Lifesciences Inc Research Articles

176 EFFECTS OF VEHICLE AND ROUTE OF ADMINISTRATION OF LETROZOLE ON OVARIAN FUNCTION IN CATTLE

Treatment with letrozole, a non-steroidal aromatase inhibitor, has been associated with elevated mean plasma LH concentrations, a prolonged period of dominance of the extant dominant follicle, and delayed emergence of the next follicular wave in cattle. As well, a luteotrophic effect was hypothesised by the observation that CL diameter was increased in heifers given 250 μg kg–1 of letrozole divided in a 3-day regimen. The objective of the present study was to determine the effects of vehicle and route of administration of letrozole on ovarian function in sexually mature beef heifers. Ovarian function was synchronized among heifers using transvaginal ultrasound-guided follicular ablation followed by a luteolytic dose of PGF b.i.d. 4 days later. The ovaries were subsequently examined daily by transrectal ultrasonography until ovulation was detected. On Day 3 (Day 0 = ovulation), heifers were assigned randomly to 4 treatment groups and given letrozole at a dose of 1 mg kg–1 intravenously (i.v. in benzyl alcohol, n = 10) or intramuscularly (i.m. in benzyl alcohol plus canola oil 1:1 v/v, n = 10), or given a placebo (i.v. in benzyl alcohol, n = 5) or (i.m. in benzyl alcohol plus canola oil 1:1 v/v, n = 5). The ovaries were monitored daily by ultrasonography, and blood samples collected twice daily by jugular venipuncture from pre-treatment to post-treatment ovulations. Comparisons among groups were made by 1-way ANOVA for single-point measurements and by ANOVA for repeated measures for time-series data. The interovulatory interval did not differ among groups, nor did the day-to-day diameter profile of the dominant follicle of wave 1 (first follicular wave after ovulation). However, the interval between emergence of waves 1 and 2 was longer in heifers treated with letrozole i.m. (11.7 ± 0.3 days) than in controls (10 ± 0.4 and 9.5 ± 0.5 days for i.v. and i.m. controls, respectively; P < 0.05), and intermediate in heifers given letrozole i.v. (10.6 ± 0.30 days). The day-to-day diameter profile of the corpus luteum was greater (P < 0.05), and plasma progesterone concentrations tended to be greater (P < 0.06) in heifers treated i.m. with letrozole v. placebo. Plasma LH concentrations did not differ among groups, whereas plasma FSH concentrations were greater (P < 0.02) in heifers treated i.v. with letrozole v. placebo. In summary, letrozole dissolved in benzyl alcohol and given intravenously at a dose of 1 mg kg–1 on Day 3 did not alter ovarian function in cattle, but the same dose given i.m. in canola oil vehicle resulted in a longer inter-wave interval, a greater CL diameter profile, and greater plasma progesterone concentrations. We conclude that i.m. letrozole in oil is a feasible route of administration and vehicle for the development of an aromatase inhibitor-based treatment for herd synchronization in cattle. Research supported by the Natural Sciences and Engineering Research Council of Canada, Canadian Institutes for Health Research, and Bioniche Life Science Inc.

CoreValve Dislocation

The natural history of all substantial innovative medical procedures generally follows the same archetype. A new, potentially revolutionary treatment approach for a certain disease is introduced and initial first-in-men, feasibility, and safety studies are conducted by expert operators in highly specialized centers and selected patients. Given promising initial results, this triggers a wave of mounting enthusiasm and a flurry of activity in this field with transfer into the real world until previously unanticipated or not reported problems or complications are recognized that may act as wave-breakers, resulting in a deceleration or even decline in the stream of exuberance. Such complications usually lead to a change of mood and a state of reconsideration with calls for caution and for training programs, the enthusiasm settling down to a healthy, realistic steady state. Necessarily, problems are addressed and techniques refined, taking the procedure to the next, matured level. Article see p 531 This archetype may be readily transferred to the setting of transcatheter aortic valve implantation (TAVI). Being a revolutionary approach for the treatment of severe aortic valve stenosis by offering—for the first time—a definite, catheter-based interventional treatment option for nonsurgical and high-risk patients, TAVI has jubilantly entered the clinical arena in an unprecedented fashion. Introduced only recently in 20021 in France with the first implantation in Germany in 2005,2 feasibility, safety, and efficacy of this novel technique have been demonstrated first for the balloon-expandable (Edwards Sapien, Edwards Lifesciences Inc, Irvine, Calif)3, 4 and a little later for the self-expandable (Medtronic CoreValve, Medtronic, Inc, Minneapolis, Minn)5–7 bioprosthesis. Meanwhile, both devices are commercially available in Europe, and an ever-increasing number of patients are being treated with these devices with remarkable clinical results. Just recently, the superiority of transfemoral TAVI over optimal medical therapy including adjunct balloon aortic …

Redo transapical aortic valve implantation: Feasibility of a repeat approach through the left ventricular apex

FIGURE 1. Perivalvar leak. CASE REPORT A 78-year-old man presented with angina and dyspnea. Comorbidities included peripheral vascular disease, obstructive lung disease, and renal insufficiency. He had undergone two sternotomies for bypass surgeries. Cardiac catheterization revealed patent grafts to the left anterior descending and obtuse marginals. He had occluded grafts to his right coronary artery that had a 70% proximal stenosis. Echocardiogram (ECHO) showed an ejection fraction of 30% and severe AS. Because of unsuitable access vessels he was offered TA-AVI. The left ventricular (LV) apex was exposed as described previously. A 26-mm Edwards SAPIEN valve (Edwards Lifesciences Inc, Irvine, Calif) was positioned and deployed. Transesophageal ECHO (TEE) revealed a trivial perivalvar leak. The following day, the patient experienced flash pulmonary edema requiring reintubation. Angiography revealed unchanged coronary anatomy, a well-seated valve, but a new moderately-severe perivalvar leak. This was confirmed with ECHO (Figure 1). The symptoms persisted. On postoperative day 5 the decision was made to address the perivalvar leak. Via the right axillary artery a 25-mm NuMed Balloon (NuMED Canada Inc, Cornwall, Ontario, Canada) was introduced and valvuloplasty performed. The leak persisted and the decision was made to reimplant a second valve as described previously. The LV apex was re-exposed via the same incision. Clot and inflammatory phlegmon en-

Successful Transapical Aortic Valve Implantation in a Congenital Bicuspid Aortic Valve

Transcatheter stent-valve implantation in stenosed congenital bicuspid aortic valves is under debate. Heavily calcified elliptic bicuspid valves represent a contraindication to catheter-based valve therapies because of a risk of stent-valve displacement, distortion, or malfunctioning after the implantation. In this case report we illustrate our experience with a patient suffering from stenosed congenital bicuspid aortic valve who successfully underwent a transapical 26-mm Edwards Sapien stent-valve (Edwards Lifesciences Inc, Irvine, CA) implantation. Postoperative distortion, malfunctioning, and paravalvular leaks were not detected.

Left Atrial Mass During a Minimally Invasive Thoracic Mitral Valve Replacement

A 72-YEAR-OLD man with a history of mitral regurgitation presented for minimally invasive mitral valve surgery through a right thoracotomy approach. Two introducers were inserted into the right internal jugular vein for the placement of retrograde cardioplegia and pulmonary artery venting catheters (Endoplegia and Endovent, Edwards Lifesciences Inc, Irvine, CA). The retrograde catheter was guided percutaneously through the coronary sinus ostium using a modified bicaval transesophageal echocardiographic view and was advanced slowly while monitoring its position.

227 EFFECTS OF A SINGLE DOSE OF A NONSTEROIDAL AROMATASE INHIBITOR ON OVARIAN FUNCTION IN CATTLE

Many countries have banned the use of estrogenic products in farm animals. Nonsteroidal aromatase inhibitors prevent the body from producing its own estrogen. The effects on the ovary are thought to be a result of suppression of estrogen-producing follicles and a rebound in endogenous levels of FSH through the removal of the negative feedback effect of estradiol. An experiment was designed to determine the effects of a nonsteroidal aromatase inhibitor, letrozole, on ovarian function in cattle. The specific objective was to test the hypothesis that letrozole will arrest growth of the dominant follicle, resulting in emergence of a new follicular wave at a predictable interval post-treatment. Beef heifers were assigned randomly to 4 groups and given phosphate-buffered saline [control; (n = 10)] or letrozole at a dose of 500 (n = 9), 250 (n = 10), or 125 (n = 10) μgkg-1 i.v. 4 days after follicular ablation (≈ 2.5 days after wave emergence, at the time dominant follicle selection is manifest). Blood samples were collected and ovarian structures were monitored daily by transrectal ultrasonography. Analysis of variance for repeated measures, one-way ANOVA, paired t-test, and 2-sample t-test were applied to the analysis of the data. The diameter profile of the dominant follicle was larger in heifers treated with letrozole than in control heifers (P < 0.05). The intervals from treatment to new wave emergence and from treatment to onset of regression of the extant dominant follicle were longer (P < 0.05) in heifers treated with letrozole than in controls, although variances in the intervals were not different. A small but significant reduction in circulating estradiol concentration was observed, and plasma LH concentrations were higher (P < 0.05) in letrozole-treated heifers than in controls. Lower plasma concentrations of FSH in letrozole-treated heifers than in controls (P < 0.03) was interpreted as an indirect effect resulting from prolonged follicular dominance. In summary, a single dose of letrozole did not induce regression of the extant dominant follicle, nor did it directly affect FSH release. Conversely, letrozole extended the lifespan of the dominant follicle, in association with increased endogenous levels of LH, thereby delaying the next FSH surge and subsequent follicular wave emergence. Results suggest that letrozole has potential as a nonsteroidal method of controlling ovarian function in cattle but further studies are needed to clarify dosage and timing of treatment. Research supported by the Natural Sciences and Engineering Research Council of Canada and Bioniche Life Science Inc.

Percutaneous aortic valve therapy: clinical experience and the role of multi-modality imaging

Degenerative aortic stenosis accounts for the majority of native valve disease.1 Surgical aortic valve replacement is a treatment option that provides good outcome in the majority of the patients, with...

Unexpected Complications of Transapical Aortic Valve Implantation

Recent series have reviewed the results of transapical aortic valve implantation (TAVI). However, specific problems of this new procedure are not well-described. Unexpected complications due to the procedure and their management are reported. Eighteen patients underwent TAVI using the Edwards Sapien bioprosthesis (Edwards Lifesciences Inc, CA) between September 2007 and June 2008 due to contraindications of conventional surgery (n = 5) or high operative risk (n = 13). The system was introduced through 2 purse string sutures in the apex under echocardiographic and fluoroscopic control. The implantation success rate and initial procedural success were 100%. There was no intraoperative death and no stroke. During the procedure, two cases of ventricular fibrillation consequent to rapid pacing were treated by cardioversion. Acute mitral regurgitation due to traction of the subvalvular apparatus by the guidewire and acute aortic regurgitation from pressure on a bioprosthesis cusp by the guidewire were diagnosed by transesophageal echocardiography and reversed by the removal of the guidewire. Another case of aortic regurgitation was due to incomplete deployment of the bioprosthesis and was managed by a "valve after valve" procedure. Two patients died on postoperative day 2 from left ventricular failure. In one patient the postmortem study showed, despite correct implantation of the bioprosthesis, a hematoma of the septum with a small ventricular septal defect. The total in-hospital death was 27.7% (5 patients). There was no periprocedural bleeding but in one patient delayed rupture of the apex (36 hours after the procedure) necessitated emergency surgery. A false aneurysm of the apex appeared 3 months after surgery in another patient. Closure of the apex was performed through sternotomy and cardiopulmonary bypass with an uneventful follow-up. The TAVI is associated with incidents and complications different to those encountered in conventional aortic valve surgery. Recognizing their existence contributes to elucidating their mechanisms and to propose solutions to avoid or treat them.

Transcatheter Aortic Valve Implantation: Selection Strategy Is Crucial for Outcome

We describe the results of transcatheter aortic valve implantation (TAVI) in high-risk patients with aortic stenosis. Transfemoral access was the first option, and if contraindicated, the transapical approach was used. Fifty patients were consecutively treated with TAVI because of high surgical risk or contraindications to operation. Mean age was 83 +/- 6 years, and most were in New York Heart Association classes III and IV. The predicted surgical mortality was 28% +/- 14% using the European System for Cardiac Operative Risk Evaluation and 16% +/- 7% using the Society of Thoracic Surgeons Predicted Risk of Mortality. The Edwards-SAPIEN (Edwards Lifesciences Inc, Irvine, CA) valve was implanted using a transfemoral approach in 35 patients and the transapical approach in 15. The transapical patients had more comorbidity (diabetes, previous myocardial infarction, previous coronary artery bypass grafting, peripheral artery disease, renal failure, porcelain aorta, and previous stroke). Successful implantation was 85.7% and 100% in the transfemoral and transapical group, respectively. Gradients were satisfactory. In-hospital mortality was 8% in the transfemoral and 27% in the transapical group. Stroke was only observed in the transfemoral group. Overall 1-year survival was 74% +/- 11% in the transfemoral group and 60% +/- 13% in the transapical. The results attributed to each approach (transfemoral or transapical) are strongly influenced by the selection strategy. Patients in the transapical group had more comorbidity and consequently a more critical early postoperative period. The respective places of transfemoral and transapical approaches need to be clarified for each approach by a randomized study.

Percutaneous Treatment of Mitral Regurgitation

Percutaneous mitral valve therapy became a reality more than 25 years ago with the first description of balloon valvuloplasty for rheumatic mitral stenosis.1 More recently, percutaneous closure of paravalvular leaks after surgical valve implantation has been shown to have a potential, but limited, role.2–4 However, valvular mitral regurgitation (MR) remains largely the purview of surgery. Recently, the potential for less invasively replicating these successful surgical procedures without the need for thoracotomy or cardiopulmonary bypass has generated considerable interest. For the most part, these new approaches are modeled after established surgical strategies. Percutaneous approaches to mitral repair can be broadly divided into procedures that address the various components of the mitral valve. For purposes of discussion, the mitral valve can be considered to have several component parts: leaflets, subvalvular apparatus (chordate tendinae and papillary muscles), annulus, left atrium, and left ventricle.5 All are integral to the normal function of the mitral valve and each is a potential avenue for repair. Although many such avenues may not lead to an effective surgical option, it may be unwise to dismiss the possibility that others will achieve some measure of success. We briefly review the current percutaneous therapies being developed and evaluated for the management of MR. The current status of various percutaneous therapies is presented in Table 1. View this table: Table 1. Current Status of Percutaneous Mitral Valve Repair Procedures ### Leaflet Repair Complex leaflet repair is currently beyond the reach of a percutaneous approach. However, the relatively simple but, in selected patients, effective “double-orifice” surgical repair initially described by Alfieri and coworkers6 can be reproduced. In the surgical procedure, the free edges of the mitral leaflets are sutured together in the mid portion creating 2 separated orifices. Generally, surgical leaflet repair is combined with implantation of an annuloplasty ring. The surgical literature …

Successful Deployment of a Transcatheter Aortic Valve in Bicuspid Aortic Stenosis

Transcatheter aortic valve replacement (TAVR) has recently emerged as a therapeutic option for patients with severe aortic stenosis who are considered inoperable.1 To avoid potential complications related to this novel procedure (such as coronary artery obstruction or perivalvular leakage), detailed information on the aortic valve anatomy is critically important.1,2 Multislice computed tomography (MSCT) enables a comprehensive 3D assessment of aortic valve anatomy and, particularly, the extent and location of valve calcifications, one of the reasons for inappropriate deployment of the valved stent together with the bicuspid anatomy.3 After TAVR, the positioning and deployment of the valve prosthesis can be evaluated by this imaging technique. This report concerns a 54-year-old woman with symptomatic bicuspid aortic valve stenosis (aortic valve area, 0.9 cm2). Comorbidity included hypertension and hypercholesterolemia. Importantly, 2 years earlier, the patient experienced a cerebrovascular accident with severe consequences that determined a high risk for cardiac surgery. Consequently, the …

Severe Valvular Regurgitation and Late Prosthesis Embolization After Percutaneous Aortic Valve Implantation

We report the case of a 79-year-old man with low-flow, low-gradient aortic stenosis who underwent transapical aortic valve implantation. The deployment of a 26-mm Edwards SAPIEN valve (Edwards Lifesciences Inc, Irvine, CA) was complicated with the occurrence of severe central aortic regurgitation that was successfully treated with the implantation of a second valve ("valve-in-valve"). Postoperative progress was satisfactory but 2 days after the procedure he suddenly developed cardiogenic shock secondary to the migration of the aortic bioprothesis into the left ventricular outflow tract. Open-heart surgery was undertaken to remove the valves and perform standard aortic valve replacement, but the patient died perioperatively.

Sixty-four multislice computed tomography after transcutaneous implantation of a Cribier-Edwards bioprosthesis in the aortic position

A 84-year-old male with severe symptomatic aortic stenosis (valve area 0.66 cm2; transvalvular gradient 48 mmHg) declined for surgical aortic valve replacement due to severe chronic obstructive pulmonary disease underwent transcatheter implantation of a 26 mm Cribier-Edwards aortic bioprosthesis (Edwards Lifesciences Inc, Irvine, CA, USA). The procedure was performed using the retrograde approach through the right femoral artery. The prosthetic heart valve made of three …

Stentless Aortic Valves are Hemodynamically Superior to Stented Valves During Mid-Term Follow-Up: A Large Retrospective Study

Several studies have compared left venticular mass (LVM) regression and hemodynamic data for stentless versus stented aortic bioprostheses with conflicting results. The major limitations of these studies are their small sample size and short-term follow-up. We therefore compared midterm LVM regression, hemodynamic data, and survival in a large population of tissue aortic valve replacement (AVR) patients. All patients undergoing tissue AVR at our institution between 1998 and 2001 were included (n = 737). Patients were divided into two groups according to type of bioprosthetic implanted: stentless patients (total n = 310) (Toronto SPV [St Jude Medical, St Paul, MN], n = 146 and Freestyle [Medtronic, Minneapolis, MN], n = 164) and stented patients (total n = 427) (Perimount [Edwards Life Sciences Inc, Irvine, CA], n = 291 and Mosaic [Medtronic], n = 136). The two groups of patients had similar preoperative transvalvular gradients and LVM index (130 +/- 47 vs 130 +/- 42 g/m2 for stentless versus stented valves, respectively). Predischarge echos revealed that stentless patients had significantly lower mean transvalvular gradients (11 +/- 5 vs 15 +/- 6 mm Hg, p < 0.001) and larger effective orifice areas (1.32 +/- 0.52 vs 1.22 +/- 0.48 cm2, p = 0.01). Follow-up echocardiograms were obtained in 99% of surviving patients 28 +/- 22 (range, 0-79) months postoperatively. Stentless patients had significantly lower LVM index during follow-up (100 +/- 32 vs 107 +/- 32 g/m2, p = 0.005) and stentless valves were an independent predictor of LVM regression. Furthermore, a higher proportion of stented patients had residual LV hypertrophy during follow-up (28% vs 18%, p = 0.001). Stentless valves were associated with improved midterm survival by univariate analysis, but not by multivariable analysis. Midterm follow-up in a large number of patients reveals that stentless bioprostheses are hemodynamically superior to stented valves.

5500339 DNA denaturation method : Fuller Carl W; Pisa-Williamson Denise A Cleveland Heights, OH, United States assigned to Amersham Life Science Inc

5500339 DNA denaturation method : Fuller Carl W; Pisa-Williamson Denise A Cleveland Heights, OH, United States assigned to Amersham Life Science Inc

Strontium-89 and carbo-platin as radiosensitizer for neoplastic bone pain

Small early postoperative hemodynamic differences were noted in a randomized comparison of 3 current-generation bioprosthetic aortic valves. Whether these differences persist and influence clinical outcomes 1 year following implantation is unknown.Three hundred adults with severe aortic stenosis undergoing valve replacement were randomized to receive the Epic (St Jude, St Paul, Minn) (n = 99), Magna (Edwards LifeSciences Inc, Irvine, Calif) (n = 100), or Mitroflow (Sorin Biomedica Spa, Saluggio, Italy) (n = 101) bioprostheses. Hemodynamic valve performance was examined by echocardiography at 1 year, and clinical outcomes were assessed in 241 patients (79 Epic, 77 Magna, and 85 Mitroflow; P = .437).Mean age was 75 ± 8 years and 164 were men (68%). Between dismissal and 1 year there were 9 deaths (3.7%) (Epic: 3.7%, Magna: 5.0%, and Mitroflow: 2.3%; P = .654), 6 episodes of heart failure (2.5%) (Epic: 1.3%, Magna: 1.3%, and Mitroflow: 5.8%; P = .265), 27 instances of atrial fibrillation/flutter (11.2%) (Epic: 8.1%, Magna: 11.0%, and Mitroflow: 7.9%; P = .577) and no strokes/transient ischemic attacks. One-year echocardiography demonstrated small hemodynamic differences between Epic, Magna, and Mitroflow bioprostheses in mean gradient (15.2 ± 5.5, 12.3 ± 4.3, and 16.2 ± 5.7 mm Hg, respectively; P < .001) and indexed aortic valve area (0.93 ± 0.28, 1.04 ± 0.28, and 0.96 ± −0.26 cm2/m2, respectively; P = .015). Several early trends persisted when stratifying data by echocardiographic annulus diameter, universal annulus size, and implant size, particularly with annular size ≥23 mm. Overall left ventricular mass index regression between dismissal and 1 year was −16.5 ± 28.1 g/m2, and was similar among groups (P = .262). There were no aortic valve reoperations.Despite midterm persistence of small hemodynamic differences amongst current-generation porcine and pericardial aortic valves, our prospective randomized comparison reveals that clinical outcomes and mass regression are equivalent between devices at 1 year. These encouraging trends must continue to be assessed during longitudinal follow-up.

Responses of isolator-derived Japanese quail and quail cell cultures to selected animal viruses

Thirteen oncogenic and necrotizing animal viruses were assayed in LIFE Sciences, Inc. (LSI)-specific pathogen-free Japanese quail and LSI-specific pathogen-free chicken embryo cell cultures. Nine viruses produced similar titers in the quail and chicken cell systems, whereas four viruses showed significantly higher titers in chickens. Young Japanese quail and chickens were inoculated with five selected avain viruses and maintained in stainless-steel isolators. Comparable responses were noted in quail and chickens injected with Newcastle disease virus and avain leukosis virus, but quail were significantly more resistant than chickens to fowl pox virus, laryngotracheitis virus, and Marek's disease herpesvirus. Although no overt symptoms of disease were observed in Japanese quail inoculated with most avain viruses, neutralizing antibody or virus was detected, indicating presence of an inapparent infection. In one experiment, neutralizing antibody was detected in a comparable number of quail and chickens after inoculation with avian leukosis virus. Avian leukosis virus viremia was observed at 12 and 70 days postinoculation, with the COFAL (complement fixation for avian leukosis) titers similar for quail and chickens. Most quail infected with Marek's disease herpesvirus produced neutralizing antibody within 70 days but showed no classical symptoms of Marek's disease even when held for 5 months. In contrast, all chickens inoculated with Marek's disease herpesvirus died within 20 days. The utility of quail embryo cell cultured in the preparation of vaccines and biological reagents is discussed.