Variable impairment of wound healing in the heterozygous collagenase-resistant mouse

Collagen undergoes dramatic reorganization during wound repair. Matrix metalloproteinases degrade and remodel collagen in a tightly controlled process. The collagenase-resistant mouse, Col1a1(tm1Jae), produces type I collagen, which is resistant to degradation by human matrix metalloproteinase 1. These mice grow normally but develop thickened skin with age. We have previously reported that the early wound repair response in homozygous mutant (Col1a1(r/r)) mice is delayed compared to wild type (Col1a1(+/+)). However, the late-stage scar of Col1a1(r/r) wounds was not significantly altered compared to Col1a1(+/+). Here we have investigated the response of heterozygous mice (Col1a1(+/r)) to wounding, not previously reported. Wound reepithelialization was delayed to a similar degree to wounds in the Col1a1(r/r) mice. However, the recovery of impaired wound contraction was faster in Col1a1(+/r) than in Col1a1(r/r) mice, but still slower than in wild-type animals. Analysis of wound protein extracts showed expression of some matrix metalloproteinases was prolonged in both the Col1a1(r/r) and Col1a1(+/r) wounds compared to wild type. We suggest the partial resistance of collagen to collagenase-mediated degradation in the heterozygous animals causes equivalent impairment of keratinocyte migration compared to homozygous collagenase-resistant mice, but that wound contraction during late-stage healing is only partially retarded.     

Large femoral bone loss after hip revision using the uncemented proximally porous-coated Bi-Metric prosthesis: 22 hips followed for a mean of 6 years

Background and purpose Periprosthetic bone loss after uncemented femoral hip revision is a matter of concern. We have used a proximally porous- and hydroxyapatite-coated prosthesis (Bi-Metric) in revision since 1989 and now we report the bone changes. This prosthesis is intended to distribute the forces more evenly and to avoid proximal femoral unloading.Methods 22 patients were unilaterally reoperated because of aseptic loosening. Only patients with a healthy contralateral hip were included. Mean age at revision was 69 (55–80) years. Bone defects were graded by Gustilo-Pasternak and Endo-Klinik classifications. Clinical assessment was performed with Harris hip score. We used radiographs and dual-energy X-ray absorptiometry to evaluate migration, femoral remodeling, and bone mineral density after 72 (30–158) months.Results The mean Harris hip score was 74 (30–100) points at follow-up. Mild thigh discomfort was present in 1 patient and moderate thigh pain in 3 patients. There was no loosening or subsidence. Osteolysis seen at revision had diminished in 19 of the 22 hips at follow-up. We noted a large reduction in bone mineral density. It was most pronounced in Gruen regions 1, 2, 6, and 7.Interpretation Revision with this stem is a reliable procedure; however, we noted a large degree of proximal bone loss that could lead to later mechanical complications or fractures.     

Bone development and age-related bone loss in male C57BL/6J mice

The objective of this study was to examine changes in the long bones of male C57BL/6J mice with growth and aging, and to consider the applicability of this animal for use in studying Type II osteoporosis. Male C57BL/6J mice were aged in our colony between 4 and 104 weeks (n=9-15/group). The right femur and humeri were measured for length and subjected to mechanical testing (3-point flexure) and compositional analysis. The left femurs were embedded and thick slices at the mid-diaphysis were assessed for morphology, formation indices, and bone structure. In young mice, rapid growth was marked by substantial increases in bone size, mineral mass, and mechanical properties. Maturity occurred between 12 and 42 weeks of age with the maintenance of bone mass and mechanical properties. From peak levels, mice aged for 104 weeks experienced decreased whole femur mass (12.1 and 18.6% for dry and ash mass, respectively), percentage mineralization (7.4%), diminished whole bone stiffness (29.2%), energy to fracture (51.8%), and decreased cortical thickness (20.1%). Indices of surface-based formation decreased rapidly from the onset of the study. However, the periosteal perimeter and, consequently, the cross-sectional moments of inertia continued to increase through 104 weeks, thus maintaining structural properties. This compensated for cortical thinning and increased brittleness due to decreased mineralization and stiffness. The shape of the mid-diaphysis became increasingly less elliptical in aged mice, and endocortical resorption and evidence of subsequent formation were present in 20-50% of femurs aged > or =78 weeks. This, combined with the appearance of excessive endocortical resorption after 52 weeks, indicated a shift in normal mechanisms regulating bone shape and location, and was suggestive of remodeling. The pattern of bone loss at the femoral mid-diaphysis in this study is markedly similar to that seen in cortical bone in the human femoral neck in Type II osteoporosis. This study has thus demonstrated that the male C57BL/6J mouse is a novel and appropriate model for use in studying endogenous, aging-related osteopenia and may be a useful model for the study of Type II osteoporosis.     

Evaluation of a novel precision template-guided biopsy system for detecting prostate cancer

OBJECTIVE

To explore the ability of a novel transrectal ultrasonography (TRUS) device (TargetScan^TM, Envisioneering Medical Technologies, St. Louis MO) that creates a three‐dimensional map of the prostate and calculates an optimal biopsy scheme, to accurately sample the prostate and define the true extent of disease, as standard TRUS‐guided prostate biopsy relies on the operator to distribute the biopsy sites, often resulting in under‐ and oversampling regions of the gland.

PATIENTS AND METHODS

In a multicentre retrospective chart review evaluating patients who had a TargetScan prostate biopsy between January 2006 and June 2007, we determined the overall cancer detection rate in all patients and in subgroups based on prostate specific antigen level, digital rectal examination, and indication for biopsy. We assessed the pathological significance of cancer detected, defined as a Gleason score of ≥7, positive margins, extracapsular disease or >20% tumour volume in the prostatectomy specimen. We also evaluated the concordance in Gleason score between the biopsy and prostatectomy specimen.

RESULTS

Cancer was detected in 50 (35.7%) of the 140 patients biopsied, including 39 (47.6%) with no previous biopsies. Of 23 prostatectomy specimens, 20 (87%) had pathologically significant disease. The biopsy predicted the prostatectomy Gleason score in 12 patients (52%), overestimated in two (9%), underestimated in eight (35%), and biopsy Gleason score could not be assigned in one (4%).

CONCLUSIONS

Template‐guided biopsy potentially produces a higher cancer detection rate and more accurate assessment of grade. Prostatectomy specimens did not have a high rate of pathologically insignificant disease.     

Outcomes in surgical treatment of "idiopathic-like" scoliosis associated with syringomyelia

Patients with "idiopathic-like" spinal deformities associated with syringomyelia were retrospectively reviewed. Ten patients had surgical stabilization of their curvatures with at least a 2-year follow-up, and an additional five patients were evaluated for deformity pattern with <2 years of follow-up. Paralytic curve patterns, scoliosis associated with spina bifida, congenital scoliosis, or other associated syndromes were discarded. All 10 patients with surgery who were followed for an average of 46 months lost 10 degrees correction above, through, or below the instrumented segments. A total of 50% lost correction through the instrumented segments. Anterior fusion stabilized the instrumented portion of the spine better than posterior instrumentation alone. Eighty percent of the 15 patients had thoracic kyphosis >40 degrees. Only one patient was lordoscoliotic. Syringomyelia deformities tend to be kyphoscoliotic in 80% of cases and behave more like paralytic curvatures postoperatively. MRI is recommended for apparent idiopathic scoliotic curvatures that are kyphoscoliotic and not lordoscoliotic.     

Changes in bone structure and mass with advancing age in the male C57BL/6J mouse.

To determine whether the mouse loses bone with aging and whether the changes mimic those observed in human aging, we examined the changes in the tibial metaphysis and diaphysis in the male C57BL/6J mouse over its life span using microcomputed tomography (microCT). Cancellous bone volume fraction (BV/TV) decreased 60% between 6 weeks and 24 months of age. Loss was characterized by decreased trabecular number (Tb.N), increased trabecular spacing (Tb.Sp), and decreased connectivity. Anisotropy decreased while the structure model index increased with age. Cortical bone thickness increased between 6 weeks and 6 months of age and then decreased continuously to 24 months (-12%). Cortical bone area (Ct.Ar) remained constant between 6 and 24 months. Fat-free weight reached a peak at 12 months and gradually declined to 24 months. Total mass lost between 12 and 24 months reached 10%. Overall, the age-related changes in skeletal mass and architecture in the mouse were remarkably similar to those seen in human aging. Furthermore, the rapid early loss of cancellous bone suggests that bone loss is not just associated with old age in the mouse but rather occurs as a continuum from early growth. We conclude that the C57BL/6J male mouse maybe a useful model to study at least some aspects of age-related bone loss in humans.     

Preoperative prediction of the risk of pulmonary complications after esophagectomy for cancer

OBJECTIVES: Pulmonary complication is a frequent morbid event after esophagectomy for cancer. Its prediction may help select patients for preoperative rehabilitation. METHODS: We performed a retrospective review of 292 patients (231 men and 61 women; mean age, 60.1 years) who underwent esophagectomy for cancer between 1980 and 2000. Data were analyzed to identify factors associated with the development of pulmonary complications (reintubation for isolated respiratory failure and pneumonia). A scoring system was developed, and its ability to predict complications was assessed. RESULTS: Resection was performed for squamous cancer (n = 100), adenocarcinoma (n = 186), and other histologic types (n = 6) in patients with stages 0 or I (n = 53), II (n = 94), III (n = 114), and IV (n = 23) disease. Pulmonary complications, which developed in 78 (27%) patients, were associated with a 4.5-fold increase in operative mortality (7%-32%). Multivariable analysis identified independent predictors of pulmonary complications to be patient age (odds ratio [OR], 1.31; 95% confidence interval [CI], 0.99-1.74; P =.059), percentage forced expiratory volume in 1 second (OR, 1.21; 95% CI, 1.07-1.38; P =.003), and possibly performance status (OR, 1.48; 95% CI, 0.88-2.50; P =.14). A scoring system using these 3 covariates was developed, which predicted incremental risk of pulmonary complications (P =.013). The incremental risks of cardiovascular and overall cardiopulmonary complications were also predicted with this scoring system (P <.01 for each). CONCLUSIONS: A scoring system using patient age, spirometry, and performance status helps predict the likelihood of pulmonary and cardiovascular complications after esophagectomy and can help select patients who may benefit from preoperative cardiopulmonary rehabilitation.