear and complex heart rate dynamics.

Effect of endurance training on blood pressure regulation, biomarkers and the heart in subjects at a higher age.

We reported previously that two otherwise identical training programs at lower (LI) and higher intensity (HI) similarly reduced resting systolic blood pressure (BP) by approximately 4-6 mmHg. Here, we determined the effects of both programs on BP-regulating mechanisms, on biomarkers of systemic inflammation and prothrombotic state and on the heart. In this cross-over study (3 × 10 weeks), healthy participants exercised three times 1 h/week at, respectively, 33% and 66% of the heart rate (HR) reserve, in a random order, with a sedentary period in between. Measurements, performed at baseline and at the end of each period, involved blood sampling, HR variability, systolic BP variability (SBPV) and cardiac magnetic resonance imaging. Thirty-nine participants (18 men; mean age 59 years) completed the study. Responses were not different between both programs (P>0.05). Pooled data from LI and HI showed a reduction in HR (-4.3 ± 8.1%) and an increase in stroke volume (+11 ± 23.1%). No significant effect was seen on SBPV, plasma renin activity, basal nitric oxide and left ventricular mass. Our results suggest that the BP reduction observed appears to be due to a decrease in systemic vascular resistance; training intensity does not significantly affect the results on mechanisms, biomarkers and the heart.

Operational point of neural cardiovascular regulation in humans up to 6 months in space.

Entering weightlessness affects central circulation in humans by enhancing venous return and cardiac output. We tested whether the operational point of neural cardiovascular regulation in space sets accordingly to adopt a level close to that found in the ground-based horizontal position. Heart rate (HR), finger blood and brachial blood pressure (BP), and respiratory frequency were collected in 11 astronauts from nine space missions. Recordings were made in supine and standing positions at least 10 days before launch and during spaceflight (days 5-19, 45-67, 77-116, 146-180). Cross-correlation analyses of HR and systolic BP were used to measure three complementary aspects of cardiac baroreflex modulation: 1) baroreflex sensitivity, 2) number of effective baroreflex estimates, and 3) baroreflex time delay. A fixed breathing protocol was performed to measure respiratory sinus arrhythmia and low-frequency power of systolic BP variability. We found that HR and mean arterial pressure did not differ from preflight supine values for up to 6 mo in space. Respiration frequency tended to decrease during prolonged spaceflight. Concerning neural markers of cardiovascular regulation, we observed in-flight adaptations toward homeostatic conditions similar to those found in the ground-based supine position. Surprisingly, this was not the case for baroreflex time delay distribution, which had somewhat longer latencies in space. Except for this finding, our results confirm that the operational point of neural cardiovascular regulation in space sets to a level close to that of an Earth-based supine position. This adaptation level suggests that circulation is chronically relaxed for at least 6 mo in space.

Effects of aerobic training intensity on resting, exercise and post-exercise blood pressure, heart rate and heart-rate variability.

We aimed to investigate the effects of endurance training intensity (1) on systolic blood pressure (SBP) and heart rate (HR) at rest before exercise, and during and after a maximal exercise test; and (2) on measures of HR variability at rest before exercise and during recovery from the exercise test, in at least 55-year-old healthy sedentary men and women. A randomized crossover study comprising three 10-week periods was performed. In the first and third period, participants exercised at lower or higher intensity (33% or 66% of HR reserve) in random order, with a sedentary period in between. Training programmes were identical except for intensity, and were performed under supervision thrice for 1 h per week. The results show that in the three conditions, that is, at rest before exercise, during exercise and during recovery, we found endurance training at lower and higher intensity to reduce SBP significantly (P<0.05) and to a similar extent. Further, SBP during recovery was, on average, not lower than at rest before exercise, and chronic endurance training did not affect the response of SBP after an acute bout of exercise. The effect of training on HR at rest, during exercise and recovery was more pronounced (P<0.05) with higher intensity. Finally, endurance training had no significant effect on sympathovagal balance. In conclusion, in participants at higher age, both training programmes exert similar effects on SBP at rest, during exercise and during post-exercise recovery, whereas the effects on HR are more pronounced after higher intensity training.

Emergence of bluetongue serotypes in Europe, part 2: the occurrence of a BTV-11 strain in Belgium.

An EDTA-blood sample from a cow without clinical signs, which gave early birth to a newborn calf that died soon after delivery, was shown to be positive for bluetongue virus (BTV)-RNA using a group-specific real-time RT-PCR (RT-qPCR). In-house serotype-specific RT-qPCR assays for bluetongue virus serotype 1 (BTV-1), -6 and -8 all gave negative results. Subsequent assays were carried out using conventional (gel-based) RT-PCR primers for all 25 BTV serotypes and only two primer sets, both specific for BTV-11, gave bands of the expected size. The cDNAs generated were sequenced and comparisons of the genome segment 2 sequence with that of the modified 'live' vaccine strain of BTV-11 from South Africa showed 100% identity. A survey of all ruminants in a 1-km area around the first positive farm using a BTV-11 serotype-specific RT-qPCR revealed five other holdings with in total nine BTV-11 positive animals. A cross-sectional monitoring of dairy cattle in Belgium showed an overall prevalence of 3.8% on herd level and 0.2% on animal level. A BTV-11 has been introduced into the Belgian cattle herd during the 2008 vector season. The source of the infection and the way by which the virus was introduced are unknown.

Bluetongue in Belgium: episode II.

Bluetongue (BT) is an arthropod-borne viral disease of ruminants. In August 2006, domestic ruminant populations in Northern Europe became infected with BT virus serotype 8 (BTV-8). The first BTV-8-case of the year 2007 in Belgium was notified in July. This case was the starting point of a second wave of BT outbreaks. The main objective of this study was to describe the evolution and the clinical impact of the second episode of BT in Belgium. In addition, the main differences with the previous episode (August-December 2006) are reported. Both outbreak and rendering plant data were analysed. Overall cumulative incidence at herd level was estimated at 11.5 (11.2-11.8) and 7.5 (7.3-7.8) per cent in cattle and sheep populations respectively. The findings went in favour of a negative association between within-herd prevalence in 2006 and the risk of showing clinical signs of BT in 2007 (via protective immunity). A high level of correlation was demonstrated between BT incidence and small ruminant mortality data when shifting the latter of 1-week backwards. This result supports the hypothesis that the high increase in small ruminant mortality observed in 2007 was the consequence of the presence of BT. For cattle, the correlation was not as high. An increase in cattle foetal mortality was also observed during the year 2007 and a fair correlation was found between BT incidence and foetal mortality.

Effect of 35 years beta-adrenergic blockade therapy on autonomic cardiovascular modulation. A case study.

The influence of long duration beta-blockade on autonomic and cardiovascular function remains not completely understood. The aim of this study was to evaluate the effect of long duration beta-adrenergic blockade treatment for hypertension control, on autonomic cardiovascular control in a 78-year-old male patient in relation to population findings. Heart rate variability was determined in the frequency domain (Total power, low frequency power and high frequency power), during baseline (supine and standing) and during 24 hour Holter recording. Results were compared with heart rate and heart rate variability data obtained from a normal healthy male population as a function of age. Circadian rhythm remained present. Heart rate during daytime was lower compared to the population group. None of the heart rate variability parameters were different from the normal population age group. Our results show that after 35 years of beta-blockade treatment, autonomic modulation of cardiac function remains within normal limits for that age group. Blood pressure remained at the higher limits (120-150/60-80 mmHg), but under control.

Transplacental infection and apparently immunotolerance induced by a wild-type bluetongue virus serotype 8 natural infection.

Until recently, bluetongue (BT) virus (BTV) serotypes reportedly causing transplacental infections were all ascribed to the use of modified live virus strains. During the 2007 BT epidemic in Belgium, a significant increase in the incidence of abortions was reported. A study including 1348 foetuses, newborns and young animals with or without suspicion of BTV infection, was conducted to investigate the occurrence of natural transplacental infection caused by wild-type BTV-8 and to check the immunocompetence of newborns. BTV RNA was present in 41% and 18.5% of aborted foetuses from dams with or without suspected BTV involvement during pregnancy, respectively. The results of dam/calf pairs sampled before colostrum uptake provide evidence of almost 10% transplacental BTV infection in newborns. Apparently immunotolerant calves were found at a level of 2.4%. The current study concludes that the combined serological and real-time PCR (RT-qPCR) result of pregnant dams gives no indication of the infection status of the offspring except in the case of a double negative result. In a group of 109 calves with clinical suspicion of BT, born during the vector-free period, 11% were found to be RT-qPCR positive. The true prevalence was estimated to be 2.3%, indicating the extent of transplacental infection in a group of 733 calves of one to 4 months of age without BT suspicion. Moreover, virus isolation was successful for two newborn calves, emphasizing the need for restricting trade to BT-free regions of pregnant dams possibly infected during gestation, even if they are BTV RT-qPCR negative.

Establishing the spread of bluetongue virus at the end of the 2006 epidemic in Belgium.

Bluetongue (BT) was notified for the first time in several Northern European countries in August 2006. The first reported outbreaks of BT were confirmed in herds located near the place where Belgium, The Netherlands and Germany share borders. The disease was rapidly and widely disseminated throughout Belgium in both sheep and cattle herds. During the epidemic, case reporting by the Veterinary Authorities relied almost exclusively on the identification of herds with confirmed clinical infected ruminants. A cross-sectional serological survey targeting all Belgian ruminants was then undertaken during the vector-free season. The first objective of this study was to provide unbiased estimates of BT-seroprevalence for different regions of Belgium. Since under-reporting was suspected during the epidemic, a second goal was to compare the final dispersion of the virus based on the seroprevalence estimates to the dispersion of the confirmed clinical cases which were notified in Belgium, in order to estimate the accuracy of the case detection based on clinical suspicion. True within-herd seroprevalence was estimated based on a logistic-normal regression model with prior specification on the diagnostic test's sensitivity and specificity. The model was fitted in a Bayesian framework. Herd seroprevalence was estimated using a logistic regression model. To study the linear correlation between the BT winter screening data and the case-herds data, the linear predicted values for the herd prevalence were compared and the Pearson correlation coefficient was estimated. The overall herd and true within-herd seroprevalences were estimated at 83.3 (79.2-87.0) and 23.8 (20.1-28.1)%, respectively. BT seropositivity was shown to be widely but unevenly distributed throughout Belgium, with a gradient decreasing towards the south and the west of the country. The analysis has shown there was a strong correlation between the outbreak data and the data from the survey (r=0.73, p<0.0001). The case detection system based on clinical suspicion underestimated the real impact of the epidemic, but indicated an accurate spatial distribution of the virus at the end of the epidemic.

Respiratory modulation of cardiovascular rhythms before and after short-duration human spaceflight.

AIM: Astronauts commonly return from space with altered short-term cardiovascular dynamics and blunted baroreflex sensitivity. Although many studies have addressed this issue, post-flight effects on the dynamic circulatory control remain incompletely understood. It is not clear how long the cardiovascular system needs to recover from spaceflight as most post-flight investigations only extended between a few days and 2 weeks. METHODS: In this study, we examined the effect of short-duration spaceflight (1-2 weeks) on respiratory-mediated cardiovascular rhythms in five cosmonauts. Two paced-breathing protocols at 6 and 12 breaths min(-1) were performed in the standing and supine positions before spaceflight, and after 1 and 25 days upon return. Dynamic baroreflex function was evaluated by transfer function analysis between systolic pressure and the RR intervals. RESULTS: Post-flight orthostatic blood pressure control was preserved in all cosmonauts. In the standing position after spaceflight there was an increase in heart rate (HR) of approx. 20 beats min(-1) or more. Averaged for all five cosmonauts, respiratory sinus dysrhythmia and transfer gain reduced to 40% the day after landing, and had returned to pre-flight levels after 25 days. Low-frequency gain decreased from 6.6 (3.4) [mean (SD)] pre-flight to 3.9 (1.6) post-flight and returned to 5.7 (1.3) ms mmHg(-1) after 25 days upon return to Earth. Unlike alterations in the modulation of HR, blood pressure dynamics were not significantly different between pre- and post-flight sessions. CONCLUSION: Our results indicate that short-duration spaceflight reduces respiratory modulation of HR and decreases cardiac baroreflex gain without affecting post-flight arterial blood pressure dynamics. Altered respiratory modulation of human autonomic rhythms does not persist until 25 days upon return to Earth.

Mode of action of 2-furylmercury chloride, an anti-rhinovirus compound.

2-Furylmercury chloride (2-FMC), an organic mercury derivative, has been found to inhibit the replication of all tested human rhinovirus (HRV) serotypes belonging to the antiviral group B and a limited number of HRV serotypes belonging to the antiviral group A. The mechanism of action of 2-FMC was tested against HRV-2 (antiviral group B, minor receptor group), and compared with an antiviral compound for which the viral target was already determined (enviroxime). 2-FMC was found to bind reversibly to virus particles. However, time-dependent plaque reduction assays revealed that 2-FMC did not interfere with early events of HRV-2 replication. Using a quantitative RT-PCR ELISA assay, we were able to prove that 2-FMC inhibits the synthesis of viral RNA. However, the mode of action of 2-FMC is not identical to that of enviroxime, another inhibitor of viral RNA synthesis. Time-of-addition and time-of-withdrawal experiments demonstrated that 2-FMC acted during a broader time interval than enviroxime.

Long-term safety and tolerability of tadalafil in the treatment of erectile dysfunction.

OBJECTIVE: To assess the long-term safety and tolerability of tadalafil for patients with erectile dysfunction (ED). PATIENTS AND METHODS: This was a multicentre, open-label, 24-month extension trial involving 1173 men with ED. The mean age was 57 (range 23-83) years and 74.8% of patients were taking concomitant medications for comorbid conditions, including diabetes mellitus in 30.5% of men and hypertension in 29.5%. These patients had participated in 1 of 5 previous 8-week or 12-week randomised, double-blind, placebo-controlled tadalafil studies. In the present trial, the starting 10mg dose of tadalafil could be increased to 20mg if the patient could not achieve satisfactory intercourse or reduced to 5mg for an adverse event that was persistent, intolerable and judged by the investigator to be related to tadalafil. RESULTS: Four hundred ninety-three (42.0%) men completed 24 months of treatment. In addition, a further 234 (19.9%) completed 18 months of treatment due to a sponsor decision to reduce the study duration. The total tadalafil exposure was 1676.0 patient-years. Tadalafil was safe and well tolerated. Headache (15.8%), dyspepsia (11.8%), nasopharyngitis (11.4%), and back pain (8.2%) were the most common treatment-emergent adverse events. The rate of discontinuations due to adverse events for this 18-24-month study was 6.3% and the rate for any individual event was <1%. Serious adverse events occurred in 8.6% of patients. No consistent pattern of serious adverse events assessed as causally associated with tadalafil administration was observed. None of the four deaths that occurred during the study was assessed as tadalafil related. There were no clinically significant laboratory or electrocardiographic findings or changes in vital signs in mean baseline-to-endpoint analysis attributable to tadalafil. Tadalafil administration was not causally associated with drug-induced hepatotoxicity, neutropenia, thrombocytopenia, or renal dysfunction. CONCLUSION: Tadalafil at doses of 5, 10, or 20mg taken as needed up to once daily for 18 to 24 months was safe and well tolerated. These findings support the long-term use of tadalafil in the clinical management of erectile dysfunction.

Quantitative RT-PCR ELISA to determine the amount and ratio of positive- and negative strand viral RNA synthesis and the effect of guanidine in poliovirus infected cells.

Quantitative reverse transcription-polymerase chain reaction enzyme linked immunosorbent assay (RT-PCR ELISA) is the method of choice to study positive- and negative strand viral RNA synthesis during poliovirus replication. In comparison with other methods used for this purpose, it fulfils all necessary requirements to accurately determine RNA of different polarity. It combines high specificity, high sensitivity, safety, speed, and the ability to perform quantitative analysis. The enterovirus specific RT-PCR ELISA method described in this work, was used to determine quantitatively the amount of de novo poliovirus positive- and negative strand RNA synthesis at different time-points in the viral replication cycle, both in presence and absence of the viral RNA synthesis inhibitor guanidine hydrochloride.

Parasympathetic heart rate modulation during parabolic flights.

During parabolic flight short periods of microgravity and hypergravity are created. These changes influence cardiovascular function differently according to posture. During the 29th parabolic flight campaign of the European Space Agency (ESA), the electrocardiogram (ECG) was recorded continuously in seven healthy volunteers in two positions (standing and supine). Five different phases were differentiated: 1 g (1 g=9.81 m/s(2)) before and after each parabola, 1.8 g at the ascending leg of the parabola (hypergravity), 0 g at the apex, 1.6 g at the descending leg (hypergravity). We assessed heart rate variability (HRV) by indices of temporal analysis [mean RR interval (meanRR), the standard deviation of the intervals (SDRR), and the square root of the mean squared differences of successive intervals (rMSSD) and coefficient of variation (CV)]. In the supine position no significant differences were shown between different gravity phases for all HRV indices. In the standing position the 0 g phase showed a tendency towards higher values of meanRR compared to the control and to the other phases ( p=NS). SDRR, rMSSD and CV were significantly higher compared to control ( p<0.05). Significantly higher values for meanRR in the supine position at 1 g and hypergravity ( p<0.05) were found when compared to standing. SDRR was significantly higher at 0 g in the standing position compared to supine [95 (44) ms vs. 50 (15) ms; p<0.05] and lower in other phases. rMSSD and CV showed the same trend ( p=NS). We confirm that, during parabolic flights, position matters for cardiovascular measurements. Time domain indices of HRV during different gravity phases showed: (1) higher vagal modulation of the autonomic nervous system in microgravity, when compared with normo- or hypergravity in standing subjects; and (2) no differences in supine subjects between different g phases.

Capsid and RNA stabilisation of the oral polio vaccine.

The oral polio vaccine is the least stable vaccine of the common childhood vaccines. Two different inactivation mechanisms are responsible for the thermolability of the vaccine, i.e. denaturation of the viral capsid and degradation of the viral RNA within the capsid. Pirodavir, a capsid-binding compound, inhibits the viral capsid thermodenaturation. In this paper we show that deuterium oxide is able to stabilise the viral RNA against thermodegradation and that a combination of pirodavir and deuterium oxide leads to an additive effect indicating that both stabilisers work indeed on different inactivation mechanisms. Furthermore, it is shown that the variation in thermostability of the different vaccine strains is due to the different thermostability of their capsids.

Can NPTR data predict the cause of organic impotence?

Conventional diagnostic evaluation, including color duplex doppler ultrasound of the penile vessels, pharmaco-cavernosometry, intracavernosal drug testing and neurologic tests, were used to classify 78 patients with complaints of erectile impotence into one of the following three groups: non-organogenic, arteriogenic, vascular and neurogenic impotence. Nocturnal penile tumescence and rigidity (NPTR) measurements were also performed. Differentiation between patients with organic and non-organic impotence proved possible. The "best night" and "best erection" alone could not outline a pathognomonic pattern for the different causes of organic impotence.

Value of transrectal prostatic echography, prostate-specific antigen and rectal examination in the diagnosis of prostate cancer. Relationship with the result of prostatic biopsies.

UNLABELLED: We retrospectively reviewed the files of patients who had undergone a prostatic biopsy between July 1992 and December 1994. A total of 368 biopsies of 340 patients between 36 and 89 years old, could be used. The pathological examination was used to make the diagnosis of prostate cancer. The specificity and sensitivity values of the diagnostic examinations (TRUS, DRE, PSA and PSAD) were calculated. An abnormal TRUS image (hypodens or hyperdens area or irregular prostate) has the best sensitivity: 91.3%. PSA has the best specificity: 57.2%. The specificity and sensitivity of PSA can be improved by using the PSAD: a PSAD limit of 0.15 has a specificity of 66.4% and a sensitivity of 88.9%. The specificity and sensitivity values are also calculated for several combinations of tests. The combination of abnormal DRE or PSAD higher than 0.15 has a sensitivity of 96.2% and a specificity of 35.0%. CONCLUSION: the combination of abnormal DRE or high PSAD has a high sensitivity with a relatively good specificity. We advise to take biopsy if two or more of the examinations are suspect or if one of them is clearly abnormal.

Transurethral microwave thermotherapy in the treatment of chronic abacterial prostatitis: a 2 years follow-up.

OBJECTIVE: Transurethral microwave thermotherapy (TUMT) is a minimally invasive, outpatient treatment, applied as a single session of 1-hour duration. SUBJECTS AND METHODS: A group of 11 patients with chronic abacterial prostatitis, who failed to respond to a variety of conventional treatments, underwent this therapy in our centre. RESULTS: The results after two years of follow-up are encouraging: 88% remain free of symptoms. CONCLUSION: Thermotherapy seems to add a new alternative for this hard to manage disease.

An unusual coincidence of endometriosis and ovarian stimulation.

This report describes a rare coincidence of ureteral endometriosis and ovarian stimulation. A patient presented with acute renal colic after ovarian stimulation. Although rare intrinsic ureteral endometriosis should be considered when establishing differential diagnosis. Laparoscopic treatment for extensive endometriosis has been described but should only be performed by very experienced operative laparoscopists. A new long-term post-operative treatment is proposed combining LH-RH analogues with the new molecule tibolone as add-back therapy.