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.

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.

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.

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.

Pharmacokinetic analysis using an electrical analogue.

After i.v. administration, the distribution and elimination of many drugs may be simulated by a compartmental mathematical model. The analogue can be used to construct such models in electrical terms. When programmed with an appropriate model, the analogue can be used in a wide range of predictive studies. The application of the analogue is illustrated by analysis of serial plasma concentrations of fentanyl and pancuronium.

Comparative pharmacokinetics of fentanyl and alfentanil.

The pharmacokinetics of fentanyl and alfentanil were compared by the simultaneous i.v. administration of both drugs, measurement of plasma concentrations and compartmental analysis. In addition, plasma protein binding, erythrocyte:plasma partition, and heptane:water partition were compared. Alfentanil was found to have a very much smaller apparent volume of distribution, smaller total clearance, and shorter terminal half-time in plasma. Alfentanil was also found to have a greater plasma protein binding, but in contrast to fentanyl, no binding to erythrocytes. It is concluded that alfentanil is less cumulative than fentanyl, has restricted hepatic clearance, and will exhibit non-linear kinetics at very high doses. An appendix describes the model-fitting procedure in detail.

Control of postoperative pain by interactive demand analgesia.

A demand analgesia apparatus is described. It communicates with the patient by means of spoken messages in any desired language, so that preliminary instruction is unnecessary. Dosage is limited by a reduction in respiratory rate, and by a series of electronic fail-safe circuits. Operation of the system is illustrated in a series of 10 patients given fentanyl "on demand" for the first 12 h after operation. The mean dose rate 0.73 +/- 0.49 microgram min-1. There was no evidence of cumulation or tolerance during the period of study.

A clinical trial of alfentanil as an adjuvant for short anaesthetic procedures.

Alfentanil 700 micrograms and fentanyl 100 micrograms were compared as anaesthetic adjuvants in 90 patients undergoing short duration gynaecological procedures. The results show that, at the chosen dose ratio, alfentanil causes a higher frequency of post-induction apnoea, but thereafter the respiratory effects of the two drugs were comparable. No differences in incremental requirements or evoked movements were found. Among patients who had been given ergometrine, the alfentanil group suffered a greater frequency of nausea and vomiting in the period immediately after operation. It is concluded that in single i.v. doses, alfentanil 700 micrograms is more potent than fentanyl 100 micrograms. Moreover, the results suggest that, unlike fentanyl, this very short acting agent would be used to greater effect if given in divided doses during surgery.

PIP: This study used a double-blind, randomized procedure to compare alfentanil with fentanyl as an adjuvant to anesthesia for short gynecological procedures. 90 healthy female patients age 16-65 years and weighing between 40-80 kg who were undergoing dilatation and curettage (D and C), evacuation of the products of conception (ERPC), or suction termination of pregnancy (TOP) were randomly assigned to group A (alfentanil) or group F (fentanyl). All patients were premedicated with lorazepam 1 mg. Each patient received either fentanyl 100 mcg or alfentanil 700 mcg, followed immediately by 1% methohexitone (plus 0.1% lignocaine) given in 10 mg increments every 15 seconds until the eyelash reflex was obtunded. The patients then breathed 66% nitrous oxide in oxygen. Patients undergoing TOP or ERPC were given ergometrine .25 mg intravenously at the start of cervical dilatation. Throughout the procedure, an online HP-8S computer gathered data on a peripheral interrupt basis. Data from the D and C patients was treated separately from that for TOP and ERPC patients; marked differences were found in incremental requirements for methohexitone, the frequency of apnea, the observed respiratory rates, and the mean arterial pressure. In both D and C and TOP groups, the mean induction doses of methohexitone in group F patients exceeded those in group A, but the differences were not significant, indicating that the analgesic effects did not differ greatly in intensity. The frequency and duration of apnea following induction were greater in patients given alfentanil. Despite the high frequency of apnea in group A patients, the frequency of physical responses to surgery and the need for incremental methohexitone did not differ. The results suggest that alfentanil does not improve the quality of anesthesia and does not discernibly reduce recovery time or the frequency of immediate postoperative nausea and vomiting.

Incremental propofol for short procedures.

Propofol was used to induce and maintain anaesthesia in patients undergoing minor gynaecological procedures. Quality of anaesthesia, the rate of recovery and the influence of different methods of premedication were assessed. Unpremedicated patients required a higher induction dose than those premedicated with either lorazepam or papaveretum and hyoscine, but maintenance dose requirements were comparable. Regardless of premedication, there were similar decreases in mean arterial pressure, although respiratory function recovered more rapidly in patients premedicated with lorazepam. No significant changes in heart rate were noted in any group. The overall incidence of pain on injection was 3.7% (lignocaine 0.5 mg added to each 9.5 mg of propofol) and a skin rash occurred in 6% of patients. All patients recovered rapidly and uneventfully.

Characterization of immunoglobulin from the Pacific hagfish, a primitive vertebrate.

Antibodies to group A streptococcal carbohydrate, demonstrable by radioimmunoassay, were elicited in Pacific hagfish, Eptatretus stoutii, after prolonged immunization with whole cell vaccine. This hagfish antibody, isolated by ion-exchange chromatography of immune serum, exhibited a single precipitin line after immunoelectrophoresis against rabbit antiserum to hagfish serum. The isolated antibodies retained high binding activity for the streptococcal carbohydrate, but lacked the natural hemagglutinating activity found in both nonimmune and immune sera. Analysis by gel filtration in neutral and dissociating buffers and by sodium dodecyl sulfate/polyacrylamide gel electrophoresis under nonreducing conditions indicated an intact molecule of molecular weight approximately 160,000 that may be noncovalently associated in a polymer of higher molecular weight. Heavy chains of mobility identical to that of murine mu chains and light chains of mobility significantly slower than murine lambda chains were obtained after sodium dodecyl sulfate gel electrophoresis under reducing conditions. Instability of the tertiary structure of the antibody molecule was indicated by partial dissociation in buffers containing sodium dodecyl sulfate and by dissociation at low concentrations of reducing agent. In contrast to its well-developed system of cell-mediated immunity, only a minimal system of circulating antibody production is evident in this primitive fish. No evidence for divergence of cyclostome lymphocytes into separate T- and B-cell systems has yet been discerned.

Fazadinium and pancuronium: a pharmacodynamic study.

The neuromuscular blocking characteristics of fazadinium and pancuronium were compared using a general pharmacodynamic model. Since it characterizes the overall relationship between dose and effect, the model can be used to determine precisely equipotent doses, compare time-effect curves, and reconcile the apparently inconsistent clinical and pharmacokinetic characteristics of the two drugs. Fazadinium was shown to have a shorter duration than pancuronium, and appeared to exhibit less variation between subjects. The potency ratio varied between 3.4 : 1 and 7.2 : 1, depending upon the definition chosen. A general solution for the three-compartment open mammillary model, following any set of initial conditions if presented as an appendix. These equations allow explicit computation of any pattern of drug incrementation into any compartment of the model.

Effects of ageing on the pharmacokinetics of pancuronium.

The effects of age on the pharmacokinetics of pancuronium were investigated. The distribution volume of pancuronium did not appear to be age-dependent, but elimination of the drug decreased with increasing age. The clinical implications of these findings are discussed.

Extradural versus intramuscular diamorphine. A controlled study of analgesic and adverse effects in the postoperative period.

The effects of diamorphine hydrochloride 0.1 mg/kg, given either extradurally or intramuscularly for postoperative analgesia were compared in two randomised double-blind studies involving 39 patients undergoing thoracotomy and major gynaecological surgery. Assessments were made at fixed intervals after the administration of diamorphine and consisted of the measurement of pain or analgesic effect. Segmental, sympathetic and any adverse effects were sought. There was no significant difference in the quality of analgesia between the two groups in either trial. Extradural diamorphine provided safe and effective analgesia of rapid onset, with no specific undesirable side-effects. In both studies, analgesia was more prolonged following extradural administration. The relative proportion of spinal binding may be increased after extradural administration and this may be reflected in the prolonged analgesia observed.

A pharmacodynamic model for pancuronium.

It has been demonstrated that a simple two-compartment kinetic model may account for the changes in plasma concentration of pancuronium after i.v. administration. However, it can be shown that this simple model does not account satisfactory for the observed changes in muscle twitch response. By the addition of a receptor (biophase) compartment, twitch response can be reconciled with model behavior and the characteristics resemble those predicted by animal studies. The complete model is applied to the problem of total renal failure, and shows that patients with this condition are likely to be marginally resistant to small doses of pancuronium, with a normal rate of recovery. However, larger doses are likely to result in delayed recovery, the duration of effect increasing in a dose-dependent manner.

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.