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Biomedical subjects

James A Lee

Publications and source records attributed to James A Lee.

10 recordsLinked to original sources

Reoperation for adrenocortical neoplasms.

Adrenocortical cancer is a highly lethal malignancy. Surgical resection remains the only potential modality for cure or appreciable disease-free intervals. Even with radical resection, most patients will recur or have metastatic disease. For these patients, surgical re-resection of local recurrence and metastases is the best chance of controlling disease and prolonging survival. Patients with widely metastatic disease or those with tumors not amenable to re-resection may benefit from tumor debulking to help control symptoms associated with oversecretion syndromes. No currently available regimen of chemotherapy, including mitotane, and/or radiotherapy achieves significant cure or response rates. Multiple promising treatments such as radiofrequency ablation, tyrosine kinase inhibitors, and competitive inhibitors of multidrug resistance gene products are in preclinical trials and may improve patient outcomes.

Adrenal Cortex Neoplasms↗

Repair of palatal bone defects using osteogenically differentiated fat-derived stem cells.

BACKGROUND: Although autogenous bone grafting remains the standard in the reconstruction of bone defects, disadvantages may include limited amount of bone and donor-site morbidity. Tissue engineering approaches can potentially obviate these problems. Fat contains a population of stem cells that can be isolated and differentiated into various cell lines, including osteocytes, adipocytes, and myocytes, depending on the culture conditions. In this study, the authors used osteogenically differentiated fat-derived stem cells to repair rat palatal bone defects. METHODS: Fat-derived stem cells were isolated, differentiated into osteocytes in osteogenic medium, and seeded onto poly-L-lactic acid scaffolds. Rat palatal bone defects were surgically made and animals divided into four groups according to the type of implant for bone repair: group I, empty defect; group II, poly-L-lactic acid without cells; group III, poly-L-lactic acid with undifferentiated fat-derived stem cells; and group IV, poly-L-lactic acid with osteogenically differentiated fat-derived stem cells. Palates were harvested at 6 or 12 weeks after implantation (n = 8 per group at each time interval). Hematoxylin and eosin staining, immunohistochemical staining for osteocalcin, and histomorphometric measurements of new bone were performed. RESULTS: Defects in groups I, II, and III had no bone and were primarily filled with fibrous tissue. In contrast, there was substantial bone regeneration in group IV, which was statistically significant by histomorphometry compared with groups I, II, and III. Newly formed bone in group IV stained positive for osteocalcin. CONCLUSIONS: The authors successfully reconstructed palatal bone defects using absorbable three-dimensional scaffolds seeded with osteogenically differentiated fat-derived stem cells. This study demonstrates the feasibility of reconstructing bony defects with fat-derived stem cells.

Adipocytes↗

Patient-reported underuse of prescription medications: a comparison of nine surveys.

Nine national surveys documenting patient underuse of prescription medications were examined to describe the variation and trends in that underuse and identify possible reasons for the substantially different rates that were reported. Underuse includes unfilled prescriptions, delayed therapy, reduced frequency, and lowered dosage. Rates of cost-related patient underuse in the studies ranged from 1.6 to 22 percent. Insurance coverage, level of wealth, age, and health status were the sociodemographic variables most strongly related to underuse. Seven additional factors in the design and administration of the surveys were identified as providing plausible explanations for the variance across surveys. The most conspicuous variation was between three government-sponsored periodic surveys and six generally one-time assessments, with the latter yielding higher rates and greater variance in underuse. Understanding the factors contributing to the variation in reported rates of underuse of medications is an important prerequisite for the design of effective prescription-drug benefit programs.

Adolescent↗

The surgeon's armamentarium to the surgical treatment of primary hyperparathyroidism.

Parathyroidectomy cures the vast majority of patients with primary hyperparathyroidism (HPT). While bilateral neck exploration has been the mainstay of therapy, recent advances in technology have revolutionized the field making a focused approach to parathyroidectomy a reality. The development of accurate pre-operative localization with sestamibi scanning, effective unilateral, endoscopic and video-assisted techniques, and rapid intra-operative parathyroid hormone (PTH) testing have made it possible to cure patients with the least amount of surgical dissection possible. In this paper, we will explore the role of focused parathyroidectomy in the surgical treatment of primary HPT.

Contraindications↗

Lentiviral transfection with the PDGF-B gene improves diabetic wound healing.

BACKGROUND: The treatment of diabetic wounds remains a difficult challenge. The present study investigates whether platelet-derived growth factor (PDGF) lentiviral gene therapy can improve diabetic wound healing in the diabetic db/dbmouse. METHODS: PDGF cDNA was cloned and lentiviral vectors were constructed with either the PDGF-B or green fluorescence protein (GFP) gene. A 2 x 2-cm full-thickness dermal wound was made on each db/db mouse. Animals were divided into three groups, with eight animals in each group as follows: group I, empty wound; group II, lentiviral PDGF; and group III, lentiviral GFP. Lentiviral vectors were injected into the wounds and healing was assessed at 21 days. Harvested wounds were assessed for residual epithelial gap, granulation tissue area, PDGF expression, collagen formation (picrosirius red), and angiogenesis (CD31 staining). RESULTS: Lentiviral vectors were constructed and transfected dermal fibroblasts demonstrated in vitro production of PDGF mRNA as measured by reverse-transcriptase polymerase chain reaction. Immunohistochemistry for PDGF confirmed successful in vivo transfection of the PDGF gene. At 21 days, reepithelialization and granulation tissue area were similar in all groups. However, there was a statistically significant increase in angiogenesis and substantially thicker, more coherently aligned collagen fibers in the PDGF group compared with controls. CONCLUSIONS: PDGF lentiviral vectors were successfully transfected into the regenerated dermis in diabetic wounds. Although reepithelialization was similar among the groups, there was enhanced angiogenesis and collagen deposition in the lentiviral PDGF group. These results demonstrate that lentiviral PDGF transfection of the diabetic wound enhances PDGF production, improves vascularization and collagen organization, and has potential clinical applications in diabetic wound treatment.

Animals↗

Lentiviral gene therapy with platelet-derived growth factor B sustains accelerated healing of diabetic wounds over time.

The treatment of diabetic wounds is a formidable clinical challenge. In this study, lentiviral vectors carrying the human platelet-derived growth factor B (PDGF-B) gene were used to treated diabetic mouse wounds. Full-thickness 2.0-cm x 2.0-cm excisional wounds were created on the dorsa of genetically diabetic C57BL/KsJ-m+/+Lepr(db) mice. Lentiviral vectors containing the PDGF-B gene were injected into the wound margins and base. Mice were killed at 14-, 21-, and 35-day intervals. Measurement of the residual epithelial gap showed a trend towards increased healing in lentiviral PDGF-treated wounds compared with untreated and saline-treated wounds at all time points. At 21 days, there was significantly increased healing in lentiviral PDGF-treated wounds (0.98+/-0.17 cm) compared with saline-treated wounds (1.22+/-0.30 cm; P<0.05). Immunohistochemistry for CD31 revealed significantly increased neovascularization in lentiviral PDGF-treated wounds compared with untreated and saline-treated wounds at 14 and 21 days (P<0.01). Picrosirius red staining demonstrated thicker and more highly organized collagen fibers in treated wounds compared with untreated and saline-treated wounds. Quantitative analysis of collagen content showed a 3.5-fold and 2.3-fold increase in lentiviral PDGF-treated wounds versus untreated and saline-treated wounds, respectively (P<0.01). Lentiviral gene therapy with PDGF-B can sustain diabetic wound healing over time and may possess promising potential in the clinical setting.

Analysis of Variance↗

Biological alchemy: engineering bone and fat from fat-derived stem cells.

Adipose tissue contains a population of pluripotent stem cells capable of differentiating along multiple mesenchymal cell lineages. In this study the authors isolated these fat-derived stem cells successfully from Lewis rats and induced differentiation along adipogenic and osteogenic lineages in vitro and in vivo. Induction was stimulated by exposing stem cells to lineage-specific induction factors. Adipocyte-inducing media contained dexamethasone, insulin, and isobutyl-methylxanthine. Osteoblast inducing media contained dexamethasone, beta-glycerophosphate, and ascorbic acid. Undifferentiated stem cells were maintained in minimal essential media alpha and fetal bovine serum. At 10 days, cells cultured in adipogenic media differentiated into adipocytes in vitro, as evidenced by positive Oil red O staining of lipid vacuoles. At 21 days, cells cultured in osteogenic media differentiated into osteoblasts in vitro as demonstrated by Alizarin red staining of a calcified extracellular matrix and immunohistochemical staining for osteocalcin. Differentiated cells were seeded at a density of 5 x 106 cells onto 15 x 15-mm polyglycolic acid grafts and implanted subcutaneously into three groups of Lewis rats: Group I contained undifferentiated stem cell grafts, group II contained adipocyte grafts, and group III contained osteoblast grafts. At weeks 4 and 8, in vivo fat formation was demonstrated in group II rats, as confirmed by Oil red O staining. At 8 weeks, group III rats demonstrated in vivo bone formation, as confirmed by the presence of osteocalcin on immunohistochemistry and the characteristic morphology of bone on hematoxylin-eosin staining. Group I rats demonstrated no in vivo bone or fat formation at either time interval. These results demonstrate the ability to isolate pluripotent stem cells from adipose tissue, to induce their differentiation into osteoblasts and adipocytes in vitro, and to form bone and fat subsequently in vivo. This is the first published report of in vivo bone formation from fat-derived stem cells. These cells may eventually serve as a readily available source of autologous stem cells for the engineering of bone and fat.

Adipocytes↗

Statistical comparison of consumer drug expenditures and discretionary purchases to assess drug affordability.

BACKGROUND: Affordability may be defined as the absence of economic barriers to a good or service. There are 2 frequently observed measures of affordability: a consumer's ability to pay and his or her physical access to a good or service. Thus, most programs designed to subsidize consumers' health care costs, especially state programs that address prescription drug expenditures for people aged > or =65 years, base eligibility on measures of income as a proxy for a consumer's ability to pay. These measures do not explicitly include a consumer's willingness to pay for medications. For example, it is possible that some Medicare beneficiaries may be resistant to paying for medication because other major health care expenditures are typically covered by insurance. This resistance could be exacerbated by the keen awareness among the general population of the rising costs of medications. Because medications are considered a necessity, expenditure levels are usually compared with expenditures for other necessities, such as housing and medical services. OBJECTIVE: In an attempt to assess consumers' potential willingness to pay for medications, this article draws on data from the US Bureau of Labor Statistics' Consumer Expenditure Surveys to compare pharmaceutical expenditures with out-of-pocket expenditures for discretionary purchases, such as dining outside the home. RESULTS: Personal out-of-pocket expenditures for medications have ranged from 0.8% to 1.0% of consumer unit income since 1985. These expenditures are relatively small compared with those for necessities, such as housing (33%) and food (13.5%). They are also less than the share of income dedicated to many nonessentials. CONCLUSION: Assessing inability versus unwillingness to pay for medication remains a problem for both researchers and health care policy makers attempting to determine the affordability of medications.

Aged↗

Prescription drug use among elderly and nonelderly families.

OBJECTIVE: This study augments existing literature by examining characteristics associated with prescription drug utilization and makes an in-depth assessment of family prescription drug economic burden within the United States. The objective of this study was to examine differences in prescription drug use and prescription drug characteristics among elderly and nonelderly families. METHODS: A measure of out-of-pocket prescription drug burden associated with family prescription drug utilization was constructed using data from the 1996 Medical Expenditure Panel Survey (MEPS). Families were designated as the unit of analysis and further divided by age (<65 and e 65 years) of the reference person. The 1996 MEPS database provides medical expenditure data on a national sample of 8,917 families (22,601 individuals) and 147,308 drug episodes, i.e., prescription procurement. The ratio of family prescription out-of-pocket expenditures to family income was used to assign families to economic burden rank-ordered quintiles, each representing 20% of U.S. families in 1996. RESULTS: Prescription size, price, and drug use were higher among elderly families. Their proportion of generic use was higher compared to nonelderly families. Additionally, out-of-pocket prescription expenditures represented 23.7% and 45.6% of the total out-of-pocket medical care burden for nonelderly and elderly families, respectively. The average prescription drug burden (total prescription out-of-pocket costs/family income) was 0.4% for nonelderly and 1.9% for elderly households. CONCLUSION: The study results demonstrate an ability to identify populations with high economic burden for prescription medications. The presumption is that persons age 65 or older, lacking purchasing leverage, are more likely to pay full retail price and, consequently, higher prices. Our findings suggest that high prescription drug burden was a function of prescription size and cost per prescription, with prescription size showing more drastic differences between the high and low prescription drug burden subgroups. Future studies should continue to assess factors influencing families. prescription drug economic burden, and the information derived from these studies should be used by benefit planners in designing drug benefits within health insurance plans.

Age Distribution↗