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Youth placed in U.S. juvenile detention facilities face multilevel barriers that contribute to disparate sexual and reproductive health (SRH) outcomes when compared to their peers in the general adolescent population. Minimal information is available about evidence-based interventions that have been effective in changing these outcomes. The aim of this scoping review was to focus on the current state of SRH and identify recommendations for SRH care. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for scoping reviews guidelines, we searched electronic databases for publications published through March 2024. The search terms were designed to find intervention studies focusing on SRH in U.S. juvenile detention facilities. Eighteen articles were identified, all of which found some combination of positive results. While some intervention content focused on SRH knowledge and attitudes, the majority of studies had sexual risk behaviors in combination with sexually transmitted infections, substance use, or partner violence as their focus. The minimal number of research interventions focused on the structurally vulnerable population of youth in detention facilities across the United States underscores a significant gap in the existing literature, with negative health outcomes for juveniles in detention facilities., (Copyright © 2024 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Long segmental congenital tracheal stenosis and long segmental congenital tracheobronchial stenosis are rare congenital airway anomalies with variable arborizations. This study aimed to analyze presentations and outcomes of slide tracheoplasty in long segmental congenital tracheal and tracheobronchial stenosis with variable arborizations., Methods: Retrospective analysis included all patients who underwent slide tracheoplasty between March 1995 and February 2023 for long segmental congenital tracheal and tracheobronchial stenosis at the Great Ormond Street Hospital for Children (London, United Kingdom). Preoperative airway morphology was divided into anatomic types on the basis of the Great Ormond Street Hospital for Children morphologic classification. Preoperative, intraoperative, postoperative, and follow-up variables were analyzed and compared among patients with different arborizations with long segmental congenital tracheal and tracheobronchial stenosis., Results: A total of 210 patients underwent slide tracheoplasty for long segmental congenital tracheal and tracheobronchial stenosis. The median age at surgery was 6 months (interquartile range, 3-15 months), and the median weight was 6.4 kg (interquartile range, 4.2-8.7 kg). Of these patients, 40% (n = 85) had abnormal arborization, and tracheobronchial morphology was the most common. A total of 24% (n = 50) patients had stenosis extending to 1 or more bronchi. Patients with carinal trifurcation presented early with critical airway stenosis, requiring ventilation support (60%) and extracorporeal membrane oxygenation support (35%) as bridge therapy to slide tracheoplasty. The duration of postoperative ventilation was higher in the patients with congenital tracheobronchial stenosis (P = .006). Patients with a morphology with trifurcation arborization had higher mortality (23%) and stent requirement (35%)., Conclusions: Slide tracheoplasty remains the standard surgery for long segmental congenital tracheal and tracheobronchial stenosis even with different arborizations. Preoperative identification of tracheal arborizations and of the extent of stenosis aids surgical strategies for better outcomes., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

Fast-acting insulin drug products (DPs) are carried and administered by diabetic patients to maintain their blood glucose level throughout the day, exposing the DPs to stress conditions. Apidra, Novolog, and Humalog insulin DPs were tested under various stress conditions. Dynamic light scattering (DLS), and size exclusion chromatography (SEC) were used to monitor the stability and aggregation. Thermal stress alone did not influence the stability. However, 24 hr exposure to vigorous mechanical stress shifted the DLS size peaks of Novolog and Humalog from 5 ± 1 nm to > 50.9 ± 25.6 nm, and the SEC native protein peak areas decreased 52% for Novolog and 18.4% for Humalog. Combined stress accelerated protein aggregation more drastically. Novolog and Humalog size shifted (>75 nm) after 3 hr and the peak area decreased > 97.9% after 6 hr exposure, indicating that high temperature accelerated the aggregation triggered by agitation. Soluble aggregates were captured by DLS early on compared to SEC. Apidra was comparably stable indicating DP formulation plays a critical role in stability. Our study provides a greater understanding of potential failure modes patients and care givers may encounter while handling insulin DPs., Competing Interests: Declaration of Competing Interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Inc.)

Background: Slide tracheoplasty (STP) is the procedure of choice for treatment of long segmental congenital tracheal stenosis (LSCTS). Few studies predict factors leading to reintervention or mortality after STP. We analyzed a pediatric population to identify such factors and compared the outcome between 2 eras (1995-2012 and 2013-2017)., Methods: We analyzed 150 consecutive children who underwent STP from February 1995 to December 2017 in our hospital., Results: Median age and weight were 6.9 months and 6.1 kg. Average tracheal diameter of LSCTS was 2.3 mm. Tracheal stenosis extended into bronchus in 36 patients and distal malacia in 38. Median follow-up was 67 months; mortality was 12.7%. Balloon dilatation was required in 81 patients (54%), stents in 29 (19%), and reoperation in 4 (3%). The presence of malacia, preoperative extracorporeal membrane oxygenation, congenital anomalies, and single lung anatomy increased the risk for reintervention. Cox regression analysis revealed preoperative ventilation to be an independent factor predicting reintervention and single lung tracheal anatomy for mortality. In the current era (after 2013), survival improved from 88% to 97% and stent requirement was reduced from 25% to 11%., Conclusions: Slide tracheoplasty can be applied to various airway configurations seen in LSCTS. The requirement for reintervention such as balloon dilatation and stenting is high in the group requiring preoperative ventilation. Mortality is highest in the single lung anatomy group. Centralization of care allowed us to develop the multidisciplinary team expertise to manage this and other rare airway conditions with acceptable outcomes., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Pulmonary artery sling (PAS) is usually associated with long-segment congenital tracheal stenosis (LSCTS). This combination of abnormalities can also be associated with lung hypoplasia abnormalities (hypoplasia, aplasia, or agenesis). This study analyzed the association of lung hypoplasia abnormalities with combined PAS and LSCTS and its influence on its surgical outcomes., Methods: All patients (0 to 18 years) who underwent surgical procedures for both PAS and LSCTS from 1995 to 2019 were analyzed retrospectively for mortality, ventilation days, and intensive care unit days by dividing them into those with normal lungs (group 1) and hypoplastic lungs (group 2)., Results: Included were 75 patients (30 girls [40%]), who were a median age of 5.7 months (interquartile range [IQR], 2.9-13.3 months), median weight of 5.5 kg (IQR, 4.1-7.9 kg), and had a median follow-up of 99.8 months (IQR, 54.5-152.0 months); of these, 8 patients (10.7%) had hypoplastic right lung, comprising hypoplasia in 7 (87.5%), aplasia in 1 (12.5%), and agenesis in 0 (0%). There was a significant difference in mortality (group 1, 9.0%; group 2, 50%; P = .007) but no significant difference in median ventilation days (group 1, 9.0; group 2, 9.0; P = .89) or in median intensive care unit days (group 1, 14.0; group 2, 11.5; P = .44)., Conclusions: Lung hypoplasia associated with PAS and LSCTS is usually right-sided. As a result of severe airway obstruction and single-lung physiology, there is a high requirement of preoperative cardiorespiratory support and a significant association with adverse surgical outcomes., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: We examined if abortion-related knowledge among women with criminal legal system involvement differed in three U.S. cities in states with varying abortion policies., Study Design: Respondents were self-identified women with criminal legal system involvement. Data come from a cross-sectional baseline survey of 381 women in three U.S. cities: Oakland, California, Kansas City, Kansas/Missouri, and Birmingham, Alabama. The primary outcome, high abortion-related knowledge, was based on a 10-item scale dichotomized into low vs high abortion-related knowledge. We used descriptive statistics, bivariable associations, and logistic regression to assess the association between high abortion-related knowledge, city of residence, and other possible related factors., Results: Respondents in Kansas City, KS/MO and Birmingham, AL had lower odds of high abortion-related knowledge compared to respondents in Oakland, CA (OR: 0.19, 95% CI: 0.10-0.38 and OR: 0.17, 95% CI: 0.11-0.28, respectively). In adjusted analysis, the association remained after controlling for race/ethnicity, insurance status, and community supervision past year., Conclusions: Findings underscore the need for communicating clear and accurate information about abortion care, especially in states where laws and ongoing political challenges make it difficult to access both reliable information and services., Implications: Efforts to disseminate accurate information regarding abortion care, particularly among marginalized people, should utilize multiple venues in addition to traditional healthcare information sources. Reproductive justice advocates should connect with jails and probation offices to reach people with criminal legal system involvement and foster increased knowledge of reproductive rights and services., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Betrayal trauma, as defined by (Freyd, 1996), refers to a subcategory of trauma characterized by a significant violation of trust surrounding interpersonal maltreatment (physical, sexual, or emotional). Previous research has shown that people with betrayal trauma histories experience greater dissociative symptoms of posttraumatic stress disorder and co-morbid substance use disorder symptoms. Women in the criminal legal system commonly have significant histories of betrayal trauma and related posttraumatic stress symptoms and substance use. However, no studies have specifically explored the impact of dissociative posttraumatic stress symptoms on substance use outcomes in this population. Additionally, no studies have explored whether betrayal trauma relates to nonfatal overdoses., Methods: This cross-sectional survey study of N = 508 women with criminal legal system involvement examined the indirect effects of betrayal trauma history on substance use outcomes through dissociative posttraumatic stress symptoms., Results: Multivariate analyses supported an indirect effect of betrayal trauma on substance use severity, daily substance use, and history of overdose, but not alcohol use severity, through dissociative symptoms., Conclusions: Women in the criminal legal system with betrayal trauma and dissociative symptoms may be at risk for substance use and related outcomes (i.e., overdose). Future work is needed to examine whether targeting such symptoms may improve substance use treatment and prevention of serious outcomes in this population., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Comorbid long segment congenital tracheal stenosis and congenital cardiovascular abnormalities in children pose significant challenges with regard to repairing these abnormalities simultaneously or in stages. The aim of this study was to explore whether this combination of abnormalities needs a staged approach for surgical repairs., Methods: All children who underwent both tracheal and cardiac surgical procedures at a tertiary hospital from 1995 to 2018 were analyzed retrospectively for mortality, ventilation days, postoperative intensive care unit days, mediastinitis, and unplanned reoperation by dividing them into simultaneous repairs (group 1), staged repairs within the same admission (group 2), and staged repairs during different admissions (group 3)., Results: Of 110 patients included in the study (group 1, 74; group 2. 10; and group 3, 26 patients), there was no significant difference in mortality (P = .85), median ventilation days (P = .99), median intensive care unit days (P = .23), unplanned airway reoperation (P = .36), and unplanned cardiac reoperation (P = .77). There was a significant difference in the rate of mediastinitis (group 1, 3%; group 2, 10%; and group 3, 19%; P = .02). There was no significant difference in 5-year survival (group 1, 86.2%; group 2, 77.8%; and group 3, 85.1%; P = .86). A higher STAT category was identified to be a risk factor for mortality in multivariate Cox regression analysis (relative risk, 5.45)., Conclusions: Combined tracheal and cardiac abnormalities need a stratified approach to facilitate better clinical outcomes. Although the trajectory of care is often based on the clinical presentation, establishing a management protocol will be helpful, for which setting an international database will be useful., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: In the appropriate clinical setting, the diagnosis of idiopathic pulmonary fibrosis (IPF) requires a pattern of usual interstitial pneumonia to be present on high-resolution chest CT (HRCT) or surgical lung biopsy. A molecular usual interstitial pneumonia signature can be identified by a machine learning algorithm in less-invasive transbronchial lung biopsy samples. We report prospective findings for the clinical validity and utility of this molecular test., Methods: We prospectively recruited 237 patients for this study from those enrolled in the Bronchial Sample Collection for a Novel Genomic Test (BRAVE) study in 29 US and European sites. Patients were undergoing evaluation for interstitial lung disease and had had samples obtained by clinically indicated surgical or transbronchial biopsy or cryobiopsy for pathology. Histopathological diagnoses were made by experienced pathologists. Available HRCT scans were reviewed centrally. Three to five transbronchial lung biopsy samples were collected from all patients specifically for this study, pooled by patient, and extracted for transcriptomic sequencing. After exclusions, diagnostic histopathology and RNA sequence data from 90 patients were used to train a machine learning algorithm (Envisia Genomic Classifier, Veracyte, San Francisco, CA, USA) to identify a usual interstitial pneumonia pattern. The primary study endpoint was validation of the classifier in 49 patients by comparison with diagnostic histopathology. To assess clinical utility, we compared the agreement and confidence level of diagnosis made by central multidisciplinary teams based on anonymised clinical information and radiology results plus either molecular classifier or histopathology results., Findings: The classifier identified usual interstitial pneumonia in transbronchial lung biopsy samples from 49 patients with 88% specificity (95% CI 70-98) and 70% sensitivity (47-87). Among 42 of these patients who had possible or inconsistent usual interstitial pneumonia on HRCT, the classifier showed 81% positive predictive value (95% CI 54-96) for underlying biopsy-proven usual interstitial pneumonia. In the clinical utility analysis, we found 86% agreement (95% CI 78-92) between clinical diagnoses using classifier results and those using histopathology data. Diagnostic confidence was improved by the molecular classifier results compared with histopathology results in 18 with IPF diagnoses (proportion of diagnoses that were confident or provisional with high confidence 89% vs 56%, p=0·0339) and in all 48 patients with non-diagnostic pathology or non-classifiable fibrosis histopathology (63% vs 42%, p=0·0412)., Interpretation: The molecular test provided an objective method to aid clinicians and multidisciplinary teams in ascertaining a diagnosis of IPF, particularly for patients without a clear radiological diagnosis, in samples that can be obtained by a less invasive method. Further prospective clinical validation and utility studies are planned., Funding: Veracyte., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: Describe contraception availability at local health departments (LHDs) serving largely rural populations., Study Design: We invited administrators at LHDs located in four Midwest states to participate in an online survey conducted from September 2017-April 2018. We collected data on clinic staffing, patient population, receipt of Title X funds, and services provided to assess the proportion of LHDs providing any prescription method of contraception; secondary outcomes included healthcare staff training level and other reproductive health services provided., Results: Of 344 LHDs invited, 237 administrators completed the survey (68.9%). Three-quarters served rural populations. One-third (34.6%) provided short-acting hormonal contraception; however, availability varied by state (Kansas: 58.0%, 40/69; Missouri: 37.5%, 33/88; Nebraska: 16.7%, 3/18; Iowa: 9.7%, 6/62; p<.01). Only 8.4% of LHDs provided IUDs; 7.6% provided implants, and 5.9% provided both methods. LHDs in Nebraska and Kansas provided any long-acting method more frequently (Kansas: 17.4%, Nebraska: 16.7%, Iowa: 8.1%, Missouri: 4.6%; p=.04). LHDs receiving Title X funds (27.0%) were much more likely to provide any prescription contraception (85.1% vs. 14.2%, p<.01). Most LHDs relied on registered nurses (RNs) to provide medical care; 81.0% reported that RNs provided care≥20 days per month. Pregnancy testing was widely available in Missouri and Kansas (>87%) and less commonly available in Iowa and Nebraska (<18%) (p<.01)., Conclusion: LHDs in these states are currently ill-equipped to offer comprehensive contraceptive services. Women seeking care at LHDs have limited, if any, contraceptive options., Implications: Local health departments in the Midwest, serving a largely rural population, rarely offer prescription contraception, especially long-acting reversible methods. Women residing in settings without broad access to publicly-funded healthcare providers may have limited access to comprehensive contraceptive services. Efforts to ensure rural access are needed., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Th1 cells are remarkably more susceptible to activation induced cell death than Th17. Here, we compared cultures of these two cell subpopulations for their expression of apoptosis-related molecules when re-exposed to their specific antigen. We also compared the expression of apoptosis-related molecules in the mouse eye with inflammation induced by Th1 or Th17 cells. Using qPCR we found that the mRNA transcript levels of the majority of tested apoptosis-related molecules were higher in the Th1 cultures, and in eyes with Th1-induced inflammation. Apoptotic intrinsic pathway molecules played minor roles in the processes in vitro or in vivo, whereas extrinsic pathway molecules, as well as PD-1, its ligands and Tim3, were heavily involved., (Published by Elsevier Inc.)

Purpose: This study assesses the impact of REAL MEN (Returning Educated African-American and Latino Men to Enriched Neighborhoods), an intervention designed to reduce drug use, risky sexual behavior and criminal activity among 16-18-year-old males leaving New York City jails., Methods: Participants (N = 552) were recruited in city jails and randomly assigned to receive an intensive 30-hour jail/community-based intervention or a single jail-based discharge planning session. All participants were also referred to optional services at a community-based organization (CBO). One year after release from jail, 397 (72%) participants completed a follow-up interview. Logistic and ordinary least squares regression was used to evaluate the impact of the intervention on drug use, risky sexual behavior, criminal justice involvement, and school/work involvement post release., Results: Assignment to REAL MEN and, independently, use of CBO services, significantly reduced the odds of substance dependence (odds ratio [OR] = .52, p ≤ .05; OR = .41, p ≤ .05, respectively) 1 year after release. Those assigned to the intervention spent 29 fewer days in jail compared with the comparison group (p ≤ .05). Compared to non-CBO visitors, those who visited the CBO were more likely to have attended school or found work in the year after release (OR = 2.02, p ≤ .01)., Conclusions: Jail and community services reduced drug dependence 1 year after release and the number of days spent in jail after the index arrest. While these findings suggest that multifaceted interventions can improve outcomes for young men leaving jail, rates of drug use, risky sexual behavior, and recidivism remained high for all participants after release from jail, suggesting the need for additional policy and programmatic interventions., (Copyright © 2010 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

The purpose of the present study was to examine the influence of heat-induced superaggregation of Amphotericin B (AmB) in the Fungizone (FZ) formulation on its interaction with human serum components and relate this to reduced toxicity. Whole serum distribution studies showed that a significantly lower percentage of AmB from HFZ was recovered in the high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglyceride-rich lipoprotein (TRL) fractions and a greater percentage recovered in the lipoprotein-deficient plasma (LPDP), though the majority of both preparations were recovered in LPDP. Circular dichroism (CD) and difference absorption spectroscopy were used to determine the stability of FZ and heat-treated FZ (HFZ) in the presence of HDL, LDL, serum, and albumin. The CD studies indicate that the "core" aggregate of HFZ is more stable in the presence of HDL and LDL, whereas the FZ is less stable and more dynamic with the core aggregate dissociating to a greater extent in the presence of either purified lipoprotein. Absorption studies with whole serum and purified albumin suggest that FZ aggregates are far less stable in the presence of albumin than HFZ and that interaction with serum albumin is a dominant feature for both drug preparations. HFZ also has a different effect on the cytokine response in vitro. Studies using THP-1 human monocytes show that HFZ provokes a smaller release of tumor necrosis factor (TNF)-alpha than FZ. This cytokine may be associated with the unpleasant side effects of AmB. These findings suggest that heat-induced superaggregation of AmB alters its interaction with HDL, LDL, serum proteins, and monocytes, and these findings may be important in explaining the reduced toxicity of the superaggregated form of AmB.

Halofantrine hydrochloride (Hf) is an orally active, highly lipophilic antimalarial indicated for the treatment of multi-drug resistant Plasmodium falciparum. In this study, we have examined the binding profile of Hf to the various classes of human and beagle plasma lipoproteins as such interactions have been implicated in a post-prandial plasma lipoprotein-induced decrease in the total clearance and volume of distribution of Hf. The distribution of Hf within plasma was dominated by interaction with the various classes of plasma lipoproteins, and the characteristics and extent of binding were markedly different between species and between pre- and post-prandial plasma. In an attempt to understand the basis for the differential binding of Hf to the various lipoprotein fractions, the relationship between the proportion of Hf associated with each lipoprotein fraction (as a function of the respective mass of protein, triglyceride, cholesterol, and phospholipid) was investigated. The data indicated that the distribution of Hf between plasma lipoproteins was highly correlated with the apolar lipid load of individual plasma lipoprotein fractions suggesting that the mechanism of association was primarily via solubilization in the lipoprotein apolar lipid core. These data suggest that acute changes in plasma lipoprotein profiles, such as encountered post-prandially or in disease states such as malaria, will likely have an impact on the plasma lipoprotein binding of Hf.

The purpose of these studies was to determine the distribution of a lipophilic antimalarial agent, halofantrine hydrochloride (Hf), in fasted plasma from hypo-, normo-, and hyperlipidemic patients that displayed differences in lipoprotein concentration and lipid transfer protein I (LTP I) activity. To assess the influence of modified lipoprotein concentrations and LTP I activity on the plasma distribution of Hf, Hf at a concentration of 1000 ng/mL was incubated in either hypo-, normo-, or hyperlipidemic human plasma for 1 h at 37 degreesC. Following incubation, the plasma samples were separated into their lipoprotein and lipoprotein-deficient plasma (LPDP) fractions by density gradient ultracentrifugation and assayed for Hf by high-pressure liquid chromatography. The activity of LTP I in the dyslipidemic plasma samples was determined in terms of its ability to transfer cholesteryl ester from low-density lipoproteins (LDL) to high-density lipoproteins (HDL). Total plasma and lipoprotein cholesterol (esterified and unesterified), triglyceride, and protein levels in the dyslipidemic plasma samples were determined by enzymatic assays. When Hf was incubated in normolipidemic plasma for 1 h at 37 degreesC, the majority of drug was found in the LPDP fraction. When Hf was incubated in human plasma of varying total lipid, lipoprotein lipid, and protein concentrations and LTP I activity, the following relationships were observed. As the triglyceride-rich lipoprotein (TRL) lipid and protein concentration increased from hypolipidemia through to hyperlipidemia, the proportion of Hf associated with TRL increased (r > 0.90). As the HDL lipid and protein concentration increased, the proportion of Hf associated with HDL decreased (r > 0.70). As the total and lipoprotein lipid levels increased, the LTP I activity of the plasma also proportionally increased (r > 0.85). Furthermore, with the increase in LTP I activity, the proportion of Hf associated with the TRL fraction increased (r > 0.70) and the proportion of Hf associated with the HDL fraction decreased (r > 0.80). In addition, a positive correlation between the proportion of apolar lipid and Hf recovered within each lipoprotein fraction was observed within hypo- (r > 0.80), normo- (r = 0.70), and hyperlipidemic (r > 0.90) plasmas. These findings suggest that changes in the HDL and TRL lipid and protein concentrations, LTP I activity, and the proportion of apolar lipid within each lipoprotein fraction may influence the plasma lipoprotein distribution of Hf in dyslipidemia.

Tamoxifen remains one of the most effective agents in the treatment of breast cancer. However, the development of persistent side effects from chronic administration of tamoxifen remains a concern. The objective of this project was to investigate the effect of long-term tamoxifen therapy (2 years) on the plasma lipoprotein concentration and lipid transfer activity in postmenopausal women diagnosed with breast cancer. Two distinct populations of breast cancer patients were recruited for this study: postmenopausal women diagnosed with breast cancer that have never been on tamoxifen and postmenopausal women diagnosed with breast cancer that have been on tamoxifen (20 mg once daily) for 2 years (n = 18 each group). Blood was collected for total and lipoprotein cholesterol (C) and triglyceride (TG) analysis by established enzymatic assays prior to and 2 years following the initial tamoxifen dose. To determine the effect of tamoxifen administration on lipid transfer between lipoprotein fractions, lipid transfer protein (LTP I) activity was measured. A significant decrease in total and low-density lipoprotein (LDL) cholesterol levels and a moderate increase in high-density lipoprotein (HDL) triglyceride levels were observed in plasma samples from postmenopausal women with breast cancer who were administered tamoxifen for 2 years. No significant differences in total and lipoprotein C and TG plasma levels were observed in samples from women with breast cancer that never received tamoxifen. LTP I activity was significantly decreased in patients receiving tamoxifen compared to patients who never received tamoxifen. These specific tamoxifen-induced effects may be important for a number of reasons. Although the apparent decrease in total C and LDL-C levels are favorable for reducing the risk of cardiovascular disease, the elevated levels of HDL-TG have been related to the increased risk of ischemic heart disease. Furthermore, understanding how tamoxifen influences LTP I activity provides valuable insight into how the administration of tamoxifen modifies plasma lipoprotein-lipid levels.

Amphiphilic diblock copolymer poly (D,L-lactide)-block-methoxy polyethylene glycol was synthesized, and paclitaxel (Taxol) was incorporated into this copolymer above its critical micelle concentration (cmc), resulting in the formation of polymeric micellar paclitaxel (PMT). Free paclitaxel dissolved in acetonitrile (TAX) and PMT, at 10 micrograms of paclitaxel/mL of human plasma, were incubated for 5, 30, and 60 min at 37 degrees C. Following incubation, the plasma was separated into its high-density (HDL), low-density (LDL), very-low-density (VLDL) lipoprotein and lipoprotein-deficient (LPDP) plasma fractions by density gradient ultracentrifugation. Each of these lipoprotein (LP) and LPDP fractions were analyzed for paclitaxel and plasma lipid levels by well-established HPLC and enzymatic assays. When TAX was incubated in human plasma for 5 min, an equal amount of drug was found in the LP and LPDP fractions. This distribution profile did not change following incubation for 30 and 60 min. Of the amount of TAX that was distributed within the LP fraction, 70-75% of TAX was associated with the HDL fraction for all time points studied. The paclitaxel plasma and LP distribution profile for PMT was similar to the distribution profile of TAX, suggesting that the plasma and LP distribution of paclitaxel is independent of the method of paclitaxel delivery and that LP distribution is not a function of mass lipid levels.