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Biomedical subjects

T Baglin

Publications and source records attributed to T Baglin.

At least 19 recordsLinked to original sources
PubMed2001

Application of tissue Doppler to interpretation of dobutamine echocardiography and comparison with quantitative coronary angiography.

The main limitation of dobutamine echocardiography (DE) is its subjective interpretation. We sought to reduce the need for expert interpretation by developing a quantitative approach to DE using myocardial Doppler velocity (MDV) in 242 patients undergoing DE. In 128 patients with a normal dobutamine echocardiogram, the normal range was designed to give a specificity of 80%. The accuracy of this range was investigated in 114 consecutive patients who underwent coronary angiography within 2 months of DE. A standard dobutamine echocardiographic protocol was used, with MDV gathered from color tissue Doppler at rest and peak stress. Wall motion at these stages was scored by experienced observers using a 16-segment model and MDV was measured off-line. Sensitivity and specificity of wall motion scoring and MDV were obtained by comparison with angiographic evidence of disease, defined as stenosis > 50% of the coronary artery diameter. The normal range in tethered segments (septum, anteroseptum, and inferior) was > or = 7 cm/s in the basal segments and > or = 5 cm/s in the midsegments. In the free wall (anterior, lateral, and posterior), the cutoff was > or = 6 cm/s in the base and > or = 4 cm/s in the midventricle. Of 114 patients undergoing angiography, 84 (75%) had significant stenoses, and the sensitivity of wall motion scoring and MDV were 88% and 83%, respectively, with specificities of 81% and 72% (p = NS). The accuracy was similar overall (86% vs 80%), as well as in each vascular territory. These data suggest that a fully quantitative interpretation of DE using site-specific normal ranges of tissue Doppler, which account for regional variations of base-apex function, is feasible and equivalent in accuracy to expert wall motion scoring.

Adult↗
PubMed2001

Assessment of regional long-axis function during dobutamine echocardiography.

Echocardiographic analysis of regional left ventricular function is based upon the assessment of radial motion. Long-axis motion is an important contributor to overall function, but has been difficult to evaluate clinically until the recent development of tissue Doppler techniques. We sought to compare the standard visual assessment of radial motion with quantitative tissue Doppler measurement of peak systolic velocity, timing and strain rate (SRI) in 104 patients with known or suspected coronary artery disease undergoing dobutamine stress echocardiography (DbE). A standard DbE protocol was used with colour tissue Doppler images acquired in digital ciné-loop format. Peak systolic velocity (PSV), time to peak velocity (TPV) and SRI were assessed off-line by an independent operator. Wall motion was assessed by an experienced reader. Mean PSV, TPV and SRI values were compared with wall motion and the presence of coronary artery disease by angiography. A further analysis included assessing the extent of jeopardized myocardium by comparing average values of PSV, TPV and SRI against the previously validated angiographic score. Segments identified as having normal and abnormal radial wall motion showed significant differences in mean PSV (7.9 +/- 3.8 and 5.9 +/- 3.3 cm/s respectively; P < 0.001), TPV (84 +/- 40 and 95 +/- 48 ms respectively; P = 0.005) and SRI (-1.45 +/- 0.5 and -1.1 +/- 0.9 s(-1) respectively; P < 0.001). The presence of a stenosed subtending coronary artery was also associated with significant differences from normally perfused segments for mean PSV (8.1+/-3.4 compared with 5.7+/-3.7 cm/s; P < 0.001), TPV (78 +/- 50 compared with 92 +/- 45 ms; P < 0.001) and SRI (-1.35 +/- 0.5 compared with -1.20 +/- 0.4 s(-1); P = 0.05). PSV, TPV and SRI also varied significantly according to the extent of jeopardized myocardium within a vascular territory. These results suggest that peak systolic velocity, timing of contraction and SRI reflect the underlying physiological characteristics of the regional myocardium during DbE, and may potentially allow objective analysis of wall motion.

Adrenergic beta-Agonists↗
PubMed2000

Influence of cytochrome P-450 CYP2C9 polymorphisms on warfarin sensitivity and risk of over-anticoagulation in patients on long-term treatment.

Cytochrome P-450 2C9 is the principle enzyme that terminates the anticoagulant effect of warfarin. Genetic polymorphisms in CYP2C9 producing variants with altered catalytic properties have been identified. Patients (n = 561) with a target international normalized ratio (INR) of 2.5 who had been treated with warfarin for more than 2 months were anonymously genotyped for the wild-type CYP2C9*1 allele and the 2C9*2 and 2C9*3 variants. The mean maintenance dose of warfarin in patients who were wild-type for both alleles was 5.01 mg. The maintenance dose of warfarin was significantly related to genotype (Kruskall-Wallis, chi(2) = 17.985, P =.001) with mean maintenance doses in patients with variant alleles between 61% and 86% of that in wild-type patients. The odds ratio for the 2C9*2 allele in patients with a maintenance dose of 1. 5 mg or less was 5.42 (95% CI 1.68-17.4). The odds ratio for one or more variant alleles in patients developing an INR of 8.0 or greater was 1.52 (95% CI 0.64-3.58). The SD of the mean INR, percentage of high INRs, and person-time spent in range were determined as parameters of stability. There was no difference between patients grouped according to genotype for any parameter of stability. This study confirmed an association between CYP2C9 genotype and warfarin sensitivity. However, the possession of a variant allele does not increase the likelihood of severe over-anticoagulation or stability of anticoagulation during long-term therapy. (Blood. 2000;96:1816-1819)

Alleles↗
PubMed2000

Effect of the angiotensin-converting enzyme gene deletion polymorphism on the risk of venous thromboembolism.

Allele frequencies for the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene were determined in a large case-control study of 517 unselected patients with venous thromboembolism and 478 blood donors. The D allele frequency was 0. 53 [95% confidence interval (CI) 0.50-0.56] in patients and 0.54 (95% CI 0.50-0.57) in controls, giving an odds ratio for the D allele of 0.97 (95% CI 0.81-1.16). In the same population, the odds ratio for the factor V Leiden mutation (F5G1691A) was 6.9 (95% CI 4. 0-11.9). Therefore, the ACE I/D polymorphism is not a risk factor in a representative group of unselected patients with venous thromboembolism. The possibility that the I/D polymorphism is a risk factor for venous thromboembolism specifically after hip replacement cannot be excluded.

Arthroplasty, Replacement, Hip↗
PubMed2000

Recurrent haematomas of the thigh: a case of von Willebrand's disease presenting to a sports clinic.

Von Willebrand's disease is a relatively common mild form of haemophilia. It should be suspected in assessing sports injuries when excessive bleeding occurs in response to relatively mild trauma. Those with the disease should remain active but avoid contact sports. They should not take aspirin or non-steroidal anti-inflammatory drugs, which may exacerbate bleeding, and should be given supportive treatment to cover dental extraction, surgery, or significant bleeding episodes.

Adult↗
PubMed2000

The factor V R2 allele: risk of venous thromboembolism, factor V levels and resistance to activated protein C.

Case-control studies have yielded conflicting results regarding the relative risk of venous thromboembolism associated with the factor V R2 allele. We calculated odds ratios in 581 patients and 469 age-matched controls. The odds ratio for the R2 allele in patients relative to controls was 1.21 (95% CI 0.84 to 1.74). These results do not support the hypothesis that the R2 allele is a risk factor for venous thromboembolism. There was no relationship between factor V levels and R2 carrier status. Normalised APC sensitivity ratios were not lower in carriers of the R2 allele. In an in vitro model progressive APC resistance was observed with factor V levels of 60% and less but ratios less than 2.4 (equivalent to a normalised ratio of 0.73) did not occur until factor V levels were less than 20%. The relationship between APC resistance and factor V level was not observed in a factor VIII-independent model.

Activated Protein C Resistance↗
PubMed1999

Lupus anticoagulant testing with optical end point automation.

The dilute Russell viper venom time and kaolin clotting time (KCT) are very sensitive screening tests for lupus anticoagulant activity. However, due to the high turbidity of the kaolin reagent it is difficult to accommodate the KCT on the optical end point automation of today. We evaluated five recently reported screening tests (the silica clotting time, the Textarin/Ecarin ratio, the Taipan venom time, the factor V ratio, and a kaolin clotting time using low-turbidity kaolin) as potential alternatives to the KCT. The sensitivity and specificity of the silica clotting time compared well to KCT, detecting 10/12 KCT positive samples and showing equal sensitivity to dilution of lupus positive plasma. In addition, the silica clotting time allows for a confirmatory phospholipid correction procedure. False-positive results were seen in 2 of 15 warfarinised samples. A second assay utilising the ratio of extrinsic/intrinsic factor V assays was not affected by either warfarin or heparin. This assay also gave positive results with 3 of 23 samples previously screened as lupus negative but exhibiting anticardiolipin positivity. It was therefore concluded that a combination of the silica clotting time and dilute Russell viper venom time met the requirements of lupus sensitivity with demonstration of phospholipid dependence and optical end point compatibility. The factor V ratio is a useful second-line screen for both anticoagulated patients and anticardiolipin antibody-positive samples.

Anticoagulants↗
PubMed1999

Activated protein C resistance: effect of platelet activation, platelet-derived microparticles, and atherogenic lipoproteins.

Plasma and platelet factor Va represent different substrates for activated protein C (APC). In this study, we have measured platelet-dependent APC resistance and the effect of aspirin and a platelet glycoprotein IIbIIIa antagonist (GR144053F) on this phenomenon. In platelet rich plasma (PRP), progressive APC resistance was observed with increasing platelet activation. APC sensitivity ratios of 1.8, 1.7, and 1.4 were observed after platelet activation with thrombin receptor activating peptide (TRAP), collagen, and A23187, respectively. Ultracentrifugation at 77,000g for 1 hour abolished APC resistance indicating that the phenotype is associated exclusively with the platelet membrane. APC resistance was not observed in the presence of phosphatidylcholine-phosphatidylserine (PCPS) vesicles or purified human plasma lipoproteins. APC resistance was observed in the presence of platelet-derived microparticles, but to a lesser degree than that in the presence of activated platelets. The platelet-dependent APC resistance phenotype was also observed when endogenous APC was generated by Protac (American Diagnostica, Inc, Greenwich, CT). In vitro inhibition of platelet activation with aspirin had no effect, but the fibrinogen receptor antagonist, GR144053F, inhibited platelet-dependent APC resistance. These results indicate that platelet activation results in an APC-resistant phenotype comparable to that observed in the plasma of patients with factor V gene mutations affecting critical APC cleavage sites. This suggests that platelet activation at the site of endothelial damage downregulates a critical natural anticoagulant mechanism. The antithrombotic effect of aspirin may be due to an indirect effect on platelet-dependent APC resistance with reduced platelet retention within a developing thrombus. The more potent antithrombotic effect of glycoprotein IIbIIIa antagonists may in addition be the result of reduced platelet factor Va expression and modulation of the platelet-dependent APC resistance phenotype.

Activated Protein C Resistance↗
PubMed1998

Factor V Cambridge: a new mutation (Arg306-->Thr) associated with resistance to activated protein C.

A new factor V mutation associated with resistance to activated protein C and thrombosis (factor V Cambridge, Arg306-->Thr) was found in one patient from a carefully selected group of 17 patients with venous thrombosis and confirmed APC resistance in the absence of the common Gln506 mutation. The Arg306 mutation was also present in a first degree relative who also had APC resistance. Other potential causes of APC resistance, such as a mutation at the Arg679 site and the factor V HR2 haplotype, were excluded. Subsequent screening of 585 patients with venous thromboembolism and 226 blood donors did not show any other individual with this mutation. Factor VThr306 is the first description of a mutation affecting the Arg306 APC cleavage site and is the only mutation, other than factor V Leiden (Arg506-->Gln), that has been found in association with APC resistance. This finding confirms the physiologic importance of the Arg306 APC-cleavage site in the regulation of the prothrombinase complex. It also supports the concept that APC resistance and venous thrombosis can result from a variety of genetic mutations affecting critical sites in the factor V cofactor.

Arginine↗
PubMed1998

Management of warfarin (coumarin) overdose.

Treatment with coumarin oral anticoagulants, such as warfarin, is effective antithrombotic therapy, but patients treated with these drugs are at significant risk of bleeding. The risk of haemorrhage increases with increasing intensity of anticoagulation and overanticoagulation is common. Reversal can be achieved by stopping the coumarin drug or administration of vitamin K, fresh frozen plasma or coagulation factor concentrates. However, there are surprisingly few studies defining the optimum dose of these products and there are no randomized studies comparing the relative benefit and risk of coagulation factor concentrates versus fresh frozen plasma. Guidelines for the management of overdose are based on level III and IV evidence and are, therefore, only grade B recommendations at best. Further studies are required to determine the most effective use of products and the dose required for safe reversal of overanticoagulation.

Anticoagulants↗
PubMed1998

Risk of recurrent venous thromboembolism in patients with the factor V Leiden (FVR506Q) mutation: effect of warfarin and prediction by precipitating factors. East Anglian Thrombophilia Study Group.

Three cohorts of patients with the factor V Leiden mutation were recruited independently (heterozygotes, homozygotes and combined thrombophilia). The antithrombotic efficacy of oral anticoagulation and the predictive value for recurrence of an idiopathic as opposed to a precipitated first event were determined. Idiopathic first events occurred at an older age than precipitated events (43 v 26 years, LR = 23.31, P < 0.001). None of the patients had a recurrent event while on warfarin but the median time to recurrence after stopping warfarin was 9 years (95% CI 0.7-17.3 years). The time to recurrence was shorter when the first event was idiopathic as opposed to precipitated (3.5 v 13 years, LR = 4.76, P = 0.029). A calculation of benefit to risk of oral anticoagulation with a target INR of 2.5 does not support the use of long-term therapy in all patients with the factor V Leiden mutation following a first thrombotic event.

Adolescent↗
PubMed1998

A common polymorphism in the tumour necrosis factor-alpha gene associated with high TNF levels is not a risk factor for venous thromboembolism.

The odds ratio of homozygosity or heterozygosity for the TNF2 polymorphism in 575 patients with venous thromboembolism compared to controls was found to be 1.0 (95% CI 0.4-2.1) and 1.1 (95% CI 0.8-1.4) respectively. Comparing subgroups of patients and controls with the factor V Leiden mutation the odds ratio for the TNF2 polymorphism was 0.7 (95% CI 0.2-2.2). Despite evidence of a link between high tumour necrosis factor (TNF) levels and hypercoagulability, our results do not indicate a link between the genetic regulation of TNF production and venous thromboembolic disease.

Adolescent↗
PubMed1998

Prevention of central venous catheter associated thrombosis using minidose warfarin in patients with haematological malignancies.

Thrombosis is a well-recognized complication following insertion of central venous catheters and is associated with significant morbidity. In an attempt to reduce line-associated thrombosis, 108 consecutive patients with haematological malignancies were commenced on prophylactic 'minidose' warfarin, 1 mg/d, at the time of line insertion. This group of patients were compared with a historic group of 115 consecutive patients who had not received warfarin. Clinically-suspected venous thrombosis was confirmed by Doppler ultrasound or venography. Patients taking prophylactic warfarin had their prothrombin time measured three times per week with the aim of maintaining an INR <1.6. Five (5%) of the 108 patients who received minidose warfarin developed a thrombosis, at a median of 72 d (range 5-166) from the time of catheter insertion. In the 115 patients who were not anticoagulated 15 (13%) developed a catheter-associated thrombosis at a median of 16 d (range 1-35). There was a significant reduction in line-associated thrombosis in patients receiving warfarin (P=0.03). These data suggest that minidose warfarin reduces the incidence of central venous catheter related thrombosis in patients with haematological malignancies.

Adult↗