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This paper describes the first demonstration of vibration isolation and suspension systems, which have been developed with view to application in the proposed Australian International Gravitational Observatory. In order to achieve optimal performance at low frequencies new components and techniques have been combined to create a compact advanced vibration isolator structure. The design includes two stages of horizontal preisolation and one stage of vertical preisolation with resonant frequencies approximately 100 mHz. The nested structure facilitates a compact design and enables horizontal preisolation stages to be configured to create a superspring configuration, where active feedback can enable performance close to the limit set by seismic tilt coupling. The preisolation stages are combined with multistage three-dimensional (3D) pendulums. Two isolators suspending mirror test masses have been developed to form a 72 m optical cavity with finesse approximately 700 in order to test their performance. The suitability of the isolators for use in suspended optical cavities is demonstrated through their ease of locking, long term stability, and low residual motion. An accompanying paper presents the local control system and shows how simple upgrades can substantially improve residual motion performance.

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BACKGROUND: NO production (NOex) in the airway epithelium is increased in asthmatic patients and is potently inhibited by anti-inflammatory treatments. The study was designed to compare the: (i) levels of NOex in two groups of asthmatic children residing in different environments (one in a national park in the mountains and the other in a large city) and (ii) the influence of glucocorticoids on levels of NOex between the children and those without treatment. METHODS: The measurements were performed during the same period in the two locations, 100 km apart. NOex was measured using a chemiluminescence analyzer in controls and two comparable groups of asthmatic children. The first group included 63 children (10+/-3 years) recruited from a specialized institution for asthmatic children, and the second group consisted of 46 asthmatic children (9+/-3 years) living in an urban area. A reference group of 17 healthy children residing in the same city was also studied. MEASUREMENTS AND RESULTS: The concentrations of NOex in children in the specialized institution were significantly lower (P<.001) than those in asthmatic children living in the city (5.1+/-2.4 vs. 13.8+/-9.3 ppb) and comparable to those in healthy controls (5.3+/-4.0 ppb). In the urban area, NOex levels increased when atmospheric pollution recorded on the previous day had increased. In contrast to that observed in the urban children, glucocorticoids had little influence on the levels of NOex in the children living in the specialized institution. CONCLUSIONS: Although these relationships need to be confirmed, our findings show that for the determination of NOex, specifying the quality of the environment, in particular, the purity of the air respired by asthmatic children, not only at the time of measurement but also over the previous days, is important.

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The placental transfer of three opioids used in peridural analgesia, fentanyl, alfentanil and sufentanil, and two reference substances, antipyrine and *H2O, was determined ex vivo in the human placental cotyledon system. (1) In the first set of experiments, the infusion rates were constant and fixed at physiological flow rates. Under these conditions, the magnitude of the materno-fetal transfer was in the following order: *H2O = antipyrine = fentanyl > alfentanil > sufentanil. No particular influence of molecular weight, lipophilia, pKa or the degree of ionization could be discerned. (2) In the second set of experiments, the influence of different flow rates, reflecting various pathophysiological conditions, was examined. There was a linear relationship between the maternal flow and the materno-fetal transfer of the three opioids. On the other hand, for antipyrine and tritiated water, the relationship was logarithmic, a difference attributed to the marked lipophilia of the opioids. (3) At high maternal flow rates, saturation was observed for all five substances due to the short duration of contact with the membrane. There were logarithmic relationships between the maternal flow and the materno-fetal transfer. (4) These findings emphasize the importance of the lipophilic and hydrophilic characteristics of drugs on placental transfer, especially in the event of fluctuations in maternal flow.

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The present study was designed to assess the effect of adrenaline on the plasma concentrations of fentanyl in mothers and umbilical vessels after epidural administration for caesarean section. Thirty patients undergoing elective caesarean section were allocated randomly into two groups. Group 1 (n = 16) received 100 microg fentanyl, 10 ml of 0.5% bupivacaine and 10 ml 2% lidocaine, while group II (n = 14) received 100 microg fentanyl, 10 ml of 0.5% bupivacaine with adrenaline 1:200 000, and 10 ml of 2% lidocaine with adrenaline 1:80 000. Blood samples were obtained from the maternal antecubital vein (MV) at various times up to 6 hours after epidural injection, and from umbilical vein (UV) and arteries (UA) at birth for determination of plasma fentanyl by radioimmunoassay. Fentanyl Cmax and Tmax in MV did not differ significantly between the two groups. In umbilical vessels, plasma fentanyl concentrations were comparable in the two groups: (0.12 +/- 0.08 ng ml(-1) and 0.13 +/- 0.08 ng ml(-1) in UV and 0.08 +/- 0.07 ng ml(-1) and 0.06 +/- 0.05 ng ml(1) in UA of groups I and II respectively). The maximum plasma concentration in UV was 0.24 ng ml(-1) in group I and 0.25 ng ml(-1) in group II. There was no significant correlation between umbilical vessel (vein or artery):MV ratio and dose to delivery interval and no difference between the two groups in Apgar score or umbilical cord pH.

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Two methods of assaying alpha interferon (IFN-alpha) were compared during an experiment aimed at determining whether IFN-alpha crosses the human placenta. Human placentas, collected after delivery following a normal pregnancy to term, were catheterized on both sides: fetal and maternal. The IFN-alpha was introduced in known amounts in the maternal circulation and was assayed in the efferent fetal fluid. The following two detection methods were used: radioimmunoassay by competition with [125I]IFN-alpha and assay with a biological system in which IFN-alpha protected Madin-Darby bovine kidney cells from destruction by vesicular stomatitis virus. The results obtained by the two methods were in perfect agreement for the efferent fetal fluid samples. They showed the absence of placental transfer of IFN-alpha. The biological method was found to be more sensitive than radioimmunoassay for low IFN-alpha titers (< 10 IU/ml) but was less reproducible, probably owing to the use of twofold dilutions. The specificities of the two methods were similar and their practicalities were equivalent; the biological method, however, was less costly. The study illustrates the complementarity of the two methods, which were based on different principles. The agreement obtained between the two methods provides a clear confirmation of the experimental results.

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Interferon can be used for VIH+ pregnant women, to decrease materno-fetal contamination. Added to maternal circulation, its behaviour was studied by human placental cotyledon ex vivo perfusion. Human recombinant IFN 2a and reference substance 3H2O were injected in intervillous chamber and their behaviours in venous fetal and maternal circulations was followed. At steady state, in fetal circulation 3H2O concentration was 37% of injected rate whereas no IFN transfer rate was observed. In both venous circulations IFN amounts were lower than injected ones 56% versus of 82% for water (p < 0.05). IFN didn't cross placental filter and disappeared partially during placental contact.

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Placental transfer of unfractionated heparin (UH), of low molecular weight heparin CY 216 (LMWH) and of Dermatan sulphate (DS) was studied using the human perfused placental cotyledon model. Two different techniques were used to assess the transfer: labelled molecules and biological activities as measured by antifactor Xa or antifactor IIa activities. No biological activity was present in the fetal circulation, for any of the drugs used; however, very low fractions of the perfused radioactivity were recorded, 0.76% +/- 0.36%, 1.46% +/- 1.44% and 2.37% +/- 0.89% for DS, UH and LMWH, respectively.

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The maternal and umbilical concentrations of fentanyl were measured after epidural analgesia for cesarean section, using a highly sensitive radioimmunoassay method. Sixteen parturients were anesthetized with a single epidural injection of a mixture of 85 mg bupivacaine 0.5%, 60 mg etidocaine 1%, and 100 micrograms fentanyl with epinephrine 1:200,000. Apparent maternal individual maximum peak concentration (Cmax) of fentanyl was 0.38 +/- 0.16 ng/ml (mean +/- SD) (range 0.12-0.59 ng/ml) and the time to reach Cmax (Tmax) was 24 +/- 14 min (range 5-60 min). Infants were born 19 to 42 min after epidural administration of fentanyl (mean 27 min). Fentanyl concentrations in neonates was 0.13 +/- 0.04 ng/ml for the umbilical vein and 0.06 +/- 0.03 ng/ml for the artery. The fetus extraction ratio was 53 +/- 19% (range 20-83%). The large difference between arterial and venous concentrations of fentanyl may be due to a metabolization by the fetus and/or an uptake of the drug in the fetal tissues. Thus, even if fentanyl levels reaching the fetus after cesarean section under epidural anesthesia, using local anesthetics with 100 micrograms of fentanyl, are within safe range values, the likelihood of fentanyl uptake by fetal tissues calls for a cautious use of repeated fentanyl administration.

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The influence of pH variations on transplacental transfer of antipyrine was studied using a human placental cotyledon perfused ex vivo. The antipyrine transfer rate is positively correlated with the pH in the fetal circulation and negatively correlated with the pH in the maternal circulation. Thus, the transfer rate is negatively correlated with the difference between pH values in maternal and fetal circulations. The antipyrine transfer rate is also positively correlated with the flows in maternal and fetal circulations. The above parameters allowed to explain 50% of the variance on the transfer rates obtained in various experimental conditions. In a final series of experiments where these parameters for each placenta were fixed at identical values, a good reproducibility in the results was obtained, the variation coefficient being 17%. Thus, establishing the effect of variations in pH allowed a good standardization of the perfused cotyledon model. This effect cannot be explained by modifications in the ionized fraction of the antipyrine molecular and is probably due to physiological mechanisms.

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The effect of naloxone (0.6 mg; 1.2 mg; 2.4 mg X kg-1) were compared in normal Long Evans (N) and Brattleboro (D.I.) conscious rats. Naloxone did not change the values of drinking, diuresis, food intake, blood pressure, Na+ and K+ urinary excretion measured during 24 hours. During the two hours following drug injection, naloxone (1.2 and 2.4 mg X kg-1) reduced diuresis in normal as well as in D.I. rats. Water drinking was only modified in D.I. rats: this effect was shown to be a consequence of antidiuresis. These results suggest that the antidiuretic properties of naloxone are independent of vasopressin secretion. They do not support in a role of opiate receptors on vasopressin secretion in normal hydrated animals.

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A series of dives was carried out to depths of 600 and 800 m seawater (msw) using baboons (Papio papio). Experiments were designed to study the effects of compression and the use of a He-N2-O2 gas mixture on high-pressure nervous syndrome (HPNS). When N2 was added to the He-O2 mixture at the beginning of a linear compression (200 msw/h), the symptoms associated with HPNS were still seen; in addition, the electroencephalogram (EEG) changes were more severe than those seen without N2. By use of an identical mixture, a 2-h exponential compression to 600 msw produced less severe signs of HPNS than the nonexponential profile. By use of a 2-h exponential compression to 600 msw and with addition of N2 at the end of compression, the HPNS that had been started under the He-O2 mixture decreased. Progressive addition of N2 during compression reduced the behavioral signs of HPNS without further EEG changes. These results show that the action of N2 is more complex than can be explained by a simple narcotic pressure antagonism and that the HPNS differed according to the gas mixture used.

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The effects of phenylephrine (alpha 1 +) and prazosin (alpha 1 -) on water intake, diuresis, food intake and blood pressure were compared in conscious normal and diabetic insipidus (DI) Long Evans rats. The two drugs did not change the values measured on 24 hours in the two groups of animals (tables I and II). Phenylephrine induced a diuretic response in both normal and DI rats during the two first hours. Water intake was decreased in normal rats and increased in DI animals (fig. 1). Prazosin induced an antidiuretic effect in the two groups of animals, an increase in water intake in normal rats and a decrease in water intake in DI animals (fig. 2). Blood pressure was not changed in the two groups of animals two hours after injection. The comparison between the different results shows that the first changes induced by phenylephrine or prazosin were changes in diuresis. Since the two drugs act in a same way on the diuresis of normal and vasopressin--deprived rats, it is concluded that the neurohypophysial peptide is not involved in the variations of urinary volume induced by the alpha 1-adrenergic drugs.

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1. The effects of clonidine on water balance were compared in normal (N.) and diabetes insipidus (Brattleboro D.I.) conscious rats. Animals were housed in individual cages and feed food and water ad libitum. The dose of clonidine was 100 microgram . kg-1 by subcutaneous route during consecutive 9 days. A control period of 12 days without drug treatment (only saline as a sham injection) separated the different period treatments. Under these experimental conditions the values of diuresis, water and food intakes, blood pressure were measured every morning before clonidine-treatment. 2. In normal rats, clonidine induced a diuretic and dipsogenic action (fig. 1). In contrast, the drug elicited an antidipsogenic and antidiuretic response in D.I. rats (fig 2). 3. In another series of experiments, the short term responses to clonidine treatment were studied in the two groups of animals. During the two first hours of treatment, clonidine elicited a rapid and marked reduction in water intake in the two groups of animals (table I). In normal rats, the drug also elicited an increase in urine flow. In contrast, in D.I. (Brattleboro) rats, an antidiuretic effect was observed during the first 30 minutes after clonidine- injection but not during the following 30 minutes periods (fig 3). 4. Clonidine increased both the natriuretic and kaliuretic excretion in normal rats, but failed to modify these values in D.I. rats (fig 4). 5. Clonidine decreased blood pressure in the two groups of animals (table II) but failed to modify the values of food intake (table III). 6. These results suggest that clonidine-induced diuresis is related to inhibition of vasopressin (ADH) secretion. Since the early observation of water balance revealed a clonidine antidipsogenic-induced effect in the two groups of animals, it is suggested that vasopressin was not involved in the clonidine induced water intake and that the daily antidiuretic response in Brattleboro (D.I.) rats was only related to the antidipsogenic property of clonidine.

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