The non-steroidal anti-inflammatory drug carprofen negatively impacts new bone formation and antibiotic efficacy in a rat model of orthopaedic-device-related infection.

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for pain management during recovery from orthopaedic surgery. NSAID use is associated with increased risk of bone healing complications but it is currently unknown whether NSAIDs increase the risk of developing an orthopaedic-device-related infection (ODRI) and/or affects its response to antibiotic therapy. The present study aimed to determine if administration of the NSAID carprofen [a preferential cyclooxygenase-2 (COX-2) inhibitor] negatively affected Staphylococcus epidermidis (S. epidermidis) bone infection, or its subsequent treatment with antibiotics, in a rodent ODRI model. Sterile or S. epidermidis-contaminated screws (~ 1.5 x 106 CFU) were implanted into the proximal tibia of skeletally mature female Wistar rats, in the absence or presence of daily carprofen administration. A subset of infected animals received antibiotics (rifampicin plus cefazolin) from day 7 to 21, to determine if carprofen affected antibiotic efficacy. Bone changes were monitored using in vivo µCT scanning and histological analysis. The risk of developing an infection with carprofen administration was assessed in separate animals at day 9 using a screw contaminated with 10² CFU S. epidermidis. Quantitative bacteriological analysis assessed bacterial load at euthanasia. In the 28-day antibiotic treatment study, carprofen reduced osteolysis but markedly diminished reparative bone formation, although total bacterial load was not affected at euthanasia. Antibiotic efficacy was negatively affected by carprofen (carprofen: 8/8 infected; control: 2/9 infected). Finally, carprofen increased bacterial load and diminished bone formation following reduced S. epidermidis inoculum (10² CFU) at day 9. This study suggests that NSAIDs with COX-2 selectivity reduce antibiotic efficacy and diminish reparative responses to S. epidermidis ODRI.

Medication-related osteonecrosis of the jaw in a minipig model: Parameters for developing a macroscopic, radiological, and microscopic grading scheme.

OBJECTIVES: To devise a macroscopic, radiological, and histological scale for assessing pathological changes associated with medication-related osteonecrosis of the jaw in a minipig model. MATERIALS AND METHODS: Medication-related osteonecrosis of the jaw was induced in Göttingen minipigs by weekly intravenous administration of bisphosphonate (zoledronic acid) combined with a tooth extraction procedure. Controls either did not receive zoledronic acid or did not undergo tooth extraction. After 20 weeks, minipigs were euthanized and underwent computed tomography and micro-computed tomography scanning. The mandible underwent additional histological examination. RESULTS: The most consistent macroscopic findings in animals that had developed bisphosphonate-related osteonecrosis of the jaw (BRONJ) were necrotic, denuded bone, and formation of fistula and pus. Under radiological examination, impaired extraction socket healing, decrease in attenuation of bone beneath the extraction site, and periosteal reaction were observed. Under histological examination, demineralization of the extracellular bone matrix, denuding of bone, and osteonecrosis were recorded. CONCLUSION: These parameters were used to develop a scoring system for grading BRONJ.

A rabbit humerus model of plating and nailing osteosynthesis with and without Staphylococcus aureus osteomyelitis.

The local mechanical environment at a fracture is known to influence biological factors such as callus formation, immune cell recruitment and susceptibility to infection. Infection models incorporating a fracture are therefore required to evaluate prevention and treatment of infection after osteosynthesis. The aim of this study was to create humane, standardised and repeatable preclinical models of implant-related bone infection after osteosynthesis in the rabbit humerus. Custom-designed interlocked intramedullary nails and commercially available locking plates were subjected to biomechanical evaluation in cadaveric rabbit humeri; a 10-week in vivo healing study; a dose response study with Staphylococcus aureus over 4 weeks; and finally, a long-term infection of 10 weeks in the plate model.Outcome measures included biomechanical testing, radiography, histology, haematology and quantitative bacteriology. Both implants offered similar biomechanical stability in cadaveric bones, and when applied in the in vivo study, resulted in complete radiographic and histological healing and osteotomy closure within 10-weeks. As expected in the infection study, higher bacterial doses led to an increasing infection rate. In both infected groups, there was a complete lack of osteotomy closure at 4 weeks. C-reactive protein (CRP), lymphocyte: granulocyte ratio and weight loss were increased in infected animals receiving IM nails in comparison with non-inoculated equivalents, although this was less evident in the plate group. In the 10-week infection group, healing does not occur in the plated rabbits. We have successfully developed a rabbit model that is suitable for further studies, particularly those looking into preventative strategies for post-traumatic implant-related osteomyelitis.

Healing pattern of reamed bone following bone harvesting by a RIA device.

Intramedullary nailing has been used for decades to treat fractures of the long bones. However, complications related to the increase in medullary pressure culminated in the development of the Reamer Irrigator Aspirator (RIA). Since its first clinical use, the RIA has moved from a reaming device to a cell and autologous bone-harvesting tool. This increase in use brings with it further clinical questions; namely, does the endosteal bone regenerate sufficiently to allow subsequent reaming procedures. In the current study, endosteal bone regeneration post reaming was assessed in an ovine model. The study included six animals that had one tibia reamed, while the contralateral tibia acted as an intact control. Animals were administered fluorochrome labels in vivo, and bone regeneration was assessed using radiographical analysis. The endpoint of the study was 12 weeks post-surgery, at which time ex vivo analysis consisted of computed tomography and histological assessments. In vivo radiographs indicated limited healing of the reamed bone. However, ex vivo computer tomographical analysis indicated no significant differences in terms of bone volume between the reamed bone and the intact bone. Histological assessment of these regions indicated new bone formation. Fluorescent labelling indicates strong bone formation from 9 weeks post-surgery and as such, the bone formed at 12 weeks was immature in nature and was actively undergoing remodelling. These results indicate that bone regeneration post-reaming was continuing at three months. Therefore, given more time it may have sufficiently healed to allow a surgeon to use the intramedullary canal for a re-reaming procedure.

Spontaneous bilateral avulsion fracture of the tuberositas tibiae in a New Zealand White rabbit - a counterpart to Osgood-Schlatter disease in humans?

The first reported case describing a spontaneous bilateral avulsion fracture of the tuberositas tibiae in a New Zealand White rabbit is presented. So far in animals, this condition has been only described in dogs and horses. In humans, this condition is also called Osgood-Schlatter disease (OSD) or syndrome, traction apophysitis of the tibial tubercle (ATT) or patellar tendon enthesopathy of the tibial tuberosity respectively. It is mainly seen in young adolescents coinciding with periods of growth spurts. In humans, its pathogenesis is believed to be caused by repetitive tendon/muscle strain at the insertion of the patellar tendon to the immature tibial tuberosity, which has its own secondary ossification center. Morphologically this case is characterized by bilateral chronic avulsion with incomplete separation of the tuberositas tibae, and proximal dislocation of the patella (patella alta). Despite these marked pathological changes, the animal was clinically without findings. Nevertheless, this case emphasizes the need for thorough clinical and radiological examination of rabbits intended for preclinical research studies prior to study begin, especially in orthopedic research.

Bone age in 116 untreated patients with Turner's syndrome rated by a computer-assisted method (CASAS).

Bone age maturation in 116 untreated patients with Turner's syndrome was evaluated in a cross-sectional and longitudinal analysis. A total of 265 radiographs were rated using the TW2-RUS method on the computer-assisted skeletal age score (CASAS) system. Bone age was found to be retarded from the chronological age of 3 to 6y. Between the ages of 7 and 12 y bone age almost equalled chronological age and progressed normally at a rate of 1 y y(-1). Bone maturation slowed down thereafter and epiphyseal closure was not reached before the age of 17 y. Reference data are presented on bone age and a bone age maturation curve for untreated patients with Turner's syndrome to be used in clinical practice. In the assessment of bone age and bone age velocity in Turner's syndrome the CASAS system produced reliable and valid results. The absolute difference between repeated bone age ratings was 0.26 "y" (median) with a range of 0.00-0.56 "y". Future studies evaluating the effect of growth-promoting treatment in Turner's syndrome should use a computerized method for the determination of bone age.

Bacterial leakage of mineral trioxide aggregate as compared with zinc-free amalgam, intermediate restorative material, and Super-EBA as a root-end filling material.

Several dye leakage studies have demonstrated the fact that mineral trioxide aggregate (MTA) leaks significantly less than other root-end filling materials. The purpose of this study was to determine the time needed for Serratia marcescens to penetrate a 3 mm thickness of zinc-free amalgam, Intermediate Restorative Material (IRM), Super-EBA, and MTA when these materials were used as root-end filling materials. Fifty-six, single-rooted extracted human teeth were cleaned and shaped with a series of .04 Taper rotary instruments (Pro-series 29 files). Once the canals were prepared in a crown down approach, the ends were resected and 48 root-end cavities were ultrasonically prepared to a 3 mm depth. The teeth were then steam sterilized. Using an aseptic technique, under a laminar air flow hood, the root-end cavities were filled with amalgam, IRM, Super-EBA, and MTA. Four root-end cavities were filled with thermoplasticized gutta-percha without a root canal sealer and served as positive controls. Another four root-end cavities were filled with sticky wax covered with two layers of nail polish and served as negative controls. The teeth were attached to presterilized (ethylene oxide gas) plastic caps, and the root ends were placed into 12-ml vials of phenol red broth. Using a micropipette, a tenth of a milliliter of S. marcescens was placed into the root canal of each tooth. To test the sterility of the apparatus set-up, the root canals of two teeth with test root-end filling materials and one tooth from the positive and negative control groups were filled with sterile saline. The number of days required for S. marcescens to penetrate the four root-end filling materials and grow in the phenol red broth was recorded and analyzed. Most of the samples filled with zinc-free amalgam leaked bacteria in 10 to 63 days. IRM began leaking 28 to 91 days. Super-EBA began leaking 42 to 101 days. MTA did not begin leaking until day 49. At the end of the study, four of the MTA samples had not exhibited any leakage. Statistical analysis of the data indicated Mineral Trioxide Aggregate to be a most effective root-end filling material against penetration of S. marcescens.

Repair of furcal perforations with mineral trioxide aggregate: two case reports.

Furcal perforation is an unfortunate incident that can occur during root canal therapy or post preparation of multirooted teeth. Studies have shown that the materials currently used to repair these iatrogenic accidents are inadequate. The poor prognosis of furcation perforations is probably due to bacterial leakage or lack of biocompatibility of repair materials. On the basis of the recent physical and biologic property studies of the newly introduced mineral trioxide aggregate, this material may be suitable for closing the communication between the pulp chamber and the underlying periodontal tissues. These case reports support this hypothesis.

An alternative treatment for the severely resorped maxillary lateral incisor: a sequela of ectopic eruption.

At times dental crowding, maxillary arch inadequacy, or an abnormal lingual or horizontal position restricts the eruption of the maxillary cuspid. This ectopic eruption can cause the canine to compress the blood supply to the periodontal tissues of the adjacent lateral incisor. If undiagnosed and untreated, physiological and chemical changes are induced, and the lateral root undergoes resorption. When the resorption is severe enough to endanger the retention of the lateral, an endeosseous stabilizer can be placed through the root and extended into the bone to stabilize the tooth artificially. Two cases demonstrate the technique and success of such treatment.

Intentional replantation. A viable alternative for selected cases.

When conventional endodontic treatment or retreatment is not possible, the operator may choose to intentionally extract and replant the involved tooth. Intentional replantation consists of extracting the tooth, finding and correcting the defect, and replanting the tooth in its socket. This article discusses the indications, contraindications, and recommended techniques for intentional replantation. Several successful case reports are described in which intentional replantation was used as a last resort.

A comparison of dentin permeability after bur and laser apicoectomies.

This investigation compared the permeability of dentinal tubules after laser beam and conventional bur apicoectomies. Twenty roots were rountinely instrumented and obturated with laterally condensed gutta-percha. A bur was used to cut the apexes of 10 teeth, while the remaining 10 were cut with a laser beam carried through an optic fiber. A 35-W pulsed Nd:YAG laser system capable of cooling the irradiated area with an air and water spray supplied the power. Except for the apex, the teeth surfaces were coated with a blue wax. The samples were stored for 36 hours in a 2.5% methylene blue solution and were washed, split, and measured for dye penetration. Linear penetration in series 1 averaged 2.4 mm, while series 2 measured 0.9 mm. The laser apicoectomy appears to reduce the permeability of dentinal tubules.

The isolated perfused bovine udder as an in vitro model of percutaneous drug absorption. Skin viability and percutaneous absorption of dexamethasone, benzoyl peroxide, and etofenamate.

Using udders from slaughtered cows as a new in vitro model of percutaneous drug absorption, the tissue viability and the percutaneous absorption of dexamethasone, benzoyl peroxide, and etofenamate were studied. The organ was perfused with gassed tyrode solution for up to 6 hr. As shown by measurement of glucose consumption, lactate production, lactate dehydrogenase activity, and pH in the perfusate, the tissue was viable over a 6-hr period. This was confirmed by a histological examination. Determination of the udder skin-fold thickness demonstrated that no edema developed within the perfusion period. A maximum skin penetration of dexamethasone was found after administration of dexamethasone dissolved in acetone with dimethyl sulfoxide, followed by ointment with salicylic acid, ointment without salicylic acid, and acetone solution. Experiments with benzoyl peroxide and etofenamate demonstrated that the perfused udder skin was capable of metabolizing drugs in vitro. In conclusion, the isolated perfused bovine udder is a new in vitro model, which maintains bovine udder skin with an isolated vasculature in a viable state. Using this in vitro model, we note it is possible to compare the dermal penetration, metabolism, and absorption of substances after topical administration of different drug formulations.

What do the neighbors think now? Community residences on Long Island, New York.

Interviews with 75 neighbors of community residences for adults disabled by mental illness assessed perceptions of impact in five suburban communities. The Not in My Backyard (NIMBY) attitude articulated during program development changed to one of acceptance over time. After a few years experience, the overwhelming majority agreed that the community residences are good neighbors; they have had no problems; and the residences had no adverse effect on property values. The New York State Site Selection Law and comparative data on property value impact are discussed.

The role of bleaching in esthetics.

Bleaching discolored teeth must be considered a viable treatment modality. Although it does not offer the predictability of many cosmetic options, its simplicity and economics demands attention. Combining bleaching with selected bonding and contouring can return a smile to the not-so affluent, conservative, or apprehensive patient who does not wish to face tooth reduction and full coverage.

Widowhood and well-being: an examination of sex differences within a causal model.

National survey data (NCOA/Harris and Associates, 1974) are analyzed in a causal model to discern differences in the effects of widowhood on the well-being of older men and women. Based on previous research on mental illness, mortality differentials, and the quality of life, it is hypothesized that widowhood has an adverse impact on well-being, and that this relation is stronger for men than women. While the data support an overall decline in well-being of persons who are widowed, a direct effect of widowhood is substantial only for the negative dimension of the well-being of women. Widowed persons experience lower levels of well-being largely because they tend to be older, in poorer health, and less active in social life than their married counterparts. In the case of widowed women, low economic resources is also a key factor. A consistent pattern of greater reductions in levels of social participation in widowhood for men was not evident.