Search PubMed⌕ Search

Biomedical subjects

D W Holt

Publications and source records attributed to D W Holt.

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

Myocardial injury induced by radiofrequency and low energy ablation: a quantitative study of CK isoforms, CK-MB, and troponin-T concentrations.

We conducted a prospective, controlled study to investigate the use of CK-MB concentration and newer methods such as troponin-T concentration and CK isoforms, in the assessment of myocardial damage caused by radiofrequency current or low energy DC catheter ablation. The study population consisted of 3 consecutive patients who underwent low energy catheter ablation, 28 consecutive patients subjected to radiofrequency ablation, and 4 patients who were subjected to radiofrequency energy ablation but also had external DC shocks for cardioversion of atrial fibrillation that occurred during the procedure. The control group comprised eight subjects undergoing electrophysiological study. Prior to ablation and at 30 minutes, 1, 2, 6, and 12 hours following the procedure, serial blood samples were taken for measurement of troponin-T and CK-MB concentrations, and calculation of the MM3/MM1 and MB2/MB1 ratios. Troponin-T concentration was raised above normal in all patients subjected to low energy ablation and in all but two patients subjected to radiofrequency ablation. Only 42% of all patients subjected to ablation had at least one raised CK-MB concentration postablation. The MB2/MB1 ratio was raised in all but had at least one raised CK-MB concentration postablation. The MB2/MB1 ratio was raised in all but two patients following radiofrequency or low energy ablation but it was also abnormal in the preablation samples in nine patients. The MM3/MM1 ratio failed to detect myocardial damage in 71% of all patients. There was a statistically significant difference between the control and patient groups regarding all four indices of myocardial damage. Low energy ablation caused a significantly higher degree of myocardial damage compared with radiofrequency (RF); this effect could not be attributed to different numbers of total energy discharges. Our results indicate that catheter ablation, regardless of the mode of energy used, inflicts detectable injury upon the myocardium. This injury can be quantitated by using newer analytical techniques, such as serial, postablation measurements of troponin-T concentration.

Adult↗
PubMed1997

Creatine kinase isoforms as circulating markers of deterioration in idiopathic dilated cardiomyopathy.

BACKGROUND: A proportion of patients with dilated cardiomyopathy (DCM) may have ongoing myocardial damage secondary to viral or immune mediated myocardial inflammation. HYPOTHESIS: The prognostic determinants identify patients with decreased survival but do not provide a measure of myocardial damage. To obtain an objective assessment of myocardial damage in DCM, we measured plasma levels of creatine kinase (CK), its isoenzymes (CK-MM and CK-MB), and separated the isoforms of CK-MM and CK-MB. METHODS: The cohort consisted of 77 consecutive patients (61 men, 16 women) with DCM (World Health Organization criteria), aged 49 +/- 14 years (range 19-60). Patients had been symptomatic for 29 +/- 38 months (range 0.5-200 months) with 48 in New York Heart Association class I/II and 29 in class III/IV at the time of diagnosis. During median follow-up of 27 months from diagnosis (range 0.6-165), 50 patients remained clinically stable and 27 had deteriorated. RESULTS: A significantly higher proportion of patients with DCM had abnormal MB2/MB1 ratio compared with normal volunteers (11, 14% vs. 1,1%, p = 0.003). Patients who deteriorated had higher MB2/MB1 ratio, (1.22 +/- 0.62 vs. 0.85 +/- 0.56; p = 0.01), and more frequently had abnormal MB2/ MB1 ratio (8, 30% vs. 3, 6%; p = 0.004) and CK and CK-MM activities (5, 19% vs. 2, 4%; p = 0.03) than those who remained stable. Patients with DCM with high CK-MB activity had 3.13-fold increased odds of sudden death or need for cardiac transplantation (95% confidence interval 1.53-6.40, p = 0.008). Thus, CK measurements, in particular CK-MB isoforms, are markers of myocardial damage in a subset of patients with DCM and could be useful in investigating the possibility of persistent myocardial damage in these patients.

Adult↗
PubMed1997

Use of troponin-T concentration and kinase isoforms for quantitation of myocardial injury induced by radiofrequency catheter ablation.

BACKGROUND: Although there remains particular concern about late malignant ventricular arrhythmias arising from myocardial damage induced by catheter ablation, the extent of myocardial injury resulting from clinical ablation procedures has not been fully studied. We conducted a prospective, controlled study to investigate the use of two newer markers of myocardial integrity, troponin-T concentration and creatine kinase isoforms, and a traditional marker, creatine kinase-MB concentration, in the assessment of myocardial injury following radiofrequency catheter ablation. METHODS AND RESULTS: The study population consisted of 28 consecutive patients subjected to radiofrequency catheter ablation, and the control group comprised eight subjects undergoing diagnostic electrophysiology study. Prior to ablation and at 30 min, 1, 2, 6, and 12 h following the procedure, blood samples were taken to measure troponin-T and creatine kinase-MB concentrations, and the separation of creatine kinase isoforms (MM3/MM1 and MB2/MB1 ratios). The troponin-T concentration was above normal in all but two patients following radiofrequency ablation, and the MB2/MB1 ratio was raised in all but one patient following ablation, but was also abnormal in the pre-ablation samples in seven patients. The MM3/MM1 ratio failed to detect myocardial injury in 75% of patients. Of patients subjected to ablation, in only 36% was the creatine kinase-MB concentration raised at least once post-ablation. Thirty minutes post-ablation, there was a statistically significant difference between the control and patient groups only as regards troponin-T concentration. There was a significant association between troponin-T concentration immediately post-procedure, the number of discharges delivered (r = 0.52, P = 0.006) and maximum power used (r = 0.48, P = 0.009). CONCLUSION: Our results indicate that catheter ablation inflicts a cumulative, detectable injury upon the myocardium. This injury can be quantitated by using newer analytical techniques, such as serial, post-ablation measurements of troponin-T concentration.

Adult↗
PubMed1997

Simple bioequivalence criteria: are they relevant to critical dose drugs? Experience gained from cyclosporine.

A critique of the current bioequivalence regulations is presented with reference to critical dose drugs. Using the development of a new cyclosporine formulation as an example, the deficiencies in current bioequivalence testing guidelines are examined and discussed. Based on the experience gained with cyclosporine, recommendations are made on how therapeutic equivalence, rather than just bioequivalence, should be established.

Area Under Curve↗
PubMed1996

Predicting patients' exposure to cyclosporin.

The introduction of a new formulation of cyclosporin, Neoral, has reduced pharmacokinetic variability and it may be possible to simplify area-under-curve (AUC) measurements using a limited sampling strategy. We have examined the timing of blood samples necessary to obtain accurate AUC predictions for cyclosporin using limited data from stable renal transplant patients dosed twice daily with Neoral. Best subset regression of blood concentration profile data obtained from ten patients at steady state indicated that two samples, timed at 2 and 8 h post-dose, accounted for 97% of the variance in AUC. The accuracy of this prediction was tested using profile data collected in a further 36 patients on three occasions separated by 4 and 44 weeks. Using the regression, AUC = 1.96 x [2 h] + 11.5 x [8 h] + 355.2, the mean (95% CI) prediction errors of the three occasions were 1.7% (-2.1-5.4%), 3.3% (-2.6-9.2%) and 0.4% (-3.4-4.2%). Data are presented that suggest AUC monitoring with a single blood sample could be feasible in a clinical setting.

Cyclosporine↗
PubMed1996

Quality assessment issues of new immunosuppressive drugs and experimental experience.

There are established quality assessment schemes for the two immunosuppressive drugs that have entered routine clinical use: cyclosporine and tacrolimus. These two drugs, together with sirolimus and mycophenolic acid, have been the subject of recent consensus panel reports that have reached broad agreement on several issues relating to therapeutic monitoring of these agents. While the current quality assessment schemes are not based on validated reference methods, the data they yield on comparative assay performance are of value as a guide to patient management and for clinical studies of drug efficacy.

Cyclosporine↗