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Biomedical subjects

L Harris

Publications and source records attributed to L Harris.

At least 37 records · Page 2Linked to original sources

Plasma D-dimer levels in operable breast cancer patients correlate with clinical stage and axillary lymph node status.

PURPOSE: To investigate the relationship between preoperative plasma D-dimer levels and extent of tumor involvement in operable breast cancer patients. PATIENTS AND METHODS: A total of 140 preoperative plasma specimens were obtained from women scheduled to undergo diagnostic breast biopsies. Ninety-five patients in the initial group went on to undergo axillary lymph node dissection. Of the 140 patients from whom plasma samples were obtained, 102 were subsequently diagnosed with invasive breast carcinoma, nine were subsequently diagnosed with ductal carcinoma-in-situ, and 20 were subsequently diagnosed with benign breast disease. Plasma D-dimer levels were quantitated using a commercially available immunoassay kit (DIMERTEST; American Diagnostica, Greenwich, CT). The relationships between plasma D-dimer and other prognostic variables (tumor size, estrogen receptor, progesterone receptor, nuclear grade, histologic grade, lymphovascular invasion, and clinical stage grouping) were then examined using univariate and multivariate linear and logistic regression analyses. RESULTS: Median plasma D-dimer levels were significantly higher in patients with invasive carcinoma than those patients with either benign breast disease or carcinoma-in-situ (P =.0001). A significant relationship existed between the presence of elevated D-dimer (> 100 ng/mL) and involved axillary lymph nodes (chi(2) test; P =.001). Elevated D-dimer levels predicted positive lymph node involvement in both univariate regression (P =.0035) and multivariate linear regression (P =.012) models. In addition, elevated D-dimer levels predicted the presence of lymphovascular invasion in univariate logistic regression (P =. 0025) and multivariate logistic regression analysis (P =.0053). Quantitative D-dimer levels were highly correlated with clinical stage grouping (analysis of variance test; P =.002). CONCLUSION: Plasma D-dimer levels were markers of lymphovascular invasion, clinical stage, and lymph node involvement in operable breast cancer. This correlation suggests that detectable fibrin degradation, as measured by plasma D-dimer, is a clinically important marker for lymphovascular invasion and early tumor metastasis in operable breast cancer.

Adult↗

Tissue disposition and pharmacokinetics of recombinant human nerve growth factor after acute and chronic subcutaneous administration in monkeys.

In this study, we have characterized the metabolism, tissue disposition, excretion routes, and plasma pharmacokinetics of recombinant human nerve growth factor after single and multiple s.c. administration in male cynomolgus monkeys. Unlabeled nerve growth factor (NGF; 2 mg/kg) was administered three times a week for 4 weeks and a full pharmacokinetic profile was obtained for doses 1 and 12. For the tissue distribution studies, 0.8 microg/kg of trace (125)I-labeled recombinant human nerve growth factor was dosed. Histological analysis of emulsion-microautoradiography indicated that specific (125)I-NGF labeling was confined to sections of nerves most frequently localized adjacent to large vessels in sections of kidney, spleen, liver, and salivary gland. A small percentage of large neurons within the sympathetic ganglia were intensely labeled, as well as large neurons within the dorsal root ganglia. We found an increased disposition of (125)I-NGF in parts of the peripheral nervous system (including sympathetic ganglia) from 8 to 24 h postdose. In contrast, radioactivity in most non-neuronal tissues declined. This suggests specific uptake in these target tissues known to express specific receptors for NGF. We also identified changes in pharmacokinetic parameters after single versus chronic s. c. administration. These studies demonstrated that s.c. administration of NGF at 0.8 microg/kg doses in monkeys is capable of accessing and localizing in the target tissues.

Animals↗

Arrhythmia and survival in patients >18 years of age after the mustard procedure for complete transposition of the great arteries.

Increasing numbers of patients who underwent Mustard repair as children are now adults. Loss of sinus rhythm, supraventricular arrhythmias, and sudden death have been described in pediatric series. However, little is known about the clinical course of adult patients. This retrospective cohort study examined 86 consecutive adults (age >18 years) who had undergone the Mustard procedure and were referred to an adult congenital cardiac clinic for ongoing follow-up. The incidence and predictors of arrhythmia, congestive heart failure, and death were determined. The median follow-up period was 8 years after age 18 or 23 years after Mustard repair. There were 8 deaths (9%), 2 were sudden. Congestive heart failure (CHF) requiring hospital admission occurred in 9 patients (10%). Pulmonary hypertension and systemic ventricular dysfunction were independent risk factors for death or CHF. Only 29 patients (34%) remained arrhythmia-free. Forty-one patients (48%) had at least 1 episode of supraventricular tachycardia (SVT), with most patients (30, 73%) having atrial flutter. SVT after the age of 18 was associated with CHF. Pulmonary hypertension, systemic ventricular dysfunction, and junctional rhythm before age 18 were independent risk factors for SVT. Pacemakers were implanted in 19 patients (22%); 13 of those were beyond age 18. Thus, adult survivors of the Mustard procedure continue to be at risk for premature death, CHF and supraventricular tachyarrhythmia.

Adolescent↗

Atrial arrhythmia after surgical closure of atrial septal defects in adults.

BACKGROUND: Atrial flutter and atrial fibrillation are causes of morbidity in adults with an atrial septal defect. In this study, we attempted to identify risk factors for atrial flutter and fibrillation both before and after the surgical closure of an atrial septal defect. METHODS: We searched for preoperative and postoperative atrial flutter or fibrillation in 213 adult patients (82 men and 131 women) who underwent surgical closure of atrial septal defects because of symptoms, a substantial left-to-right shunt (ratio of pulmonary to systemic blood flow, >1.5:1), or both at Toronto Hospital between 1986 and 1997. RESULTS: Forty patients (19 percent) had sustained atrial flutter or fibrillation before surgery. As compared with the patients who did not have atrial flutter or fibrillation before surgery, those who did were older (59+/-11 vs. 37+/-13 years, P<0.001) and had higher mean pulmonary arterial pressures (25.0+/-9.7 vs. 19.7+/-8.2 mm Hg, P=0.001). There were no perioperative deaths. After a mean follow-up period of 3.8+/-2.5 years, 24 of the 40 patients (60 percent) continued to have atrial flutter or fibrillation. The mean age of these patients was greater than that of the 16 who converted to sinus rhythm (P=0.02). New-onset atrial flutter or atrial fibrillation was more likely to have developed at follow-up in patients who were older than 40 years at the time of surgery than in those who were 40 or younger (5 of 67 vs. 0 of 106, P=0.008). Late events (those occurring more than one month after surgery) included stroke in six patients (all but one with atrial flutter or fibrillation, one of whom died) and death from noncardiac causes in two patients. Multivariate analysis showed that older age (>40 years) at the time of surgery (P=0.001), the presence of preoperative atrial flutter or fibrillation (P<0.001), and the presence of postoperative atrial flutter or fibrillation or junctional rhythm (P=0.02) were predictive of late postoperative atrial flutter or fibrillation. CONCLUSIONS: The risk of atrial flutter or atrial fibrillation in adults with atrial septal defects is related to the age at the time of surgical repair and the pulmonary arterial pressure. To reduce the morbidity associated with atrial flutter and fibrillation, the timely closure of atrial septal defects is warranted.

Adolescent↗

Outcome of previous tricuspid valve operation and arrhythmias in adult patients with congenital heart disease.

BACKGROUND: Tricuspid valve operation or replacement has been associated with high perioperative mortality and poor long-term results. The prevalence of atrial arrhythmias before and after operation in these patients is undefined. METHODS: We retrospectively examined the outcome and frequency of atrial arrhythmias in 85 adult patients (46% men) with congenital heart defects who underwent tricuspid valve operation between 1961 and 1995. RESULTS: The majority had either Ebstein's anomaly (22%), congenitally corrected transposition (19%), tetralogy of Fallot (15%), atrial (13%), or ventricular (11%) septal defects. Forty-two (49%) patients had sustained arrhythmias within 1 year before operation. After tricuspid valve operation, 21 patients (50%) had recurrence of atrial arrhythmias, and 7 in preoperative sinus rhythm developed late rhythm disturbances. Multivariate analysis identified age at operation and preoperative arrhythmias as independent predictors of late arrhythmias. Perioperative mortality was 5%, and there were seven late deaths. Survival was 91% at 5 years, and 83% at 10 years. CONCLUSIONS: Surgical intervention does not prevent recurrence of atrial arrhythmias. Tricuspid valve operation in patients with congenital heart disease can be performed with a low risk of perioperative mortality and good long-term outcome.

Adolescent↗

Reoperation in adults with repair of tetralogy of fallot: indications and outcomes.

OBJECTIVE: The purpose of this study is to review indications, surgical procedures, and outcomes in adults with repaired tetralogy of Fallot referred for reoperation. METHOD: Sixty consecutive adults (age >/= 18 years) who underwent reoperation between 1975 and 1997 after previous repair of tetralogy of Fallot were reviewed. Mean age at corrective repair was 13.3 +/- 9.6 years and at reoperation 33.3 +/- 9.6 years. Mean follow-up after reoperation is 5.0 +/- 4.9 years. RESULTS: Long-term complications of the right ventricular outflow tract (n = 45, 75%) were the most common indications for reoperation: severe pulmonary regurgitation (n = 23, 38%) and conduit failure (n = 13, 22%) were most frequent. Less common indications were ventricular septal patch leak (n = 6) and severe tricuspid regurgitation (n = 3). A history of sustained ventricular tachycardia was present in 20 patients (33%) and supraventricular tachycardia occurred in 9 patients (15%). A bioprosthetic valve to reconstruct the right ventricular outflow tract was used in 42 patients. Additional procedures (n = 115) to correct other residual lesions were required in 46 patients (77%). There was no perioperative mortality. Actuarial 10-year survival is 92% +/- 6%. At most recent follow-up, 93% of the patients are in New York Heart Association classification I or II. Sustained ventricular tachycardia occurred in 4 patients (7%) during follow-up. CONCLUSIONS: Long-term complications of the right ventricular outflow tract were the main reason for reoperation. Mid-term survival and functional improvement after reoperation are excellent.

Adolescent↗

Thoracoscopic repair of a recurrent diaphragmatic hernia four years after initial trauma, laparotomy, and repair.

Traumatic diaphragmatic hernia is not an uncommon problem and has been noted after either penetrating or blunt trauma. A high index of suspicion must be maintained in order to identify patients with this injury, as delay in identification may result in significant morbidity and death. It is essential that a thorough evaluation be performed, and if a diaphragmatic hernia is found, surgical repair is necessary. We present a case of thoracoscopic repair of an incarcerated recurrent diaphragmatic hernia appearing several years after successful open (via laparotomy) repair of an acute blunt traumatic hernia. A brief review of the surgical literature is also presented. With the broadening use of minimally invasive surgical techniques, we feel that their application to the repair of chronic diaphragmatic hernia is safe and effective, reduces morbidity, and results in a faster recovery.

Hernia, Diaphragmatic, Traumatic↗

Antiemetic prophylaxis does not improve outcomes after outpatient surgery when compared to symptomatic treatment.

BACKGROUND: Although prophylactic administration of antiemetics reduces the incidence of postoperative nausea, vomiting, or both (PONV), there is little evidence to suggest this improves patient outcomes. The authors hypothesized that early symptomatic treatment of PONV will result in outcomes, including time to discharge, unanticipated admission, patient satisfaction, and time to return to normal daily activities, that are similar to those achieved with routine prophylaxis. METHODS: Men and women (n = 575) scheduled for outpatient surgery during general anesthesia were randomized to receive either 4 mg intravenous ondansetron or placebo before operation and either 1 mg intravenous ondansetron or placebo if postoperative symptomatic treatment of PONV was necessary. Patients were stratified into subgroups by risk factors for PONV. RESULTS: No differences occurred in the time to discharge, rate of unanticipated admission, or time to return to normal activity between the prophylaxis and treatment groups. The reported level of satisfaction with control of PONV was 93% in the treatment arm and 97% in the prophylaxis arm, which fall within the limits defined a priori as clinically equivalent. Female patients with a history of motion sickness or PONV who were undergoing highly emetogenic procedures had a higher reported level of satisfaction with prophylaxis than with treatment (100% vs. 90%, P = 0.043); however, the level of satisfaction with the overall outpatient surgical experience was not different. CONCLUSION: Although PONV is unpleasant, the data indicate little difference in outcomes when routine prophylactic medications are administered versus simply treating PONV should symptoms occur.

Adolescent↗

Transient monocyte release of interleukin-10 in response to traumatic brain injury.

A significant component of the immune response to trauma results in the systemic presence of cytokines which have the potential to suppress the patient's immune response to infection and contribute to post-injury complications. We assayed peripheral blood leukocytes obtained from 10 patients with head trauma to determine their production of interleukin (IL). Serum was assayed for the presence of IL-10, TGFbeta1, and IFNgamma by ELISA. Peripheral blood leukocytes were screened for intracellular IL-10 and IFNgamma by fluorescence-activated flow cytometry, and cytokine-specific mRNA was detected by the polymerase chain reaction. We detected an immediate, but transient, presence of IL-10 in the sera of all 10 patients who suffered head trauma. IL-10-specific intracytoplasmic immunofluorescence was also detected immediately after injury in peripheral blood monocytes, but not in lymphocytes or granulocytes. IL-10-specific mRNA was detected in peripheral blood leukocytes in only 50% of patients immediately after injury, when the highest serum levels of IL-10 were observed. Our data indicates that release of pre-formed IL-10 by monocytes contributes to the presence of IL-10 found in patient peripheral blood immediately after head injury.

Adolescent↗

Safety and antitumor activity of recombinant soluble Apo2 ligand.

TNF and Fas ligand induce apoptosis in tumor cells; however, their severe toxicity toward normal tissues hampers their application to cancer therapy. Apo2 ligand (Apo2L, or TRAIL) is a related molecule that triggers tumor cell apoptosis. Apo2L mRNA is expressed in many tissues, suggesting that the ligand may be nontoxic to normal cells. To investigate Apo2L's therapeutic potential, we generated in bacteria a potently active soluble version of the native human protein. Several normal cell types were resistant in vitro to apoptosis induction by Apo2L. Repeated intravenous injections of Apo2L in nonhuman primates did not cause detectable toxicity to tissues and organs examined. Apo2L exerted cytostatic or cytotoxic effects in vitro on 32 of 39 cell lines from colon, lung, breast, kidney, brain, and skin cancer. Treatment of athymic mice with Apo2L shortly after tumor xenograft injection markedly reduced tumor incidence. Apo2L treatment of mice bearing solid tumors induced tumor cell apoptosis, suppressed tumor progression, and improved survival. Apo2L cooperated synergistically with the chemotherapeutic drugs 5-fluorouracil or CPT-11, causing substantial tumor regression or complete tumor ablation. Thus, Apo2L may have potent anticancer activity without significant toxicity toward normal tissues.

Animals↗

Pharmacokinetics of radiolabeled polyclonal antiferritin in patients with Hodgkin's disease.

The objective was to identify pharmacokinetic parameters predictive for tumor response and normal tissue side effects after i.v. administered radiolabeled rabbit antihuman ferritin IgG. Twenty-eight patients with recurrent Hodgkin's disease received 2 mg of rabbit antihuman ferritin i.v., labeled with 4-7 mCi of In-111 followed by two doses of 0.25, one dose of 0.3, or one dose of 0.4 mCi of Y-90-labeled antiferritin per kg of body weight 1 week later. Radioactivity and HPLC measurements of blood and urine samples and liver and tumor volumes identified on sequential whole-body scans provided the data for a pharmacokinetic analysis covering the first 6 days after the administration of the radioimmunoconjugate. Side effects and tumor response were recorded. Temporary hematological toxicity was noted in all patients. Sixteen patients showed a tumor response. The Y-90 blood level at 1 h after administration correlated with the severity of subsequent hematological toxicity. The rapid blood elimination half-life of radioactivity was 4.4 h. Less than 5% of the administered radioactivity was eliminated in the first 24 h urine. The slow blood elimination half-life was 44 and 37 h for In-111 and Y-90, respectively. One of 12 retreated patients produced anti-rabbit IgG antibodies. The volume of distribution was larger for Y-90 than for In-111-labeled antiferritin (160 versus 110% of estimated blood volume). Accidentally extravasated rabbit IgG was rapidly catabolized in perivascular tissues with an effective half-life of less than 35 h. Slower catabolism was noted for rabbit IgG in blood (t(1/2) = 40 h), liver (t(1/2) = 62 h) or tumor (t(1/2) = 40-80 h). Twelve of 13 patients with an effective tumor half-life > 57 h showed a tumor response. I.v. administered polyclonal rabbit antihuman ferritin, labeled with In-111 or Y-90 is stable in vivo and targets Hodgkin's disease. Intravascular Y-90 causes a vascular leak and a larger volume of distribution for antiferritin. Elevated Y-90 blood levels at 1 h and a tumor half-life of >57 h predict for hematological toxicity and tumor response, respectively.

Adult↗

Fractionated radiolabeled antiferritin therapy for patients with recurrent Hodgkin's disease.

The objective of this study was to determine the therapeutic ratio of fractionated radiolabeled immunoglobulin therapy (RIT) for patients with recurrent Hodgkin's disease. Ninety patients with recurrent Hodgkin's disease received 2 mg of yttrium-90-labeled polyclonal rabbit antihuman ferritin IgG i.v. Fifty-seven patients received a single (unfractionated) administration per treatment cycle; 11 of them were treated with 0.3 mCi/kg body weight, 39 were treated with 0.4 mCi/kg body weight, and 7 received 0.5 mCi/kg body weight per treatment cycle. Thirty-three patients had their radiolabeled immunoglobulin administration separated (fractionated) in 2 x 0.25 mCi/kg body weight (total activity, 0.5 mCi/kg). The interval between fractions was 1 week. Radioimmunoconjugates did not cause serious acute side effects. In vivo radioimmunoconjugates were stable. Human antirabbit IgG antibodies were found in 2 of 50 retreated patients (<5%). Hematological toxicity was the only side effect noted in all patients, and it was usually temporary. Response rates (RRs) were 20%, 61%, and 86% after 0.3, 0.4, or 0.5 mCi/kg unfractionated yttrium-90-labeled antiferritin. The RR for patients treated with fractionated RIT was 42%. In the fractionated RIT group, complete responses were decreased, and progressive disease increased (P < 0.05). Complete responses had a medium duration of 6 months. Median survival times were 390 days for 1 x 0.4 mCi/kg and 300 days for the 2 x 0.25 mCi/kg patient group. Fractionation did not provide the expected decrease in hematological toxicity or the expected increase in tumor RRs.

Adolescent↗

Characteristics of local electrograms with diastolic potentials: identification of different components of return pathways in ventricular tachycardia.

BACKGROUND: Diastolic potentials are often sought as a possible site for catheter ablation in post-infarct ventricular tachycardia. However, delivery of energy at such sites is often unsuccessful. The purpose of this study was to determine the characteristics of local electrograms with diastolic potentials and to identify activation pattern which might indicate the critical portion of the return path of the ventricular tachycardia reentry circuit. METHODS: In 17 patients with post-myocardial infarction ventricular tachycardia, 30 ventricular tachycardias were mapped with an 112 bipolar endocardial balloon at the time of surgery. Diastolic mapping of the return tract in ventricular tachycardia was performed. Four activation patterns were observed (15 figure 8 patterns, 2 circular patterns, 2 biregional patterns and 11 monoregional patterns). Of 3,360 local electrograms, 207 (6.2%) demonstrated a diastolic potential in ventricular tachycardia. They were classified into following four categories, based on the appearance and timing of the systolic component. Type A-1 electrogram: systolic activation was of low amplitude (< 2 mV) and was prolonged (> or = 100 msec), but preceded the onset of the surface QRS in ventricular tachycardia. Type A-2 electrogram: systolic activation was of low amplitude, was prolonged, but followed the onset of the surface QRS. Type B electrogram: systolic electrogram was fractionated, but relatively normal amplitude (2.0-3.6 mV). Type C electrogram: systolic electrogram was almost normal. RESULTS: Of all electrograms with diastolic potentials, three type A-1 electrograms (1.4%) were located at the exit of the return pathway, 11 type A-1 electrograms (5.3%) were located at the pre-exit site. No type A-1 was found at an entrance/bystander area. 21 type A-2 electrograms (10.1%) were at the pre-exit and 83 type A-2 electrograms (40.2%) were located at the entrance/bystander area, but such electrograms were never found at the exit site. 71 type B electrograms (34.3%) and 18 type C electrograms (8.7%) were located at the entrance/bystander area. To distinguish the type A-2 electrograms at the pre-exit site from those at the entrance/bystander area, the diastolic potential to QRS interval was measured. This interval at the pre-exit was significantly shorter than that at the entrance/bystander area (-47.2 +/- 10.7 vs -96.3 +/- 31.3 msec, p = 0.0001). CONCLUSION: Type A-1 electrograms indicated the exit or pre-exit site of return pathway. Type A-2 electrograms with diastolic potential to QRS interval < -50 msec indicated the pre-exit site. However, the other types of local electrograms with diastolic potential did not indicate the critical portion of the ventricular tachycardia circuit. These observations may be helpful during catheter mapping and ablation of patients with post-infarct ventricular tachycardia. CONDENSED ABSTRACT: Diastolic potentials are often sought to direct catheter ablation in post-infarct ventricular tachycardia. We investigated the characteristics of local electrograms showing diastolic activity in an attempt to determine whether critical portions of the ventricular tachycardia circuit could be identified by a typical "signature." In 17 patients with a remote myocardial infarction, 30 ventricular tachycardias were mapped with 112 bipolar endocardial balloon at the time of surgery. Diastolic potentials in association with low amplitude (< 2 mV) and prolonged (> or = 100 msec) systolic electrograms preceding the onset of QRS were found at the exit site and pre-exit site of return pathway. A similar systolic electrogram occurring after QRS onset with a diastolic potential to QRS interval of < -50 msec was found at the pre-exit site. However, other local electrograms with diastolic activity were at sites remote from the exit or pre-exit of the return pathway. These observations may be helpful during catheter mapping and ablation in patients with ventricular tachycardia.

Body Surface Potential Mapping↗

Rheumatic fever in the Kimberley region of Western Australia.

The objective of this study was to assess the incidence and clinical presentation of acute rheumatic fever in children and young adults in the north west of Western Australia--a region known as the Kimberley. In this five year retrospective study, residents aged less than 30 years, suspected of having had acute rheumatic fever from 1988 to 1992, were identified and their hospital and clinic records were reviewed. There were 96 cases of acute rheumatic fever that met the revised Jones criteria during the five year period. There were 59 initial attacks and 37 recurrences that occurred in 81 people, of whom 80 were of Aboriginal descent. The overall incidence of acute rheumatic fever in the Kimberley region for those aged under 30 years is 136 cases per 100,000 per year and in the Aboriginal population is 241 per 100,000 per year. The group most at risk are Aboriginal school children aged 5-14 years who accounted for 50 cases and have an annual incidence of 375 cases per 100,000 per year. The clinical presenting features were carditis in 50 per cent, polyarthritis in 59 per cent, chorea in 22 per cent, and subcutaneous nodules in 1 per cent. The hospitalization rate was 80 per cent for new cases and 73 per cent for recurrences with average stays of 14.6 and 1.5 days respectively. Rheumatic heart disease (RMD) developed in 31 of the cases; two required surgery and there was one death attributable to RHD in this group. Rheumatic fever continues to be a significant health problem in the Aboriginal population in this region and the recurrence rate, despite secondary prophylaxis, is also unacceptably high.

Acute Disease↗

Sustained ventricular tachycardia in adult patients late after repair of tetralogy of Fallot.

OBJECTIVES: We sought to determine the features associated with sustained monoform ventricular tachycardia (VT) in adult patients late after repair of tetralogy of Fallot (TOF) and to review their management. BACKGROUND: Patients with repair of TOF are at risk for sudden death. Risk factors for ventricular arrhythmia have been identified from patients with ventricular ectopic beats because of the low prevalence of sustained VT. METHODS: From a retrospective chart review of patients assessed between January 1990 and December 1994, 18 adult patients with VT were identified and compared with 192 with repaired TOF free of sustained arrhythmia. RESULTS: There was no significant difference in age at repair, age at follow-up or operative history. Patients with VT had frequent ventricular ectopic beats (6 of 9 vs. 21 of 101), low cardiac index ([mean +/- SD] 2.4 +/- 0.4 vs. 3.0 +/- 0.8) and more structural abnormalities of the right ventricle (outflow tract aneurysms and pulmonary or tricuspid regurgitation) than control patients. Electrophysiologic map-guided operation was performed in 10 of 14 patients who required reoperation. VT has reoccurred in three of these patients. Four patients did not undergo operation (three received amiodarone; one underwent defibrillator implantation). Two patients with VT also had severe heart failure and died. CONCLUSIONS: Most patients with VT late after repair of TOF have outflow tract aneurysms or pulmonary regurgitation, or both. These patients have a greater frequency of ventricular ectopic beats than arrhythmia-free patients after repair of TOF. A combined approach of correcting significant structural abnormalities (pulmonary valve replacement or right ventricular aneurysmectomy, or both) with intraoperative electrophysiologic-guided ablation may reduce the potential risk of deterioration in ventricular function and enable arrhythmia management to be optimized.

Adult↗

Sequence specificity and biochemical characterization of the RusA Holliday junction resolvase of Escherichia coli.

The RusA protein of Escherichia coli is an endonuclease that resolves Holliday intermediates in recombination and DNA repair. Analysis of its subunit structure revealed that the native protein is a dimer. Its resolution activity was investigated using synthetic X-junctions with homologous cores. Resolution occurs by dual strand incision predominantly 5' of CC dinucleotides located symmetrically. A junction lacking homology is not resolved. The efficiency of resolution is related inversely to the number of base pairs in the homologous core, which suggests that branch migration is rate-limiting. Inhibition of resolution at high ratios of protein to DNA suggests that binding of RusA may immobilize the junction point at non-cleavable sites. Resolution is stimulated by alkaline pH and by Mn2+. The protein is unstable in the absence of substrate DNA and loses approximately 80% of its activity within 1 min under standard reaction conditions. DNA binding stabilizes the activity. Junction resolution is inhibited in the presence of RuvA. This observation probably explains why RusA is unable to promote efficient recombination and DNA repair in ruvA+ strains unless it is expressed at a high level.

Base Composition↗