Implantation of the VentrAssist Implantable Rotary Blood Pump in sheep

The VentrAssist Implantable Rotary Blood Pump (IRBP) is a hydrodynamically suspended, electromagnetically driven, centrifugal blood pump that provides continuous flow of up to 10 L/min at 3,000 rpm. In vivo studies in sheep were conducted to assess system design and performance. Surgery involved thoracotomy with subdiaphragmatic pump placement. Cannulae were transdiaphragmatic, with inflow in the left ventricular apex and outflow anastomosed to the descending aorta. Animals had no anticoagulation or antiplatelet therapy after surgery and no prophylactic antibiotics after recovery. Twelve sheep were supported for 622 pump days. Estimated pump flow ranged from 1 to 5.5 L/min at 1,800 to 2,000 rpm using 2.5 to 4.5 W. There was no clinical evidence of hemolysis or cardiovascular, renal, or hepatic dysfunction. Adverse outcomes included kinking/disconnection of the outflow cannula caused by the graft bend relief (n = 4), which was addressed through cannula redesign. Pump electrical malfunction (n = 4), caused by a silicone potting compound, was corrected using a neutral curing potting material. Surgical/husbandry issues (n = 2) also were addressed. The VentrAssist IRBP provides high flow at low rotational speed and power consumption. Further trials are in progress in advance of in vivo studies of the safety and efficacy of the final system.     

Structure-based design of novel inhibitors of 3-deoxy-D-manno-octulosonate 8-phosphate synthase

3-Deoxy-D-manno-octulosonate 8-phosphate (KDO8P) is the phosphorylated precursor of KDO, an essential sugar of the lipopolysaccharide of Gram negative bacteria. KDO8P is produced by a specific synthase (KDO8PS) by condensing arabinose 5-phosphate (A5P) and phosphoenolpyruvate (PEP), with release of inorganic phosphate. As KDO8PS is present in bacteria and plants, but not in mammalian cells, and mutations that inactivate KDO8PS also block cell replication, KDO8PS is a promising target for the design of new antimicrobials that act by blocking lipopolysaccharide biosynthesis. Previous studies have shown that a compound mimicking an intermediate of the condensation reaction is a good ligand and a powerful inhibitor. Here we report on the crystallographic investigation of the binding to KDO8PS of new derivatives of this original inhibitor. The structures of the enzyme in complex with these compounds, and also with the PEP analogs, 2-phosphoglyceric acid (2-PGA) and Z-methyl-PEP, point to future strategies for the design of novel inhibitors of KDO8PS.     

Epilepsy surgery outcome among US veterans

We retrospectively studied the outcome of anterior temporal lobectomy (ATL) among a population of veterans and evaluated outcome related to comorbidities. Veterans who underwent ATL between 1990 and 2001 at the Veterans Administration Hospital in Madison, Wisconsin, were included. Data related to postoperative seizure outcome, quality of life outcome, and employment outcome were collected. Factors associated with favorable outcome and outcome related to comorbidities were evaluated. Twenty-seven patients were entered into the study. The mean age at onset of seizures was 25 years (+/-10.2). History of a non-substance abuse psychiatric diagnosis, and substance abuse was present in 26% (7/27) and 30% (9/27), respectively, prior to surgery. While 66.6% (18/27) had a good outcome (Engel's Class I), no difference in the frequency of good outcome was seen among the patients with a history of substance abuse, other psychiatric diagnosis (71%), or no psychiatric diagnosis (67%). There was a significant correlation between seizure outcome and quality of life score (r(s)=0.67, p<0.001) and postoperative employment gains (r(s)=0.48, p=0.01). Outcomes among veterans that underwent ATL can be satisfactory even in the context of the late mean age of epilepsy onset and the psychiatric diagnoses that were present in this sample.     

Non-invasive flow estimation in an implantable rotary blood pump: a study considering non-pulsatile and pulsatile flows

Non-invasive estimation of flow was investigated in an implantable rotary blood pump (iRBP) with a hydrodynamic bearing. The effects of non-pulsatile and pulsatile flows were studied using in vitro mock loops, and acute (N = 3) and chronic (N = 6) ovine experiments. Using the non-pulsatile and pulsatile mock loops an average flow estimation algorithm was derived from root mean square (RMS) pump impeller speed and RMS input power. These algorithms were programmed into the iRBP controller for subsequent validation in vivo. In the acute experiments, venous return and systemic vascular resistance were adjusted through pharmacological intervention and exsanguination to produce an average range of pump flows from 0.0 to 2.6 l min(-1). Over this range the RMS estimation error was 88 +/- 12 ml, with a linear correlation slope of 0.992 +/- 0.006 (R2 = 0.986 +/- 0.004). In the chronic experiments, animals were monitored daily for up to three months and an average range of flows from 2.8 to 4.8 l min(-1) recorded. A linear correlation between the estimated and measured pump flows yielded a slope of 1.005 +/- 0.006 (R2 = 0.966 +/- 0.004). The RMS estimation error was 120 +/- 11 ml. Using this algorithm it is possible to effectively estimate flow in a rotary blood pump without implanting additional invasive sensors.     

Initial experience with intraoperative magnetic resonance imaging in spine surgery

STUDY DESIGN: A case series of 12 patients who underwent spine surgery in an intraoperative magnetic resonance imager (IMRI). OBJECTIVES: To determine the advantages, limitations, and potential applications to spine surgery of the IMRI. SUMMARY OF BACKGROUND DATA: Existing stereotactic navigational systems are limited because images are obtained before surgery and are not updated to reflect intraoperative changes. In addition, they necessitate manual registration of fiducial landmarks on the patient's anatomy by the surgeon to the previously obtained image data set, which is a potential source of error. The IMRI eliminates these difficulties by using intraoperative acquisition of MRI images for surgical navigation with the capacity for both image update and image-guided frameless stereotaxy. The IMRI is a novel cryogenless superconducting magnet with an open configuration that allows the surgeon full access to the patient during surgery and intraoperative imaging. METHODS: T1- and T2-weighted fast spin echo images were obtained for localization, after surgical exposure and after decompression during the course of 12 spine surgeries performed in the IMRI. RESULTS: The authors performed a series of 12 procedures in the IMRI that included three lumbar discectomies, three anterior cervical discectomies with allograft fusion, three cervical vertebrectomies with allograft fusion, two cervical foraminotomies, and one decompressive cervical laminectomy. The system provided rapid and accurate localization in all cases. The adequacy of decompression by MRI during surgery was confirmed in 10 of 12 cases. CONCLUSIONS: The IMRI provided accurate and rapid localization in all cases and confirmed the adequacy of decompression in the majority of cases. Future applications of the IMRI to spine surgery may include intraoperative guidance for resection of spine and spinal cord tumors and trajectory planning for spinal endoscopy or screw fixation.     

Volumetric rendering techniques: applications for three-dimensional imaging of the hip

Volumetric rendering is a new approach to three-dimensional (3D) imaging that overcomes many of the drawbacks of currently available surface-rendering systems. Its application on the Pixar Imaging System in two cases of acetabular fracture was assessed to illustrate the features of the technique. The fast-computing architecture and large memory of this system allow rapid generation of a series of high-quality 3D images in each plane of rotation (x or spinal axis, z or somersaulting axis) that can be viewed as independent static images or as an animated real-time video loop. Editing to remove the normal contralateral hemipelvis enhances appreciation of acetabular abnormalities. Every pixel of computed tomographic data is preserved, allowing representation of both soft tissue and bone as translucent overlap. The presentation of data also allows detection of subtle abnormalities and features and minimizes the artifact generation common in surface-rendered images.     

The effect of local controlled release of sodium fluoride on the stimulation of bone growth

This study was performed to test the feasibility of using a biodegradable delivery system for the local controlled release of sodium fluoride as a mechanism for the stimulation of local bone growth. Sodium fluoride grains were mixed with poly-DL-lactic acid (PLA), and the mixture was then dissolved in acetone. After driving off the solvent, sheets of this material were rolled into rods 3.2 mm in diameter and 28.6 mm long. These were inserted into the intramedullary canals of the right femora of adult New Zealand White rabbits. A sham implant, made the same way but containing no fluoride, was inserted into the contralateral left leg. The effects of three different concentrations of sodium fluoride, 0.125 g NaF/g PLA, 0.250 g NaF/g PLA, and 0.500 g NaF/g PLA, were determined after a 4-week implantation period. In a second set of experiments, the concentration was fixed at 0.500 g NaF/g PLA with implantation durations of 4, 8, and 16 weeks. Expressed in terms of property ratios (experimental/control), bending strengths of the femora were significantly raised in most groups with the notable exception of Group 3 (0.500 g NaF/g PLA, 4 weeks). Cross-sectional area ratios in the distal femora were increased in all groups compared to right/left values for a normal unoperated group (p less than 0.05), with the highest ratio being 1.50 (SD = 0.44) for Group 4 (0.500 g NaF/g PLA, 8 weeks). Only Group 4 animals showed significant (p less than 0.05) increases in midshaft area ratio and none had responses proximally. Growth rates, measured by sequential fluorochrome labeling of bone followed the area ratio data and were only significant for the distal femora.     

Postradiation malignant fibrous histiocytoma of bone. A clinicopathologic study of 20 patients

Among the 130 primary or secondary malignant fibrous histiocytomas of bone diagnosed and treated at Memorial Hospital for Cancer and Allied Diseases during the previous half century, 20 (15.4%) arose as a direct consequence of irradiation. This type is the commonest secondary osseous malignant fibrous histiocytoma at this institution. It affects the ilium, the scapula, and the distal end of the femur most frequently, predominantly in patients whose age peaks in the fifth decade of life, when their sarcomas developed. Grounds for the irradiation were either nonosseous conditions (13 patients) or preexistent skeletal lesions (seven patients). Reasons for the incidental bone irradiation included Hodgkin's disease; carcinoma of cervix, breast, or lung; bilateral retinoblastoma, and others; giant cell tumors predominated among the irradiated skeletal lesions. The mean and the median radiation doses were 6,040 and 5,700 rads, respectively. The latent period between irradiation and the appearance of the bone sarcoma ranged from 4 to 47 years with a mean of 16.5 and a median of 14.5 years, respectively. The cumulative disease-free survival rate at 3 years was 58%. Although all patients who received their radiation therapy for a preexistent bone lesion survived, only 27% of patients whose bone was normal at the time of irradiation are alive and well at the 3-year mark.