Rodents Versus Pig Model for Assessing the Performance of Serotype Chimeric Ad5/3 Oncolytic Adenoviruses.

Oncolytic adenoviruses (Ad) are promising tools for cancer therapeutics. Most Ad-based therapies utilize species C serotypes, with Adenovirus type 5 (Ad5) most commonly employed. Prior clinical trials demonstrated low efficiency of oncolytic Ad5 vectors, mainly due to the absence of Ad5 primary receptor (Coxsackie and Adenovirus Receptor, CAR) on cancer cells. Engineering serotype chimeric vectors (Ad5/3) to utilize Adenovirus type 3 (Ad3) receptors has greatly improved their oncolytic potential. Clinical translation of these infectivity-enhanced vectors has been challenging due to a lack of replication permissive animal models. In this study, we explored pigs as a model to study the performance of fiber-modified Ad5/3 chimeric vectors. As a control, the Ad5 fiber-unmodified virus was used. We analyzed binding, gene transfer, replication, and cytolytic ability of Ad5 and Ad5/3 in various non-human cell lines (murine, hamster, canine, porcine). Among all tested cell lines only porcine cells supported active binding and replication of Ad5/3. Syrian hamster cells supported Ad5 replication but showed no evidence of productive viral replication after infection with Ad5/3 vectors. Transduction and replication ability of Ad5/3 in porcine cells outperformed Ad5, a phenomenon often observed in human cancer cell lines. Replication of Ad5 and Ad5/3 was subsequently evaluated in vivo in immunocompetent pigs. Quantitative PCR analyses 7 days post infection revealed Ad5 and Ad5/3 DNA and replication-dependent luciferase activity in the swine lungs and spleen indicating active replication in these tissues. These studies demonstrated the flaws in using Syrian hamsters for testing serotype chimeric Ad5/3 vectors. This is the first report to validate the pig as a valuable model for preclinical testing of oncolytic adenoviruses utilizing Adenovirus type 3 receptors. We hope that these data will help to foster the clinical translation of oncolytic adenoviruses including those with Ad3 retargeted tropism.

Telepsychiatry services for Korean immigrants.

Asian Americans often face cultural and language barriers when obtaining mental health treatment. With the small number of Asian mental health providers, it is difficult to ensure the linguistic and ethnic matching of providers and patients. Telepsychiatry holds great promise to address the unique needs of Asian Americans. We developed a project to establish telepsychiatry services that connect Korean mental health patients in Georgia with a linguistically and culturally competent psychiatrist in California and assessed the level of acceptability of psychiatric treatment via real-time teleconferencing among these patients. Upon the completion of the program, 16 patients (5 men, 11 women) completed a questionnaire that measured their acceptability of the telepsychiatry service. The findings indicate a high level of acceptance of the program among Korean patients. The quantitative and qualitative data show that they especially appreciated the cultural sensitivity of the consultation and the comfortable interaction with the provider. However, challenges such as technical issues of teleconferencing may negatively affect the quality of the clinical interaction. Our study expands the knowledge base regarding the acceptability of such services to a population that experiences disparities in mental health care. Future research should extend telepsychiatry services to other Asian population groups that experience lower access to mental health services.

Internal aortic annuloplasty: a novel technique.

BACKGROUND: The purpose of this study was to define an experimental model and a reproducible surgical technique for the preclinical assessment of safety and biocompatibility of a novel intra-annular internal aortic annulus repair device. METHODS: Adult sheep were implanted with HAART Inc's 19 mm aortic annulus repair device via a transverse aortotomy using standard anesthetic, surgical, and cardiopulmonary bypass techniques. Animals were closely monitored throughout the study period until the time of elective sacrifice at 30 or 60 days. RESULTS: Six adult sheep, mean age 63.2 weeks, mean weight 68.8 kg, underwent aortic annuloplasty with a 19 mm annuloplasty frame. Five of the sheep remained stable until scheduled sacrifice. The primary outcome of this study was animal mortality. Early mortality was seen in only one animal (16.7%), due to a surgical complication. Mild-to-moderate aortic insufficiency was observed in all animals upon echocardiographic examination at the time of elective sacrifice. CONCLUSIONS: Of the six animals that underwent aortic annuloplasty, there was one early death due to surgical complication. The remaining five subjects were clinically stable at the time of elective sacrifice. Any conclusions regarding the cause of the observed aortic insufficiency are beyond the scope of this feasibility study but would need to be fully evaluated in the preclinical assessment of any internal aortic annuloplasty device. We have shown that we have developed a reproducible surgical technique in a physiologically appropriate model for the preclinical assessment of internal aortic annulus repair devices.

Laser vaporization of the prostate in vivo: Experience with the 150-W 980-nm diode laser in living canines.

BACKGROUND AND OBJECTIVE: Anatomic, tissue ablation and coagulation, and histopathologic outcomes of the 150-W 980-nm diode laser selective light vaporization (SLV™) of the prostate in the first survival study of living canines were analyzed. STUDY DESIGN/MATERIALS AND METHODS: Ten dogs underwent anterograde SLV™ with the 150-W 980-nm laser delivered by its side-firing fiber (Fusion™). Postoperatively, two dogs were euthanized at 3 hours as planned, six at 2-7 days due to complications, and two, without complications, at 8 weeks as planned. Laser energy and time were recorded. Prostates were sectioned, measured, and histologically analyzed after hematoxylin and eosin (H&E), triphenyltetrazolium chloride (TTC), or Gomori trichrome (GT) staining. RESULTS: SLV™ acutely and hemostatically created a 0.6 ± 0.3 cm(3) cavity in the 3-hour group accompanied by H&E- and TTC-identified coagulation necrosis of up to 9.5 mm (6.1 ± 1.2 mm) that led to prostatic slough-induced obstruction and perforation in six of eight (75%) surviving animals, necessitating unplanned euthanasia within 2-7 days. H&E- and GT-stained prostates at 8 weeks postoperatively showed large (9.6 ± 1.4 cm(3)) re-epithelialized prostatic cavities with persistent diffuse interstitial Prostatitis and collagenous fibrosis. CONCLUSION: SLV™ with the 150-W 980-nm diode laser in living canines produced small cavities acutely, and was accompanied by deeply necrotic prostatic slough-induced obstruction and perforation in a majority of animals. A minority survived SLV and had favorable anatomic outcomes whereas histology revealed persisting inflammation. Further in vivo studies and a cautious clinical approach are recommended to finally evaluate the potential of SLV™ with the 150-W 980-nm diode laser.

Evaluation of the Rebound Hernia Repair device for laparoscopic hernia repair.

BACKGROUND: The characteristics of the ideal type of mesh are still being debated. Mesh shrinkage and fixation have been associated with complications. Avoiding shrinkage and fixation would improve hernia recurrence rates and complications. To our knowledge, this is the first study of a device with a self-expanding frame for laparoscopic hernia repair. METHODS: Six Rebound Hernia Repair Devices were placed laparoscopically in pigs. This device is a condensed polypropylene, super-thin, lightweight, macroporous mesh with a self-expanding Nitinol frame. The devices were assessed for adhesions, shrinkage, and histological examination. Laboratory and radiologic evaluations were also performed. RESULTS: The handling properties of the devices facilitated their laparoscopic placement. They were easily identified with simple x-rays. The mesh was firmly integrated within the surrounding tissue. One device was associated with 3 small adhesions. The other 5 HRDs had no adhesions. We noted no shrinkage or folding. All devices preserved their original size and shape. CONCLUSIONS: At this evaluation stage, we found that the Rebound Hernia Repair Device may serve for laparoscopic hernia repair and has favorable handling properties. It prevents folding and shrinkage of the mesh. It may eliminate the need for fixation, thus preventing chronic pain. The Nitinol frame also allowed radiologic evaluation for gross movement. Further studies will be needed to evaluate its clinical application.

New distal embolic protection device the FiberNet 3 dimensional filter: first carotid human study.

OBJECTIVE: Evaluate the performance and safety of the FiberNet Embolic Protection System during carotid artery intervention. BACKGROUND: Carotid Angioplasty and Stenting (CAS) can be proposed to treat the majority of carotid stenoses. Brain embolization takes place and routine use of Embolic Protection Devices (EPD) is warranted. Many EPDs have significant limitations, which may be addressed by a new EPD, the FiberNet (Lumen Biomedical, Plymouth, MN). METHODS: The system consists of a 3-dimensional expandable filter made of fibers, which expand radially, mounted onto a 0.014'' wire and retrieval catheter. FiberNet can capture particles as small as 40 microm without compromising flow. RESULTS: 35 lesions treated in 34 patients. Male 67.6%. Age: 71.4 +/- 8.8 (50-85). Average stenosis 84.5% +/- 7.9 (70-99). 29.4% were symptomatic. Technical success: 34/35 (97%). No stroke or death within 30 days. Neurological events: two permanent amaurosis, one amaurosis fugax. All samples visually contained significant amounts of emboli. The mean surface area of debris caught was 63.8 mm(2) (37.7-107.5). Comparisons were made with other EPDs. The mean surface area of debris caught was 12.2 mm(2) (2.7-34.3). No changes were noted in CT/MRI at 30-day post procedure. CONCLUSION: The first human use of this new novel EPD in carotid artery stenting is encouraging. The FiberNet was easy to use and confirmed the ability to capture particles less than 100 microm. The feasibility of the FiberNet has been demonstrated. Additional patients will demonstrate the overall safety and efficacy of this new EPD device.

Bovine pericardium buttress reinforces colorectal anastomoses in a canine model.

PURPOSE: The consequences of an anastomotic leak or disruption can be devastating, particularly in the colorectal surgery population. The purpose of this study was to evaluate and compare colon anastomoses with or without a collagen matrix buttress derived from bovine pericardium. METHODS: A circular stapler was used to create colon-colon anastomoses in a canine model. Twenty animals underwent two anastomoses each: one buttressed with bovine pericardium, and one without any reinforcement. Staple lines were evaluated at Days 0, 3, 7, 14, 42, and 84. Three animals were killed at each time interval, and evaluation included bursting pressure, bursting location, and histology. RESULTS: Colon segments with nonbuttressed anastomoses were more likely to burst at the staple line (63 percent), whereas buttressed anastomoses were more likely to burst at the adjacent intestine (74 percent; P=0.048). The burst pressure of nonbuttressed staple lines tended to be consistently, although not significantly, higher than the burst pressure of buttressed staple lines (P=0.651). At histologic analysis, the bovine pericardium buttress demonstrated an ability to allow cellular ingrowth at Day 3 and neovascularization at Day 7. There was no evidence of stenosis or infection. CONCLUSIONS: The use of a collagen matrix buttress in colorectal anastomoses was safe in a canine model. Our study indicates that true burst strength of the majority of buttressed anastomoses was greater than the adjacent intestine.

Safety and biocompatibility of the Myosplint system--a passive implantable device that alters ventricular geometry for the treatment of heart failure.

A passive implantable device developed for the treatment of heart failure, the Myosplint System, has demonstrated therapeutic efficacy in a canine model of pacing induced heart failure. The current study sought to demonstrate chronic device safety and biocompatibility, in vivo, in a normal porcine model. Two devices were implanted into each normal, beating heart of 6 juvenile and 15 adult pigs without cardiopulmonary bypass. Animals survived 90 (juvenile and adult) or 180 days (adult only). Serial hematologic and biochemical profiles were evaluated in each pig during the study period. A comprehensive necropsy study was performed in each pig to evaluate device stability, healing response, thromboembolism, hemorrhage, and intravascular hemolysis related to the Myosplint system. Six adult animals died from infectious disease (four) or perioperative (two) complications unrelated to device design or function and were excluded from the final analysis. No clinical, biochemical or pathologic evidence of significant, device related adverse events was observed in surviving animals. The chronic myocardial healing response appeared normal at term, and all devices maintained their structural integrity throughout the study. The Myosplint system was easily implanted in beating hearts and was rapidly incorporated into host tissues without clinically significant morbidity in this porcine model.