Influence of physical exercise on baroreceptor sensitivity during pregnancy.

BACKGROUND: Baroreceptor sensitivity (BRS) refers to the magnitude of change in the heart rate in response to change in blood pressure (e.g. upon standing). The impact of regular antenatal exercise on maternal BRS is unclear. AIMS: To determine whether supervised weekly exercise influences BRS, and to determine if posture and calculation method are important in antenatal BRS measurement. STUDY DESIGN AND SUBJECTS: Eighty-one healthy pregnant women were randomly assigned to an exercise or control group. The exercise group attended weekly classes from the 20th week of pregnancy onwards. OUTCOME MEASURES: Cardiovascular assessments (beat-to-beat blood pressure, heart rate) were performed at 12-16, 26-28, 34-36 weeks and 12 weeks following birth. BRS was calculated using two methods ("sequence" and "beat-to-beat"). RESULTS: Fifty-one women (63%) completed the study. Mean BRS reduced progressively in all women (p < 0.025) and was lowest in those who exercised (0.046 < p < 0.002). Postnatal increases in BRS were independent of posture. Training-induced BRS (beat-to-beat) reduction occurred earlier than BRS (sequence), and only BRS (sequence) was affected by posture. Heart rate variability reduced with advancing gestation (p < 0.002) and was more pronounced in the exercise group (p < 0.029). CONCLUSIONS: Weekly exercise exaggerated the reductions in BRS and HRV during pregnancy and is likely linked to diminished parasympathetic activity.

Influence of antenatal physical exercise on heart rate variability and QT variability.

OBJECTIVE: We sought to characterise the influence of an antenatal exercise programme on ECG-derived cardiac variables. METHODS: Fifity-one healthy pregnant women were recruited and randomly assigned (2 × 2×2 design) to an exercise group or a control group. Exercising groups attended weekly classes from the 20th week of pregnancy onwards. Cardiovascular assessments (heart rate variabiliy (HRV), QT, and the QT variability index (QTVI)) were performed at 12-16, 26-28, 34-36 weeks and 12 weeks following birth, during supine rest and exercise conditions. RESULTS: Advancing gestation was associated with an increased maternal heart rate (p = 0.001), shorter QT interval (p = 0.003), diminished HRV (p = 0.002) and increased QTVI (p = 0.002). Each of these changes was reversed within 12 weeks postpartum (p < 0.004). The Exercise group displayed exaggerated changes for all variables (except QT) but only during supine rest in the third trimester (p < 0.029). CONCLUSION: Advancing gestation is associated with a shift in HRV/QTVI towards values that have been associated with an elevated risk of arrhythmia. A 20-week exercise programme undertaken between mid and late pregnancy exaggerated these changes during rest in the third trimester of pregnancy.

Recruitment of pregnant women to an exercise-intervention study.

We share here our experience of recruiting pregnant women into an exercise intervention study. Recruitment challenges were anticipated owing to the study design, which required four hospital visits for cardiovascular assessment, a long-term (nine-month) commitment, and adherence to a 20-week exercise programme. Fifty-three women were assigned to one of three groups (no-exercise, land exercise or water exercise) using a 2 × 2 × 2 flexible randomisation design. Seven hundred forty-four women were screened at an antenatal clinic, of whom 501 were eligible to participate in the study. One hundred forty-five women were subsequently approached: 46 (32%) of whom agreed to participate, 42 (29%) were interested but then declined and 57 (39%) declined outright. Our study design helped recruit pregnant women as it allowed them some choice of group membership. We also noted that the participant-researcher relationship is important in reducing attrition. Our experience provides indications of likely recruitment and attrition rates for future randomised controlled trials of this type.

Changes in heart rate variability and QT variability during the first trimester of pregnancy.

The risk of new-onset arrhythmia during pregnancy is high, presumably relating to changes in both haemodynamic and cardiac autonomic function. The ability to non-invasively assess an individual's risk of developing arrhythmia during pregnancy would therefore be clinically significant. We aimed to quantify electrocardiographic temporal characteristics during the first trimester of pregnancy and to compare these with non-pregnant controls. Ninety-nine pregnant women and sixty-three non-pregnant women underwent non-invasive cardiovascular and haemodynamic assessment during a protocol consisting of various physiological states (postural manoeurvres, light exercise and metronomic breathing). Variables measured included stroke volume, cardiac output, heart rate, heart rate variability, QT and QT variability and QTVI (a measure of the variability of QT relative to that of RR). Heart rate (p < 0.0005, p < 0.0005, p < 0.0005) and cardiac output (p = 0.043, p < 0.0005, p < 0.0005) were greater in pregnant women in all physiological states (respectively for the supine position, light exercise and metronomic breathing state), whilst stroke volume was lower in pregnancy only during the supine position (p < 0.0005). QTe (Q wave onset to T wave end) and QTa (T wave apex) were significantly shortened (p < 0.05) and QTeVI and QTaVI were increased in pregnancy in all physiological states (p < 0.0005). QT variability (p < 0.002) was greater in pregnant women during the supine position, whilst heart rate variability was reduced in pregnancy in all states (p < 0.0005). Early pregnancy is associated with substantial changes in heart rate variability, reflecting a reduction in parasympathetic tone and an increase in sympathetic activity. QTVI shifted to a less favourable value, reflecting a greater than normal amount of QT variability. QTVI appears to be a useful method for quantifying changes in QT variability relative to RR (or heart rate) variability, being sensitive not only to physiological state but also to gestational age. We support the use of non-invasive markers of cardiac electrical variability to evaluate the risk of arrhythmic events in pregnancy, and we recommend the use of multiple physiological states during the assessment protocol.

Transcriptome meta-analysis of peripheral lymphomononuclear cells indicates that gestational diabetes is closer to type 1 diabetes than to type 2 diabetes mellitus.

We performed a meta-analysis of the transcription profiles of type 1, type 2 and gestational diabetes to evaluate similarities and dissimilarities among these diabetes types. cRNA samples obtained from peripheral blood lymphomononuclear cells (PBMC) of 56 diabetes mellitus patients (type 1 = 19; type 2 = 20; gestational = 17) were hybridized to the same whole human genome oligomicroarray platform, encompassing 44,000 transcripts. The GeneSpring software was used to perform analysis and hierarchical clustering, and the DAVID database was used for gene ontology. The gene expression profiles showed more similarity between gestational and type 1 diabetes rather than between type 2 and gestational diabetes, a finding that was not influenced by patient gender and age. The meta-analysis of the three types of diabetes disclosed 3,747 differentially and significantly expressed genes. A total of 486 genes were characteristic of gestational diabetes, 202 genes of type 1, and 651 genes of type 2 diabetes. 19 known genes were shared by type 1, type 2 and gestational diabetes, highlighting EGF, FAM46C, HBEGF, ID1, SH3BGRL2, VEPH1, and TMEM158 genes. The meta-analysis of PBMC transcription profiles characterized each type of diabetes revealing that gestational and type 1 diabetes were transcriptionally related.

Interferon-γ +874 polymorphism in the first intron of the human interferon-γ gene and kidney allograft outcome.

BACKGROUND: Despite advances in immunosuppressive therapy in the past decade, allograft rejection remains an important cause of kidney graft failure. Cytokines play a major role in the inflammatory and immune responses that mediate allograft outcomes. Several studies have shown that the production of cytokines varies among individuals. These variations are determined by genetic polymorphisms, most commonly within the regulatory region of cytokine genes. The aim of the present study was to assess the effect of allelic variation on acute rejection episodes (ARE) or chronic allograft nephropathy (CAN) after kidney transplantation. METHODS: To determine a possible correlation between the interferon (INF)-γ +874 polymorphism and kidney allograft outcome, we isolated genomic DNA from 74 patients who underwent isolated kidney allografts and were classified into 2 groups--a rejection and a nonrejection group--for comparison with a control group of 163 healthy subjects. RESULTS: We genotyped INF-γ +874 polymorphisms in all groups. The transplant group showed a significantly increased homozygous genotype T/T (P = .0118) compared with healthy controls. Similarly, considering only patients with CAN, the homozygous genotype T/T (P = .0067) was significantly increased compared with the healthy controls. The rejection group indicated a significant increased homozygous genotype T/T compared with the control group (P = .0061). CONCLUSION: Homozygous genotype T/T was associated with increased levels of INF-γ and greater numbers among the rejection and CAN cohorts.

Interleukin-17 and kidney allograft outcome.

UNLABELLED: Acute rejection episodes (ARE) are important complications that involve the interplay between mechanisms that maintain graft tolerance and promote rejection. The proinflammatory cytokine interleukin-17 (IL-17) has been implicated in many conditions in humans and mice. In kidney transplant patients, the evaluation IL-17 levels has been performed in only a few patients. We performed a cross-sectional study correlating quantitative IL-17 levels and clinical outcomes. PATIENTS AND METHODS: We studied 19 specimens from biopsies performed in patients (n = 19) who received isolated kidney grafts. ARE signs were present in 9 (47%) patients who provide specimens; whereas, 10 (53%) others showed no signs of rejection. Eighteen healthy control sample IL-17 underwent measurement, all of which were performed by an enzyme-linked immunosorbent assay method. We assessed other factors, such as the recipients demographic data, cold ischemia time, HLA mismatches, time elapsed from transplantation to the biopsy, posttransplantation status, antibody panel, donor type, and immunosuppressive treatment. RESULTS: IL-17 levels were clearly increased among samples derived from patients with ongoing rejection (125.7 +/- 27.06 pg/mL) in contrast, to the nonrejection group, (30 +/- 13.32 pg/mL) (P < .05). Healthy controls showed no detectable IL-17 levels. CONCLUSIONS: These findings suggested that IL-17 was important in the pathophysiology of acute kidney rejection.

HLA polymorphisms as incidence factor in the progression to end-stage renal disease in Brazilian patients awaiting kidney transplant.

Chronic renal failure (CRF) leads in the majority of instances to end-stage renal disease (ESRD) requiring renal replacement therapy. Age, gender, genetics, race, hypertension, and smoking among others are factors associated with ESRD. Our interest was to evaluate the possible associations of class I and II HLA antigens with ESRD renal disease independent of other factors, among patients with CRF, having various diagnoses in the Brazilian population of the São Paulo state. So 21 HLA-A, 31 HLA-B, and 13 HLA-DR were detected in 105 patients who were compared with 160 healthy controls of both sexes who were not related to the patients evaluated until 2005. We calculated allelic frequencies, haplotypes frequencies, etiological fractions (EF), preventive fractions, and relative risks (RR). We compared demographic data of patients and controls. The antigens positively associated with ESRD were: HLA-A78 (RR = 30.31 and EF = 0.96) and HLA-DR11 (RR = 18.87 and EF = 0.65). The antigens HLAB14 (RR = 29.90 and EF = 0.75) was present at a significantly lower frequency among patients compared with controls. In contrast, no haplotype frequency showed statically significant associations. Further molecular studies may clarify types and subtypes of alleles involved with ESRD progression.

Analysis of the QT interval and its variability in healthy adults during rest and exercise.

The aim of the present study was to quantify the variability of electrocardiographic QT and RR intervals during rest and dynamic physical exercise, and to interpret these variabilities in terms of relative autonomic modulation of the atrial and ventricular myocardium. We also sought to characterize the relationships between QT, heart rate-corrected QT (QT(c)) and RR intervals, and to consider their associations with differential autonomic regulation. Nine males and eight females of similar age (22.8 +/- 4.7 years), mass (75.5 +/- 13.0 kg) and aerobic fitness (43.6 +/- 7.7 ml kg(-1) min(-1)) (mean +/- SD) undertook progressive bicycle exercise. A three-lead Holter ECG was recorded continuously during pre-exercise, exercise and recovery, and mean values of RR, QT, QT(c), QT variability index (QTVI) and mean-normalized QT variance (QTVN) were determined. At the onset of exercise QTVI increased rapidly compared with rest and remained significantly elevated throughout exercise and recovery. There were significant differences between QT(a)VI and QT(e)VI (QT measured from Q wave onset to T wave apex (QT(a)) and T wave end (QT(e)), respectively) throughout the experimental protocol. QTVI was significantly reduced in males compared with females prior to exercise but was similar thereafter. We suggest that physical exercise perturbs the resting QT-RR relationship owing to the onset of differential parasympathetic modulation of the atrial and ventricular myocardium. QTVI can be used to quantify the relative autonomic influence on the atrial and ventricular myocardium during rest and exercise, and might be related to HR-dependent and HR-independent influences on the QT interval.

Time domain correlation analysis of heart rate variability in preterm neonates.

BACKGROUND AND AIM: A fuller understanding of the neural control mechanisms of heart rate during the early stages of human development would be of great value to obstetric and neonatal management. In this paper, we investigate the correlation between heart rate variability (HRV) and other physiological parameters such as blood pressure and respiration in preterm neonates with the aim of developing a numerical model to explain and predict heart rate variability. STUDY DESIGN AND SUBJECTS: All the required data are readily available for premature babies who are routinely monitored while being nursed in intensive care, and we have collected large data sets for a random group of such neonates. For the quantitative analysis of the data, we have developed a time domain correlation method, which has a number of advantages over the more commonly used power spectral analysis. We have been able to study the dynamics of the different frequency components of HRV by this method. RESULTS: Highly correlated behaviour of the different HRV components, previously observed in our work on fetal HRV, is also present in the neonate, with similar characteristic time constants. Furthermore, the correlation of high-frequency (HF) oscillations of HRV with respiration and that of low-frequency (LF) oscillations of HRV with blood pressure are demonstrated on timescales of a single oscillation. In neonates receiving artificial ventilation, the correlation between HRV and respiration depends on the type of ventilation involved and assumes opposite polarities for the two main types of equipment currently in use. CONCLUSION: We demonstrate that it is possible to analyse HRV quantitatively by calculating the relative gains and characteristic time constants for the correlated parameters and components.

[Comparison of nicardipine and isradipine in hypertension following coronary artery bypass graft]. / Comparaison de la nicardipine et de l'isradipine dans l'hypertension artérielle observée après pontage aorto-coronarien.

OBJECTIVE: Compare the efficacy of isradipine to that of nicardipine for the control of arterial hypertension following coronary artery bypass graft (CABG). STUDY DESIGN: Clinical prospective, randomised study. MATERIAL AND METHODS: 40 patients ASA II or III, mean age 66 +/- 8 years, scheduled for elective CABG were included. If the mean arterial pressure (MAP) was > or = 100 mmHg within the first six post operative hours, the patients were included and randomly attributed to either one of the 2 groups: Gr I (n = 20) received nicardipine, Gr II (n = 20) received isradipine in bolus then in continuous perfusion. HR, MAP, MPAP, CVP, PCWP, CI, SVRI, PVRI and SVI were recorded at: T0 before administration of drugs, T1 = 2 min after the first bolus. T2 when MAP reached 85 +/- 5 mmHg. T3, T4, T5, T6, T7 and T8 at 5, 10, 30, 60, 90 and 120 min after the continuous perfusion. T9 before stopping the perfusion. RESULTS: No significant changes in HR, CVP, PCWP, MPAP or PVRI at any time in both groups. Significant increase in CI at T2 in both groups. Reduction of MAP at T2 was more important (-27%) in Gr I compared to that in Gr II (-22%). This was mainly due to a significant decrease in SVRI. CONCLUSION: Isradipine is effective in the treatment of arterial hypertension following CABG. However there is not any significant beneficial effect of isradipine over nicardipine.

Power spectral analysis of the foetal magnetocardiogram.

The results of power spectral analysis of foetal magnetocardiographic (FMCG) data, acquired using a DC-SQUID-based system, are reported. Similar analyses have been previously reported using foetal electrocardiographic data, but it is believed that our work represents one of the first attempts to analyse, in the frequency domain, the magnetic fields produced by foetal cardiac activity. Analysis of the data in this way may enable the integrity of the foetal nervous system, and thus the status of the foetus as a whole, to be monitored and evaluated during a significant part of the antenatal period. The results obtained are discussed with reference to the probable underlying physiological mechanisms. This preliminary study highlights some of the advantages of FMCG as a novel, non-invasive technique for obtaining clinically useful information. Fourier analysis of the FMCG data is likely to yield new information, not only about cardiac function but also about the foetal central nervous system.

Sequential recording of the abdominal fetal electrocardiogram and magnetocardiogram.

The aim of this study was to demonstrate the acquisition of both the fetal magnetocardiogram (FMCG) and fetal electrocardiogram (FECG) from the abdomen of the same subject. This contrasts with previous reported studies which have generally recorded one or other of these signals but not the two together. Both signals were successfully recorded and averaged to produce a typical complex, thus allowing their direct comparison.

Magnetic susceptibility mapping of the human thorax using a SQUID biomagnetometer.

Biomagnetism is essentially the study of the weak magnetic fields generated by biological organisms, in particular the human body. The human thorax is composed of a variety of tissues and organs of slightly different magnetic susceptibility. In an applied magnetic field (of the order of milliTeslas) these small differences in susceptibility lead to measurable field variations (of the order of nanoTeslas) at the body surface which may be of diagnostic value. Physiological processes such as cardiac activity, cardiac output, blood flow and respiratory related lung volume changes also contribute to the observed signal. In this study susceptibility 'maps' were obtained by measuring the magnetic field at several hundred points over the thorax. Results indicate that magnetic susceptibility mapping produces low-resolution images of internal body structures from which is should be possible to detect pathologies that cause alterations in tissue susceptibility.

Tratamento das dermatomicoses com ketoconazole por via oral - estudo multicentrico. / Treatment of dermatomycosis with ketoconazole by oral route - multicenter study

Neste estudo foram incluidos 148 doentes, sendo 65 com pitiriase versicolor e 83 com dermatofitoses, submetidos a tratamento com ketoconazole por via oral. A dose diaria foi de 200mg (um comprimido) durante duas a quatro semanas para os casos de pitiriase versicolor e de quatro a oito semanas para os de dermatofitoses. O tratamento determinou, nos doentes de pitiriase versicolor, cura clinica e micologica em 50 (78,1%), apenas cura clinica em dois (3,1%) e cura micologica em um (1,6%). Nos doentes com dermatofitoses, em 69 (84,1%) houve cura clinica e micologica, quatro (4,9%) apresentaram cura micologica e cinco (6,1%) tiveram apenas cura clinica. Efeitos colaterais foram observados em 11 doentes (7,4%), sendo que dois necessitaram abandonar o tratamento por intolerancia (um teve nauseas de grau moderado e outro, nauseas, vomitos e tonturas de grau moderado, ambos no 1o. dia de tratamento).O ketoconazole por via oral demonstrou ser bastante eficaz no tratamento de pitiriase versicolor e de dermatofitoses

Note on the classification of the Leishmania sp. responsible for cutaneous leishmaniasis in the East Central Region of Brazil.

The authors studied a species of Leishmania which is the causative agent of cutaneous leishmaniasis in Mato Grosso, Brazil. The parasite displays unusual characteristics which do not fit exactly into either the L. mexicana or L. brasiliensis complexes. The buoyant density DNA resembles that of the L. mexicana complex but the culture and hamster inoculation results resemble those of the L. brasiliensis complex. Further comparative studies are required to elucidate the relationship of the Mato Grosso Leishmania to the L. mexicana complex.