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Biomedical subjects

J E Lowe

Publications and source records attributed to J E Lowe.

At least 91 records · Page 5Linked to original sources

Determinants of reoperation after 960 valve replacements with Carpentier-Edwards prostheses.

During the period of 1977 to 1990, 960 Carpentier-Edwards standard prostheses (Baxter Healthcare Corp., Santa Ana, Calif.) were placed in 875 operations. Freedom from reoperation at 10 years was 57% +/- 4%, 76% +/- 3%, and 95% +/- 5% for mitral, aortic, and tricuspid valve replacement, respectively. Age was the only independent determinant of reoperation for both aortic and mitral valves. Likelihood of reoperation decreased with age, with freedom from reoperation after 10 years in patients aged less than 60 years versus 60 or more years being 65% +/- 5% versus 90% +/- 4% after aortic valve replacement and 48% +/- 5% versus 75% +/- 6% after mitral valve replacement. For mitral valve replacement, larger valve size made reoperation more likely, with freedom from reoperation at 10 years being 71% +/- 6% for sizes median less than 31 mm and 57% +/- 5% for sizes 31 mm or larger. For aortic valve replacement, prior median sternotomy reduced freedom from reoperation at 10 years from 80% +/- 3% to 25% +/- 5%. The low prevalence of reoperation affirms the suitability of the Carpentier-Edwards prosthesis for selected elderly patients and for tricuspid valve replacement. Because of their influence on the probability of reoperation, valve size and prior cardiac procedures also merit consideration in the choice of valvular prosthesis.

Aged↗

Endogenous nitric oxide induced by interleukin-1 beta in rat islets of Langerhans and HIT-T15 cells causes significant DNA damage as measured by the 'comet' assay.

We have used the comet assay (single cell gel electrophoresis) to measure nitric oxide-induced DNA damage in rat islets of Langerhans and insulin-containing HIT-T15 cells. Damage was induced following treatment with the nitric oxide donor SIN-1, which also releases superoxide, but was not reduced by exogenous superoxide dismutase, suggesting that nitric oxide itself, rather than superoxide or peroxynitrite may be the active species. The DNA damaging effect of nitric oxide was easily detectable at the earliest time point tested (15 min). Damage also resulted following induction of nitric oxide synthase by the cytokine interleukin-1 beta in both islets and HIT-T15 cells and was prevented by replacing the substrate, arginine, with nitromonomethyl arginine. Thus intracellular levels of nitric oxide generated by interleukin-1 beta-induced nitric oxide synthase were sufficient to cause DNA damage in islet cells and HIT-T15 cells.

Animals↗

Hypersensitivity of human lymphocytes to UV-B and solar irradiation.

T-lymphocytes from three normal human donors, irradiated with broad-spectrum UV-B (peak emission, 312 nm), are 20-fold more sensitive than fibroblasts from four normal donors in a clonogenic assay. We have compared the formation of thymine cyclobutane dimers and pyrimidine-(6-4)-pyrimidone photoproducts following irradiation by UV-C (254 nm) and UV-B and studied killing at doses giving equal dimer formation. UV-B killing of fibroblasts appears to be associated with dipyrimidine photoproduct formation, whereas UV-B killing of lymphocytes is mediated by nondimer damage. Strand breakage following UV-B irradiation measured using the "Comet" assay (single cell gel electrophoresis) reflects this nondimer damage and has kinetics consistent with excisable damage. Lymphocytes from three excision-deficient xeroderma pigmentosum donors show reduced strand breakage and increased killing following UV-B irradiation, compared with lymphocytes from normal donors. We therefore suggest that UV-B kills human lymphocytes by excisable nondimer damage and that xeroderma pigmentosum lymphocytes are defective in its repair. The putative nondimer damage does not appear to be associated with radical attack, and the strand breakage is not a manifestation of apoptosis. A 1-min exposure of human lymphocytes in vitro to natural sunlight is sufficient to produce damage measurable by the Comet assay.

Apoptosis↗

Argon beam coagulation compared with cryoablation of ventricular subendocardium.

The Argon Beam Coagulator uses radiofrequency energy to excite argon gas that may be used for ventricular ablation. The effects of power level and number of applications of the Argon Beam Coagulator were compared wtih cryothermia. Ten mongrel dogs underwent cardiac extirpation. The endocardial surfaces of 5 hearts were used for the creation of lesions using the Argon Beam Coagulator at five power levels with either one or two applications. Five hearts were used for endocardial and epicardial lesions using cryothermia (15-mm-diameter probe at -70 degrees C) for 1, 2, 3, or 4 minutes. The Argon Beam Coagulator lesions showed an increase in depth with increasing power levels (2.25 +/- 1.05 mm at 50 W to 6.64 +/- 0.75 mm at 150 W) and number of applications (maximum depth of 6.64 +/- 0.75 mm with one application, 11.2 +/- 1.1 mm with two applications). Cryothermia lesions were similar in depth regardless of duration or site of application (range, 6.1 to 10.2 mm). Both techniques resulted in homogeneous and well-demarcated lesions. These data show that the Argon Beam Coagulator results in discrete endocardial lesions, which may be created quickly and reproducibly. This may be a useful alternative for the operative ablation of endocardial scar in the treatment of ventricular tachycardia.

Animals↗

Pulsatile versus nonpulsatile reperfusion improves cerebral blood flow after cardiac arrest.

Cardiopulmonary bypass using nonpulsatile flow (NF) is currently advocated for treating refractory cardiac arrest. Although the heart can be revived using cardiopulmonary bypass support, the brain must recover if such therapy is to be considered successful. Previous studies have demonstrated that pulsatile flow (PF) reperfusion can improve neurologic outcome compared with NF reperfusion after cardiac arrest. The purpose of this study was to assess cerebral perfusion and oxygen consumption during either PF or NF reperfusion after cardiac arrest. Dogs (n = 22) underwent a 15-minute cardiac arrest followed by 1 hour of either PF or NF reperfusion. Microsphere techniques were used to assess cerebral perfusion and oxygen consumption at 3, 15, and 60 minutes of reperfusion. Mean arteriovenous gradients and total brain flows were similar in both groups. However, cerebral oxygen consumption was significantly improved at 3 minutes of reperfusion with PF versus NF (1.8 +/- 0.3 versus 0.9 +/- 0.3 mL O2.dL-1.min-1, respectively; p < 0.05). These results were coincident with improved gray-to-white flow ratios at 3 minutes of PF versus NF reperfusion (5.2 +/- 1.0 versus 2.0 +/- 0.3, respectively; p < 0.05). There were no statistically significant differences in brain perfusion variables by 15 minutes of reperfusion. However, a relative hyperemia was exhibited at 15 minutes of NF versus PF reperfusion, which suggests nutrient flow was insufficient during early NF versus PF reperfusion. In conclusion, PF reperfusion can better restore cerebral blood flow and oxygen consumption than can NF reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Coronary artery bypass in patients with severely depressed ventricular function.

This study evaluates whether patients with coronary artery disease and severely depressed left ventricular ejection fraction benefit from coronary artery bypass grafting. From 1981 to 1991, 118 consecutive patients with ejection fraction less than or equal to 0.25 underwent isolated coronary artery bypass grafting at Duke University Medical Center. Operative mortality was 11%. Ventricular arrhythmia requiring treatment was the most common postoperative complication (27%), followed by low cardiac output state (22%). Median length of postoperative hospitalization was 9 days. Kaplan-Meier estimate of survival at 1 year and 5 years was 77.2% and 57.5%, and was better than estimated survival with medical therapy alone. Survivors experienced significant improvement in angina class (p < 0.0001), congestive failure class (p < 0.0001), and follow-up ejection fraction (p < 0.005). Of 22 preoperative factors evaluated by univariate survival analysis, five were associated with significantly greater mortality: other vascular disease (p < 0.005), female sex (p < 0.005), hypertension (p < 0.005), elevated left ventricular end-diastolic pressure (p < 0.05), and depressed cardiac index (p < 0.05). Considering length of hospitalization, three factors showed significant adverse effect in a multivariate Cox model: time on cardiopulmonary bypass (p < 0.005), acute presentation (p < 0.005), and female sex (p < 0.01). These data and review of the literature suggest that patients with coronary artery disease and severely depressed ejection fraction benefit from coronary artery bypass grafting, and specific preoperative factors may help determine optimal treatment.

Aged↗

Stimulation of myocyte insulin-responsive glucose transporters by the inhibition of fatty acid oxidation.

The effects of the fatty acid inhibitor 4-bromocrotonic acid (4-BCA) on glucose utilization was studied in isolated rat myocytes. In contrast to its potent inhibition of [1-14C]palmitate oxidation, 4-BCA strongly stimulated the oxidation of [1-14C]glucose and [2-14C]-pyruvate in a concentration-dependent manner. At a concentration of 300 microM, 4-BCA increased glucose oxidation threefold and that of pyruvate oxidation twofold. The rate of transport of [U-14C]-2-deoxyglucose was significantly stimulated by 4-BCA. The transport of 2-deoxyglucose was increased sevenfold with 200 microM 4-BCA, whereas insulin (10 microU)/ml enhanced 2-deoxyglucose transport twofold. The addition of insulin to myocytes preincubated with 4-BCA did not further increase glucose transport. Cytochalasin B and anti-GLUT 4 antibody decreased the 4-BCA-induced stimulation of glucose transport. These results suggest that the stimulation of 2-deoxy-glucose transport by 4-BCA occurs through an increase in the activity of insulin-responsive glucose transporters, GLUT 4, in the sarcolemmal membrane.

Animals↗

Technique for long-term right dorsal colon fistulization in ponies.

Right dorsal colon fistulas, 2.5 cm in diameter, were created in 2 healthy ponies, using a 2-stage surgical procedure. The first stage consisted of resection of portions of the 16th and 17th ribs on the right side, followed by surgical creation of a 6- to 8-cm-diameter adhesion between the right dorsal colon and the body wall. Fistulas were created approximately 2 weeks after the first surgery by sharp dissection through the adhesion into the lumen of the colon. The fistulas have been satisfactorily maintained for > 2 years by de Pezzer catheters (45 F). Ponies with fistulas have been used for gastrointestinal experiments.

Animals↗

Acute isovolemic hemodilution and blood transfusion. Effects on regional function and metabolism in myocardium with compromised coronary blood flow.

The use of isovolemic hemodilution to prevent adverse side effects of homologous blood transfusions has increased. The lowest level of hemoglobin that can be tolerated without regional myocardial dysfunction, however, had not been precisely defined for left ventricular myocardium with compromised coronary blood flow. This level was determined in our study in 19 dogs with critical stenosis of the left anterior descending coronary artery during graded isovolemic hemodilution. Regional function was assessed by sonomicrometry in the territory supplied by the left anterior descending coronary artery, as well as in two noncompromised left ventricular areas; oxygen extraction and consumption in the left anterior descending coronary artery region were assessed by analysis of anterior descending coronary venous oxygen saturation. The median lowest level of hemoglobin tolerated without contractile dysfunction of the territory supplied by the left anterior descending artery was 7.5 gm/dl, with lower and upper quartiles of 6 and 9 gm/dl. In addition to a marked increase in cardiac output and transstenotic left anterior descending flow, global cardiac and regional myocardial functions were unchanged at a hemoglobin level of 7.5 gm/dl, as compared with a control level of hemoglobin of 12.0 +/- 0.4 gm/dl. At a mean level of hemoglobin of 6.0 +/- 0.4 gm/dl, marked contractile dysfunction developed in the left anterior descending region: Systolic shortening decreased from 24.2% +/- 2.1% to 17.9% +/- 1.9% (p < 0.01); postsystolic shortening increased from 4.0% +/- 3.0% to 12.2% +/- 3.8% (p < 0.01); and in the left anterior descending region, oxygen consumption decreased. The increase of arterial level of hemoglobin by only 1.9 +/- 0.2 gm/dl restored contractile function in the left anterior descending region, regional oxygen consumption, and oxygen extraction across the left anterior descending region. Moderate isovolemic hemodilution is relatively well tolerated in left ventricular myocardium with compromised coronary blood flow, and hemodilution regional contractile dysfunction induced by hemodilution is reversible by minimal blood transfusion.

Animals↗

Current morbidity, mortality, and survival after bronchoplastic procedures for malignancy.

The number of patients reported to have undergone bronchoplastic procedures has increased nearly fourfold in the past decade. These techniques represent excellent surgical therapy for patients with benign endobronchial lesions, traumatic airway disruptions, or tumors of low-grade malignant potential, and for select patients with surgically resectable lung cancer. Eighty-nine percent of bronchoplastic procedures are performed for malignancy. We reviewed 1,915 bronchoplastic procedures for carcinoma reported over the past 12 years to determine the incidence of complications and survival. Complications included local recurrence (10.3%), 30-day mortality (7.5%), pneumonia (6.7%), atelectasis (5.4%), benign stricture or stenosis (5.0%), bronchopleural fistulas (3.5%), empyema (2.8%), bronchovascular fistulas (2.6%), and pulmonary embolism (1.9%). Results were further stratified into sleeve lobectomy and sleeve pneumonectomy groups. Five-year survivals for stage I, II, and III carcinoma were 63%, 37%, and 21%, respectively. Sleeve lobectomy for carcinoma extends surgical therapy to select patients with complication rates comparable to pneumonectomy and long-term survival similar to that for conventional resections.

Bronchi↗

UV-C sensitivity of unstimulated and stimulated human lymphocytes from normal and xeroderma pigmentosum donors in the comet assay: a potential diagnostic technique.

We have studied incision-break formation in unstimulated and stimulated populations of human T-lymphocytes using the comet (single-cell microgel electrophoresis) assay. The frequency of strand breaks 1 h after UV-irradiation appears to be far greater in unstimulated than in stimulated lymphocytes from normal donors and the excess of strand breaks was observed for a far longer time after irradiation. This result corroborates the greater sensitivity of UV-C irradiation observed in a colony-forming assay but suggests that the defect may relate to a defect in strand rejoining rather than a defect in incision. Few strand breaks were seen in either unstimulated or stimulated lymphocytes of four xeroderma pigmentosum donors, suggesting that the method may offer a rapid diagnostic assay for XP.

Cells, Cultured↗

Effect of Ebstein's anomaly on short- and long-term outcome of surgically treated patients with Wolff-Parkinson-White syndrome.

BACKGROUND: Ebstein's anomaly is the most commonly occurring congenital abnormality associated with the Wolff-Parkinson-White (WPW) syndrome. However, the effects of Ebstein's anomaly on the risks and benefits of surgical ablation of accessory pathways in patients with WPW syndrome are unknown. METHODS AND RESULTS: This study compared the long-term outcome of 38 WPW patients with Ebstein's anomaly undergoing accessory pathway ablation to a reference population of 384 similarly treated patients without the anomaly. Ebstein's anomaly was mild in 21 patients (55%) and moderate-to-severe in 17 patients (45%). Sixteen patients (42%) required tricuspid valve surgery, and 23 (61%) had an atrial septal defect or patent foramen ovale repaired. Baseline clinical characteristics and preoperative clinical arrhythmias were similar in both groups. Ten-year survival was 92.4% and 91.2% for patients with and without Ebstein's anomaly, respectively (p = NS). During a mean follow-up of 6.2 +/- 3.8 and 5.3 +/- 3.6 years, 82% of patients with and 90% without Ebstein's anomaly had either clinically insignificant or no arrhythmias, and 18% versus 10% reported symptoms suggesting arrhythmias lasting longer than 1 minute, respectively. Atrial fibrillation was reduced postoperatively to 9% (p less than 0.001) in patients with and to 4% (p less than 0.001) in those without the anomaly. Fewer hospitalizations were reported postoperatively by 90% versus 96% of patients with and without Ebstein's anomaly; 9.4% versus 6.0% of patients were disabled at follow-up, respectively (p = NS). CONCLUSIONS: Patients with Ebstein's anomaly are improved significantly after accessory pathway ablation. The presence of this anomaly should not preclude accessory pathway ablation in these patients.

Adolescent↗

First successful bridge to cardiac transplantation using direct mechanical ventricular actuation.

Currently available ventricular assist devices are technically difficult to implant, require continuous anticoagulation, and are associated with hemorrhagic and thromboembolic complications. Direct mechanical ventricular actuation is a biventricular assist device that can be applied in 3 to 5 minutes through a left anterior thoracotomy and has no direct blood contact or need for anticoagulation. The present study was designed to determine the effects of direct mechanical ventricular actuation in total biventricular circulatory support. Cardiogenic shock refractory to standard therapy developed in 2 patients awaiting cardiac transplantation. Direct mechanical ventricular actuation was applied and provided immediate hemodynamic stabilization in both. All inotropic agents and intraaortic balloon support were then discontinued. Fifty-six hours of circulatory support bridged the first patient to successful cardiac transplantation without complication. The patient is alive and well more than 1 year later without incident of infection or rejection. The second patient suffered cardiac arrest and required closed chest cardiopulmonary resuscitation before device application. After 45 hours of support, it was determined that irreversible neurologic injury had occurred and direct mechanical ventricular actuation was discontinued. Neither patient's native heart exhibited any histologic evidence of device-related trauma. Direct mechanical ventricular actuation has undergone limited clinical investigation since its original description 25 years ago, but in these initial trials, the device has proved effective. The concept of mechanically actuating the ventricles appears to be a valuable, yet under-utilized method of total circulatory support.

Blood Pressure↗

Reducing the concentration of selected marker improves efficiency of cotransfer of unselected DNA into SV40-transformed human fibroblasts.

A substantial increase in transfer of unselected DNA to two human SV40-transformed fibroblast cell lines was obtained by reducing the concentration of the cotransferred selected marker DNA. The average amount of unselected DNA transferred, even under favorable conditions, was still low compared to that reported for some rodent cell lines. Our results suggest that in human fibroblasts there is strong competition between exogenous DNA molecules for integration and maintenance, and that more unselected DNA is retained in the presence of only one copy of the selected marker.

Cell Line, Transformed↗

Direct mechanical ventricular actuation: a review.

Direct mechanical ventricular actuation (DMVA) is a non-blood contacting method of circulatory support that can be rapidly instituted for resuscitation. DMVA is superior to conventional methods (open and closed-chest cardiac massage) in providing reliable cardiovascular stabilization for resuscitation following cardiac arrest. Furthermore, DMVA has important advantages including rapid application, technical simplicity, and avoidance of blood contact compared to other resuscitation devices (cardiopulmonary bypass and blood pumps). This review summarizes laboratory and clinical applications of DMVA.

Animals↗

Intraoperative identification of cardiac patients at risk to develop postoperative atrial fibrillation.

Postoperative atrial fibrillation (AF) is a complication occurring in 11% to 36% of patients after cardiac operations, which results in increased morbidity and hospital costs. A new electrophysiologic screening test was developed to identify those patients at risk for development of postoperative AF. The test was validated in 50 patients (43 men and 7 women) with a mean age of 59.6 +/- 1.3 years who underwent coronary artery bypass grafting with or without other cardiac surgical procedures. After aortic and venous cannulation, but before initiation of bypass, the mid-right atrium was stimulated with a bipolar probe at 25 microA for 3 seconds. Alternating current was increased by 25 microA until AF was induced or up to a maximum of 200 microA. Postoperative AF occurred in 18 patients (36%), 17 of whom had inducible AF (sensitivity = 0.94). Of the remaining 32 AF-free patients, 13 had negative tests (specificity = 0.41). Age and sex were not factors affecting inducibility, although patients who developed AF were older than those who were AF free (63.6 versus 57.3 years, p = 0.02). Length of stay in the intensive care unit was longer for those with postoperative AF than for AF-free patients (3.6 versus 1.9 days, p = 0.02). The negative predictive value of the test was 0.93, and the positive value was 0.47. These data show that this new intraoperative technique may be used to identify patients at risk for postoperative AF. Prophylactic therapy can therefore be directed to only those patients at risk for postoperative AF.

Atrial Fibrillation↗