Perioperative myocardial ischaemia in patients undergoing surgery for fractured hip randomized to incremental spinal, single-dose spinal or general anaesthesia.

Quantitative assessment of myocardial ischaemia during incremental spinal, single-dose spinal and general anaesthesia may provide guidelines for the choice of anaesthetic technique for osteosynthesis of hip fractures in the elderly atherosclerotic individual. Forty-three patients with coronary artery disease were allocated to receive either incremental spinal anaesthesia (bupivacaine 0.5% plain) (A), single-dose spinal anaesthesia (2.5 mL of bupivacaine 0.5% plain) (B) or general anaesthesia (fentanyl, thiopentone, atracurium, enflurane, N2O/O2) (C) for hip surgery. ST segment monitoring was performed from the induction of anaesthesia and for the following 48 h, and perioperative hypotension, blood loss and fluid therapy were recorded. ST depression developed in two out of 14 (A), seven out of 15 (B) and six out of 14 (C) patients (P = 0.14). In (A), a total of seven ST depressions occurred in the observation period as opposed to 125 in (B) and 16 in (C) (P < 0.05). Intra-operative ST depression only occurred in (B). Three (A), 33 (B) and 40 (C) hypotensive events were recorded (P < 0.002). Altogether, 56% of hypotensive patients developed ST depression compared with 10% of normotensive patients (P < 0.003). In (A), 1.6 mL of 0.5% bupivacaine were used as opposed to the fixed 2.5 mL dose in (B) (P < 0.001). In the first post-operative week, mortality was higher in (B) (P < 0.05) but, after 1 month, there was no significant difference in mortality between the three groups. The incidence of hypotension and myocardial ischaemia was lowest in the group receiving incremental spinal anaesthesia.

Extradural anaesthesia for repeated surgical treatment in the presence of infection.

The use of extradural catheters in patients with systemic or localized infection is controversial. The catheter may act as a focus for secondary infection resulting in an extradural abscess. in this study we have examined the use of extradural catheters for anaesthesia over the past 7 yr in patients with localized infections. The records of 69 patients were reviewed and patients interviewed (letter/phone). These patients had a total of 120 extradural catheters placed and received, on average, four anaesthetics, with the extradural catheter remaining in place for a mean of 9 days. On 12 occasions (eight patients) the catheter was removed because of signs or symptoms of local infection. Specific antibiotic therapy was not initiated, but ongoing therapy was continued. A single case of spondylitis was the only serious complication found but was not related to the extradural technique. We conclude that extradural anaesthesia for patients who require repeated surgical treatments for abscesses or infected wound is a relatively safe procedure.

Postoperative throat complaints after tracheal intubation.

We have investigated the incidence of throat complaints 6-24 h after tracheal intubation in 1325 patients. Variables such as anaesthetic drug, intubation time, number of intubation attempts, gastric tube, sex and age were recorded. The incidence of sore throat was considerably lower (14.4%) compared with other reports in the literature and was significantly greater in females (17.0% vs 9.0%) and after thyroid surgery. The incidence of sore throat was not increased after multiple intubation attempts or after administration of suxamethonium or a non-depolarizing neuromuscular blocker.

[Use of colloids in acute hypovolemia]. / Anvendelsen af kolloider ved akut hypovolaemi.

In Denmark several natural and synthetic colloids are available. Natural colloids are fresh frozen plasma (FFP) and human albumin (HA). Both are ideal as plasma expanders, but FFP can carry infectious agents and HA is quite expensive. The synthetic colloids or modified macromolecules are the dextrans (Macrodex (MD) and Rheomacrodex (RMD)), Haemaccel (HC), and Haes-steril (HS) in 6 and 10% solutions. HC has few indications because of a questionable volume expansion and a relatively high frequency of side effects. RMD is useful in cases of compromised regional blood flow. HS 10% and HA 20% are hyperoncotic and are effective in redistributing interstitial fluid to the intravascular space. HS and MD are both effective as volume substitutes. In addition HS and MD have beneficial side effects such as an inhibition of erythrocyte aggregation and inhibition of leucocyte marginalisation. Furthermore, MD has an anti-thrombotic effect. However, MD has in contrast to HS a dose dependent effect on the bleeding time. HS and MD are effective in restoring the colloid osmotic pressure and can in many cases replace HA in treatment of hypovolaemia.

[Aspiration pneumonia]. / Aspirationspneumoni.

Pulmonary aspiration of stomach contents is a common clinical problem. Symptoms and consequences depend on the aspired volume, the pH and the content of food particles and bacteria. There are two phases following an aspiration of stomach contents into the lungs. The first phase is nonspecific and begins a few minutes after the aspiration. This phase is due to the chemical injury. The second phase is an inflammatory reaction. The reaction is haemorrhagic, granulocytic and necrotizing when the aspirate is acid (pH < 2.5). The presence of food particles causes granulomas. The immunological reactions are biphasic as well. The bacterial infection is mainly secondary to the chemical inflammation and occurs with an infection rate of 25-50%. The optimum management is symptomatic and should entail immediate endotracheal suction, aggressive ventilatory support with supplemental oxygen, CPAP or PEEP if indicated by clinical assessment and blood gas measurements, adequate fluid replacement and antibiotics if there is evidence of bacterial infection.

A basement-membrane permeability assay which correlates with the metastatic potential of tumour cells.

We describe an in vitro assay for measuring the ability of tumour cells to permeabilize basement membranes, using transwell chambers coated with the reconstituted basement membrane, matrigel. Unlike previous matrigel-based procedures which quantified passage of tumour cells across a matrigel barrier, the new assay measures the ability of tumour cells to degrade the basement membrane and increase the diffusion rate of fluorescent (FL) dextran through the barrier. The procedure has the major advantage that permeability can be rapidly and accurately quantified, either by fluorometry or by the use of radiolabelled dextran, thus avoiding tedious and subjective scoring methods. Optimal conditions for the assay are described. In addition, it is demonstrated that the assay can clearly discriminate between metastatic and non-metastatic tumour cell lines, metastatic tumours permeabilizing the basement membrane and non-metastatic counterparts failing to do so. A range of enzyme inhibitors suggested that the increase in basement-membrane permeability caused by the metastatic mammary adenocarcinoma 13762 MAT is probably dependent upon the synergistic action of several degradative enzymes, namely proteases, type-IV collagenase, and heparanase. Furthermore, the ability to permeabilize the basement membrane was dependent upon intact tumour cells; tumour cell extracts, lysates and supernatants were inactive.

Isolation and characterization of cell adhesion molecules from the marine sponge, Ophlitaspongia tenuis.

Previous studies suggested that cell adhesion in the marine sponge, Ophlitaspongia tenuis, is mediated by a 35 kDa cell surface protein which interacts with an extracellular sulfated polysaccharide. This paper describes a simple and efficient procedure for isolating both putative cell adhesion molecules from detergent lysates of O. tenuis cells, the procedure being based on the fortuitous affinity of the sponge polysaccharide for heparin. The purified polysaccharide inhibits O. tenuis sponge cell aggregation, is highly sulfated and represents a glycosaminoglycan containing glucuronic acid. N-sulfated glucosamine and, possibly, glucose. The purified 35 kDa protein has a high affinity for the sponge polysaccharide and also, selectively interacts with dextran sulfate, a polysaccharide that has been shown previously to both bind to the sponge cell surface and inhibit aggregation of O. tenuis cells. Collectively, the data supports the hypothesis that the 35 kDa molecule is the major cell adhesion protein in O. tenuis. Preliminary data also suggests that the sponge contains an endogenous glycan hydrolase which can cleave the sponge polysaccharide.

Evidence that sulphated polysaccharides inhibit tumour metastasis by blocking tumour-cell-derived heparanases.

Recent studies in this laboratory demonstrated that several sulphated polysaccharides can inhibit metastasis of the rat mammary adenocarcinoma 13762 MAT, probably by preventing the passage of tumour cells through the walls of blood vessels. In order to directly test this possibility, 13762 MAT cells were cultured with (35S)O4(=)-labelled subendothelial extracellular matrices (ECM) and ECM degradation was monitored in either the presence or absence of different sulphated polysaccharides. Degradation products were detected by sodium dodecyl sulphate polyacrylamide gel electrophoresis and subsequent autoradiography. The 5 sulphated polysaccharides that had previously been shown to possess anti-metastatic activity were potent inhibitors of the degradation of subendothelial ECM by 13762 MAT cells. In contrast, of the 4 polysaccharides tested that failed to inhibit metastasis, 3 had no effect on ECM breakdown and one (carrageenan-kappa) was substantially less effective at inhibiting ECM degradation than the anti-metastatic preparations. It was also shown that 13762 MAT cells produce a heparan sulphate-specific glycosidase (heparanase) that degrades the heparan sulphate side-chains of the ECM, the action of this enzyme rather than that of other ECM-solubilizing enzymes being inhibited by the antimetastatic sulphated polysaccharides. Additional experiments indicated that the anti-coagulant activity of the polysaccharides probably plays a minor role in their anti-metastatic effects since heparin, almost completely depleted (98-99.5%) of heparin molecules with anti-coagulant activity by passage over an anti-thrombin III column, retained its ability to inhibit 13762 MAT heparanases and was almost as effective as unfractionated heparin at inhibiting tumour-cell metastasis. Collectively, these data suggest that sulphated polysaccharides inhibit the metastasis of 13762 MAT cells by inhibiting tumour-cell-derived heparanases involved in the penetration of the vascular endothelium and its underlying basement membrane by tumour cells.

A role for sulfated polysaccharide recognition in sponge cell aggregation.

Molecules binding sulfated polysaccharides were detected as lectins in cholate lysates of cells from twelve sponge species. Each species exhibited a unique binding profile. The pattern of binding indicated that the specificity was most probably determined by the orientation of the sulfate groups on the polysaccharide chains. Cells from each of the three species examined in more detail were found to express sulfated polysaccharide-binding molecules at their surface and at least one of the polysaccharides recognized was found to inhibit the reaggregation of cells from each species. Moreover, in all but one instance, lectins for the inhibitory polysaccharide were both detected in cell lysates and shown to be expressed at the cell surface. Sulfated polysaccharides, therefore, appeared to be involved in cell interaction events in the Porifera. This conclusion was confirmed by the isolation via ion exchange chromatography of an endogenous polysaccharide from an O. tenuis cell extract. This molecule contained uronic acid and hexose units in a ratio of 2:1, 11.9% sulfur and less than 0.5% protein. It inhibited the aggregation of O. tenuis cells and the agglutination of dextran-sulfate- and polyvinyl-sulfate-coupled erythrocytes by O. tenuis cell lysates. O. tenuis cell aggregation was also inhibited by polyvinyl sulfate and dextran sulfate and molecules binding these compounds were expressed on the surface of O. tenuis cells. Thus, is was probable that the cell surface receptor for polyvinyl sulfate and dextran sulfate and isolated sponge sulfated polysaccharide are one and the same. Finally, using a dextran sulfate affinity procedure, a 35 kD dextran-sulfate-binding protein was isolated from the surface of O. tenuis cells. The possibility that the polysaccharide isolated from O. tenuis cell extracts in the absence of calcium is the monomeric form of a cell aggregation-enhancing factor is discussed.