PubMed HealthSearch

Biomedical subjects

J L Cox

Publications and source records attributed to J L Cox.

At least 19 recordsLinked to original sources

Improved detection of accessory pathways that bridge posterior septal and left posterior regions in the Wolff-Parkinson-White syndrome.

To improve the detection of accessory pathways that bridge the posterior septum and left posterior free wall, catheter maps of the coronary sinus from 21 patients (group I) who needed dissection of both these anatomic regions were compared with data from 23 (group II) with pathways confined to the posterior septum and from 9 (group III) with left posterior pathways. A decapolar catheter was used to map the coronary sinus in 0.5 to 1 cm steps. Intraoperative mapping was performed with a 16-electrode band. Catheter maps during atrial pacing and orthodromic supraventricular tachycardia were analyzed for the site of earliest activation and for differences in a new directional measure of conduction time between adjacent mapping sites. The site of earliest activation alone did not distinguish accessory pathways that bridged both anatomic regions, because 14 of 21 patients (66%) in group I would have been misclassified to either group II or III. In contrast, anterograde and retrograde directional conduction times distinguished patients in group I from those in groups II (p less than 0.01 to less than 0.0003) and III (p less than 0.04 to less than 0.0001). A multivariate model that incorporated the observed differences in directional interelectrode conduction times improved the identification of group I patients, with a sensitivity of 87% and a specificity of 90%. The results define new features in activation patterns measurable during catheter mapping that identify accessory pathways that bridge the posterior septum and left posterior free wall.

Adolescent

Importance of left ventricular function and systolic ventricular interaction to right ventricular performance during acute right heart ischemia.

To determine whether modulation of systolic ventricular interaction influences right ventricular performance during right heart ischemia, the effects of septal ischemia and inotropic stimulation were studied in 15 dogs in an open chest preparation. Right coronary branch occlusions led to right ventricular dilation and free wall dyskinesia, reversed septal curvature and reduced left ventricular diastolic volume. In systole, the septum thickened but bulged paradoxically into the right ventricle generating an active but depressed right ventricular systolic pressure (28.9 +/- 5.5 to 22.1 +/- 4.5 mm Hg), with associated decreases in right ventricular stroke work (5.66 +/- 0.94 to 1.92 +/- 0.53 g.m/m2) and left ventricular systolic pressure (123 +/- 11 to 80 +/- 10 mm Hg). Septal ischemia induced systolic septal thinning, left ventricular dilation and decreased left ventricular systolic pressure (80 +/- 10 to 55 +/- 10 mm Hg) and stroke work. Although the extent of paradoxic septal displacement increased, there were further decrements in right ventricular systolic pressure (22.1 +/- 4.5 to 18.7 +/- 4.3 mm Hg) and stroke work (1.92 +/- 0.53 to 0.7 +/- 0.2 g.m/m2). Dopamine infusion augmented left ventricular free wall contraction and increased left ventricular systolic pressure (55 +/- 10 to 172 +/- 17 mm Hg) and stroke work. Although systolic septal thinning persisted, the extent of paradoxic septal displacement increased strikingly and, despite continued right ventricular free wall dyskinesia, right ventricular systolic pressure increased (18.7 +/- 4.3 to 39.6 +/- 6.2 mm Hg) as did right ventricular stroke work (0.7 +/- 0.2 to 7 +/- 1.6 g.m/m2).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease

Structure, organization and regulation of a rat cysteine proteinase inhibitor-encoding gene.

During postnatal development, submandibular glands of rats produce the secretory protein, cystatin S (CysS), which belongs to family 2 of the mammalian cysteine proteinase inhibitor superfamily. While the rat CysS gene is not expressed in the salivary glands of adult rats, it can be induced by isoproterenol (IPR), which acts via beta-adrenergic receptor/adenylate cyclase/cyclic AMP (cAMP) mechanisms. In addition, IPR-induction of CysS mRNA in submandibular glands is more pronounced in females than in males, at both prepuberal and mature ages. These results suggest that sex hormones may participate in the regulation of the rat CysS gene via estrogen-responsive elements (ERE), and IPR induction of this gene supports the hypothesis that cAMP-responsive elements (CRE) may also play a role in regulating CysS gene expression. We have isolated, sequenced and characterized the complete gene. The CysS gene contains three exons interrupted by two intervening sequences, with consensus splice junctions. The transcription start point is 73 nucleotides upstream from the start codon which is surrounded by a typical Kozak sequence. CCAAT and TATA boxes are present in the 5'-flanking region of the CysS gene. This region also contains several possible regulatory elements that resemble those of other eukaryotic genes, i.e., ERE, CRE, and glucocorticoid-responsive elements. The first intron sequence contains other potential CRE highly homologous to those found in the IPR-inducible mouse and hamster proline-rich-protein-encoding genes.

Amino Acid Sequence

Intraoperative echocardiographic diagnosis of previously unrecognized cor triatriatum.

Cor triatriatum is a congenital heart defect resulting in abnormal septation of the left atrium by a fibromuscular membrane. Echocardiography has improved the preoperative diagnosis of this rare congenital heart defect. We report a case where transesophageal echocardiography proved useful in the intraoperative diagnosis of a previously undetected cor triatriatum.

Aged

Intraaortic balloon counterpulsation: patterns of usage and outcome in cardiac surgery patients.

Between January 1, 1986, and May 6, 1991, 7,884 cardiac surgical procedures requiring cardiopulmonary bypass were performed at our institution, including 672 (9.8% of adult procedures) performed in 669 patients that were associated with preoperative (n = 240), intraoperative (n = 353), or postoperative (n = 79) use of an intraaortic balloon pump. The mean age of recipients was 65.3 years (range, 16 to 89 years). Intraaortic balloon pump usage increased during the study period from 6.4% of patients (83/1,298) in 1986 to 12.7% of patients (169/1,333) in 1990. The relative distribution between preoperative (mean, 35.7%), intraoperative (52.5%), and postoperative (11.8%) insertion remained nearly constant during the study period. The overall operative (30-day) mortality for patients with preoperative, intraoperative, or postoperative insertion of the intraaortic balloon pump was 19.6%, 32.3%, and 40.5%, respectively (X2 = 16.4; p less than 0.001). Although use of the intraaortic balloon pump in the intraoperative and postoperative settings is accompanied by a favorable outcome in most patients, the high associated mortality suggests the need for earlier use of the intraaortic balloon pump or other supportive measures such as the ventricular assist device.

Angina, Unstable

Reentrant and focal mechanisms underlying ventricular tachycardia in the human heart.

BACKGROUND: To determine the mechanisms of ventricular tachycardia (VT) in humans, three-dimensional intraoperative mapping of up to 156 intramural sites was performed in 13 patients with healed myocardial infarction and refractory VT. METHODS AND RESULTS: Mapping was of sufficient density to define the mechanism of 10 VTs in eight patients. In five of 10 cases, sustained VT was initiated in the subendocardium or epicardium by intramural reentry with marked conduction delay as well as functional and anatomic block most prominent in the subendocardium and midmyocardium. The initiating beats of reentrant VT induced by programmed electrical stimulation arose in the endocardium or midmyocardium by progressive slowing of conduction leading to unidirectional block. Multiple simultaneous reentrant circuits can be present. In contrast, five of the 10 sustained VTs were initiated by a focal mechanism as defined by the absence of electrical activity between the termination of one beat and the initiation of the next despite the presence of multiple intervening intramural electrode recording sites. Comparisons of the mapping data with results of histopathological analysis of tissue demonstrated that the location of infarction as well as that of adjacent fibrotic muscle determined sites of both fixed and functional conduction block during macroreentrant VT and that slowing of conduction occurred in a direction transverse rather than longitudinal to fiber orientation. CONCLUSIONS: Both intramural reentry and a focal mechanism underlie sustained VT in patients with healed myocardial infarction.

Adult

Cholinergically mediated tachyarrhythmias induced by a single extrastimulus in the isolated canine right atrium.

Cholinergic agonists and vagal stimulation potentiate the inducibility of atrial fibrillation. To describe the activation patterns and determine the mechanisms that sustain cholinergic fibrillation, tachyarrhythmias were induced with a single extrastimulus in the isolated Krebs-Henseleit-perfused canine right atrium (n = 11) at increasing concentrations of acetylcholine (from 10(-7.5) to 10(-4.5) M). Bipolar electrograms were recorded from 250 epicardial sites simultaneously during control conditions and during extrastimulation (S1S1, 300 msec; S1S2, effective refractory period+5 msec) with and without acetylcholine. Activation sequence maps were constructed from each recording. Without acetylcholine, no tachyarrhythmias were induced. With increasing concentrations of acetylcholine, the refractory period decreased, and nonsustained (< 2 seconds) rapid repetitive responses were induced. At higher concentrations, a sustained (> 2-minute) fibrillation was induced. Activation sequence maps revealed that the rapid repetitive responses were characterized by multiple reentrant circuits. The number of circuits and wavelets increased in a dose-dependent fashion. However, unexpectedly, this trend did not continue when the tachyarrhythmia became sustained. Instead, the reentry tended to stabilize to a small, single, relatively stable reentrant circuit. In conclusion, the data suggest that, in this model, below a critical level of refractory period (< 95 msec) atrial reentrant circuits, unassociated with anatomic obstacles, can become stable and dominate activation.

Acetylcholine

Transesophageal echocardiography predicts successful withdrawal of ventricular assist devices.

Transesophageal echocardiography has been found to be an effective technique for the real-time assessment of myocardial and valvular function in postoperative patients. To determine the value of transesophageal echocardiography in patients with mechanical assist devices, we performed daily, bedside transesophageal echocardiography on 16 patients with right (n = 3), left (n = 1), or biventricular assist devices (n = 12). We obtained four-chamber and short-axis views in all patients. Valvular function and the presence of left-to-right shunts were evaluated by means of color flow Doppler imaging. During the echocardiographic study ventricular assist device flow was diminished to less than 1.5 L/min, and inotropic agents (dobutamine or epinephrine) were given to assess ventricular reserve. Changes in day-to-day ventricular function were assessed in comparisons made by two observers (one unaware of the study sequence) using a semiquantitative method for wall motion analysis. The left ventricular wall motion scores in the patients successfully weaned from left or biventricular assist devices (n = 5) improved (14.2 +/- 1.6 versus 8.2 +/- 1.5, p < 0.0001). The scores did not improve in patients who remained dependent on the devices (n = 8). Two patients with only right ventricular assist devices were successfully weaned after documentation of improvement of right ventricular function by transesophageal echocardiography. Transesophageal echocardiography documented a clot compressing the heart in three patients; intracavitary thrombi were seen in two other patients. Marked hemodynamic improvement occurred after surgical decompression. In conclusion, transesophageal echocardiography is a safe, effective method for the assessment of ventricular function of patients on ventricular assist device support. In addition, it allows one to assess valvular function and the presence or absence of impaired ventricular filling.

Adult

The effect of augmented atrial hypothermia on atrial refractory period, conduction, and atrial flutter/fibrillation in the canine heart.

The purpose of this study was to test the assumption that the cause for postoperative atrial flutter/fibrillation after cardiopulmonary bypass is inadequate atrial myocardial protection. Dogs were subjected to cardioplegic arrest for 60 minutes without augmented atrial hypothermia (seven dogs, control group) or augmented atrial hypothermia with topical atrial cooling (seven dogs, study group). Twenty-five electrodes (15 on the right atrium and 10 on the left atrium) were fixed on the atria to measure effective refractory period and conduction time. Data were taken before bypass, immediately after bypass, and 2 hours after bypass. During cardioplegic arrest the mean temperatures measured in the atria were significantly lower (p less than 0.001) in the study group (13.5 degrees +/- 7.0 degrees C) than in the control group (23.7 degrees +/- 3.2 degrees C). There was no significant change in the mean effective refractory period after bypass in the control or study groups or in the prevalence of inducibility of atrial flutter/fibrillation by extrastimulation (3/7 dogs in the control group and 2/7 in the study group). During right atrial pacing, total conduction times were significantly longer (p less than 0.025 at cycle lengths of 300 and 350 msec) in the control group (74 +/- 5 msec and 75 +/- 7 msec, respectively) than in the study group (65 +/- 9 msec and 64 +/- 8 msec, respectively) immediately after bypass. Two hours after bypass, however, there were no significant differences under the same conditions between the two groups. There were no significant differences in conduction during left atrial pacing after bypass. Comparing those atria that were inducible with those not inducible demonstrated a significantly increased dispersion of effective refractory period (90 +/- 23 msec versus 74 +/- 18 msec, p less than 0.05) and increased conduction time in the inducible group. We concluded that augmented atrial hypothermia during cardioplegic arrest had no effect on the inducibility of fibrillation, had no effect on repolarization, and had only a small effect on conduction, which resolved within 2 hours after bypass. However, the study demonstrates that when the atria are inducible the substrates are an increased dispersion of refractoriness and a prolongation of conduction time.

Animals

Noninvasive detection of cardiac allograft rejection by prospective telemetric monitoring.

A method for cardiac allograft surveillance that is less invasive than endomyocardial biopsy is needed. A fall in the unipolar peak-to-peak amplitude recorded from cardiac allografts has been shown to detect rejection when retrospectively compared with endomyocardial biopsy. This study was performed to assess the sensitivity and specificity of prospective telemetric unipolar peak-to-peak amplitude surveillance in detecting rejection of heterotopic canine cardiac allografts occurring through triple drug immunosuppression. Native heart and graft amplitudes were telemetrically acquired on a daily basis. A fall in normalized unipolar peak-to-peak graft amplitude to less than 85% was used as an indication for biopsy. A quantitative rejection score was calculated for each endomyocardial biopsy (rejection score greater than 0.66 = histologic rejection). Rejection was documented in all animals. Thirty-six biopsies were performed (10 control biopsies and 26 amplitude-directed biopsies); 25 of the 36 demonstrated rejection. Sensitivity and specificity were 88% and 91%, respectively. A linear correlation between unipolar peak-to-peak amplitude and rejection severity was seen (R = 0.87, p less than 0.001). The first true positive amplitude was associated with mild-to-moderate rejection (rejection score = 1.63 +/- 0.45). Unipolar peak-to-peak amplitude recorded from native hearts remained stable during allograft rejection. It is concluded that prospective, telemetric cardiac allograft surveillance can accurately detect rejection occurring through ongoing immunosuppression.

Animals

Transdermal nicotine replacement and smoking cessation.

Transdermal nicotine systems are a useful adjunct to smoking cessation. The larger-sized nicotine patches provide steady-state replacement of approximately 50 percent of the average serum nicotine level obtained by smoking one to one and one-half packs of cigarettes a day. This level is sufficient to prevent many symptoms of nicotine withdrawal, including physical craving, irritability, anxiety, restlessness, hostility, hunger and difficulty concentrating. In double-blind, placebo-controlled trials, transdermal nicotine systems have been about twice as successful as placebo in helping patients stop smoking.

Administration, Cutaneous

Pediatric chest disease: evaluation by computerized tomography, magnetic resonance imaging, and ultrasonography.

The initial method for evaluating pediatric chest disease remains the plain chest roentgenogram. When more precise definition of chest disease is required, computerized tomography (CT), magnetic resonance imaging (MRI), or ultrasonography (US) may be useful. In general, CT offers the widest spectrum of applicability. MRI is especially useful because no ionizing radiation is used and images can be acquired in multiple planes. MRI is most valuable when vascular anatomy needs to be defined or when tumor invasion of the spinal canal is suspected. US is helpful in evaluating diseases of the pleura and for characterizing and localizing pleural fluid and masses. US can differentiate normal thymus from other anterior mediastinal masses. Doppler techniques are valuable in evaluating suspected pulmonary sequestration and identifying the feeding vessel.

Child

Right atrial ischemia exacerbates hemodynamic compromise associated with experimental right ventricular dysfunction.

To determine the importance of right atrial function with acute right ventricular dysfunction, sequential right ventricular and right atrial ischemia were induced in 15 dogs. Right ventricular ischemia resulted in right ventricular free wall dyskinesia, right ventricular dilation by ultrasound, elevated right ventricular filling pressure and paradoxic septal motion. There were decrements in right ventricular systolic pressure (28.9 +/- 5.5 to 25.5 +/- 4.6 mm Hg) (p less than 0.05 for these and all subsequent values) and stroke work (5.66 +/- 0.94 to 2.66 +/- 0.62 g.m/m2), resulting in reductions in left ventricular preload, systolic pressure (123 +/- 11 to 97 +/- 12 mm Hg) and stroke volume (24.2 +/- 4.3 to 19.1 +/- 5.2 ml). Right atrial contractility was augmented, as indicated by increases in peak A wave amplitude (ratio of peak A wave to mean right atrial pressure 1.22 +/- 0.02 to 1.46 +/- 0.3) and right atrial stroke work (0.11 +/- 0.02 to 0.25 +/- 0.05 g.m/m2). Right atrial ischemia depressed right atrial contraction, as indicated by decreased A wave amplitude (ratio of peak A wave to mean right atrial pressure 1.46 +/- 0.3 to 1.04 +/- 0.2) and stroke work (0.25 +/- 0.05 to 0.04 +/- 0.01 g.m/m2).(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance

Successful surgical treatment of atrial fibrillation. Review and clinical update.

Atrial fibrillation is the most common of all sustained cardiac arrhythmias, yet it has no effective medical or surgical therapy. During the past decade, multipoint computerized electrophysiological mapping systems were used to map both experimental and human atrial fibrillation. On the basis of these studies, a new surgical procedure was developed for atrial fibrillation. Between September 25, 1987, and July 1, 1991, this procedure was applied in 22 patients with paroxysmal atrial flutter (n = 2), paroxysmal atrial fibrillation (n = 11), or chronic atrial fibrillation (n = 9) of 2 to 21 years' duration. All patients were refractory to all antiarrhythmic medications, and each patient failed to receive the desired therapeutic benefits of an average of five drugs administered preoperatively. There were no operative deaths and all perioperative morbidity resolved. All 22 patients have been successfully treated for atrial fibrillation with surgery alone. Three patients developed one late isolated episode of atrial flutter at 5, 6, and 15 months postoperatively, and each of these patient's symptoms is now controlled by a single antiarrhythmic drug. Preservation of atrial transport function has been documented in all patients postoperatively, and all have experienced marked clinical improvement.

Adult

Sequence and transcriptional activity of the Escherichia coli K-12 chromosome region between rrnC and ilvGMEDA.

We previously identified a protein related to the expression of the ilvGMEDA cluster of Escherichia coli K-12. It was observed that this ilv-related protein was produced at higher levels in UV irradiated cells infected with lambda dilvGMEDA phage with specific ilvG mutations (ValR), compared to phage carrying the wild-type(ValS) ilvG allele. The gene encoding this protein was further localized to a region between rrnC and ilvGMEDA by analyzing restriction fragment subsets in maxicells. We have now determined the nucleotide (nt) sequence of the 3.5-kb segment between rrnC and ilvGMEDA, and two open reading frames (ORFs) are present in the region expected to contain the ilv-related gene. These ORFs predicts Mrs of 18,751 (ORFI) and 20,085 (ORFII) Da, and both ORFs have a strong probability to encode proteins based on codon frequency analysis. Maxicell analysis revealed that a 1319-bp HindIII-SmaI fragment containing ORFI encodes the ilv-related peptide. We deleted a ClaI fragment that removed a portion of ORFI encoding the C-terminal region of the peptide, and maxicell analysis revealed a decrease in the size of the protein produced in accord with the prediction. RNA slot blots and Northern blots were used to characterize transcripts encoding ORFI. A transcript initiated 112 nt from the ilvGp2 promoter, but proceeding in the opposite direction, may encode the ORFI peptide.

Amino Acid Sequence

Operations for atrial fibrillation.

Atrial fibrillation is the most common of all sustained cardiac arrhythmias, yet it has no effective medical or surgical therapy. During the past decade, multipoint computerized electrophysiological mapping systems were used to map both experimental and human atrial fibrillation. On the basis of these studies, a new surgical procedure was developed for atrial fibrillation. Between September 25, 1987, and May 1, 1991, this procedure was applied in 22 patients with either paroxysmal atrial flutter (n = 2), paroxysmal atrial fibrillation (n = 11), or chronic atrial fibrillation (n = 9) of 2 to 21 years' duration. All patients were refractory to all antiarrhythmic medications and each patient failed an average of 5.2 drugs preoperatively. There were no operative deaths and all perioperative morbidity resolved. All 22 patients have been cured of atrial fibrillation with surgery alone. One late isolated episode of atrial flutter occurred in a patient who is now receiving encainide. Preservation of atrial transport function has been documented in all of the patients postoperatively and all have experienced marked clinical improvement.

Adult

Left ventricular outflow obstruction resulting from insertion of mitral prostheses leaving the native leaflets intact: adverse clinical outcome in seven patients.

Left ventricular (LV) outflow obstruction may result from retaining the anterior mitral leaflet when a mitral prosthesis is inserted in the mitral anulus. We retrospectively reviewed the echocardiograms (two-dimensional Doppler and Doppler color flow imaging, or transesophageal with color flow imaging) obtained in seven patients with preoperative mitral regurgitation who had a prosthesis implanted with the native mitral leaflets left intact. Systolic anterior motion of the native anterior mitral leaflet, as seen in dynamic LV outflow tract obstruction, was observed in six of seven patients. LV fractional shortening preoperatively was less than or equal to 0.25 in all (mean 0.20 +/- 0.04) and did not significantly (p = ns) increase postoperatively (mean 0.27 +/- 0.12). Color flow imaging revealed disturbed systolic flow in the LV outflow tract in five patients, and all had systolic anterior motion of the native anterior mitral leaflet. Continuous wave Doppler detected significant systolic LV outflow tract jets in five patients averaging 4.1 +/- 0.9 m/sec. Mitral prosthetic function was normal (pressure half-time of 81 +/- 25 msec and mean gradient of 7 +/- 3 mm Hg +/- SD) in five patients. Clinical follow-up revealed that all had died, six of them within 2 months of their operation. Thus systolic anterior motion of the native anterior mitral leaflet occurs commonly after prosthetic mitral valve insertion with the native leaflets left intact. Continuous wave Doppler often demonstrates increased systolic LV outflow tract velocities consistent with dynamic LV outflow obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged