Teriparatide for treatment of patients with bisphosphonate-associated atypical fracture of the femur.

The Fracture Improvement with Teriparatide (Fix-IT) study randomized 13 women with an atypical femur fracture to immediate vs delayed teriparatide therapy; all were followed for 12 months. Results suggested a trend for superior healing and lesser bone mineral density declines in the immediate vs delayed group with no differences in adverse events. PURPOSE: Little clinical data are available on the use of teriparatide for the treatment of bisphosphonate-associated atypical femur fractures (AFF). The goal of the Fix-IT study was to determine if immediate therapy with teriparatide was superior for fracture healing after an AFF compared to a 6-month delay in teriparatide therapy. METHODS: This randomized pilot clinical trial included 13 women with an AFF who were randomized to immediate teriparatide vs a delay of 6 months. All were followed for 12 months on teriparatide. The primary outcomes included individual and composite measures of radiologic bone healing (scored 1 point [no healing] to 4 points [complete healing]) at 6 and 12 months. Secondary outcomes included bone mineral density of the unfractured contralateral hip, spine, 1/3 distal radius, and adverse events. RESULTS: We found there was a trend for superior healing with the composite score (12.6 vs 11.2 at 6 months and 15.4 vs 13.2 at 12 months), and lesser bone mineral density declines at the 1/3 distal radius (12-month change - 1.9 vs - 6.1%) in the immediate vs the delayed group. There were no differences in adverse events. There was one implant failure in the delayed group. CONCLUSIONS: There is a preliminary signal for greater improvements with immediate teriparatide therapy vs delayed therapy. However, because an AFF is a rare event, and only a small number of patients were included, the results must be interpreted with caution.

Integrating the Forensic Sciences in Wildlife Case Investigations: A Case Report of Pentobarbital and Phenytoin Toxicosis in a Bald Eagle (Haliaeetus leucocephalus).

The application of medical knowledge to the purpose of law is the foundation of forensic pathology. A forensic postmortem examination often involves the expertise of multiple scientific disciplines to reconstruct the full story surrounding the death of an animal. Wildlife poses additional challenges in forensic investigations due to little or no associated history, and the disruptive effects of decomposition. To illustrate the multidisciplinary nature of wildlife forensic medicine, the authors outline a case of secondary pentobarbital/phenytoin toxicosis in a bald eagle (Haliaeetus leucocephalus). The eagle was the single fatality in a group of 8 birds that fed on euthanized domestic cat remains that had been improperly disposed of in a landfill. Cooperation between responding law enforcement officers, pathologists, and other forensic scientists led to the successful diagnosis and resolution of the case.

Electrically tunable partial coalescence of oppositely charged drops.

We report the existence of a critical ionic conductivity below which oppositely charged drops only partially coalesce. The extent of coalescence between dissimilarly sized water drops in oil can be tuned from complete coalescence at low electric field strengths to complete noncoalescence at high field strengths, thus providing external control over the daughter droplet size. Strikingly, the size and charge of the daughter droplet are both independent of the ionic conductivity. We present evidence suggesting the charge transfer is instead strongly influenced by convection associated with the capillary-driven penetration of a vortex into the larger drop, and we demonstrate that the size of the daughter droplet is consistent with a scaling model based on a balance between capillary-driven inertia and electrostatic repulsion.

Retention of all-polyethylene acetabular components after femoral revision of a cemented total hip replacement.

BACKGROUND: This study was undertaken to provide a basis for decision-making when a well-fixed cemented cup is encountered at the time of a revision of a femoral component of a total hip replacement. It may be beneficial to retain the cup in some instances and thus reduce morbidity, complications, blood loss, operative time, and cost. METHODS: All patients who had a revision of the femoral component and retention of an all-polyethylene acetabular component from 1971 to 1996 were identified. Three hundred and seventy-four patients with a total of 395 cemented total hip replacements fit the inclusion criteria. The gender, date of and age at the index surgery, type of acetabular implant, and time of and reason for the revision of the femoral component were reviewed. The time to subsequent cup revision or latest surveillance was noted. The average age (and standard deviation) was 66.5 +/- 11.8 years at the time of the femoral revision, which was performed at an average of 8.0 +/- 4.4 years after the primary arthroplasty. For the purposes of this study, the end point for survival of the acetabular component was cup revision for any reason. RESULTS: At the time of the latest follow-up, at an average of nine years after the femoral revision and 17.3 years after the primary arthroplasty, 342 (86.6%) of the 395 cups remained in situ. Fifty-three cups (13.4%) in fifty-two patients had been revised, at an average of 10.0 +/- 5.7 years after the femoral revision and 16.7 +/- 5.3 years after the primary arthroplasty. The rate of survival of the retained acetabular components was 96.9% at five years, 89.3% at ten years, and 78.7% at fifteen years after the femoral revision and was 95.1% at fifteen years and 87.1% at twenty years after the primary arthroplasty. Increased age (p < 0.0001) and a shorter time-interval (less than 7.5 years) between the primary arthroplasty and the femoral revision (p = 0.05) were significantly associated with an increased likelihood of survival free of cup revision. Femoral head size, acetabular component design, gender, and primary diagnosis did not affect prosthetic survival in this sample of patients. CONCLUSIONS: The likelihood of survival of the unrevised cup was associated with patient age and duration of implantation, with the age of the patient being the more dominant factor predicting failure of the acetabular component.

Total knee arthroplasty in patients who have pigmented villonodular synovitis.

We reviewed the results of all eighteen total knee arthroplasties that had been performed at the Mayo Clinic between 1974 and 1992 for the treatment of pigmented villonodular synovitis. The diagnosis had been confirmed histologically in all patients. Fourteen patients had diffuse disease, which was active in eleven and inactive in three, and four had focal disease. In addition to the arthroplasty, the eleven patients who had active diffuse disease were managed with a complete synovectomy and the four patients who had focal disease had a partial synovectomy. The three remaining patients had a history of diffuse pigmented villonodular synovitis but had no evidence of disease at the time of the arthroplasty, so a synovectomy was not performed. At an average of 9.9 years (range, 3.6 to 20.1 years) after the arthroplasty, fourteen of the eighteen total knee prostheses were well fixed and functioning satisfactorily. The average knee score was 89 points (range, 80 to 99 points) and the average functional score was 77 points (range, 20 to 100 points) for these fourteen patients. The four failures were in patients who had active diffuse disease at the time of the arthroplasty. Three of the failures were due to aseptic loosening, and one was due to recurrence of the disease. Sixteen patients had no evidence of recurrence when they were last seen, at an average of 10.3 years (range, 3.6 to 20.1 years) after the arthroplasty. The two patients who had a recurrence were among the eleven who had active diffuse disease. In one of these patients, the recurrence was diagnosed at the time of a revision arthroplasty performed because of aseptic loosening. The other patient had two recurrences, necessitating an above-the-knee amputation.

Thermal effects of acrylic cementation at bone tumour sites.

The use of acrylic bone cement as an adjunct to surgical excision of giant cell tumour of bone appears to reduce the incidence of tumour recurrence. Possible mechanisms for this apparent tumour inhibition include cytotoxic effects from the methylmethacrylate monomer and tissue hyperthermia from the heat of polymerization of the cement. This work presents a method for the prediction of temperature fields and resulting tissue necrosis arising from the implantation of polymethylmethacrylate (PMMA) at the site of a curretted giant cell tumour of bone. This is accomplished using a two-dimensional model based on geometry obtained from digitized MRI images of the distal femur. A general-coordinate, non-orthogonal grid generation technique is used and solutions are obtained with an alternating-direction implicit (ADI) finite-difference scheme. The nodal temperature histories are then used to evaluate the effect of variable defect size on the zone of thermally induced cell necrosis. The results suggest the depth of the necrotic region is quite sensitive to the size of the implant. In at least some cases, the heating effect is sufficient to cause significant necrosis of tumorigenic cells. Implanting a large mass of acrylic may risk overkill, damaging substantial amounts of healthy tissue.

Identification of DNA methylation markers for human breast carcinomas using the methylation-sensitive restriction fingerprinting technique.

We have developed a PCR-based method, called methylation-sensitive restriction fingerprinting (MSRF), to screen changes in DNA methylation in breast carcinomas. Two hypermethylation-containing fragments, HBC-1 (for "hypermethylation in breast cancer") and HBC-2, were identified in the amplified breast tumor DNA relative to the amplified normal breast DNA of a patient. Nucleotide sequence analysis revealed no significant matches between the sequence of HBC-1 and the known sequences in the GenBank database, whereas the sequence of HBC-2 matched the upstream region of an antisense WT1 (Wilms' tumor suppressor gene) promoter. The methylation status in the breast tumor DNA from this patient was confirmed by Southern hybridization using HBC-1 and HBC-2 as probes, respectively. Further analysis showed that HBC-1 was methylated aberrantly in 90% (17 of 19 patients) of the primary breast carcinomas examined. This study demonstrates that MSRF provides a useful means for screening aberrant changes in DNA methylation during tumorigenesis. The commonly methylated fragments identified by MSRF could potentially supplement pathological markers currently used for cancers and additionally lead to the discovery of novel methylated tumor suppressor genes.