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Biomedical subjects

Alicia Terando

Publications and source records attributed to Alicia Terando.

6 recordsLinked to original sources

Osteomyelitis of the foot and toe in adults is a surgical disease: conservative management worsens lower extremity salvage.

OBJECTIVE: To characterize the national epidemiology of adult osteomyelitis (OM) and, using a single institutions' experience, test the hypothesis that early surgical therapy as compared with antibiotics alone results in an improved chance of wound healing and limb salvage. BACKGROUND: Foot and digit OM is a very common problem for which management is variable and for which few guidelines exist. METHODS: The Nationwide Inpatient Sample (NIS) and a single institution review from 1993 to 2000 form the basis of this study, using ICD-9CM codes for lower extremity foot and digit OM. Demographics, risk factors, and treatments were analyzed against the outcomes of a healed wound, limb salvage, and death. RESULTS: The NIS included 51,875 patients (incidence = 9/10,000 patients per year) with a mean age of 60 years, and 59% were men. The median length of stay decreased from 9 to 6 days (P < 0.001), but the average admission charge of 19,000 dollars did not significantly decrease over 7 years. Of these patients, 23% underwent a digit amputation and 8.5% suffered proximal limb loss. Single-institution analysis of 237 consecutive patients with OM confirmed a similar mean age (58 years), gender (67% men), and most presented with a foot or digit ulcer (56%). Wound healing was achieved in 56% and overall limb salvage was 80%. Decreased wound healing was associated with peripheral vascular occlusive disease (odds ratio, 0.4; 95% confidence interval, 0.2-0.8, P = 0.006) and preadmission antibiotic use (odds ratio, 0.2; 95% confidence interval, 0.05-1.1, P=0.07), while surgical debridement (odds ratio, 2.2; 95% confidence interval, 1.2-4.2, P = 0.02) was associated with increased healing. Limb salvage was improved with an arterial bypass (odds ratio, 3.9; 95% confidence interval, 1.1-14, P = 0.04), while preadmission solid organ transplant (odds ratio, 0.37; 95% confidence interval, 0.14-0.96, P = 0.04), peripheral vascular occlusive disease (odds ratio, 0.25; 95% confidence interval, 0.12-0.5, P = 0.001), and preadmission antibiotic use (odds ratio, 0.34; 95% confidence interval, 0.15-0.77, P = 0.009) were associated with greater limb loss. CONCLUSION: Digit OM is an expensive and morbid disease. Aggressive surgical debridement/digit amputation and selected use of arterial bypass should improve wound healing and limb salvage, respectively. In contrast, antibiotic therapy alone is associated with decreased wound healing and limb salvage.

Aged↗

Chemokine gene modification of human dendritic cell-based tumor vaccines using a recombinant adenoviral vector.

Previous animal studies conducted in our laboratory have shown that tumor antigen-pulsed dendritic cells (TP-DC) can mediate antitumor effects in vivo. However, durable and complete regression of established tumors has been difficult to achieve through the administration of TP-DC alone. To better augment immune priming to tumors in vivo, we have hypothesized that it is necessary to achieve an increased number of host-derived, naïve T cells at the site of TP-DC vaccine injections. To accomplish this goal, we have embarked on a series of studies that utilize defined chemokines. One of these molecules, secondary lymphoid tissue chemokine (SLC), has been shown to be uniquely chemoattractant for naïve T cells and dendritic cells. We propose that gene modification of DC-based tumor vaccines to produce human SLC will enhance T-cell recruitment and immune priming to tumor-associated antigens, and thereby translate into improved antitumor vaccine efficacy in vivo. Utilizing an E1-, E3-deleted adenoviral vector containing the gene for human SLC, we have been able to transduce human DC to produce biologically active human SLC that chemoattracts human T cells in vitro. SLC production by transduced DC was markedly enhanced upon DC maturation. Additionally, these SLC-secreting DC were found to be viable to a large extent despite the cytopathic effect inherent in adenoviral gene transfer and, most importantly, functional as determined by their ability to prime autologous T cells to a known melanoma-associated antigen, MART-1. Based on these encouraging results, we plan to initiate Phase I clinical studies utilizing DC-SLC to treat patients with advanced solid tumors.

Adenoviridae↗

Melanoma: adjuvant therapy and other treatment options.

Melanoma, diagnosed and treated at its earliest stages, can be successfully cured by surgery alone. However, when metastatic beyond the regional nodes, it is almost uniformly deadly. Adjuvant therapy targeted toward the treatment of microscopic residual disease after surgical resection is the subject of intense scientific investigation because this is the stage at which it is possible to have the greatest impact on disease-free and overall survival. However, standard therapies commonly used for other solid tumors have had disappointing results in the treatment of melanoma in the adjuvant setting. These disappointing results have led researchers and clinicians to work to develop innovative treatment strategies for this disease, most of which center on the use of immunotherapy. The realm of cancer immunotherapy is broad and rapidly expanding; it encompasses strategies using immunomodulating agents, such as interferon and interleukin-2, in addition to a wide range of novel vaccination strategies for the induction of active antitumor immune responses. Although clinical trials continue to be conducted to sort out the safety and efficacy of a myriad of new treatment modalities and novel combinations of the old and the new, data indicate that high-dose interferon-alfa-2b should be offered to appropriately selected intermediate- and high-risk patients with melanoma not involved in an experimental protocol.

Antineoplastic Agents↗

Applications of gene transfer to cellular immunotherapy.

Adoptive cellular therapy remains a potentially powerful method of eradicating established tumors. T-cells have been particularly potent effector cells, as demonstrated in animal models and clinical studies, and it is apparent that the stimulation of certain subpopulations of T-cells that are reactive to tumor antigens can lead to more therapeutic T-cells. The use of gene transfer techniques has resulted in more effective and specific methods to generate these tumor-specific T-cells. Another area of tremendous interest is in the adoptive transfer of DCs manipulated to present tumor antigen to resting, naive T-cells. Gene transfer techniques may offer more optimal ways to generate therapeutic DCs. Adoptive immunotherapy may ultimately [figure: see text] have its greatest use in patients undergoing cellular rescue after ablative chemotherapy; the infusion of immunocompetent T-cells, genetically modified stem cells, or programmed DCs may offer the opportunity to direct a patient's immune response to eliminate residual microscopic disease.

Adenoviridae↗