Faculty Bibliography

Normal and abnormal extracellular matrix turnover is thought to result, in part, from the balance in the expression of metalloproteinases and tissue inhibitors of metalloproteinases (TIMPs). The clinical manifestations of an imbalance in these relationships are evident in a variety of pathologic states, including osteoarthritis, deficient long-bone growth, rheumatoid arthritis, tumor invasion, and inadequate cartilage repair. Articular cartilage defects commonly heal as fibrocartilage, which is structurally inferior to the normal hyaline architecture of articular cartilage. Transforming growth factor-beta 1 (TGF-beta1), a cytokine central to growth, repair, and inflammation, has been shown to upregulate TIMP-1 expression in human and bovine articular cartilage. Additionally, members of the TGF-beta superfamily are thought to play key roles in chondrocyte growth and differentiation. Bone morphogenetic protein-2 (BMP-2), a member of this superfamily, has been shown to regulate chondrocyte differentiation states and extracellular matrix composition. It was proposed that, by optimizing extracellular matrix composition, BMP-2 would enhance articular cartilage healing. After determining the release kinetics of BMP-2 from a collagen type I implant (Long-Evans male rats; two implants/rat, n = 14), it was found that, in a tissue engineering application, BMP-2 induced a hyaline-like repair of New Zealand White rabbit knee articular cartilage defects (3-mm full-thickness defects in the femoral trochlea; 2 defects/rabbit, n = 36). The quality of cartilage repair with BMP-2 (with or without chondrocytes) was significantly better than defects treated with BMP-2, as assessed by a quantitative scoring scale. Immunohistochemical staining revealed TIMP-1 production in the cartilage defects treated with BMP-2. When studied in vitro, it was found that BMP-2 markedly increased TIMP-1 mRNA by both bovine articular and human rib chondrocytes. Additionally, increased TIMP-1 mRNA was translated into increased TIMP-1 protein production by bovine chondrocytes. Taken together, these data suggest that BMP-2 may be a useful cytokine to improve healing of cartilaginous defects. Furthermore, these data suggest that the beneficial effects of BMP-2 may be, in part, related to alterations in extracellular matrix turnover

Residents of the dense urban core neighborhoods of New York City (NYC) have expressed increasing concern about the potential human health impacts of diesel vehicle emissions. We measured concentrations of particulate matter [less than/equal to] 2.5 micro in aerodynamic diameter (PM(2.5)) and diesel exhaust particles (DEP) on sidewalks in Harlem, NYC, and tested whether spatial variations in concentrations were related to local diesel traffic density. Eight-hour (1000-1800 hr) air samples for PM(2.5 )and elemental carbon (EC) were collected for 5 days in July 1996 on sidewalks adjacent to four geographically distinct Harlem intersections. Samples were taken using portable monitors worn by study staff. Simultaneous traffic counts for diesel trucks, buses, cars, and pedestrians were carried out at each intersection on [Greater/equal to] 2 of the 5 sampling days. Eight-hour diesel vehicle counts ranged from 61 to 2,467 across the four sites. Mean concentrations of PM(2.5) exhibited only modest site-to-site variation (37-47 microg/m(3)), reflecting the importance of broader regional sources of PM(2.5). In contrast, EC concentrations varied 4-fold across sites (from 1.5 to 6 microg/m(3)), and were associated with bus and truck counts on adjacent streets and, at one site, with the presence of a bus depot. A high correlation (r = 0.95) was observed between EC concentrations measured analytically and a blackness measurement based on PM(2.5) filter reflectance, suggesting the utility of the latter as a surrogate measure of DEP in future community-based studies. These results show that local diesel sources in Harlem create spatial variations in sidewalk concentrations of DEP. The study also demonstrates the feasibility of a new paradigm for community-based research involving full and active partnership between academic scientists and community-based organizations

OBJECTIVE: To determine and describe the extent to which European dietary data collected in disparate surveys can be meaningfully compared. DESIGN: Seven independent population-based surveys from six European countries were initially included. Differences in study designs and methodological approaches were examined. Risk factor data for 31,289 adults aged 40-59 y were harmonized and pooled in a common, centralized database. RESULTS: Direct comparisons of dietary measures across studies were not deemed appropriate due to methodological heterogeneity. Nonetheless, comparisons of intra-population contrasts by gender across sites were considered valid. Women consumed fruit and vegetables more often than men. Age-standardized gender differences in the prevalence of low fruit and vegetable consumption ranged from 7 to 18% and 5 to 15%, respectively. Data on energy intake showed good agreement across study populations. The proportion of total energy from macronutrients was similar for women and men. Gender differences for relative intakes of saturated fatty acids (percentage energy) were small and only in France were they significant. Dietary fibre density was significantly higher in women than in men. Overall, the participating Southern European populations from Italy and Spain exhibited more healthful food composition patterns. CONCLUSIONS: Contrasts in dietary patterns by gender across populations may provide the basis for health promotion campaigns. The most favourable patterns observed may serve as attainable goals for other populations. An international risk factor surveillance programme based upon locally run, good quality studies has the potential to provide the needed data. SPONSORSHIP: European Community (DG V), project 96CVVF3-446-0; Swiss Federal Office for Education and Science, OFES 96.0089.

Recent research has suggested that inequality in the distribution of income is associated with increased mortality, even after accounting for average income levels. Using data from the Behavioral Risk Factor Surveillance System (BRFSS), we investigated whether inequality in the distribution of income within US states is related to the prevalence of four cardiovascular disease risk factors (body mass index (BMI), history of hypertension, sedentarism, and smoking). Multilevel models (including both state-level and individual-level variables) were used to examine associations of state inequality with risk factor levels before and after adjustment for individual-level income. For three of the four risk factors investigated (BMI, hypertension, and sedentarism), state inequality was associated with increased risk factor levels, particularly at low income levels (annual household incomes <$25,000), with associations persisting after adjustment for individual-level income. Inequality was also positively associated with smoking, but associations were either stronger or only present at higher income levels. Associations of inequality with the outcomes were statistically significant in women but not in men. Although not conclusive, findings for three of the four risk factors are suggestive of a contextual effect of income inequality, particularly among persons with lower incomes.

Wound extracellular matrix is a key regulator of cell adhesion, migration, proliferation, and differentiation during cutaneous repair. The amount and organization of normal wound extracellular matrix are determined by a dynamic balance among overall matrix synthesis, deposition, and degradation. Matrix metalloproteinases (MMPs) are one family of structurally related enzymes that have the collective ability to degrade nearly all extracellular matrix components. The MMPs are broadly categorized into collagenases, gelatinases, stromelysins, and membrane-type MMPs by their substrate specificity. The aim of this study was to characterize the temporal changes in mRNA profiles for rat collagenase [matrix metalloproteinase-1 (MMP-1)], gelatinase A (MMP-2), matrilysin (MMP-7), gelatinase B (MMP-9), and membrane type 1-MMP (MT1-MMP), as well as tissue inhibitor of metalloproteinases-1 (TIMP-1), TIMP-2, and TIMP-3 during the inflammatory, granulation, and early remodeling phases of excisional skin repair. Eight full-thickness skin wounds were made on the backs of each rat (7-mm2 wounds; 16 rats; n = 128 wounds). Two animals at a time were reanesthetized, and all eight wounds on each animal were excised at 12 and 24 hours and at 2, 3, 5, 7, 10, and 14 days after injury. Six wounds from each animal were excised for RNA isolation, whereas two wounds were excised for histology. Controls consisted of nonwounded skin from identical locations in four animals. Total RNA from each time point was isolated and relative mRNA quantitation performed by using reduced-cycle reverse transcription-polymerase chain reaction. Correct polymerase chain reaction product amplification was confirmed by probing the blotted polymerase chain reaction product with a 32P-labeled oligonucleotide specific for a given MMP or TIMP. We demonstrated that the majority of MMP and TIMP mRNA induction and peak expression coincided temporally with the well-characterized inflammatory and granulation stages of repair. In conclusion, there is a distinct pattern of MMP and TIMP expression during normal excisional wound repair

This randomized double-blind placebo-controlled study aimed to determine whether oral intake of 200 microg/d of sodium selenite, a dose within the safe and adequate daily intake (50-200 microg/d) recommended by the U.S. Food and Nutrition Board, will abrogate depressed or enhance normal-level immune functions of patients receiving therapy for squamous cell carcinoma of the head and neck. Subjects were given one selenium/placebo tablet/d for 8 wk, beginning on the day of their first treatment for the disease (e.g., surgery, radiation, or surgery and radiation) and their immune functions were monitored. Supplementation with selenium (Se) during therapy resulted in a significantly enhanced cell-mediated immunue responsiveness, as reflected in the ability of the patient's lymphocytes to respond to stimulation with mitogen, to generate cytotoxic lymphocytes, and to destroy tumor cells. The enhanced responsiveness was evident during therapy and following conclusion of therapy. In contrast, patients in the placebo arm of the study showed a decline in immune responsiveness during therapy, which was followed, in some patients, by an enhancement, but the responses of the group remained significantly lower than baseline values. The data also show that at baseline, patients entered in the study had significantly lower plasma Se levels than healthy individuals, and patients in stage I or II of disease had significantly higher plasma selenium levels than patients in stage III or IV of disease.

Many plastic surgeons develop technologies that are manufactured by Wall Street-financed companies. Others participate in the stock market as investors. This study examines the bioengineered skin industry to determine whether it integrates clinical and financial information as Wall Street tenets would predict, and to see whether the financial performance of these companies provides any lessons for practicing plastic surgeons. In efficient markets, the assumptions on which independent financial analysts base their company sales and earnings projections are clinically reasonable, the volatility of a company's stock price does not irrationally differ from that of its industry sector, and the buy/sell recommendations of analysts are roughly congruent. For the companies in this study, these key financial parameters were compared with a benchmark index of 69 biotech companies of similar age and annual revenues (Student's t test). Five bioengineered skin companies were included in the study. Analysts estimated that each company would sell its product to between 24 and 45 percent of its target clinical population. The average stock price volatility was significantly higher for study companies than for those in the benchmark index (p < 0.05). Similarly, buy/sell recommendations of analysts for the study companies were significantly less congruent than those for the benchmark companies (p < 0.05). These results indicate clinically unrealistic projections for market penetration, significantly high price volatility, and significantly high discordance among professional analysts. In all cases, the market is inefficient-an unusual finding on Wall Street. A likely explanation for this market failure is a cycle of poor clinical correlation when assigning sales projections, which in turn leads to price volatility and discordance of buy/sell recommendations. This study's findings have implications for plastic surgeons who develop new technology or who participate in the equities markets as investors. Plastic surgeons who develop new medical devices or technology cannot universally depend on the market to drive clinically reasonable financial performance. Although inflated sales estimates have benefits in the short term, failure to meet projections exacts severe financial penalties. Plastic surgeons who invest in the stock market, because of their unique clinical experience, may sometimes be in the position to evaluate new technologies and companies better than Wall Street experts. Well-timed trades that use this expertise can result in opportunities for profit.