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Electrocardiographic body surface mapping in patients with ventricular tachycardia. Assessment of utility in the identification of effective pharmacological therapy.

BACKGROUND: Body surface maps of net QRST deflection areas (isointegrals) reflect regional ventricular repolarization properties. Vulnerability to ventricular tachyarrhythmias is associated with maps that feature multiple islands (extrema) of positive and negative values; such maps reflect regional disparity of ventricular recovery properties. The value of body surface mapping in prediction of the efficacy of antiarrhythmic therapy for ventricular tachyarrhythmias has not been determined. METHODS AND RESULTS: Isointegral ECG body surface mapping was performed in 51 patients with inducible ventricular tachycardia having programmed stimulation studies at baseline and after oral quinidine therapy. The degree of nondipolarity of QRST isointegral distribution was expressed by the number of extrema and by the percentage contribution of nondipolar eigenvectors after Karhunen-Loeve transformation. QRST isointegral nondipolarity was greater in ventricular tachycardia patients than in 51 age- and sex-matched normal subjects expressed as mean number of extrema (4.1 +/- 2.8 versus 2.0 +/- 0.2, respectively), mean eigenvector-determined nondipolar content percentages (12.4 +/- 10.1% versus 4.5 +/- 4.9%), prevalence of abnormal numbers of extrema (63% versus 4%), or prevalence of abnormal nondipolar content percentages (33% versus 4%) (each p less than 0.01). Quinidine prevented ventricular tachycardia induction in 14 patients. Patients for whom quinidine was or was not effective had similar nondipolarity indexes at baseline. However, maps on quinidine differed as a function of antiarrhythmic efficacy. Although effective therapy produced no significant mean changes in nondipolarity, ineffective therapy increased the number of extrema compared with baseline (5.4 +/- 3.4 versus 3.8 +/- 2.5, respectively) (p = 0.002). Individually, 43% of patients on effective therapy had drug-induced decreases in numbers of extrema compared with 14% of those on ineffective therapy (p = 0.02). Furthermore, 29% of patients on effective therapy showed drug-induced increases in numbers of extrema compared with 62% of those on ineffective therapy (p = 0.03). CONCLUSIONS: QRST isointegral body surface mapping shows promise as a noninvasive measure of drug efficacy in patients with ventricular tachycardia.

Anti-Arrhythmia Agents↗

Effect of moxisylyte hydrochloride (alpha 1-blocker) on the retinal circulation of patients with diabetes mellitus.

Moxisylyte hydrochloride (alpha 1-blocker) selectively vasodilates cerebral vessels without reducing blood pressure. We investigated the effect of the drug on retinal circulation in 15 patients (17 eyes) with diabetes mellitus, using the video-densitometric image analysis of fluorescein angiography. We compared the build-up time (BT), the time constant of washout rate (TC) and the mean circulation time (MCT) before and after oral therapy with moxisylyte. In 16 eyes, BT was shortened significantly and MCT was only slightly shortened 1 h after oral therapy with moxisylyte. After 2 weeks of daily administration, MCT was shortened and TC of the artery was increased significantly in 6 eyes. Since retinal circulation in patients with diabetes mellitus was improved by moxisylyte, the drug may be useful to treat ocular disorders such as diabetic retinopathy.

Administration, Oral↗

The use of parallel EEL spectral imaging and elemental mapping in the rapid assessment of anti-cancer drug localization.

Both electron spectroscopic imaging (ESI) and electron energy-loss spectroscopy (EELS) have great potential for use in several areas of cancer research. In biologically targeted radiotherapy, cytotoxic drug therapy and boron neutron capture therapy the effectiveness of many drugs is often critically dependent upon the intracellular localization of the agent employed. We describe the use of parallel EEL spectral imaging to assess the penetration and location of the iodine-containing drug meta-iodobenzyl guanidine, of potential value in targeted radiotherapy, and for the rapid detection of boron within borate-adsorbed polystyrene beads, of potential value in boron neutron capture therapy. We also describe elemental mapping of boron following low-temperature embedding. These results show how the techniques could be applied to many forms of cancer research by discussing the validity and limitations of the techniques experimentally. We also provide an outline of other areas in this field which could benefit from the future application of ESI and EELS.

3-Iodobenzylguanidine↗

Computerized Electroencephalogram. A model of understanding the brain function in childhood psychosis and its treatment.

Computer analysis of the electroencephalogram (CEEG) in psychotic children before and after pharmacotherapy, normal children of schizophrenic mothers, and matched normal children of normal parents indicated significant intergroup differences. The psychotic children had more slow, as well as very fast, EEG waves. With drug therapy the EEG showed a partial "normalization," as fast EEG activity decreased. The EEG and auditory evoked potential of children of schizophrenic mothers were strikingly similar to those of psychotic children and schizophrenic adults, with significant decreases of the average EEG amplitude and the evoked potential latencies. Psychotic children were distinctly differentiated from the normal children by discriminant function analysis of the EEG and EP. Quantitative analysis of brain functions in the mentally ill can help determine the neurophysiological correlates of behavior, a more scientific diagnostic classification, prognosis, and selection of therapy.

Acoustic Stimulation↗

Left ventricular hypertrophy.

OBJECTIVE: To review the pathophysiology, epidemiology, patterns, diagnosis, and treatment of left ventricular hypertrophy with emphasis on the elderly. DATA SOURCES: A computer-assisted search of the English-language literature (MEDLINE database) followed by a manual search of the bibliographies of pertinent articles. STUDY SELECTION: Studies on the pathophysiology, epidemiology, patterns, diagnosis, and treatment of left ventricular hypertrophy were screened for review. Studies on left ventricular hypertrophy in the elderly and recent studies were emphasized. DATA EXTRACTION: Pertinent data were extracted from the reviewed articles. Emphasis was on studies involving the elderly. Relevant articles were reviewed in depth. DATA SYNTHESIS: Available data about the pathophysiology, epidemiology, patterns, diagnosis, and treatment of left ventricular hypertrophy with emphasis on studies involving the elderly were summarized. CONCLUSIONS: Left ventricular hypertrophy caused by hypertension or other cardiovascular disease is not only a marker for but also a contributor to cardiovascular morbidity and mortality in elderly and young patients. The question of whether regression of left ventricular mass in patients with hypertension will decrease cardiovascular morbidity and mortality needs to be answered by prospective studies using different types of antihypertensive drugs. Future studies on the efficacy of antihypertensive drugs and on stratification of therapy should include echocardiographic estimates of left ventricular mass index.

Aging↗

Reduction of intimal thickening in canine coronary bypass vein grafts with dipyridamole and aspirin.

The potential benefit of platelet inhibitor drugs on coronary arterial bypass vein grafts was assessed in dogs with magnification-corrected angiographic luminal measurements and quantitative histologic evaluation of the vein grafts. There were 11 control animals and 11 animals treated with dipyridamole, 55 mg/day, plus aspirin, 325 mg/day. Eighteen animals with patent grafts were studied when electively killed 2, 4 or 6 months after grafting. At 14 days, there was greater angiographic narrowing in the most distal 1 cm of vein grafts in control than in treated dogs (P less than 0.01). This same angiographic narrowing persisted in control dogs until they were killed (P less than 0.03). Computer-assisted measurements of the entire area of intimal thickening were done on vein graft cross sections taken 1 cm from the distal anastomosis. The circumference of the vein grafts at the intimal-media junction was measured from the same section and the potential maximal luminal area calculated. The calculated luminal narrowing due to intimal thickening was greater in control than in treated dogs (P less than 0.03). These data correlate well with the demonstrated angiographic narrowing. The findings indicate that the degree of early intimal thickening that persists 2 to 6 months postoperatively in canine coronary bypass vein grafts may be reduced by the platelet inhibitor combination of dipyridamole plus aspirin.

Animals↗

[Ventricular arrhythmia and late potentials in patients with hypertrophic cardiomyopathy].

Holter monitoring (48 h) and registration of signal-averaged late potentials (method of Simson, high pass filter 40 Hz) were performed in outpatiens with hypertrophic cardiomyopathy. A prevalence of spontaneous ventricular arrhythmias could be determined in 51 patients; the results of 45 patients not taking antiarrhythmic drugs are presented here. 96% of these showed ventricular premature beats, 76% had multiform extrasystoles, 27% showed pairs of ectopic beats and 20% had runs of ventricular tachycardia (more than 3 QRS complexes). Absolute counts of premature beats were low in most patients, but important interindividual differences could be observed: M = 34 extrasystoles/24 h (0-4943). Ventricular tachycardias were of short duration (maximum 11 QRS) with heart rate ranging from 120 to 200/min. All patients were asymptomatic during tachycardia. Signal-averaged late potentials could be registered in 30 patients, 28 of them without antiarrhythmic drug therapy. Mean QRS duration (QRSdur) was 108 +/- 12 ms, mean duration of low amplitude signals (less than 40 microV) in the terminal portion of the QRS (LAdur) was 27 +/- 13 ms, and mean amplitude of the last 40 ms of the filtered QRS (LAamp) was 65 +/- 43 microV. A patient was considered to show late potentials if two of the following criteria were present: QRSdur greater than 120 ms, LAdur greater than or equal to 40 ms, LAamp less than 20 microV. This was found in four patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Concept of an antiatherosclerotic efficacy of calcium entry blockers. INTACT Investigators.

Animal experiments suggest an inhibitory effect of calcium entry blockers on arterial calcinosis and the formation of atherosclerotic plaques. Experiments with isolated tissues suggest various mechanisms for an antiatherosclerotic effect of calcium entry blockers. INTACT, the International Nifedipine Trial on Antiatherosclerotic Therapy, is the first study investigating, with a prospective, placebo-controlled, randomized, double-blind design, the influence of a calcium entry blocker (nifedipine 80 mg/day) on the progression of coronary atherosclerosis in patients with proven coronary artery disease. Study endpoints were changes of established coronary stenoses (diameter reduction greater than or equal to 20%), as well as the formation of new stenoses as documented by coronary angiography. Standardized coronary angiograms were taken before and after a treatment period of 3 years. The angiograms were quantitatively analyzed with the computer-assisted edge detection system CAAS. Of the 425 patients included in the study, 282 patients (134 on nifedipine and 148 on placebo) revealed no protocol violations. In the inclusion angiograms of these patients, 893 coronary stenoses were detected which were not significantly influenced in their development by nifedipine. However, 196 entirely new coronary lesions, 185 stenoses and 11 occlusions, were found in the follow-up angiograms. There were 78 lesions in 54 patients (40%) on nifedipine (0.58 new lesions/patient) and 118 lesions in 73 patients (49%; n.s.) on placebo (0.8 new lesions/patient; p = 0.031). In two other studies on the inhibiting effect of dihydropyridine calcium entry blockers on the progression of coronary artery disease in man defining angiographic endpoints, the drugs were also shown to reduce the number of newly formed significant coronary lesions. If further trials in man confirm a protective role of calcium entry blockers against the formation of atherosclerotic coronary lesions, a new strategy in the prevention of coronary artery disease has to be considered.

Animals↗

Effect of carbamazepine treatment on EEG changes induced by different cortical activation patterns in newly referred epileptic patients.

Sixteen epileptic patients suffering from focal epilepsy who underwent antiepileptic drug treatment with carbamazepine (CBZ) for the first time were studied. The EEG was recorded at rest with eyes closed, during blocking reaction (BR), fixation (FIX) and mental arithmetic tasks. The computerized EEG study, performed before and after CBZ therapy, utilized spectral analysis. Data underwent statistical evaluation through Anova and correlation analysis. The parameters evaluated were the mean frequency and the mean absolute and relative power. The results have shown that after CBZ treatment there is a decrease in the alpha reactivity during BR and FIX, while a significant increase in beta activity was observed during all tasks. The effect of CBZ therapy on EEG activity during cortical activation patterns are discussed.

Adult↗

Ventricular late potentials: another expression of cardiotoxicity of cytostatic drugs in children?

With the aim of finding a sensitive method to detect early anthracycline-induced myocardial damage ultimately resulting in cardiomyopathy, we studied the occurrence of ventricular late potentials, using a signal averaged electrocardiogram, in 68 children with cancer during or after chemotherapy. Ten (15%) of the children showed late potentials; in addition, patients treated with cytostatic drugs had significantly lower voltages of the last 40 ms of the QRS complex (RMS40) and a longer duration of low amplitude signals in the terminal QRS (LAS) than control patients. The occurrence of late potentials was not significantly correlated with anthracycline therapy or dosage, nor with the presence of echocardiographic abnormalities; in none of the patients we found late potentials during therapy with anthracyclines. We therefore conclude that late potentials are not helpful for early detection of myocardial injury. The occurrence of late potentials, however, does show another expression of cardiotoxicity not specifically related to anthracycline therapy. The occurrence of these late potentials may have prognostic significance with regard to the risk of ventricular arrhythmias during longer follow-up of these patients.

Action Potentials↗

Benzodiazepines in the treatment of schizophrenia: a review and reappraisal.

OBJECTIVE: Benzodiazepines, either alone or added to neuroleptics, have been studied extensively as treatments for schizophrenia, but no consensus regarding their efficacy has been reached. The authors review the double-blind trials in the literature and relate the findings to the neurobiology of benzodiazepine actions. METHOD: The clinical review included all double-blind studies through 1989 that could be identified by means of Index Medicus and computer-assisted searches and by the cross-referencing of articles. The findings from the 14 studies of benzodiazepines used alone and the 16 studies of adjunctive therapy are presented separately. RESULTS: The studies reviewed suggest that 1) response is highly variable, and about one-third to one-half of patients improve; 2) benzodiazepines are potentially most useful as adjuncts to neuroleptics in the acute management of psychotic agitation, although actual antipsychotic effects have also been observed in some patients; 3) relatively higher doses of benzodiazepines may be associated with better response; and 4) therapeutic effects, when seen, develop rapidly but diminish after several weeks in some patients. The authors explore the neurobiological bases of benzodiazepine action, which presumably underlie their efficacy in schizophrenia and may help explain the variability of response. CONCLUSIONS: Future research on benzodiazepines in the treatment of schizophrenia should focus on features that predict response, the relation of dopamine or other neurotransmitter systems to therapeutic effects, the schizophrenic symptoms most amenable to benzodiazepine treatment, changes in neuroleptic dose during benzodiazepine augmentation, the role of benzodiazepines in maintenance therapy, and the optimal characteristics of benzodiazepine treatment.

Antipsychotic Agents↗

Prospective detection of vulnerability to sustained ventricular tachycardia in patients awaiting cardiac transplantation.

This prospective study tested the hypothesis that abnormal signal-averaged electrocardiograms (ECGs) and inducible ventricular arrhythmias identify patients awaiting cardiac transplantation who are prone to sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). Thirty-seven patients with advanced symptoms of heart failure and a mean left ventricular ejection fraction of 20 +/- 7 were studied. In response to programmed ventricular stimulation using up to 3 extrastimuli, sustained monomorphic VT was induced in 8 (22%) and polymorphic VT or VF was induced in 5 patients (13%). Patients with inducible arrhythmias underwent drug therapy guided by results of programmed ventricular stimulation or implantation of a defibrillator. Patients in whom ventricular arrhythmias could not be induced were not treated for arrhythmias. The signal-averaged ECG was abnormal and sustained VT or VF was induced in 10 patients (27%). Follow-up ranged from 1 to 33 months (mean 12). Four patients (11%) died suddenly and 4 (11%) had nonfatal sustained VT or VF. The positive predictive value for sudden death or nonfatal VT/VF was 27% for the signal-averaged ECG, 38% for programmed ventricular stimulation, and 50% if both tests were abnormal. The negative predictive values for these tests were 87, 88 and 88%, respectively. The actuarial incidence of arrhythmic events was significantly higher in patients with inducible ventricular arrhythmias (p = 0.017) and in patients in whom both the results of signal-averaged electrocardiographic analysis and the response to programmed ventricular stimulation were abnormal (p = 0.002). This study demonstrates that results of signal-averaged electrocardiographic analysis and the response to programmed ventricular stimulation improve risk stratification for sudden cardiac death in patients awaiting cardiac transplantation.

Actuarial Analysis↗

Analysis of the mechanisms underlying the changes in left ventricular filling dynamics during oral nisoldipine therapy in patients with anterior myocardial infarction.

The aim of this study was to clarify the mechanisms responsible for the increase in early filling rate observed during oral nisoldipine therapy in patients with ischaemic left ventricular (LV) dysfunction. For that purpose, the global and regional LV function was analysed before and after 2 months of double-blind monotherapy with nisoldipine (10 mg twice daily) or a placebo, in 17 patients with a previous anterior myocardial infarction. The baseline LV ejection fraction ranged from 34-51% and no patient had heart failure. Compared to the placebo, nisoldipine significantly lowered LV systolic pressure and end-diastolic pressure (-3 mmHg vs +6 with the placebo; P less than 0.01) and the LV pressure at the time of mitral opening (-2.0 +/- 3.4 mmHg vs +3.5 +/- 3.0; P less than 0.01). Despite this reduction in driving pressure, the global LV early peak filling rate improved with nisoldipine only and this improvement was related to a selective increase in expansion rate of the anterior areas, from 1010 +/- 360 to 1339 +/- 496 mm2.s-1 (P less than 0.001). The time to regional peak filling rate (-8%; P less than 0.01), the asynchrony of diastolic wall motion and the regional ejection fraction (33 +/- 10 to 38 +/- 12%; P less than 0.001) also improved in the anterior areas with nisoldipine but not with the placebo. In contrast, in the inferior, control zones, the regional ejection fraction and filling rate remained unchanged, both when compared to baseline and to the placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

EEG-brain mapping. A method to optimize therapy in schizophrenics using absolute power and center frequency values.

In this study EEG-spectral parameters like mean alpha-power values and center frequency values are computed as maps and compared using significant probability mapping. The parameters are used to describe changes of the functional state of the brain after neuroleptic depot injection (Haldol-Decanoate) in schizophrenic patients. The absolute alpha-power increased significantly (p < 0.01), especially within the first week after injection mostly in the left hemispheric regions. The center frequency decreased most significantly (p < 0.02) between the first and second week after haldol depot injection at the right occipital regions. Both parameters are efficient to describe functional changes correlated with clinical symptomatology, even 3-5 days earlier. Thus, EEG power and center frequency mapping can be used very efficiently to estimate the optimal time between sequential neuroleptic depot injections.

Adult↗

Accuracy of drug infusion pumps under computer control.

Prototype systems implementing algorithms for automated drug infusions are typically constructed by coupling a microcomputer to a drug infusion pump through a serial communications interface. Infusion rates demanded of the infusion pump in many computed-controlled drug delivery applications are made to change at intervals much shorter than those encountered under routine clinical use. Because the ability of infusion pumps to maintain accurate flow rates during high frequency rate changes has not been documented, the purpose of this study was to validate the volumetric accuracy of three commercially available infusion pumps operating in a demanding computer-controlled application. In independent 2-h evaluations, the infusion rate demanded of each pump changed as often as every 5, 10, or 15 s using an algorithm for computer-controlled pharmacokinetic model-driven intravenous infusion. Accuracy of the infusion devices was determined gravimetrically. At all measurement times, each of the infusion pumps was accurate to within approximately +/- 5% of the expected volumetric output under each of the infusion rate intervals tested. Flow rate accuracy of +/- 5% is equal to the nominal expected accuracy of these infusion pumps in conventional clinical use.

Algorithms↗

Computer-assisted review of digoxin therapy in the elderly.

Current practice with digoxin was assessed in a group of 42 elderly patients by comparing plasma digoxin concentrations attained on previously established maintenance doses with those generated by a computer programme designed to calculate dosage schedules to suit individual patients. Discrepancies between measured and computed plasma levels and between established and computed doses dictated withdrawal of the drug or revision of dosage in 26 patients (62%), with obvious clinical benefit. An important determinant of dosage was renal function; reduction in creatinine clearance provided good evidence for the loss of ability of the elderly kidney to eliminate digoxin. Simple bedside methods are available which permit a reliable estimate of creatinine clearance without a 24-hour urine collection, provoding a rational basis for the choice of digoxin dosage in the elderly.

Aged↗

Computers in healthcare: overview and bibliography.

OBJECTIVE: The objective of this article is to provide an overview of computer technology and an associated bibliography, emphasizing institutional-based healthcare applications and pharmacoinformatics. DATA SOURCES: References were selected from the authors' files and from a computerized search over the last five years on computers in healthcare/medical informatics and in pharmacy. STUDY SELECTION: Articles selected for review and discussion were considered to be important contributions to the respective areas listed in the bibliography and representative of advancements in computer applications in healthcare and pharmacy. DATA SYNTHESIS: The computer has become an important support tool for healthcare professionals. Medical informatics and the discipline related to pharmacy, called pharmacoinformatics, have evolved from the cognitive underpinnings of medicine, pharmacy, and computer science. Recent developments in computer technology have resulted in computers that are fast, increasingly portable, and user friendly. Hospital information systems employ computers in various ways to deal with the vast amount of information used by various departments. Standards for electronic data exchange are being developed to increase the integration potential of these systems. Hospital pharmacists have used computers for drug distribution, financial analysis and inventory control, drug interaction detection, pharmacokinetic dosing, drug information, and drug therapy monitoring. Expert systems are being developed in several areas of drug therapy. Pharmacy educators have developed interactive courseware to help students learn problem-solving skills in the areas of calculations, therapeutics, and drug information. CONCLUSIONS: Pharmacists need to become more involved with applications of technology to pharmacy. Properly implemented, computers can provide more time for pharmacists to use their cognitive skills in the delivery of pharmaceutical care.

Clinical Pharmacy Information Systems↗

Decision analysis as a quality-assurance screening tool.

BACKGROUND: The purpose of this pilot study was to examine whether the technique of decision analysis, including sensitivity analysis, could be used in a clinical quality-assurance program. METHODS: This research was performed in a family practice residency clinical practice. A computerized decision analysis model was developed for selection of initial drug therapy for hypertension. The medical records of 52 resident-managed patients with hypertension were then reviewed. The residents' drug prescribing was evaluated by faculty reviewers and also by the decision analysis model, including a sensitivity analysis. RESULTS: Faculty reviewers rated the residents' drug choices as "most appropriate" or "acceptable" in 59.6% of cases. There was good agreement between faculty reviewers and the computerized decision analysis model. For example, in those cases in which the resident chose the computer model's first-choice drug, faculty deemed the management as "most appropriate" or "acceptable" 93.3% of the time. When residents selected the computer model's third or fourth choice, faculty judged the residents' therapy as "inappropriate" or "an alternate drug would have been more desirable" in 61.9% of cases. CONCLUSION: The results suggest that computerized decision analysis techniques may be a useful adjunct to other clinical quality-assurance procedures in residency training programs.

Adult↗