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Biomedical subjects

R A Falcone

Publications and source records attributed to R A Falcone.

At least 37 records · Page 2Linked to original sources

Intestinal adaptation and enterocyte apoptosis following small bowel resection is p53 independent.

Adaptation following small bowel resection (SBR) signals enterocyte proliferation and apoptosis. Because p53-induced p21(waf1/cip1) may be important for apoptosis in many cells, we hypothesized that these genes are required for increased enterocyte apoptosis during adaptation. Male C57BL/6 (wild-type) or p53-null mice underwent 50% proximal SBR or sham operation (bowel transection-reanastomosis). Adaptation (DNA-protein content, villus height-crypt depth, enterocyte proliferation), appearance of apoptotic bodies, and p53 and p21(waf1/cip1) protein expression were measured in the ileum after 5 days. Adaptation was equivalent after SBR in both wild-type and p53-null mice as monitored by significantly increased ileal DNA-protein content, villus height, and enterocyte proliferation. The number of crypt apoptotic bodies increased significantly after SBR evenly in both wild-type and p53-null mice. In the p53-null mice, SBR substantially induced the expression of p21(waf1/cip1) protein in villus enterocytes. The p53-independent induction of p21(waf1/cip1) may account for the similar intestinal response to SBR between wild-type and p53-null mice. Intestinal adaptation and increased enterocyte apoptosis following intestinal resection occur via a p53-independent mechanism.

Adaptation, Physiological↗

Zone I retroperitoneal hematoma identified by computed tomography scan as an indicator of significant abdominal injury.

OBJECTIVE: All zone I retroperitoneal hematomas (Z1RPHs) identified at laparotomy for blunt trauma traditionally require exploration. The purpose of this study was to correlate patient outcome after blunt abdominal trauma with the presence of Z1RPH diagnosed on admission computed tomography (CT) scan. METHODS: This is a retrospective review of patients with blunt trauma who were admitted to a Level 1 trauma center and who underwent CT scan during a 40-month period. All scans with a traumatic injury were reviewed to identify and grade Z1RPH as mild, moderate, or severe. Patients requiring operative treatment were compared with those who were observed. Statistical analysis was performed with Student's t test and chi-square test, with P < .05 considered significant. RESULTS: Eighty-five (15.5%) of the CT scans were positive for Z1RPH. None of the 50 patients with a mild Z1RPH had their treatment altered. Of the 29 patients with a moderate or severe Z1RPH, 8 required celiotomy. The patients requiring celiotomy had significant elevations of solid viscus score (SVS) (4.9 +/- 1.6 versus 1.8 +/- 0.3), abdominal Abbreviated Injury Scale (3.8 +/- 0.3 versus 2.6 +/- 0.3), and transfusion requirements (13 +/- 4 versus 2 +/- 1). All patients (N = 4) with an SVS >4 required operative treatment. Seventy-two percent of patients with more than 1 intra-abdominal injury required abdominal exploration. CONCLUSIONS: The presence of a moderate or severe Z1RPH and more than 1 intra-abdominal injury or an SVS >4 on admission CT scan is an important radiographic finding. This injury pattern should be considered a contraindication for nonoperative treatment of the associated solid organ injury.

Abdominal Injuries↗

Epidermal growth factor augments adaptation following small bowel resection: optimal dosage, route, and timing of administration.

BACKGROUND: In assorted animal models of small bowel resection (SBR), exogenous epidermal growth factor (EGF) has been shown to augment intestinal adaptation. This study was designed to elucidate the optimal dose, route, and timing of exogenous EGF to boost adaptation in our murine model of SBR. METHODS: Male ICR mice underwent either 50% proximal SBR or sham surgery (bowel transection with reanastomosis) and then randomized to receive either saline or human recombinant EGF (5, 50, 150, or 300 microg/kg/day) by twice daily intraperitoneal (i.p.) injection or orogastric gavage (o.g.). At 7 days, protein and DNA content, crypt depth, and villus height were determined in the ileum. The premium dose and route was then given for 1 week either during (1 week after SBR) or after the adaptive phase (1 month after SBR). Differences between group means were analyzed using ANOVA. A P < 0.05 was considered significant. RESULTS: EGF enhanced DNA and protein content, crypt depth, and villus height to the greatest extent at a dosage of 50 microg/kg/day by the o.g. route. EGF had no significant effect on enhancing adaptation when given after the adaptive response had already occurred. CONCLUSIONS: Intestinal adaptation is optimally enhanced by a specific dose and route of EGF. Exogenous EGF enhances adaptation only during the adaptive response to SBR and not after it has already taken place. Determination of the best circumstances for EGF administration will permit a systematic approach toward understanding a mechanism for the beneficial effect of EGF during intestinal adaptation.

Adaptation, Physiological↗

Transesophageal echocardiographic evaluation of left atrial appendage function and spontaneous contrast formation after chemical or electrical cardioversion of atrial fibrillation.

Changes in left atrial (LA) appendage pulsed-wave Doppler velocities and changes in grades of spontaneous contrast occur immediately after electrical cardioversion of atrial fibrillation (AF) using transesophageal echocardiography (TEE). The effect of sequential ineffective electrical cardioversion attempts or chemical cardioversion on these parameters is unknown. TEE was performed in 23 patients with chronic AF. Doppler velocities and grades of spontaneous contrast were assessed before and after each cardioversion attempt until sinus rhythm was achieved. Doppler emptying and filling velocities were significantly decreased after electrical (0.39 +/- 0.14 vs 0.27 +/- 0.16 [p = 0.01] and 0.43 +/- 0. 18 vs 0.30 +/- 0.14 m/s [p = 0.01]) or chemical cardioversion to sinus rhythm (0.65 +/- 0.18 vs 0.31 +/- 0.06 [p = 0.03] and 0.64 +/- 0.22 vs 0.44 +/- 0.17 m/s [p = 0.04]). Spontaneous contrast developed in 1 of 3 patients after chemical conversion to sinus rhythm and was present in 11 of 20 patients before electrical cardioversion, developing in 4 patients and intensifying in 2 patients immediately after successful cardioversion. These phenomena were not seen after ineffective electrical or chemical cardioversion attempts. This suggests that restoration of sinus rhythm is in itself responsible for these phenomena, not the method by which sinus rhythm is achieved.

Aged↗

Intravenous albunex during dobutamine stress echocardiography: enhanced localization of left ventricular endocardial borders.

Albunex is an intravenous contrast agent that opacifies the left ventricle (LV). This study evaluated the effect of Albunex on the enhancement of LV endocardial border localization during dobutamine stress echocardiography (DSE). Albunex was infused in 30 patients at baseline and with low- and high-dosage dobutamine. Apical two- and four-chamber views were divided into six segments each, and enhancement of LV border localization was compared with precontrast images graded as follows: 0 = none; 1 = faint; or 2 = optimal. The mean grade and percentage of segments with optimal localization of LV endocardial borders were determined. There was a significant increase in enhancement with low- and high-dosage dobutamine when compared with baseline. Of 179 segments with suboptimal enhancement at baseline, 137 (77%) became optimal during DSE with Albunex. We conclude that Albunex improves localization of LV endocardial borders and that this localization is enhanced during DSE.

Aged↗

Alterations in the initial portion of the signal-averaged QRS complex in acute myocardial infarction with ventricular tachycardia.

This study was designed to examine 2 hypotheses: that acute myocardial infarction (AMI) alters early cardiac activation measured by signal-averaging; and that the magnitude of abnormality of early activation may be greater in patients with post-AMI ventricular tachycardia (VT). We examined the root-mean square voltage amplitude in 10-ms intervals over the first 80-ms of the signal-averaged QRS complex. Data from 42 healthy volunteers were compared with those from 52 patients with previous AMI (24 anterior) but no VT and 46 post-AMI patients (33 anterior AMI) with recurrent sustained VT. Patients with VT differed from other post-AMI patients because of lower left ventricular ejection fraction, more frequent aneurysm formation and higher levels of ventricular ectopic activity. A significant decrease in initial voltage amplitude occurred at 30 to 40 ms after the beginning of the QRS in both anterior and inferior AMI patients compared with the normal group. A further significant decrease in initial amplitude occurred in VT patients both after anterior and inferior AMI. These differences persisted for the remainder of the 80-ms interval. These changes were weakly related to QRS duration (r = 0.45), ejection fraction (r = 0.50) and poorly correlated with the presence of Q waves on 12-lead electrocardiogram (r = 0.21). Direct endocardial catheter recordings performed in VT patients confirmed abnormalities of local septal activation after anterior and inferior AMI.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Results of signal-averaged electrocardiography and electrophysiologic study in patients with nonsustained ventricular tachycardia after healing of acute myocardial infarction.

Programmed stimulation and signal-averaged electrocardiography were performed in 43 consecutive patients with nonsustained ventricular tachycardia (VT) after healing of inferior (29 patients) or anterior wall (14 patients) acute myocardial infarction. Twenty-two patients had inducible sustained VT. Patients with inferior infarction and inducible sustained VT had significantly longer filtered QRS durations (125 +/- 19 vs 112 +/- 15 ms, p less than 0.01) and significantly lower voltage in the last 40 ms of the filtered QRS complex (19 +/- 5 vs 30 +/- 14 microV, p less than 0.05) than those without inducible sustained VT. In contrast, the signal-averaged electrocardiographic measurements in patients with anterior infarction and inducible sustained VT did not differ significantly from those without inducible sustained VT. The results of these studies were compared with those of 2 control groups: 45 patients without ventricular arrhythmias after myocardial infarction and 95 patients with spontaneous and inducible sustained VT after myocardial infarction. The signal-averaged electrocardiographic measurements in patients with spontaneous nonsustained VT after inferior infarction were intermediate between the control group without arrhythmias and the control group with sustained VT. The signal-averaged electrocardiograms in patients with nonsustained VT after anterior infarction were not significantly different from those in patients without ventricular arrhythmias. The study shows that the site of infarction influences the signal-averaged electrocardiogram in patients with VT after myocardial infarction. The signal-averaged electrocardiogram may be useful in identifying patients with nonsustained VT after a remote inferior myocardial infarction who have inducible sustained VT.

Cardiac Pacing, Artificial↗

Anatomic and hemodynamic effects of catheter-delivered ablation energies in the ventricle.

Twenty dogs were studied to characterize the anatomic, hemodynamic and pathologic effects of catheter-delivered cardioversion (CDCV) in the left ventricle. Five dogs each received 1 CDCV of either 50, 100, 200 or 300 J at the left ventricular apex. The injury occurred at the posteroinferior apex. Structural integrity of the ventricle remained intact. Energy doses of 50 and 100 J resulted in focal subendomyocardial injury. Higher energy levels resulted in localized transmural injury. There was a linear dose-related correlation between the volume of injury and delivered energy. Electrocardiographic changes were seen immediately in all dogs. Fifteen dogs had acute, transient ventricular arrhythmias. One dog died with refractory arrhythmias. Minimal hemodynamic changes were associated with the CDCV. Unique histopathologic changes were observed. Thus, local tissue destruction can be produced with CDCV. The extent of injury is dose-related and is associated with minimum hemodynamic changes. The lesion may be acutely arrhythmogenic.

Animals↗

Electrophysiologic evaluation and follow-up characteristics of patients with recurrent unexplained syncope and presyncope.

One hundred nineteen patients with unexplained syncope (82%) or presyncope (18%) underwent complete electrophysiologic study (EPS). Symptoms were recurrent in 72% of the patients. Fifty-two percent of the patients had structural heart disease. Forty-one patients had normal EPS results and 78 had electrophysiologic abnormalities (ventricular tachycardia in 31, induced atrial flutter/fibrillation in 17, vasovagal syncope in 8, hypersensitive carotid sinus syndrome in 7, supraventricular tachycardia in 6, heart block in 5 and sick sinus syndrome in 4). The presence of structural heart disease (p = 0.0033) and previous myocardial infarction (p = 0.05) were the only clinical or electrocardiographic predictors of a positive EPS response. Therapy was guided by EPS and patients were followed for 27 +/- 20 months (mean +/- standard deviation). In the patients with negative EPS results, 76 +/- 11% (mean +/- standard error) were symptom-free at follow-up, compared to 68 +/- 10% in the group with positive EPS responses. No clinical variables helped to predict remission in the absence of therapy. One patient in the negative EPS response group and 2 patients in the EPS positive group died suddenly (cumulative survival 94 +/- 4%). Total cardiovascular mortality was 13% in the positive EPS response group, and 4% in the negative EPS response group. Thus, certain clinical characteristics are helpful in selecting patients for study. Electrophysiologically guided therapy is associated with a recurrence and sudden death rate similar to an untreated control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effects of infarction, procainamide, coupling interval, and cycle length on refractoriness of extrastimuli.

The effects of prematurity, cycle length, site of stimulation, and procainamide on ventricular refractoriness following an extrastimulus (S2) were assessed in 10 dogs with and 10 dogs without infarction. Extrastimuli were introduced at preselected coupling intervals (S1-S2) from normal right and left ventricular sites and from left ventricular sites of infarction during drive cycle lengths (S1-S1) of 350 and 250 ms. At each S1-S2 interval, the effective refractory period of S2 was determined by introducing a second extrastimulus (S3). At all stimulation sites, cycle lengths, and before and during infusion of procainamide (mean concn 18.6 +/- 3.5 micrograms/ml), shortening (greater than 10 ms change) in refractoriness was most marked over a narrow range of closely coupled S1-S2 intervals. Regardless of stimulation site, the effective refractory period of S2 was less during a cycle length of 250 ms compared with a cycle length of 350 ms. In dogs without infarction, the effective refractory periods of S2 from left ventricular sites tended to be longer than from right ventricular sites, particularly during procainamide administration. The refractory period of S2 at sites of infarction did not differ consistently from those at normal sites. Finally, at all stimulation sites and cycle lengths, procainamide prolonged refractoriness of S2 at each S1-S2 interval and blunted the total shortening in refractoriness in response to S2.

Animals↗

Abnormal signal-averaged electrocardiograms in patients with nonischemic congestive cardiomyopathy: relationship to sustained ventricular tachyarrhythmias.

We assessed whether signal-averaged electrocardiography could identify patients with sustained ventricular arrhythmias in 41 patients with non-ischemic cardiomyopathy. Twelve of these patients presented with sustained ventricular arrhythmia and 29 patients had no history of sustained ventricular arrhythmias. The mean ejection fractions in the groups were 30 +/- 9% and 24 +/- 9%, respectively. Results were compared with signal-averaged electrocardiograms in 55 normal individuals. The filtered QRS duration was longest in patients with sustained ventricular arrhythmias (130.2 +/- 19.5 vs 105.0 +/- 13.1 msec in the group without sustained ventricular arrhythmia, p less than .001 and 95.9 +/- 9.1 in the normal group, p less than .001). The voltage in the last 40 msec of the filtered QRS was lower in the sustained ventricular arrhythmia group (11.3 +/- 9.3 microV) than the group without sustained ventricular arrhythmia (53.5 +/- 28.3 microV; p less than .001) or the normal group (53.7 +/- 25.2 microV; p less than .001). Eighty-three percent of patients in the sustained ventricular arrhythmia group had an abnormal signal-averaged electrocardiogram characterized by both a long filtered QRS duration and a late potential of low voltage level; only 2% of normal subjects and 14% of patients without sustained ventricular arrhythmias had an abnormal signal-averaged electrocardiogram. The signal-averaged electrocardiogram can identify patients with nonischemic congestive cardiomyopathy and sustained ventricular arrhythmias.

Adult↗

Identification of patients with ventricular tachycardia after myocardial infarction: signal-averaged electrocardiogram, Holter monitoring, and cardiac catheterization.

Electrocardiographic signal averaging techniques have demonstrated a low-amplitude late potential and a long filtered QRS complex in patients with ventricular tachycardia (VT) after myocardial infarction. Complex ventricular ectopy and left ventricular aneurysms have also been associated with VT. The purposes of this study were (1) to determine whether the findings from the signal-averaged electrocardiogram (ECG) were independent of those from Holter monitoring and cardiac catheterization and (2) to determine the combination of findings from the signal-averaged ECG, cardiac catheterization, and Holter monitoring that best characterize patients with VT after myocardial infarction. We studied 174 patients after myocardial infarction, 98 of whom had recurrent sustained VT. By multivariate logistic regression only three parameters were found to be independently significant, listed in order of power: positive signal-averaged ECG (presence of a late potential or a long filtered QRS duration), peak premature ventricular contraction greater than 100/hr, and presence of a left ventricular aneurysm (p less than .001). The signal-averaged ECG provides independent information in identifying patients with VT after myocardial infarction.

Adolescent↗

Body surface late potentials: effects of endocardial resection in patients with ventricular tachycardia.

We studied 37 patients undergoing endocardial resection for medically refractory ventricular tachycardia (VT). Each was studied before and after surgery by programmed ventricular stimulation and signal-averaged electrocardiography. Low-amplitude late potentials were identified preoperatively in 76% of patients. In the 24 patients without postoperative VT the effect of surgery was to shorten the filtered QRS duration (137 +/- 27 to 121 +/- 26 msec; p = .003), increase the voltage in the last 40 msec of the filtered QRS (16.5 +/- 16.1 to 39.0 +/- 29.4 microV; p = .003), and decrease the incidence of late potentials (71% to 33%; p = .03). The filtered QRS complex was unchanged in 13 patients whose VT persisted after surgery. No preoperative variable predicted which patients would not have inducible VT after surgery. However, loss of a late potential after surgery in nine of 10 patients was associated with absence of inducible VT (p less than .02). Loss of a late potential was not necessary for surgical success. Eight of 18 patients with a persistent late potential did not have inducible VT. The signal-averaged electrocardiogram predicted a successful outcome after endocardial resection if the late potential was no longer present.

Cardiac Pacing, Artificial↗

Intraoperative endocardial mapping during sinus rhythm: relationship to site of origin of ventricular tachycardia.

Mapping-guided endocardial resection has proved to be an effective therapy for recurrent sustained ventricular tachycardia. However, some patients cannot be mapped during ventricular tachycardia, so that guidance from findings during normal sinus rhythm would be highly desirable. We examined the frequency, timing, and duration of several abnormal types of electrograms recorded endocardially during sinus rhythm and related these findings to activation mapping during sustained ventricular tachycardia. Thirteen patients with extensive myocardial infarction complicated by recurrent sustained ventricular tachycardia were studied intraoperatively during sinus rhythm and induced ventricular tachycardia with a standardized mapping scheme involving the entire endocardial surface. Fractionated electrograms (multicomponent with amplitude less than 1 mV and duration greater than 50 msec) were recorded in all patients. This type of electrogram could be recorded at up to 36% of mapped sites. Split electrograms (two components separated by isoelectric period) were also frequently seen but involved only a mean of 5.8% of mapped sites. Late electrograms (inscribed entirely after the QRS complex) were only recorded in four of 13 patients at a mean of 5% of mapped sites. The location of these electrograms was related to an arbitrary 8 cm2 zone around the earliest site of endocardial activation recorded during ventricular tachycardia. The longest fractionated electrogram was closely related to nine of 22 morphologies of induced ventricular tachycardia, split electrograms were related to seven of 16 morphologies, and late electrograms to two of four morphologies. We have concluded that extremely abnormal electrograms recorded endocardially during sinus rhythm are widespread in patients with extensive myocardial infarction complicated by ventricular tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

Relation between late potentials on the body surface and directly recorded fragmented electrograms in patients with ventricular tachycardia.

The relation between low-amplitude, late potentials on the body surface and directly recorded electrograms in 8 patients with and 11 patients without ventricular tachycardia (VT) was studied. Bipolar X,Y,Z leads were signal-averaged and filtered with a digital technique. All patients had catheter endocardial left ventricular maps. The VT group had medically intractable VT and an endocardial excision was performed for control of VT. Before bypass, epicardial maps were obtained in the operating room. All studies were performed during normal sinus rhythm. Four patients without VT, each with a previous myocardial infarction, had fragmented endocardial electrograms recorded at 2.0 +/- 1.2 sites. The latest electrogram for each patient ended 87 +/- 8 ms after QRS onset, within the high-amplitude portion of the filtered QRS complex. All patients with VT had fragmented electrograms recorded at 6.1 +/- 3.1 sites/patient. Eighty-eight percent of the fragmented electrograms were endocardial. The latest fragmented electrogram for each patient ended 161 +/- 43 ms after QRS onset, significantly later than the fragmented electrograms from the patients without VT (p = 0.002). Six VT patients had low-amplitude, late potentials at the end of the filtered QRS complex. In these patients, the last 40 ms of the filtered QRS complex contained a higher proportion of fragmented electrograms compared with earlier segments of the QRS complex (68% versus 27%, p less than 0.001). Two patients with VT did not have late potentials. One patient with left bundle branch block had delayed left ventricular epicardial activation which masked the fragmented electrograms. The other had fragmented electrograms of brief duration which ended 80 +/- 12 ms after QRS onset, during the time of normal ventricular activation. It is concluded that the late potential corresponds to delayed, fragmented electrographic activity. Failure to record a late potential may arise from delayed ventricular activation at other sites from bundle branch block or fragmented electrograms of a brief duration.

Adolescent↗

The incidence and clinical significance of epicardial late potentials in patients with recurrent sustained ventricular tachycardia and coronary artery disease.

Seventy-eight patients with ventricular tachycardia associated with coronary artery disease underwent intraoperative mapping while in sinus rhythm to evaluate the frequency and significant of late potentials. In 30 of these patients, the surface ECG was subjected to signal averaging to correlate the incidence and duration of low-amplitude, delayed electrograms with the presence of late potentials recorded during epicardial mapping. One to four epicardial late potentials were observed in nine patients (11.5%). These nine patients did not differ hemodynamically from patients without late potentials. In four patients, the site of epicardial breakthrough during ventricular tachycardia bore no relationship (i.e., greater than 3 cm away) to the late potential or the site of origin of the tachycardia. In the five other patients with late potentials, epicardial breakthrough and site of origin of ventricular tachycardia were closely related to the free wall of an apical aneurysm. However, three of these patients had additional tachycardias from disparate sites. Twenty-seven of 30 patients in whom signal averaging was used had a low-amplitude signal in the terminal 40 msec of the amplified QRS complex. In 24 of these 27 patients (89%), the low-amplitude tail was demonstrated in the absence of epicardial late potentials. We conclude that epicardial late potentials are found infrequently in patients with ventricular tachycardia associated with coronary artery disease; epicardial late potentials cannot be used to localize ventricular tachycardia; and the specific low-amplitude tail on the signal-averaged electrogram is unrelated to epicardial events.

Adult↗