Objectives. This study sought to assess the feasibility, safety and efficacy of sustained intracoronary delivery of dexamethasone by a novel polymer-coated eluting stent.
Background. Development of ...techniques to provide sustained local drug delivery has focused on polymers as matrices for drug incorporation and elution.
Methods. A tantalum wire stent was coated with dexamethasone (0.8 mg) suspended in a matrix of either low (∼80 kD) or high (∼321 kD) molecular weight poly-l-lactic acid (PLLA 0.4 mg). Uncoated stents, stents coated with PLLA or stents coated with dexamethasone in PLLA were overexpanded by 30% to the normal vessel diameter in the coronary arteries of juvenile farm pigs. Animals were euthanized 28 days later, and neointimal thicknesses were measured. Additional pigs underwent placement of stents coated with high molecular weight PLLA–dexamethasone for assessment of arterial tissue and serum concentrations of dexamethasone at 1 h and 1, 2, 10 and 28 days after stent implantation.
Results. In vitro dexamethasone release occurred over the first 6 days. Stents coated with low molecular weight PLLA produced an intense inflammatory neointimal response. Stents utilizing the high molecular weight PLLA were well tolerated within the coronary vessel during the 28-day experiment. However, dexamethasone did not decrease neointimal hyperplasia. Dexamethasone concentrations in the arterial tissue were ∼300,000-fold higher than those in the serum 24 h after stent implantation, remaining ∼3,000-fold higher at 28 days.
Conclusions. The eluting stent utilizing high molecular weight PLLA appeared to be a well tolerated and effective means of providing sustained, site-specific drug delivery to the porcine coronary artery wall for at least 28 days.
(J Am Coll Cardiol 1997;29:808–16)
Abstract Recent anatomical studies have found that cortical neurons are mainly preserved during the aging process while myelin damage and even axonal loss is prominent throughout the forebrain. We ...used diffusion tensor imaging (DT-MRI) to evaluate the hypothesis that during the process of normal aging, white matter changes preferentially affect the integrity of long corticocortical association fiber tracts, specifically the superior longitudinal fasciculus II and the cingulum bundle. This would disrupt communication between the frontal lobes and other forebrain regions leading to cognitive impairments. We analyzed DT-MRI datasets from seven young and seven elderly behaviorally characterized rhesus monkeys, creating fractional anisotropy (FA) maps of the brain. Significant age-related reductions in mean FA values were found for the superior longitudinal fasciculus II and the cingulum bundle, as well as the anterior corpus callosum. Comparison of these FA reductions with behavioral measures demonstrated a statistically significant linear relationship between regional FA and performance on a test of executive function. These findings support the hypothesis that alterations to the integrity of these long association pathways connecting the frontal lobe with other forebrain regions contribute to cognitive impairments in normal aging. To our knowledge this is the first investigation reporting such alterations in the aging monkey.
To assess the effect of a NO-eluting stent on reducing neointimal thickening in a porcine coronary artery stent injury model, sodium nitroprusside (SNP), a NO donor, was incorporated into ...polyurethane (PU) polymer and coated onto metallic coil stents, and two types of stents with thin and thick barrier coatings were characterized. In vivo biological activity of the NO-eluting stents was assessed by measurement of coronary arterial cGMP levels in 32 pigs/64 arteries at days 1, 2, 7 and 14. Morphometric analyses were performed in 16 pigs to determine the effect of NO-eluting stents on neointimal hyperplasia 28 days following arterial injury. The SNP-coated stents released NO in a controlled manner for up to 4 weeks in the in vitro experiments and an increase in local tissue cGMP levels was demonstrated for up to 14 days. The neointimal area at 28 days was not diminished, however, by NO eluded from either stents of thin or thick barriers (control bare stent - 0.66 mm2, control PU stent - 0.68 mm2, SNP-PU thin coating stent - 0.78 mm2, SNP-PU thick coating stent - 0.85 mm2; all p=NS). In conclusion, the SNP-coated polymer stent exerted a local biological effect on the arterial wall, with sustained elevation of cGMP level. Although local delivery of NO from this device did not reduce neointimal hyperplasia in this porcine model, this polymer-coated stent might be a promising tool for administration of other agents that may modify the reparative tissue responses leading to restenosis.
Background
Caregiver perceived autonomy support by the oncologist is important for caregiver well‐being and may be affected by the patient's survival. We determined the association of ...caregiver‐oncologist discordance in patient's life expectancy estimates with perceived autonomy support over time and whether the association differed by patient survival status.
Materials and Methods
We used data from a geriatric assessment cluster‐randomized trial (URCC 13070) that recruited patients aged at least 70 years with incurable cancer considering or receiving treatment, their caregivers, and their oncologists. At baseline, caregivers and oncologists were asked to estimate patient's life expectancy (0–6 months, 7–12 months, 1–2 years, 2–5 years, and >5 years; any difference in response was considered discordant). At 4–6 weeks, 3 months, and 6 months, caregivers completed the Health Care Climate Questionnaire (HCCQ), which measured perceived autonomy support by the oncologist. Generalized estimating equation modeling was conducted to assess the association of baseline caregiver‐oncologist discordance with longitudinal HCCQ scores, stratified by patient 6‐month survival status.
Results
Discordant life expectancy estimates were present in 72.0% of dyads. In multivariate analyses, caregiver‐oncologist discordance in patient's life expectancy estimates was associated with higher caregiver HCCQ scores. In stratified analysis, caregiver‐oncologist discordance was associated with lower caregiver HCCQ scores (β = −3.46; 95% CI, −4.64 to −2.29) among patients who died within 6 months but with higher caregiver HCCQ scores (β = 1.33; 95% CI, 0.63–2.04) among patients who survived beyond 6 months.
Conclusion
Interventions aimed at mitigating discordance need to consider its association with caregiver perceived autonomy support and patient's survival in order to better inform caregiver expectations.
Implications for Practice
Among patients who died within the first 6 months, caregivers who estimated a different length of life for the patient compared with oncologists were more likely to report lower support from the oncologist, whereas the opposite relationship was seen within patients who survived beyond the first 6 months. When designing interventions to improve caregiver understanding of the patient's prognosis, its relationship with caregiver‐perceived support and patient's survival needs to be considered.
Prognostic discordance refers to a discrepancy in estimates of prognosis by two individuals. This article evaluates the association between caregiver‐oncologist prognostic discordance regarding a patient's life expectancy estimates and caregiver perceived autonomy support.
Between one and six cultured human fetal pancreata were allografted into five insulin-dependent diabetic recipients and their progress monitored for a year on each occasion. To prevent rejection the ...tissue was cultured for 1-3 weeks before transplantation, the HLA-DR antigens of the donor tissue were matched with those of the recipient when a single pancreas was used, and four of the recipients were immunosuppressed, three because of coexisting renal grafts. Graft function was observed transiently in one of the recipients. In three others human fetal pancreas was recovered 9-14 months after transplantation, although it was being slowly rejected during this time. Beta cells were present in the graft but did not function adequately to enable immunoreactive C-peptide to be measured in peripheral blood. The issues of rejection and immaturity of the human fetal pancreas will need to be surmounted if the potential of the human fetal pancreas to normalize blood glucose levels in diabetic man is ever to be realized.
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