Investigation of factors relating to neuropsychological change following cardiac surgery.

BACKGROUND: An analysis of neuropsychological impairment following cardiopulmonary bypass was performed in 55 patients undergoing elective coronary artery bypass grafting. METHODS: Neurocognitive function was measured preoperatively using the MicroCog: Assessment of Cognitive Functioning computer-based testing tool. Testing was repeated in the postoperative period immediately prior to discharge from hospital. Analysis of significant score decline was performed using the standardised regression-based technique. A patient was classified as overall impaired when > or = 20% of test scores were significantly impaired. The proposed marker of neurological damage S-100beta was also used. Prothrombin Fragment 1+2 (F1+2) was measured as a marker of thrombin development to test the hypothesis that excessive haemostatic activation may lead to thromboembolic damage to the brain. RESULTS AND CONCLUSIONS: 32.7% of patients were classified as significantly impaired. No relationship was detected between F1+2 and any neuropsychological test score; however, the study was limited due to small sample size. F1+2 levels were higher in patients undergoing prolonged bypass times. Neuropsychological decline was significantly correlated with patient age, suggesting a degree of caution is warranted when operating on an elderly cohort. An unexpected relationship was detected between higher heparin concentrations and increased risk of neuropsychological impairment; however, this requires re-evaluation.

Gaboon viper (Bitis gabonica) envenomation resulting from captive specimens--a review of five cases.

BACKGROUND: Five cases of illegitimate bite by captive specimens of the Gaboon viper (Bitis gabonica) snake have demonstrated the dangers of keeping exotic African snakes in captivity. CASE SERIES: Four cases necessitated hospitalization for the bite and were characterized by progressive swelling of the affected limb, local necrosis and hemorrhagic edema near the wound, chest tightness and prolonged coagulation times. However, platelet counts were not altered. All patients received antivenom and had uneventful recovery, except for one who underwent amputation of a distal phalanx and one who required debridement. In the fifth case, the patient died without being able to summon help. DISCUSSION: The results of this case series emphasize the need for extreme care to be exercised with the captivity of exotic snakes, such as the Gaboon viper. The increasing popularity of this snake as a captive pet predicates the need for private collectors to have a pre-existing treatment strategy with their local emergency centers. Such arrangements may facilitate the treatment of envenomation by this snake.

Test-retest norms and reliable change indices for the MicroCog Battery in a healthy community population over 50 years of age.

The increasing availability of computerized test batteries used to assess neuropsychological changes requires the availability of suitable test-retest normative data. Reliable change indices can then be used to evaluate significance of change in an individual's performance on retesting. We tested (N = 40) neurologically normal adults on three occasions (initially, two weeks, and three months) on the MicroCog: Assessment of Cognitive Functioning computerized testing instrument. Normative retest data are presented for two analytic techniques: the Reliable Change Index adjusted for practice and the Standardized Regression-Based technique. At two weeks, the correlation coefficients ranged from .49 to .84, with all scores demonstrating significant practice effects. At 3 months, coefficients ranged from .50 to .83, with all scores except Attention / Mental Control demonstrating significant practice compared to baseline. Regression equations were generated for all scores using age, sex, education level, and score at Time 1 as predictors. For all measures the only significant predictor was the Time 1 score. The reliable change indices and regression equations presented here can be used to determine the significance of change from predicted retest scores in a matched interventional cohort.

Assessment of statistical change criteria used to define significant change in neuropsychological test performance following cardiac surgery.

OBJECTIVE: This paper compares four techniques used to assess change in neuropsychological test scores before and after coronary artery bypass graft surgery (CABG), and includes a rationale for the classification of a patient as overall impaired. METHODS: A total of 55 patients were tested before and after surgery on the MicroCog neuropsychological test battery. A matched control group underwent the same testing regime to generate test-retest reliabilities and practice effects. Two techniques designed to assess statistical change were used: the Reliable Change Index (RCI), modified for practice, and the Standardised Regression-based (SRB) technique. These were compared against two fixed cutoff techniques (standard deviation and 20% change methods). RESULTS: The incidence of decline across test scores varied markedly depending on which technique was used to describe change. The SRB method identified more patients as declined on most measures. In comparison, the two fixed cutoff techniques displayed relatively reduced sensitivity in the detection of change. CONCLUSIONS: Overall change in an individual can be described provided the investigators choose a rational cutoff based on likely spread of scores due to chance. A cutoff value of > or =20% of test scores used provided acceptable probability based on the number of tests commonly encountered. Investigators must also choose a test battery that minimises shared variance among test scores.

Comparative analysis of prothrombin activators from the venom of Australian elapids.

A key component of the venom of many Australian snakes belonging to the elapid family is a toxin that is structurally and functionally similar to that of the mammalian prothrombinase complex. In mammals, this complex is responsible for the cleavage of prothrombin to thrombin and is composed of factor Xa in association with its cofactors calcium, phospholipids, and factor Va. The snake prothrombin activators have been classified on the basis of their requirement for cofactors for activity. The two major subgroups described in Australian elapid snakes, groups C and D, are differentiated by their requirement for mammalian coagulation factor Va. In this study, we describe the cloning, characterization, and comparative analysis of the factor X- and factor V-like components of the prothrombin activators from the venom glands of snakes possessing either group C or D prothrombin activators. The overall domain arrangement in these proteins was highly conserved between all elapids and with the corresponding mammalian clotting factors. The deduced protein sequence for the factor X-like protease precursor, identified in elapids containing either group C or D prothrombin activators, demonstrated a remarkable degree of relatedness to each other (80%-97%). The factor V-like component of the prothrombin activator, present only in snakes containing group C complexes, also showed a very high degree of homology (96%-98%). Expression of both the factor X- and factor V-like proteins determined by immunoblotting provided an additional means of separating these two groups at the molecular level. The molecular phylogenetic analysis described here represents a new approach for distinguishing group C and D snake prothrombin activators and correlates well with previous classifications.

Practical applications of snake venom toxins in haemostasis.

Snake venom toxins affecting haemostasis have facilitated extensively the routine assays of haemostatic parameters in the coagulation laboratory. Snake venom thrombin-like enzymes (SVTLE) are used for fibrinogen/fibrinogen breakdown product assay and for the detection of fibrinogen dysfunction. SVTLE are not inhibited by heparin and can thus can be used for assaying antithrombin III and other haemostatic variables in heparin-containing samples. Snake venoms are a rich source of prothrombin activators and these are utilised in prothrombin assays, for studying dysprothrombinaemias and for preparing meizothrombin and non-enzymic forms of prothrombin. Russell's viper (Daboia russelli) venom (RVV) contains toxins which have been used to assay blood clotting factors V, VII, X, platelet factor 3 and, importantly, lupus anticoagulants (LA). Other prothrombin activators (from the taipan, Australian brown snake and saw-scaled viper) have now been used to assay LA. Protein C and activated protein C resistance can be measured by means of RVV and Protac, a fast acting inhibitor from Southern copperhead snake venom and von Willebrand factor can be studied with botrocetin from Bothrops jararaca venom. The disintegrins, a large family of Arg-Gly-Asp (RGD)-containing snake venom proteins, show potential for studying platelet glycoprotein receptors, notably, GPIIb/IIIa and Ib. Snake venom toxins affecting haemostasis are also used in the therapeutic setting: Ancrod (from the Malayan pit viper, Calloselasma rhodostoma), in particular, has been used as an anticoagulant to achieve 'therapeutic defibrination'. Other snake venom proteins show promise in the treatment of a range of haemostatic disorders.

Increased platelet-derived microparticles in the coronary circulation of percutaneous transluminal coronary angioplasty patients.

Platelet-derived microparticles that are produced during platelet activation are capable of adhesion and aggregation. Endothelial trauma that occurs during percutaneous transluminal coronary angioplasty (PTCA) may support platelet-derived microparticle adhesion and contribute to development of restenosis. We have previously reported an increase in platelet-derived microparticles in peripheral arterial blood with angioplasty. This finding raised concerns regarding the role of platelet-derived microparticles in restenosis, and therefore the aim of this study was to monitor levels in the coronary circulation. The study population consisted of 19 angioplasty patients. Paired coronary artery and sinus samples were obtained following heparinization, following contrast administration, and subsequent to all vessel manipulation. Platelet-derived microparticles were identified with an anti-CD61 (glycoprotein IIIa) fluorescence-conjugated antibody using flow cytometry. There was a significant decrease in arterial platelet-derived microparticles from heparinization to contrast administration (P = 0.001), followed by a significant increase to the end of angioplasty (P = 0.004). However, there was no significant change throughout the venous samples. These results indicate that the higher level of platelet-derived microparticles after angioplasty in arterial blood remained in the coronary circulation. Interestingly, levels of thrombin-antithrombin complexes did not rise during PTCA. This may have implications for the development of coronary restenosis post-PTCA, although this remains to be determined.

Increased generation of platelet-derived microparticles following percutaneous transluminal coronary angioplasty.

Platelet-derived microparticles that are produced during platelet activation bind to traumatized endothelium. Such endothelial injury occurs during percutaneous transluminal coronary angioplasty. Approximately 20% of these patients subsequently develop restenosis, although this is improved by treatment with the anti-platelet glycoprotein IIb/IIIa receptor drug abciximab. As platelet activation occurs during angioplasty, it is likely that platelet-derived microparticles may be produced and hence contribute to restenosis. This study population consisted of 113 angioplasty patients, of whom 38 received abciximab. Paired peripheral arterial blood samples were obtained following heparinization and subsequent to all vessel manipulation. Platelet-derived microparticles were identified using an anti-CD61 (glycoprotein IIIa) fluorescence-conjugated antibody and flow cytometry. Baseline clinical characteristics between patient groups were similar. The level of platelet-derived microparticles increased significantly following angioplasty in the group without abciximab (paired t test, P = 0.019). However, there was no significant change in the level of platelet-derived microparticles following angioplasty in patients who received abciximab, despite requiring more complex angioplasty procedures. In this study, we have demonstrated that the level of platelet-derived microparticles increased during percutaneous transluminal coronary angioplasty, with no such increase with abciximab treatment. The increased platelet-derived microparticles may adhere to traumatized endothelium, contributing to re-occlusion of the arteries, but this remains to be determined.