Worldwide snapshot of trauma team structure and training: an international survey.

INTRODUCTION: Trauma teams (TTs) are a key tool in trauma care, as they bring a multidisciplinary approach to the trauma patient, improving outcomes. Excellent teamwork (TW) requires not only individual skills but also training at non-technical skills (NTS). Although there is evidence supporting TTs, there is little information regarding how they are organized and trained. With this study, we intend to assess the reality of TTs all over the world, focusing on how they are organized and trained. MATERIALS AND METHODS: We composed a 42-question sheet on Google Forms, in four different languages (English, Polish, Portuguese, and Spanish). The questions regarded the respondents' background, and their respective hospitals' trauma patient management, TT features and its training, NTS and TW. The survey was shared on social media, through the International Assessment Group of Online Surgical & Trauma Education community, and the European Society of Trauma and Emergency Surgery. Statistical analysis was performed on Statistical Package for the Social Sciences (SPSS®) version 27. RESULTS: We obtained 296 answers from 52 different countries, with 6 having at least 10 answers (Brazil, Portugal, Poland, Spain, Italy, and USA). While the majority of the respondents (97%) agreed that TTs can improve outcomes, only 61% have a TT in their hospital, with 69% of these being dedicated TTs. General surgery (76%), trauma surgery (68%), and anesthesia (66%) were the three most common specialties in the teams. Teams performed briefings and debriefings with a frequency of, at least, "often" in only 49% and 38%, respectively. Only 50% and 33% of the respondents stated that their hospital provided trauma management courses focusing on individual technical skills, and TT training courses, respectively. The Advanced Trauma Life Support (85%), the Definitive Surgical and Anesthetic Trauma Care (38%), and the European Trauma Course (31%) were the three trauma management courses of choice. Regarding TT training courses, the European Trauma Course (52%) and local/in-house (42%) courses were the most common ones. Most participants (93%) stated that NTS were highly important in trauma care. However, only 60% of the respondents had postgraduate training on NTS and TW, and only 24% had this type of training on an undergraduate level. CONCLUSION: The number of TTs worldwide does not match their relevance in trauma care. Institutions are not providing enough trauma courses, particularly TT training courses and NTS teaching. Implementing TT should include promotion of team courses, as well as team briefings and debriefings.

International cooperation group of emergency surgery during the COVID-19 pandemic.

PURPOSE: The COVID-19 pandemic has changed working conditions for emergency surgical teams around the world. International surgical societies have issued clinical recommendations to optimize surgical management. This international study aimed to assess the degree of emergency surgical teams' adoption of recommendations during the pandemic. METHODS: Emergency surgical team members from over 30 countries were invited to answer an anonymous, prospective, online survey to assess team organization, PPE-related aspects, OR preparations, anesthesiologic considerations, and surgical management for emergency surgery during the pandemic. RESULTS: One-hundred-and-thirty-four questionnaires were returned (N = 134) from 26 countries, of which 88% were surgeons, 7% surgical trainees, 4% anesthetists. 81% of the respondents got involved with COVID-19 crisis management. Social media were used by 91% of the respondents to access the recommendations, and 66% used videoconference tools for team communication. 51% had not received PPE training before the pandemic, 73% reported equipment shortage, and 55% informed about re-use of N95/FPP2/3 respirators. Dedicated COVID operating areas were cited by 77% of the respondents, 44% had performed emergency surgical procedures on COVID-19 patients, and over half (52%), favored performing laparoscopic over open surgical procedures. CONCLUSION: Surgical team members have responded with leadership to the COVID-19 pandemic, with crisis management principles. Social media and videoconference have been used by the vast majority to access guidelines or to communicate during social distancing. The level of adoption of current recommendations is high for organizational aspects and surgical management, but not so for PPE training and availability, and anesthesiologic considerations.

Increased adiposity by feeding growing rats a high-fat diet results in iron decompartmentalisation.

The present study reports the effects of a high-fat (HF) diet of over 8 weeks on the Fe status of growing rats. Tissue Fe levels were analysed by atomic absorption spectrophotometry, and whole-body adiposity was measured by dual-energy X-ray absorptiometry. Histopathology and morphometry of adipose tissue were performed. Liver homogenates were used for measuring ferroportin-1 protein levels by immunoblotting, and transcript levels were used for Fe genes measured by real-time PCR. Tissue Fe pools were fit to a compartmental biokinetic model in which Fe was assessed using fourteen compartments and twenty-seven transfer constants (kj,i from tissue 'i' to tissue 'j') adapted from the International Commission on Radiological Protection (ICRP) 69. Ten kj,i were calculated from the experimental data using non-linear regression, and seventeen were estimated by allometry according to the formula ${k_{i,j}} = a \times {M^b}$. Validation of the model was carried out by comparing predicted and analysed Fe pool sizes in erythrocytes, the liver and the spleen. Body adiposity was negatively associated with serum Fe levels and positively associated with liver Fe stores. An inferred increase in Fe transfer from bone marrow to the liver paralleled higher hepatic Fe concentrations and ferritin heavy-chain mRNA levels in the HF diet-fed animals, suggesting that liver Fe accumulation occurred at least in part due to a favoured liver erythrocyte uptake. If this feeding condition was to be prolonged, impaired Fe decompartmentalisation may occur, ultimately resulting in dysmetabolic Fe overload.

Improving Intraoperative Communication in Trauma: The Educational Effect of the Joint DSTC™-DATC™ Courses.

BACKGROUND: Operative management of severe trauma requires excellent communication among team members. The surgeon and anesthesiologist need to interact efficiently, exchanging vital information. The Definitive Surgical Trauma Care (DSTC) and Definitive Anesthesia Trauma Care (DATC) courses provide an excellent opportunity for teamwork training. Our goal was to study the impact of the joint DSTC-DATC courses in candidates' self-reported assessment in communication skills and techniques in a simulated intraoperative trauma scenario. METHODS: Study population consists of 93 candidates (67 surgeons and 26 anesthesiologists) participating in four consecutive joint DSTC-DATC courses in May and June 2019 in Brazil (3) and in Portugal (1). Median age was 30 years; 53 (60%) of subjects were male (46 senior residents and 47 specialists). All participants attended joint lectures, case discussions and surgical skills session, emphasizing intraoperative communication. Post-course survey on several aspects of perioperative communication (responses on a Likert scale) was conducted with participants being asked which aspects of intraoperative communication they valued the most. RESULTS: All participants responded to the survey. Results displayed an increase in the self-assessed importance of team briefing and intraoperative communication, particularly routine periodic communication, rather than only at critical moments. Postoperative team debriefing was also valued as highly relevant. Closed-loop and direct, by-name communication were highly rated. Self-reported communication skills improved significantly during the course. CONCLUSIONS: Joint training in the DSTC-DATC courses improved candidates' perception and skills on proficient intraoperative communication. Further studies should address both the durability of these changes and the potential impact on patient care.

Acute airway obstruction due to benign multinodular goitre.

Benign multinodular goitre is a common illness. When accompanied by obstructive symptoms, such as dyspnoea, it carries an indication for surgery. Benign multinodular goitres rarely cause acute airway obstruction. We report the case of a 88-year-old woman who presented with acute shortness of breath and stridor. A chest CT revealed marked enlargement of the thyroid gland, with an extensive intrathoracic component. She was proposed for total thyroidectomy. Her intraoperative course was unremarkable, but the patient passed away in postoperative period from ventricular fibrillation. Recognition of these cases is important, as they constitute a preventable cause of mortality if timely diagnosed and treated.

Sepse neonatal - perfil microbiológico e sensibilidadeantimicrobiana em um hospital no Nordeste do Brasil / Neonatal sepsis - microbiological profile and antimicrobial sensitivity in a hospital in the Northeast of Brazil

Objetivo: Determinar a prevalência de microrganismos e o perfil de sensibilidade antimicrobiana em hemoculturas positivas de pacientes com infecção de corrente sanguínea na Unidade de Terapia Intensiva neonatal de um hospital no Nordeste brasileiro. Métodos: Estudo transversal, retrospectivo, com descrição quantitativa dos resultados de hemoculturas de neonatos admitidos na unidade terapia intensiva neonatal de um hospital do Nordeste brasileiro. Resultados: A sepse neonatal teve como principal etiologia bactérias Gram-positivas, responsáveis por 73,1% das culturas positivas, sendo o Staphylococcus Coagulase-negativa o principal agente, enquanto que 21,5% se deram por um agente Gram-negativo. As bactérias Gram-positivas apresentaram boa sensibilidade ao linezolida e à vancomicina e a maioria das Gram-negativas foi sensível a colistina, meropenem e imipenem. Todos os isolados de Staphylococcus coagulase negativa foram sensíveis ao linezolida, à vancomicina e à tigeciclina. Conclusão: O conhecimento das características relacionadas à sensibilidade e resistência antimicrobiana é fundamental para uma melhor abordagem ao paciente com sepse neonatal, promovendo um manejo mais direcionado que possibilita uma recuperação mais rápida do recém-nascido. O conhecimento adquirido com esse estudo possibilitará um tratamento mais eficiente em cada caso, com base no quadro apresentado pelo paciente e as características do agente causador.

Objective: To determine the prevalence of microorganisms and the antimicrobial sensitivity profile in positive blood cultures of patients with bloodstream infection in the neonatal Intensive Care Unit of a hospital in the Brazilian Northeast. Methods: Cross-sectional, retrospective study with quantitative description of hemoculture results of neonates admitted to the neonatal intensive care unit of a Brazilian Northeast hospital. Results: Neonatal sepsis had as its main etiology Gram-positive bacteria responsible for 73.1% of the positive cultures, with coagulase-negative Staphylococcus being the main agent, while 21.5% were due to a Gramnegative agent. Gram-positive bacteria showed good sensitivity to linezolid and vancomycin and most Gram-negative strains were susceptible to colistin, meropenem and imipenem. All coagulase-negative Staphylococcus isolates were sensitive to linezolid, vancomycin and tigecycline. Conclusion: Knowledge of the characteristics related toantimicrobial susceptibility and resistance is fundamental for a better approach to the patient with neonatal sepsis, promoting a more targeted management that allows a faster recovery of the newborn. The knowledge gained from this study will allow a more efficient treatment in each case, based on the patient's presentation and the characteristics of the causative agent

Removal of Chylomicron Remnants from the Bloodstream is Delayed in Aged Subjects.

Dietary fats absorbed in the intestine are transported in the circulation as chylomicrons and remnants that have atherogenic potential. Although postprandial lipidemia is increased in older subjects, the specific chylomicron metabolism has not been explored in older subjects nor compared to young subjects, which is the focus of this study. After a 12 h fast, artificially-made emulsions similar to lymph chylomicrons and doubly labeled with radioactive cholesteryl esters and triglycerides were intravenously injected in 23 older (66±4 years) and 20 young (24±3 years) subjects. Sequential blood samples were collected to determine fractional clearance rates (FCR, in min-1) by compartmental analysis. Older subjects had higher LDL-cholesterol (p<0.001) and triglycerides (p<0.0001) than young subjects; HDL-cholesterol presented no difference. The emulsion cholesteryl-ester FCR was lower in older subjects compared to the young (p=0.0001). The emulsion triglyceride FCR did not differ in the two groups. Tested in vitro, however, the lipolysis of the emulsion triglycerides was less intense in the older than in the young subjects. As delayed removal of remnants, indicated by the pronouncedly smaller cholesteryl ester FCR, is related to the presence of cardiovascular diseases, this can be a risk factor which could accelerate atherogenic complications occurring in aged subjects.

2017 WSES guidelines for the management of iatrogenic colonoscopy perforation.

Iatrogenic colonoscopy perforation (ICP) is a severe complication that can occur during both diagnostic and therapeutic procedures. Although 45-60% of ICPs are diagnosed by the endoscopist while performing the colonoscopy, many ICPs are not immediately recognized but are instead suspected on the basis of clinical signs and symptoms that occur after the endoscopic procedure. There are three main therapeutic options for ICPs: endoscopic repair, conservative therapy, and surgery. The therapeutic approach must vary based on the setting of the diagnosis (intra- or post-colonoscopy), the type of ICP, the characteristics and general status of the patient, the operator's level of experience, and surgical device availability. Although ICPs have been the focus of numerous publications, no guidelines have been created to standardize the management of ICPs. The aim of this article is to present the World Society of Emergency Surgery (WSES) guidelines for the management of ICP, which are intended to be used as a tool to promote global standards of care in case of ICP. These guidelines are not meant to substitute providers' clinical judgment for individual patients, and they may need to be modified based on the medical team's level of experience and the availability of local resources.

Tissue Uptake Mechanisms Involved in the Clearance of Non-Protein Nanoparticles that Mimic LDL Composition: A Study with Knockout and Transgenic Mice.

Lipid core nanoparticles (LDE) resembling LDL behave similarly to native LDL when injected in animals or subjects. In contact with plasma, LDE acquires apolipoproteins (apo) E, A-I and C and bind to LDL receptors. LDE can be used to explore LDL metabolism or as a vehicle of drugs directed against tumoral or atherosclerotic sites. The aim was to investigate in knockout (KO) and transgenic mice the plasma clearance and tissue uptake of LDE labeled with 3H-cholesteryl ether. LDE clearance was lower in LDLR KO and apoE KO mice than in wild type (WT) mice (p < 0.05). However, infusion of human apoE3 into the apoE KO mice increased LDE clearance. LDE clearance was higher in apoA-I KO than in WT. In apoA-I transgenic mice, LDE clearance was lower than in apoA-I KO and than in apoA-I KO infusion with human HDL. Infusion of human HDL into the apoA-I KO mice resulted in higher LDE clearance than in the apoA-I transgenic mice (p < 0.05). In apoA-I KO and apoA-I KO infused human HDL, the liver uptake was greater than in WT animals and apoA-I transgenic animals (p < 0.05). LDE clearance was lower in apoE/A-I KO than in WT. Infusion of human HDL increased LDE clearance in those double KO mice. No difference among the groups in LDE uptake by the tissues occurred. In conclusion, results support LDLR and apoE as the key players for LDE clearance, apoA-I also influences those processes.

Expression of Genes Involved in Porphyrin Biosynthesis Pathway in the Human Renal Cell Carcinoma.

Renal cell carcinoma (RCC) remains one of the greatest challenges of urological oncology and is the third leading cause of death in genitourinary cancers. Surgery may be curative when patients present with localized disease. Our previous results demonstrated the autofluorescence of blood PpIX in primary RCC mouse model and an increase in fluorescence intensity as a function of growth of the subcutaneous tumor mass. In another work, a nice correlation between the growth of the tumor mass and tissue fluorescence intensity was found. The aim of this study was to evaluate the expression profile of porphyrin biosynthesis pathway-related genes of human kidney cells. We used two kidney cell lines, one normal (HK2) and another malignant (Caki-1). Endogenous and 5-aminolevolinic acid (ALA) induced protoporphyrin IX (PpIX) HK2 and Caki-1 cells were analyzed by fluorescence spectroscopy. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to measure mRNA of those genes. Emission spectra were obtained by exciting the samples at 405 nm. For ALA untreated cells the maximum fluorescence intensity was detected at 635 nm. The mean peak area of emission spectra in both cells types increased linearly in function of cell number. Besides, basal levels of PpIX autofluorescence of each cell concentration of HK2 samples were significantly lower than those of Caki-1 samples. For ALA-treated cells the mean PpIX spectra shows PpIX emission peak at 635 nm with a shoulder at 700 nm. Analysis of PpIX fluorescence intensity ratio between tumor cells and HK2 cells showed that fluorescence intensity was, on average, 26 times greater in tumor cells than in healthy cells. qRT-PCR revealed that in Caki-1 ALA-treated cells, PEPT gene was significantly up-regulated and FECH and HO-1 genes were significantly down regulated in comparison with HK2 ALA-treated cells. In conclusion, our results demonstrate the preferential accumulation of ALA-induced PpIX in human RCC and also indicate that PEPT1, FECH and HO-1 genes are major contributors to this accumulation.

Favorable effects of ezetimibe alone or in association with simvastatin on the removal from plasma of chylomicrons in coronary heart disease subjects.

OBJECTIVE: Reductions on the clearance from plasma of chylomicrons are associated with atherosclerosis. Statins improve the removal from plasma of chylomicrons in a dose dependent manner. There is controversy whether ezetimibe modifies the plasma clearance of chylomicrons. Effects of ezetimibe alone or in combination with simvastatin were compared with low and high dose of the latter, upon the kinetics of a chylomicron-like emulsion in coronary heart disease (CHD) patients. METHODS: 25 CHD patients were randomized for treatment with ezetimibe 10 mg (group 1) or simvastatin 20 mg (group 2) with progression to ezetimibe + simvastatin 10/20 mg or simvastatin 80 mg, respectively. Kinetic studies were performed at baseline and after each treatment period of 6 weeks. The fractional catabolic rates (FCR) of the emulsion labeled with (14)C-CE and (3)H-TG, that represent respectively chylomicron remnant and triglyceride removal, were calculated. Comparisons were made by ANOVA. RESULTS: The (14)CE-FCR in group 1 were 0.005 ± 0.004, 0.011 ± 0.008 and 0.018 ± 0.005 min(-1) and in group 2 were 0.004 ± 0.003, 0.011 ± 0.008 and 0.019 ± 0.007 min(-1) respectively at baseline, after 6 and 12 weeks (p < 0.05 vs. baseline, and 6 vs. 12 weeks). The (3)H-TG-FCR in group 1 were 0.017 ± 0.011, 0.024 ± 0.011 and 0.042 ± 0.013 min(-1) and in group 2 were 0.016 ± 0.009, 0.022 ± 0.009 and 0.037 ± 0.012 min(-1) at baseline, after 6 and 12 weeks (p < 0.05 vs. baseline, and 6 vs. 12 weeks). There were no differences between groups in time. CONCLUSION: Both treatments increased similarly the removal from plasma of chylomicron and remnants in CHD patients.

Seasonal variation in the serum 25-hydroxyvitamin D levels of young and elderly active and inactive adults in São Paulo, Brazil: The São PAulo Vitamin D Evaluation Study (SPADES).

OBJECTIVE: To evaluate the 25-hydroxyvitamin D [25(OH)D] concentrations in individuals in the city of São Paulo belonging to different age groups and exhibiting specific behavioral characteristics and to correlate the 25(OH)D concentration with the level of UV radiation (UVR). PATIENTS AND METHODS: A total of 591 individuals were included, distributed as follows: 177 were living in institutions (NURSING, 76.2 ± 9.0 y old), 243 were part of the community elderly (COMMUNITY, 79.6 ± 5.3 y old), 99 were enrolled in a physical activity program targeting the elderly (ACTIVE, 67.6 ± 5.4 y old) and 72 were young (YOUNG, 23.9 ± 2.8 y old). Blood samples from all individuals were collected throughout the year. UVR measurements were taken by an official meteorology institution. RESULTS: The UVR values varied throughout the year, following a sinusoidal-like pattern. Because of the Earth's orbit, we hypothesized that there would be cyclic patterns for the 25(OH)D and UVR values that repeat every 12 mo. The general formula is represented by the equation P1+P2⋅sin(-2⋅π12⋅(t-P3)) The mean 25(OH)D concentration and the amplitude of the variation were significantly higher for the YOUNG and ACTIVE groups than for the COMMUNITY and NURSING groups. The nadir for UVR was in June, whereas the nadir for the 25(OH)D concentration was in the spring, corresponding to a delay of one season. CONCLUSIONS: There was seasonal variation in the 25(OH)D concentration for all the groups studied; however, the amplitude of the variation was higher for the groups of young and physically active people, possibly due to the higher level of sunlight exposure for these groups. The lowest 25(OH)D concentration was detected in the spring.

Resistance training changes LDL metabolism in normolipidemic subjects: a study with a nanoemulsion mimetic of LDL.

OBJECTIVE: To evaluate the effects of resistance training (RT) on the metabolism of an LDL-like nanoemulsion and on lipid transfer to HDL, an important step of HDL metabolism. METHODS: LDL-like nanoemulsion plasma kinetics was studied in 15 healthy men under regular RT for 1-4 years (age = 25 ± 5 years, VO(2)peak = 50 ± 6 mL/kg/min) and in 15 healthy sedentary men (28 ± 7 years, VO(2)peak = 35 ± 9 mL/kg/min). LDL-like nanoemulsion labeled with (14)C-cholesteryl-ester and (3)H-free-cholesterol was injected intravenously, plasma samples were collected over 24-h to determine decay curves and fractional clearance rates (FCR). Lipid transfer to HDL was determined in vitro by incubating of plasma samples with nanoemulsions (lipid donors) labeled with radioactive free-cholesterol, cholesteryl-ester, triacylglycerols and phospholipids. HDL size, paraoxonase-1 activity and oxidized LDL levels were also determined. RESULTS: The two groups showed similar LDL and HDL-cholesterol and triacylglycerols, but oxidized LDL was lower in RT (30 ± 9 vs. 61 ± 19 U/L, p = 0.0005). In RT, the nanoemulsion (14)C-cholesteryl-ester was removed twice as fast than in sedentary individuals (FCR: 0.068 ± 0.023 vs. 0.037 ± 0.028, p = 0.002), as well as (3)H-free-cholesterol (0.041 ± 0.025 vs. 0.022 ± 0.023, p = 0.04). While both nanoemulsion labels were removed at the same rate in sedentary individuals, RT (3)H-free-cholesterol was removed slower than (14)C-cholesteryl-ester (p = 0.005). HDL size, paraoxonase 1 and the transfer rates to HDL of the four lipids were the same in both groups. CONCLUSIONS: RT accelerated the clearance of LDL-like nanoemulsion, which probably accounts for the oxidized LDL levels reduction in RT. RT also changed the balance of free and esterified cholesterol FCR's. However, RT had no effect on HDL metabolism related parameters.

Methodological analysis of gamma tomography system for large random packed columns.

Gamma ray tomography experiments have been carried out to detect spatial patterns in the porosity in a 0.27 m diameter column packed with steel Rashig rings of different sizes: 12.6, 37.9, and 76 mm. using a first generation CT system (Chen et al., 1998). A fast Fourier transform tomographic reconstruction algorithm has been used to calculate the spatial variation over the column cross section. Cross-sectional gas porosity and solid holdup distribution were determinate. The values of cross-sectional average gas porosity were epsilon=0.849, 0.938 and 0.966 for the 12.6, 37.9, and 76 mm rings, respectively. Radial holdup variation within the packed bed has been determined. The variation of the circumferentially averaged gas holdup in the radial direction indicates that the porosity in the column wall region is a somewhat higher than that in the bulk region, due to the effect of the column wall.

Deposition of free cholesterol in the blood vessels of patients with coronary artery disease: a possible novel mechanism for atherogenesis.

A cholesterol-rich nanoemulsion (LDE) that mimics the composition of low-density lipoprotein (LDL) acquires apoE in the plasma and is taken-up by the cells by LDL receptors. In this study, to verify whether free cholesterol (FC) and the cholesteryl ester (CE) components of LDL are taken-up differently by the vessels. LDE labeled with (3)H-cholesterol and (14)C-cholesteryl oleate was injected into 20 coronary artery disease patients 24 h before a scheduled myocardial coronary artery bypass grafting. The plasma kinetics of both radiolabels was determined from plasma samples collected over 24 h, and fragments of vessels discarded during surgery were collected and analyzed for radioactivity. LDE FC was removed faster than CE. The radioactive counting of LDE CE was greater than that of LDE FC in the blood, but the uptake of FC was markedly greater than that of CE in all fragments: fivefold greater in the aorta (p = 0.04), fourfold greater in the internal thoracic artery (p = 0.03), tenfold greater in the saphenous vein (p = 0.01) and threefold in the radial artery (p = 0.05). In conclusion, the greater removal from plasma of FC compared with CE and the remarkably greater vessel tissue uptake of FC compared with CE suggests that, in the plasma, FC dissociates from the nanoemulsion particles and precipitates in the vessels. Considering LDE as an artificial nanoemulsion model for LDL, our results suggest that dissociation of FC from lipoprotein particles and deposition in the vessel wall may play a role as an independent mechanism in atherogenesis.

Diminished macrophage cholesterol removal rate by the altered HDL metabolism in the Nagase analbuminemic rat.

Dyslipoproteinemia of the Nagase analbuminemic rat (NAR) is characterized by elevated concentrations of VLDL and LDL attributed to increased rates of liver lipoprotein synthesis. Increased lysophosphatidylcholine (LPC) in NAR HDL has been attributed to high plasma LCAT activity. We show here that, as compared with Sprague-Dawley rats (SDR), NAR plasma triacylglycerol (TAG), total cholesterol (TC), HDL TAG, protein, total phospholipids (PL), LPC, and PS are increased. These alterations rendered the NAR HDL particle more susceptible to the activity of the enzyme hepatic lipoprotein lipase (HL), which otherwise was unaltered in our study. Fractional catabolic rates in blood of the autologous 125I-apoHDL (median and lower quartile values), were, respectively, 0.231 and 1.645 (n = 10) in NAR as compared with 0.140 and 0.109 (n = 10) in SDR (P = 0.012), corresponding to synthesis rates of HDL protein of 89.8 +/- 33.7 mg/d in NAR and 17.4 +/- 6.5 mg/d in SDR (P = 0.0122). Furthermore, Swiss mouse macrophage free-cholesterol (FC) efflux rates, measured as the percent [14C]-cholesterol efflux/6 h, were 8.2 +/- 2.3 (n = 9) in NAR HDL and 11.2 +/- 3.2 (n = 10) in SDR HDL (P = 0.03). Therefore, in NAR the modification of the HDL composition slows down the cell FC efflux rate, and together with the increased rate of plasma HDL metabolism influences the reverse cholesterol transport system.

High cholesterol intake modifies chylomicron metabolism in normolipidemic young men.

Whether the consumption of egg yolk, which has a very high cholesterol content without excess saturated fats, has deleterious effects on lipid metabolism is controversial. Absorbed dietary cholesterol enters the bloodstream as chylomicrons, but the effects of regular consumption of large amounts of cholesterol on the metabolism of this lipoprotein have not been explored even though the accumulation of chylomicron remnants is associated with coronary artery disease (CAD). We investigated the effects of high dietary cholesterol on chylomicron metabolism in normolipidemic, healthy young men. The plasma kinetics of a chylomicron-like emulsion, doubly-labeled with 14C-cholesteryl ester (14C-CE) and 3H-triolein (3H-TG) were assessed in 25 men (17-22 y old, BMI 24.1 +/- 3.4 kg/m2). One group (n = 13) consumed 174 +/- 41 mg cholesterol/d and no egg yolk. The other group (n = 12) consumed 3 whole eggs/d for a total cholesterol intake of 804 +/- 40 mg/d. The nutritional composition of diets was the same for both groups, including total lipids and saturated fat, which comprised 25 and 7%, respectively, of energy intake. Serum LDL and HDL cholesterol and apoprotein B concentrations were higher in the group consuming the high-cholesterol diet (P < 0.05), but serum triacylglycerol, apo AI, and lipoprotein (a) did not differ between the 2 groups. The fractional clearance rate (FCR) of the 14C-CE emulsion, obtained by compartmental analysis, was 52% slower in the high-cholesterol than in the low-cholesterol group (P < 0.001); the 3H-TG FCR did not differ between the groups. Finally, we concluded that high cholesterol intakes increase the residence time of chylomicron remnants, as indicated by the 14C-CE kinetics, which may have undesirable effects related to the development of CAD.

Plasma kinetics of a cholesterol-rich microemulsion (LDE) in patients with Hodgkin's and non-Hodgkin's lymphoma and a preliminary study on the toxicity of etoposide associated with LDE.

BACKGROUND: Neoplastic diseases are often associated with low plasma low-density lipoprotein (LDL) cholesterol and diminished LDL clearance due to upregulation in cancer cells of the receptors that internalize the lipoprotein. Thus, it is possible to use LDL or cholesterol-rich microemulsions (LDE) that bind to LDL receptors as carriers of antineoplastic agents to concentrate those drugs into cancer tissues. Our aim was to determine whether LDL cholesterol concentration plus LDE increased clearance occur in lymphomas. PATIENTS AND METHODS: The LDE labeled with [(3) H]-cholesteryl oleate was injected into four Hodgkin's and 12 non-Hodgkin's lymphoma patients and into 16 healthy control subjects and the LDE plasma residence time (RT) was determined from sequential plasma samples. Two volunteers with relapsed/refractory lymphoma were treated with 300 mg/m(2) body surface etoposide associated with LDE in six cycles at 3-week intervals. RESULTS: The LDL cholesterol was lower in lymphoma patients than in controls (94+/-52 and 115+/-16 mg/dL, p=0.0362, respectively). The LDE RT was 49% smaller in lymphoma patients than in controls (RT=21.9 and 45.7 h; p=0.0134), with positive correlation between RT and LDL cholesterol. LDE-etoposide showed no considerable toxicity in all cycles in the two treated patients and the disease remained stable during the treatment. CONCLUSIONS: Our results suggest that lymphomas overexpress LDL receptors that make room for using LDE as drug-targeting vehicle and that the LDE-etoposide preparation is suitable for patient use.

Malignant teratoma of the thyroid: case report.

Teratomas in the neck are rare neoplasms. Most of them occur in infants less than 1 year and are benign. In contrast, thyroid teratomas in adults are malignant and have fatal outcomes because of spread of tumor refractory to treatment. We report a case of a primary thyroid malignant teratoma in a 37-year-old woman. She was treated successfully with a combination of surgery, postoperative cis-platinum-based chemotherapy, and radiation therapy to the neck. Although the time of follow-up is short (24 months), we attribute her successful outcome to the use of this intensive therapeutic approach.