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Biomedical subjects

J L Weiss

Publications and source records attributed to J L Weiss.

At least 91 records · Page 5Linked to original sources

Effects of halothane and fentanyl anesthesia on plasma beta-endorphin immunoreactivity during cardiac surgery.

We studied the effects of halothane anesthesia (n = 6) and fentanyl anesthesia (n = 9; 50-100 micrograms/kg) on plasma beta-endorphin immunoreactivity as a measure of stress response during coronary artery bypass grafting, including cardiopulmonary bypass. Plasma levels of beta-endorphin immunoreactivity measured prior to induction, after induction, after intubation, after skin incision, during cardiopulmonary bypass, and on leaving the operating room were significantly higher in patients given halothane during cardiopulmonary bypass and on leaving the operating room than they were in patients given fentanyl.

Anesthesia↗

Immediate improvement of dysfunctional myocardial segments after coronary revascularization: detection by intraoperative transesophageal echocardiography.

To ascertain the immediate effects of coronary artery bypass grafting on regional myocardial function, intraoperative transesophageal two-dimensional echocardiograms were obtained in 20 patients using a 3.5 MHz phased array transducer at the tip of a flexible gastroscope. Cross-sectional images of the left ventricle were obtained at multiple levels before skin incision and were repeated serially before and immediately after cardiopulmonary bypass. Using a computer-aided contouring system, percent systolic wall thickening was determined for eight anatomic segments in each patient at similar loading conditions (four each at mitral and papillary muscle levels). Of the 152 segments analyzed, systolic wall thickening improved from a prerevascularization mean value (+/- SEM) of 42.7 +/- 2.9% to a postrevascularization mean value of 51.6 +/- 2.6% (p less than 0.001). Thickening improved most in those segments with the worst preoperative function (p less than 0.001). Chest wall echocardiograms obtained 8.4 +/- 2.3 days after operation showed no deterioration or further improvement in segmental motion compared with transesophageal echocardiograms obtained after revascularization. Thus: regional myocardial function frequently improves immediately after bypass grafting, with increases in regional thickening being most marked in those segments demonstrating the most severe preoperative dysfunction, and this improvement appears to be sustained; and in some patients, chronic subclinical ischemic dysfunction is present which can be improved by revascularization.

Aged↗

Early dilation of the infarcted segment in acute transmural myocardial infarction: role of infarct expansion in acute left ventricular enlargement.

Left ventricular enlargement after myocardial infarction is a poor prognostic sign, the mechanism of which has not been well defined. Early left ventricular dilation may be due to the Frank-Starling effect, which results in an increase in the length of uninfarcted segments in response to a reduction in contractile muscle mass. In contrast to this adaptive physiologic mechanism, left ventricular dilation may alternatively be caused by a pathologic process that stretches and thins the infarcted myocardial segment (that is, infarct expansion). To determine the relative contributions of these two mechanisms to left ventricular dilation after an initial transmural anterior myocardial infarction, two-dimensional echocardiograms were obtained from 27 patients within 72 hours of the onset of symptoms of myocardial infarction and from 13 healthy control subjects. In the minor-axis echocardiographic view at the level of the papillary muscles, anterior and posterior endocardial segment lengths at end-diastole were measured with a microprocessor-based graphic system. The papillary muscles were used as internal landmarks to demarcate the anterior and posterior segments. Anterior (infarcted) segment length in patients with myocardial infarction was 11.6 +/- 2.2 cm (mean +/- SD), whereas in control subjects, anterior segment length was 8.6 +/- 1.2 cm (p less than 0.001). Posterior (uninfarcted) segment length in the patients was not significantly different from posterior segment length in the control subjects (5.4 +/- 1.2 versus 5.3 +/- 1.0 cm, respectively). Measurable left ventricular dilation during the first 3 days after transmural anterior myocardial infarction is due to dilation of the infarcted segment and not of the normal uninfarcted segment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Myocardial injury and induction of arrhythmia by direct current shock delivered via endocardial catheters in dogs.

Although electrical ablation of ventricular tachycardia via percutaneous catheters has been recently accomplished in human beings, little is known of its pathologic or arrhythmogenic effects. We studied 21 open-chest anesthetized dogs in which an endocardial electrode catheter was percutaneously introduced into the left ventricle. Direct current (DC) shock was delivered by a standard defibrillator through the distal electrode to a back paddle. Cross-sectional two-dimensional echocardiographic studies were performed in the plane of the catheter (confirmed by epicardial metal beads), and blood flow was determined by the microsphere technique before DC shock and when the animals were killed 2 to 8 days later. Of 11 dogs receiving a total of 100 to 400 J, only three survived 48 hr compared with nine of 10 receiving 50 J and all three control dogs. Holter monitoring demonstrated sustained ventricular tachycardia (VT) (greater than or equal to 30 sec) in all 11 dogs monitored (six received greater than or equal to 100 J), beginning within 5 hr of the DC shock; three control dogs had no VT. Two dogs that died suddenly while being monitored showed ventricular fibrillation. Histologic examination revealed hemorrhagic contraction band necrosis in the shock zone, a type of injury similar to that observed in reperfusion necrosis. Necrosis of the left ventricle was 0.5% to 5%. There was no significant difference in necrosis between dogs receiving 100 J or more and those receiving 50 J (2.5 vs 1.7 g; p greater than .10). Percent systolic thickening determined in eight equally divided regions around the left ventricle showed no difference between the shock zone, perishock zone, or remote normal zone in dogs receiving 50 J.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Fentanyl preloading for rapid-sequence induction of anesthesia.

Protecting the patient's airway is of paramount importance in the induction of general anesthesia. For the patient at risk of regurgitation of stomach contents, the rapid-sequence (crash) induction provides protection, but at the expense of increased stress response to laryngoscopy and intubation. This stress response is especially dangerous for the patient at risk for myocardial ischemia. The purpose of this study was to examine the efficacy of using low-dose fentanyl (5 micrograms/kg) to reduce cardiovascular and neuroendocrine stress responses to rapid-sequence induction. Thirty patients were randomly assigned to a rapid-sequence induction protocol either with or without fentanyl preloading. Fentanyl-preloaded patients (fentanyl group) received 2 mg/kg of thiopental whereas patients who were not preloaded with fentanyl (control group) received 4 mg/kg of thiopental. Data collected as indices of the stress response included heart rate, systolic, diastolic, and mean blood pressures, and plasma concentrations of catecholamines (epinephrine, norepinephrine, dopamine) and beta-endorphin. Electrocardiograms (modified V5 lead) were monitored for dysrhythmias and ST segment depression. Control patients had higher systolic, diastolic, and mean blood pressures after intubation than did patients given fentanyl (P less than 0.05). Although the incidence of dysrhythmias was decreased by fentanyl (20% vs 42%), this difference was not statistically significant. Plasma concentrations of beta-endorphin and norepinephrine increased significantly in control patients but not in patients given fentanyl (P less than 0.05). Low-dose fentanyl (5 micrograms/kg) reduces some aspects of the stress response to rapid-sequence induction of anesthesia.

Adult↗

Doxepin's effects on chronic pain and depression: a controlled study.

Sixty patients with chronic pain of the low back or cervical spine concomitant with clinical depression were studied in a 6-week, randomized, double-blind comparison of doxepin and placebo. Significant improvements in the doxepin-treated group compared to placebo or to baseline values were seen on Hamilton depression scores, Global Assessment Scale scores, pain severity, percent of time pain felt, and effect of pain on activity, sleep, and muscle tension. Some improvements were observed after 1 week of treatment; the most improvement occurred at 6 weeks, when the mean doxepin dosage was approximately 200 mg/day and plasma doxepin and nordoxepin averaged 80 ng/ml. No significant harmful effects were observed. Neither plasma beta-endorphin nor enkephalin-like activity demonstrated significant differences from baseline. These data indicate that doxepin is a valuable treatment for patients with chronic pain and depression.

Chronic Disease↗

Corneal ulcer-infiltrate associated with soft contact lens use following penetrating keratoplasty.

A review of 100 patients who underwent penetrating keratoplasty revealed 47 who required therapeutic soft contact lenses in the early postoperative period. Twelve corneal ulcer-infiltrates, 11 of which were culture positive, occurred during soft contact lens wear (23% incidence of this complication in contact lens fitted eyes). The most common offending organism was coagulase-negative staphylococcus. The only statistically significant risk factor for infection if a lens was used was the presence of a persistent epithelial defect (p = 0.03). Factors which could not be statistically correlated with corneal ulcer-infiltrate included keratoconjunctivitis sicca, the type of contact lens, the method of donor cornea preservation, lens hygiene, antibiotic and steroid usage, the presence of blepharitis, preoperative bacterial keratitis, and the history of a previously failed penetrating keratoplasty.

Contact Lenses, Hydrophilic↗

The use of tissue adhesive in corneal perforations.

Eighty patients with either corneal perforation or impending perforation were treated with the application of tissue adhesive that remained in place on the average of 50 days. Forty-four percent of these cases healed with the application of glue alone. Complications occurred in nine patients (11%). Two developed marked increase in intraocular pressure that was controlled with antiglaucoma medications and seven developed corneal infiltrates. Five of the infiltrates were culture-proven bacterial infections occurring on the average of 73 days after gluing. The relationships between diagnosis, duration of glue, and complications are reviewed.

Adolescent↗

Modulator sequences mediate oxygen regulation of CYC1 and a neighboring gene in yeast.

Three transcripts from Saccharomyces cerevisiae--CYC1 mRNA (transcribed from the iso-I cytochrome c gene) and two RNAs of unknown function, designated tr-1 and tr-2-were identified by reverse Southern blot analysis and found to be regulated in response to oxygen. CYC1 mRNA and tr-1 accumulation occurred only in the presence of oxygen while tr-2 appeared only under anaerobic conditions. tr-2 was transcribed from a region approximately 1 kilobase 5' from the CYC1 coding sequence and in the opposite direction. tr-1 showed homology to the same region as tr-2 but was transcribed from elsewhere in the genome. Expression of tr-2 and CYC1 was observed to be normal in cells transformed with centromeric plasmids carrying the two genes. Mutant transforming plasmids were constructed in which a 400-base-pair region between tr-2 and CYC1 was either deleted or inverted. The deletion led to low-level nearly unregulated expression of both the CYC1 and tr-2 genes, suggesting that sequences upstream from both genes are important for their expression and regulation. The inversion mutation produced a reversed pattern of CYC1 regulation in which the mRNA was present in anaerobically grown cells but absent in the presence of oxygen, mimicking wild-type tr-2 regulation and suggesting that the CYC1 transcription unit is under the control of the translocated tr-2 modulator sequences. Models for the function of these modulators are discussed.

Cytochrome c Group↗

Impaired function of salvaged myocardium: two-dimensional echocardiographic quantification of regional wall thickening in the open-chest dog.

This study was designed to examine the functional properties of myocardium subjected to acute coronary occlusion but surviving the ischemic insult. Ten conscious mongrel dogs underwent mild-circumflex coronary occlusion and were treated for 6 hours with prostacyclin, 540 ng/kg/min, and ibuprofen, 110 micrograms/kg/min, or dipyridamole (7-9.7 micrograms/kg/min). At 7 days, each dog was anesthetized, the chest was opened, and cross-sectional two-dimensional echocardiograms were obtained through the middle of the occluded vascular bed. A computer-aided contouring system was used to assess percent systolic thickening in 16 equally spaced segments around the left ventricle. Metal markers sewn to the epicardium permitted precise regional correlation of histology, percent systolic thickening, and flow, as measured by radioactive microspheres. Necrosis was minimal, averaging only 2.2 +/- 0.8% (+/- SEM) of the left ventricular ring corresponding to the echocardiographic cross section. Percent systolic thickening was 28.6 +/- 4.7 in the nonischemic anterior wall, but was reduced to -4.5 +/- 3.1 in the occluded bed (p less than 0.01). In individual echo segments, percent systolic thickening correlated with local flow (r = 0.69, p less than 0.001), but was still depressed even when flow was normal. In six segments within the occluded bed that had normal histology and flow, percent systolic thickening was 52% less than that in the nonischemic region (p less than 0.02). Thus, coronary artery occlusion combined with drug treatment results in myocardium that, although histologically normal and supplied by normal myocardial blood flow, remains functionally abnormal 7 days after occlusion.

Animals↗

Accuracy of volume determination by two-dimensional echocardiography: defining requirements under controlled conditions in the ejecting canine left ventricle.

The accuracy of two-dimensional echocardiographic left ventricular volume measurement in an isolated heart preparation was tested using Simpson's reconstruction of progressively fewer short-axis cross sections of known location. Echocardiographic images from five ejecting hearts submerged in a special tank were obtained under conditions designed for maximal accuracy of echocardiographic volume assessment. Echocardiographic determinations of 52 volumes at various times throughout the cardiac cycle were compared, by least-squares linear regression, with simultaneous direct-volume measurements by volumetric chamber (range 9.4-44.8 ml). Echocardiographic and direct measurements correlated well for all numbers of cross sections from 1-19 (r = 0.84-0.97); however, variability of direct volume predicted from a given echocardiographic measurement increased nonlinearly as the number of cross sections per heart decreased, and was especially large when three or fewer cross sections were used (SEE = 4.6-7 ml). The accuracy of echocardiographic measures was compared for each number of cross sections per heart, varying from one to 19; accuracy was defined as the mean absolute difference between echocardiographic and direct measurements of volume, ejection fraction, and maximal rate of ejection. The accuracy of echocardiographic measurements was significantly reduced with fewer than four cross sections per heart for ventricular volume, three cross sections for ejection fraction, and five cross sections for maximal rate of ejection. In light of what appears to be required for accurate echocardiographic volume measurement in this controlled, ejecting, noninfarcted, in vitro preparation, additional cross sections may be required in intact animals and human subjects, especially in those with diseases that cause ventricular asymmetry or regional dysfunction.

Animals↗

Effect of nitroprusside on hydraulic vascular loads on the right and left ventricle of patients with heart failure.

We studied the effect of nitroprusside on the hydraulic vascular load of the right and left ventricle in seven patients with severe left ventricular failure. At doses of 0.25-0.75 micrograms/kg/min, stroke volume increased progressively from 40.1 to 48.6 ml and left ventricular end-diastolic pressure decreased from 24.5 to 11.2 mm Hg. Accompanying this improvement in left ventricular performance were dose-related decreases in mean ventricular pressures, pulmonic and systemic resistances and the lower-frequency components of input impedance moduli. Characteristic impedance and both total and oscillatory external power were decreased in the pulmonic, but not the aortic, vasculature. In this class of patients, right ventricular unloading is a striking and direct effect of nitroprusside and may account, in part, for improved left ventricular performance through ventricular interdependence.

Adult↗

Incomplete filling and incoordinate contraction as mechanisms of hypotension during ventricular tachycardia in man.

We sought to determine mechanisms for decrease of cardiac output and for hypotension during ventricular tachycardia (VT) in man. Two-dimensional and M mode echocardiograms and left ventricular pressure from micromanometer-tipped catheters were obtained in 20 patients before, during, and at the end of induced hypotensive VT. Patients were divided into two groups according to left ventricular function in sinus rhythm as assessed by angiographic ejection fraction (EF) before electrophysiologic study. Group 1 (n = 8) had angiographic EF greater than or equal to 50% in normal sinus rhythm, and group 2 (n = 12) had EF less than or equal to 40%. During VT, left ventricular cavity volume (as indexed by short- and long-axis two-dimensional end-diastolic cavity areas) was markedly reduced in group 1, from 19.7 +/- 2 to 8.6 +/- 2 cm2 (p less than .001) and from 32.0 +/- 8 to 22.5 +/- 7 cm2 (p less than .001), respectively, but was only slightly reduced in group 2, from 34.1 +/- 6 to 31.5 +/- 7 cm2 (p = .044) and from 45.0 +/- 8 to 49.4 +/- 7 cm2 (p = NS), respectively. Conversely, left ventricular systolic function during VT (as indexed by fractional reduction in two-dimensional short- and long-axis areas) was markedly depressed in group 2, from 25.6 +/- 6% to 4.2 +/- 4% (p = .005) and from 13.7 +/- 3% to 1.8 +/- 0.8% (p less than .001), respectively, but remained at control levels in group 1. Left ventricular end-diastolic pressures increased in group 1, from 11.8 +/- 2 to 27.7 +/- 8 mm Hg (p = .005) and did not change in group 2 during VT. Pressure-dimension loops from left ventricular pressure and M mode echocardiographically determined cavity dimensions generated from the end of the VT episodes showed that diastolic pressure-dimension relationships returned to control levels with the first prolonged diastolic interval in group 1 patients, indicating that incomplete relaxation was the mechanism responsible for reduction of cardiac output during VT in these patients. Coordination of contraction and relaxation (indicated by the percent ratio of the pressure-dimension loop area to the area of the rectangle just enclosing the loop) decreased from 37 +/- 11% to 16 +/- 13% in group 2 patients during VT (p = .013) but remained at control levels in group 1 patients. Thus, during VT patients with impaired left ventricular function in sinus rhythm (group 2) developed severe discoordination, and patients with normal or near-normal function (group 1) developed incomplete relaxation to account for stroke volume deterioration and hypotension.

Adolescent↗

Amiodarone in refractory life-threatening ventricular arrhythmias.

Ninety-six patients with life-threatening ventricular arrhythmias refractory to two or more conventional agents were treated with amiodarone and followed for 6 to 40 months (mean, 15 months). Currently, 75 are alive and well. Seven patients died from nonarrhythmic and five from arrhythmic causes. Nonfatal arrhythmias recurred in four patients, one with early and three with late onset. Intolerable side effects occurred in five patients but heart failure was not aggravated by the drug. On 24-hour Holter recordings done before and serially during therapy in 72 patients, amiodarone eliminated episodes of ventricular tachycardia and complex ectopy and reduced total ectopic beat counts by 90% or more in all but 4 patients. In contrast, ventricular tachycardia inducible by programmed electrical stimulation was suppressed in only 50% of patients, but failure of such suppression did not compromise an excellent clinical outcome. Thus, amiodarone is highly effective in the prophylaxis of recurrent refractory life-threatening ventricular arrhythmias.

Acute Disease↗

Expression of the yeast CYC genes and CYC1/GalK fusion genes on yeast plasmids.

We have presented the results of our studies of the expression of the CYC genes from plasmids. All our data indicate that the levels of expression and the regulation of expression are very similar for the plasmid-borne genes and the chromosomal genes when care is taken to construct the appropriate plasmids. The usefulness of these plasmids has been demonstrated: mutations affecting regulatory sites adjacent to genes of interest have been constructed [such as the Xho I deletion and inversion in the YCpCYC1(2.4) plasmid] and selected [as in the case of the IS1 insertion into the YCpCYC7(2) plasmid], and these mutations have led us to some tentative conclusions about the location and nature of the regulatory sites of these genes. Furthermore, transformation with plasmids containing modified genes or fusions has permitted isolation of genomic regulatory mutants, as in the selection of lac+ suppressors of the lac- CYC1 1/x inversion carried on the YCpCYC1(2.4) 1/x plasmid. Although we cannot rule out the possibility that use of plasmids might cause us to miss a class of regulatory effects that can be propagated only along a chromosomal structure, we believe that the regulatory effects that we do observe can be more quickly and completely defined by working with plasmids. If any regulatory effects occur only on chromosomes, they can be studied more easily once the basic regulatory phenomena have been analyzed. The regulatory regions of the CYC1, CYC7, and TR2 genes that we have crudely mapped so far all exert their effects 100-300 bp away from the putative transcriptional starting sites. How the information in these regions is transmitted along the DNA is an intriguing question. We are engaged in a mutational analysis of these sites to locate them more precisely, to map second-site mutations that moderate the effects of the original mutations, to obtain genomic mutations that define the genes whose products interact with these sites, and to test combinations of genomic and plasmid mutations to define the sites with which regulatory elements interact. This approach should aid our understanding of the spatial relationships between yeast regulatory sites and transcriptional signals. Ultimately, obtaining mutations in regulatory genes, such as the mutations described here for the anaerobic regulation of TR2, will allow the cloning of these genes by complementation. This will lead to the isolation of the protein encoded and ultimately to an approach to the molecular mechanism of regulation through study of protein-DNA interactions.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

A randomized clinical trial of intravenous nitroglycerin in patients with acute myocardial infarction: benefits of early treatment.

A prospective randomized clinical trial of intravenous nitroglycerin administered for 48 hours following acute infarction was undertaken to determine whether clinical improvement and/or preservation of ischemic myocardium could be demonstrated. One hundred four patients were randomized to receive either nitroglycerin or placebo infusion. Nitroglycerin infusion was titrated to lower mean arterial pressure 10% using non-invasive monitoring. Early nitroglycerin treatment, defined as treatment initiated less than 10 hours after symptom onset, resulted in a lower incidence of new congestive heart failure, myocardial infarct extension, and/or early death from pump failure (15%) compared to late nitroglycerin treatment (50%, p = 0.008) or early placebo treatment (48%, p = 0.01). Improvement in ejection fraction of greater than or equal to 10% was demonstrated in 7 of 20 (35%) early nitroglycerin treated patients compared to 6, 11 and 0% of patients in the three other subgroups, respectively (p = 0.004). Similarly, thallium-201 perfusion scintigrams showed a greater than 75% improvement in defect score in 23 (48%) patients receiving nitroglycerin within 10 hours compared to 14%, 33% and 0% respectively, in the remaining subgroups (p = 0.035). However, before routine administration of nitroglycerin can be recommended for all patients with acute infarction, larger clinical trials will be required.

Clinical Trials as Topic↗