Background: Limonene, a major component in citrus oil, has demonstrated anti-cancer effects in preclinical mammary cancer models. However, the effective oral dose translates to a human dose that may not be feasible fo...Background: Limonene, a major component in citrus oil, has demonstrated anti-cancer effects in preclinical mammary cancer models. However, the effective oral dose translates to a human dose that may not be feasible for chronic dosing. We proposed to evaluate topical application of limonene to the breast as an alternative dosing strategy. Materials and Methods: We conducted a mouse disposition study to determine whether limonene would be bioavailable in the mammary tissue after topical application. SKH-1 mice received topical or oral administration of limonene in the form of orange oil every day for 4 weeks. Plasma and mammary pads were collected 4 hrs after the final dosing. We also conducted an exploratory clinical study to evaluate the safety and feasibility of topically applied limonene in the form of orange oil to the breast. Healthy women were recruited to apply orange oil containing massage oil to their breasts daily for four weeks. Safety and feasibility were assessed by reported adverse events, clinical labs, and usage compliance. Pre and post-intervention nipple aspirate fluid (NAF) and plasma were collected for limonene concentration determination. Results: The mouse disposition study showed that topical and oral orange oil administration resulted in similar mammary tissue disposition of limonene with no clinical signs of toxicity. In the clinical study, the topical application of limonene containing massage oil to the breast was found to be safe with high levels of usage compliance for daily application, although NAF and plasma limonene concentrations were not significantly changed after the massage oil application. Conclusions: Our studies showed that limonene is bioavailable in mammary tissue after topical orange oil application in mice and this novel route of administration to the breast is safe and feasible in healthy women.展开更多
Introduction: Fast track (FT) cardiac surgery and early extubation (EE) are aimed at safe and effective rapid post-operative progression to discharge, and have been practiced for more than two decades. Their goal is t...Introduction: Fast track (FT) cardiac surgery and early extubation (EE) are aimed at safe and effective rapid post-operative progression to discharge, and have been practiced for more than two decades. Their goal is to optimize patient care perioperatively in order to decrease costs without negatively affecting morbidity and mortality. However, the factors that predict successful EE are poorly understood, and patients with significant co-morbidities are frequently excluded from protocols. We hypothesize that independent of disease severity, early extubation leads to shorter hospital stays and can be performed safely without negatively affecting outcomes. Materials and Methods: We performed a retrospective review of 919 patients who underwent coronary artery bypass grafting (CABG) at the Southern Arizona Veteran’s Affairs Health Care System medical center over 7 years. We collected pre-operative data regarding patients’ NYHA classification, presence and severity of cerebral vascular disease, peripheral vascular disease, pulmonary disease, diabetes and hypertension. Intra-operative variables were also recorded including ASA scores, ischemic times, and time to extubation. Finally, post-operative variables such as rates of reintubation and tracheotomy, and both length of ICU and total hospital stay were also compared. Results: Prolonged periods of ischemia were found to predict a delayed extubation (HR = 0.992;CI = 0.988 - 0.997, p = 0.0015) while small body surface area (HR = 1.57;CI = 1.13, 2.17, p = 0.007) and higher pre-operative functional status of the patient, such as independent versus dependent status (HR =1.68;CI = 1.30 - 2.16, p = 1.33;CI = 1.03 - 1.70, p = 0.03) were found to be associated with earlier extubation. The early extubation (EE) group (those extubated in less than the median 7.3 hours) had an average hospital stay of 5.1 ± 4.0 days, versus 7.8 ± 8.1 days in the delayed group (>4 hours), p Conclusions: In our study population, pre-operative functional class and total body surface area predicted those patients able to tolerate early extubation after cardiac surgery. Prolonged ischemia resulted in delayed extubation. Patients that were extubated in less than 4 hours had shorter ICU and hospitalization stays, while there was no significant difference between the two groups in rate of reintubation or tracheotomy.展开更多
文摘Background: Limonene, a major component in citrus oil, has demonstrated anti-cancer effects in preclinical mammary cancer models. However, the effective oral dose translates to a human dose that may not be feasible for chronic dosing. We proposed to evaluate topical application of limonene to the breast as an alternative dosing strategy. Materials and Methods: We conducted a mouse disposition study to determine whether limonene would be bioavailable in the mammary tissue after topical application. SKH-1 mice received topical or oral administration of limonene in the form of orange oil every day for 4 weeks. Plasma and mammary pads were collected 4 hrs after the final dosing. We also conducted an exploratory clinical study to evaluate the safety and feasibility of topically applied limonene in the form of orange oil to the breast. Healthy women were recruited to apply orange oil containing massage oil to their breasts daily for four weeks. Safety and feasibility were assessed by reported adverse events, clinical labs, and usage compliance. Pre and post-intervention nipple aspirate fluid (NAF) and plasma were collected for limonene concentration determination. Results: The mouse disposition study showed that topical and oral orange oil administration resulted in similar mammary tissue disposition of limonene with no clinical signs of toxicity. In the clinical study, the topical application of limonene containing massage oil to the breast was found to be safe with high levels of usage compliance for daily application, although NAF and plasma limonene concentrations were not significantly changed after the massage oil application. Conclusions: Our studies showed that limonene is bioavailable in mammary tissue after topical orange oil application in mice and this novel route of administration to the breast is safe and feasible in healthy women.
文摘Introduction: Fast track (FT) cardiac surgery and early extubation (EE) are aimed at safe and effective rapid post-operative progression to discharge, and have been practiced for more than two decades. Their goal is to optimize patient care perioperatively in order to decrease costs without negatively affecting morbidity and mortality. However, the factors that predict successful EE are poorly understood, and patients with significant co-morbidities are frequently excluded from protocols. We hypothesize that independent of disease severity, early extubation leads to shorter hospital stays and can be performed safely without negatively affecting outcomes. Materials and Methods: We performed a retrospective review of 919 patients who underwent coronary artery bypass grafting (CABG) at the Southern Arizona Veteran’s Affairs Health Care System medical center over 7 years. We collected pre-operative data regarding patients’ NYHA classification, presence and severity of cerebral vascular disease, peripheral vascular disease, pulmonary disease, diabetes and hypertension. Intra-operative variables were also recorded including ASA scores, ischemic times, and time to extubation. Finally, post-operative variables such as rates of reintubation and tracheotomy, and both length of ICU and total hospital stay were also compared. Results: Prolonged periods of ischemia were found to predict a delayed extubation (HR = 0.992;CI = 0.988 - 0.997, p = 0.0015) while small body surface area (HR = 1.57;CI = 1.13, 2.17, p = 0.007) and higher pre-operative functional status of the patient, such as independent versus dependent status (HR =1.68;CI = 1.30 - 2.16, p = 1.33;CI = 1.03 - 1.70, p = 0.03) were found to be associated with earlier extubation. The early extubation (EE) group (those extubated in less than the median 7.3 hours) had an average hospital stay of 5.1 ± 4.0 days, versus 7.8 ± 8.1 days in the delayed group (>4 hours), p Conclusions: In our study population, pre-operative functional class and total body surface area predicted those patients able to tolerate early extubation after cardiac surgery. Prolonged ischemia resulted in delayed extubation. Patients that were extubated in less than 4 hours had shorter ICU and hospitalization stays, while there was no significant difference between the two groups in rate of reintubation or tracheotomy.
