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Biomedical subjects

B Rotman

Publications and source records attributed to B Rotman.

At least 37 records · Page 2Linked to original sources

New concepts in ischemia prevention.

Transient myocardial ischemia may result from obstruction to flow in the large epicardial coronary arteries or diminished flow reserve due to small vessel disease or left ventricular hypertrophy. In patients with coronary heart disease, calcium blockers have proven to reduce stress induced ischemia in patients with normal left ventricular function and in those with ischemic cardiomyopathy. However, recent studies indicate a need for caution when giving calcium antagonists to patients with postinfarction left ventricular systolic dysfunction. Moreover, calcium antagonists that reduce heart rate (diltiazem) are able as a monotherapy to reduce total ischemic burden. Calcium antagonists that may increase rate (dihydropiridines) have to be combined with beta-blockers to achieve this goal. For 24-h control of ischemia the ischemic threshold should be determined for a differentiated therapy in the individual patient. Is the ischemic threshold of the majority of episodes lower than the exercise threshold, a calcium blocker should work. Angiotensin-converting enzyme (ACE) inhibitors are not effective in stress-induced ischemia, but may reduce total ischemic burden, although this effect is not significant. In patients with left ventricular hypertrophy and/or small vessel disease, calcium blockers and ACE inhibitors are probably effective in regression of left ventricular hypertrophy and vascular hypertrophy. However, it remains to be shown that ischemia is reduced by these drugs.

Angiotensin-Converting Enzyme Inhibitors↗

[Silent myocardial ischemia. Current concepts of pathophysiology and diagnosis].

Silent myocardial ischemia (SMI) is divided into 3 groups: type I: completely asymptomatic patients, type II: patients after acute myocardial infarction with SMI, type III: patients with angina pectoris (AP) and SMI. Pathophysiology on the lack of pain-perception and the cause for high tolerance against pain in SMI-patients has not yet been cleared up. It is most likely that more than one mechanism is involved in every patient, e.g. generally lower pain-perception in SMI-patients, physically counter-regulation in pain, duration and strength of myocardial ischemia. Diagnosis of SMI can be made by exercise- and long-term-ECG, thalliumszintigraphy and coronary angiography, in doing so the pros and cons of the 4 established methods have to be noted. The summary of the findings together with the lack of pain leads to the diagnosis of SMI.

Angina Pectoris↗

[Silent myocardial ischemia. Current concepts of prognosis and therapy].

Type-I-patients with silent myocardial ischemia (SMI) have a 2-4fold higher longterm-risk for coronary-events than healthy people. With increasing gravity and duration of ischemia type-II-patients have an increased event-risk. Reliable statements about prognosis of type-III-patients are very difficult. Therapy of SMI is equivalent to therapy of "loud" ischemia and comprises: 1) treatment of cardiovascular risk-factors (nicotine, arterial hypertension, hyperlipidemia, adiposis), 2) nitrates as effective straight at the coronary stenosis, 3) beta-blockers, which influence the circadian ischemic rhythm, 4) calcium-channel-blockers with especially for nifedipine little effect, 5) thrombocyte-aggregation inhibitors and 6) invasive therapeutical methods (percutaneous transluminal coronary angioplasty [PTCA] and aorto-coronary bypass grafting [ACBG]).

Angina Pectoris↗

[Correlation between late potentials, left ventricular function and coronary heart disease].

By signal averaging it is possible to registrate late, fragmented low amplitude signals (late potentials, LP's) from the bodysurface 26 patients (21 males, 5 females) with a mean age of 57 years were investigated by signal averaging, Holter-monitoring and cardiac catheterization. 11 patients had a dilative cardiomyopathy (group A), 10 patients a coronary heart disease (group B), 5 of them with an ejection fraction greater than 50%, 5 of them with a reduced ejection fraction, whereas the control-group with 5 patients (group C) showed no coronary stenosis or reduced ventricular function, 6 out of 11 patients with dilative cardiomyopathy showed LP's; all of these with Lown IVb had LP's. In 2 patients with coronary heart disease and good left ventricular function late potentials were found, and in all 5 patients with disturbed left ventricular function. The control-group revealed no late potentials although 4 patients had Lown IVa or more in Holter-ECG. In conclusion, late potentials show a good correlation to malignant ventricular ectopic beats in patients with dilative cardiomyopathy and coronary heart disease, especially when the left ventricular function is reduced.

Adult↗

[The patient following PTCA].

Diagnostic measures after PTCA consist of history, clinical findings, after 3 months and thereafter in 6 months intervals as well as ergometry in case of recurrency of complaints of after 3 months and then in 6 months intervals. A thallium-scintigraphy is done eventually. A repetition of a coronarography is indicated only in cases of typical symptoms or registration of ischemia. Therapy consists of lifelong ASS and calcium channel blockers for 3 months and treatment of risk-factors. Repetition of a PTCA, atherectomy, stent-implantation, laser-angioplasty or bypass-surgery varies from case to case; the decision has to be made individually.

Angioplasty, Balloon, Coronary↗

Coronary revascularization: influence on ventricular arrhythmias.

Myocardial ischemia may cause severe cardiac arrhythmias. In the present study, the influence of revascularization on ventricular arrhythmias was investigated. A total of 68 patients (61 male, 7 female; mean age 53 years) with coronary artery disease was divided into three groups: Group A (21 patients) underwent percutaneous transluminal coronary angioplasty (PTCA); Group B (37 patients) had coronary artery bypass grafting (CABG); and Group C were 10 patients who served as controls, who had simple coronary angiography. All patients had a Holter ECG on the day before angiography. PTCA patients and controls were restudied on the day after the procedure, while in Group B, Holter ECG was repeated three weeks after surgery. Groups A and B were again studied 18 months after the first Holter ECG. The PTCA group showed a slight reduction in complex arrhythmias immediately following PTCA, which increased again after 18 months; the CABG group, however, revealed a significant increase in complex arrhythmias three weeks after bypass surgery, but a decrease after 18 months. There was no significant change in the control group before or after angiography. Thus, successful revascularization has no influence on ventricular arrhythmias after 18 months.

Adult↗

Noninvasive and invasive diagnosis of a huge congenital aneurysm of the left atrium: a case report.

An intrapericardial aneurysm of the left atrium in a twenty-eight-year old asymptomatic woman is reported. The aneurysm was diagnosed by two-dimensional echocardiography and the specific intraaneurysmatic flow pattern was described by color blood flow imaging. To the authors' knowledge such a noninvasive diagnosis of a left atrial aneurysm has never been reported in the literature before. The diagnosis was confirmed by angiocardiography. The aneurysm was successfully resected. The patient was discharged without medication and continues to do well.

Adult↗

Ketanserin prevents early restenosis following percutaneous transluminal coronary angioplasty.

In the treatment of coronary artery stenoses restenosis represents the main problem in 25-35% of cases following successful percutaneous transluminal coronary angioplasty (PTCA). In the present trial the effect of the 5HT2-serotonergic receptor antagonist ketanserin on the rate of restenosis after 24 h ('early restenosis') or 4-9 months ('late restenosis') was investigated. Preliminary studies demonstrated that ketanserin infused at the dose of 0.1 mg/min inhibited platelet aggregation without evidence of side effects. In the restenosis study, 43 patients (37 males, 6 females; mean 55 years) were randomized into two groups. After PTCA, 22 patients were treated with conventional therapy (group A), whereas 21 received additionally ketanserin (0.1 mg/min for 24 h, group B). The angiograms (prior to, after, 24 h after, and 4-9 months after PTCA) were examined in a blind manner using a computer-based quantitative angiographic system. After 24 h, 3 patients of group A, but none of group B showed restenosis (more than 50% decrease in diameter stenosis). In total, the diameter at the site of stenosis prior to PTCA decreased by 11% in the controls, but remained unchanged in the ketanserin-treated patients. After 4-9 months, 26% of group A (5 out of 19 patients examined) and 22% of the controls (4 out of 18 patients examined) developed restenosis of more than 50%; there was no statistical difference in the degree of residual stenosis between both groups. These findings suggest that a 24-hour infusion of ketanserin following PTCA may prevent early restenosis, but does not influence the incidence of late restenosis.

Adenosine Diphosphate↗

[Preoperative risk assessment: long-term electrocardiography for directed diagnosis of arrhythmias].

The role of ambulatory electrocardiography for detection, confirmation, or exclusion of severe forms of arrhythmias was investigated in our preoperative anesthesia clinic. In a prospective study over a period of 21 months, 30 of 8935 preoperatively evaluated patients (0.3%) scheduled for noncardiac surgery were monitored by 24-h ambulatory ECG. Indications included common clinical reasons for ordering an ambulatory ECG and additional specific "anesthesiologic" indications: Syncopes, dizziness, or other manifestations possibly related to cardiac arrhythmias; Rhythm disturbances under antiarrhythmic drug therapy; Suspected paroxysms of supraventricular tachycardia; Q-T syndrome, R- on-T phenomenon; Insignificant rhythm disturbances in patients with significant cardiac disease such as cardiomyopathy, aortic stenosis, mitral valve prolapse; Rhythm disturbances in patients with poor general medical status; Recent myocarditis with arrhythmias; Previous known or suspected intraoperative cardiac complications; Suspected sick sinus syndrome. The mean age of the patients was 63.9 years; most (24/30) were classified as ASA III. In 4 patients with suspected bradycardic rhythm disturbances the ambulatory ECG proved a useful method for further decision-making compared to the routine resting ECG. According to the long-term ECG recordings 22 patients were classified as Lown IV. After effective antiarrhythmic therapy--usually with propafenon--none of these patients (n = 13) or those classified as Lown 0 to III (n = 8) showed intraoperative arrhythmias or other hemodynamic problems. In contrast, of the patients with complex rhythm disturbances refractory to antiarrhythmic drug therapy (n = 4) or those in whom emergency operations were performed without antiarrhythmic drug therapy (n = 2), 4 developed severe arrhythmias or other intraoperative hemodynamic problems. Two died on the 1st postoperative day.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Redilatation with the trefoil balloon catheter in 2 patients with a high degree of aortic stenosis].

Percutaneous transluminal balloon valvuloplasty (PTBV) is successfully applied in the treatment of calcified aortic stenosis. However, results following redilatation have not yet been dealt with in the literature. This method was successfully used in two patients (62a m/70a f) suffering from severe sclerotic aortic stenoses. Redilatation was undertaken in the first case after one month and after four in the second. A second redilatation by balloon catheter was done upon request of the patients after a further nine months. Following this third dilatation both patients suffered from femoral thrombosis which was treated surgically in the second case, while in the first local thrombolysis was done. In the management of the first patient valve replacement had to be performed four months after the last dilatation due to renewed complaints, while the second patient showed no evidence of recurrence within three months after the last dilatation.

Aged↗

Cellular viability in human tumor micro-organ cultures: in situ quantitation by image processing.

At present, cytotoxicity measurements using the fluorescent cytoprint assay are based on achieving complete cell death in cultures of drug-sensitive tumors. Thus, the usefulness of the assay would be extended if partial effects of chemotherapeutic drugs could be quantified. In this study, we addressed the issue by developing and validating a thresholding algorithm for automatic image processing that can be used to quantify the areas occupied by viable (i.e., fluorescent) micro-organs in the culture.

Drug Screening Assays, Antitumor↗

[Do thrombocyte aggregation inhibitors modify silent episodes of unstable angina pectoris in combined anti-angina therapy?].

Pathological and clinical studies suggest that platelets play role in the pathogenesis of unstable angina. This study investigated the effect of aspirin on silent episodes of unstable angina. Patient exclusion criteria were acute infarction, left bundle branch block, and ST-depression greater than 0.1 mV in the ECG. 27 patients (pts; 20 m, 7 f; 42-72 yrs) in the CCU with unstable angina were randomized in two groups. Group A received a combination on nitrates, beta-blockers, and calcium entry blockers; in group B aspirin (500 mg/day) was added. 6 h after initiating therapy, Holter-ECG was implemented for 48 h. One pt of group A was excluded owing to infarction within these 48 h. 4 of 13 pts in group A and 5 of 13 in group B showed no ST-Segment abnormalities. 6 pts from each group displayed 2 to 5 ST-depressions greater than 0.1 mV from up to 10 min in 24 h; 3 in group A and 2 in group B had 1-5 lasting 11 to 25 min. In the second 24 h period, the number of ST-depressions decreased distinctly. Statistically, the results obtained did not differ significantly in the two groups. Furthermore, the duration of the silent ischemia did not correlate with the severity of coronary stenosis (angiography 3-8 days after admission). Thus, when combined with the aforementioned triple therapeutic regimen, aspirin does not appear to influence the silent episodes of unstable angina pectoris.

Aged↗

Individual human tumors in short-term micro-organ cultures: chemosensitivity testing by fluorescent cytoprinting.

Using innovative approaches, we addressed several problems often associated with in vitro chemosensitivity testing of individual human tumors: 1) obtaining a high rate of evaluability; 2) excluding participation of nonmalignant stromal and vascular components usually present in tumor specimens; 3) preserving cell-to-cell interactions present in the original tumor; 4) assessing drug-induced cytotoxicity without sacrificing the tumor culture. To circumvent these problems, tumor specimens were processed as follows: i) tissue (fresh or cryopreserved) was mechanically or enzymatically dissociated under mild conditions into cellular clusters (termed micro-organs); ii) large micro-organs were separated by a brief decantation, resuspended, and then exposed to fluorescein acetate to visualize (under naked eye) viable micro-organs; iii) fluorescent (i.e., viable) micro-organs were collected using a Pasteur pipette, and then planted on a solid support made of cellulose fibers impregnated with collagen. Since tumor micro-organs have been previously shown to consist solely of malignant cells, the procedure described here not only preserves a critical portion of the tumor architecture but eliminates at the onset necrotic tissue and nonmalignant cellular components that could interfere with the chemosensitivity testing. Drug-induced cytotoxicity was measured by "fluorescent cytoprinting", a novel, nondestructive procedure for assessing micro-organ viability in situ. The key feature of fluorescent cytoprinting is that cytotoxic effects are not measured against control cultures but against a baseline provided by a cytoprint of the same culture before drug addition. Using three experimental designs, we tested the potential of the method for clinical applications. The results using 469 human malignant tumors showed that the micro-organ culture assay can distinguish individual tumor chemosensitivity profiles with an overall success rate of 96%. For three commonly used chemotherapeutic drugs, the observed frequency of responding tumors was found to be comparable to previously reported clinical results using single agents.

Antineoplastic Agents↗

Comparison of different methods of ST measurement for evaluation of myocardial ischaemia in Holter monitoring.

Long-term ambulatory electrocardiographic monitoring [AEM] of the ST segment is clinically the most practical test for the documentation and quantification of myocardial ischaemia. However, there is still some controversy about the validity of ST measurements in Holter monitoring. Therefore, in the present study, in a series of 26 patients with angiographically proven (greater than 70%) coronary heart disease and a positive exercise electrocardiogram, the number, duration and the severity of symptomatic and asymptomatic ischaemic episodes were measured by (1) the ST change at the J point, (2) the ST change 0.07-0.10 s after the J point (immediately before the T wave), (3) the change of the slope of the ST segment, and (4) the area under the ST segment, with a Reynolds Pathfinder III and compared with visual analysis. At the J point (1) there were a total of 264 episodes with a duration of 3947 min and a maximum of 0.35 mV, before the T wave (2) 276 episodes with a duration of 3440 min and a maximal change of 0.40 mV; looking at the slope of the ST segment (3) the figures were 118, 1041 min and regarding the area under the ST segment they were 198, 2385 min. In conclusion, ST deviations are safely detected by automated analysis of the ST segment. Compared with visual analysis (220 episodes), deviation of the ST1 (J point) and ST2 point (80 ms thereafter) overestimate the incidence of true ischaemic ST depression by about 20%.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Disease↗

Identification of the mglA gene product in the beta-methylgalactoside transport system of Escherichia coli using plasmid DNA deletions generated in vitro.

Three genes (mglA, mglB, and mglC) required for active transport of substrate by the methylgalactoside permease were identified in a hybrid ColE1-DNA plasmid isolated from a clone (pLC3-14) of the Clarke-Carbon bank of Escherichia coli genes. A 4.6-kilobase DNA fragment obtained from pLC3-14 was cloned into the plasmid vector pBR322. The presence of the three mgl genes in the resultant plasmid, pMG3, was verified by genetic complementation and biochemical analysis of mgl mutants transformed with pMG3 DNA. Derivatives of pMG3 containing deletions in each mgl gene were constructed; restriction endonuclease mapping and functional analysis of these plasmids allowed us to physically locate the mgl genes within the inserted plasmid DNA and also to identify a heretofore unknown protein component of the transport system. Expression of these plasmids in vivo resulted in the specific synthesis of three major proteins of apparent molecular weight of 19,000, 36,000, and 52,000. The 36,000-dalton protein is the galactose-binding protein previously identified as the mglB product. The 19,000-dalton protein maybe the product of mglD, a regulatory gene mapping outside of the mgl gene cluster. The 52,000-dalton protein is a new permease component which we have identified here as the mglA product based on the observation that pMG6, a plasmid with a 0.6-kilobase mglA deletion, failed to encode for this protein but produced a truncated polypeptide showing a reduction in molecular weight comparable to the extent of the deletion. In bacteria bearing an mglA+, B-, C+ plasmid (Pmg4), the 52,000-dalton protein is located to a large extent (73%) in the membrane fraction.

Autoradiography↗