BCR-ABL transcript with an e19a2 (c3a2) junction in classical chronic myeloid leukemia.
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Aged↗
Biomedical subjects
L Frost
Publications and source records attributed to L Frost.
Efficacy and safety of dofetilide, a new class III antiarrhythmic agent, in acute termination of atrial fibrillation or flutter after coronary artery bypass surgery. Dofetilide Post-CABG Study Group.
Ninety-eight patients, who developed atrial fibrillation/flutter after coronary artery bypass grafting within 1-6 days after surgery, were included into a double-blind, placebo-controlled, randomized trial to assess the efficacy and safety of dofetilide. Patients were randomly allocated to dofetilide 4 micrograms/kg i.v. (n = 33), dofetilide 8 micrograms/kg i.v. (n = 32) or placebo (n = 33) given intravenously over 15 min at a constant infusion rate. Responders were defined as patients who converted to sinus rhythm at any time during the initial 3 h after the start of the infusion. The conversion rates were 24% (8/33) on placebo, 36% (12/33) on dofetilide 4 micrograms/kg, and 44% (14/32) on dofetilide 8 micrograms/kg. The P-values (two-tailed) were 0.27 for dofetilide 4 micrograms/kg vs. placebo, 0.11 for dofetilide 8 micrograms/kg vs. placebo, and 0.10 for dose-response relationship. Short episodes of aberrant ventricular conduction and ventricular tachycardia were seen separately in three subjects after dofetilide 8 micrograms/kg. No episodes of torsades de pointes were noted. No negative inotropic effect was noted. In conclusion, dofetilide was well tolerated, but the effects on atrial fibrillation/flutter did not attain statistical significance, possibly due to the high placebo conversion rate.
Aged↗
Repetitive strain injuries and cumulative trauma disorders.
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Cumulative Trauma Disorders↗
Clonal stability in late-relapsing childhood lymphoblastic leukaemia.
We report stability of a clonal immunoglobulin heavy chain (IgH) gene rearrangement in a case of childhood acute lymphoblastic leukaemia (ALL) relapsing 17 years after completion of first-line therapy. Clonal stability was shown by polymerase chain reaction amplification of the hypervariable CDRIII region of IgH gene. Identically sized products from the original diagnostic and the second presentation samples were obtained and direct sequencing confirmed complete sequence homology. Absence of clonal evolution together with recent reports of persistent minimal residual disease in patients in long-term complete remission, suggests that 'cure' of childhood ALL may be critically dependent on effective immune surveillance to keep such disease below clinically significant levels.
Adult↗
Cytobrush and endocervical curettage in the diagnosis of dysplasia and malignancy of the uterine cervix.
BACKGROUND: The validity of cytobrush and endocervical curettage combined with colposcopically directed biopsies in the diagnosis of cervical dysplasia and malignancy has not been evaluated in randomized trials. We aimed to elucidate the diagnostic validity of the two methods. METHODS: A prospective, randomized study of 180 consecutive patients. All patients were examined without anesthesia by colposcopically directed biopsies of the ectocervix and randomly assigned to either cytobrush or endocervical curettage. Patients with < or = CIN 1 were investigated with the alternative method three months later. Patients with > or = CIN 2 had a cone biopsy. RESULTS: One hundred and thirty-one patients were evaluable. The sensitivity of cytobrush and endocervical curettage combined with colposcopically directed biopsies of the ectocervix was 96% and 84% (p = 0.08), respectively. The specificities of the two investigations were 95% and 88%, respectively (p = 0.78). All cytobrush specimens were evaluable but because of a low recovery of endocervical material a diagnosis could not be made in 12% of the patients examined by endocervical curettage. CONCLUSION: The sensitivity of the combined use of cytobrush and biopsies of the ectocervix was equal to or higher than the sensitivity of endocervical curettage and ectocervical biopsies. The specificities of the two investigations were much alike. All cytobrush specimens were evaluable but a diagnosis could not be performed in 12% of the endocervical curettage specimens because of too little endocervical material. Furthermore, cytobrush is less inconvenient to the patient. Therefore, in the follow-up of patients with cervical dysplasia endocervical curettage may be replaced with cytobrush.
Adolescent↗
[Atrial fibrillation after coronary artery bypass surgery. The significance of preoperative vagus modulation and ectopic atrial activity].
To investigate the impact of pre-operative autonomic balance and atrial ectopic activity on the risk of atrial fibrillation or flutter after aorto-coronary artery bypass surgery 24-hour Holter monitoring was analyzed in 102 patients before coronary artery bypass grafting. Index for vagal tone was calculated as % successive RR-interval differences > 6%. Twenty-nine (28%) of the 102 patients developed atrial fibrillation or flutter. Independent predictors (90% confidence interval) of postoperative atrial fibrillation or flutter were identified by logistic regression analysis: the independent predictors were older age, relative risk 1.07/year (1.02-1.12), vagal index < 10%, relative risk 4.50 (1.40-14.5), > or= 10 ectopic supraventricular beats/24 hour, relative risk 3.03 (1.05-8.72), and one or more event of non-sustained supraventricular tachycardia, relative risk 3.02 (1.11-8.22). Thus, age of the patient, attenuated preoperative cardiac vagal modulation, ectopic supraventricular beats, and paroxysmal non-sustained supraventricular tachycardia are independent risk factors for the development of atrial fibrillation or flutter after coronary artery bypass surgery.
Atrial Fibrillation↗
Impaired bile flow and disordered hepatic calcium homeostasis are early features of halothane-induced liver injury in guinea pigs.
To characterize the early events in liver injury produced by halothane, experiments were performed in genetically susceptible guinea pigs 19 hours after halothane exposure. Serum bile acid concentrations were fourfold increased in halothane-exposed animals compared with controls. In isolated perfused liver experiments, livers from halothane-exposed animals did not differ in hepatic oxygen uptake or in perfusion pressure at the end of experiments, but bile flow and biliary bile salt concentrations were reduced. Hepatic calcium content was increased in halothane-exposed guinea pigs compared with controls, and further experiments were performed to explore the reason for this. As determined by infusion of 45Ca to steady-state perfusate concentrations, hepatic calcium clearance was increased in halothane-exposed guinea pigs compared with controls (0.37 +/- 0.06 vs. 0.28 +/- 0.02 mL/min, P < .01). Decreased biliary excretion of calcium was also noted and was entirely attributable to reduced bile flow. However, although decreased excretion contributed to hepatic accumulation of calcium, it was quantitatively less important than enhanced hepatic uptake. As indicated by passage of a bolus of horseradish peroxidase from perfusate into bile, hepatic tight junction permeability was increased five-fold after halothane exposure. It is concluded that cholestasis, as exemplified by reduced bile flow, is an early feature of the liver injury produced by halothane in guinea pigs and is associated with increased tight junction permeability. Although the decrease in bile flow contributes to an early increase in hepatic calcium content, entry of calcium from the perfusion compartment is quantitatively more important.
Animals↗
Effect of residual noise level on reproducibility of the signal-averaged ECG.
Late potentials are detected at various noise levels in clinical studies. The aim of this study was to assess the effect of residual noise level on the reproducibility of the signal-averaged electrocardiogram (ECG). Two consecutive raw 15-minute ECG from each of 188 patients with coronary artery disease were digitized and stored on optical discs. Each raw ECG was analyzed by two signal-averaging procedures to noise level 0.2 microV or 0.4 microV. Standard time-domain parameters were measured: QRS duration (SA-QRS), late potential (LP) duration, and root-mean-square voltage of the terminal 40 ms of the filtered QRS (RMS40). The SA-QRS was prolonged by 12 +/- 14 ms by the reduction in noise level from 0.4 microV to 0.2 microV, LP duration was prolonged by 10 +/- 10 ms, and RMS40 was reduced by 19 +/- 22 microV. The temporal variation of the measured SA-QRS from ECG1 to ECG2 was significantly lower at noise level 0.2 microV (9 +/- 13 ms) than at noise level 0.4 microV (13 +/- 14 ms) (P < .001). The LP duration was also more stable at noise level 0.2 microV than at noise level 0.4 microV (0.5 +/- 11 ms vs 2 +/- 13 ms, P < .05). The presence of any two of three abnormal parameters (SA-QRS > 120 ms, RMS40 < 25 microV, LP duration > 40 ms) was used as the criterion for the presence of LPs. At noise level 0.4 microV, the proportion of patients with diagnosed LPs in ECG1 was 25% and at noise level 0.2 microV it was 62%. At noise level 0.4 microV, 20% were reclassified from LP-negative in ECG1 to LP-positive in ECG2, and 7% were reclassified from LP-positive in ECG1 to LP-negative in ECG2. At noise level 0.2 microV, 20% were reclassified from LP-negative in ECG1 to LP-positive in ECG2, and 9% were reclassified from LP-positive in ECG1 to LP-negative in ECG2. It was concluded that (1) the diagnosis of LPs is significantly dependent on the extent of noise reduction by signal averaging: and (2) the numerical reproducibility of signal-averaged QRS duration and LP duration is lower at noise level 0.4 microV then at noise level 0.2 microV; and the diagnostic reproducibility of LPs is similar at both noise levels.
Aged↗
Construction of derivatives of the F plasmid pOX-tra715: characterization of traY and traD mutants that can be complemented in trans.
A derivative of the F plasmid, pOX38-tra715, expresses the entire F tra operon from a foreign promoter (PT7) derived from phage T7. A series of plasmids related to pOX38-tra715 were constructed which carry either deletion mutations or point mutations in traY. When the PT7 promoter was induced, these plasmids expressed the F pilus but were transfer deficient unless TraY was supplied In trans from compatible plasmids. Insertion of a kanamycin-resistance cassette in the traY gene of the pOX38 plasmid, which contains the wild-type PY promoter, resulted in loss of F piliation and transfer ability. Introduction of TraY in trans partially restored piliation and transfer suggesting that TraY has a role in positively regulating the PY promoter, pOX38-tra719-traD411, which contains a chloramphenicol-resistance cassette in place of the kanamycin-resistance cassette in pOX38-tra715 and a mutation in traD, was constructed to demonstrate the utility of this series of plasmids in studying the long (30 kb) F tra operon.
Bacterial Proteins↗
Noise in the signal-averaged electrocardiogram and accuracy for identification of patients with sustained monomorphic ventricular tachycardia after myocardial infarction.
Late potentials are detected at various noise levels in clinical studies. The aim of this study was, in a case-control design, to assess the effect of residual noise level on the identification of patients with sustained monomorphic ventricular tachycardia after myocardial infarction. Electrocardiograms from 16 patients with prior myocardial infarction and documented sustained monomorphic ventricular tachycardia and 41 patients with prior myocardial infarction and without ventricular tachycardia, were analysed by two signal averaging procedures to noise level 0.2 and 0.4 muV. Standard time domain parameters were measured. Two definitions of late potential were analysed: (1) if any two of the following criteria were present (signal-averaged QRS duration > 120 ms, late potential duration > 40 ms, and root-mean-square voltage of the terminal 40 ms of the filtered QRS < 25 muV); or (2) if the signal-averaged QRS duration > or = 120 ms. Overall the signal-averaged electrocardiogram performed better at noise level 0.4 muV compared to noise level 0.2 muV with respect to identification of patients with or without ventricular tachycardia after myocardial infarction. Reducing noise level from 0.4 to 0.2 muV increased the sensitivity, but the consequence was a substantial decrease in specificity. Our data indicate that when a high sensitivity is the goal, the definition based only on signal-averaged QRS duration > or = 120 ms should be applied; sensitivity was 88% and specificity 59% at noise level 0.4 muV. If a high specificity is the goal, the definition should be based on the definition with two abnormal parameters; sensitivity was 69% and specificity 68% at noise level 0.4 muV.
Adult↗
Re-evaluation of the role of P-wave duration and morphology as predictors of atrial fibrillation and flutter after coronary artery bypass surgery.
To evaluate the significance of P-wave duration and morphology for the development of post-operative atrial fibrillation/flutter, we investigated 189 consecutive patients scheduled for elective coronary artery bypass surgery. The longest pre-operative total P-wave duration was measured from the standard electrocardiogram at a paper speed of 50 mm.s-1 (mean of two independent observers). By the signal averaging technique we determined the pre-operative total P-wave duration, and root-mean square voltage of the last 10, 20, and 30 ms of the filtered (40-250 Hz) P-wave from a vector composite of three orthogonal leads at noise level 0.2 microV. Forty-two (22%) of the patients developed atrial fibrillation/flutter. Older age (mean +/- SD) 62 +/- 8 vs 56 +/- 8 years (P < 0.000), increasing body weight 83 +/- 11 vs 79 +/- 12 kg (P = 0.05), treatment for hypertension 26 vs 13% (P = 0.04), and a longer P-wave duration in the standard electrocardiogram 129 +/- 12 vs 124 +/- 12 ms (P = 0.01) were associated with development of atrial fibrillation/flutter documented by a 12-lead electrocardiogram. Logistic regression analysis identified independent predictors, estimated adjusted relative risk (95% confidence interval) of atrial fibrillation/flutter: with age > 60 years, the relative risk was 4.46 (2.05-9.73), and body weight > 80 kg, the relative risk was 3.81 (1.71-8.46). Thus, P-wave duration and morphology did not provide significant information on the risk of atrial fibrillation/flutter when controlling for the effects of increasing age and body weight.
Aged↗
Halothane-induced liver injury in guinea-pigs: importance of cytochrome P450 enzyme activity and hepatic blood flow.
The basis for susceptibility to halothane-induced liver necrosis in guinea-pigs was examined. In hepatic microsomes, the following were similar in susceptible and resistant animals: total cytochrome (CYP) P450 (P450), phenobarbital-inducible pathways of mixed function oxidation (androstenedione 6 beta- and 16 beta-hydroxylase activities) and the CyP2E1-catalysed pathway of N-nitrosodimethylamine N-demethylase activity. Similarly, immunohistochemical staining of CYP2E1 protein was equivalent in livers from susceptible and resistant guinea-pigs. Prior treatment with the P450-inhibitors, metyrapone and SKF-525A ameliorated halothane-induced liver damage in susceptible animals. Conversely, in resistant guinea-pigs, stimulation of hepatic CYP2E1 activity by treatment with 4-methylpyrazole produced severe hepatotoxicity after re-exposure to halothane. These results confirm the conclusions of others, that P450-mediated metabolism produces halothane-induced liver necrosis in the guinea-pig model but, as in other work, the data fail to explain why no difference in activity of these enzymes could be found between susceptible and resistant guinea-pigs. To establish whether a differential effect on hepatic blood flow between susceptible and resistant guinea-pigs could explain this paradox, studies were performed using a radiolabelled microsphere technique. The effect of halothane on lowering cardiac output was identical in both groups of animals and halothane significantly reduced hepatic arterial but not portal blood flow. The effect on arterial blood flow was more profound in susceptible guinea-pigs (0.67 +/- 0.17% of injected microspheres) than in resistant animals (0.99 +/- 0.13%; P < 0.005). It is concluded that P450-catalysed metabolism and reduced hepatic blood flow are both necessary to produce halothane-induced liver injury in susceptible guinea-pigs, but it is the effect of halothane on hepatic arterial blood flow that differs between susceptible and resistant animals.
Animals↗
Within- and between-patient variation of the signal-averaged P wave in coronary artery disease.
OBJECTIVES: To estimate interobserver, within-patient and between-patient variation of the signal-averaged P wave. To determine whether demographic, clinical, conventional ECG information, and coronary angiographic data are associated with the signal-averaged P wave duration in patients with documented coronary artery disease. BACKGROUND: A prolonged signal-averaged P wave may indicate the presence of a substrate for atrial tachyarrhythmias and may predict subsequent development of atrial fibrillation. However, information on variation, reproducibility, and determinants of the signal-averaged P wave are sparse. METHODS: One hundred ninety-three patients with angiographically documented coronary artery disease underwent two consecutive procedures of signal-averaging of P waves (SAECG1 and SAECG2). Interobserver, within-patient, and between-patient variation of the signal-averaged P wave was estimated (coefficient of variation: SD/mean). Multiple linear regression analysis was applied to identify parameters independently associated with signal-averaged P wave duration (SA-P). Atrial late potentials were considered if SA-P > 140 ms, and logistic regression analysis was applied to identify parameters associated with the presence of atrial late potentials. RESULTS: The interobserver, within-patient, and between-patient coefficients of variation for the signal-averaged P wave duration were 7.5%, 6.0% and 8.4%, respectively. The signal-averaged P wave duration correlated significantly with standard ECG P wave duration and height of the patient (r = 0.59). Forty-nine percent of the patients had atrial late potentials. P wave duration in the standard ECG correctly classified 73% (140/188) of the patients with respect to atrial late potential positivity or negativity. The sensitivity was 67% and the specificity was 78%. Agreement on the presence or absence of atrial late potentials between two observers was present in 71% (136/193) of the patients, and in 78% (151/193) between SAECG1 and SAECG2. CONCLUSIONS: The signal-averaged P wave has limited reproducibility in patients with coronary artery disease, and a normal or abnormal signal-averaged P wave can be predicted from the conventional ECG with high accuracy. It is recommended that the signal-averaged P wave be compared with the standard ECG P wave duration in follow-up studies with the aim of predicting atrial fibrillation.
Action Potentials↗
The Tra2 core of the IncP(alpha) plasmid RP4 is required for intergeneric mating between Escherichia coli and Streptomyces lividans.
Escherichia coli cells and Streptomyces mycelia are able to form close contacts in the absence of a conjugative system which might facilitate intergeneric plasmid transfer without the genes required for mating pair formation (Tra2) of the RP4 plasmid. The same Tra2 genes found to be essential for RP4 plasmid transfer, RSF1010 mobilization, and donor-specific phage propagation in E. coli were also required for intergeneric transfer between E. coli and Streptomyces lividans.
Bacterial Adhesion↗
Atrial ectopic activity and atrial fibrillation/flutter after coronary artery bypass surgery. A case-base study controlling for confounding from age, beta-blocker treatment, and time distance from operation.
To evaluate the impact of ectopic atrial activity and cardiac autonomic function for development of atrial fibrillation or flutter we studied 128 consecutive patients undergoing elective coronary artery bypass grafting. The patients were Holter monitored during a 96-h postoperative period. Autonomic balance was estimated by heart rate variability measurement. Thirty-eight (30%) patients developed sustained atrial fibrillation or flutter. Holter recordings were analyzed in a case-base design matching for age, beta-blocker treatment, and time elapsed after the operation. The number of supraventricular ectopic beats/h was increased (P < 0.01) in the case group during each of the last 7 h before onset of atrial fibrillation or flutter. Episodes of supraventricular tachycardia 62% vs. 26%; cases vs. controls (P = 0.007), episodes of non-sustained atrial fibrillation 29% vs. 0% (P = 0.0009), and episodes of non-sustained atrial flutter 15% vs. 0% (P = 0.05) were significant predictors of atrial fibrillation or flutter. Mean heart rate/h was increased in each of the 24 h preceding the arrhythmia. However, indexes of autonomic heart function did not differ significantly between groups. Patients developing atrial fibrillation or flutter after coronary artery bypass surgery present 'warning' atrial arrhythmias: numerous supraventricular ectopic beats, paroxysmal supraventricular tachycardia, and episodes of nonsustained atrial fibrillation and flutter.
Adrenergic beta-Antagonists↗
[Short and long term prognosis of acute renal failure requiring dialysis. An analysis of 419 consecutive patients].
To describe the relationship between morbidity, mortality, and year of admission we studied 419 patients with acute dialysis-requiring renal failure. Effects of various follow-up periods and stratification on main prognostic factors were evaluated. There was a significantly higher (p < 0.001) number of organ failures/patient during the second six-year period compared with the first six-year period. Early (day 90) mortality was 46% and unchanged during the period. Estimated five year survival rate (95% confidence limits) was 52% (44-60) in patients with a medical etiology, and 28% (20-36) in patients with a surgical etiology. Prognosis was dependent on the severity and progression of the underlying disease process. Changed censoring time and stratification were important tools for enhancing the yield of information from the study. Time(s) and method(s) of risk scoring, stratification(s) of patients, time(s) of censorship, and method of statistical analysis should be identical when comparing results of treatment for acute renal failure from different centres.
Acute Kidney Injury↗
Premature atrial beat eliciting atrial fibrillation after coronary artery bypass grafting.
Of patients undergoing coronary artery bypass grafting 30% develop atrial fibrillation (AF) or flutter. To determine if AF is initiated from the right or left atrium, atrial electrograms were continuously recorded in patients undergoing this procedure. In addition, to study whether the prematurity index of premature atrial contractions (PACs) eliciting AF differs from PACs not provoking AF, the distribution of prematurity indices was evaluated from R-R interval analysis. The right and left atrial recording electrodes were first activated by the ectopic beat provoking AF in six and eight patients, respectively. The prematurity index of the PAC eliciting AF was located in the middle (in half of the patients) or to the left of the median distribution of prematurity indices. The variability in activation of the atrial electrodes suggests that the PAC provoking AF can have its origin in the right, the septal, or the left region of the atrium. The initiation of AF depends on the prematurity index of the PAC.
Atrial Fibrillation↗
Low vagal tone and supraventricular ectopic activity predict atrial fibrillation and flutter after coronary artery bypass grafting.
To investigate the impact of pre-operative autonomic balance and atrial ectopic activity on the risk of atrial fibrillation or flutter after aorto-coronary artery bypass surgery 24-h Holter monitoring was analysed in 102 patients before coronary artery bypass grafting. Index for vagal tone was calculated as % successive RR interval differences > 6%. Twenty-nine (28%) of the 102 patients developed atrial fibrillation or flutter. Independent predictors (90% confidence interval) of postoperative atrial fibrillation or flutter were identified by logistic regression analysis: the independent predictors were older age, relative risk 1.07.year-1 (1.02-1.12), vagal index < 10%, relative risk 4.50 (1.40-14.5), > or = 10 ectopic supraventricular beats . 24 h-1, relative risk 3.03 (1.05-8.72), and one or more events of non-sustained supraventricular tachycardia, relative risk 3.02 (1.11-8.22). Thus, age of the patient, attenuated pre-operative cardiac vagal modulation, ectopic supraventricular beats, and paroxysmal non-sustained supraventricular tachycardia are independent risk factors for the development of atrial fibrillation or flutter after coronary artery bypass surgery.
Adrenergic beta-Antagonists↗