Normal sex differences in prenatal growth and abnormal prenatal growth retardation associated with 46,XY disorders of sex development are absent in newborns with congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Background

Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is the most common presentation of a disorder of sex development (DSD) in genetic females. A report of prenatal growth retardation in cases of 46,XY DSD, coupled with observations of below-optimal final height in both males and females with congenital adrenal hyperplasia due to 21-hydroxylase deficiency, prompted us to investigate prenatal growth in the latter group. Additionally, because girls with congenital adrenal hyperplasia are exposed to increased levels of androgens in the absence of a male sex-chromosome complement, the presence or absence of typical sex differences in growth of newborns would support or refute a hormonal explanation for these differences.

Methods

In total, 105 newborns with congenital adrenal hyperplasia were identified in our database. Gestational age (weeks), birth weight (kg), birth length (cm) and parental heights (cm) were obtained. Mid-parental height was considered in the analyses.

Results

Mean birth weight percentile for congenital adrenal hyperplasia was 49.26%, indicating no evidence of a difference in birth weight from the expected standard population median of 50th percentile (P > 0.05). The expected sex difference in favor of heavier males was not seen (P > 0.05). Of the 105 subjects, 44 (27%; 34 females, 10 males) had birth length and gestational age recorded in their medical chart. Mean birth length for this subgroup was 50.90 cm (63rd percentile), which differed from the expected standard population median of 50th percentile (P = 0.0082). The expected sex difference in favor of longer males was also not seen (P > 0.05).

Conclusion

The prenatal growth retardation patterns reported in cases of 46,XY disorders of sex development do not generalize to people with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Sex differences in body weight and length typically seen in young infants were not seen in the subjects who participated in this study. We speculate that these differences were ameliorated in this study because of increased levels of prenatal androgens experienced by the females infants.     

Automatic noninvasive measurement of systolic blood pressure using photoplethysmography

Background

Systolic blood flow has been simulated in the abdominal aorta and the superior mesenteric artery. The simulations were carried out using two different computational hemodynamic methods: the finite element method to solve the Navier Stokes equations and the lattice Boltzmann method.

Results

We have validated the lattice Boltzmann method for systolic flows by comparing the veloCity and pressure profiles of simulated blood flow between methods. We have also analyzed flow-specific characteristics such as the formation of a vortex at curvatures and traces of flow.

Conclusion

The lattice Boltzmann Method is as accurate as a Navier Stokes solver for computing complex blood flows. As such it is a good alternative for computational hemodynamics, certainly in situation where coupling to other models is required.     

Cardiac functional stress imaging: A sequential approach with stress echo and cardiovascular magnetic resonance

Background

An adequate placental perfusion is crucial for the normal growth and well being of the fetus and newborn. The blood flow through the placenta can be compromised in a variety of clinical situations, always causing important damage to the gestation. Our objective is to identify significant predictors for adverse neonatal outcome in severe fetal compromise.

Methods

Consecutive premature fetuses at between 25 and 32 weeks with severe placental insufficiency were examined prospectively. Inclusion criteria were: (i) singletons (ii) normal anatomy; (iii) abnormal umbilical artery Doppler pulsatility index (PI); (iv) abnormal cerebroplacental ratio; (v) middle cerebral artery (MCA) PI < - 2SD ("brain sparing"); (vi) last Doppler examination performed within 24 hours prior to delivery. All 46 patients that met criteria and started the study were followed to the end. We considered as independent potential predicting variables: absent or reversed end diastolic flow in umbilical artery, abnormal ductus venosus S/A ratio, absent or reversed flow during atrial contraction in the ductus venosus and birth weight Z score. Outcome parameters were: neonatal mortality and severe neonatal morbidity.

Results

Backward stepwise logistic regression analysis was used to determine the optimal model for the prediction of neonatal mortality and severe neonatal morbidity. In this analysis birth weight Z score index showed the strongest association OR = 1,87 [1,17-2,99] with all neonatal outcome, all other independent variables were excluded for the optimal model. There was no mortality for the group with normal birth weight Z score.

Conclusion

Our study suggests that birth weight Z score is the strongest predictor of adverse neonatal outcome in severe placental insufficiencies. Such use of Z scores, allowing to get rid of gestational age or sex covariates could be extended to estimated fetal weight and might help in making important decisions in the management of compromised pregnancies.     

Prognostic Value of Umbilical and Cerebral Doppler in Fetal Growth Restriction: Comparison of Dichorionic Twins and Singletons

Objective

To compare the prognostic value of fetal Doppler in dichorionic twins and singletons by measuring the interval between diagnosis of an abnormal Doppler flow and birth in fetuses who are small for gestational age (SGA).

Design

Comparative retrospective study using a prospectively collected database.

Setting

A level 3 maternity unit in France.

Population

Fetuses from singleton and dichorionic pregnancies who are SGA (vascular or unexplained), defined by an abdominal circumference (AC) measurement below the 10^th percentile and confirmed by a birth weight below the 10^th percentile.

Methods

Fisher''s exact and Chi-2 tests were used to compare frequencies, and the Mann-Whitney-Wilcoxon test was used to compare medians in non-Gaussian distributions.

Main outcome measures

Both neonatal outcomes and intervals between the first Doppler abnormality and birth were compared in the groups of dichorionic twins and singletons.

Results

Obstetric and neonatal outcome were similar in the 104 SGA dichorionic twins and 170 SGA singletons. Abnormalities of umbilical artery Doppler, regardless of type, appeared at the same frequency in both groups (52.9%) but were identified earlier in twins (25 versus 28 weeks, p = 0.02). Among fetuses with abnormal Doppler flow, the interval between the finding and birth was significantly longer in the twins than the singletons (44 vs 15 days, p<0.01).

Conclusions

The prognostic value of an abnormal Doppler finding for the course of a pregnancy may be different in dichorionic twins and singletons. The management of women carrying SGA twins and the information provided to them should take these results into account.     

Dehydroepiandrosterone (DHEA) supplementation in diminished ovarian reserve (DOR)

Background

Exposure of pregnant mothers to elevated concentrations of circulating testosterone levels is associated with fetal growth restriction and delivery of small-for-gestational-age babies. We examined whether maternal testosterone crosses the placenta to directly suppress fetal growth or if it modifies placental function to reduce the capacity for transport of nutrients to the fetus.

Methods

Pregnant rats were exposed to testosterone propionate (TP; 0.5 mg/kg) by daily subcutaneous injection from gestational days (GD) 15-19. Maternal and fetal testosterone levels, placental nutrient transport activity and expression of transporters and birth weight of pups and their anogenital distances were determined.

Results

This dose of TP doubled maternal testosterone levels but had no effect on fetal testosterone levels. Maternal daily weight gain was significantly lower only on GD 19 in TP treated dams compared to controls. Placental weight and birth weight of pups were significantly reduced, but the anogenital distance of pups were unaffected by TP treatment. Maternal plasma amino acids concentrations were altered following testosterone exposure, with decreases in glutamine, glycine, tyrosine, serine, proline, and hydroxyproline and increases in asparagine, isoleucine, leucine, lysine, histidine and arginine. In the TP dams, placental system A amino acid transport activity was significantly reduced while placental glucose transport capacity was unaffected. Decreased expression of mRNA and protein levels of slc38a2/Snat2, an amino acid transporter, suggests that reduced transporter proteins may be responsible for the decrease in amino acid transport activity.

Conclusions

Taken together, these data suggest that increased maternal testosterone concentrations do not cross the placenta to directly suppress fetal growth but affects amino acid nutrient delivery to the fetus by downregulating specific amino acid transporter activity.     

Studies on the enzymatic activities related to varied pattern of diets in the air-breathing cat fish,clarias batrachus (Linn.)

1. Specific activity of amylase, cellulase, protease and lipase in the intestines of the air-breathing catfish, Clarias batrachus (Linn.) has been studied.
2. Excepting amylase and protease, the activity of lipase and cellulase showed practically no changes with change in the nutritional status of the diets.
3. pH optima of all enzymes were between 6.9 and 7.6
4. There is reason to believe from cellulase and high amylase activity in the intestine of the species that its culture operation could be done more economically by giving them a supplementary diet from indigeneously available raw material particularly from plant origin.

     

Medium chain fatty acids in intrauterine growth restricted and small for gestational age pregnancies

Introduction

Low birth weight is associated with an increased risk of heart disease, high blood pressure and diabetes in adult life. Fetal growth is determined by nutrient availability, which is related to placenta nutrient transport. Medium chain fatty acids (MCFAs) are a particular class of nutrients, known to be a readily available energy source. Until now no data are reported on these MCFAs in low birth weight fetus.

Aim

This is a prospective study conducted in a tertiary center of prenatal diagnosis to investigate the maternal and fetal MCFAs levels in appropriate for gestational age (AGA), intrauterine growth restricted (IUGR), and small for gestational age (SGA) pregnancies.

Method

The plasmatic levels of MCFAs in AGA, IUGR and SGA mother–infant pairs were quantified by gas chromatography–mass spectrometry. The analytical method had a linearity range of 0.1–50 mg/L and a limit of quantification of 0.03 mg/L. Reduced fetal growth was defined as an estimated fetal weight below the 3rd–10th percentile for gestational age, with (IUGR) or without (SGA) fetal Doppler abnormalities.

Result

Maternal and fetal MCFAs plasma levels were significantly different among SGA, IUGR and AGA groups. Additionally, the observed MCFAs fetal to maternal ratio is >1 for IUGR group, whilst for SGA and AGA the fetal to maternal ratio is less than one.

Conclusion

Changes in MCFAs levels in fetal and maternal plasma are not related to placental functionality or nutrients availability, suggesting the presence of a de novo biosynthesis.

     

A randomised, controlled crossover comparison of the C-MAC videolaryngoscope with direct laryngoscopy in 150 patients during routine induction of anaesthesia

Background

The insertion of Ventricular Assist Devices is a common strategy for cardiovascular support in patients with refractory cardiogenic shock. This study sought to determine the impact of ventricular assist devices on the dynamic relationship between arterial blood pressure and cerebral blood flow velocity.

Methods

A sample of 5 patients supported with a pulsatile ventricular assist device was compared with 5 control patients. Controls were matched for age, co-morbidities, current diagnosis and cardiac output state, to cases. Beat-to-beat recordings of mean arterial pressure and cerebral blood flow velocity, using transcranial Doppler were obtained. Transfer function analysis was performed on the lowpass filtered pressure and flow signals, to assess gain, phase and coherence of the relationship between mean arterial blood pressure and cerebral blood flow velocity. These parameters were derived from the very low frequency (0.02-0.07 Hz), low frequency (0.07-0.2 Hz) and high frequency (0.2-0.35 Hz).

Results

No significant difference was found in gain and phase values between the two groups, but the low frequency coherence was significantly higher in cases compared with controls (mean ± SD: 0.65 ± 0.16 vs 0.38 ± 0.19, P = 0.04). The two cases with highest coherence (~0.8) also had much higher spectral power in mean arterial blood pressure.

Conclusions

Pulsatile ventricular assist devices affect the coherence but not the gain or phase of the cerebral pressure-flow relationship in the low frequency range; thus whether there was any significant disruption of cerebral autoregulation mechanism was not exactly clear. The augmentation of input pressure fluctuations might contribute in part to the higher coherence observed.     

Preliminary clinical study of left ventricular myocardial strain in patients with non-ischemic dilated cardiomyopathy by three-dimensional speckle tracking imaging

Background

Different diagnostic criteria limit comparisons between populations in the prevalence of diastolic left ventricular (LV) dysfunction. We aimed to compare across populations age-specific echocardiographic criteria for diastolic LV dysfunction as well as their correlates and prevalence.

Methods

We measured the E and A peaks of transmitral blood flow by pulsed wave Doppler and the e' and a' peaks of mitral annular velocities by tissue Doppler imaging (TDI) in 2 cohorts randomly recruited in Belgium (n = 782; 51.4% women; mean age, 51.1 years) and in Italy, Poland and Russia (n = 476; 55.7%; 44.5 years).

Results

In stepwise regression, the multivariable-adjusted correlates of the transmitral and TDI diastolic indexes were similar in the 2 cohorts and included sex, age, body mass index, blood pressure and heart rate. Similarly, cut-off limits for the E/A ratio (2.5th percentile) and E/e' ratio (97.5th percentile) in 338 and 185 reference subjects free from cardiovascular risk factors respectively selected from both cohorts were consistent within 0.02 and 0.26 units (median across 5 age groups). The rounded 2.5th percentile of the E/A ratio decreased by ~0.10 per age decade in these apparently healthy subjects. The reference subsample provided age-specific cut-off limits for normal E/A and E/e' ratios. In the 2 cohorts combined, diastolic dysfunction groups 1 (impaired relaxation), 2 (possible elevated LV filling pressure) and 3 (elevated E/e' and abnormally low E/A) encompassed 114 (9.1%), 135 (10.7%), and 40 (3.2%) subjects, respectively.

Conclusions

The age-specific criteria for diastolic LV dysfunction were highly consistent across the study populations with an age-standardized prevalence of 22.4% vs. 25.1%.     

The optimization of the diagnostic work-up in patients with suspected obstructive lung disease

Background

Liver dysfunction reflects the status of heart failure, with congestion and low perfusion of the liver serving as causative mechanisms. Previous studies demonstrated relationship between the results of liver function test and the prognosis in patients with heart failure. However, few studies have examined this relationship in patients with pulmonary arterial hypertension (PAH).

Methods

The subjects were 37 patients with PAH (8 men and 29 women; 18 with idiopathic PAH and 19 with connective tissue disease-associated PAH). A blood test was performed after a 3-month period free from hospitalization and without changes in functional class, treatment, heart sounds, body weight, or heart rate.

Results

In a mean follow-up period of 635 ± 510 days, 12 patients died due to heart failure, 2 died due to pulmonary hemorrhage, and 23 patients survived. Cox proportional hazard analyses identified functional class (p < 0.001), plasma concentration of brain natriuretic peptide (BNP) (p = 0.001), and hyperbilirubinemia (serum total bilirubin > 1.2 mg/dL; p < 0.001; hazard ratio = 13.31) as predictors of mortality. Patients with hyperbilirubinemia had a worse functional class (P = 0.003), a higher right atrial pressure (p < 0.001), a higher plasma concentration of BNP (p = 0.004), and a larger Doppler right ventricular index of the right ventricle (p = 0.041).

Conclusion

Elevated serum bilirubin is a risk factor for death in patients with PAH.     

A rare cause of chronic mesenteric ischemia from fibromuscular dysplasia: a case report

Introduction

Chronic mesenteric ischemia is a condition that is classically associated with significant atherosclerosis of the abdominal arteries, causing postprandial abdominal pain out of proportion to physical examination. The abdominal pain is exacerbated after meals due to the shunting of blood away from the intestines to the stomach, causing relative ischemia. More than 95% of chronic mesenteric ischemia cases are due to atherosclerosis. We report the first known case of chronic mesenteric ischemia from fibromuscular dysplasia. To the best of our knowledge, this is also the first known case in the literature where postprandial abdominal pain was the presenting symptom of fibromuscular dysplasia.

Case presentation

A 44-year-old Caucasian woman with a history of hypertension and preeclampsia, who had taken oral contraceptive pills for 15 years, presented with an intractable, colicky abdominal pain of two weeks duration. This abdominal pain worsened with oral intake. It was also associated with diarrhea and vomiting. Physical examination revealed stage III hypertension out of proportion to her risk factors and diffuse abdominal pain without peritoneal signs. An abdominal computed tomography scan, completed in the emergency room, revealed nonspecific colitis. Laboratory work revealed leukocytosis with a left shift, an erythrocyte sedimentation rate of 79 and a C-reactive protein level of 100. She was started on intravenous flagyl and intravenous ciprofloxacin. However, all microbial cultures were negative including three cultures for clostridium difficile. Urine analysis revealed nephritic range proteinuria. The laboratory profile was within normal limits for perinuclear-anti-neutrophil cytoplasmic antibody, cytoplasmic-anti-neutrophil cytoplasmic antibody, anti-saccharomyces cerevisiae antibody, antinuclear antibody test, celiac profile, lactate, carbohydrate antigen-125 and thyroid stimulating hormone. A colonoscopy was completed, which revealed diffuse colonic lymphoid reactive hyperplasia. A small bowel series was negative for any inflammation. An indium scan, pan-computed tomography scan and transvaginal ultrasound were also negative. Magnetic resonance angiography of her abdomen revealed proximal superior mesenteric artery stenosis, which was confirmed by computed tomography angiogram findings of severe proximal and distal superior mesenteric artery stenosis, consistent with the appearance of fibromuscular dysplasia on angiography in the absence of vasculitis or atherosclerotic disease. The patient's superior mesenteric artery stenosis was subsequently angioplastied suboptimally and had to be stented with an Angioplus stent. One month after she was admitted, her abdominal pain and tolerance to oral feeds improved tremendously.

Conclusion

Fibromuscular dysplasia most commonly presents with renal artery stenosis, which rarely causes abdominal pain. This case illustrates how fibromuscular dysplasia can present as a rare cause of chronic mesenteric ischemia, similar to chronic mesenteric ischemia from atherosclerosis.     

Cerebral blood flow during cardiopulmonary bypass in pediatric cardiac surgery: the role of transcranial Doppler – a systematic review of the literature

Background

Transcranial Doppler Ultrasound (TCD) is a sensitive, real time tool for monitoring cerebral blood flow velocity (CBFV). This technique is fast, accurate, reproducible and noninvasive. In the setting of congenital heart surgery, TCD finds application in the evaluation of cerebral blood flow variations during cardiopulmonary bypass (CPB).

Methodology

We performed a search on human studies published on the MEDLINE using the keyword "trans cranial Doppler" crossed with "pediatric cardiac surgery" AND "cardio pulmonary by pass", OR deep hypothermic cardiac arrest", OR "neurological monitoring".

Discussion

Current scientific evidence suggests a good correlation between changes in cbral blood flow and mean cerebral artery (MCA) blood flow velocity. The introduction of Doppler technology has allowed an accurate monitorization of cerebral blood flow (CBF) during circulatory arrest and low-flow CPB. TCD has also been utilized in detecting cerebral emboli, improper cannulation or cross clamping of aortic arch vessels. Limitations of TCD routine utilization are represented by the need of a learning curve and some experience by the operators, as well as the need of implementing CBF informations with, for example, data on brain tissue oxygen delivery and consumption.

Conclusion

In this light, TCD plays an essential role in multimodal neurological monitorization during CPB (Near Infrared Spectroscopy, TCD, processed electro encephalography) that, according to recent studies, can help to significantly improve neurological outcome after cardiac surgery in neonates and pediatric patients.     

Assessment of atrial regional and global electromechanical function by tissue velocity echocardiography: a feasibility study on healthy individuals

Background

Myocardial contrast echocardiography and coronary flow velocity pattern with a rapid diastolic deceleration time after percutaneous coronary intervention has been reported to be useful in assessing microvascular damage in patients with acute myocardial infarction.

Aim

To evaluate myocardial contrast echocardiography with harmonic power Doppler imaging, coronary flow velocity reserve and coronary artery flow pattern in predicting functional recovery by using transthoracic echocardiography.

Methods

Thirty patients with anterior acute myocardial infarction underwent myocardial contrast echocardiography at rest and during hyperemia and were quantitatively analyzed by the peak color pixel intensity ratio of the risk area to the control area (PIR). Coronary flow pattern was measured using transthoracic echocardiography in the distal portion of left anterior descending artery within 24 hours after recanalization and we assessed deceleration time of diastolic flow velocity. Coronary flow velocity reserve was calculated two weeks after acute myocardial infarction. Left ventricular end-diastolic volumes and ejection fraction by angiography were computed.

Results

Pts were divided into 2 groups according to the deceleration time of coronary artery flow pattern (Group A; 20 pts with deceleration time ≧ 600 msec, Group B; 10 pts with deceleration time < 600 msec). In acute phase, there were no significant differences in left ventricular end-diastolic volume and ejection fraction (Left ventricular end-diastolic volume 112 ± 33 vs. 146 ± 38 ml, ejection fraction 50 ± 7 vs. 45 ± 9 %; group A vs. B). However, left ventricular end-diastolic volume in Group B was significantly larger than that in Group A (192 ± 39 vs. 114 ± 30 ml, p < 0.01), and ejection fraction in Group B was significantly lower than that in Group A (39 ± 9 vs. 52 ± 7%, p < 0.01) at 6 months. PIR and coronary flow velocity reserve of Group A were higher than Group B (PIR, at rest: 0.668 ± 0.178 vs. 0.248 ± 0.015, p < 0.0001: during hyperemia 0.725 ± 0.194 vs. 0.295 ± 0.107, p < 0.0001; coronary flow velocity reserve, 2.60 ± 0.80 vs. 1.31 ± 0.29, p = 0.0002, respectively).

Conclusion

The preserved microvasculature detecting by myocardial contrast echocardiography and coronary flow velocity reserve is related to functional recovery after acute myocardial infarction.     

Refractive Status at Birth: Its Relation to Newborn Physical Parameters at Birth and Gestational Age

Background

Refractive status at birth is related to gestational age. Preterm babies have myopia which decreases as gestational age increases and term babies are known to be hypermetropic. This study looked at the correlation of refractive status with birth weight in term and preterm babies, and with physical indicators of intra-uterine growth such as the head circumference and length of the baby at birth.

Methods

All babies delivered at St. Stephens Hospital and admitted in the nursery were eligible for the study. Refraction was performed within the first week of life. 0.8% tropicamide with 0.5% phenylephrine was used to achieve cycloplegia and paralysis of accommodation. 599 newborn babies participated in the study. Data pertaining to the right eye is utilized for all the analyses except that for anisometropia where the two eyes were compared. Growth parameters were measured soon after birth. Simple linear regression analysis was performed to see the association of refractive status, (mean spherical equivalent (MSE), astigmatism and anisometropia) with each of the study variables, namely gestation, length, weight and head circumference. Subsequently, multiple linear regression was carried out to identify the independent predictors for each of the outcome parameters.

Results

Simple linear regression showed a significant relation between all 4 study variables and refractive error but in multiple regression only gestational age and weight were related to refractive error. The partial correlation of weight with MSE adjusted for gestation was 0.28 and that of gestation with MSE adjusted for weight was 0.10. Birth weight had a higher correlation to MSE than gestational age.

Conclusion

This is the first study to look at refractive error against all these growth parameters, in preterm and term babies at birth. It would appear from this study that birth weight rather than gestation should be used as criteria for screening for refractive error, especially in developing countries where the incidence of intrauterine malnutrition is higher.     

Relationships between Neonatal Weight,Limb Lengths,Skinfold Thicknesses,Body Breadths and Circumferences in an Australian Cohort

Background

Low birth weight has been consistently associated with adult chronic disease risk. The thrifty phenotype hypothesis assumes that reduced fetal growth impacts some organs more than others. However, it remains unclear how birth weight relates to different body components, such as circumferences, adiposity, body segment lengths and limb proportions. We hypothesized that these components vary in their relationship to birth weight.

Methods

We analysed the relationship between birth weight and detailed anthropometry in 1270 singleton live-born neonates (668 male) from the Mater-University of Queensland Study of Pregnancy (Brisbane, Australia). We tested adjusted anthropometry for correlations with birth weight. We then performed stepwise multiple regression on birth weight of: body lengths, breadths and circumferences; relative limb to neck-rump proportions; or skinfold thicknesses. All analyses were adjusted for sex and gestational age, and used logged data.

Results

Circumferences, especially chest, were most strongly related to birth weight, while segment lengths (neck-rump, thigh, upper arm, and especially lower arm and lower leg) were relatively weakly related to birth weight, and limb lengths relative to neck-rump length showed no relationship. Skinfolds accounted for 36% of birth weight variance, but adjusting for size (neck-rump, thigh and upper arm lengths, and head circumference), this decreased to 10%. There was no evidence that heavier babies had proportionally thicker skinfolds.

Conclusions

Neonatal body measurements vary in their association with birth weight: head and chest circumferences showed the strongest associations while limb segment lengths did not relate strongly to birth weight. After adjusting for body size, subcutaneous fatness accounted for a smaller proportion of birth weight variance than previously reported. While heavier babies had absolutely thicker skinfolds, this was proportional to their size. Relative limb to trunk length was unrelated to birth weight, suggesting that limb proportions at birth do not index factors relevant to prenatal life.     

The velocity of the arterial pulse wave: a viscous-fluid shock wave in an elastic tube

Background

The arterial pulse is a viscous-fluid shock wave that is initiated by blood ejected from the heart. This wave travels away from the heart at a speed termed the pulse wave velocity (PWV). The PWV increases during the course of a number of diseases, and this increase is often attributed to arterial stiffness. As the pulse wave approaches a point in an artery, the pressure rises as does the pressure gradient. This pressure gradient increases the rate of blood flow ahead of the wave. The rate of blood flow ahead of the wave decreases with distance because the pressure gradient also decreases with distance ahead of the wave. Consequently, the amount of blood per unit length in a segment of an artery increases ahead of the wave, and this increase stretches the wall of the artery. As a result, the tension in the wall increases, and this results in an increase in the pressure of blood in the artery.

Methods

An expression for the PWV is derived from an equation describing the flow-pressure coupling (FPC) for a pulse wave in an incompressible, viscous fluid in an elastic tube. The initial increase in force of the fluid in the tube is described by an increasing exponential function of time. The relationship between force gradient and fluid flow is approximated by an expression known to hold for a rigid tube.

Results

For large arteries, the PWV derived by this method agrees with the Korteweg-Moens equation for the PWV in a non-viscous fluid. For small arteries, the PWV is approximately proportional to the Korteweg-Moens velocity divided by the radius of the artery. The PWV in small arteries is also predicted to increase when the specific rate of increase in pressure as a function of time decreases. This rate decreases with increasing myocardial ischemia, suggesting an explanation for the observation that an increase in the PWV is a predictor of future myocardial infarction. The derivation of the equation for the PWV that has been used for more than fifty years is analyzed and shown to yield predictions that do not appear to be correct.

Conclusion

Contrary to the theory used for more than fifty years to predict the PWV, it speeds up as arteries become smaller and smaller. Furthermore, an increase in the PWV in some cases may be due to decreasing force of myocardial contraction rather than arterial stiffness.     

Mesenteric resistance arteries in type 2 diabetic db/db mice undergo outward remodeling

Objective

Resistance vessel remodeling is controlled by myriad of hemodynamic and neurohormonal factors. This study characterized structural and molecular remodeling in mesenteric resistance arteries (MRAs) in diabetic (db/db) and control (Db/db) mice.

Methods

Structural properties were assessed in isolated MRAs from 12 and 16 wk-old db/db and Db/db mice by pressure myography. Matrix regulatory proteins were measured by Western blot analysis. Mean arterial pressure and superior mesenteric blood flow were measured in 12 wk-old mice by telemetry and a Doppler flow nanoprobe, respectively.

Results

Blood pressure was similar between groups. Lumen diameter and medial cross-sectional area were significantly increased in 16 wk-old db/db MRA compared to control, indicating outward hypertrophic remodeling. Moreover, wall stress and cross-sectional compliance were significantly larger in diabetic arteries. These remodeling indices were associated with increased expression of matrix regulatory proteins matrix metalloproteinase (MMP)-9, MMP-12, tissue inhibitors of matrix metalloproteinase (TIMP)-1, TIMP-2, and plasminogen activator inhibitor-1 (PAI-1) in db/db arteries. Finally, superior mesenteric artery blood flow was increased by 46% in 12 wk-old db/db mice, a finding that preceded mesenteric resistance artery remodeling.

Conclusions

These data suggest that flow-induced hemodynamic changes may supersede the local neurohormonal and metabolic milieu to culminate in hypertrophic outward remodeling of type 2 DM mesenteric resistance arteries.     

Maternal malaria, birth size and blood pressure in Nigerian newborns: insights into the developmental origins of hypertension from the Ibadan growth cohort

Background

Hypertension is an increasing health issue in sub-Saharan Africa where malaria remains common in pregnancy. We established a birth cohort in Nigeria to evaluate the early impact of maternal malaria on newborn blood pressure (BP).

Methods

Anthropometric measurements, BP, blood films for malaria parasites and haematocrit were obtained in 436 mother-baby pairs. Women were grouped to distinguish between the timing of malaria parasitaemia as ‘No Malaria’, ‘Malaria during pregnancy only’ or ‘Malaria at delivery’, and parasite density as low (<1000 parasites/µl of blood) and high (≥1000/µl).

Results

Prevalence of maternal malaria parasitaemia was 48%, associated with younger maternal age (p<0.001), being primigravid (p = 0.022), lower haematocrit (p = 0.028). High parasite density through pregnancy had the largest effect on mean birth indices so that weight, length, head and mid-upper arm circumferences were smaller by 300 g, 1.1 cm, 0.7 cm and 0.4 cm respectively compared with ‘No malaria’ (all p≤0.005). In babies of mothers who had ‘malaria at delivery’, their SBPs adjusted for other confounders were lower respectively by 4.3 and 5.7 mmHg/kg compared with ‘malaria during pregnancy only’ or ‘none’. In contrast the mean newborn systolic (SBP) and diastolic BPs (DBP) adjusted for birth weight were higher by 1.7 and 1.4 mmHg/kg respectively in babies whose mothers had high compared with low parasitaemia.

Conclusions

As expected, prenatal malarial exposure had a significant impact on fetal growth rates. Malaria at delivery was associated with the lowest newborn BPs while malaria through pregnancy, which may attenuate growth of the vascular network, generated higher newborn BPs adjusted for size. These neonatal findings have potential implications for cardiovascular health in sub-Saharan Africa.     

Palmitate and insulin synergistically induce IL-6 expression in human monocytes

Objectives

To summarize data supporting the effects of antidiabetes agents on glucose control and cardiovascular risk factors in patients with type 2 diabetes.

Methods

Studies reporting on the effects of antidiabetes agents on glycemic control, body weight, lipid levels, and blood pressure parameters are reviewed and summarized for the purpose of selecting optimal therapeutic regimens for patients with type 2 diabetes.

Results

National guidelines recommend the aggressive management of cardiovascular risk factors in patients with type 2 diabetes, including weight loss and achieving lipid and blood pressure treatment goals. All antidiabetes pharmacotherapies lower glucose; however, effects on cardiovascular risk factors vary greatly among agents. While thiazolidinediones, sulfonylureas, and insulin are associated with weight gain, dipeptidyl peptidase-4 inhibitors are considered weight neutral and metformin can be weight neutral or associated with a small weight loss. Glucagon-like peptide-1 receptor agonists and amylinomimetics (e.g. pramlintide) result in weight loss. Additionally, metformin, thiazolidinediones, insulin, and glucagon-like peptide-1 receptor agonists have demonstrated beneficial effects on lipid and blood pressure parameters.

Conclusion

Management of the cardiovascular risk factors experienced by patients with type 2 diabetes requires a multidisciplinary approach with implementation of treatment strategies to achieve not only glycemic goals but to improve and/or correct the underlying cardiovascular risk factors.     

Comparison of intima-media thickness and ophthalmic artery resistance index for assessing subclinical atherosclerosis in HIV-1-infected patients

Background

The determination of coronary flow reserve (CFR) is an essential concept at the moment of decision-making in ischemic heart disease. There are several direct and indirect tests to evaluate this parameter. In this sense, dobutamine stress echocardiography is one of the pharmacological method most commonly used worldwide. It has been previously demonstrated that CFR can be determined by this technique. Despite our wide experience with dobutamine stress echocardiography, we ignored the necessary heart rate to consider sufficient the test for the analysis of CFR. For this reason, our main goal was to determine the velocity of coronary flow in each stage of dobutamine stress echocardiography and the heart rate value necessary to double the baseline values of coronary flow velocity in the territory of the left anterior descending (LAD) coronary artery.

Methods

A total of 33 consecutive patients were analyzed. The patients included had low risk for coronary artery disease. All the participants underwent dobutamine stress echocardiography and coronary artery flow velocity was evaluated in the distal segment of LAD coronary artery using transthoracic color-Doppler echocardiography.

Results

The feasibility of determining CFR in the territory of the LAD during dobutamine stress echocardiography was high: 31/33 patients (94%). Mean CFR was 2.67 at de end of dobutamine test. There was an excellent concordance between delta HR (difference between baseline HR and maximum HR) and the increase in the CFR (correlation coefficient 0.84). In this sense, we found that when HR increased by 50 beats, CFR was ≥ 2 (CI 93-99.2%). In addition, 96.4% of patients reached a CFR ≥ 2 (IC 91.1 - 99%) at 75% of their predicted maximum heart rate.

Conclusions

We found that the feasibility of dobutamine stress echocardiography to determine CFR in the territory of the LAD coronary artery was high. In this study, it was necessary to achieve a difference of 50 bpm from baseline HR or at least 75% of the maximum predicted heart rate to consider sufficient the test for the analysis of CFR.