A review of neuroendoscopy and potential applications in veterinary medicine.

The endoscope was first developed over 200 yr ago. Endoscopy has since been applied to many disciplines of medicine. Its application to the nervous system was initially slow and not widely accepted and mainly involved the biopsy of tumors and the treatment of hydrocephalus. Several reasons for neuroendoscopy's limited use include inadequate endoscope technology, high skill level required, the advent of the surgical microscope, and the development of other treatments such as ventricular shunting. Over the past 50 yr, improvements in optical glass lenses, fiber optics, and electrical circuitry has led to better equipment and a revival of neuroendoscopy. Neuroendoscopy is now used in many diseases in human medicine including hydrocephalus, neoplasia, and intracranial cysts. This review presents the history of neuroendoscopy, the equipment and technology used, and the possible translation of techniques currently used in human medicine to veterinary medicine.

Impact of cardiac resynchronization therapy on exercise performance, functional capacity, and quality of life in systolic heart failure with QRS prolongation: COMPANION trial sub-study.

BACKGROUND: A total of 405 participants in the Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure trial were prospectively enrolled in an exercise sub-study designed to study the influence of cardiac resynchronization therapy (CRT) on measures of exercise capacity, functional capacity, and quality of life (QOL). METHODS AND RESULTS: Substudy eligibility included New York Heart Association (NYHA) functional Class III or IV heart failure, left ventricular ejection fraction < or =0.35, QRS interval of > or =120 ms, normal sinus rhythm, a heart failure hospitalization (or equivalent) within 1 year, a peak VO2 < or =22 mL x kg x min, the ability to walk 150 to 425 meters in 6 minutes, forced expiratory volume in 1 second/forced vital capacity > or =50%, and no clinical indication for a pacemaker or implantable cardioverter-defibrillator. Patients were randomized in a 1:4 ratio to optimal medical therapy (OPT) or to OPT plus CRT. Cardiopulmonary exercise testing (peak VO2 and 6-minute walk distance [6MWD]) and assessment of NYHA functional class and QOL were assessed at baseline and at 3 and 6 months of assigned therapy. There was no significant improvement in peak VO2 at 6 months in the CRT group compared with the OPT group (+0.63 mL x kg x min) by unadjusted analysis (P = .05) or by analyses adjusted for missing data. Thus the primary end point of the study was not met. There was significantly greater improvement in the 6MWD in the CRT group compared with the OPT group at both 3 and 6 months by both statistical methods (P < or = .045). Likewise, a greater proportion of CRT patients improved by 1 or more NYHA functional classes (P < .01) at 3 months and had better QOL scores (P < .01) at 3 and 6 months compared with the OPT patients. Baseline peak VO2 predicted clinical events (time to death, time to death or first hospitalization, or time to death and first heart failure hospitalization: P < .05) in CRT participants. CONCLUSION: CRT patients with moderate to advanced symptoms of systolic heart failure and prolonged QRS intervals benefit from the addition of CRT to OPT in terms of exercise capacity, functional status, and QOL. CRT should be considered standard therapy in this select group of heart failure patients.

A cooperative network of trained sites for the conduct of a complex clinical trial: a new concept in multicenter clinical research.

BACKGROUND: The purpose of this report is to present a model of physicians in full-time clinical practice participating as investigators in multicenter clinical trials, sponsored by a pharmaceutical or medical device company. METHODS: This gas-exchange substudy was conducted as a pilot study to establish the feasibility of the 10-member EXERcise testing group of the Duke University Cooperative Cardiovascular Society (EXERDUCCS) consortium to perform a complex multicenter trial using cardiopulmonary exercise testing. An active interchange of information was established involving the principal investigator for the substudy, a dedicated full-time project coordinator, a medical director of the overall EXERDUCCS network site, the project coordinator for the sponsor, and all the participating EXERDUCCS investigators and coordinators. RESULTS: The sponsor set as a goal of enrollment of 6 subjects per site, and 8 of the 10 sites met this goal. As a result of the successful enrollment and completion of the study and substudy by the EXERDUCCS sites, the sponsor subsequently increased the payment stipends to the sites to compensate for the extra work and expense incurred. CONCLUSIONS: This cooperative experience accomplished several goals: (1) it allowed a complex clinical trial to be successfully completed in a time frame which would not have been possible using only single unconnected sites; (2) it educated the physician-investigators (and their personnel) in exercise cardiopulmonary; and (3) it prepared the sites for future clinical trials involving this methodology.

Effect of body position on cranial migration of epidurally injected methylene blue in recumbent dogs.

OBJECTIVE: To determine the relationship between different body positions during recumbency on the cranial migration of epidurally injected methylene blue in canine cadavers. SAMPLE POPULATION: 21 fresh cadavers of clinically normal adult female mixed-breed dogs. PROCEDURE: Dogs were randomly assigned to the following 3 groups: dogs remaining in right lateral recumbency (n = 7), dogs rotated from left to right lateral recumbency (7), and dogs rotated from dorsal to right lateral recumbency (7). Each dog received an epidural injection of 0.05% methylene blue (0.1 mL/kg) at the lumbosacral space. A dorsal laminectomy of the vertebral column was made, and cranial extent of methylene blue in 4 quadrants (right lateral, left lateral, ventral, and dorsal) was determined by examining dura mater staining. RESULTS: No significant difference was found among groups in regard to body weight or body condition score. Epidural cranial migration of methylene blue in the right lateral quadrant was significantly greater in dogs that remained in right lateral recumbency than in dogs that were rotated from left to right lateral recumbency. No significant difference was found within groups for epidural cranial migration of methylene blue between each quadrant. No significant relationship was found between body weight or body condition score and epidural cranial migration of methylene blue. CONCLUSIONS AND CLINICAL RELEVANCE: Body positioning and amount of recumbency time influence cranial migration of epidurally injected methylene blue. If greater cranial migration of an epidurally administered drug is desired, placing the patient in lateral recumbency with the surgical site on the dependent side may precede surgery.

Cardiac resynchronization therapy for the treatment of heart failure in patients with intraventricular conduction delay and malignant ventricular tachyarrhythmias.

OBJECTIVES: This study was conducted to assess the safety and effectiveness of cardiac resynchronization therapy (CRT) when combined with an implantable cardioverter defibrillator (ICD). BACKGROUND: Long-term outcome of CRT was measured in patients with symptomatic heart failure (HF), intraventricular conduction delay, and malignant ventricular tachyarrhythmias (ventricular tachycardia/ventricular fibrillation [VT/VF]) requiring therapy from an ICD. METHODS: Patients (n = 490) were implanted with a device capable of providing both CRT and ICD therapy and randomized to CRT (n = 245) or control (no CRT, n = 245) for up to six months. The primary end point was progression of HF, defined as all-cause mortality, hospitalization for HF, and VT/VF requiring device intervention. Secondary end points included peak oxygen consumption (VO(2)), 6-min walk (6 MW), New York Heart Association (NYHA) class, quality of life (QOL), and echocardiographic analysis. RESULTS: A 15% reduction in HF progression was observed, but this was statistically insignificant (p = 0.35). The CRT, however, significantly improved peak VO(2) (0.8 ml/kg/min vs. 0.0 ml/kg/min, p = 0.030) and 6 MW (35 m vs. 15 m, p = 0.043). Changes in NYHA class (p = 0.10) and QOL (p = 0.40) were not statistically significant. The CRT demonstrated significant reductions in ventricular dimensions (left ventricular internal diameter in diastole = -3.4 mm vs. -0.3 mm, p < 0.001 and left ventricular internal diameter in systole = -4.0 mm vs. -0.7 mm, p < 0.001) and improvement in left ventricular ejection fraction (5.1% vs. 2.8%, p = 0.020). A subgroup of patients with advanced HF (NYHA class III/IV) consistently demonstrated improvement across all functional status end points. CONCLUSIONS: The CRT improved functional status in patients indicated for an ICD who also have symptomatic HF and intraventricular conduction delay.

Neospora caninum: adoptive transfer of immune lymphocytes precipitates disease in BALB/c mice.

Neospora caninum is a recently described apicomplexan parasite first isolated from a dog in 1988 and has subsequently been shown to infect a wide range of mammals. In mice, Neospora can cause primary pneumonia, myositis, encephalitis, radiculoneuritis, and pancreatitis. Whereas, certain aspects of the host immune response to Toxoplasma gondii have been well studied, not as much is known about the full immune response to Neospora. This paper examines whether or not immune splenocytes are able to adoptively transfer protection against N. caninum infection in BALB/c mice. Mice receiving immune enriched CD8+ cells had severe neurological signs by 19 days post infection. Mice receiving immune enriched CD4+ cells had mild neurological signs on day 22 post infection. It would appear that additional immune cells can precipitate disease in the presence of circulating lymphocytes.

Seroprevalence of Neospora caninum and Toxoplasma gondii in captive and free-ranging nondomestic felids in the United States.

Seven serum samples of 101 samples from nondomestic, captive and free-ranging felids from the United States were indirect fluorescent antibody positive for antibodies to Neospora caninum, whereas 44 samples were positive for antibodies to T. gondii. Although none of the captive animals displayed clinical signs of disease, nondomestic felids in the United States have been exposed to, and are likely infected with, N. caninum and T. gondii. This may have serious implications for zoological gardens exhibiting susceptible animals, such as kangaroos, close to felids.

Noninfectious inflammatory central nervous system diseases in dogs.

Inflammatory diseases of the central nervous system are often challenging to diagnose. Necrotizing meningoencephalitis, necrotizing leukoencephalitis, and granulomatous meningoencephalomyelitis have characteristic locations of lesions on histopathologic examination and, therefore, characteristic findings from advanced imaging. Together with clinical signs and clinicopathologic data, these characteristic imaging findings may aid in establishing an accurate antemortem diagnosis. Prompt diagnosis can lead to initiation of treatment using a combination of immunosuppressive drugs.

A comparison of cardiac resynchronization by sequential biventricular pacing and left ventricular pacing to simultaneous biventricular pacing: rationale and design of the DECREASE-HF clinical trial.

BACKGROUND: The first generation of cardiac resynchronization therapy (CRT) devices approved for the treatment of heart failure used simultaneous biventricular (BiV) pacing to achieve ventricular resynchronization. Left ventricular pacing alone and sequential BiV pacing also show promise as alternative ways to deliver CRT, but have not been studied together in a large randomized trial. METHODS: The Device Evaluation of CONTAK RENEWAL 2 and EASYTRAK 2: Assessment of Safety and Effectiveness in Heart Failure (DECREASE-HF) Trial is a randomized, double-blind, 3-arm study of patients in New York Heart Association Class III or IV with an ejection fraction of 35% or less and a QRS duration > or =150 ms. Patients are randomized to receive either left ventricular pacing, simultaneous BiV pacing, or sequential BiV pacing. CONCLUSION: The study uses a novel composite endpoint that combines peak oxygen consumption and left ventricular end systolic dimension, thus combining a measure of symptomatic improvement (peak oxygen consumption) with a physiologic measure of ventricular reverse remodeling (left ventricular end systolic dimension) into a single composite score. Additionally, the safety and effectiveness of the CONTAK RENEWAL 2/4/4HE/EASYTRAK 2 system will be evaluated using: heart failure-related adverse events; system-related complications; left ventricular lead-related complications; detection time of induced ventricular fibrillation; and left ventricular lead performance (pacing threshold, pacing impedance, and R-wave amplitude).

Outcomes with an alternate list strategy for heart transplantation.

BACKGROUND: Heart transplantation (HT) is an effective therapy for end-stage heart failure, but its impact is limited by the scarcity of donor organs and stringent selection criteria for both donors and recipients. The creation of an alternate list to match recipients with contraindications to traditional HT with sub-optimal donor organs has been implemented at some centers, but outcomes using this approach are uncertain. METHODS: We created an alternate list that matched recipients in whom standard HT was contraindicated with donor organs that had been rejected for use in standard transplantation. Data on patient characteristics and outcomes were compared with a control group of patients transplanted on the standard list over the same time period. RESULTS: Fifty patients received HT on the alternate list, compared with 195 on the standard list. The most common reasons for recipient listing on the alternate list were age >65 years (n = 28) and diabetes with end-organ dysfunction (n = 9). Alternate-list patients were older and more likely to have an ischemic etiology and diabetes mellitus. The most common reasons for allocation of donor organs to alternate-list patients were coronary artery disease (n = 12), positive hepatitis serology (n = 12) or left ventricular (LV) dysfunction (n = 8). Two-year survival was 70% for alternate-list patients compared with 88% for standard-list patients (p = 0.02). Post-transplant morbidity did not differ significantly between the 2 groups except that alternate-list patients were hospitalized more frequently. CONCLUSIONS: The use of an alternate list can expand the applicability of HT to patients who would otherwise be denied this therapy. Although associated with greater morbidity and mortality than standard-list HT, alternate-list HT resulted in clinical outcomes that were significantly better than the natural history of end-stage heart failure.