Imaging aortic valve calcification: significance, approach and implications.

Aortic stenosis is the most prevalent valvular heart disease worldwide, and rates are increasing with the growing and more elderly population. Although the precise mechanisms that underpin aortic valve stenosis are incompletely understood, pathological valvular calcification has emerged as a key instigator in mediating the biomechanical stiffening that can lead to symptoms, the need for aortic valve replacement, and death if left untreated. Here, we review the currently understood processes leading to aortic valve calcification, summarise the contemporary imaging assessments of valve calcification, and highlight how these might improve patient care and accelerate our pathological understanding and the development of an effective medical therapy.

Echocardiographic RV-E/e' for predicting right atrial pressure: a review.

Right atrial pressure (RAP) is a key cardiac parameter of diagnostic and prognostic significance, yet current two-dimensional echocardiographic methods are inadequate for the accurate estimation of this haemodynamic marker. Right-heart trans-tricuspid Doppler and tissue Doppler echocardiographic techniques can be combined to calculate the right ventricular (RV) E/e' ratio - a reflection of RV filling pressure which is a surrogate of RAP. A systematic search was undertaken which found seventeen articles that compared invasively measured RAP with RV-E/e' estimated RAP. Results commonly concerned pulmonary hypertension or advanced heart failure/transplantation populations. Reported receiver operating characteristic analyses showed reasonable diagnostic ability of RV-E/e' for estimating RAP in patients with coronary artery disease and RV systolic dysfunction. The diagnostic ability of RV-E/e' was generally poor in studies of paediatrics, heart failure and mitral stenosis, whilst results were equivocal in other diseases. Bland-Altman analyses showed good accuracy but poor precision of RV-E/e' for estimating RAP, but were limited by only being reported in seven out of seventeen articles. This suggests that RV-E/e' may be useful at a population level but not at an individual level for clinical decision making. Very little evidence was found about how atrial fibrillation may affect the estimation of RAP from RV-E/e', nor about the independent prognostic ability of RV-E/e' . Recommended areas for future research concerning RV-E/e' include; non-sinus rhythm, valvular heart disease, short and long term prognostic ability, and validation over a wide range of RAP.

Adsorption of Pb(II) ions from contaminated water by 1,2,3,4-butanetetracarboxylic acid-modified microcrystalline cellulose: Isotherms, kinetics, and thermodynamic studies.

Microcrystalline cellulose (MCC) has been utilized as an adsorbent material for the removal of Pb(II) ions from aqueous solution after treatment with 1,2,3,4-butanetetracarboxylic acid (BTCA) at elevated temperature to obtain MMCC. The resulting adsorbent was characterized for point of zero point charge (pHZPC), estimation of carboxyl content, Fourier transform infrared spectroscopy (FT-IR), scan electron microscopy (SEM), and textural properties, including surface area, and subsequently utilized for the removal of Pb(II) ions from aqueous solution. The adsorption process was probed by investigating the effect of adsorbent dose, pH of solution, temperature, agitation time, and Pb(II) ion concentration. The results showed successful functionalization of MCC using BTCA, significantly improved the binding properties of the adsorbent towards Pb(II) ions. Isothermal adsorption data was analyzed using Langmuir, Freundlich and Temkin models, evaluated via nonlinear regression analysis. The maximum adsorption capacity was found to be 1155 mg/g (at pH 5 and 30 °C) from Langmuir theory, and appears independent of surface area. The Freundlich model was found to provide the best fit and the constant n was determined to be 2.69, indicating that adsorption of Pb(II) ions onto MMCC is favorable. Kinetic modelling showed good agreement for the pseudo-second order kinetic model, supporting the theory that chemisorption is involved in the adsorption process, which is promoted by a high density of active sites. Thermodynamic analysis showed that the adsorption of Pb(II) ions onto MMCC was endothermic and nonspontaneous; hence, MMCC offers an effective method of Pb(II) ion removal from aqueous solutions, with potential for water remediation processes.

Nitric oxide-mediated nonadrenergic noncholinergic relaxation of piglet pulmonary arteries decreases with postnatal age.

Nonadrenergic noncholinergic (NANC) vasodilator mechanisms may contribute to the maintenance of adult pulmonary and systemic vascular tone. However, their actions in the neonatal circulation have not been studied. We aimed to investigate NANC vasorelaxation in neonatal and 2-week-old piglet pulmonary and mesenteric arteries and to examine the potential role of nitric oxide (NO) in this phenomenon. Responses to electric field stimulation (EFS, 50V, 0.25-32 Hz) were investigated in pulmonary and mesenteric artery rings (external diameter 150-200 microm) precontracted with the thromboxane A2 mimetic U46619, in the presence of guanethidine (10 microM) and atropine (10 microM). Under these conditions, EFS resulted in a frequency dependent relaxation of newborn pulmonary (maximal relaxation of 53+/-9.1%), mesenteric (68.8.2+/-7.1%) and 2-wk-old mesenteric (46 6.3%) arteries but this relaxation was significantly reduced (4.5+/-2.2%) in 2-week-old pulmonary arteries. In neonatal pulmonary arteries, the neurotoxin tetrodotoxin (0.3 muM), the NO synthase inhibitor L-NAME (0.1 mM), and the guanylyl cyclase inhibitor ODQ (10 microM) abolished EFS-induced relaxations, suggesting that NANC relaxation of porcine neonatal pulmonary arteries is mediated by NO, which is probably neuronal in origin. However, The expression in pulmonary arteries of the neuronal NO synthase (nNOS), as determined by Western-blot analysis, increased with postnatal age whereas the expression of the endothelial NOS (eNOS) did not change. In conclusion, NANC relaxation is present in neonatal pulmonary and mesenteric arteries and it is, at least partially, mediated through NO. NANC relaxation of porcine pulmonary and mesenteric arteries decreases with postnatal maturation.

Hydrogen adsorption on functionalized nanoporous activated carbons.

There is considerable interest in hydrogen adsorption on carbon nanotubes and porous carbons as a method of storage for transport and related energy applications. This investigation has involved a systematic investigation of the role of functional groups and porous structure characteristics in determining the hydrogen adsorption characteristics of porous carbons. Suites of carbons were prepared with a wide range of nitrogen and oxygen contents and types of functional groups to investigate their effect on hydrogen adsorption. The porous structures of the carbons were characterized by nitrogen (77 K) and carbon dioxide (273 K) adsorption methods. Hydrogen adsorption isotherms were studied at 77 K and pressure up to 100 kPa. All the isotherms were Type I in the IUPAC classification scheme. Hydrogen isobars indicated that the adsorption of hydrogen is very temperature dependent with little or no hydrogen adsorption above 195 K. The isosteric enthalpies of adsorption at zero surface coverage were obtained using a virial equation, while the values at various surface coverages were obtained from the van't Hoff isochore. The values were in the range 3.9-5.2 kJ mol(-1) for the carbons studied. The thermodynamics of the adsorption process are discussed in relation to temperature limitations for hydrogen storage applications. The maximum amounts of hydrogen adsorbed correlated with the micropore volume obtained from extrapolation of the Dubinin-Radushkevich equation for carbon dioxide adsorption. Functional groups have a small detrimental effect on hydrogen adsorption, and this is related to decreased adsorbate-adsorbent and increased adsorbate-adsorbate interactions.

Adrenocortical responsiveness is blunted in twin relative to singleton ovine fetuses.

Twin fetuses experience much higher rates of perinatal mortality/morbidity than age- and weight-matched singletons. Across species, the prepartum increase in fetal plasma cortisol is responsible for maturing a number of systems in preparation for birth and the immediate postnatal period. In sheep, it is known that basal adrenocortical function is delayed in twins relative to singletons. Thus, it could be argued that relative immaturity in twins may explain their increased susceptibility to stress in the perinatal period and their relatively poor perinatal outcome. However, whether adrenocortical responsiveness to stress is also diminished in the twin fetus and whether the fetal cardiovascular, metabolic and endocrine defences to acute stress are comparatively weak in the twin fetus is unknown. This study investigated the effect of twinning on adrenocortical responsiveness to either the physiological stress of acute hypoxaemia or to an exogenous ACTH test, and on the fetal cardiovascular, metabolic and endocrine responses to acute hypoxaemic stress. Twenty Welsh Mountain sheep fetuses were chronically instrumented (1-2% halothane) at 121 +/- 3 days of gestation (term is ca 145 days) with amniotic and vascular catheters and with a transit-time flow probe around a femoral artery. The animals were divided into two groups based upon fetal number (singletons, n= 10; twins, n= 10), as determined at surgery. At 130 +/- 2 days, a 1 h episode of acute, isocapnic hypoxaemia (to reduce carotid P(O(2)) to 12 +/- 1 mmHg) was induced in all fetuses by reducing the maternal inspired O(2) fraction (F(IO(2)); 9% O(2) in N(2)). Fetal cardiovascular variables were recorded at 1 s intervals throughout the experimental protocol and arterial blood samples taken at appropriate intervals for biophysical (blood gases, glucose, lactate) and endocrine (catecholamines, vasopressin, cortisol, ACTH) measures. At 133 +/- 2 days a 2.5 microg bolus dose of synthetic ACTH (Synacthen; Ciba Pharmaceuticals, UK) was injected i.v. into eight of the singleton and six of the twin fetuses to determine adrenocortical steroidogenic sensitivity to exogenous ACTH. Under basal conditions, twins had lower plasma cortisol concentration, arterial blood pressure and femoral blood flow relative to singleton fetuses. Twins responded to acute hypoxaemia with similar pressor and vasopressor responses compared to singleton fetuses. However, the rate pressure product, an index of myocardial work, tended to decrease during hypoxaemia in twins, in contrast to the increase observed in singletons. Similar increases in the fetal plasma concentrations of ACTH, AVP, noradrenaline and adrenaline were observed during hypoxaemia in both groups; however, both the increments in fetal plasma concentration of cortisol in response to acute hypoxaemia and to exogenous ACTH were blunted in twins relative to singletons. This study shows that basal adrenocortical function as well as adrenocortical responsiveness is blunted in the twin relative to the singleton fetus. Further, the mechanism for adrenocortical blunting resides at the level of the adrenal cortex rather than higher up the axis. Relative adrenocortical immaturity in the twin fetus may reflect a specific endocrine adaptation to prolong gestation in multiple ovine pregnancies; however, such an adaptation does not affect the cardiovascular, metabolic or endocrine defence responses to acute hypoxaemia in the twin fetus.

Effects of prevailing hypoxaemia, acidaemia or hypoglycaemia upon the cardiovascular, endocrine and metabolic responses to acute hypoxaemia in the ovine fetus.

Although it is established that the fetus can successfully withstand a single, acute hypoxaemic challenge during gestation, little is known about what effects prevailing adverse intrauterine conditions might have on the fetal response to acute hypoxaemia. The aims of this study were therefore: (1) to characterise the effects of prevailing and sustained hypoxaemia, acidaemia or hypoglycaemia on the fetal cardiovascular responses to an episode of acute hypoxaemia; and (2) to determine the effects of these adverse intrauterine conditions on mechanisms mediating these cardiovascular responses. Thirty-three Welsh Mountain sheep fetuses were chronically instrumented (1-2 % halothane) between 117 and 125 days of gestation (term is ca 145 days) with amniotic and vascular catheters and with a transit-time flow probe around a femoral artery. The animals were divided retrospectively into four groups based upon post-surgical, sustained, basal blood oxygen (chronically hypoxaemic; P(a,O2), 17.3 +/- 0.5 mmHg; n = 8), glucose (chronically hypoglycaemic; blood glucose, 0.49 +/- 0.03 mmol l(-1); n = 6) and acid-base (chronically acidaemic; pH(a), 7.25 +/- 0.01; n = 5) status. Values for compromised fetuses were -2 S.D. from a group of control (n = 14) fetuses. At 130 +/- 4 days, a 1 h episode of acute, isocapnic hypoxaemia (9 % O(2) in N(2), to reduce carotid P(a,O2) to 12 +/- 1 mmHg) was induced in all fetuses by reducing the maternal inspired O(2) fraction (F(I,O2)). Fetal cardiovascular variables were recorded at 1 s intervals throughout the experimental protocol and arterial blood samples taken at appropriate intervals for biophysical (blood gases, glucose, lactate) and endocrine (catecholamines, vasopressin, cortisol, ACTH) measures. During acute hypoxaemia all fetuses elicited hypertension, bradycardia and femoral vasoconstriction. However, prevailing fetal compromise altered the cardiovascular and endocrine responses to a further episode of acute hypoxaemia, including: (1) enhanced pressor and femoral vasoconstriction; (2) greater increments in plasma noradrenaline and vasopressin during hypoxaemia; and (3) basal upward resetting of hypothalamic-pituitary-adrenal axis function. Only chronically hypoxaemic fetuses had significantly elevated basal concentrations of noradrenaline and enhanced chemoreflex function during acute hypoxaemia. These data show that prevailing adverse intrauterine conditions alter the capacity of the fetus to respond to a subsequent episode of acute hypoxaemia; however, the partial contributions of hypoxaemia, acidaemia or hypoglycaemia to mediating these responses can vary.

Adsorption dynamics of gases and vapors on the nanoporous metal organic framework material Ni2(4,4'-bipyridine)3(NO3)4: guest modification of host sorption behavior.

This study combines measurements of the thermodynamics and kinetics of guest sorption with powder X-ray diffraction measurements of the nanoporous metal organic framework adsorbent (host) at different adsorptive (guest) loadings. The adsorption characteristics of nitrogen, argon, carbon dioxide, nitrous oxide and ethanol and methanol vapors on Ni2(4,4'-bipyridine)3(NO3)4 were studied over a range of temperatures as a function of pressure. Isotherm steps were observed for both carbon dioxide and nitrous oxide adsorption at approximately 10-20% of the total pore volume and at approximately 70% of total pore volume for methanol adsorption. The adsorption kinetics obey a linear driving force (LDF) mass transfer model for adsorption at low surface coverage. At high surface coverage, both methanol and ethanol adsorption follow a combined barrier resistance/diffusion model. The rates of adsorption in the region of both the carbon dioxide and methanol isotherm steps were significantly slower than those observed either before or after the step. X-ray diffraction studies at various methanol loadings showed that the host structure disordered initially but underwent a structural change in the region of the isotherm step. These isotherm steps are ascribed to discrete structural changes in the host adsorbent that are induced by adsorption on different sites. Isotherm steps were not observed for ethanol adsorption, which followed a Langmuir isotherm. Previous X-ray crystallography studies have shown that all the sites are equivalent for ethanol adsorption on Ni2(4,4'-bipyridine)3(NO3)4, with the host structure undergoing a scissoring motion and the space group remaining unchanged during adsorption. The activation energies and preexponential factors for methanol and ethanol adsorption were calculated for each pressure increment at which the linear driving force model was obeyed. There was a good correlation between activation energy and ln(preexponential factor), indicating a compensation effect. The results are discussed in terms of reversible adsorbate/adsorbent (guest/host) structural changes and interactions and the adsorption mechanism. The paper contains the first evidence of specific interactions between guests and functional groups leading to structural change in flexible porous coordination polymer frameworks.

A novel method for controlled and reversible long term compression of the umbilical cord in fetal sheep.

1. In fetal sheep during late gestation the aims of the present study were to (1) develop a technique for inducing prolonged but reversible periods of controlled compression of the umbilical cord and (2) characterise the cardiovascular, endocrine and metabolic responses to this challenge. 2. Under 1-2 % halothane anaesthesia, 16 Welsh Mountain sheep fetuses were chronically instrumented at 118 +/- 2 days of gestation (term is ca 145 days) with an inflatable occluder cuff around the umbilical cord, amniotic and femoral vascular catheters and with transit-time flow probes around the contra-lateral femoral artery and an umbilical artery. At 125 days, umbilical blood flow was reduced by 30 % from a pre-determined 24 h baseline for 3 days by automated servo-controlled inflation of the occluder cuff (n = 8). The occluder was then deflated allowing return of umbilical blood flow to baseline. The remaining eight fetuses were used as sham-operated controls in which the occluder was not inflated throughout the protocol. Fetal cardiovascular variables were recorded at 8 s intervals and arterial blood samples taken for measurement of blood gases, glucose and lactate and plasma adrenaline, noradrenaline and vasopressin concentration throughout the study. 3. Automated servo-controlled inflation of the occluder cuff, programmed to reduce umbilical blood flow by 30 % from baseline, reduced umbilical blood flow by 30.2 +/- 1.7 %, with a coefficient of variation during compression of 6.5 +/- 1.1 %. Sustained partial compression of the umbilical cord produced falls in fetal arterial pH, P(a,O2), percentage O(2) saturation of haemoglobin, and hindlimb oxygen delivery, and increases in P(a,CO2), haemoglobin concentration, arterial blood oxygen carrying capacity and in blood glucose and lactate concentrations. While the reductions in P(a,O2), percentage saturation of haemoglobin and hindlimb oxygen delivery and the increase in P(a,CO2) were sustained throughout compression, the reduction in arterial pH and the increase in arterial oxygen carrying capacity had returned towards baseline values by 48 h compression. Fetal blood lactate concentrations reached a peak at 8 h of compression and, thereafter, were maintained at an elevated level relative to baseline. 4. Partial compression of the umbilical cord produced fetal hypertension, a reduction in femoral blood flow and, consequently, an increase in calculated fetal femoral vascular resistance for the duration of the challenge. In addition, the fall in heart rate measured in sham control fetuses by the end of the study, did not occur in cord-compressed fetuses. Cosinor analysis on 24 h rhythms of cardiovascular data indicated a significant increase in the amplitude of the 24 h rhythm in heart rate in cord-compressed fetuses relative to sham controls during the period of compression or sham-compression. Furthermore, cord compression led to an increase in fetal plasma noradrenaline, but not adrenaline and vasopressin concentrations relative to sham control fetuses. 5. In conclusion, a novel reversible method for controlled, long-term compression of the umbilical cord in sheep has been developed. The data show that sustained, partial compression of the umbilical cord produced moderate but sustained asphyxia, which resolved after the end of the compression period, and induced changes in fetal cardiovascular, endocrine and metabolic functions.

Purinergic contribution to circulatory, metabolic, and adrenergic responses to acute hypoxemia in fetal sheep.

This study investigated the effects on femoral vascular resistance, blood glucose and lactate levels, and plasma catecholamine concentrations of fetal treatment with an adenosine receptor antagonist during acute hypoxemia in fetal sheep during late gestation. Under anesthesia, seven fetal sheep were instrumented between 117 and 118 days gestation (term is approximately 145 days) with vascular and amniotic catheters and an ultrasonic probe around a femoral artery. Six days after surgery, all fetuses were randomly subjected to a 3-h experiment consisting of 1 h of normoxia, 1 h of hypoxemia, and 1 h of recovery. This was done during either intravenous infusion of vehicle or the adenosine receptor antagonist [8-(p-sulfophenyl)-theophylline; 8-SPT] dissolved in vehicle. During vehicle infusion, all fetuses responded to hypoxemia with bradycardia, an increase in arterial blood pressure, and femoral vasoconstriction. Increases in blood glucose and lactate concentrations and in plasma epinephrine and norepinephrine concentrations also occurred in all fetuses during hypoxemia. Fetal treatment with 8-SPT markedly attenuated the bradycardic, hypertensive, vasoconstrictor, glycemic, and adrenergic responses to hypoxemia, but it did not affect the increase in blood lactate concentrations during hypoxemia. These data show that adenosine is involved in the mechanisms mediating fetal cardiovascular, metabolic, and adrenergic responses to hypoxemia in fetal sheep. Fetal treatment with 8-SPT mimics the effects of carotid sinus nerve section on fetal cardiovascular function during hypoxemia, suggesting a role for adenosine in mediating fetal cardiovascular chemoreflexes.

Plasma adrenocorticotropin and cortisol concentrations during acute hypoxemia after a reversible period of adverse intrauterine conditions in the ovine fetus during late gestation.

The present study determined the pituitary-adrenal responses to acute hypoxemia after a period of reversible adverse intrauterine conditions produced by partial compression of the umbilical cord for 3 days in the sheep fetus during late gestation. At 118 +/- 2 days gestation (term is approximately 145 days), 12 sheep fetuses were instrumented under halothane anesthesia with an occluder cuff around the umbilical cord, amniotic and vascular catheters, and a transit-time flow probe around an umbilical artery. In 6 of the fetuses at 125 days, umbilical blood flow was reduced by about 30% from baseline for 3 days (UCC), after which the occluder was deflated. The remaining 6 fetuses acted as sham-operated controls in which the occluder was not inflated. All fetuses were then subsequently subjected to 2 periods of acute hypoxemia, elicited by reducing the maternal inspired fraction of oxygen (FiO(2)) at 2 +/- 1 and 5 +/- 2 days after the end of cord compression or sham compression. In addition, 4 fetuses from each group were subjected to an ACTH challenge 1-2 days after the final episode of acute hypoxemia. Maternal and fetal arterial blood samples were taken at appropriate intervals during cord compression, acute hypoxemia, and ACTH challenge for analyses of blood gases, pH, and plasma ACTH and cortisol concentrations. Partial compression of the umbilical cord produced reversible mild fetal asphyxia, a transient increase in fetal plasma ACTH, and a progressive increase in fetal plasma cortisol. At 5 +/- 2 days after the end of compression, despite similar blood gas status between the groups, basal plasma cortisol, but not ACTH, concentrations were significantly greater in compressed fetuses relative to sham controls. However, this dissociation did not affect a similar increment in fetal plasma ACTH and cortisol concentrations during acute hypoxemia or in the fetal plasma cortisol response to the ACTH challenge in either group. An increase in adrenocortical mass occurred in fetuses preexposed to partial compression of the umbilical cord relative to sham controls. The data suggest that fetal exposure to a reversible period of adverse intrauterine conditions produced by partial compression of the umbilical cord does not affect the magnitude of the fetal hypothalamic-pituitary-adrenal axis response to subsequent acute hypoxemia, but it leads to resetting of basal hypothalamic-pituitary-adrenal axis function in the fetus. The mechanism for this resetting may include an increase in adrenocortical steroidogenic synthetic capacity, but it is not due to a change in adrenocortical sensitivity to ACTH. Inappropriate fetal glucocorticoid exposure after reversible periods of adverse intrauterine conditions has important implications for fetal and postnatal development.

Neuropeptide Y in the sheep fetus: effects of acute hypoxemia and dexamethasone during late gestation.

Plasma concentrations of neuropeptide Y (NPY) were measured in pregnant ewes and their fetuses under basal conditions and in response to acute hypoxemia during late gestation. The effects of fetal treatment with dexamethasone on these NPY responses were also examined. Under general anesthesia, 10 Welsh Mountain ewes and their fetuses were chronically instrumented between 117-120 days gestation (dGA; term is approximately 145 dGA) with vascular and amniotic catheters, and an ultrasonic probe around a femoral artery of each fetus. At 124 dGA, five fetuses were continuously infused i.v. with dexamethasone for 48 h at a rate of 1.73 +/- 0.16 microg x kg(-1) x h(-1) while the remaining five fetuses received vehicle at the same rate. At 126 dGA, 45 h from the onset of either infusion, 1 h of materno-fetal hypoxemia was induced by reducing maternal FiO2. During normoxia, maternal plasma NPY concentrations were three times those measured in fetal plasma in both groups. During hypoxemia, PaO2 fell to similar levels in the control and dexamethasone-treated groups in both mothers and fetuses. In control animals, there was a significant increase in the NPY concentration in fetal, but not maternal, plasma during hypoxemia. Fetal treatment with dexamethasone significantly enhanced the fetal NPY response to acute hypoxemia but had no effects on basal NPY levels in the fetal or maternal plasma or on the maternal response to acute hypoxemia. These data show: 1) differences between the maternal and fetal plasma NPY response to maternal inhalation hypoxia; 2) that NPY may play a role in mediating fetal defense responses to acute hypoxemia; and 3) that fetal exposure to glucocorticoids modifies the fetal plasma NPY response to acute hypoxemia.

Low doses of dexamethasone suppress pituitary-adrenal function but augment the glycemic response to acute hypoxemia in fetal sheep during late gestation.

Despite the widespread use of antenatal glucocorticoid therapy in obstetric practice, little is known about the effects of synthetic glucocorticoids on the fetal capacity to respond to episodes of acute hypoxemia, such as may occur during labor and delivery. This study investigated the effects of prolonged fetal exposure to low concentrations of dexamethasone on the fetal ACTH, cortisol, and glycemic responses to an episode of acute hypoxemia during the period of dexamethasone treatment in sheep. At 118 d of gestation (term is approximately 145 d), 11 fetal sheep had catheters implanted under halothane anesthesia. From 124 d, five fetuses were infused i.v. continuously with dexamethasone (1.80 +/- 0.15 microg x kg(-1) x h(-1) in 0.9% saline at 0.5 mL/h) for 48 h, and the other six fetuses received saline solution i.v. at the same rate. At 45 h of infusion, acute hypoxemia was induced in all fetuses for 1 h by reducing the maternal inspired fraction of oxygen. During glucocorticoid treatment, fetal plasma dexamethasone concentrations increased to 3.9 +/- 0.2 nM by 24 h and remained elevated for the rest of the infusion period. During hypoxemia, a similar fall in fetal arterial PO2 occurred in both saline-infused and dexamethasone-treated fetuses. In control fetuses, significant increases in plasma ACTH and cortisol concentrations and in blood glucose concentrations occurred during hypoxemia. Dexamethasone treatment prevented the increases in fetal plasma ACTH and cortisol, and augmented the blood glucose response, induced by hypoxemia. These data indicate that prolonged fetal exposure to low concentrations of dexamethasone suppresses pituitary-adrenal function, but augments the glycemic response, to acute hypoxemia in fetal sheep during late gestation.

A comparison of the effects of intravenous tramadol, codeine, and morphine on gastric emptying in human volunteers.

UNLABELLED: We compared the effects of i.v. tramadol (1.25 mg/kg), codeine (1 mg/kg), morphine (0.125 mg/kg), and saline on gastric emptying in 10 healthy human volunteers using a double-blind, randomized, cross-over design. Subjects received one treatment at each of four sessions, 2 wk apart. Gastric emptying was studied using the paracetamol absorption test. There were significant differences when comparing all treatments for concentration-time data (P = 0.002), peak serum paracetamol concentrations (Cmax; P < 0.001), times at Cmax (Tmax; P = 0.003), and areas under the curves from Time 0 to 360 min (AUC(0-360); P = 0.049). Morphine profoundly inhibited gastric emptying. Tramadol had measurable but statistically insignificant inhibitory effects on gastric emptying compared with saline (mean +/- SEM: Cmax 22.4 +/- 2.2 vs 26.8 +/- 2.5 mg/L [P = 0.19], Tmax 33 +/- 5.4 vs 19.5 +/- 2.3 min [P = 0.054] for tramadol versus saline, respectively). Compared with morphine, the Cmax (P < 0.01), Tmax, and AUC(0-360) (P < 0.05) values for tramadol were significantly different. The Tmax value for codeine (63.3 +/- 11.7) was greater than that for tramadol (P = 0.034). We conclude that tramadol has a measurable but smaller inhibitory effect on gastric emptying compared with other opioids. IMPLICATIONS: We compared the effect of tramadol, an unconventional opioid painkiller, on stomach emptying with that of codeine and morphine in a human volunteer study. Tramadol had a measurable but smaller effect and may have clinical and economic advantages in acute pain management compared with conventional painkillers.

Influence of a changed care environment on bacterial colonization of burn wounds.

This study investigated the influence of a conditioned care environment per se on bacterial colonization of burn wounds. Two cohorts of burn patients were treated in the successive years 1992 and 1993, the first group in a (permanent) purpose-designed unit and the second in wards of traditional 'open' design, during renovation of the unit. Patients who were admitted to the permanent and temporary units numbered 224 and 231 respectively, the groups being similar in features that generally influence the course and outcome of burn injuries. The principles and practice of treatment by the burn care team remained the same in both years. No significant difference in wound colonization rates was found between the two groups. We conclude that while the other known advantages of managing burn patients in purpose-designed units remain valid, a conditioned care environment per se does not influence bacterial colonization rates of burn wounds.

Glutaraldehyde concentration in the sterilization of endoscopes.

Controversy over appropriate disinfection of endoscopes continues with the most commonly utilized solution in Australian hospitals, despite concern over its efficacy, being 1% glutaraldehyde (AIDAL). Review of the in-use concentrations of glutaraldehyde at Princess Alexandra Hospital has documented a significant dilutional effect in 1% glutaraldehyde by gastrointestinal endoscopes. Each hospital should determine the minimum in-use concentration acceptable for any given disinfecting solution and any given range of endoscopes. Once this level is reached, a solution change should routinely occur. Such decisions can only be made by regularly monitoring in-use concentrations of disinfectants.

Structure-function analysis of the vitamin B12 receptor of Escherichia coli by means of informational suppression.

We describe a genetic analysis of the vitamin B12 receptor of Escherichia coli. Through the use of informational suppression, we have been able to generate a family of receptor variants, each identical save for a single, known substitution (Ser, Gln, Lys, Tyr, Leu, Cys, Phe) at a known site. We have studied 22 different mutants, 14 in detail, distributed throughout the length of the btuB gene. Most amino acid substitutions have a pleiotropic effect with respect to all ligands tested, the two colicins E1 and E3, the T5-like bacteriophage BF23, and vitamin B12. (The dramatic effect of a single amino acid substitution is also well exemplified by the G142A missense change which renders the receptor completely non-functional.) In some instances, however, we have been able to modify a subset of receptor functions (viz. Q62, Q150 and Q299 and the response to phage BF23). These data are summarized on a two-dimensional folding model for the BtuB protein in the outer membrane (devised using both amphipathic beta-strand analysis and sequence conservation amongst the TonB-dependent receptors). In addition, we report that the extreme C-terminus of BtuB is vital for receptor localization and provide evidence for it being a membrane-spanning beta-sheet with residue L588 situated on its hydrophobic surface. Two of the C-terminal btuB mutations are located within the region of overlap with the recently identified dga (murl) gene.