Soft X-Ray Second Harmonic Generation as an Interfacial Probe.

Nonlinear optical processes at soft x-ray wavelengths have remained largely unexplored due to the lack of available light sources with the requisite intensity and coherence. Here we report the observation of soft x-ray second harmonic generation near the carbon K edge (∼284 eV) in graphite thin films generated by high intensity, coherent soft x-ray pulses at the FERMI free electron laser. Our experimental results and accompanying first-principles theoretical analysis highlight the effect of resonant enhancement above the carbon K edge and show the technique to be interfacially sensitive in a centrosymmetric sample with second harmonic intensity arising primarily from the first atomic layer at the open surface. This technique and the associated theoretical framework demonstrate the ability to selectively probe interfaces, including those that are buried, with elemental specificity, providing a new tool for a range of scientific problems.

Pharmacokinetics and pharmacodynamics of cisatracurium in young and elderly adult patients.

BACKGROUND: The effects of a muscle relaxant may differ in elderly compared with young adult patients for a variety of reasons. The authors compared the effects of a new muscle relaxant (cisatracurium) in young and elderly adults and used pharmacokinetic/pharmacodynamic modeling to identify factors explaining differences in time course of effect. METHODS: Thirty-one young (18-50 yr) and 33 elderly ( > 65 yr) patients anesthetized with nitrous oxide, isoflurane, and fetanyl were studied. Cisatracurium (0.1 mg/kg) was given after induction of anesthesia and later additional boluses of 0.025 mg/kg or an infusion of cisatracurium was given. Neuromuscular transmission was measured using the first twitch of the train-of-four response at the adductor pollicis after supramaximal stimulation of the ulnar nerve at 2 Hz every 15 s. Five venous blood samples were obtained for plasma drug concentration at intervals ranging from 2 to 120 min from every patient. Three additional samples were obtained from those who received an infusion. A population pharmacokinetic/pharmacodynamic model was fitted to the plasma concentration and effect data. The parameters of the model were permitted to vary with age to identify where differences existed between young and elderly adults. RESULTS: Onset of block was delayed in the elderly; values being mean 3.0 (95% confidence interval 1.75-11.4) min and 4.0 (2.4-6.5) min in the young and elderly, respectively (P < 0.01). Duration of action was similar in the two groups. Plasma clearance was 319 (293-345) ml/min in the study population and did not differ between young and elderly patients. Apparent volume of distribution was 13.28 (9.9-16.7) 1 and 9.6 (7.6-11.7) 1 in the elderly and young adults, respectively (P < 0.05). There also were differences in pharmacodynamic parameters between the young and elderly; the predominant change being a slower rate of biophase equilibration (ke0) in the elderly (0.060 [0.052-0.068])/min compared with the young (0.071 [0.065-0.077]/min; P < 0.05). CONCLUSIONS: The pharmacokinetics of cisatracurium differ only marginally between young and elderly adults. Onset is delayed in the elderly because of slower biophase equilibration.

Pharmacokinetics and pharmacodynamics of the benzylisoquinolinium muscle relaxants.

The benzylisoquinolinium class of drugs comprises atracurium, 51W89, doxacurium, and mivacurium. Atracurium can be used as a pharmacokinetic benchmark; it has at least two distinct metabolic pathways, of which Hofmann elimination and ester hydrolysis are the most significant. The relative importance of each of these two routes is still a matter of speculation, and this, coupled with the fact that atracurium is a mixture of 10 isomers, has led to the development of many innovative pharmacokinetic modelling concepts. 51W89 is a cis-cis-isomer of atracurium and probably has a pharmacokinetic profile very similar to that of atracurium. Doxacurium, a long-acting benzylisoquinolinium, has a small apparent volume of distribution and an elimination half-time similar to that of pancuronium, and is excreted by the kidneys. Mivacurium is a short-acting benzylisoquinolinium that is rapidly hydrolysed by plasma cholinesterases. Two isomers of mivacurium are very similar, whereas the third isomer differs greatly in both pharmacological activity and elimination half-time, so that analysis requires complex pharmacokinetic methods.

Repetitive elastance measurement as a means of recording pharmacological responses in vascular smooth muscles.

We describe a method of recording pharmacological responses in isolated arterial segments, based on the direct measurement of vascular wall elastance. The segment outflow is intermittently occluded, and the elastance determined from the subsequent pressure-flow relationship. Since the measurement cycle can be repeated 12 times per minute, rapid pharmacological responses can be studied. The method is capable of demonstrating a sigmoid dose-response relationship to noradrenaline added to the perfusate.

The Maillard reaction in vivo.

The Maillard or browning reaction between reducing sugars and protein contributes to the chemical deterioration and loss of nutritional value of proteins during food processing and storage. This article presents and discusses evidence that the Maillard reaction is also involved in the chemical aging of long-lived proteins in human tissues. While the concentration of the Amadori adduct of glucose to lens protein and skin collagen is relatively constant with age, products of sequential glycation and oxidation of protein, termed glycoxidation products, accumulate in these long-lived proteins with advancing age and at an accelerated rate in diabetes. Among these products are the chemically modified amino acids, N epsilon-(carboxymethyl)lysine (CML), N epsilon-(carboxymethyl)hydroxylysine (CMhL), and the fluorescent crosslink, pentosidine. While these glycoxidation products are present at only trace levels in tissue proteins, there is strong evidence for the presence of other browning products which remain to be characterized. Mechanisms for detoxifying reactive intermediates in the Maillard reaction and catabolism of extensively browned proteins are also discussed, along with recent approaches for therapeutic modulation of advanced stages of the Maillard reaction.

Case-control study of lung cancer in Los Angeles county welders.

A case-control study of lung cancer in white male welders was undertaken to investigate possible environmental and occupational causes of a 50% excess of lung cancer observed in this occupational group. The subjects were identified from a population-based cancer registry in Los Angeles County. A standardized questionnaire was administered to either subjects or proxy informants of 90 lung cancer cases and 116 non-lung-cancer controls. Significantly increased risks of lung cancer were associated with tobacco smoking (odds ratio 7.6, p less than .005) and shipyard welding with at least a 10-year latency since first exposure (odds ratio 1.7, p less than .05). Although there were elevated risks associated with some specific welding processes, none were statistically significant. Control subjects were more likely to have had exposure to confined-space welding (odds ratio 0.6, 95% CI = 0.3-1.2), and this association was greatest where there had been at least a 20-year latency since first exposure (0.5, 95% CI = 0.3-1.0). We conclude that the excess of lung cancer in this welding population is contributed to by a higher frequency of smoking and probable exposure to asbestos in shipyards. Other factors may be important, but probably because of limited power and reliance on proxy information, this study failed to detect other statistically significant risks.

The Amadori product on protein: structure and reactions.

The Amadori Rearrangement Product is the first stable adduct formed during glycation (nonenzymatic glycosylation) of protein. This review deals with the structure of the Amadori adduct on protein, factors affecting the kinetics and specificity of glycation of protein, measurements of the extent of glycation of proteins in vivo, and the possible significance of glycation itself, versus post-glycation reactions, in the development of pathophysiology in diabetes.

Phagocytosis of yeast by Biomphalaria glabrata: carbohydrate specificity of hemocyte receptors and a plasma opsonin.

In vitro phagocytosis of yeast cells by hemocytes of the mollusc Biomphalaria glabrata can occur in the absence of plasma, but is enhanced by opsonization in plasma from certain snail strains. We have investigated the carbohydrate specificity of the hemocyte-bound receptor for phagocytosis and the free plasma opsonin using two dominant carbohydrate components of the yeast cell wall (laminarin and mannan). Phagocytic uptake in the absence of plasma of both untreated and opsonized yeast is strongly inhibited by laminarin, but is unaffected by mannan. In contrast, laminarin does not interfere with opsonization whereas mannan blocks the process, blocking the binding of a 57 kD plasma component as detected by Western immunoblot. These results suggest that the opsonic lectin in plasma is not simply a free form of the hemocyte-bound receptor for yeast phagocytosis.

The host-parasite interface in molluscan schistosomiasis: biotin as a probe for sporocyst and hemocyte surface peptides.

Hemocytes of Biomphalaria glabrata mediate the internal defensive response which, in resistant snail strains, kills sporocysts of Schistosoma mansoni. Lacking a gut, the sporocyst has only its tegument to interact with the host milieu (hemolymph). We have, therefore, focused our study on the surface-exposed proteins of hemocytes and sporocyst tegument. Using gentle biotinylation of living systems, labelled proteins were studied after SDS-PAGE electrophoresis and transfer to nitrocellulose. Results validate the utility of surface biotinylation in studies of host and parasite interfaces. A low diversity characterizes hemocyte surfaces and strain-specific differences are not in evidence. Hemocyte surfaces differ distinctly from the plasma in which these cells reside. In contrast, sporocyst surfaces expose a wide variety of peptides. These are remarkably stable even when sporocysts procured in snail plasma-free media are exposed to plasma. Thus, antigenic differences seen previously when Western immunoblotting was used to study sporocyst surfaces appear to be manifestations of minor changes in the exposed peptides or changes not detectable with this methodology. Hemoglobin, acquired by sporocysts from snail plasma, is processed and disappears from the surface during an overnight chase in culture medium.

Alfentanil for caesarean section complicated by severe aortic stenosis. A case report.

Alfentanil 35 micrograms kg-1, was used successfully in a patient with severe aortic stenosis, in order to minimize the haemodynamic responses to intubation and surgery during Caesarean section. The baby was delivered apnoeic, unresponsive and with poor muscle tone, but responded rapidly to naloxone. Plasma alfentanil concentrations and percentage binding to plasma proteins were measured in both maternal and neonatal blood. Free drug concentrations were similar in both mother and neonate, but maternal plasma proteins had a higher affinity for alfentanil. Only 67.26% of neonatal plasma alfentanil was bound to plasma protein. This value did not differ significantly from those estimated from the blood of a further 12 healthy neonates.

Phaeochromocytoma. Diagnosis, preoperative preparation and anaesthetic management.

Unless patients harbouring this uncommon tumour are correctly prepared and protected from the effects of excessive catecholamine release, they are greatly at risk when undergoing surgical procedures of any kind. This short review describes the clinical syndromes associated with phaeochromocytoma, the diagnostic procedures which may identify and localize the tumour(s), the principles and practical aspects of pharmacological control, and a method of anaesthetic management which has proved safe and effective in many patients.