Invited article: polarization "down under": the polarized time-of-flight neutron reflectometer PLATYPUS.

This review presents the implementation and full characterization of the polarization equipment of the time-of-flight neutron reflectometer PLATYPUS at the Australian Nuclear Science and Technology Organisation (ANSTO). The functionality and efficiency of individual components are evaluated and found to maintain a high neutron beam polarization with a maximum of 99.3% through polarizing Fe/Si supermirrors. Neutron spin-flippers with efficiencies of 99.7% give full control over the incident and scattered neutron spin direction over the whole wavelength spectrum available in the instrument. The first scientific experiments illustrate data correction mechanisms for finite polarizations and reveal an extraordinarily high reproducibility for measuring magnetic thin film samples. The setup is now fully commissioned and available for users through the neutron beam proposal system of the Bragg Institute at ANSTO.

Structure of SP-B/DPPC mixed films studied by neutron reflectometry.

The structures of films of pulmonary surfactant protein B (SP-B) and mixtures of SP-B and dipalmitoylphosphatidylcholine (DPPC) at the air/water interface have been studied by neutron reflectometry and Langmuir film balance methods. From the film balance studies, we observe that the isotherms of pure DPPC and SP-B/DPPC mixtures very nearly overlay one another at very high pressures, suggesting that the SP-B is being excluded from the film. The use of multiple contrasts with neutron reflectometry at a range of surface pressures has enabled the mixing and squeeze out of the DPPC and SP-B mixtures to be studied. We can identify the SP-B component of the interfacial structure and its position as a function of surface pressure. The mixtures are initially a homogeneous layer at low surface pressures. At higher surface pressures, the SP-B is squeezed out of the lipid layer into the subphase, with the first signs detected at 30 mN m(-1). At 50 mN m(-1), the subphase is almost completely excluded from the DPPC layer, with the SP-B content significantly reduced. Only a small amount of DPPC appears to be associated with the squeezed out SP-B.

The interfacial structure and Young's modulus of peptide films having switchable mechanical properties.

We report the structure and Young's modulus of switchable films formed by peptide self-assembly at the air-water interface. Peptide surfactant AM1 forms an interfacial film that can be switched, reversibly, from a high- to low-elasticity state, with rapid loss of emulsion and foam stability. Using neutron reflectometry, we find that the AM1 film comprises a thin (approx. 15A) layer of ordered peptide in both states, confirming that it is possible to drastically alter the mechanical properties of an interfacial ensemble without significantly altering its concentration or macromolecular organization. We also report the first experimentally determined Young's modulus of a peptide film self-assembled at the air-water interface (E=80MPa for AM1, switching to E<20MPa). These findings suggest a fundamental link between E and the macroscopic stability of peptide-containing foam. Finally, we report studies of a designed peptide surfactant, Lac21E, which we find forms a stronger switchable film than AM1 (E=335MPa switching to E<4MPa). In contrast to AM1, Lac21E switching is caused by peptide dissociation from the interface (i.e. by self-disassembly). This research confirms that small changes in molecular design can lead to similar macroscopic behaviour via surprisingly different mechanisms.

Self-assembling layers created by membrane proteins on gold.

Membrane systems are based on several types of organization. First, amphiphilic lipids are able to create monolayer and bilayer structures which may be flat, vesicular or micellar. Into these structures membrane proteins can be inserted which use the membrane to provide signals for lateral and orientational organization. Furthermore, the proteins are the product of highly specific self-assembly otherwise known as folding, which mostly places individual atoms at precise places in three dimensions. These structures all have dimensions in the nanoscale, except for the size of membrane planes which may extend for millimetres in large liposomes or centimetres on planar surfaces such as monolayers at the air/water interface. Membrane systems can be assembled on to surfaces to create supported bilayers and these have uses in biosensors and in electrical measurements using modified ion channels. The supported systems also allow for measurements using spectroscopy, surface plasmon resonance and atomic force microscopy. By combining the roles of lipids and proteins, highly ordered and specific structures can be self-assembled in aqueous solution at the nanoscale.

Tensometry of carbon fibres and elastomers at the diffractometer at BL20B of the Photon Factory.

Two systems have been developed for the simultaneous recording of the SAXS and the WAXS patterns from carbon fibre and elastomer samples which are placed under stress. The systems have been designed to fit inside the versatile vacuum diffractometer (BIGDIFF) at the Photon Factory. In one system, use is made of the ability to move the imaging-plate cassette. In the other, use has been made of an imaging-plate changer which can deliver up to 13 plates into position with a duty cycle of about 60 s. In this case each imaging plate can record SAXS/WAXS patterns in the range 0.5-20 degrees due to the passage of the beam through the specimen which is mounted in a specially designed tensometer. Because BIGDIFF is a vacuum diffractometer and parasitic scattering is small, exposure times as short as 2 s can give acceptable SAXS/WAXS patterns. The systems have been used for the study of both the change of structure with strain, and the relaxation processes which occur as a result of the sample being strained at a fixed rate by a predetermined amount.

Application of imaging-grazing-incidence X-ray diffraction and specular reflectivity to the structural investigation of quantum-confinement semiconductor devices.

X-ray reflectivity and grazing-incidence X-ray diffraction techniques have been employed to investigate the structure of quantum-well and quantum-dot semiconductor devices. This work has been performed using both laboratory and synchrotron radiation sources. The use of synchrotron radiation enabled reflectivity studies to be performed on small samples, and established the feasibility of imaging-grazing-incidence diffraction studies on quantum-confinement structures. Interdiffusion effects in quantum-well and quantum-dot structures, the disordering of overlayers grown on quantum dots, and the variation in diffraction pattern with incident angle have been observed. It is evident that X-ray reflectivity and imaging-grazing-incidence X-ray diffraction yield quite different but complementary information.

Lung scan interpretation: a physiologic, user-friendly approach.

A physiologically-oriented, user-friendly algorithm for interpretation of ventilation-perfusion (V/P) lung scans was compared to the widely used Biello criteria. The physiologic algorithm relies primarily on the observer's degree of certainty that a V/P mismatch is present rather than on the size (relative to a whole segment) and number of V/P mismatches. One hundred five patients who had undergone a ventilation study with 133Xe gas, a perfusion study with 99mTc-MAA and pulmonary angiography were reviewed. Each V/P lung scan was interpreted once with the physiologic algorithm and once with the Biello criteria by two observers. Fifty-nine percent of the 105 studies were classified as indeterminate with the physiologic algorithm versus 62% with the Biello criteria. The prevalence of pulmonary embolism in the high probability, indeterminate, low probability and normal categories for the physiologic algorithm were 60%, 26%, 7% and 0%, respectively; and for the Biello criteria were 50%, 31%, 11% and 0%, respectively. Analysis of the data with receiver-operating-characteristic curves indicated that the physiologic algorithm performed better than the Biello criteria (p less than 0.05). In addition, the physiologic algorithm has the advantages of being more intuitive and easier to remember. We conclude that further evaluation of the physiologic approach for the interpretation of V/P lung scans is warranted.

Effect of dietary n-3 fatty acids on cerebral microcirculation.

The purpose of these studies was to determine the effects of dietary n-3 fish oil on cerebrovascular reactivity and cerebrospinal fluid prostaglandin levels. Adult rabbits (n = 30) received fish oil (200 mg/kg eicosapentaenoic + 143 mg/kg docosahexaenoic acid), corn oil, or water by daily gavage for 6 wk and were then tested for their pial arteriolar diameter response to topical acetylcholine, bradykinin, or systemic asphyxia using the cranial window technique. Plasma and platelet fatty acids were measured by gas chromatography. Cerebrospinal fluid prostaglandin E and serum thromboxane B2 were measured by radioimmunoassay. n-3 Fatty acids were enriched in the plasma and platelets of the fish oil group (P less than 0.05). Serum thromboxane B2 was decreased by 31% in the fish oil group (P less than 0.05). The diameter response to acetylcholine and asphyxia was the same in all groups; however, the dilator response to bradykinin, which is known to be mediated by oxygen radicals, was significantly diminished in the fish oil group (P less than 0.05). Cerebrospinal fluid prostaglandin E concentration increased in response to acetylcholine, bradykinin, and asphyxia; however, the percent increase was less in the fish oil group. In summary, dietary n-3 fatty acids, which are purported to decrease heart disease, appear to selectively affect cerebral arteriolar reactivity, which is normally dependent on cyclooxygenase metabolism of arachidonic acid and formation of vasoactive oxygen radicals.

Effect of fish oil n-3 fatty acids on cerebral microcirculation.

Dietary fish oil containing the n-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA, 20:5) and docosahexaenoic acid (DHA, 22:6) is being consumed by many individuals in an effort to reduce thrombosis and heart disease. However, little is known about how these fatty acids can affect cerebrovascular function. The purpose of the present study was to begin to examine the effects of these fatty acids on cerebral arteriolar diameter and to compare their effects with that of arachidonic acid (AA). Pial arteriolar diameter responses to the topically applied fatty acids [0.2-200 micrograms/ml cerebrospinal fluid (CSF)] were measured in rabbits using in vivo microscopy and the acute cranial window technique. Prostaglandin E2 (PGE2) formed by the brain in response to AA, EPA, and DHA was measured in CSF using radioimmunoassay. EPA induced a dose-dependent dilation response of which the maximum was 29%, whereas the maximal dilation produced by AA was 100%. The arteriolar effect of EPA was reduced by indomethacin or superoxide dismutase plus catalase, indicating vasoactivity due to oxygen radicals formed by cyclooxygenase metabolism of EPA. DHA itself had no effect on diameter or adenosine-induced dilation but reduced dilation by AA when coapplied with AA. AA induced a 65-fold maximal increase in PGE2, whereas EPA and DHA had comparatively little effect. These results imply that substitution of n-3 fatty acids for AA in brain phospholipids may result in less cyclooxygenase-dependent cerebrovascular reactivity. This alteration in reactivity may produce important effects with respect to the brain's blood flow response to a number of physiological and pathological challenges.

Kinins induce abnormal vascular reactivity.

Previous studies have shown that after experimental neural trauma or acute hypertension the brain produces superoxide anion radicals, and brain arterioles display endothelial lesions, dilation, and loss of normal reactivity in response to a decrease in CO2 tension. Because these abnormalities are prevented by pretreatment with free radical scavengers or inhibitors of the cyclooxygenase component of prostaglandin (PG) H synthase, arachidonic acid metabolism by PGH synthase with concomitant formation of tissue injuring oxygen radicals causes the vascular damage. The purpose of the present experiments was to determine whether kinins, which are known to stimulate arachidonate metabolism and to induce cerebral arteriolar dilation via production of superoxide anion, may be involved in initiating the cerebrovascular abnormalities produced by neural trauma in cats. The diameter and reactivity of untreated in vivo pial arterioles on one cerebral cortex was compared with the diameter and reactivity of pial arterioles on the contralateral cortex, which were pretreated topically with a competitive receptor antagonist, which is specific for kinins. Before fluid percussion neural trauma was induced, arterioles on both cerebral hemispheres constricted normally to a decrease in CO2 tension. After injury, the arterioles on the untreated cortex dilated and did not constrict in response to a decrease in arterial CO2 tension, whereas the arterioles pretreated with the kinin antagonist dilated less and displayed normal reactivity to CO2. These experiments demonstrate that a specific kinin receptor stimulates PGH synthase-dependent, free radical-mediated cerebrovascular injury. Given the ubiquitous distribution of the kallikrein-kinin system, we propose that kinins may be an important common mediator of systemic vascular injury and abnormal vascular reactivity.

Inhibition of bradykinin- and kallikrein-induced cerebral arteriolar dilation by a specific bradykinin antagonist.

We have previously shown that topical brain application of kallikrein, an enzyme which converts kininogen to bradykinin, induces rabbit pial arteriole dilation. The purpose of the present investigation was to utilize a newly developed competitive kinin receptor antagonist to test the hypothesis that kallikrein-induced dilation was due to the conversion of brain kininogen to vasoactive kinins. As in our previous study, we measured rabbit pial arteriole diameter with a microscope using the closed cranial window technique. The kinin antagonist (6 microM) reduced the dose-dependent dilation produced by bradykinin and blocked the dilation induced by kallikrein. In addition, the kinin antagonist was specific since it did not alter the cerebral arteriole dilation produced by adenosine, acetylcholine, or vasoactive intestinal polypeptide. These experiments provide further evidence for a possible role of the endogenous brain kallikrein-kinin system in the modulation of the cerebral circulation and provide the necessary pharmacologic foundation for future use of this antagonist in testing the role of kinins in the normal or altered cerebral circulation.

Unilateral simultaneous renal angiomyolipoma and oncocytoma.

A 70-year-old woman with simultaneous unilateral renal angiomyolipoma and renal oncocytoma presented to the hospital with syncope and abdominal pain. Diagnostic studies indicated a left renal neoplasm consistent with renal cell carcinoma and a radical nephrectomy was performed. Histological examination of the resected specimen demonstrated the presence of the 2 unusual renal neoplasms.

Effect of hydration and dehydration on technetium-99m CO2 DADS renal studies in normal volunteers.

Ten normal volunteers were studied in the hydrated and dehydrated states with the new renal radiopharmaceutical technetium-99m N,N'-bis(mercapto acetyl)-2, 3-diaminopropanoate [( 99mTc]CO2 DADS). The data were used to determine the effect of hydration and dehydration and to determine the normal range in each state. Visual evaluation of the images indicated that the first appearance of tracer in the collecting system was approximately the same in either state, that the concentration of tracer in the collecting system was always higher in the dehydrated state (p less than 0.01), and that the ureters always appeared more segmented in the dehydrated state (p less than 0.01). Quantitative analysis of the images indicated that the kidney to background ratio 1-2 min after injection was somewhat greater in the dehydrated state (13.5 +/- 4.0) than in the hydrated state (9.8 +/- 2.2) (p less than 0.05), that the size of the bladder was always greater in the hydrated state (p less than 0.05), and there was no difference in the amount of tracer in the bladder at 30 min after injection. The results define the normal hydrated and dehydrated [99mTc]CO2 DADS renal study and identify several differences between the two states which can be explained primarily by differences in urine flow rates.

Protein binding as a component of drug interaction in cellular pharmacokinetic studies. Effects of probenecid on transport and accumulation of methotrexate in Ehrlich ascites tumor cells in vitro.

The organic acid probenecid has been shown to interfere with the active extrusion of methotrexate (MTX) from L1210 tumor cells in vitro leading to enhanced MTX accumulation and increased formation of MTX polyglutamate derivatives. In the presence of serum albumin (4 g/100 ml), to which probenecid is bound, the inhibition by probenecid of [3H]MTX efflux from the Ehrlich ascites tumor cell was reduced markedly. While half-maximal inhibition of MTX efflux occurred with 0.12 mM probenecid in the absence of albumin, 1.45 mM probenecid was required in its presence. The presence of albumin also modified the probenecid-induced elevation of steady-state MTX levels in the tumor cell. Maximal elevation of cellular MTX levels occurred with 0.5 mM probenecid in the absence of albumin, and 3 mM probenecid in its presence. Serum albumin further reversed the effects of probenecid on MTX influx. While probenecid inhibited influx of 1 microM [3H]MTX in the absence of albumin (half-maximal inhibition at approximately 1 mM probenecid), probenecid stimulated MTX influx in its presence (half-maximal effect at 0.5 to 1 mM). Equilibrium dialysis studies demonstrated that probenecid displaced MTX from albumin, increasing the effective free concentration of MTX in the incubation medium, and hence the rate of MTX influx. Therefore, probenecid may enhance the accumulation of MTX in the tumor cells by increasing the level of free (as opposed to albumin bound) MTX in the extracellular medium as well as by direct inhibition of MTX efflux. These observations may provide an additional explanation for probenecid enhancement of the therapeutic efficacy of MTX in tumor bearing mice and highlight the importance of assessing drug-protein interactions in an in vitro experimental model.

Selective intra-arterial vasopression in fusion for upper gastrointestinal tract hemorrhage: a controlled trial.

In a prospective randomized study, 38 patients with massive upper gastrointestinal tract hemorrhage, mostly due to esophageal varices or erosive gastritis, were treated with either standard medical therapy or standard therapy plus selective intra-arterial vasopressin infusion. Cessation of hemorrhage occurred more frequently in the vasopressin-treated group. The study design did not permit meaningful comparisons of mortality of transfusion requirements. We conclude that in patients bleeding from esophageal varices or gastritis, selective intra-arterial vasopressin is more effective in controlling hemorrhage than standard therapy.

Parent-child communication about sexuality.

PIP: The Project on Human Sexual Development carried out a study of more than 1400 parents of 3-11 year-old children. The study was designed to determine the process of sexual learning in the home environment. It was seen that most children, both boys and girls, took their questions regarding sexual matters to their mothers. A very small percentage of either mother or fathers had ever discussed premarital sex, venereal disease, or contraception with their children, although they nearly universally wanted their children to be familiar with these matters before adolescence. In fact, most parents said that they waited for the children to broach the subject of sexuality. Despite their desires to communicate wth their children regarding sexual matters, they were generally unable to move beyond the traditional manner in which they themselves had been taught sexuality in their childhoods. Beneath the traditional surface, there is a movement away from the status quo. Some of the parent respondents were dissatisfied with traditional gender roles, especially in relation to childrearing. To correct this situation, sexuality must be recognized as broad-based, not genital-related. "Sexual learning is social learning, from birth throughout life."^ieng

Traumatic renal artery occlusion: 21 cases.

Sixteen cases of unilateral and 5 cases of bilateral traumatic renal artery occlusion caused by avulsion or thrombosis are presented. The injury typically follows automobile-pedestrian accidents to young male subjects. Associated extrarenal injuries are usual but non-pedicle renal injury is infrequent. Suspicion of the unilateral injury depends upon recognition of absence of visible excretion at urography. The clue to bilateral occlusion is anuria. Diagnosis is confirmed by urgent arteriography. Hematuria was absent in 24 per cent and the injury was missed at laparotomy in 29 per cent of the initial explorations. Renal function was salvaged by arterial reconstruction in 2 cases, 12 hours and 5 months after injury respectively. Hypertension developed in 50 per cent of the cases and was generally mild.

Permanent nephrostomy via percutaneous puncture.

A technique to convert a standard temporary percutaneous nephrostomy to prolonged or permanent nephrostomy diversion with Foley catheters up to 16F in diameter is described herein. The method has been used for up to 22 months of drainage and is likely to be of principal benefit in the management of obstructive nephropathy in adults when the primary lesion is not readily amenable to repair. There have been no serious complications in our 4 cases.