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Biomedical subjects

L Mitchell

Publications and source records attributed to L Mitchell.

At least 55 records · Page 3Linked to original sources
PubMed1998

The relationship of antiphospholipid antibodies to thromboembolic events in pediatric patients with systemic lupus erythematosus: a cross-sectional study.

The purpose of this study was to evaluate pediatric patients with systemic lupus erythematosus (SLE) to determine 1) the incidence of thrombosis, 2) the incidence of antiphospholipid antibodies, and 3) whether there is an association between the presence of antiphospholipid antibodies and thrombosis. We performed a cross-sectional cohort study in 59 consecutive SLE patients who had been managed at rheumatology clinics in two pediatric hospitals. A history, questionnaire, and chart review were completed by the study nurse blinded to laboratory results. Only the thrombotic events that could be substantiated by review of radiographic tests were accepted. The presence of antiphospholipid antibodies was determined by prospective analysis for a lupus anticoagulant and anticardiolipin antibodies on two separate occasions at least 3 mo apart. Patients were considered to be positive if one or more tests were positive on both occasions. Thirteen thrombotic events occurred in 10 of the 59 patients (17%). Fourteen patients (24%) were classified as positive for lupus anticoagulant, and 19 patients (27%) were classified as positive for anticardiolipin antibodies. A significant relationship between the presence of a lupus anticoagulant and a thrombotic event was shown: odds ratio 28.7 (95% confidence interval 4.03-138.2, p < 0.001). A nonsignificant trend was seen for the presence of an anticardiolipin antibody and a thrombotic event: odds ratio 2.12 (95% confidence interval 0.71-22.8, p=0.08). We conclude that in pediatric patients with SLE: 1) a significant proportion of patients have thrombotic events, 2) a significant proportion of patients have antiphospholipid antibodies, and 3) there is a significant relationship between the presence of a lupus anticoagulant and thrombotic events.

Adolescent↗
PubMed1998

The correlation of the radiologic extent of lung transplantation edema with pulmonary oxygenation.

OBJECTIVE: The study set out to evaluate the relationship between the efficiency of pulmonary oxygenation and the extent of the reimplantation response as revealed on chest radiography after bilateral lung transplantation. MATERIALS AND METHODS: Postoperative chest radiographs of 31 patients who had undergone bilateral lung transplantation were evaluated for the extent of the reimplantation response. For each patient, the contemporaneous oxygenation indexes (partial pressure of oxygen in arterial blood divided by fraction of inspired oxygen) were calculated and correlated with a radiographic score produced from the evaluation of chest radiographs. RESULTS: The method of evaluating chest radiographs for the extent of the reimplantation response was shown to be reproducible. Although mean oxygenation indexes were found to decrease with increasing radiographic scores, this trend was not statistically significant. CONCLUSION: Although the extent of the reimplantation response on the early postoperative chest radiography inversely correlated with the oxygenation efficiency of the transplanted lungs, this finding was not statistically significant.

Adult↗
PubMed1998

A novel antithrombin-heparin covalent complex: antithrombotic and bleeding studies in rabbits.

Heparin has been used extensively for prophylaxis and treatment of deep vein thrombosis. However, heparin has several limitations including a short intravenous half-life, inability to inhibit clot-bound thrombin, and bleeding. We have developed a covalent antithrombin-heparin complex (ATH) that has a longer intravenous half-life and greater anticoagulant activity than heparin. The antithrombotic activity of ATH was tested in a rabbit jugular vein thrombosis treatment model. Administration of ATH caused a 17% reduction in clot weight compared with an increase of 24, 60, 172 and 135% for administration of antithrombin plus heparin, heparin, antithrombin and saline, respectively. Clot weight and fibrin accretion were both significantly lower in the ATH group than in the antithrombin plus heparin group (P < 0.05). The peak anti-factor-Xa activity was fourfold higher in the ATH group than in the antithrombin plus heparin group. Using a rabbit bleeding ear model, there was no significant difference in cumulative blood loss between ATH and antithrombin plus heparin groups, at similar plasma anti-factor-Xa levels. In conclusion, ATH has superior antithrombotic activity and similar bleeding effect compared with heparin on a mass basis. The enhanced antithrombotic activity of ATH may be a result of its increased anticoagulant activity or its longer half life, or both.

Animals↗
PubMed1997

Covalent antithrombin-heparin complexes with high anticoagulant activity. Intravenous, subcutaneous, and intratracheal administration.

Although heparin has been used clinically for prophylaxis and treatment of thrombosis, it has suffered from problems such as short duration within compartments in vivo that require long term anticoagulation. A covalent antithrombin-heparin complex has been produced with high anticoagulant activity and a long half-life relative to heparin. The product had high anti-factor Xa and antithrombin activities compared with noncovalent mixtures of antithrombin and heparin (861 and 753 units/mg versus 209 and 198 units/mg, respectively). Reaction with thrombin was rapid with bimolecular and second order rate constants of 1.3 x 10(9) M-1 s-1 and 3.1 x 10(9) M-1 s-1, respectively. The intravenous half-life of the complex in rabbits was 2.6 h as compared with 0.32 h for similar loads of heparin. Subcutaneous injection of antithrombin-heparin resulted in plasma levels (peaking at 24-30 h) that were still detectable 96 h post-injection. Given the increased lifetime in these vascular and intravascular spaces, use of the covalent complex in the lung was investigated. Activity of antithrombin-heparin instilled into rabbit lungs remained for 48 h with no detection of any complex systemically. Thus, this highly active agent has features required for pulmonary sequestration as a possible treatment for thrombotic diseases such as respiratory distress syndrome.

Animals↗
PubMed1997

Sympathetic reinnervation and heart rate variability after cardiac transplantation.

BACKGROUND: Heart rate variability is thought to measure autonomic modulation, but the relation has never been demonstrated directly in humans. AIM: To test the hypothesis that increased low frequency heart rate variability reflects sympathetic reinnervation after cardiac transplantation. PATIENTS: 24 cardiac transplant recipients at the time of routine surveillance coronary angiography two or more years after cardiac transplantation, and 10 controls with normal coronary arteries undergoing angiography for investigation of chest pain. SETTING: Regional cardiothoracic centre. METHODS: Sympathetic effector function at the sinus node was assessed by measuring the fall in cycle length for two minutes after injection of tyramine to the artery supplying the sinus node. Heart rate variability was measured from three-minute RR interval sequences at rest, during metronomic respiration, and before and after atropine. RESULTS: The logarithm of the low frequency component of heart rate variability during metronomic respiration was linearly related to the logarithm of the change in cycle length after injection of tyramine (R2 = 0.28, P = 0.007). Absolute units more accurately reflected sympathetic effector function than did normalised units or the ratio of low frequency to high frequency. Atropine did not affect high frequency heart rate variability in transplant recipients. CONCLUSIONS: The low frequency component of heart rate variability is directly related to sympathetic reinnervation to the sinus node.

Coronary Angiography↗
PubMed1997

Effects of changes in blood flow rate on cell death and cell proliferation in carotid arteries of immature rabbits.

Spontaneous and experimental changes in arterial blood flow rates affect tissue accumulation in developing arteries. To examine whether cell proliferation and/or cell death are affected by alterations in blood flow, we ligated the left external carotid artery of 3-week-old rabbits, which reduces left common carotid blood flow by 71%. In control arteries and after 2 days of flow reduction, agarose gel electrophoresis of DNA extracted from all carotid arteries resolved multiple low molecular weight bands characteristic of apoptosis; however, DNA fragmentation in arteries carrying reduced blood flow was 2.5-fold higher than that of control arteries. The effect of reduced blood flow on cell death subsequently waned but remained significant at 7 days. Cell death in carotid arteries was also detected by in vivo uptake of propidium iodide, a DNA-binding fluorescent dye that labels the nuclei of nonviable cells. Both smooth muscle and endothelial cells exhibited large and statistically significant increases in labeling index in the flow-reduced artery. Propidium iodide-labeled cells were cleared from the vessel wall within 1 to 4 hours of labeling, and nuclear staining displayed condensation (clumping) of chromatin in all labeled cells at later time points. This time course and nuclear morphology and the rapid clearance of labeled cells are consistent with death via apoptosis. Many propidium iodide-positive cells did not display chromatin condensation immediately after labeling; however, this was also true of cultured endothelial cells that were driven into apoptosis with sphingomyelinase treatment and then double-labeled with propidium iodide and the apoptosis marker annexin V. We infer that propidium iodide can label apoptotic vascular cells before these cells display chromatin condensation that is detectable with fluorescence labeling of DNA. Replication rates of smooth muscle and endothelial cells, determined by 5-bromo-2'-deoxyuridine uptake, were inhibited by >75% with decreased blood flow. The inhibition of proliferation was unabated after 7 days of reduced flow. These findings indicate that the coordinated regulation of cell death and cell proliferation, in response to changes in arterial blood flow rates, contributes to arterial remodeling during development.

Animals↗
PubMed1997

Coagulation and fibrinolytic profile of paediatric patients undergoing cardiopulmonary bypass.

The haemostatic system and the use of heparin during cardiopulmonary bypass (CPB) have been studied extensively in adults but not in children. Results from adult trials cannot be extrapolated to children because of age-dependent physiologic differences in haemostasis. We studied 22 consecutive paediatric patients who underwent CPB at The Hospital for Sick Children, Toronto. Fibrinogen, factors II, V, VII, VIII, IX, XII, prekallikrein, protein C, protein S, antithrombin (AT), heparin cofactor II, alpha 2-macroglobulin, plasminogen, alpha 2-antiplasmin, tissue plasminogen activator (tPA), plasminogen activator inhibitor, thrombin-AT complexes (TAT), D-dimer, heparin (by both anti-factor Xa assay and protamine titration) and activated clotting time (ACT) were assayed perioperatively. The timing of the sampling was: pre heparin, post heparin, after initiation of CPB, during hypothermia, post hypothermia, post protamine reversal and 24 h post CPB. Plasma concentrations of all haemostatic proteins decreased by an average of 56% immediately following the initiation of CPB due to haemodilution. During CPB, the majority of procoagulants, inhibitors and some components of the fibrinolytic system (plasminogen, alpha 2 AP) remained stable. However, plasma concentrations of TAT and D-dimers increased during CPB showing that significant activation of the coagulation and fibrinolytic systems occurred. Mechanisms responsible for the activation of haemostasis are likely complex. However, low plasma concentrations of heparin (< 2.0 units/ml in 45% of patients) during CPB were likely a major contributing etiology. ACT values showed a poor correlation (r = 0.38) with heparin concentrations likely due to concurrent haemodilution of haemostatic factors, activation of haemostatic system, hypothermia and activation of platelets. In conclusion, CPB in paediatric patients causes global decreases of components of the coagulation and fibrinolytic systems, primarily by haemodilution and secondarily by consumption.

Adolescent↗
PubMed1997

Differential pulmonary flow after heart transplantation in patients with malposition of the great arteries.

In transposition of the great arteries the right lung is preferentially perfused, and this may be due to the orientation of the right pulmonary artery when the main pulmonary artery comes off in a posterior position. In this study the mean perfusion of the right lung was 61% in six patients who had "correction" of the great artery malposition at the time of heart transplantation. This suggests that anatomic correction of pulmonary artery orientation does not correct the preferential perfusion to the right lung.

Adult↗
PubMed1996

Study of booster doses of two Haemophilus influenzae type b conjugate vaccines including their interchangeability.

A prospective, two center study of 319 children was undertaken to assess responses to booster immunization in healthy 18-month-olds who completed primary immunization 12 months earlier with Haemophilus influenzae type b (Hib) conjugate vaccine (either HbOC or PRP-T). Interchangeability of these products as boosters was also assessed, using combination products containing diphtheria, pertussis and tetanus components. The study was randomized and evaluator blinded. Sera obtained prior to booster vaccination and 4 weeks later were tested for anti-PRP using an IgG-specific enzyme immunoassay. Pre-immunization anti-PRP levels were low: unmeasurable levels (< 0.06 microgram ml-1) were present in 47% of those primed with HbOC and 35% of those primed with PRP-T (P < 0.05). Most children responded strongly to booster vaccination. Interchanging the products had no detrimental effect. Children who lacked measurable antibody prior to re-vaccination had significantly weaker responses 4 weeks afterward. Earlier Hib booster vaccination should be considered in Canada to avoid low anti-PRP trough levels. Extended follow-up of antibody levels and vaccine protective efficacy is also advisable given the observed heterogeneity of responses to booster vaccination.

Antibodies↗
PubMed1996

Three teams improving thrombolytic therapy.

BACKGROUND: The American Heart Association (AHA) standard for delivering thrombolytic therapy to chest pain patients is 30 to 60 minutes after patient presentation to the emergency department. Three acute care hospitals in an integrated health system in northern California shortened the time of administration of thrombolytic agents to appropriate patients presenting with chest pain in the emergency department. FINDING THE SOLUTIONS: Physician-led multidisciplinary teams developed algorithms to reduce variation and decrease the thrombolytic administration process to 30 minutes. Changes were made to prehospital and hospital thrombolytic policies and staff practices. REALIZING RESULTS: Each of the three acute care hospitals reduced their thrombolytic administration time by 48% to 59% to levels within the AHA standard. LEARNING FROM THE PROCESS: Internal benchmarking for clinical processes promotes a synergy between hospitals and medical staffs for the improvement of patient care. Multidisciplinary teams, which include community representatives, achieve a thorough understanding of a process, which in turn reduces variation in practice and improves quality.

Algorithms↗
PubMed1996

Exercise response after cardiac transplantation: correlation with sympathetic reinnervation.

OBJECTIVE: To investigate the relation between sympathetic efferent reinnervation and chronotropic competence during exercise testing after cardiac transplantation. PATIENTS: Twenty five long-term cardiac transplant recipients and 11 normal controls. SETTING: Regional cardiothoracic centre. METHODS: Intracoronary tyramine was given to the transplant recipients and the per cent heart rate change measured. Exercise tests were performed in patients and controls according to the chronotropic assessment exercise protocol, and the per cent heart rate reserve measured at peak exercise and 6 min afterwards to estimate the recovery rate. RESULTS: The mean (SD) percentage heart rate change after intracoronary tyramine was 15.7 (15.4). Heart rate reserve achieved at peak exercise was 68.3 (20.6)% compared with 102.7 (9.3)% in the controls (P < 0.001). Heart rate recovery at 6 min was 41.7 (20.1)% compared with 79.5 (9.0)% in the controls (P < 0.001). Total workload was 69.0 (33.0) METS.min compared with 117.2 (41.9) METS.min in the controls (P < 0.01). There was a positive correlation between heart rate reserve achieved at peak exercise and response to tyramine (r = 0.66, P < 0.01), between heart rate recovery and response to tyramine (r = 0.69, P < 0.001), and between total workload and response to tyramine (r = 0.63, P = 0.04). CONCLUSION: Functional sympathetic efferent reinnervation of the sinus node occurred in some patients after transplantation, and was associated with improved heart rate response during and recovery after exercise, as well as with increased total workload.

Adult↗
PubMed1996

Decreased thrombin activity of fibrin clots prepared in cord plasma compared with adult plasma.

We hypothesized that the immaturity of the newborn coagulation system may influence the procoagulant activity of clotbound thrombin. 125I-Labeled fibrin clots were prepared from adult and cord plasma, incubated in their respective plasmas, and fibrinopeptide A (FPA) production was measured. Cord plasma clots generated significantly less FPA compared with adult plasma clots (p < 0.001). Cord plasma clots incubated in adult plasma generated similar amounts of FPA as cord plasma clots in cord plasma. Adult plasma clots incubated in cord plasma clots generated more FPA than adult plasma clots in adult plasma. Adult and cord plasma clots were then incubated with purified human adult fibrinogen, and the discrepancy between adult and newborn plasma clots remained (p < 0.01). To compare the amount of clot bound thrombin, adult and cord plasma clots were sonicated and incubated with fibrinogen. Again, significantly less thrombin was seen in cord clots compared with adult clots (p < 0.01). Because cord plasma has lower prothrombin concentrations (0.5 U/mL) we increased cord plasma prothrombin concentration by the addition of purified prothrombin. Prothrombin supplemented cord plasma clots generated more thrombin than unsupplemented clots (p < 0.01) and in amounts similar to the adult system. In conclusion, decreased amounts of thrombin present in cord plasma clots compared with adult plasma clots results in less FPA production. The low plasma concentration of prothrombin in cord plasma is responsible for this phenomenon.

Adult↗
PubMed1995

Coil embolization of a coronary fistula in a post-transplant patient.

A 23-year-old man 6 months after post-orthotopic heart transplant was troubled by fatigue and breathlessness and noted to have a continuous murmur. Coronary angiography revealed five fistulae from the left anterior descending artery draining into the right ventricle. The left-to-right shunt was obliterated by coil embolization and this was associated with improvement in the patient's symptoms and a reduction in the murmur.

Adult↗
PubMed1995

Resources for ethical decision making.

Nurses often encounter ethical dilemmas during the course of their practice and play a key role in the ethical decision-making process. This article identifies resources available to assist the nurse in making sound ethical decisions. Institution-based resources, such as institutional review boards and pastoral care, and unit-based resources, including nursing ethics rounds and peer support, are discussed.

Decision Making↗