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Biomedical subjects

R Brooks

Publications and source records attributed to R Brooks.

At least 73 records · Page 4Linked to original sources
PubMed1996

EuroQol: the current state of play.

The EuroQol Group first met in 1987 to test the feasibility of jointly developing a standardised non-disease-specific instrument for describing and valuing health-related quality of life. From the outset the Group has been multi-country, multi-centre, and multi-disciplinary. The EuroQol instrument is intended to complement other forms of quality of life measures, and it has been purposefully developed to generate a cardinal index of health, thus giving it considerable potential for use in economic evaluation. Considerable effort has been invested by the Group in the development and valuation aspects of health status measurement. Earlier work was reported upon in 1990; this paper is a second 'corporate' effort detailing subsequent developments. The concepts underlying the EuroQol framework are explored with particular reference to the generic nature of the instrument. The valuation task is reviewed and some evidence on the methodological requirements for measurement is presented. A number of special issues of considerable interest and concern to the Group are discussed: the modelling of data, the duration of health states and the problems surrounding the state 'dead'. An outline of some of the applications of the EuroQol instrument is presented and a brief commentary on the Group's ongoing programme of work concludes the paper.

Cost-Benefit Analysis↗
PubMed1996

Pharmacodynamics of ZM 241385, a potent A2a adenosine receptor antagonist, after enteric administration in rat, cat and dog.

4-(2-[7-Amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5] triazin-5-ylamino]ethyl)phenol (ZM 241385) is currently the most selective for the A2a adenosine receptor antagonist. This paper describes the in-vivo activity of ZM 241385 after administration by both oral and intraduodenal routes. In conscious spontaneously hypertensive rats, ZM 241385 (1-10 mg kg-1) selectively attenuated the mean arterial blood pressure response produced by exogenous adenosine (1 mg kg-1 min-1, i.v.) by up to 45% after oral administration. Activity of ZM 241385 was maintained for at least 6 h after 3 and 10 mg kg-1 (p.o.). In conscious normotensive cats, ZM 241385 attenuated the blood pressure responses to adenosine (0.6-1.0 mg kg-1, i.v.) by 94% after 10 mg kg-1 (p.o.) and by up to 74% after 0.3 mg kg-1 (i.v.). Duration of action of ZM 241385 up to 12 h (36% inhibition) was observed after 3 mg kg-1 (p.o.). In anaesthetized dogs and cats, ZM 241385, after intraduodenal administration (1-10 mg kg-1), produced a rapid (dose ratio 100-fold 15 min after administration of 10 mg kg-1 in the cat) and prolonged (dose ratio of 14 at 6 h after administration of 10 mg kg-1) attenuation of the vasodilatation responses to adenosine receptor stimulation. When administered by this route ZM 241385 was six times more potent than theophylline in the cat and at least twice as potent as theophylline in the dog. In conclusion, ZM 241385 is a potent, selective A2a adenosine receptor antagonist which is orally active, with a good duration of action by the enteric route in cat, rat and dog. It could therefore be used to evaluate the role of adenosine A2a receptors in the action of adenosine in-vivo.

Administration, Oral↗
PubMed1995

Implantation of transvenous nonthoracotomy cardioverter-defibrillator systems in patients with permanent endocardial pacemakers.

Among 177 patients in whom a nonthoracotomy approach was initially used to implant a cardioverter-defibrillator system, 11 (6%) patients also received a separately implanted permanent pacemaker. The main problem encountered in these patients were previously implanted unipolar pacemakers (n = 3) and ventricular pacing leads positioned at the right ventricular apex, the latter interfering with optimal placement of the tripolar implantable cardioverter-defibrillator (ICD) lead (n = 9). The approaches used to solve these problems were individualized and included placement of the ICD sensing lead at the right ventricular outflow tract (n = 3), initial placement (n = 1) or subsequent repositioning (n = 2) of the right ventricular pacing lead at the outflow tract, upgrade from unipolar to bipolar systems (n = 2), reprogramming from the DDD to AAI mode (n = 2), inactivation of the pacemaker (n = 1), and simultaneous placement of a single-chamber atrial pacemaker with the ICD lead (n = 2). These revisions fulfilled the pacing needs in each patient and prevented unfavorable sensing interaction between the two systems.

Aged↗
PubMed1995

Malfunction of implantable cardioverter defibrillators placed by a nonthoracotomy approach: frequency of malfunction and value of chest radiography in determining cause.

OBJECTIVE: The purpose of this study was to determine the frequency of system malfunction in patients with nonthoracotomy implantable cardioverter defibrillators and to assess the role of chest radiography in detecting and determining the cause of malfunction. MATERIALS AND METHODS: The study population consisted of 300 consecutive patients in whom implantable cardioverter defibrillators were implanted using an initial nonthoracotomy approach between September 1990 and October 1994. Transvenous electrodes were placed via the subclavian or cephalic vein under local anesthetic. Intraoperative testing, pulse generator implantation, and, if necessary, subcutaneous patch or extrapericardial patch placement via thoracotomy were done in the operating room under general anesthetic. Follow-up consisted of routine device interrogation every 2-3 months and annual chest radiography. Chest radiographs were obtained more often if patients were symptomatic or if results of device interrogation were abnormal. RESULTS: Patients were followed up for a mean +/- SD of 19 +/- 14 months following implantation. Implantable cardioverter-defibrillator malfunction occurred in 17 patients (6%) during the follow-up period. Of these, 12 (71%) had component abnormalities on chest radiographs. Patients with radiographically apparent implantable cardioverter-defibrillator abnormalities presented in two discrete time periods after device implantation, early (mean, 35 +/- 14 days) and late (mean, 18 +/- 5 months). CONCLUSION: Malfunction of nonthoracotomy implantable cardioverter-defibrillator systems develops infrequently after device implantation. In most cases, the cause can be identified on chest radiographs.

Adolescent↗
PubMed1995

IgH and L chain variable region gene sequence analyses of twelve synovial tissue-derived B cell lines producing IgA, IgG, and IgM rheumatoid factors structure/function comparisons of antigenic specificity, V gene sequence, and Ig isotype.

In the present study, the complete sequences of the Ig H and L chain variable region genes of twelve RF+ B cell lines from two patients with RA were analyzed. Seven of the RF-producing B cells used VH3 family genes, four used VH4 genes, and one a VH1 gene. All but two of the cell lines expressing VH3 genes utilized different family members; among the VH4-expressing cells, a more restricted pattern was noted. V kappa gene use was restricted to the V kappa I and III families; V lambda gene use was more diverse, involving five different families. Computer comparisons of the expressed VH genes with their presumed germline progenitors indicated significant differences in every instance; eight of the corresponding VL genes also were significantly different. In many cases, assignment of the germline D segment(s) incorporated into the rearranged VH genes was impossible. These differences from the germline gene segments indicated the extensive changes induced by rearrangement, enzymatic activities, and somatic mutation. In hopes of defining a structural reason for the disparate antigen specificities of these cells, the CDR3 amino acid sequences of the multi- vs. the mono-reactive RF-producers were compared. Although CDR3 length was not appreciably different between these two sets of mAb, a greater than two-fold increase in charged amino acids was found in the H chain CDR3 of the multireactive RF. This relationship did not exist for the L chain CDR3. Thus, these sequence data indicate the use of a broad base of Ig V gene segments that have undergone extensive diversification. Based on the localization of R substitutions in the CDR of most of the V genes studied, the diversification appears to be antigen driven and selected. The significance of these findings for the evolution of these B cell clones into isotype-switched producers that are heterogeneous for antigen specificity (mono- vs. multi-reactivity) is discussed.

Aged↗
PubMed1994

Three-year outcome of a nonthoracotomy approach to cardioverter-defibrillator implantation in 189 consecutive patients.

To date, no long-term clinical data have been published in patients undergoing a nonthoracotomy approach to cardioverter-defibrillator system implantation. In the present report, 189 consecutive patients prospectively underwent a standardized approach to cardioverter-defibrillator system implantation in which the nonthoracotomy configurations were tested first. If satisfactory defibrillation thresholds were not obtained, thoracotomy was performed during the same intraoperative session. A nonthoracotomy system was successfully implanted in 149 of 189 patients (79%), with a higher success rate (90%) observed in patients who had more recent implantations. The overall rate of complications associated with these systems was low (11%). Over a mean follow-up of 12.5 +/- 9.3 months, 17 patients (9%) died. Three-year total, cardiac, and sudden death-free actuarial survival for all patients was 83 +/- 11%, 88 +/- 7%, and 94 +/- 2%, respectively. Three-year sudden death-free actuarial survival was higher in the nonthoracotomy than in the thoracotomy patients (97 +/- 2% vs 87 +/- 6%, p = 0.047), although total survival was similar (77 +/- 11% vs 83 +/- 7%, p = 0.77). These data suggest that a majority of patients (> 80%) requiring a cardioverter-defibrillator system can undergo implantation using a nonthoracotomy approach. Patients receiving nonthoracotomy systems have 3-year outcomes comparable to those implanted via thoracotomy. If these results are maintained, a nonthoracotomy approach will supplant thoracotomy-implanted systems as the preferred method because of the simpler implant procedure and lower overall cost involved.

Actuarial Analysis↗
PubMed1994

Myocardial infarction and purine transport inhibition in anaesthetised ferrets.

The potential cytoprotective effect of the purine transport inhibitor S-(p-nitrobenzyl)-6-thioinosine (NBTI) in a model of myocardial ischaemia and reperfusion was investigated in the anaesthetised ferret. The left anterior descending coronary artery (LAD) was occluded for 90 min, producing ischaemia in 53 +/- 3% of the left ventricular free wall, followed by 240 min reperfusion. NBTI (0.5 mg kg-1, i.v.) was given prior to ischaemia or prior to reperfusion. In addition the effect of purine transport inhibition was investigated in animals subjected to ischaemia without reperfusion. NBTI reduced infarct size from 84.0 +/- 1.7 to 71.4 +/- 3.7% of the area at risk (P < 0.05) when given prior to occlusion of the LAD. NBTI was ineffective however when given 15 min prior to reperfusion. NBTI had no effect upon infarct size produced by ischaemia without reperfusion. The effect of NBTI was independent of significant changes in myocardial blood flow during ischaemia and reperfusion or upon neutrophil infiltration.

Adenosine↗
PubMed1993

Prospective evaluation of day-to-day reproducibility of upright tilt-table testing in unexplained syncope.

To evaluate the day-to-day reproducibility of upright tilt-table testing, 109 patients with unexplained syncope prospectively underwent testing on 2 consecutive days using a uniform protocol. Results of testing on 2 separate days were concordant in 69 of 109 patients (63%), and discordant in 40 of 109 patients (37%). Thirty-six of 109 patients (33%) had vasodepressor syncope on 1 or both days of testing. Nineteen of 30 patients (63%) with vasodepressor responses on the first day did not reproduce this response during the second day of testing. An additional 6 patients with an initial negative tilt test had a vasodepressor response on the second day. Only 11 of 36 patients (31%) had reproducible vasodepressor responses on both days of testing. Patients with reproducible vasodepressor responses had a significantly higher mean number of preceding clinical syncopal events than patients with 2 normal tests (p < 0.02) or nonreproducible results (p < 0.04). In addition, these patients had a significantly longer duration of clinical symptoms relative to patients with 2 tests that yielded negative results (p < 0.008) and nonreproducible results (p < 0.01). The elapsed time between the most recent clinical event and the performance of tilt-table testing was not significantly different among the 3 groups, and did not appear to influence the outcome of testing. These data show that vasodepressor responses elicited by upright tilt-table testing show day-to-day variability in many patients, a finding that may limit the interpretation of initial and follow-up test results.

Adult↗
PubMed1993

Monoclonal IgM, IgG, and IgA human rheumatoid factors produced by synovial tissue-derived, EBV-transformed B cell lines.

In an effort to study disease-related autoantibodies in rheumatoid arthritis (RA), rheumatoid factor (RF)-producing B cell lines were developed from the heterogeneous B cell populations infiltrating the synovial tissue of patients with arthritis. Over 125 EBV-transformed B cell cultures were derived from three patients: one with early pre-erosive RA, one with advanced RA, and one with osteoarthritis (OA). IgM, IgG, and IgA RF-producing B cell lines were found in all three series but with several significant differences. In each of the two RA patients, 22% of the Ig-producing cell lines secreted RF compared to 7% in the OA patient. The isotypes of these RF were mostly IgM in the early RA (62%) and the OA patient (60%) as contrasted to predominantly IgA (75%) and, to a lesser extent, IgG (12.5%) in the advanced RA patient. Analyses of the light (L) chain composition of these RF revealed that 82% of the IgM RF used kappa L chains whereas only 31% of the non-IgM RF used kappa chains. Antigen-binding analyses of these RF revealed that all the synovial tissue-derived RF from the advanced RA patient exhibited antigen binding specificities restricted to a narrow range of gamma globulins. In contrast, the synovial RF of the other two patients were either reactive with a broader spectrum of gamma globulins or reactive with a variety of unrelated antigens. In every instance, the gamma globulin-specific RF were of all three major isotypes whereas the polyreactive RF were restricted to the IgM isotype. These data demonstrate that synovial B cells from both RA and OA patients can produce RF and that significant differences can exist among patients in the percentage of RF generated and their H and L chain isotype distribution. The reversal of the kappa:lambda ratio among the IgG and IgA RF and the more restricted antigen-binding specificities of the IgG and IgA vs IgM RF suggest that a non-stochastic, possibly antigen-driven selection process was involved in their generation. The relevance of these differences in RF precursor frequency, H and L chain distribution, and antigen specificity to these two diseases warrants further investigation.

Aged↗
PubMed1993

Successful implantation of cardioverter-defibrillator systems in patients with elevated defibrillation thresholds.

OBJECTIVES: . The purpose of this study was to conduct a retrospective analysis of 16 patients with high initial defibrillation thresholds in whom a three-electrode system was used to lower defibrillation thresholds and permit implantation of a cardioverter-defibrillator system. BACKGROUND: Patients with high defibrillation thresholds (> 25 J) are uncommon but may be problematic to physicians implanting cardioverter-defibrillator systems. Most conventional systems use two defibrillating electrodes, most commonly two epicardial patches. When defibrillation thresholds remain elevated despite extensive testing of a two-electrode system, a third electrode can be incorporated and tested. However, few published data exist on the use of a three-electrode system in patients with high defibrillation thresholds. METHODS: After failure to achieve satisfactory defibrillation thresholds < 25 J with a two-patch electrode system, a third electrode was incorporated and tested. In all cases, two electrodes were joined to form a common cathode or anode, while a single electrode was used as the opposite polarity electrode. Various three-electrode configurations were then tested. RESULTS: In all 16 patients, satisfactory defibrillation thresholds were achieved and a cardioverter-defibrillator was implanted (95% confidence interval [CI] = 0% to 21%). The mean final defibrillation threshold using the revised three-electrode system was 19.5 +/- 3.7 J (p < 0.0001). A mean of 6 +/- 3 electrode configurations/patient were tested before the final configuration was selected. A total of nine different electrode configurations were used in the 16 study patients; the most common of these incorporated left and right ventricular patches as combined cathode and a superior vena cava coil (n = 5) or right atrial patch electrode (n = 3) as single anode. CONCLUSION: Patients with high initial defibrillation thresholds can generally undergo successful cardioverter-defibrillator implantation with a three-electrode system if enough electrode configurations are tested after a third electrode is incorporated.

Aged↗
PubMed1993

Determinants of successful nonthoracotomy cardioverter-defibrillator implantation: experience in 101 patients using two different lead systems.

OBJECTIVES: This study was conducted to identify the determinants of successful nonthoracotomy cardioverter-defibrillator implantation. BACKGROUND: Until recently, either median sternotomy or thoracotomy was necessary to implant the electrodes used for internal cardioverter-defibrillator systems. A number of manufacturers have developed nonthoracotomy lead systems comprising two transvenous coil electrodes and a subcutaneous patch electrode. At present, the factors associated with the success or failure of a nonthoracotomy approach are unknown. METHODS: A total of 101 consecutive patients requiring a cardioverter-defibrillator underwent an initial nonthoracotomy approach. Factors associated with successful nonthoracotomy implantation were prospectively determined. RESULTS: A nonthoracotomy system was implanted in 72 (71%) of 101 patients. Twenty-nine patients (29%) required thoracotomy. Univariate predictors of successful nonthoracotomy implantation included smaller cardiac size (p < 0.0001), smaller cardiothoracic ratio (p < 0.0002), QRS duration < 120 ms (p = 0.003), female gender (p = 0.006), ventricular fibrillation as the presenting arrhythmia (p = 0.03) and smaller echocardiographic left ventricular size (p = 0.04). Multivariate predictors included smaller cardiac size (p < 0.002) and female gender (p < 0.007). Total actuarial survival over a mean (+/- SD) follow-up interval of 12 +/- 7 months was 91 +/- 0.03% and was not different in the thoracotomy and nonthoracotomy groups. CONCLUSIONS: A nonthoracotomy cardioverter-defibrillator system can be implanted in a majority of patients. Smaller cardiac size and female gender are associated with a high probability of successful implantation.

Actuarial Analysis↗