Biomedical subjects

S B Harvey

Publications and source records attributed to S B Harvey.

13 recordsLinked to original sources

PubMed2004

Bisphosphonate-ciprofloxacin bound to Skelite is a prototype for enhancing experimental local antibiotic delivery to injured bone.

BACKGROUND: The risk of osteomyelitis after open bone fracture may be reduced by locally applied antibiotics. ENC-41-HP (E41), which comprises ciprofloxacin linked to a 'bone seeking' bisphosphonate, loaded on to carrier Skelite calcium phosphate granules (E41-Skelite) has favourable in vitro characteristics for application to wounded bone. This study assessed E41-Skelite in a rat model of acute tibial osteomyelitis. METHODS: Mechanically induced tibial troughs were contaminated with approximately log10 4 colony forming units (c.f.u.) of Staphylococcus aureus (Cowan 1 strain) 'resistant' to E41 (minimum inhibitory concentration 8-16 microg/ml), lavaged and packed with Skelite alone, or with E41-Skelite slurry. Animals were killed at 24 h (n = 62), 72 h (n = 46) or 14 days (n = 12), and each tibia was assessed for S. aureus load (c.f.u./g tibia) and histological appearance (14 days only). RESULTS: At 24 and 72 h, the tibias of rats treated with E41-Skelite (n = 54) had a significantly lower mean (s.e.m.) load of S. aureus than animals that received Skelite alone (n = 54): log10 3.6(0.2) versus 6.4(0.1) c.f.u./g respectively at 24 h (P < 0.001, Mann-Whitney rank sum test) and log10 4.4(0.2) versus 6.6(0.1) c.f.u./g at 72 h (P < 0.001). At 14 days, E41-Skelite-treated tibias had fewer bacteria, no signs of osteomyelitis and histological signs of healing. CONCLUSION: E41-Skelite, a prototype granulated topical antibiotic delivery system, reduced the development of infection in experimental bone wounds.

Animals↗

PubMed2001

Elevated function of blood clotting factor VIIa mutants that have enhanced affinity for membranes. Behavior in a diffusion-limited reaction.

Blood clotting factor VIIa is involved in the first step of the blood coagulation cascade, as a membrane-associated enzyme in complex with tissue factor (TF). Factor VIIa is also an important therapeutic agent for hemophilia where its function may include TF-independent as well as TF-dependent mechanisms. This study compared the activity of wild type factor VIIa (WT-VIIa) with that of a mutant with elevated affinity for membrane (P10Q/Q32E, QE-VIIa). Phospholipid and cell-based assays showed the mutant to have up to 40-fold higher function than WT-VIIa in both TF-dependent and TF-independent reactions. Tissue factor-dependent reactions displayed the maximum enhancement when binding had reached equilibrium in competition with another TF-binding protein. In liposome-based assays, the association rate of WT-VIIa with TF occurred at a physical maximum and could not be improved by site-directed mutagenesis. A practical consequence was identical function of WT-VIIa and QE-VIIa in assays that depended entirely on assembly kinetics. Thus, factor VIIa mutants provided unique reagents for probing the mechanism of factor VIIa action. They may also offer superior agents for therapy.

Animals↗

PubMed2001

The effect of dental implant spacing on peri-implant bone using the rabbit (Oryctolagus cuniculus) tibia model.

PURPOSE: This study investigated the effects of implant proximity on inter-implant bone height, density, and osseointegration using digital radiography and histology. MATERIALS AND METHODS: After a feasibility study, a total of 80 endosteal implants were placed in 20 New Zealand White Rabbit tibias. With the aid of a surgical jig, four 8.5-mm implants were placed in the medial aspect of the tibial crest at inter-implant distances of approximately 1, 1.5, and 3 mm. Standardized digital radiographs using a paralleling device were made immediately after placement of implants. Implants were allowed to osseointegrate for 90 days. After this healing period, the animals were sacrificed, and the standardized radiographs were repeated. The tibias were harvested, processed, and invested in epoxy. Sagittal sections were made from each specimen for histologic evaluation. The initial and postmortem digital radiographs were evaluated for inter-implant distances, vertical bone height changes over time and between implant pairs, and bone density changes over time and between implant pairs using a computer image analysis program and computer statistics program. RESULTS: The actual inter-implant distances were consistent in a range of 0.2 mm. Bone height increased significantly from presurgical levels at all 3 locations (p < .0005). Repeated measures analysis of variance comparing change in bone height at the 3 implant pair distances showed significant differences among the 3 (p = .002). Paired t tests showed that the amount of bone growth at the 1-mm separation site was significantly greater than the 1.5-mm site (p = .026) and the 3-mm site (p = .001), whereas bone growth at the 1.5- and 3-mm sites did not show significant differences (p = .162). A repeated measures analysis of variance comparing change in bone density showed no significant differences (p > .05) among the 3 inter-implant distances for either the 8-mm position (approximately crestal bone height) or the 6-mm position (approximately 2 mm subcrestal). CONCLUSION: Within the limits of this study, it seems placing implants closely together does not adversely affect bone height or density. Conversely, it seems that placing implants closer together may increase bone growth.

Analysis of Variance↗

PubMed2001

Adaptation of a dental RadioVisioGraph unit as a laboratory animal research tool.

We have adapted the RadioVisioGraph (RVG), a digital radiography system designed for dentistry, to become a versatile research tool in a small research facility. We have used this modified digital imaging system in our institution to assess bone fractures and ossification in rabbit tibias in which titanium posts were placed in close proximity to one another, to evaluate bone fill in rats with experimental cranial critical-size defects, and to ensure the proper placement of oral gavage tubes in rodents. This method provides instantaneous digital radiographs, thus not requiring a dedicated X-ray suite or film-processing equipment, and reduces scatter radiation by < or =95%. The use of this technology in a small research facility has greatly improved the quality of both the care our animals receive and the research data we obtain.

Animal Welfare↗

PubMed2000

Vitamin K-dependent proteins.

Vitamin K is required for the synthesis of gamma-carboxyglutamate (Gla) during postribosomal protein modification. Substrates include blood clotting proteins, bone proteins, cell signaling, and receptor proteins. In addition, Gla is a component of short toxin peptides from the marine snail Conus. Studies of structure-function relationships are the most advanced for the blood coagulation proteins. Reviews of vitamin K action and blood coagulation are presented. Special focus is on the structure-function role of Gla in blood coagulation and the impact of this amino acid on enzyme reaction kinetics. This amino acid forms calcium and membrane binding sites for these proteins. Two proposed mechanisms of protein-membrane attachment are reviewed. One involves membrane attachment by protein insertion into the hydrocarbon region of the membrane, while another considers attachment by specific interactions with phospholipid head groups. Membrane attachment generates the potential for several forms of nonclassical enzyme kinetic behaviors, all of which have been observed in vitro. For example, the reaction may be limited by properties of the enzyme active site, a condition that allows use of classic steady-state enzyme kinetic parameters. However, the reaction may be limited by substrate binding to the membrane, by substrate flux through solution, and/or by solvent flow rates across the membrane surface. These states provide special mechanisms that are not anticipated by classical steady-state kinetic derivations. They may be used to regulate coagulation in vivo. Overall, vitamin K research spans the spectrum of biological research and experience. Exciting new ideas and findings continue to emanate from vitamin K-related research.

Animals↗

PubMed2000

Prevention of adhesions to polypropylene mesh in a traumatized bowel model.

BACKGROUND: Polypropylene mesh (PPM) is an effective material for the repair of abdominal wall defects, but has a tendency to induce dense adhesions when in contact with viscera. Seprafilm (Genzyme Corp, Cambridge, MA), a bioresorbable membrane, has been shown to reduce adhesion formation after midline closures in humans and to PPM in animals. Given the increased inflammatory response expected with surgical trauma, its efficacy under surgical conditions has been questioned. STUDY DESIGN: A prospective, randomized, blinded study was conducted using a rabbit model. Standardized abdominal wall defects were created in three groups of New Zealand white rabbits. The cecum was deserosalized to simulate the effects of trauma. The abdominal defect was then repaired with PPM. In the control group, no Seprafilm was used. In the first experimental group Seprafilm was placed between the mesh and the abdominal viscera. In the second experimental group Seprafilm was placed over the deserosalized area and between the mesh and abdominal viscera. Animals were sacrificed at 30 days and adhesions were categorized and quantified using digital image analysis of inked specimens. The strength of incorporation was also determined. RESULTS: The formation of adhesions between the viscera and mesh repair was dramatically reduced in both experimental groups compared with the control group. The incidence of visceral adhesions was reduced by 80% in the single film group (p = 0.0004) and 90% in the double film group (p = 0.00008). The reduction in surface area of adhesions was 96.4% in the single film group (p = 0.000019) and 99.4% in the double film group (p = 0.00002). Omental adhesions were reduced by 30% but this did not achieve statistical significance. Strength of incorporation was not adversely affected in either group. CONCLUSIONS: Seprafilm is highly effective in preventing adhesions to PPM. This effect was not diminished by the presence of visceral trauma and its resultant inflammatory response. The use of Seprafilm does not adversely affect tissue incorporation. Clinical trials are warranted to determine if the protective effects of Seprafilm demonstrated in this study are applicable in the clinical setting.

Abdominal Muscles↗

PubMed1998

Measurement of lumbar spinal flexion-extension kinematics from lateral radiographs: simulation of the effects of out-of-plane movement and errors in reference point placement.

Flexion-extension of the spine is defined in the sagittal plane, which divides the body into right and left halves, and can be measured from lateral radiographs, including those obtained by videofluoroscopy. The effects of axial rotation and lateral bending, which lead to movement out of the sagittal plane, were investigated by generating a three-dimensional computer model of two adjacent vertebrae and projecting it on to the sagittal plane. The projected model was measured as if it were a radiograph, allowing the effects of out-of-plane movement and errors in reference point placement to be calculated. Reference points were defined as the corners of a quadrilateral which fully enclosed the two-dimensional image of each vertebral body, and their projected locations were randomly displaced by 0.5 mm in order to simulate the measurement process. A combination of lateral bending with 1 degree of flexion can lead to a root mean squared (RMS) variation in the calculated position of the instantaneous centre of rotation (ICR) of 292 mm, reducing to 5 mm for 10 degrees of flexion. When the reference point quadrilaterals were divided into two triangles, the RMS variation in the calculated position of the centroid of one of the triangles was only 0.42 mm under the same conditions, remaining constant over the same flexion range. Similar results were obtained when axial rotation was combined with flexion. The calculated centroid provides a robust reference point for kinematic calculations.

Biophysical Phenomena↗

PubMed1998

Measurement of lumbar spine flexion-extension using a low-field open-magnet magnetic resonance scanner.

RATIONALE AND OBJECTIVES: The authors investigated the feasibility of using a low-field open-magnet magnetic resonance (MR) scanner to acquire functional flexion-extension images for range of motion (ROM) measurements on the lumbar spine. METHODS: Seventeen healthy subjects with no symptoms of back pain (age range, 22-59 years) were scanned in a low-field open-magnet MR scanner in the flexed, neutral, and extended positions. Each image was downloaded to a computer workstation for subsequent flexion-extension, lordosis, and ROM measurement. RESULTS: Data from two subjects were not analyzed because their images did not show all the lumbar vertebrae. For the remaining 15, there was a large variation in the magnitude of the ROM values (range, 9 degrees-70 degrees; mean 36.4 degrees, SD 16.5 degrees). However, there was a significant correlation between age and ROM (r = -0.63; P < 0.05). CONCLUSIONS: The low-field open-magnet MR scanner provides a method for noninvasive imaging of the lumbar spine, allowing the subject freedom of movement in the horizontal plane. This enables functional flexion-extension images of the lumbar spine to be acquired.

Adult↗

PubMed1998

Rabbit genital tissue is susceptible to infection by rabbit oral papillomavirus: an animal model for a genital tissue-targeting papillomavirus.

Rabbit oral papillomavirus (ROPV) is a mucosatropic papillomavirus which naturally infects oral mucosal sites of domestic rabbits. In this study, we tested the hypothesis that rabbit genital mucosa is also susceptible to ROPV infection by using the athymic mouse xenograft system and adult immunocompetent rabbits. Subrenal xenografts of ROPV-infected rabbit vulvar and penile sheath tissues were strongly positive for ROPV infection by histologic, in situ hybridization, and Southern analyses. Direct inoculation of adult rabbit penises with infectious ROPV produced small raised lesions of approximately 1 by 1 by 1 mm that were ROPV positive by both in situ hybridization and Southern analyses and were also viral capsid antigen positive by immunohistological staining. Infection of rabbit genital tissues with ROPV may be a useful animal model for the study of genital tissue-targeting papillomaviruses.

Animals↗

PubMed1998

Comparison of the precision of two vertebral morphometry programs for the lunar EXPERT-XL imaging densitometer.

Comparative precision tests of the vertebral height measurement function of the Aberdeen Vertebral Morphometry System (AVMS) software and Lunar EXPERT-XL software were undertaken using four vertebrae from the same lateral spine dual energy X-ray absorptiometry (DXA) image of the same subject (male, 67 years). Two of the vertebrae were abnormal and two were normal. Three observers inexperienced in morphometry and one experienced observer took part in the study. Repeatability was obtained from 10 sequential measurements of the posterior, middle and anterior heights at the same sitting by the same observer. Intraobserver reproducibility compared the means of one set of measurements for all vertebrae with another taken 1 week later. Interobserver reproducibility compared the means of one set of measurements for all vertebrae from an experienced and an inexperienced observer, and from two inexperienced observers. The AVMS software had significantly higher (p < 0.05) repeatability (mean coefficient of variability, CV = 3.5%) than the Lunar software (mean CV = 5%), significantly higher (p < 0.01) intraobserver reproducibility (mean CV = 4.6%) than the Lunar software (mean CV = 8.5%), and significantly higher (p < 0.05) interobserver reproducibility (mean CV = 4.7%) than the Lunar software (mean CV = 7.5%). In conclusion, the new AVMS method possessed higher precision when measuring both abnormal and normal vertebrae and when used by both experienced and inexperienced observers.

Absorptiometry, Photon↗

PubMed1996

Reaction of nitric oxide and its derivatives with sulfites: a possible role in sulfite toxicity.

The reaction between sulfites and nitric oxide or proposed carriers of nitric oxide (nitrosylated bovine serum albumin and S-nitrosoglutathione) was investigated as a potential source of the adverse effects of sulfites on biological systems. Rapid reaction occurred between sulfites and all of these reagents. Also, the ability of nitric oxide and these carriers of nitric oxide to inhibit platelet aggregation was reversed by low concentrations of sulfites. Counteraction of nitric oxide's ability to function in cell signaling processes may be a major cause of sulfite toxicity.

Animals↗

PubMedDate not supplied

Port-site recurrence reproduced in the VX-2 rabbit carcinoma model: an in vivo model comparing laparoscopic port sites and open incisions.

BACKGROUND: The use of advanced laparoscopy remains controversial in the field of surgical oncology because the potential for port-site recurrence may violate sound oncologic principles. Two mechanisms are theorized to be the cause of port-site recurrences: first, indirect contamination caused by pneumoperitoneum, aerosolization, or intraperitoneal spread, and second, direct contamination by physical trocar seeding. METHODS: A VX-2 carcinoma cell suspension was transferred under the left renal capsule of 31 rabbits with either an open flank incision (16) or laparoscopy (15). Animals were observed for tumor recurrence at the video port, the working port, and the open incision. Intraoperative findings and necropsy were used to document recurrence. RESULTS: The open incision technique resulted in local tumor recurrence in 1/16 animals with 16/16 viable intraabdominal tumors. The laparoscopic technique resulted in 0/15 video port-site recurrences and 9/15 working port-site recurrences, with 14/15 viable intraabdominal tumors. Recurrence at the laparoscopic working port occurred more frequently than in the open (P < 0.02) or laparoscopic video port groups (P < 0.007). No significant difference existed in recurrence between the open incision and the laparoscopic video port (P > 0.5). CONCLUSIONS: Laparoscopic port-site recurrences can be reproduced using the transplantable VX-2 rabbit carcinoma model. In the VX-2 model, trocar recurrence is the result of direct contamination via surgical instrumentation of viable tumor cells. The effect of the pneumoperitoneum or intraperitoneal cytological spillage (indirect contamination) does not have any effect on trocar recurrence. This model can be used to test and improve laparoscopic techniques to minimize the risk of port-site recurrence. Until technological advances have eliminated the risk of trocar recurrences, direct contact between malignant cells and laparoscopic instruments should be performed with caution.

Animals↗