"Large Diameter" Aortic Endografts are Associated With Aneurysm Sac Expansion.

BACKGROUND: The purpose of this study was to evaluate the association between aortic endograft diameter and long-term outcomes following endovascular aneurysm repair (EVAR) performed in accordance with manufacturer instructions for use (IFU). METHODS: A retrospective review of consecutive patients undergoing on-IFU EVAR (2000-2018) was performed to facilitate a comparative analysis of long-term patient outcomes based on device diameter. "Large diameter" devices were defined as >34 mm. The primary outcome of interest was freedom from sac expansion throughout long-term follow-up. Analyses included standard bivariate analyses, Kaplan-Meier with log-rank comparison, and Cox proportional hazards multivariate analysis. RESULTS: A total of 1,099 underwent on-IFU EVAR from 2000-2018. Follow-up data were available for 980 patients. Of these, 75 patients (7.6%) were treated with >34-mm devices. There were no significant differences in demographics or comorbidities between the 2 groups, although preoperative abdominal aortic aneurysm size was greater in patients undergoing implantation of >34-mm devices (58 ± 8.5 mm vs. 56 ± 17.4 mm; P = 0.05). Median follow-up was 10.3 years. Patients with grafts >34 mm had reduced freedom from sac expansion throughout follow-up (P = 0.038). There were no significant differences in reintervention rates, open conversion, or rupture when stratified by graft diameter. A multivariate Cox regression identified patient age, preoperative abdominal aortic aneurysm size, need for reintervention, and use of >34-mm endografts as independent factors associated with expansion. CONCLUSIONS: The use of large diameter aortic endografts is associated with higher rates of sac expansion during long-term follow-up. Although there is undoubtedly a role for large diameter graft use in selected patients, it is important to recognize that these devices were typically approved post hoc without the same regulatory scrutiny of smaller endografts. These findings underscore the importance of ongoing surveillance for patients treated with >34-mm grafts, irrespective of compliance with manufacturer IFU.

Impact of "Defensive Medicine" on the Costs of Diabetes and Associated Conditions.

BACKGROUND: Geographic variation in health care spending is typically attributed to differences in patient health status and provider practice patterns. While medicolegal considerations (i.e., "defensive medicine") anecdotally impact health care spending, this phenomenon is difficult to measure. The purpose of this study was to explore the association between the medicolegal environment and Medicare costs for diabetes and associated conditions of interest to vascular surgeons. Specifically, we hypothesized that an adverse medicolegal environment is associated with higher per capita Medicare costs for diabetic patients. METHODS: Medicare data including the most recent (2018) Medicare Geographic Variation Public Use Files and Chronic Conditions Data Files were linked to National Practitioner Data Bank files from the preceding 5 years (2013-2017), in addition to the US census data and American Medical Association workforce statistics. The state-level medicolegal environment was characterized by K-means clustering across a panel of metrics related to malpractice payment magnitude and prevalence. Per capita Medicare spending for diabetes was compared across 5 distinct medicolegal environments. Costs were standardized and risk-adjusted to account for known geographic variation in health care costs and patient population. Analysis of variance was applied to unadjusted data, followed by multivariate regression modeling. Readmission rates, per capita imaging studies, per capita tests, per capita procedures, and lower extremity amputation rates were compared between the least litigious quintile from the K-means clustering and the 2 most litigious quintiles. RESULTS: The median unadjusted Medicare per capita expenditure on diabetic patients was $15,963 ($14,885-$17,673), ranging from $13,762 (Iowa) to $21,865 (D.C.). A 1.6-fold variation persisted after payment standardization. Cluster analysis based on malpractice-related variables yields 5 distinct medicolegal environments, based on litigation frequency and malpractice payment amounts. Per capita spending on diabetes varied, ranging from $15,799 in states with low payments and infrequent litigation to $18,838 in states with the most adverse medicolegal environment (P < 0.05). After cost standardization and risk adjustment with multiple linear regression, malpractice claim prevalence (per 100 physicians) remained an independent predictor of states with the highest diabetes mellitus spending (P = 0.022). Moreover, diabetic patients in states with adverse medicolegal environments had more procedures, imaging studies, and readmissions (P < 0.05 for all) but did not have significant differences in amputation rates compared to less litigious states. CONCLUSIONS: An adverse medicolegal environment is independently associated with higher health care costs but does not result in improved outcome (i.e. amputation rate) for diabetic Medicare beneficiaries. Across states, a 1% increase in lawsuits/100 physicians was associated with a >10% increase in risk-adjusted standardized per capita costs. These findings demonstrate the potential contribution of "defensive medicine" to variation in health care utilization and spending in a population of interest to vascular surgeons.

Can We Use mTOR Inhibitors for COVID-19 Therapy?

Infection by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) provokes acute inflammation due to extensive replication of the virus in the epithelial cells of the upper and lower respiratory system. The mammalian target of rapamycin (mTOR) is a l signalling protein with critical functions in cell growth, metabolism, and proliferation. It is known for its regulatory functions in protein synthesis and angiogenesis cascades. The structure of mTOR consists of two distinct complexes (mTORC1 and mTORC2) with diverse functions at different levels of the signalling pathway. By activating mRNA translation, the mTORC1 plays a key role in regulating protein synthesis and cellular growth. On the other hand, the functions of mTORC2 are mainly associated with cell proliferation and survival. By using an appropriate inhibitor at the right time, mTOR modulation could provide immunosuppressive opportunities as antirejection regimens in organ transplantation as well as in the treatment of autoimmune diseases and solid tumours. The mTOR also has an important role in the inflammatory process. Inhibitors of mTOR might indeed be promising agents in the treatment of viral infections. They have further been successfully used in patients with severe influenza A/H1N1 pneumonia and acute respiratory failure. The officially accepted mTOR inhibitors that have undergone clinical testing are sirolimus, everolimus, temsirolimus, and tacrolimus. Thus, further studies on mTOR inhibitors for SARS-CoV-2 infection or COVID-19 therapy are well merited.

Surgical and reconstructive outcomes in primary venous leiomyosarcoma.

OBJECTIVE: Primary venous leiomyosarcomas (PVL) are rare and pose challenges in surgical management. This study evaluates the clinical outcomes and identifies predictors of survival in our surgical series of PVL. METHODS: A retrospective review was performed of patients who had resection of PVL at three centers between 1990 and 2018. Patient demographics, comorbidities, intraoperative data, survival, and graft-related outcomes were recorded. Survival analysis was performed using Kaplan-Meier curves and Cox proportional hazards regression. RESULTS: Seventy patients with a diagnosis of PVL were identified between 1990 and 2018. Fifty-four patients (77%) had PVL of the inferior vena cava (IVC) and 16 (23%) had peripheral PVL. The mean follow-up for the series was 55.0 months (range, 1-217 months). Fifty-one patients (96%) with IVC-PVL needed caval reconstruction and 3 (4%) had resection only. There were no deaths within 30 days of surgery. Five patients (9%) required early reintervention including one (2%) IVC stent. Sixteen peripheral PVL were identified. Eight patients (50%) had venous reconstructions performed and 8 (50%) had the vein resected without reconstruction. There were no deaths within 30 days. Five-year survival was 57.5% for IVC-PVL and 70.0% for peripheral PVL. Kaplan-Meier survival analysis for IVC and peripheral PVL revealed no difference in overall survival (P = .624) at 5 years. CONCLUSIONS: PVL is a rare and aggressive disease even with surgical resection. We found no difference in survival between IVC and peripheral lesions, suggesting that aggressive management is warranted for PVL of any origin. Management of PVL requires a multidisciplinary approach to provide patients with the best long-term outcomes.

Malpractice allegations against vascular surgeons: Prevalence, risk factors, and impact on surgeon wellness.

OBJECTIVE: The contemporary medicolegal environment has been linked to procedure overuse, health care variation, and higher costs. For physicians accused of malpractice, there is also a personal toll. The objective of this study was to evaluate the prevalence of and risk factors for involvement in medical malpractice lawsuits among United States vascular surgeons, and to examine the association between these allegations with surgeon wellness. METHODS: In 2018, the Society of Vascular Surgery (SVS) Wellness Task Force conducted a confidential survey of active members using a validated burnout assessment (Maslach Burnout Index) embedded into a questionnaire. This survey included questions related to medical errors and malpractice litigation. De-identified demographic, personal, and practice-related characteristics were assessed in respondents who reported malpractice allegations in the preceding 2 years, then compared with those without recent medicolegal litigation. Risk factors for malpractice allegations were identified (χ2, Kruskal-Wallis tests), and the association between malpractice allegations with wellness was examined. Multivariate logistic regression models were developed to identify independent risk factors for malpractice accusations. RESULTS: Of 2905 active SVS members, 871 responses from practicing vascular surgeons were analyzed. A total of 161 (18.5%) were named in a malpractice lawsuit within 2 years. Malpractice allegations were significantly associated with surgeon burnout (odds ratio, 1.47; 95% confidence interval, 1.01-2.15; P = .041), but not with self-reported depression or suicidal ideation. The nature of malpractice claims included procedural errors (23.1%), failure to treat (18.8%), and error/delay in diagnosis (16.9%). Twenty percent of claims were settled prior to trial, and 19% were dismissed. Defendant vascular surgeons reported a "fair" resolution in 26.4% of closed cases. By unadjusted analysis, factors significantly associated with recent malpractice claims included mean age (51.7 ± 10.0 vs 49.3 ± 11.2 years; P = .0044) and mean years in practice (18.0 ± 10.7 vs 15.2 ± 11.8; P = .0007). Multivariate analysis revealed independent variables associated with malpractice allegations, including on-call frequency (P = .0178), recent medical errors (P = .0189), and male surgeons (P = .045). CONCLUSIONS: Malpractice allegations are common for vascular surgeons and are significantly associated with surgeon burnout. Nearly 20% of survey respondents reported being named in a lawsuit within the preceding 2 years. Our findings underscore the need for SVS initiatives to provide counseling and peer support for vascular surgeons facing litigation.

Procedure Reimbursement, Inflation, and the Declining Buying Power of the Vascular Surgeon (2011-2021).

PURPOSE: The purpose of this study was to evaluate trends in Medicare reimbursement for common vascular procedures over the last decade. To enrich the context of this analysis, vascular procedure reimbursement is directly compared to inflation-adjusted changes in other surgical specialties. METHODS: The Centers for Medicare & Medicaid Services Physician/Supplier Procedure Summary file was utilized to identify the 20 procedures most commonly performed by vascular surgeons from 2011-2021. A similar analysis was performed for orthopedic, general, and neurological surgeons. The Centers for Medicare & Medicaid Services Physician-Fee Schedule Look-Up Tool was queried for each procedure, and reimbursement data was extracted. All monetary data was adjusted for inflation to 2021 dollars utilizing the consumer price index. Average year-over-year and total percentage change in reimbursement were calculated based on adjusted data for included procedures. Comparisons to other specialty data were made with ANOVA. RESULTS: From 2011-2021, the average, unadjusted change in reimbursement for vascular procedures was -7.2%. Accounting for inflation, the average procedural reimbursement declined by 20.1%. The greatest decline was observed in phlebectomy of varicose veins (-50.6%). Open arteriovenous fistula revision was the only vascular procedure with an increase in inflation-adjusted reimbursement (+7.5%). Year-over-year, inflation-adjusted reimbursement for common vascular procedures decreased by 2.0% per year. Venous procedures experienced the largest decrease in average adjusted reimbursement (-42.4%), followed by endovascular (-20.1%) and open procedures (-13.9%). These changes were significantly different across procedural subgroups (P < 0.001). During the same period, the average adjusted change in reimbursement for the 20 most common procedures in orthopedic surgery, general surgery, and neurosurgery was -11.6% vs. -20.1% for vascular surgery (P = 0.004). CONCLUSION: Medicare reimbursement for common surgical procedures has declined over the last decade. While absolute reimbursement has remained relatively stable for several procedures, accounting for a decade of inflation demonstrates the true diminution of buying power for equivalent work. The most alarming observation is that vascular surgeons have faced a disproportionate decrease in inflation-adjusted reimbursement in comparison to other surgical specialists. Awareness of these trends is a crucial first step towards improved advocacy and efforts to ensure the "value" of vascular surgery does not continue to erode.

Practice Patterns of Vascular Surgery's "1%".

BACKGROUND: Public focus on health care spending has increased attention on variation in practice patterns and overutilization of high-cost services. Mainstream news reports have revealed that a small number of providers account for a disproportionate amount of total Medicare payments. Here, we explore variation in Medicare payments among vascular surgeons and compare practice patterns of the most highly reimbursed surgeons to the rest of the workforce. METHODS: 2016 Medicare Provider Utilization Data were queried to identify procedure, charge, and payment data to vascular surgeons, identified by National Provider Identification taxonomy. Commonly performed services (>10/year) were stratified into categories (endovascular, open surgery, varicose vein, evaluation and management, etc.). Practice patterns of vascular surgeons comprising the top 1% Medicare payments (n = 31) were compared with the remainder of the workforce (n = 3,104). RESULTS: In 2016, Medicare payments to vascular surgeons totaled $589 M. 31 vascular surgeons-1% of the workforce-received $91 million (15% of total payments). Practice patterns of the 1% differed significantly from the remainder of vascular surgeons (P < 0.05), with endovascular procedures accounting for 85% of their reimbursement. Specifically, the 1% received 49% of total Medicare payments for atherectomy ($121 M), 98% of which were performed in the office setting. CONCLUSIONS: One percentage of vascular surgeons receive an inordinate amount of total Medicare payments to the specialty. This discrepancy is due to variations in volume, utilization, and site of service. Disproportionate use of outpatient atherectomy in a small number of providers, for example, raises concerns regarding appropriateness and overutilization. Given current scrutiny over health care spending, these findings should prompt serious discussion regarding the utility of personal and societal self-regulation.

Medicinal plants for diabetes associated neurodegenerative diseases: A systematic review of preclinical studies.

Diabetes mellitus is a metabolic defect with many complications for the patients. Deaths due to diabetes and its complications are increasing, and one of the most serious consequences are the neurological disorders. Chemical treatments have irreversible side effect and therefore the aim of this study is to evaluate the medicinal plants used for treatment of cognitive impairments and neurodegenerative diseases associated with diabetes in 2004-2020 period. Electronic databases used were PubMed, Scopus and Cochrane library. The keywords used were "diabetes," "plant," "herb," "neurodegenerative," "neurodegeneration," "cognitive," "cognition," "Alzheimer," "dementia." The non-English articles, repetitive articles and review studies were excluded. From total of 3,590 results, 58 articles are included in the study. The results show that many chemical treatments considered for this disease simply control hyperglycemia, but cannot improve the complications of diabetes. Herbal medicine could be more effective due to the high antioxidant activity of some medicinal plants. Biologically active substances of medicinal plants can improve the neurological disorders caused by diabetes via several pathways. The most important pathway is related to antioxidant properties. Other pathways include antiinflammatory, anti-apoptotic, neurotoxicity inhibition, neuronal death, increasing the uptake of glucose by cells and improve neurotransmitters levels involved in learning and memory.

Carotid endarterectomy surgeon volumes in contemporary practice: A comparison to randomized trial inclusion criteria.

BACKGROUND: Clinical decisions regarding the utility of carotid revascularization are informed by randomized controlled trial (RCT) results. However, RCTs generally require participating surgeons to meet strict inclusion criteria with respect to procedure volume. The purpose of this study was to compare annual surgeon volume for carotid endarterectomy (CEA) in contemporary practice to RCT inclusion thresholds. METHODS: Surgeon volume thresholds were identified in 17 RCTs evaluating the efficacy of CEA (1986-present, n = 17). Contemporary annual surgeon volumes (2012-2017) were identified by aggregating data from the Medicare Provider Utilization Database and Healthcare Cost and Utilization Project Network (HCUP), and compared to RCT inclusion thresholds. Further comparisons were performed over time, and across specialties (i.e., vascular surgeon vs. other, based on board certification associated with provider NPI). RESULTS: Minimal surgeon volume in 17 RCTs ranged from 10 to 25 CEA annually when specific case volumes were required. From 2012 to 2017, CEA incidence in Medicare beneficiaries declined from 68,608 to 56,004 and became increasingly consolidated in fewer providers (7,331 vs. 6,626). However, in 2016 only 26.2% of surgeons performing CEA in Medicare beneficiaries would have met the least stringent volume requirement (10 CEA/year). Only 6.5% of surgeons performing CEA met the most stringent RCT volume threshold (25 cases/year) during the same time period. In 2017, 819 vascular surgeons (25.5% of those certified in the specialty) performed >10 CEA in Medicare beneficiaries. CONCLUSIONS: The majority of surgeons performing CEA do not meet the annual volume thresholds required for participation in the RCTs that have evaluated the efficacy of carotid revascularization. Given the established volume-outcome relationship in CEA, the disparity between surgeon experience in the context of RCTs versus contemporary practice is concerning. These findings have potential implications for informed decision-making, hospital privileging, and regionalization of care.

Metabolite profiling by means of GC-MS combined with principal component analyses of natural populations of Nectaroscordum siculum ssp. bulgaricum (Janka) Stearn.

Nectaroscordum siculum ssp. bulgaricum (Janka) Stearn (Allium siculum subsp. dioscoridis (Sm.) K. Richt.) is a traditional culinary spice from South-East Europe. Studies of N. siculum have focused mainly on the botanical and taxonomic characteristics of this species and there is no data available in the scientific literature about its metabolite profile. Thus, the aim of the current study was metabolite profiling of four wild populations of N. siculum grown in Bulgaria by gas chromatography coupled to mass spectrometry (GC-MS) and subsequent principal component analysis (PCA) of the data obtained. The identified primary metabolites (carbohydrates, amino acids, organic acids and lipids) are initial compounds for the biosynthesis of different plant secondary metabolites, such as polyphenols and flavour compounds with valuable biological activities for humans. The health benefits of the phenolic acids identified in this study have been a prerequisite for the implementation of N. siculum in different food systems in order to increase their quality and biological value.

Authenticity and quality evaluation of different Rhodiola species and commercial products based on NMR-spectroscopy and HPLC.

INTRODUCTION: The main concern regarding the authenticity and quality of Rhodiola rosea L. (Sedum rosea (L.) Scop.) products is their adulteration with other Rhodiola species. OBJECTIVE: The aim of the study was the development of a reliable and practical analytical platform for quality and quantity assessment of the characteristic molecules in three Rhodiola species (R. rosea, R. kirilowii (Regel) Maxim and R. crenulata (Hook. f. & Thomson) H. Ohba), commercial products and their possible application as markers for the authentication of R. rosea based products. MATERIAL AND METHODS: The major molecules were identified by one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR)-based metabolomics and quantitatively determined by high-performance liquid chromatography ultraviolet (HPLC-UV) analysis. The orthogonal projections to latent structures discriminant analysis (OPLS-DA) revealed the specific patterns in the metabolite profiles of R. rosea and R. crenulata. RESULTS: The coumarin crenulatin was only identified in R. crenulata and can be used as a marker to detect potential adulteration of the commercial products. Crenulatin was identified in two of the four analysed products by NMR-spectroscopy. According to the HPLC data, in less than a quarter of all products, the labelled amounts of salidroside and total rosavins were confirmed. CONCLUSIONS: The developed analytical platform was found to be useful in the investigations of the phytochemical diversity of different Rhodiola species, the recognition of the unique metabolites between them and the identification of adulterated products. Therefore, this approach could be applied from the earliest to the latest stages of the value chain in the manufacturing of R. rosea based products.

Clinopodium vulgare L. (wild basil) extract and its active constituents modulate cyclooxygenase-2 expression in neutrophils.

Clinopodium vulgare L. (wild basil) has a wide range of ethnopharmacological applications and accumulates a broad spectrum of phenolic compounds, recognized for their anti-inflammatory and anticancer properties. The triggered cyclooxygenase-2 (COX-2) expression is creating an immunosuppressive microenvironment in the inflamed tissue and considered to be the main cause of failure of even new anticancer-/immune-therapies. Nowadays, selective and novel plant-derived COX-2 inhibitors with safe profile are subject of profound research interest. This study aimed to analyze the metabolic profile of C. vulgare and search for phenolic molecules with potential biological properties. By application of 1H and 2D-NMR (Nuclear Magnetic Resonance) profiling, caffeic, chlorogenic acids and catechin were identified along with a bunch of primary and secondary metabolites. Further, the biological effect of C. vulgare extract (CVE) and its constituents on zymosan-induced COX-2 expression and apoptosis of murine neutrophils have been studied. The CVE, caffeic and chlorogenic acids inhibited zymosan-induced COX-2 expression in bone marrow neutrophils, in vitro and in vivo activated. The obtained data indicate that CVE may have a good potential to manipulate neutrophil functions, however, its action may depend on the cellular state, the inflammatory milieu and the relative content of caffeic and chlorogenic acid in the extract.

Alkaloid profiles and acetylcholinesterase inhibitory activities of Fumaria species from Bulgaria.

GC-MS analysis of alkaloid profiles of five Fumaria species, naturally grown in Bulgaria (F. officinalis, F. thuretii, F. kralikii, F. rostellata and F. schrammii) and analysis of acetylcholinesterase inhibitory activity of alkaloid extracts were performed. Fourteen isoquinoline alkaloids were identified, with the principle ones being protopine, cryptopine, sinactine, parfumine, fumariline, fumarophycine, and fumaritine. Protopine contents, defined by HPLC analysis varied between 210.6 ± 8.8 µg/g DW (F. schrammii) and 334.5 ± 7.1 µg/g DW. (F. rostellata). While all of the investigated alkaloid extracts significantly inhibited acetylcholinesterase activity, the F. kralikii demonstrated the highest level of inhibition (IC(50) 0.13 ± 0.01 mg extract/mL).

Optimized flow cytometry isolation of murine spermatocytes.

Meiotic prophase I (MPI), is an initial stage of meiosis characterized by intricate homologous chromosome interactions, synapsis, and DNA recombination. These processes depend on the complex, but poorly understood early MPI events of homologous chromosome search, alignment, and pairing. Detailed molecular investigation of these early events requires isolation of individual MPI substages. Enrichment for Pachytene (P) and Diplotene (D) substages of late MPI was previously accomplished using flow cytometry. However, separation of early MPI spermatocytes, specifically, of Leptotene (L) and Zygotene (Z) substages, has been a challenge due to these cells' similar characteristics. In this report, we describe an optimized Hoechst-33342 (Hoechst)-based flow cytometry approach for isolating individual MPI populations from adult mouse testis. We get significant enrichment for individual L and Z spermatocytes, previously inseparable from each other, and optimize the isolation of other MPI substages. Our flow cytometry approach is a combination of three optimized strategies. The first is optimization of testis dissociation protocol that yields more consistent and reproducible testicular single cell suspension. The second involves optimization of flow cytometric gating protocol where a critical addition to the standard protocol for cell discrimination based on Hoechst fluorescence, involves a back-gating technique based on light scattering parameters. This step specifies selection of individual MPI substages. The third, is an addition of DNA content restriction to the gating protocol to minimize contamination from non-meiotic cells. Finally, we confirm significant enrichment of high-purity Preleptotene (PreL), L, Z, P, and D MPI spermatocytes using stage-specific marker distribution. The technique will facilitate understanding of the molecular events underlying MPI.

A thematic review of resident commentary on duty hours and supervision regulations.

BACKGROUND: The implementation on July 1, 2011, of new Accreditation Council for Graduate Medical Education (ACGME) standards for resident supervision and duty hours has prompted considerable debate about the potential positive and negative effects of these changes on patient care and resident education. A recent large-sample study analyzed resident responses to these changes, using a Likert scale response. In this same study, 874 residents also provided free-text comments, which provide added insight into resident perspectives on duty hours and supervision. METHODS: A mixed-methods quantitative and qualitative survey of residents was conducted in August 2010 to assess resident perceptions of the proposed ACGME regulations. Common concerns in the residents' free responses were synthesized and quantified using content analysis, a common method for qualitative research. RESULTS: A total of 11 617 residents received the survey. Completed surveys were received from 2561 residents (22.0%), with 874 residents (34.1%) providing free-text responses. Most residents (83.0%) expressed unfavorable opinions about the new standards. The most frequently cited concerns included coverage issues, and a negative impact on patient care and education, as well as lack of preparation for senior roles. A smaller portion of residents commented they thought the standards would contribute to improvements in quality of life (36.1%) and patient care (4.9%). CONCLUSIONS: ACGME standards are important for graduate medical education, and their aim is to promote high-quality education and better care to patients in teaching institutions. Yet, many residents are concerned about the day-to-day impact of the 2011 regulations, in particular the 16-hour duty period for interns. Most residents who provided free-text responses had a negative impression of the new ACGME regulations. Residents' resistance to duty hour changes may represent a realization that residents are losing a central role in patient care. The concerns identified in this study demonstrate important issues for administrators and policymakers. Resident ideas and opinions should be considered in future revisions of ACGME requirements.

Root and periodontal tissue development after allogenic tooth transplantation between rat littermates.

OBJECTIVE: The study was designed to investigate the development of roots and periodontal tissues after allogenic tooth transplantation between rat littermates by micro-computed tomography (micro-CT) and histology. MATERIALS AND METHODS: The upper right second molars in 2-week-old rats were extracted and immediately transplanted into the upper right first molar socket of rat littermates under anesthesia. The upper left second molars in 2-week-old recipient rats were used as a control. The rats were fixed and tissues analyzed at 0, 4, 8, or 12 weeks after transplantation. Root development of seven rats in each group was analyzed quantitatively using micro-CT. Periodontal tissue formation was examined qualitatively by histologic methods. RESULTS: Roots developed after allogenic transplantation, but they were significantly shorter than control roots. The number of roots varied from one to four in transplanted teeth, while it was consistently four in control teeth. Periodontal tissue formation in transplanted teeth was equivalent to that of the control teeth. CONCLUSION: Allogenic transplantation between rat littermates permits root development and periodontal tissue formation.

Root development of rat tooth germs implanted in the tooth socket and in the subcutaneous tissue.

OBJECTIVE: This study was designed to investigate root development of a rat tooth germ implanted in a tooth socket or in a subcutaneous region. MATERIALS AND METHODS: Tooth germs of the upper left first molars in 2-week-old rats were extracted and implanted in the original tooth socket or in the subcutaneous region of the back. The upper right first molar was used as a control. The rats were fixed in weeks 1, 2, 4, 8 and 12. The root development was examined quantitatively with X-ray radiographic morphometry. The cellular activity of producing matrix proteins was assessed using in situ hybridization for type I collagen. RESULTS: Root development was observed in the implanted teeth in the tooth socket as also in the control teeth. In contrast, roots hardly developed in subcutaneously implanted teeth. Histology showed that periodontal ligaments were arranged around roots of implanted teeth in the tooth socket as around control teeth, but few periodontal ligaments were identified in the subcutaneous implantation. Dentin and cementum formed in both the implanted teeth as also in the control teeth and odontoblasts, cementoblasts and cementocytes expressed type I collagen. CONCLUSION: Tooth sockets may possess specific environments that allow root development of a tooth germ.

New approach for measurement of sympathetic nervous abnormality in conscious, spontaneously hypertensive rats.

We previously reported a highly sensitive chemiluminescence high-performance liquid chromatographic method to determine catecholamines in plasma. In this study, we employed this method to measure the cardiac function and plasma norepinephrine (NE) concentration in conscious rats. Benidipine, 1,4-dihydropyridine calcium antagonist (4 mg/kg), and beta-blocker (propranolol, 30 mg/kg) were administered orally to conscious spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) rats, and blood pressure, heart rate and plasma NE levels were measured. Plasma NE concentration was used as an index of sympathetic nervous system activity in conscious rats. The basal plasma NE levels were significantly higher in SHRs than in WKY rats (P<0.05), indicating the activity of the basal sympathetic nervous system in SHRs was elevated. The sensitivity of the baroreflex-mediated sympathetic nervous response was reduced in SHRs as compared to that in WKY rats. The concomitant administration of benidipine and a beta-blocker decreased heart rate without affecting the baroreflex-mediated sympathetic nervous response, indicating that propranolol might suppress mainly the cardiac beta-adrenoceptor. The present study suggested the high activity of the basal sympathetic nervous system and the reduced response of the baroreflex-mediated sympathetic nervous system in SHRs compared to WKY rats in the conscious condition.

Antioxidant effects of calcium antagonists in rat brain homogenates.

We studied the antioxidant activities of calcium antagonists against autoxidation in rat brain homogenates. The homogenates were incubated for 30 min at 37 degrees C with or without a calcium antagonist and subsequently assayed for lipid peroxide content. Percent inhibition of the lipid peroxidation was used as an index of the antioxidant effect. Dihydropyridine calcium antagonists exhibited concentration-dependent (3-300 micromol/l) inhibitory effects against lipid peroxidation. The relative order of antioxidant potency and associated IC50 values (micromol/l) of the calcium antagonists for inhibition of the lipid peroxidation were as follows: nifedipine (51.5)>barnidipine (58.6)>benidipine (71.2)>nicardipine (129.3)>amlodipine (135.5)>nilvadipine (167.3)>nitrendipine (252.1)>> diltiazem (>300)=verapamil (>300). These results suggest that some dihydropyridine calcium antagonists show antioxidant properties. The antioxidant effects of the calcium antagonists may contribute to their pharmacological actions.