Prosthetic vascular graft infections: diagnosis and treatment

The diagnosis of infection in prosthetic vascular grafts is difficult clinically but very important due to the high associated morbidity and mortality. Various radiographic and imaging procedures have been used. 111In-labeled white cells have been used with a sensitivity approaching 100% and a specificity of approximately 90%. Computed tomography (CT) has also been advocated as a means of detecting these infections by some. Similarly, ultrasound has been used. More recently, magnetic resonance imaging (MRI) has been advocated in hopes that the signal of the infected graft would differ from that of the noninfected graft. This article reviews the data supporting each of these modalities.     

Arthrotomy--a prearthrotic factor?

Light-microscopic and electron microscopic findings of the synovial membrane and cartilage were compared, of rabbit knee joints on which arthrotomy and surgical induced instabilisation operation were performed. The joint opening was followed by an inflammation of the synovial membrane, and cartilage changes were similar in joints of arthrotomy and surgically induced instability. Clinical relevance: To prevent joints from further damage after arthrotomy or arthroscopy, joints should be spared from weight bearing during the time of synovial inflammation.     

Quantitative bone mineral analysis using dual energy computed tomography

This preliminary evaluation indicates that CT scanning permits measurement of cancellous, cortical or integral bone. With the single energy technique, precision is high and with mode, CT scanning may prove an important tool for assessing the axial skeleton is osteoporotic conditions.     

Temporal changes in tectal cell surface specificity induced by nerve growth factor.

The change in cell surface adhesive specificity previously shown to occur between day 7 and 8 of development in the chick optic tectum ]Gottlieb et al. (1974), Proc. Nat. Acad. Sci. USA 71, 1800-1802] can be induced in rotating cultures of tectal cells by the addition of 10(-7) M mouse submaxillary gland nerve growth factor. Insulin, proinsulin, dexamethasone, and performic-acid-oxidized nerve growth factor are individually inactive in this system, but nerve growth factor in which the three tryptophan residues/subunit have been oxidized with N-bromosuccinimide is active. Thus, the specificity of this system for nerve growth factor is different than that observed with embryonic dorsal root or sympathetic ganglia, where the oxidized tryptophan derivative is inactive in stimulating neurite production. It is possible that in this system nerve growth factor serves as an analog of another specific trophic factor, presumably structurally related to nerve growth factor, may be active at much lower concentrations.     

Effects of fractionated radiation on the brain vasculature in a murine model: blood-brain barrier permeability, astrocyte proliferation, and ultrastructural changes

PURPOSE: Radiation therapy of CNS tumors damages the blood-brain barrier (BBB) and normal brain tissue. Our aims were to characterize the short- and long-term effects of fractionated radiotherapy (FRT) on cerebral microvasculature in mice and to investigate the mechanism of change in BBB permeability in mice. METHODS AND MATERIALS: Intravital microscopy and a cranial window technique were used to measure BBB permeability to fluorescein isothiocyanate (FITC)-dextran and leukocyte endothelial interactions before and after cranial irradiation. Daily doses of 2 Gy were delivered 5 days/week (total, 40 Gy). We immunostained the molecules to detect the expression of glial fibrillary acidic protein and to demonstrate astrocyte activity in brain parenchyma. To relate the permeability changes to endothelial ultrastructural changes, we used electron microscopy. RESULTS: Blood-brain barrier permeability did not increase significantly until 90 days after FRT, at which point it increased continuously until 180 days post-FRT. The number of adherent leukocytes did not increase during the study. The number of astrocytes in the cerebral cortex increased significantly; vesicular activity in endothelial cells increased beginning 90 days after irradiation, and most tight junctions stayed intact, although some were shorter and less dense at 120 and 180 days. CONCLUSIONS: The cellular and microvasculature response of the brain to FRT is mediated through astrogliosis and ultrastructural changes, accompanied by an increase in BBB permeability. The response to FRT is delayed as compared with single-dose irradiation treatment, and does not involve leukocyte adhesion. However, FRT induces an increase in the BBB permeability, as in the case of single-dose irradiation.     

Accuracy of BRCA1 and BRCA2 Founder Mutation Analysis in Formalin-Fixed and Paraffin-Embedded (FFPE) Tissue

Background A major limitation in counseling unaffected women from families with inherited breast and ovarian cancer is that a “true-negative” interpretation of wild type BRCA analysis of the proband cannot be inferred in the absence of demonstration of a BRCA mutation segregating in the kindred. Documentation of familial BRCA mutations from paraffin-derived DNA of deceased patients has been limited due to reports of technical complications leading to lack of reproducibility of BRCA testing of archival material.Methods DNA was extracted from formalin-fixed paraffin-embedded (FFPE) morphologically normal tissue of 161 blinded, coded samples from women previously genotyped for the three Ashkenazi Jewish BRCA founder mutations from lymphocyte-derived DNA.Multiplex PCR followed by denaturing polyacrylamide gel electrophoresis was performed for the three founder mutations to determine if analysis on FFPE tissue could produce results concordant with those of the lymphocyte-derived DNA.Results After disclosure of the sample codes, the results were compared with the original lymphocyte-derived DNA genotypes. Excluding one sample unevaluable due to PCR failure, there was 100% concordance of 160 genotypes (120 mutation samples) derived from DNA from archival FFPE tissue compared to peripheral lymphocytes.Conclusions The method described reliably detected BRCA founder mutations in archival DNA derived from FFPE tissue. These results suggests that this technique may be useful in clinical settings to inform wild type BRCA results of unaffected probands, leading to avoidance of unnecessary intensified surveillance or risk-reducing surgery. With further validation this approach can also be applied to other populations where founder mutations are observed.M. A. Adank and E. Brogi are contributed equally to this work.     

Clinical features of high-risk older persons identified by predictive modeling.

The objective of this study was to describe the clinical features of older persons identified as high risk by a predictive modeling algorithm and to determine their suitability for clinical interventions like case management or disease management. A cross-sectional survey was undertaken at a community-based general internal medicine practice with 826 older patients enrolled in a Medicare-like health plan for military retirees and their dependents. Administrative claims data provided information about all 826 enrollees' chronic conditions, their use of health services, and the cost of those services during the past year. A survey mailed to 150 identified high-risk enrollees provided information about sociodemographic characteristics, general health, bed disability days, restricted activity days, activities of daily living (ADL) limitations, and instrumental activities of daily living (IADL) limitations. Compared to the 676 low-risk enrollees, the 150 high-risk enrollees had higher prevalence of eight individual chronic conditions, higher total chronic conditions (2.93 vs. 1.48, p < 0.001), higher annual rates of hospital admission (1.1 vs. 0.1, p < 0.001), more annual hospital days (7.3 vs. 0.5, p < 0.001), and higher total health insurance expenditures ($22,815 vs. $3,726, p < 0.001). The high-risk respondents to the survey (response rate = 80.0%) had suboptimal health (42.8% "fair or poor"), impaired functional ability (36.3% with 1+ ADL limitations, 58.1% with 1+ IADL limitations), and frequent health-related disruptions in their activities during the previous six months (38.7% with 1+ bed disability day, 52.3% with 1+ restricted activity day). A claims-based predictive modeling algorithm identifies older persons whose health, functional ability, and use of health services suggest they are good candidates for clinical interventions such as case management and disease management.