The role of ultrasound and fetal fibronectin in predicting the length of induced labor when the cervix is unfavorable.

OBJECTIVE: To compare cervical clinical data, ultrasound parameters and fetal fibronectin assessment in the prediction of the duration of induced labor when the cervix is unfavorable. METHODS: This was a prospective study of 90 pregnant women with a Bishop score /= 27 mm (P = 0.002 and P = 0.005). CONCLUSION: Cervical dilatation as assessed by digital examination is the best predictor of the duration of the latent phase and of that of the whole of labor. Ultrasound measurement of cervical length is not more accurate at predicting the duration of labor than are clinical data.

Does ultrasound examination when the cervix is unfavorable improve the prediction of failed labor induction?

OBJECTIVE: To compare the Bishop score, ultrasound cervical parameters and fetal fibronectin assessment for predicting failed labor induction when the cervix is unfavorable. METHOD: A prospective observational study was performed in 106 consecutive pregnant women with a Bishop score < or =5 undergoing labor induction. Assessment of fetal fibronectin and ultrasound measurement of cervical length, cervical wedging and cervical lip areas were performed. The relationship between these parameters and failure of labor induction was determined. RESULTS: Failure of labor induction was defined as failure to reach a cervical dilatation of > or =5 cm, and it occurred in 16 patients (15.1%). Induction failure was associated with low Bishop scores before (P = 0.004) and 6 h after the start of induction (P = 0.007), increased clinical cervical length (P = 0.02) and increased ultrasound anterior cervical lip area (P = 0.04). The logistic regression model identified the Bishop score before induction (odds ratio = 2.25; 95% CI, 1.30-3.91; P = 0.003) and the clinical cervical length (odds ratio = 3.95; 95% CI, 1.3-11.7; P = 0.01) as being independent predictors of failed induction. To predict an induction failure, the best Bishop score cut-off value was 4, with a sensitivity of 87.5%, a specificity of 45.6%, a likelihood ratio of 1.58, a positive predictive value of 22.2% and a negative predictive value of 95.4%. CONCLUSION: Compared with the Bishop score, cervical length by ultrasound is not a better predictor for the outcome of labor induction in an unfavorable cervix. Nevertheless, the Bishop score appears to be of poor predictive value for failed induction of labor.

Thrombophilia and fetal growth restriction.

OBJECTIVE: Genetic thrombophilia may represent a new risk factor for obstetrical complications. The aim of the study was to determine which subgroups may be associated with genetic thrombophilia for small for gestational age infants (SGA). METHODS: A case-control study was performed in three different maternity wards in Normandy. Cases (n=203) were women who had pregnancies complicated by unexplained SGA infants defined as a birth weight below the 3rd centile and control subjects (n=203) were women who had infants with birth weight > or =10th centile. Patients were tested in the immediate postpartum period and 2 months later for factor V Leiden mutation, and prothrombin 20210A mutation. Frequencies of these mutations were observed in different subgroups of SGA infants depending on pregnancy or neonatal outcomes usually associated with intrauterine growth restriction (IUGR), and were then compared with the overall prevalence for these mutations detected in the control group. RESULTS: Prevalences for factor V Leiden mutation (or=2.58; 95% confidence interval: 0.83-8.04), prothrombin 20210A mutation (or=2.03; 95% confidence interval: 0.51-8.01), were comparable between cases and controls (4.9% versus 1.9% and 2.9% versus 1.4%, respectively). Frequencies for these two polymorphisms significantly increased in subgroups of SGA infants with a normal Pourcelot index (13/133 versus 7/203; P=0.04), a gestational age > or =37 weeks of gestation (15/143 versus 7/203; P=0.01), a vaginal delivery (11/117 versus 7/203; P=0.04), a birth weight > or =2000 g (12/121 versus 7/203; P=0.03), no admission to paediatric ward (11/116 versus 7/203; P=0.01), a low Ponderal index <2.5(e) centile (6/45 versus 7/203; P=0.04), and normal head circumference >10th centile (7/53 versus 7/203; P=0.01) in comparison with the control group. CONCLUSIONS: An association was found between polymorphisms for factor V Leiden and prothrombin, and asymmetrical intrauterine growth restriction with immediate favourable neonatal outcomes.

Abnormal placentation and selective embolization of the uterine arteries.

OBJECTIVE: Abnormal placentation accounts for more than 50% of uterine artery embolization failure. The authors report their experience in this situation. STUDY DESIGN: Seven women presented with abnormal placentation. Uterine artery embolization was carried out in emergency or prophylactic control of postpartum bleeding. RESULTS: In five patients, control of postpartum hemorrhage was obtained without hysterectomy. In two cases with no placental removal and prophylactic procedures, hysterectomy and blood transfusion were not necessary. The manual removal of the placenta was achieved secondarily, respectively on the 25th and the 12th day. CONCLUSIONS: The success rate of uterine artery embolization for postpartum bleeding appears to be lower with abnormal placentation. In none of the cases with the placenta present was it possible to leave the residual placenta in place. However, embolization may permit a safe waiting period and spontaneous migration of the placenta. When the diagnosis is made before delivery, prophylactic uterine artery embolization without placental removal should be considered to reduce blood transfusion and preserve fertility.

[Metopic craniosynostosis, probable effect of intrauterine exposure to maternal valproate treatment]. / La craniosténose de la métopique, effet probable de l'exposition intra-utérine à un traitement maternel par le valproate.

UNLABELLED: Metopic craniosynostosis may be an adverse effect of valproic acid exposed fetus. CASES: We report two infants with metopic craniosynostosis, born to mothers who were treated with valproic acid. In one case, a prenatal diagnosis was made. In the other case, only the male dizygotic twin was affected. CONCLUSION: Trigonocephaly may be a symptom of valproate embryofoetopathy detectable by antenatal ultrasound examination.

Early alterations of myocardial blood flow reserve in heart transplant recipients with angiographically normal coronary arteries.

BACKGROUND: The evaluation of the coronary reserve provides valuable information on the status of coronary vessels. Therefore, we studied with positron emission tomography (PET) and 13N-ammonia the myocardial blood flow (MBF) reserve in heart transplant recipients free of allograft rejection and with angiographically normal coronary arteries early after heart transplantation (HTx). The MBF reserve was calculated as the ratio between MBF after dipyridamole injection and basal MBF normalized for the rate-pressure product. METHODS: Patients were studied within 3 months (group A, n = 12) or more than 9 months (group B, n = 12) after HTx. Five patients have been studied both during the early and late period after HTx. Results were compared to those obtained in 7 normal volunteers (NL). RESULTS: Group A recipients had a significantly lower dipyridamole MBF (in ml/min/100 gr of tissue) than that of group B recipients (142+/-34 vs 195+/-59, p<0.05). This resulted in a significant decrease in MBF reserve early after HTx (group A: 1.82+/- 0.33) and a restoration to normal values thereafter (group B: 2.52+/- 0.53 vs NL: 2.62+/-0.51, p = ns). Separate analysis of 5 patients studied twice is consistent with these results. CONCLUSION: This study shows that in heart transplant recipients free of allograft rejection and with normal coronary angiography, MBF reserve is impaired early after HTx. Restoration within one year suggests that this abnormality does not represent an early stage of cardiac allograft vasculopathy.

Amniotic fluid alpha-fetoprotein is not a useful biological marker of pregnancy outcome.

The aim of our study was to determine if the amniotic fluid alpha-fetoprotein (AFP) level could be a useful predictive biochemical marker of pregnancy outcome. Amniotic fluid AFP measurement was prospectively carried out over a three-year period. After excluding factors susceptible to modifying AFP measurements, 587 subjects with gestational age between 14 and 20 weeks were selected to compare the amniotic fluid AFP mean levels depending on the occurrence of an adverse outcome. No significant associations between amniotic fluid AFP level and poor pregnancy outcome, i.e. pre-eclampsia, preterm delivery, premature rupture of fetal membranes, fetal growth retardation and placental abnormalities were observed. The routine measurement of amniotic fluid alpha-fetoprotein during an amniocentesis procedure was not considered useful in predicting pregnancy complications.

Haemodynamic response to dynamic exercise after heart-lung transplantation.

The purpose of this study was to investigate the haemodynamic response to dynamic exercise after heart-lung transplantation (HLT). Nine stable HLT recipients (6 males) were studied 12-55 months after transplantation. While sitting on a cycle ergometer, they first underwent a maximal symptom-limited exercise test (power increment was 10 W x min(-1)) to determine the maximal tolerable workload. On the next day, they performed a second exercise test at 0, 40, 60 and 80% of their predetermined maximal workload (mean+/-sD: 108+/-20 W). Stage duration was 6 min. Respiratory, gas exchange, and haemodynamic measurements were performed at rest, during the last minute of each stage, and after recovery. Haemodynamic variables at rest were within normal limits except heart rate (HR) which was greater and stroke volume index (SVI) which was lower than normal. Peak oxygen consumption was 61+/-8% of predicted. HR showed an initial slow increase followed by a steeper rise, and a delayed return to baseline during the recovery period. SVI and cardiac index (CI) increased at the onset of exercise but did not change significantly at 40-80% of the maximal workload. Pulmonary capillary wedge pressure increased from 4+/-2 mmHg at rest to 14+/-3 mmHg at maximal exercise. It is concluded that during dynamic exercise, heart-lung transplantation recipients demonstrate a chronotropic incompetence, a reduced increase in cardiac index and stroke volume index, and an excessive rise in left ventricular filling pressures. These alterations may contribute to the persistent exercise limitation.

Effects of spironolactone-altizide on left ventricular hypertrophy.

OBJECTIVE: To investigate the effects of the association spironolactone (25 mg)/altizide (15 mg) as monotherapy on left ventricular hypertrophy (LVH) in patients with mild to moderate hypertension. Additionally, to study the correlation between left ventricular mass (LVM) index and electrocardiographic (ECG) criteria for LVH. METHODS AND RESULTS: This was an open, prospective study of 6 months. Patients with mild to moderate essential hypertension were treated with spironolactone/altizide for two months and were included in the study if their blood pressure (BP) at the end of this first treatment period was normalised according to protocol criteria (systolic BP < 160 mm Hg and diastolic BP < 95 mm Hg). Patients then entered a second 4-month treatment period. LVM was determined by echocardiography performed at the beginning of treatment and after 6 months. LVH was defined as LVM > or = 100 g/m2 in women and LVM > or = 131 g/m2 in men. Echocardiograms were interpreted blindly by two echocardiography reading laboratories. Seventy-one patients with a normalised BP after two months of treatment, were enrolled in the study. Changes in LVM index were studied in 31/71 patients with LVH (25 women and 6 men, mean LVM index +/- (SD) 119.9 +/- 16.4 g/m2 in women and 147.8 +/- 10.9 g/m2 in men). Spironolactone/altizide significantly reduced LVM index by 10%, from 125.3 +/- 22.5 to 114.2 +/- 25.1 g/m2 (p < 0.005). Posterior and septal wall thickness decreased by 4% (p = 0.06) and 5% (p = 0.026), respectively. End-diastolic dimension was reduced by 3%, from 50.3 +/- 3.3 to 48.9 +/- 3.4 mm (p = 0.006). The posterior wall thickness to end-diastolic dimension ratio remained unchanged. Complete regression of LVH according to mass criteria occurred in 11 patients out of 31 (34.5%). The observed changes in ECG voltage criteria were in accordance with a decrease of LVM index. CONCLUSION: In this open study, the potassium-sparing diuretic spironolactone/altizide decreases LVM index in hypertensive patients, who were selected for follow-up because they had echocardiographic LVH and because their BP had normalised during an initial 2-month treatment period.

Coronary vasomotility and myocardial blood flow early after heart transplantation.

Serotonin constricts coronary arteries with endothelial dysfunction, a common abnormality in cardiac transplant recipients. To assess whether endothelial dysfunction is associated with myocardial blood flow (MBF) abnormalities, 24 patients were studied 1 to 12 months after transplantation. Serotonin in increasing doses (1, 10, and 20 micrograms/min for 2.5 min each) was infused into the coronary circulation. Diameters were measured by quantitative angiography. Fourteen patients (group A) had a pronounced artery constriction (diameter reduction > 40%), while in 10 other patients (group B), such a constriction was never reached. No patient had evidence of rejection and all had angiographically normal coronary arteries. MBF was measured at rest and after intravenous dipyridamole with dynamic nitrogen-13 ammonia positron emission tomography (PET). The resting MBF was higher in group A than in group B (94 +/- 12 vs 74 +/- 15 ml/min/100 g of tissue; p < 0.05). During dipyridamole, MBF was not significantly different (191 +/- 53 vs 184 +/- 64 ml/min/100 g; p = NS). Coronary flow reserve (the ratio of perfusion after dipyridamole to perfusion at rest) was significantly lower in group A than in group B (2.08 +/- 0.54 vs 2.66 +/- 0.57; p < 0.05). Thus, coronary hypersensitivity to serotonin in cardiac transplant recipients is associated with elevated resting MBF and reduced coronary flow reserve. Immune mechanisms inducing endothelial injuries and inflammation-related hyperemia may account for these abnormalities.

[Prevention of coronary diseases in daily clinical practice]. / La prévention des maladies coronaires dans la pratique clinique journalière.

Coronary heart disease mortality has declined in a number of European countries, included Belgium, but has remained unchanged or increased in others. In all these countries, coronary heart disease mortality remains the leading cause of mortality in men over 45 years and women over 65 years. The progress, when present, is related both with a better understanding of the physiopathological mechanisms, a better pharmacological and interventional approach and with a better application of prevention. Enthusiasms are nevertheless less important in application of prevention measures than in technical progresses. We present here the recommendations for prevention of coronary heart disease proposed by the European Society of Cardiology in clinical practice.

Long-term follow-up of heart transplant patients.

The present study was designated to assess long term functional capacity, blood pressure and renal function at 12 and 60 months after heart transplantation. The data of sixty heart transplant recipients were retrospectively reviewed. At rest, radionuclide ejection fraction and cardiac index measured by thermodilution were within normal range, demonstrating normal left systolic function. In all patients, exercise tests were performed sitting on a bicycle. Peak oxygen uptake decreased from 23 +/- 6 to 19 +/- 6 ml/kg/min (mean +/- S.D.) respectively at 12 and 60 months after surgery (p < 0.01), which represent a 17% diminution in functional capacity. This decrease is nevertheless only related with a 10 kg increase in total body weight (69 +/- 9; 79 +/- 12 kg; p < 0.001) and thus absolute peak oxygen uptake remained unchanged. Blood pressure rised significantly since the first month after transplantation. Sixty-seven percent of recipients had systemic hypertension at 60 months, despite medical therapy. A decline in renal function was observed in all patients, beginning after the first year of transplantation.

Ankle/arm pressure index in asymptomatic middle-aged males: an independent predictor of ten-year coronary heart disease mortality.

PURPOSE OF THE STUDY: to evaluate the predictive power of a reduced ankle/brachial pressure index (ABPI) (< or = .90) in an asymptomatic middle-aged male working population free of coronary heart disease. MATERIALS AND METHODS: 2023 subjects forty to fifty-five years old were screened at their work place. Standard techniques were used. Blood was drawn in the fasting state. Ankle and brachial blood pressures were measured by Doppler signals and all measures were done by one observer, duly trained in epidemiologic methodology. RESULTS: in univariate analysis, an ABPI < or = .90 was significantly associated with age, total serum cholesterol, body mass index, smoking, and awareness of diabetes. In multivariate analysis, it was associated with awareness of diabetes, age, Ln triglycerides (P = .073), and smoking (P = .088). Relative risks for reduced versus normal ABPI are 2.77 (P = .010), 4.16 (P = .011) and 4.97 (P = .006) for ten-year all causes, cardiovascular, and coronary mortality, respectively. In a multiple logistic regression analysis, the following variables were significant independent predictors of coronary mortality: smoking (odds ratio [OR] = 4.84), reduced ABPI (OR = 3.63), and low density lipoprotein cholesterol (OR for 1 SD = 1.69). Reduced ABPI is also an independent predictor of cardiovascular mortality. CONCLUSION: a reduced ABPI is an independent risk factor for coronary and cardiovascular mortality in asymptomatic middle-aged Belgian males.

Does cardiac denervation affect the short-term blood pressure variability in humans?

OBJECTIVE: To explore the repercussion of cardiac denervation on the short-term blood pressure variability in humans, in order to assess the extent to which the variability of blood pressure is linked to the variability of heart rate. METHODS: Beat-to-beat blood pressure and RR interval time were recorded in 16 heart-transplanted patients and were compared with those of 10 healthy control subjects in the resting supine, sitting and standing positions. Blood pressure and RR interval variabilities were assessed by spectral analysis. RESULTS: The total blood pressure power and the sitting very low-frequency, low-frequency, low-frequency and high-frequency blood pressure variability were similar in the heart-transplanted patients and in the controls, despite a marked reduction in the RR interval variability in the heart-transplanted patients. However, the heart-transplanted patients had lower standing low-frequency blood pressure variability than the control subjects. Moreover, very low-frequency and low-frequency RR interval variabilities reappeared in the long-term heart-transplanted patients but not in the short-term heart-transplanted patients (range of time after transplantation 53-124 and 3-25 months, respectively). CONCLUSIONS: Short-term RR interval fluctuations are not mandatory for the maintenance of normal blood pressure variability in the supine and sitting positions, but may contribute to the increase in the low-frequency blood pressure variability which occurs normally in the standing position. Moreover, the long-term heart-transplanted patients had increased RR interval variability, which may have been caused by the reappearance of limited autonomic cardiac modulation. However, this increased RR interval variability did not affect the corresponding blood pressure variability.

Pharmacokinetics of linsidomine (SIN 1) after single and multiple intravenous short infusions in patients with renal insufficiency.

Pharmacokinetic measurements were performed in two groups of patients with coronary heart disease (CHD) after single and multiple dosing of 2 mg linsidomine (SIN 1). The drug was administered by intravenous short time infusion in 12 CHD-patients with renal insufficiency (RI group, Clcr: 11 +/- 6 ml/min) and in 12 CHD-patients with normal kidney function (control group, Clcr: 88 +/- 22 ml/min). The measurement of plasma concentration time courses of total SIN 1C (SIN 1 + SIN 1C) was found to be suitable for an estimation of the SIN 1C related half-life of the terminal phase (t50% = 1.5 +/- 0.5 h), as SIN 1 was eliminated from plasma rapidly (t50% = 12 to 20 min). Furthermore, the mean total SIN 1C plasma profiles were equal after single and multiple administration of the drug giving evidence that SIN 1C is not accumulating during repetitive dosing of SIN 1 in patients with renal disease. The mean maximum renal fraction of total SIN 1C excretion of RI-subjects (fe = 0.8 +/- 0.8% of dose) was significantly different from the corresponding mean value of the control group (fe(N) = 5.8 +/- 5.1% of dose). No differences were found for fe and fe(N) between day 1 and day 4. As SIN 1 is degraded in plasma very rapidly and as SIN 1C is cleared mainly extrarenally, any restrictions concerning repetitive SIN 1 dosage regimen should not be considered for CHD-patients with renal failure.

[Adaptation of the denervated heart to physical effort]. / L'adaptation du coeur dénervé a l'effort physique.

In a transplanted heart, increased stroke volume secondary to the Starling mechanism and increased heart rate and contractility secondary to noradrenaline effect appear sequentially whereas they appear simultaneously in normal innervated heart. Cardiac output adaptation at exercise is thus delayed and responsible for metabolic acidosis and abnormally high exercise ventilation. Moreover, stroke volume adaptation to exercise is compromised by abnormally high right and left afterload and by systolic and diastolic impairement of the ventricular function related with chronic rejections' episodes.

Effects of chronic congestive heart failure on 24-hour blood pressure and heart rate patterns: a hemodynamic approach.

For 29 patients with congestive heart failure (CHF), 24-hour noninvasive ambulatory blood pressure (ABP) and heart rate (HR) measurement profiles were described, using the periodogram method, and were compared with the same findings in 22 matched controls. Right-sided heart catheterization was performed in all patients. The mean cardiac index was 2.2 L/min/m2 (range 1.3 to 2.9 L/min/m2). More severe CHF, as assessed by cardiac index, pulmonary artery wedge pressure, and right atrial pressure, correlated significantly with a reduction in the amplitude of the circadian ABP and HR rhythms (0.38 less than r less than 0.63; p less than 0.05). Moreover, a reduced increase in cardiac index during cycloergometric exercise in 11 CHF patients correlated with a blunting of the circadian systolic ABP and HR profiles (0.57 less than r less than 0.90; p less than 0.05). Our results indicate that there is a reduction in the amplitude of the circadian BP and HR rhythms related to the severity of CHF.

Hemodynamic response to molsidomine in patients with ischemic cardiomyopathy tolerant to isosorbide dinitrate.

Unlike nitrates, molsidomine is able to relax vascular smooth muscle without depending on the availability of sulfhydryl groups. To assess the clinical relevance of this property, the hemodynamic effects of a 24-h i.v. infusion of molsidomine were studied in 14 patients with ischemic cardiomyopathy rendered tolerant to i.v. isosorbide dinitrate. In order to determine the role of neurohormonal activation, six of these patients were studied in the presence of an angiotensin-converting enzyme (ACE) inhibitor (enalapril, 5 mg, b.i.d.) (group 2). Six patients out of eight in group 1 (without ACE inhibition) and all patients in group 2 responded to molsidomine with a marked reduction of pulmonary artery wedge pressure (PAWP) (49% +/- 5 and 50% +/- 4 versus baseline value, respectively). However, the reduction of PAWP in group 1 was no longer significant at 12 h, and at 24 h the loss of the peak effect reached 67% +/- 7. On the contrary, PAWP remained persistently reduced in group 2 (loss of peak effect, 20% +/- 3 at 24 h, p less than 0.005). In addition, a significant decrease in hematocrit and increase in epinephrine occurred in group 1 but not in group 2. These results suggest that both the absence of dependence on sulfhydryl groups and the blockade of neurohormonal reactions are needed to avoid nitrate tolerance.