Administration of growth hormone or IGF-I to pregnant rats on a reduced diet throughout pregnancy does not prevent fetal intrauterine growth retardation and elevated blood pressure in adult offspring

Increasing evidence from human epidemiological studies suggests that poor growth before birth is associated with postnatal growth retardation and the development of cardiovascular disease in adulthood. We have shown previously that nutritional deprivation in the pregnant rat leads to intrauterine growth retardation (IUGR), postnatal growth failure, changes in the endocrine parameters of the somatotrophic axis, and to increased blood pressure in later life. In the present study, we investigated whether administration of insulin-like growth factor-I (IGF-I) or bovine growth hormone (GH) during pregnancy could prevent IUGR and/or alter long-term outcome. Dams h-om day 1 of pregnancy throughout gestation received a diet of nd libitum available food or a restricted dietary intake of 30% of ad libitum fed dams. From day 10 of gestation, dams were treated for 10 days with three times daily subcutaneous injections of saline (100 mu l), IGF-I (2 mu g/g body weight) or GH (2 mu g/g body weight). Maternal weight gain was significantly increased (P

Variable temperature and pressure study of the aquation reactions of cobalt(III) and chromium(III) penta- and tetra-amines

Preparation of a series of specific penta- and tetra-amine derivatives of Co-III and Cr-III with a neutral leaving ligand has been carried out in order to accomplish a fine tuning of the associativeness/dissociativeness of their substitution reactions. Spontaneous aquation reactions of the neutral ligands have been studied at variable temperature and pressure. Although rate constants and thermal activation parameters show an important degree of scatter, the values determined for the activation volumes of the substitution process illustrate the mechanistic fine tuning that may be achieved for these reactions. In all cases, in the absence of important steric constraints in the molecule, electronic inductive effects seem to be the most important factor accounting for the dissociative shifts observed both for pentaamine (i.e.Delta V double dagger=+4.0 or +14.0 cm(3) mol(-1) and +5.2 or +16.5 cm(3) mol(-1) for the aquation of cis- or trans-[Co(MeNH2)(NH3)(4)(DMF)](3+) and cis- or trans-[CoL15(DMF)](3+) respectively, where L-15 represents a pentaamine macrocyclic ligand), and tetraamine systems (i.e.Delta V double dagger=+4.1 or +8.4 cm(3) mol(-1) and -10.8 or -7.4 cm(3) mol(-1) for the aquation of cis-[Co(NH3)(4)Cl(DMAC)](2+) (DMAC=dimethylacetamide) or cis-[Co(en)(2)Cl(DMAC)](2+) and cis-[Cr(NH3)(4)Cl(DMF)](2+) or cis -[Cr(en)(2)Cl(DMF)](2+)). From the results, clear evidence is obtained which indicates that, only when the situation is borderline I-a/I-d, or the steric demands are increased dramatically, dissociative shifts are observed; in all other cases electronic inductive effects seem to be dominant for such a tuning of the substitution process.

Severity of hypertension in familial hyperaldosteronism type I: Relationship to gender and degree of biochemical disturbance

In familial hyperaldosteronism type I (FH-I), inheritance of a hybrid 11 beta-hydroxylase/aldosterone synthase gene causes ACTH-regulated aldosterone overproduction. In an attempt to understand the marked variability in hypertension severity in FH-I, we compared clinical and biochemical characteristics of 9 affected individuals with mild hypertension (normotensive or onset of hypertension after 15 yr, blood pressure never >160/100 mm Hg, less than or equal to 1 medication required to control hypertension, no history of stroke, age >18 yr when studied) with those of 17 subjects with severe hypertension (onset before 15 yr, or systolic blood pressure >180 mm Hg or diastolic blood pressure >120 mm Hg at least once, or greater than or equal to 2 medications, or history of stroke). Severe hypertension was more frequent in males (11 of 13 males vs. 6 of 13 females; P

Changes in intra-abdominal pressure during postural and respiratory activation of the human diaphragm

In humans, when the stability of the trunk is challenged in a controlled manner by repetitive movement of a limb, activity of the diaphragm becomes tonic but is also modulated at the frequency of limb movement. In addition, the tonic activity is modulated by respiration. This study investigated the mechanical output of these components of diaphragm activity. Recordings were made of costal diaphragm, abdominal, and erector spinae muscle electromyographic activity; intra-abdominal, intrathoracic, and transdiaphragmatic pressures; and motion of the rib cage, abdomen, and arm. During limb movement the diaphragm and transversus abdominis were tonically active with added phasic modulation at the frequencies of both respiration and limb movement. Activity of the other trunk muscles was not modulated by respiration. Intra-abdominal pressure was increased during the period of limb movement in proportion to the reactive forces from the movement. These results show that coactivation of the diaphragm and abdominal muscles causes a sustained increase in intra-abdominal pressure, whereas inspiration and expiration are controlled by opposing activity of the diaphragm and abdominal muscles to vary the shape of the pressurized abdominal cavity.

Quantification of free mycophenolic acid by high-performance liquid chromatography-atmospheric pressure chemical ionisation tandem mass spectrometry

To facilitate the investigation of free mycophenolic acid concentrations we developed a high-performance liquid chromatography tandem mass spectrometry method using indomethacin as an internal standard. Free drug was isolated from plasma samples (500 mul) using ultrafiltration, The analytes were extracted from the ultrafiltrate (200 mul) using C-18 solid-phase extraction. Detection was by selected reactant monitoring of mycophenolic acid (m/z 318.9-->190.9) and the internal standard (m/z 356.0-->297.1) with an atmospheric pressure chemical ionisation interface. The total chromatographic analysis time was 12 min. The method was found to be linear over the range investigated, 2.5-200 mug/l (r>0.990, n=6). The relative recovery of the method for the control samples studied (7.5, 40.0 and 150 mug/l) ranged from 95 to 104%. The imprecision of the method, expressed in terms of intra- and inter-day coefficients of variation, was

In vivo measurement of the effect of intra-abdominal pressure on the human spine

In humans, intra-abdominal pressure (IAP) is elevated during many everyday activities. This experiment aimed to investigate the extent to which increased IAP-without concurrent activity of the abdominal or back extensor muscles-produces an extensor torque. With subjects positioned in side lying on a swivel table with its axis at L3, moments about this vertebral level were measured when IAP was transiently increased by electrical stimulation of the diaphragm via the phrenic nerve. There was no electromyographic activity in abdominal and back extensor muscles. When IAP was increased artificially to similar to 15% of the maximum IAP amplitude that could be generated voluntarily with the trunk positioned in flexion, a trunk extensor moment (similar to6 Nm) was recorded. The size of the effect was proportional to the increase in pressure. The extensor moment was consistent with that predicted from a model based on measurements of abdominal cross-sectional area and IAP moment arm. When IAP was momentarily increased while the trunk was flexed passively at a constant velocity, the external torque required to maintain the velocity was increased. These results provide the first in vivo data of the amplitude of extensor moment that is produced by increased IAP. Although the net effect of this extensor torque in functional tasks would be dependent on the muscles used to increase the IAP and their associated flexion torque, the data do provide evidence that IAP contributes, at least in part, to spinal stability. (C) 2001 Elsevier Science Ltd. All rights reserved.

Positive end expiratory pressure during resuscitation of premature lambs rapidly improves blood gases without adversely affecting arterial pressure

Positive end expiratory pressure (PEEP) is important for neonatal ventilation but is not considered in guidelines for resuscitation. Our aim was to investigate the effects of PEEP on cardiorespiratory parameters during resuscitation of very premature lambs delivered by hysterotomy at similar to125 d gestation (term similar to147 d). Before delivery, they were intubated and lung fluid was drained. Immediately after delivery, they were ventilated with a Drager Babylog plus ventilator in volume guarantee mode with a tidal volume of 5 mL/kg. Lambs were randomized to receive 0, 4, 8, or 12 cm H2O of PEEP. They were ventilated for a 15-min resuscitation period followed by 2 h of stabilization at the same PEEP. Tidal volume, peak inspiratory pressure, PEEP, arterial pressure, oxygen saturation, and blood gases were measured regularly, and respiratory system compliance and alveolar/ arterial oxygen differences were calculated. Lambs that received 12 cm H2O of PEEP died from pneumothoraces; all others survived without pneumothoraces. Oxygenation was significantly improved by 8 and 12 cm H2O of PEEP compared with 0 and 4 cm H2O of PEEP. Lambs with 0 PEEP did not oxygenate adequately. The compliance of the respiratory system was significantly higher at 4 and 8 cm H2O of PEEP than at 0 PEEP. There were no significant differences in partial pressure of carbon dioxide in arterial blood between groups. Arterial pressure was highest with 8 cm H2O of PEEP, and there was no cardiorespiratory compromise at any level of PEEP. Applying PEEP during resuscitation of very premature infants might be advantageous and merits further investigation.

Prevalence of peripheral arterial disease: persistence of excess risk in former smokers

Objective: To determine the age-standardised prevalence of peripheral arterial disease (PAD) and associated risk factors, particularly smoking. Method: Design: Cross-sectional survey of a randomly selected population. Setting: Metropolitan area of Perth, Western Australia. Participants: Men aged between 65-83 years. Results: The adjusted response fraction was 77.2%. Of 4,470 men assessed, 744 were identified as having PAD by the Edinburgh Claudication Questionnaire and/or the ankle-brachial index of systolic blood pressure, yielding an age-standardised prevalence of PAD of 15.6% (95% confidence intervals (CI): 14.5%, 16.6%). The main risk factors identified in univariate analyses were increasing age, smoking current (OR=3.9, 95% CI 2.9-5.1) or former (OR=2.0, 95% CI 1.6-2.4), physical inactivity (OR=1.4, 95% CI 1.2-1.7), a history of angina (OR=2.2, 95% CI 1.8-2.7) and diabetes mellitus (OR=2.1, 95% CI 1.7-2.6). The multivariate analysis showed that the highest relative risk associated with PAD was current smoking of 25 or more cigarettes daily (OR=7.3, 95% CI 4.2-12.8). In this population, 32% of PAD was attributable to current smoking and a further 40% was attributable to past smoking by men who did not smoke currently. Conclusions: This large observational study shows that PAD is relatively common in older, urban Australian men. In contrast with its relationship to coronary disease and stroke, previous smoking appears to have a long legacy of increased risk of PAD. Implications: This research emphasises the importance of smoking as a preventable cause of PAD.

Persistence of ventilatory defect after resolution of pulmonary interstitial emphysema in a preterm baby

Pulmonary interstitial emphysema is a common complication of mechanical ventilation in preterm babies. We report a case of severe unilateral pulmonary interstitial emphysema in a premature newborn, treated with high-frequency oscillatory ventilation, lateral decubitus positioning and selective intubation. After complete radiological resolution of the pulmonary emphysema in the left lung, the patient was studied by electrical impedance tomography and a marked reduction of ventilation was identified in the left lung despite radiological resolution of the cysts. This finding indicates that functional abnormalities may persist for longer periods after radiologic resolution of such lesions.

Pulmonary Hypertension in Latin America Pulmonary Vascular Disease: The Global Perspective

Latin America is here defined as all of the Americas south of the United States. In the setting of pulmonary hypertension, there are social inequalities and geophysical aspects in this region that account for a high prevalence of certain etiologies. This review aimed to analyze some of these factors. Data were collected from the existing literature. Information also was obtained from local tertiary-care centers to where patients with pulmonary hypertension generally are referred. Further, local experience and expertise was taken into consideration. Three etiologies of pulmonary hypertension were found to be the most prevalent: schistosomiasis (similar to 1 million affected people in Brazil), high altitude (particularly in the Andes), and congenital heart disease (late diagnosis of congenital left-to-right shunts leading to development of pulmonary vasculopathy). The diversity in terms of ancestries and races probably accounts for the differences in phenotype expression of pulmonary hypertension when a given region is considered (eg, schistosomiasis-, high-altitude-, or congenital heart disease-associated pulmonary hypertension). Governmental measures are needed to improve social and economic inequalities with an obvious impact on certain etiologies, such as schistosomiasis and congenital heart disease. Early diagnosis of pulmonary hypertension and access to medication remain important challenges all over Latin America. CHEST 2010; 137(6)(Suppl):78S-84S