Surgical Specialist
22 years of experience
Video profile
Accepting new patients
609 W Germantown Pike
Suite 270
Norristown, PA 19403
484-622-7100
Locations and availability (4)

Education ?

Medical School Score
New York Medical College (1988)
Surgery
  • Currently 1 of 4 apples

Awards & Distinctions ?

Awards  
Castle Connolly's Top Doctors™ (2012 - 2013)
Patients' Choice Award (2008 - 2009, 2011)
Compassionate Doctor Recognition (2011)
Appointments
University Of Miami School Of Medicine
ASSISTANT PROFESSOR OF SURGERY
Umdnj Robert Wood Johnson Medical School
Associate Professor of Surgery
Associations
American Board of Surgery
American Board of Thoracic Surgery
American College of Surgeons

Affiliations ?

Dr. Anderson is affiliated with 13 hospitals.

Hospital Affilations

Score

Rankings

  • Somerset Medical Center
    Thoracic Surgery (Cardiothoracic Vascular Surgery)
    110 Rehill Ave, Somerville, NJ 08876
    • Currently 4 of 4 crosses
    Top 25%
  • Montgomery Hospital XXXXX
    Thoracic Surgery (Cardiothoracic Vascular Surgery)
    900 E Fornance St, Norristown, PA 19401
    • Currently 3 of 4 crosses
    Top 50%
  • Albert Einstein Medical Center
    Thoracic Surgery (Cardiothoracic Vascular Surgery)
    5501 Old York Rd, Philadelphia, PA 19141
    • Currently 3 of 4 crosses
    Top 50%
  • Robert Wood Johnson Univ Hosp *
    Thoracic Surgery (Cardiothoracic Vascular Surgery)
    1 Robert Wood Johnson Pl, New Brunswick, NJ 08901
    • Currently 2 of 4 crosses
  • St. Peter's University Hospital
    Thoracic Surgery (Cardiothoracic Vascular Surgery)
    254 Easton Ave, New Brunswick, NJ 08901
    • Currently 1 of 4 crosses
  • University Community Hospital
  • Rwj University Hospital
  • Robert Wood Johnsonuniversityhospital
  • Jackson Memorial Hospital
  • Mossrehab & Albert Einstein Med Ctr
    60 Township Line Rd, Elkins Park, PA 19027
  • Elkins Park Hospital
    60 Township Line Rd, Elkins Park, PA 19027
  • Germantown Hospital & Community Health Services
    1 Penn Blvd, Philadelphia, PA 19144
  • Miami Va Medical Center
  • * This information was reported to Vitals by the doctor or doctor's office.

    Publications & Research

    Dr. Anderson has contributed to 90 publications.
    Title Potential Mechanisms for Hypoalgesia Induced by Anti-nerve Growth Factor Immunoglobulin Are Identified Using Autoimmune Nerve Growth Factor Deprivation.
    Date January 2012
    Journal Neuroscience
    Excerpt

    Nerve growth factor (NGF) antagonism has long been proposed as a chronic pain treatment. In 2010, the FDA suspended clinical trials using tanezumab, a humanized monoclonal anti-NGF antibody, to treat osteoarthritis due to worsening joint damage in 16 patients. Increased physical activity in the absence of acute pain which normally prevents self-harm was purported as a potential cause. Such an adverse effect is consistent with an extension of tanezumab's primary mechanism of action by decreasing pain sensitivity below baseline levels. In animal inflammatory pain models, NGF antagonism decreases intraepidermal nerve fiber (IENF) density and attenuates increases in expression of nociception-related proteins, such as calcitonin gene-related peptide (CGRP) and substance P (SP). Little is known of the effects of NGF antagonism in noninflamed animals and the hypoalgesia that ensues. In the current study, we immunized rats with NGF or cytochrome C (cytC) and examined (1) nocifensive behaviors with thermal latencies, mechanical thresholds, the hot plate test, and the tail flick test, (2) IENF density, and (3) expression of CGRP, SP, voltage-gated sodium channel 1.8 (Nav1.8), and glutaminase in subpopulations of dorsal root ganglion (DRG) neurons separated by size and isolectin B4 (IB4) labeling. Rats with high anti-NGF titers had delayed responses on the hot plate test but no other behavioral abnormalities. Delayed hot plate responses correlated with lower IENF density. CGRP and SP expression was decreased principally in medium (400-800 μm(2)) and small neurons (<400 μm(2)), respectively, regardless of IB4 labeling. Expression of Nav1.8 was only decreased in small and medium IB4 negative neurons. NGF immunization appears to result in a more profound antagonism of NGF than tanezumab therapy, but we hypothesize that decreases in IENF density and nociception-related protein expression are potential mechanisms for tanezumab-induced hypoalgesia.

    Title Medical Education in the United States and Canada, 2010.
    Date September 2010
    Journal Academic Medicine : Journal of the Association of American Medical Colleges
    Excerpt

    The authors present an overview of the educational programs, infrastructure to support them, and the assessment strategies of 128 medical schools in the United States and Canada, based on reports submitted by those schools and published in this supplement to Academic Medicine. The authors explore many important changes that have occurred since the publication of the Flexner Report in 1910 as well as the progress that is evident since a similar collection of medical school reports was published in September 2000, also as a supplement to Academic Medicine. Drawing on the reports, the authors summarize, among other topics, the advances that have taken place in the support for faculty, the funding of medical student education, changes in pedagogy and assessment, and the expansion of medical education to distributed models and regional campuses.The authors observe that the reports from the 128 schools illustrate that medical student education has undergone and continues to undergo substantive change, has advanced markedly since the reforms stimulated by the Flexner Report, and has continued to evolve during the past decade. The reports illustrate the strength of support for the educational programs, even in a time of financial constraints, and the increasing recognition of the scholarly contributions of faculty through teaching. The authors provide examples of the changes in pedagogy and new topics in the required curriculum in the past decade and describe selected highlights of the 128 educational programs.

    Title Postoperative Recovery Advantages in Patients Undergoing Thyroid and Parathyroid Surgery Under Regional Anesthesia.
    Date August 2010
    Journal Seminars in Cardiothoracic and Vascular Anesthesia
    Excerpt

    Thyroid or parathyroid surgery may be performed using general anesthesia or regional anesthesia. Ninety-five (95) patients underwent thyroid or parathyroid surgery using general anesthesia (n=64) or bilateral superficial cervical plexus block with sedation (n=31) and completed a postoperative questionnaire regarding the perioperative experience. Patients undergoing parathyroid surgery under regional anesthesia (n=24) were more likely to experience better energy levels (p=0.012) and earlier return to work (p=0.045) postoperatively. Overall, 96% of patients undergoing either type of surgery with either type of anesthetic reported satisfaction with the anesthetic.

    Title Leland Stanford Junior University.
    Date July 2010
    Journal Science (new York, N.y.)
    Title Triterpene Based Compounds with Potent Anti-maturation Activity Against Hiv-1.
    Date April 2009
    Journal Bioorganic & Medicinal Chemistry Letters
    Excerpt

    Efforts towards developing orally bioavailable HIV-1 maturation inhibitors starting from betulinic acid 1 are described. SAR resulted in improved potency, physicochemical properties, and enhanced oral absorption in rats.

    Title The National Evaluation of Senior Mentor Programs: Older Adults in Medical Education.
    Date March 2009
    Journal Journal of the American Geriatrics Society
    Excerpt

    To identify models for senior mentor programs (SMPs), critical factors in program development, achievement of goals and objectives, effect on medical school environment, and future of programs.

    Title International Exchange Programs and U.s. Medical Schools.
    Date November 2008
    Journal Academic Medicine : Journal of the Association of American Medical Colleges
    Excerpt

    International health experiences have been shown to increase students' and residents' interest in public health, their likelihood of choosing a career in primary care, and their commitment to serving the underserved. The purpose of the current study is to describe the international experiences available to students and residents at U.S. allopathic medical schools.

    Title Discovery of 2-chloro-n-(4-methoxyphenyl)-n-methylquinazolin-4-amine (ep128265, Mpi-0441138) As a Potent Inducer of Apoptosis with High in Vivo Activity.
    Date September 2008
    Journal Journal of Medicinal Chemistry
    Excerpt

    Using a live cell, high-throughput caspase-3 activator assay, we have identified a novel series of 4-anilinoquinazolines as inducers of apoptosis. In this report, we discuss the discovery of 2-chloro-N-(4-methoxyphenyl)-N-methylquinazolin-4-amine, compound 2b (EP128265, MPI-0441138) as a highly active inducer of apoptosis (EC50 for caspase activation of 2 nM) and as a potent inhibitor of cell proliferation (GI50 of 2 nM) in T47D cells. Compound 2b inhibited tubulin polymerization, was effective in cells overexpressing ABC transporter Pgp-1, and was efficacious in the MX-1 human breast and PC-3 prostate cancer mouse models. In contrast to the SAR of 4-anilinoquinazolines as EGFR kinase inhibitors, the methyl group on the nitrogen linker was essential for the apoptosis-inducing activity of 4-anilinoquinazolines and substitution in the 6- and 7-positions of the quinazoline core structure decreased potency.

    Title But What Do the Numbers Really Tell Us? Arbitrary Metrics and Effect Size Reporting in Sport Psychology Research.
    Date January 2008
    Journal Journal of Sport & Exercise Psychology
    Excerpt

    Many of the measurements used in sport psychology research are arbitrary metrics, and researchers often cannot make the jump from scores on paper-and-pencil tests to what those scores actually mean in terms of real-world behaviors. Effect sizes for behavioral data are often interpretable, but the meaning of a small, medium, or large effect for an arbitrary metric is elusive. We reviewed all the issues in the 2005 volumes of the Journal of Sport & Exercise Psychology, The Sport Psychologist, and the Journal of Applied Sport Psychology to determine whether the arbitrary metrics used in sport psychology research were interpreted, or calibrated, against real-world variables. Of the 54 studies that used quantitative methods, 25 reported only paper-and-pencil arbitrary metrics with no connections to behavior or other real-world variables. Also, 44 of the 54 studies reported effect sizes, but only 7 studies, using both arbitrary and behavioral metrics, had calculated effect indicators and interpreted them in terms of real-world meaning.

    Title Caring Attitudes in Medical Education: Perceptions of Deans and Curriculum Leaders.
    Date November 2007
    Journal Journal of General Internal Medicine
    Excerpt

    BACKGROUND: Systems of undergraduate medical education and patient care can create barriers to fostering caring attitudes. OBJECTIVE: The aim of this study is to survey associate deans and curriculum leaders about teaching and assessment of caring attitudes in their medical schools. PARTICIPANTS: The participants of this study include 134 leaders of medical education in the USA and Canada. METHODS: We developed a survey with 26 quantitative questions and 1 open-ended question. In September to October 2005, the Association of American Medical Colleges distributed it electronically to curricular leaders. We used descriptive statistics to analyze quantitative data, and the constant comparison technique for qualitative analysis. RESULTS: We received 73 responses from 134 medical schools. Most respondents believed that their schools strongly emphasized caring attitudes. At the same time, 35% thought caring attitudes were emphasized less than scientific knowledge. Frequently used methods to teach caring attitudes included small-group discussion and didactics in the preclinical years, role modeling and mentoring in the clinical years, and skills training with feedback throughout all years. Barriers to fostering caring attitudes included time and productivity pressures and lack of faculty development. Respondents with supportive learning environments were more likely to screen applicants' caring attitudes, encourage collaborative learning, give humanism awards to faculty, and provide faculty development that emphasized teaching of caring attitudes. CONCLUSIONS: The majority of educational leaders value caring attitudes, but overall, educational systems inconsistently foster them. Schools may facilitate caring learning environments by providing faculty development and support, by assessing students and applicants for caring attitudes, and by encouraging collaboration.

    Title The Gcr1, Gpa1, Prn1, Nf-y Signal Chain Mediates Both Blue Light and Abscisic Acid Responses in Arabidopsis.
    Date June 2007
    Journal Plant Physiology
    Excerpt

    Different classes of biotic (e.g. plant hormones) and abiotic (e.g. different wavelengths of light) signals act through specific signal transduction mechanisms to coordinate higher plant development. While a great deal of progress has been made, full signal transduction chains have not yet been described for most blue light- or abscisic acid-mediated events. Based on data derived from T-DNA insertion mutants and yeast (Saccharomyces cerevisiae) two-hybrid and coprecipitation assays, we report a signal transduction chain shared by blue light and abscisic acid leading to light-harvesting chlorophyll a/b-binding protein expression in etiolated Arabidopsis (Arabidopsis thaliana) seedlings. The chain consists of GCR1 (the sole Arabidopsis protein coding for a potential G-protein-coupled receptor), GPA1 (the sole Arabidopsis Galpha-subunit), Pirin1 (PRN1; one of four members of an iron-containing subgroup of the cupin superfamily), and a nuclear factor Y heterotrimer comprised of A5, B9, and possibly C9. We also demonstrate that this mechanism is present in imbibed seeds wherein it affects germination rate.

    Title Improving Outcomes in Patients with Ventricular Assist Devices Transferred from Outlying to Tertiary Care Hospitals.
    Date June 2007
    Journal The Journal of Extra-corporeal Technology
    Excerpt

    In this retrospective study, the implant course and outcome of patients with ventricular assist devices (VADs) transferred from outlying "spoke" hospitals and converted nonsurgically to a device designed for ambulation at tertiary care "hub" hospitals are evaluated. Factors affecting the crucial decision to transfer and to convert devices have not previously been characterized. Data from 50 patients at 26 US hub institutions were voluntarily submitted to a VAD data registry at ABIOMED, between December 2003 and December 2005. The patients were transferred from 40 spokes on the BVS 5000 Blood Pump and converted to the AB5000 Ventricle (both ABIOMED) at hubs. Comparisons were made on implant indications, time-course, and end-organ function at the time of conversion between surviving patients and patients that had died. Patients who were transferred and converted had a survival to recovery or to next therapy rate of 42%. Eighteen of the surviving patients were still alive 30 days after the explant: 61% were weaned, 33% were transplanted, and 5.6% received a destination device. Average implant-to-transfer time was 1.5 vs. 2.0 days for 30-day survivors and expired patients, respectively, whereas support time from transfer to conversion was 4.8 vs. 4 days, respectively. At the time of device conversion, a total bilirubin below a threshold level of 3.5 mg/dL was predictive of 30-day survival (n = 26, p = .03, odds ratio = 2.73, 95% confidence interval: 1.22-6.16). Patients who survived 30 days were supported longer than those who died (35 vs. 21.1 days, p = .026). At least 18 patients recovered sufficiently on the AB5000 Ventricle to tolerate extubation and 11 patients were able to ambulate. Liver function after implant both at the spoke and before conversion at the hub may be a good indicator of patient survivability. Patients transferred from the BVS 5000 Blood Pump benefited from easy, safe conversion to the AB5000 Ventricle, which provided them with additional support time and afforded the opportunity to recover native heart function.

    Title Educational Commission for Foreign Medical Graduates Certification and Specialty Board Certification Among Graduates of the Caribbean Medical Schools.
    Date February 2007
    Journal Academic Medicine : Journal of the Association of American Medical Colleges
    Excerpt

    BACKGROUND: To determine the variability among Caribbean medical schools in the performance of their students against markers of quality. METHOD: The Educational Commission for Foreign Medical Graduates (ECFMG) database and the American Medical Association (AMA) Masterfile were linked. Analyses were restricted to ECFMG applicants, from 1980 to 2000, who attended the 12 Caribbean medical schools that produced 200 or more U.S. International Medical School Graduates (USIMGs). RESULTS: The schools produced 17,049 USIMG (48% of all USIMGs) and 5,840 non-USIMG (5% of all non-USIMGs) applicants for ECFMG certification. By school, the ECFMG certification rate ranged from 28% to 86% for USIMGs and from 27% to 82% for non-USIMGs. Specialty Board certification for graduates of these schools also varied widely. CONCLUSIONS: Medical schools in the Caribbean play an increasingly important role in supplying the U.S. workforce. There is considerable variability among them, both in the numbers of physicians they produce and the performance of their students against indicators of quality such as ECFMG and specialty Board certification.

    Title The Arabian Gulf University College of Medicine and Medical Sciences: a Successful Model of a Multinational Medical School.
    Date January 2007
    Journal Academic Medicine : Journal of the Association of American Medical Colleges
    Excerpt

    In the late 1970s, leaders of the Arabian [corrected] Gulf countries proposed a novel idea of a joint educational and cultural venture: establishing a new regional university based in the Kingdom of Bahrain that would be managed as a multinational consortium of Gulf countries including Saudi Arabia, United Arab Emirates, Kuwait, Oman, Qatar, and Bahrain. It was intended to promote higher education and research in the Gulf region; to serve the development needs of the region; to reflect the unique economic, social, and cultural attributes of the Gulf communities and their environments; and to respond to the health care needs of the member countries.Since its inception in 1982, the College of Medicine and Medical Sciences (CMMS) at Arabian Gulf University (AGU) has adopted the educational philosophy of problem-based learning (PBL) and self-directed, student-centered education. The curriculum is integrated, with early introduction of education to foster clinical skills and professional competencies. The strategic alliance with the health care systems in Bahrain and other Gulf regions has created a successful model of efficient and effective initialization of health care resources in the community. The experience that has accumulated at the AGU-CMMS from introducing innovative medical education has allowed it to take a leadership position in medical education in the Gulf region.The original goals of this unique experiment have been realized along with unanticipated outcomes of spearheading changes in medical education in the Gulf region. Old and new medical schools have adopted several characteristics of the AGU educational program. Several elements contributed to its success: a clear vision of providing quality medical education and realizing and sustaining this vision by a supportive leadership at the university and college levels; an alliance with the regional health care systems; a dedicated faculty who have been able to work as a team while continually developing themselves; proper student selection and the creation of a culture of student/faculty partnerships in education and in building an international reputation and credibility by cooperating with reputable international universities and organizations.

    Title The Medical Education of United States Citizens Who Train Abroad.
    Date October 2006
    Journal Surgery
    Excerpt

    BACKGROUND: Graduates of international medical schools (IMGs) make up approximately one quarter of the physician workforce in the United States. Among IMGs are a number of US citizens (USIMGs) who take graduate training positions and ultimately practice in the United States. Compared with graduates of US medical schools (USMGs), relatively little is known about the undergraduate educational experiences of these US citizens. The objective of this study was to identify the schools that produce the most USIMGs and to describe the educational experiences and examination performance of graduates of these schools. METHODS: The 10 largest schools were identified based on the number of USIMGs who were certified by the Educational Commission for Foreign Medical Graduates between 2001 and 2004. Information about the institutions was collected from the International Medical Education Directory; educational experience information was gathered from 100 randomly selected transcripts and from a survey that was completed by 418 graduates of the schools. These data were compared with information about USMGs from the curriculum management and information tool and the graduation questionnaire of the Association of American Medical Colleges. Performance on steps 1 and 2CK of the United States Medical Licensing Examination were also analyzed. RESULTS: Some differences existed between USIMGs and USMGs in the required clinical clerkships, the sites where educational experiences occurred, and the special topics that were covered. USMGs and non-US citizen IMGs had better examination scores than USIMGs. CONCLUSION: There are many similarities; however, there are some noteworthy differences between the educational experiences of USIMGs and USMGs. Further work is needed to better understand the educational experiences of USIMGs, particularly in the clinical clerkships.

    Title Imaging of Anterior Knee Pain.
    Date September 2006
    Journal Clinics in Sports Medicine
    Title Beme Systematic Review: Predictive Values of Measurements Obtained in Medical Schools and Future Performance in Medical Practice.
    Date July 2006
    Journal Medical Teacher
    Excerpt

    BACKGROUND: Effectiveness of medical education programs is most meaningfully measured as performance of its graduates. OBJECTIVES: To assess the value of measurements obtained in medical schools in predicting future performance in medical practice. METHODS: SEARCH STRATEGY: The English literature from 1955 to 2004 was searched using MEDLINE, Embase, Cochrane's EPOC (Effective Practice and Organization of Care Group), Controlled Trial databases, ERIC, British Education Index, Psych Info, Timelit, Web of Science and hand searching of medical education journals. INCLUSION & EXCLUSIONS: Selected studies included students assessed or followed up to internship, residency and/or practice after postgraduate training. Assessment systems and instruments studied (Predictors) were the National Board Medical Examinations (NBME) I and II, preclinical and clerkship grade-point average, Observed Standardized Clinical Examination scores and Undergraduate Dean's rankings and honors society. Outcome measures were residency supervisor ratings, NBME III, residency in-training examinations, American Specialty Board examination scores, and on-the-job practice performance. DATA EXTRACTION: Data were extracted by using a modification of the BEME data extraction form study objectives, design, sample variables, statistical analysis and results. All included studies are summarized in a tabular form. DATA ANALYSIS AND SYNTHESIS: Quantitative meta-analysis and qualitative approaches were used for data analysis and synthesis including the methodological quality of the studies included. RESULTS: Of 569 studies retrieved with our search strategy, 175 full text studies were reviewed. A total of 38 studies met our inclusion criteria and 19 had sufficient data to be included in a meta-analysis of correlation coefficients. The highest correlation between predictor and outcome was NBME Part II and NBME Part III, r = 0.72, 95% CI 0.30-0.49 and the lowest between NBME I and supervisor rating during residency, r = 0.22, 95% CI 0.13-0.30. The approach to studying the predictive value of assessment tools varied widely between studies and no consistent approach could be identified. Overall, undergraduate grades and rankings were moderately correlated with internship and residency performance. Performance on similar instruments was more closely correlated. Studies assessing practice performance beyond postgraduate training programs were few. CONCLUSIONS: There is a need for a more consistent and systematic approach to studies of the effectiveness of undergraduate assessment systems and tools and their predictive value. Although existing tools do appear to have low to moderate correlation with postgraduate training performance, little is known about their relationship to longer-term practice patterns and outcomes.

    Title Discovery of a Novel, Orally Active, Small Molecule Gonadotropin-releasing Hormone (gnrh) Receptor Antagonist.
    Date July 2006
    Journal Journal of Medicinal Chemistry
    Excerpt

    Gonadotropin releasing hormone (GnRH) plays an important role in the biology of reproduction. The use of GnRH receptor antagonists has been reported in the literature for the treatment of breast, ovarian, and prostate cancers. In this article, we report the synthesis, in vitro characterization, pharmacokinetics, and pharmacodynamics of an orally bioavailable, potent, small molecule GnRH receptor antagonist N-{4,6-dimethoxy-2-[(3-morpholin-4-ylpropyl)amino]pyrimidin-5-yl}-5-[3,3,6-trimthyl-2,3-dihydro-1H-inden-5-yl)oxy]-2-furamide (compound 1).

    Title Peripheral Arterial Cannulation for Abiomed Bvs 5000 Left Ventricular Assist Device Support.
    Date May 2006
    Journal The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation
    Excerpt

    The Abiomed BVS 5000 is an external, pulsatile, ventricular assist device typically used for short-term mechanical support in post-cardiotomy patients experiencing cardiogenic shock when myocardial recovery is expected. We describe an as yet unreported approach where the left common femoral artery was utilized for Abiomed left ventricular assist device cannulation after reoperative mitral valve surgery.

    Title Policies of U.s. Heart Transplant Programs Regarding Transplantation of Human Immunodeficiency-positive Patients.
    Date March 2005
    Journal The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation
    Title Anomalous Coronary Artery in a Transplanted Heart: a Technical Modification.
    Date January 2005
    Journal The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation
    Excerpt

    We report the case of a 47-year-old man who underwent orthotopic heart transplantation for valvular cardiomyopathy. At the time of cardiac catheterization we identified an anomalous origin of the donor left main coronary artery from the right coronary sinus of Valsalva. To decrease the risk of left main coronary artery compression during re-implantation of the transplanted heart, we performed a careful geometric arrangement of the aortopulmonary artery angle. This simple technical modification suggests that a heart with an anomalous left coronary artery may be safely used for organ donation.

    Title A Thematic Summary of the Geriatrics Curricula at 40 U S Medical Schools.
    Date August 2004
    Journal Academic Medicine : Journal of the Association of American Medical Colleges
    Title Characterization of Mono- and Diaminopyrimidine Derivatives As Novel, Nonpeptide Gonadotropin Releasing Hormone (gnrh) Receptor Antagonists.
    Date July 2003
    Journal Bioorganic & Medicinal Chemistry Letters
    Excerpt

    A novel series of derivatives of mono- and diaminopyrimidines 1 potently displaced binding of a radiolabeled GnRH analogue to human and rat GnRH receptors. Analogues from these series competitively antagonized GnRH-stimulated increases in extracellular acidification in vitro and suppressed GnRH-mediated increases in circulating luteinizing hormone (LH) in castrated rats and testosterone in intact rats. These compounds or their analogues may be useful in treating sex hormone-dependent disease.

    Title Electrophilic Tetraalkylammonium Nitrate Nitration. Ii. Improved Anhydrous Aromatic and Heteroaromatic Mononitration with Tetramethylammonium Nitrate and Triflic Anhydride, Including Selected Microwave Examples.
    Date July 2003
    Journal The Journal of Organic Chemistry
    Excerpt

    A new one-pot nitration employing tetramethylammonium nitrate and trifluoromethanesulfonic anhydride in dichloromethane to provide a ready source of the nitronium triflate nitrating agent is presented. Rapid and selective nitration with a variety of aromatic and heteroaromatic substrates is achieved resulting in the synthesis of several novel organic compounds. A distinct advantage is the removal of undesired byproducts by aqueous workup. This very mild nitration permits large-scale syntheses and gives high isolated product yields that often require no further purification. This tetramethylammonium nitrate-based nitration also has been applied to microwave-assisted conditions, and the results with several compounds are outlined.

    Title Biological Characterization of a Novel, Orally Active Small Molecule Gonadotropin-releasing Hormone (gnrh) Antagonist Using Castrated and Intact Rats.
    Date May 2003
    Journal The Journal of Pharmacology and Experimental Therapeutics
    Excerpt

    Gonadotropin-releasing hormone (GnRH) receptor antagonists have potential in treating numerous hormone-dependent pathologies including cancers of the prostate, breast, and ovary, endometriosis, and fertility disorders. An unmet clinical need exists for an orally available GnRH receptor antagonist. Guided by structure-activity relationships, ligand-based targeted library designs, and biomarker measurements, our discovery efforts have yielded a novel, small molecule GnRH receptor antagonist, 5-[(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthalenyl)methyl]-N-(2,4,6-trimethoxyphenyl)-2-furamide (CMPD1). CMPD1 bound with low nanomolar affinities to human, rat, and mouse GnRH receptors (6.0, 3.8, and 2.2 nM, respectively). CMPD1 was more than 100-fold selective for GnRH receptors versus various G-protein-coupled receptors and other enzymes and ion channels. In cells expressing recombinant rat GnRH receptors, CMPD1 was a competitive antagonist of GnRH-stimulated increases in extracellular acidification rates in Cytosensor microphysiometer assays. In cells expressing recombinant human GnRH receptors, CMPD1 was a potent inhibitor of GnRH-stimulated total inositol phosphate accumulation. The effects of CMPD1 on circulating levels of luteinizing hormone (LH) and testosterone were studied in castrated and intact male rats, respectively. Intravenous and oral administration of CMPD1 dose dependently suppressed GnRH-mediated elevations of LH in castrated male rats and testosterone in gonad-intact male rats. Moreover, CMPD1, when given at 20 mg/kg i.v. to intact male rats, inhibited the elevations of LH and testosterone stimulated by the superagonist of GnRH, [d-Ala(6), des-Gly(10)]GnRH (GnRH-A). These data suggest that CMPD1 is a potent, selective, orally active GnRH receptor antagonist that may have potential application as a therapeutic agent for treating hormone-dependent cancers and diseases.

    Title The Discovery of Novel Small Molecule Non-peptide Gonadotropin Releasing Hormone (gnrh) Receptor Antagonists.
    Date May 2003
    Journal Bioorganic & Medicinal Chemistry Letters
    Excerpt

    A novel series of non-peptide derivatives 1, 14, and 15 that bind with high affinity to the human GnRH receptors is discussed. The discovery was made from screening our in-house libraries that contained the active structure 2 along with a trace amount of a second active structure 1 that was derived from an acid-induced rearrangement. From this structure type 1, a series of guanidine and non-guanidine containing analogues were prepared and tested as GnRH receptor antagonists. Compounds derived from this series bind to both human and rat GnRH receptors and antagonize GnRH-mediated increases in inositol phosphate production in cells containing recombinant human receptors. These compounds or their analogues may be useful as therapeutic agents for the treatment of hormone-dependent pathologies including prostate, breast and ovarian cancers.

    Title Currmit: a Tool for Managing Medical School Curricula.
    Date April 2003
    Journal Academic Medicine : Journal of the Association of American Medical Colleges
    Excerpt

    The AAMC Curriculum Management & Information Tool (CurrMIT) is a relational database containing curriculum information from medical schools throughout the United States and Canada. CurrMIT can be used to document details of instruction, such as outcome objectives, resources, content, educational methods, assessment methods, and educational sites, which are being employed in curricula. CurrMIT contains basic information about nearly all required courses and clerkships being offered in the United States and Canada. The database contains descriptions of more than 15,000 courses and clerkships; approximately 115,000 "sessions"--e.g., lectures, labs, small-group discussions--and more than 400,000 keywords and word strings documenting the specific details of instruction associated with the courses, clerkships, and sessions. Some specific uses that schools have made of CurrMIT include review of demographics among patient cases being used in a case-based curriculum; comparisons of educational experiences between two geographically separate clinical campuses; and identification of unplanned redundancies and gaps in curricular content. CurrMIT has been designed to accommodate data from virtually any medical school curriculum; "traditional 2+2" curricula, problem-based curricula, and systems-based curricula, and variations of each of these, have been entered in CurrMIT by medical schools. The authors give an overview of the technology upon which the system is built and the training materials and workshops that the AAMC provides to faculty to support CurrMIT's use, and end by describing enhancements being planned for the system.

    Title Faculty Views of Reimbursement Changes and Clinical Training: a Survey of Award-winning Clinical Teachers.
    Date February 2003
    Journal Teaching and Learning in Medicine
    Excerpt

    BACKGROUND: Prominent authorities believe that managed care and governmental policies are compromising the clinical education of future physicians. PURPOSE: This study sought the views of clinical teachers to quantify the extent to which managed care and governmental policies have changed clinical education. METHODS: Questionnaires were mailed to faculty that U.S. medical schools had recognized for clinical teaching excellence. Measures included reports of change in quality of clinical teaching due to payment regulations, Liaison Committee on Medical Education (LCME) and Residency Review Committee (RRC) requirements, and institutional support for teaching; change in numbers of students-trainees in clinics; need to generate more clinical revenue; and change in enjoyment of teaching. Other measures about clinical teaching included faculty attitudes, institutional rewards, and teaching different levels of students. Characteristics of the respondents also were measured. RESULTS: Faculty reported that payment regulations have affected clinical teaching negatively and that faculty need to generate more clinical revenue. Institutions tend to provide a supportive teaching environment but do not reward teaching financially. Intrinsic incentives for teaching increase as the level of student increases. Faculty reports did not differ by medical specialty or other faculty characteristics. Differences among medical schools occurred on all measures. CONCLUSIONS: Clinical education is being negatively affected, but not yet critically. Continued clinical financial pressures on faculty will affect all levels of clinical education, particularly for medical students. Differences among institutions indicate that individual schools can moderate or exacerbate the impact of external forces on the teaching faculty. Medical schools should monitor increasing pressures on faculty and ensure that goals, processes, support, and rewards for clinical teaching are proportionate to those for clinical care.

    Title Placental Endocrine Disruption Induced by Cadmium: Effects on P450 Cholesterol Side-chain Cleavage and 3beta-hydroxysteroid Dehydrogenase Enzymes in Cultured Human Trophoblasts.
    Date January 2003
    Journal Biology of Reproduction
    Excerpt

    We previously suggested that cadmium (Cd), an environmental toxicant and constituent of tobacco smoke, inhibits progesterone secretion in cultured human placental trophoblasts by inhibiting low-density lipoprotein receptor mRNA expression. In the current study, we investigated whether Cd also disrupts progesterone synthesis via P450 cholesterol side-chain cleavage (P450(scc)) and 3beta-hydroxysteroid dehydrogenase (3beta-HSD), enzymes that play important roles in placental steroidogenesis. Human cytotrophoblasts were purified by density gradient centrifugation and incubated in Dulbecco modified Eagle medium + 10% fetal bovine serum with 0, 5, 10, or 20 microM CdCl(2) for 96 h. Cells progressed to syncytiotrophoblastic maturity regardless of treatment. No differences (P > 0.05) in cell protein and lactate dehydrogenase activity were observed between untreated trophoblasts and those treated with CdCl(2). However, P450(scc) and 3beta-HSD mRNA transcript levels declined in a dose-dependent manner (P <0.05) in trophoblasts cocultured with 5, 10, or 20 microM CdCl(2). P450(scc) activity was similarly inhibited (P < 0.05) by CdCl(2) treatment, although 3beta-HSD activity was not significantly affected. Coculture with 8-bromo-cAMP enhanced progesterone secretion in untreated cultures but did not reverse the decline in progesterone secretion induced by CdCl(2) treatment. CdCl(2) failed to influence cAMP content in cultured cells. Collectively, results suggest that P450(scc) enzyme is another site at which Cd interferes with placental progesterone production. However, it is unlikely that an inhibition of cAMP is involved with the inhibition of progesterone biosynthesis by Cd in human trophoblasts.

    Title Tumor Prevention by 9-cis-retinoic Acid in the N-nitroso-n-methylurea Model of Mammary Carcinogenesis is Potentiated by the Pineal Hormone Melatonin.
    Date October 2002
    Journal Breast Cancer Research and Treatment
    Excerpt

    Our laboratory has demonstrated that treatment of MCF-7 breast cancer cells with melatonin (Mlt) followed 24h later with physiological concentrations of all-trans retinoic acid (atRA) results in apoptosis. These studies were extended into trials using the N-nitroso-N-methylurea (NMU)-induced rat mammary tumor model. Initial studies conducted by feeding the animals 9-cis-retinoic acid (9cRA in the chow) and administering melatonin by subcutaneous injection in the late afternoon demonstrated that the combination of Mlt and 9cRA was able to significantly prevent tumor development, and that the combination was more efficacious that either Mlt or 9cRA alone. In this report, we conducted studies to determine if lower doses of 9cRA could be used in combination with Mlt while still maintaining anti-tumor activity and if the route of administration of 9cRA (bolus (gavage) v.s. chronic (chow) routes) affected its interaction with Mlt. The studies presented here demonstrate that significantly reduced doses of 9cRA can be used in combination with Mlt while maintaining anti-tumor efficacy. Furthermore, our studies demonstrate that 9cRA is equally effective when it is administered chronically (chow) or as a bolus (gavage). These data demonstrate that the combined use of Mlt and 9cRA produces additive or synergistic effects, which are more efficacious than 9cRA alone. This combination of Mlt and 9cRA could be a potentially useful clinical treatment regimen for breast cancer since it allows the use of lower doses of retinoic acid, thus, avoiding the toxic side effects associated with the use of high dose retinoids.

    Title Thoracic Epidural Anesthesia for Cardiac Surgery Via Left Anterior Thoracotomy in the Conscious Patient.
    Date September 2002
    Journal The Heart Surgery Forum
    Excerpt

    BACKGROUND: Cardiac surgery is perceived to be maximally invasive and fraught with complications. In response to this perception, cardiothoracic surgeons have been refining traditional techniques to minimize their invasive nature. Epidural anesthesia has been used safely and effectively for numerous surgical procedures to reduce morbidity associated with general anesthesia. In hopes of achieving a similar result, we set out to determine the feasibility of using thoracic epidural anesthesia for limited cardiac surgery through a left anterior thoracotomy for patients who were awake and spontaneously breathing. METHODS: A high thoracic epidural technique was used in all cases. In each instance, the chest was entered through a small left anterior thoracotomy. The procedures included minimally invasive direct coronary artery bypass (MIDCAB) and transmyocardial revascularization (TMR). These procedures were performed in routine fashion using standard techniques. Pulmonary function tests were performed preoperatively, and the adequacy of respiratory function was serially monitored throughout each operation. The epidural catheters were left in place for 24 hours after operation for pain control. RESULTS: A total of 10 operations were performed. These included 7 MIDCAB, 2 TMR and 1 MIDCAB/TMR hybrid. The mean preoperative forced expiratory volume for one second (FEV1) was 1.9 liters. Significant intra-operative hypoxia or hypercarbia was not seen. One patient required intubation during the procedure for restlessness not associated with hypoxia. Two others required brief periods of assisted ventilation. All procedures were completed without incident. The mean operating time and length of stay were 70 minutes and 4.7 days. Postoperative pain control and patient satisfaction were excellent. CONCLUSIONS: Thoracic epidural anesthesia for limited cardiac surgical procedures by means of a left anterior thoracotomy is feasible, even in patients with diminished pulmonary function. Furthermore, this method offered no significant technical hurdles. Nevertheless, the applicability of this technique to other procedures remains unclear. We believe that these results warrant controlled comparison of regional versus general anesthesia for limited cardiac surgery.

    Title Effect of Testosterone Suppression on the Pharmacokinetics of a Potent Gnrh Receptor Antagonist.
    Date September 2002
    Journal Pharmaceutical Research
    Excerpt

    PURPOSE: The expression of cytochrome P450 enzymes (CYPs) in animals and humans is under complex hormonal regulation. Chronic treatment with drugs that alter sex hormone levels such as GnRH receptor agonists or antagonists may affect the expression of hormone-dependent CYPs, and as a result the pharmacokinetics of drugs metabolized by them. METHODS: Enzyme kinetic parameters were obtained by incubating AG-045572 (0.1-30 microM) with human or rat liver microsomes, or expressed CYP3A4 and CYP3A5. The pharmacokinetics of AG-045572 (10 mg/kg i.v. or 20 mg/kg p.o.) were studied in intact male, female, castrated male and male rats pretreated with AG-045572 for 4 days. RESULTS: AG-045572 is metabolized by CYP3A in both rats and humans. The Km values were similar in male and female human, female rat liver microsomes, and expressed CYP3A4 and CYP3A5 (0.39, 0.27, 0.28, 0.25, and 0.26 microM, respectively). The Km in male rat liver microsomes was 1.5 microM, suggesting that in male and female rats AG-045572 is metabolized by different CYP3A isozymes. The oral bioavailability of AG-045572 in intact male rats was 8%, while in female or castrated male rats it was 24%. Pretreatment of intact male rats with AG-045572 i.m. for 4 days resulted in suppression of testosterone to castrate levels, accompanied by an increase in oral bioavailability of AG-045572 to 27%. In the same experiment, the male-specific pulsatile pattern of growth hormone remained unchanged with slightly elevated baseline levels. CONCLUSIONS: The potent GnRH receptor antagonist AG-045572 is metabolized by hormone-dependent CYP3A. As a result, suppression of testosterone by pretreatment with AG-045572 "feminized" its own pharmacokinetics.

    Title Thoracic Epidural Anesthesia for Coronary Bypass Via Left Anterior Thoracotomy in the Conscious Patient.
    Date October 2001
    Journal European Journal of Cardio-thoracic Surgery : Official Journal of the European Association for Cardio-thoracic Surgery
    Excerpt

    Cardiac surgery is perceived to be maximally invasive and fraught with complications. Secondary to this, cardiothoracic surgeons have been refining traditional techniques to minimize their invasive nature. Epidural anesthesia has been utilized safely and effectively for numerous surgical procedures to reduce the associated morbidity. In hopes of achieving a similar result, we utilized thoracic epidural anesthesia for a coronary artery bypass via a left anterior thoracotomy, in an awake, spontaneously breathing patient. To the best of our knowledge, this is the first reported case utilizing this approach. Herein we report the results and technique utilized.

    Title Gonadal Cysts in Spotted Gar (lepisosteus Oculatus) from Bayou Trepagnier, Louisiana, Usa.
    Date August 2001
    Journal Marine Environmental Research
    Excerpt

    Gonadal cysts of spotted gar (Lepisosteus oculatus), an air-breathing teleost commonly found in Louisiana waters, are described. Fish were collected from two sites: Bayou Trepagnier, a petroleum-contaminated site (30 males and 42 females), and Bayou Traverse, a control site (17 males and 15 females). After fish were evaluated for gross abnormalities, they were necropsied and the gonads, gonadal ducts, and gonadal cysts were evaluated histologically. Multilocular fluid-filled cysts were noted in the testes, or spermatic ducts of four spotted gars from the Bayou Trepagnier. Unilateral ovarian cystadenomas were present in one female from Bayou Trepagnier. No cysts were observed in the gonads of spotted gar from the control site.

    Title Chemoprevention of Nmu-induced Rat Mammary Carcinoma with the Combination of Melatonin and 9-cis-retinoic Acid.
    Date July 2001
    Journal Cancer Letters
    Excerpt

    In experimental trials using the N-nitroso-N-methylurea (NMU)-induced rat mammary tumor model, a significant decrease in tumor incidence (to 5%) was observed in rats treated with melatonin and 9-cis-retinoic acid (9 cRA) compared to controls (55%). Although 9cRA alone decreased tumor incidence to 26%, this response did not reach statistical significance. Tumor incidence was significantly inhibited to 20% in the animals that received melatonin and 9cRA on alternating days. Latency to tumor onset was prolonged in animals receiving either of the combination treatments compared with controls, and tumor multiplicity was also significantly decreased.

    Title Tricuspid Valvectomy for Right Ventricular Outflow Cannula Occlusion with the Thoratec Ventricular Assist Device.
    Date May 2001
    Journal The Journal of Thoracic and Cardiovascular Surgery
    Title A Christmas Story.
    Date February 2001
    Journal Medical Education
    Title A Guide to the 130 Reports in This Snapshot Supplement to Academic Medicine.
    Date October 2000
    Journal Academic Medicine : Journal of the Association of American Medical Colleges
    Title Medical Teachers and Evidence.
    Date July 2000
    Journal Medical Education
    Title Effects of Cadmium Cell Viability, Trophoblastic Development, and Expression of Low Density Lipoprotein Receptor Transcripts in Cultured Human Placental Cells.
    Date January 2000
    Journal Reproductive Toxicology (elmsford, N.y.)
    Excerpt

    Previously, we have demonstrated that cadmium inhibits progesterone release in cultured human trophoblast cells. In the present study, we investigated potential mechanism(s) by which cadmium may elicit this effect. Cytotrophoblasts were obtained via enzymatic dispersion, purified by density gradient centrifugation, and cultured with increasing concentrations of cadmium. Cadmium-induced suppression of progesterone release seemed to be independent of cell death, as no significant decline in viability was observed with cadmium treatment. Further, immunocytochemical localization of cellular boundaries and nuclei indicated approximately 94% syncytial maturity was attained by both untreated and cadmium-treated cells, demonstrating that cadmium did not inhibit syncytial development. However, the abundance of LDL receptor (LDL-R) mRNA transcripts, as determined by competitive RT-PCR, was reduced (P < 0.05) by cadmium exposure in an apparent dose-dependent manner. Thus, the LDL-R, by which cholesterol substrate is supplied to the syncytiotrophoblast, is one site at which cadmium may interfere with placental progesterone production.

    Title Transformation of Medical Students' Education: Work in Progress and Continuing Challenges.
    Date November 1999
    Journal Academic Medicine : Journal of the Association of American Medical Colleges
    Excerpt

    In his book Time to Heal: American Medical Education from the Turn of the Century to the Era of Managed Care, Ludmerer expresses concern about the erosion of the environment in which medical students and residents learn the clinical skills, attitudes, and behaviors that they will need to practice high-quality medicine. Importantly, while he attributes the erosion of the clinical environment largely to the impact of managed care, he also places some responsibility within academic medicine itself, primarily the redirection of the clinical faculty's efforts away from traditional academic pursuits to the generation of clinical revenues. The Association of American Medical Colleges has information about the kinds of changes already occurring. In the preclinical curriculum, schools have introduced a wide range of new courses and topics, and there is more attention on professionalism and values. Schools are making fundamental changes in the design and conduct of the curriculum, primarily by adopting more integrated (non-departmental) approaches to course design and management. The clinical curriculum is changing primarily through the greatly expanded use of ambulatory care sites, and medical schools are developing new approaches to managing dispersed and varied instruction. Also, faculty are paying more attention to the role of residents as teachers and role models. These changes speak well for medical education. Nonetheless, substantial and sustained work remains to be done despite the present uncertainty about the future of academic medical centers. This work is essential--a challenge that the leaders of academic medicine must not fail.

    Title Blue Light-directed Destabilization of the Pea Lhcb1*4 Transcript Depends on Sequences Within the 5' Untranslated Region.
    Date November 1999
    Journal The Plant Cell
    Excerpt

    Pea seedlings grown in continuous red light accumulate significant levels of Lhcb1 RNA. When treated with a single pulse of blue light with a total fluence >10(4) micromol m(-2), the rate of Lhcb1 transcription is increased, whereas the level of Lhcb1 RNA is unchanged from that in control seedlings. This RNA destabilization response occurs in developing leaves but not in the apical bud. The data presented here indicate that the same response occurs in the cotyledons of etiolated Arabidopsis seedlings. The blue light-induced destabilization response persists in long hypocotyl hy4 and phytochrome phyA, phyB, and hy1 mutants as well as in far-red light-grown seedlings, indicating that neither CRY1 (encoded by the hy4 locus) nor phytochrome is the sole photoreceptor. Studies with transgenic plants indicate that the destabilization element in the pea Lhcb1*4 transcript resides completely in the 5' untranslated region.

    Title Cadmium Accumulation and Effects on Progesterone Release by Cultured Human Trophoblast Cells.
    Date September 1999
    Journal Reproductive Toxicology (elmsford, N.y.)
    Excerpt

    This study was designed to examine the characteristics of cadmium bioaccumulation by human trophoblast cells in culture and the subsequent effect of cadmium exposure on progesterone production and syncytial formation. The accumulation of cadmium suggested a time- and dose-dependent relationship, although it was not significant. The rate of metal accumulation was similar in all cadmium-treated groups. After 72 h of continuous exposure to cadmium concentrations of 5, 10, and 20 microM, progesterone release was diminished to 69, 51, and 38% of control values (P < 0.05), respectively. When cells were exposed to cadmium from 72 to 96 h (after syncytial development), progesterone release exhibited the same pattern of decline in response to increasing cadmium concentrations. Histologic evaluation of whole mounts of trophoblast cells exposed to 20 microM CdCl2 for 96 h revealed that syncytial formation seemed to be uninhibited. The pattern of cadmium-accumulation by normal cultured human trophoblast cells suggests a time- and dose-relationship with a concomitant decrease in progesterone release that occurs without apparent inhibition of syncytial development.

    Title Thoracic Complications in Solid Organ Transplantation.
    Date May 1999
    Journal Chest Surgery Clinics of North America
    Excerpt

    Thoracic complications of solid organ transplantation are common and can arise from the implantation surgical procedure or can be secondary to the need for lifelong immunosuppression. Problems that arise can be general to cardiothoracic surgery or unique to transplant patients. This article provides an overview of these complications and some approaches to their avoidance and management.

    Title Murine Strain Differences and the Effects of Zinc on Cadmium Concentrations in Tissues After Acute Cadmium Exposure.
    Date April 1999
    Journal Archives of Toxicology
    Excerpt

    The role of strain differences in cadmium tissue distribution was studied using sensitive (129/J) and resistant (A/J) mice. These murine strains have previously been shown to differ in their susceptibility to cadmium-induced testicular toxicity. Cadmium concentration was measured in testis, epididymis, seminal vesicle, liver, and kidney at 24 h after cadmium chloride exposure (4, 10, and 20 micromol/kg CdCl2). The 129/J mice exhibited a significant increase in cadmium concentration in testis, epididymis, and seminal vesicle at all cadmium doses used, compared to A/J mice. However, cadmium concentrations in liver and kidney were not different between the strains, at any dose, indicating that cadmium uptake is similar in these organs at 24 h. These murine strains demonstrate similar hepatic and renal cadmium uptake but significantly different cadmium accumulation in the reproductive organs at 24 h. The mechanism of the protective effect of zinc on cadmium toxicity was studied by assessing the impact of zinc acetate (ZnAc) treatment on cadmium concentrations in 129/J mice after 24 h. Zinc pretreatment (250 micromol/kg ZnAc), given 24 h prior to 20 micromol/kg CdCl2 administration, significantly decreased the amount of cadmium in the testis, epididymis, and seminal vesicle of 129/J mice, and significantly increased the cadmium content of the liver after 24 h. Cadmium levels in the kidney were unaffected at this time. Zinc pretreatment also prevented the cadmium-induced decrease in testicular sperm concentration and epididymal sperm motility seen in 129/J mice. These findings suggest that the differences in the two murine strains may be attributed partly to the differential accumulation of cadmium in murine gonads. This may be caused by strain differences in the specificity of cadmium transport mechanisms. The protective role of zinc in cadmium-induced testicular toxicity in the sensitive strain may be due to an interference in the cadmium uptake by susceptible reproductive organs.

    Title Antagonism of Selectin-dependent Adhesion of Human Eosinophils and Neutrophils by Glycomimetics and Oligosaccharide Compounds.
    Date December 1998
    Journal American Journal of Respiratory Cell and Molecular Biology
    Excerpt

    Early in inflammation, adhesion occurs between leukocytes and endothelium when selectins bind to sialyl Lewis X (sLex) and related oligosaccharides. We tested novel compounds that mimic sLex for their ability to inhibit selectin-mediated adhesion of human eosinophils and neutrophils in vitro. Neutrophils and eosinophils were isolated by density gradient centrifugation, and eosinophils were further purified by immunomagnetic negative selection. Adhesion to unstimulated or interleukin-1beta-stimulated (5 ng/ml, 4-6 h) umbilical vein endothelial monolayers was tested under static or rotating conditions, where adhesion is primarily E- or L-selectin dependent, respectively. P-selectin-dependent adhesion was tested on immobilized platelets treated with or without phorbol myristate acetate (10(-7) M, 10 min). Stimulus-induced adhesion was always at least 4-fold higher than without stimulus, and selectin dependence was confirmed with specific blocking monoclonal antibodies. E-selectin-dependent adhesion of eosinophils and neutrophils was inhibited by compound GM2296 (the concentration producing 50% inhibition of adhesion [IC50] approximately 0.5-1 mM). E-selectin-dependent adhesion of neutrophils, but not eosinophils, was also inhibited by another compound, sLex with a lipid tail (30 +/- 6% inhibition at 3 mM), whereas compound GM1292 slightly inhibited adhesion of both (23 +/- 5 and 20 +/- 6% inhibition, respectively, at 1 mM). L-selectin-dependent adhesion was more effectively inhibited by GM2296 (IC50 approximately 0.2-0.5 mM), although P-selectin-dependent adhesion was also inhibited (IC50 approximately 1 mM). Inhibition was reversible without affecting viability, and no effect was seen with these compounds in assays testing neutrophil adhesion to immobilized intercellular adhesion molecule-1. Thus, compound GM2296, a carbon-fucosylated derivative of glycyrrhetinic acid, inhibits E-, L-, and P-selectin-dependent eosinophil and neutrophil adhesion. The ability of these and perhaps other related glycomimetic compounds to interfere with the function of more than one type of selectin makes them desirable candidates as anti-inflammatory agents.

    Title The Carbohydrate Sialyl Lewis(x) (sle(x)) Sulfated Glycomimetic Gm2941 Attenuates Glucan-induced Pulmonary Granulomatous Vasculitis in the Rat.
    Date August 1998
    Journal The Journal of Pharmacology and Experimental Therapeutics
    Excerpt

    We examined the protective effects of GM2941, a sulfated glycomimetic of the complex carbohydrate sialyl Lewis(x), in a model of pulmonary granuloma development. This study was based on the rationale that formation of glucan-induced lung granulomas is dependent on neutrophils and that sialyl Lewis(x) glycomimetic (GM2941) interferes, in vitro, with P-selectin-dependent neutrophil-endothelial adhesive interactions. Infusion of particulate yeast cell wall glucan into rats results in the rapid (48 hr) formation of monocyte/macrophage-rich angiocentric pulmonary granulomas. Development of granulomas exhibits a temporal pattern characterized by the early, transient influx of neutrophils into blood vessel walls at sites of glucan embolization, followed by accumulation of monocytes and macrophages that constitute the definitive angiocentric lesions. Within 1 hr after the infusion of glucan, immunohistochemical analysis revealed up-regulation of blood vessel wall-associated P-selectin. Previous studies utilizing neutrophil-depleted animals have revealed that neutrophils, although not present in definitive lesions, are required for full granuloma development. The potential of GM2941 to inhibit neutrophil-endothelial cell adhesive interactions was demonstrated by the ability of the compound to inhibit P-selectin-mediated adhesion to histamine-stimulated HUVECs. Infusion of GM2941 retarded pulmonary granuloma development in a dose-dependent manner. Whole-lung myeloperoxidase activity, measured at the time of peak neutrophil accumulation, was significantly reduced in animals pretreated with GM2941 (30 mg/kg, 24 microM/kg), which suggests that this compound affords protection, at least in part, through impedance of neutrophil recruitment. These data indicate that GM2941 affords a significant degree of protection against granuloma formation associated with glucan infusion, probably through the interruption of neutrophil recruitment.

    Title Reduction of Myocardial Infarct Size in Vivo by Carbohydrate-based Glycomimetics.
    Date February 1998
    Journal The Journal of Pharmacology and Experimental Therapeutics
    Excerpt

    One of the foremost mechanisms involved in the pathogenesis of myocardial reperfusion injury is the adhesion of neutrophils within the myocardium. The initial neutrophil-endothelial cell interactions are mediated by the selectin family of adhesion molecules. Blockade of this group of adhesion molecules, through the use of synthetic carbohydrate analogs to the selectin ligand sialyl Lewisx and glycomimetics, has been beneficial in reducing neutrophil influx and infarct size. In the present study, glycyrrhizin (GM1292), a natural structural glycomimetic, was analyzed for the ability to decrease myocardial infarct size after regional myocardial ischemia/reperfusion. To determine the structural requirements for optimal cardioprotective activity, two additional compounds related to glycyrrhizin, GM3290 and GM1658 (glycyrrhetinic acid), were studied. The molecular structures of the latter two compounds differ in the number of glucuronic acid residues in their respective molecules. Open-chest, anesthetized rabbits were subjected to 30 min occlusion of the left coronary artery followed by 5 hr of reperfusion. Vehicle or glycomimetic (10 mg/kg/hr) was administered intravenously immediately before the onset of reperfusion and every hour during the reperfusion period. Myocardial infarct size in rabbits treated with GM1292 (two glucuronic acid residues) and GM3290 (one glucuronic acid residue) was reduced significantly when compared with vehicle-treated animals (P < .05). GM1658, which lacks glucuronic acid residues, did not provide a protective effect in vivo. The data suggest that GM1292 and GM3290, which contain carbohydrate moieties, are effective in reducing the degree of myocardial injury after an acute period of ischemia/reperfusion.

    Title False Positive Cervicovaginal Cytology. A Follow-up Study.
    Date December 1997
    Journal Acta Cytologica
    Excerpt

    OBJECTIVE: To determine what percentage of cervical cytologic diagnoses initially classified as false positives (based on a negative cervical biopsy within three months of the cervical cytologic smear) are recategorized as histologic false negatives when subsequent studies reveal abnormalities. STUDY DESIGN: A three-year review of 1,242 cervicovaginal biopsies with corresponding cytology in the preceding three months revealed 68 cases (5.5%) where the cytology was positive for a squamous intraepithelial lesion but the biopsy was within normal limits or showed benign cellular changes. Follow-up cytologic and/or histologic diagnoses were obtained for 53 of the 68 cases from the patients' hospital and physician office records. RESULTS: Of the 53 cases with follow-up, 24 (45%) were found to have a subsequent squamous intraepithelial lesion (indicating a sampling error at the time of the initial biopsy), and 9 showed atypical squamous cells of undetermined significance. In addition, 9 of the 20 patients (45%) who had negative follow-up studies had benign abnormalities on the initial, noncorrelating biopsy that may have contributed to the discrepancy. CONCLUSION: This study emphasized the importance of diligent follow-up of patients with noncorrelating studies since they represent a population at high risk for the subsequent detection of premalignant conditions.

    Title Correct Blue-light Regulation of Pea Lhcb Genes in an Arabidopsis Background.
    Date November 1997
    Journal Plant Molecular Biology
    Excerpt

    Irradiation of etiolated Arabidopsis or pea, or dim-red-light-grown pea seedling with a single, short (under 10 s) pulse of blue light (threshold at 0.1 mumol/m2) is sufficient to induce the expression of specific members of the Lhcb gene family including the pea Lhcb1*4 gene and the Arabidopsis Lhcb1*3 gene. Other Lhcb genes, such as the pea Lhcb1*3 gene and the Arabidopsis Lhcb1*1 and 1*2 genes are unaffected by this blue-light treatment. Transgenic Arabidopsis bearing pea Lhcb1*3::Gus (beta-glucuronidase), pea Lhcb1*4::Gus or Arabidopsis Lhcb1*3::Gus constructs were used to determine if pea and Arabidopsis employ a similar mechanism to achieve blue-light induced Lhcb expression. Examination of the respective Gus expression patterns in white-light-grown seedlings indicates that the pea promoters are active and properly expressed in the Arabidopsis background. Irradiation of dark-grown Arabidopsis with a 20 s pulse of blue light with a total fluence of 100 mumol/m-2 results in expression of the pea Lhcb1*4::Gus (beta-glucuronidase) construct, but not of the pea Lhcb1*3::Gus construct indicating that the pea promoters respond correctly to blue light in the Arabidopsis background. Fluence-response, time-course and reciprocity characteristics for the blue-light-induced expression of the pea Lhcb1*4::Gus construct closely resemble those of the endogenous Arabidopsis Lhcb genes, confirming the proper interpretation of the Arabidopsis blue-light-signaling mechanism by the pea Lhcb1*4 promoter and suggesting that the signaling mechanisms in the two plants are very similar, if not identical. Fluence response data for the steady-state level of transcript derived from an Arabidopsis Lhcb1*3::Gus construct extending 200 bp upstream of the site of transcription indicate that the blue light responsive elements(s) are contained within this 200 bp region.

    Title Metal Accumulation in Crayfish, Procambarus Clarkii, Exposed to a Petroleum-contaminated Bayou in Louisiana.
    Date November 1997
    Journal Ecotoxicology and Environmental Safety
    Excerpt

    Red swamp crayfish (Procambarus clarkii) were placed for a period of 7 days in Bayou Trepagnier, a Louisiana waterway which received petroleum-laden effluents from a manufacturing complex several decades ago. However, coolant water from the plant continued to be released into the bayou until 1995. Analyses of sediments at the exposure site revealed heavy contamination by lead, chromium, and copper, while concentrations of arsenic and cadmium were very low. Significant bioaccumulation of lead was observed in the hepatopancreas and gills of 7-day-exposed crayfish, whereas chromium accumulated the most in the gills and blood. Concentrations of copper in the crayfish did not change during the course of the study, suggesting that this essential metal constituent of the respiratory pigment is successfully regulated even when crayfish are exposed to relatively high levels of copper in the sediments. There was no metal accumulation in the abdominal muscle of the crayfish. That damage to the hepatopancreas occurred during the exposure is suggested by histopathological studies which revealed swollen and vacuolated R cells and an increase in the pH of the digestive juices. Blood glucose levels, as well as ovarian and hepatopancreatic indices, were unchanged. This study demonstrates that accumulation of nonessential metals in crayfish tissues in a wetland environment contaminated by mixed pollution (metals and hydrocarbons) reflects the concentrations of metals in the sediment.

    Title Volume Reduction Surgery in the Native Lung After Single Lung Transplantation for Emphysema.
    Date September 1997
    Journal The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation
    Excerpt

    The natural history of emphysema suggests that progression of disease in the native lung may contribute to late deterioration in respiratory function after single lung transplantation. In this report, we describe our experience with unilateral volume reduction surgery in three single lung transplant recipients with emphysema. Each patient had had a late decline in lung function with a recurrence of symptoms. Chest radiographs demonstrated hyperinflation of the native lungs with encroachment on the grafts. Serial pulmonary function testing documented progressive reduction in expiratory flows with increases in residual volumes. Exercise testing confirmed severe intolerance to maximal exercise. Unilateral volume reduction surgery was undertaken at 36, 39, and 55 months after transplantation without incident. Radiographs obtained after the procedures demonstrated restoration of normal diaphragmatic contour, decreased aeration of the native lungs, and improved inflation of the allografts. Exercise testing at 3 months documented a mean improvement in maximal oxygen consumption of 35%. Expiratory flows improved by a mean of 60%. Quantitative ventilation and perfusion scans, however, were essentially unchanged. This experience suggests that unilateral volume reduction surgery may be considered as an alternative strategy in single lung transplant recipients with emphysema who exhibit clinically significant functional deterioration. Differentiation of the adverse effects of hyperinflation of the native lung from other potential causes of late deterioration might not be necessary but may be predictive of the degree of functional improvement after volume reduction. The relief of thoracic overdistention seems to play a primary role in the improvement pulmonary function.

    Title Sulfo-lewis(x) Diminishes Neutrophil Infiltration and Free Radicals with Minimal Effect on Serum Cytokines After Liver Ischemia and Reperfusion.
    Date August 1997
    Journal The Journal of Surgical Research
    Excerpt

    BACKGROUND: Cell adhesion plays a central role in the pathogenesis of neutrophil-induced hepatic injury after ischemia and reperfusion. Sialyl Lewis(x) binds to selectins mediating neutrophil adherence to endothelium, thereby facilitating subsequent migration and tissue damage. AIM: We studied the effect of a novel sulfo-derivative of sialyl Lewis(x), GM-1998, on the liver inflammatory response after ischemia and reperfusion. Specifically, we evaluated its impact on three key inflammatory mediators: neutrophil migration, free radicals, and serum cytokines. MATERIAL AND METHODS: Rats were subjected to total hepatic ischemia for 90 min using an extracorporeal portosystemic shunt to avoid splanchnic congestion. GM-1998 was given at a total dose of 20 mg/kg both prior to and after reperfusion. Liver function tests, liver tissue free radicals, and myeloperoxidase (MPO), serum cytokines (IL-1, TNF-alpha), and liver histology were analyzed 4 hr after reperfusion. Additionally, survival was followed for up to 7 days. RESULTS: Seven-day survival significantly increased from 20% in the control group to 65% in the sulfo-Lewis(x) treated group. Liver function tests and histological damage scores were improved in comparison to controls. We observed significant downregulation of free radicals and neutrophil migration. This compound did not significantly affect serum cytokine levels. CONCLUSIONS: GM-1998 showed a protective effect in an in vivo model of severe liver ischemia and reperfusion by decreasing tissue free radical levels and selectin-mediated neutrophil migration. This protective effect was also reflected in improved liver function tests and histological response leading to better survival. We confirmed the beneficial effect of neutrophil blockade as a key target to prevent damage after the reperfusion phenomenon by using a glycomimetic sulfo-Lewis(x).

    Title Cerebral Perfusion Pressure Monitoring Alert!
    Date July 1997
    Journal Critical Care Medicine
    Title Percutaneous Dilational Tracheostomy--a Clinical Study Evaluating Two Systems.
    Date July 1997
    Journal Anaesthesia and Intensive Care
    Title Introducing Information Technologies into Medical Education: Activities of the Aamc.
    Date April 1997
    Journal Academic Medicine : Journal of the Association of American Medical Colleges
    Excerpt

    Previous articles in this column have discussed how new information technologies are revolutionizing medical education. In this article, two staff members from the Association of American Medical College's Division of Medical Education discuss how the Association (the AAMC) is working both to support the introduction of new technologies into medical education and to facilitate dialogue on information technology and curriculum issues among AAMC constituents and staff. The authors describe six AAMC initiatives related to computing in medical education: the Medical School Objectives Project, the National Curriculum Database Project, the Information Technology and Medical Education Project, a professional development program for chief information officers, the AAMC ACCESS Data Collection and Dissemination System, and the internal Staff Interest Group on Medical Informatics and Medical Education.

    Title Clinical Value of Radiologists' Interpretations of Perioperative Radiographs of Orthopedic Patients.
    Date March 1997
    Journal Orthopedics
    Excerpt

    The content and accuracy of radiographic interpretations by radiologists was assessed to determine the reports' ability to provide sufficient information necessary to make clinical treatment decisions. A retrospective review was performed of 371 radiographic studies (211 consecutive patients) and their reports which had been generated by three Board-certified radiologists. Data were collected regarding fracture assessment and description as well as the description and assessment of orthopedic implants. These descriptions were categorized by their ability to be used clinically (precise) or not (general). Fracture descriptions were considered complete for 85% of reports, while their assessment of alignment and displacement (necessary to determine fracture care) was complete on only 9%. Orthopedic implants were described precisely on 12% of reports with 7% of the descriptions in error. The effect and position of orthopedic implants were described precisely for only 27% and 25% of cases, respectively, while implant stability was assessed precisely in only 4% of cases. For 61% of preoperative studies, the radiologist's report was not available until after the surgical procedure had already been performed. For all variables considered, an average of 3% of descriptions contained an error. Radiologists' reports of radiographs of these patients undergoing orthopedic procedures did not contain sufficient descriptive information to be used clinically, were not promptly available, and contained an error for 3% of variables studied. The attending orthopedic surgeon has traditionally interpreted such radiographs and should continue to do so to provide patients with more immediate and complete clinical evaluation and management.

    Title Techniques for Bronchial Anastomosis.
    Date September 1996
    Journal The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation
    Excerpt

    BACKGROUND: Many techniques have been described to optimize the construction of the bronchial anastomosis in lung transplantation. Over the past 60 months we have performed 86 bronchial anastomoses in 70 patients receiving single lung or bilateral single lung transplants. METHODS: No anastomosis was wrapped and no attempt was made at revascularization of bronchial arteries. A continuous nonabsorbable suturing technique was used in all cases. Standard triple-drug immunotherapy with cyclosporine, azathioprine, and prednisone (starting at day 7) was used for each patient. RESULTS: There were no anastomotic leaks, and seven stenoses were identified in five patients (7%). All complications were managed conservatively with stenting, and there were no related deaths. Mean time to stent placement was 109 days. One patient had bilateral stents placed prophylactically during an episode of severe infection for questionable anastomotic viability but without evidence of airway necrosis or obstruction. This patient died of infection at 16 days. Another patient died with stents in place at 71 days. In the four remaining patients, all stents have been removed after a mean of 310 days. These patients were followed up with serial bronchoscopy and were without evidence of recurrent obstruction at 2, 34, 35, and 36 months. Six of seven stenoses occurred in patients with cystic fibrosis. In each patient where stenosis developed the anastomosis was telescoped. Since abandoning the telescoping technique in the remaining 50 anastomoses (14 in patients with cystic fibrosis), no dehiscence or stenosis was encountered. CONCLUSIONS: These data suggest that elaborate techniques aimed at construction of the bronchial anastomosis are not necessary. Moreover, attempts at telescoping may be detrimental. Patients with cystic fibrosis may be a population at higher risk for anastomotic complications. Airway complications can be managed conservatively with good results and little risk to the patient.

    Title Volume Reduction of the Native Lung After Single-lung Transplantation for Emphysema.
    Date June 1996
    Journal The Journal of Thoracic and Cardiovascular Surgery
    Title Organizational and Psychological Consultation in Collegiate Sports Medicine Groups.
    Date December 1995
    Journal Journal of American College Health : J of Ach
    Excerpt

    The complex authority, accountability, and supervisory structures of sports medicine groups in athletic departments can lead to conflicts that affect healthcare delivery for student-athletes. The authors review consultation models that counselors, sport psychologists, and other organizational consultants can use in dealing with these problems in collegiate sports medicine groups and offer examples of improved functioning through systemic, group, and individual intervention.

    Title Primary Pulmonary Artery Sarcoma: a Report of Six Cases.
    Date July 1995
    Journal The Annals of Thoracic Surgery
    Excerpt

    Pulmonary artery tumors are rare and a frequently overlooked cause of pulmonary artery occlusion. The presentation is one of progressive pulmonary dysfunction and right ventricular failure. The diagnosis seldom is made preoperatively. We report 6 cases of primary sarcoma of the pulmonary artery identified at operation, which were treated surgically. Resection with or without adjuvant therapy currently offers the only chance for survival. Emphasis must be placed on earlier identification of these tumors.

    Title Differential Activation of Protein Kinase C Isoforms by Endothelin-1 and Phenylephrine and Subsequent Stimulation of P42 and P44 Mitogen-activated Protein Kinases in Ventricular Myocytes Cultured from Neonatal Rat Hearts.
    Date January 1995
    Journal The Journal of Biological Chemistry
    Excerpt

    The translocation of protein kinase C (PKC) isoforms PKC-alpha, PKC-delta, PKC-epsilon, and PKC-zeta from soluble to particulate fractions was studied in ventricular cardiomyocytes cultured from neonatal rats. Endothelin-1 (ET-1) caused a rapid ETA receptor-mediated translocation of PKC-delta and PKC-epsilon (complete in 0.5-1 min). By 3-5 min, both isoforms were returning to the soluble fraction, but a greater proportion of PKC-epsilon remained associated with the particulate fraction. The EC50 of translocation for PKC-delta was 11-15 nM ET-1 whereas that for PKC-epsilon was 1.4-1.7 nM. Phenylephrine caused a rapid translocation of PKC-epsilon (EC50 = 0.9 microM) but the proportion lost from the soluble fraction was less than with ET-1. Translocation of PKC-delta was barely detectable with phenylephrine. Neither agonist caused any consistent translocation of PKC-alpha or PKC-zeta. Activation of p42 and p44 mitogen-activated protein kinase (MAPK) by ET-1 or phenylephrine followed more slowly (complete in 3-5 min). Phosphorylation of p42-MAPK occurred simultaneously with its activation. The proportion of the total p42-MAPK pool phosphorylated in response to ET-1 (50%) was greater than with phenylephrine (20%). In addition to activation of MAPK, an unidentified p85 protein kinase was activated by ET-1 in the soluble fraction whereas an unidentified p58 protein kinase was activated in the particulate fraction.

    Title Sialyl Lewis X Mimics Derived from a Pharmacophore Search Are Selectin Inhibitors with Anti-inflammatory Activity.
    Date September 1994
    Journal The Journal of Biological Chemistry
    Excerpt

    The selectins, a family of adhesion receptors involved in leukocyte extravasation, recognize sialyl Lewis X (sLe(x); NeuAc alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc) and related oligosaccharides. We used conformational energy computations, high field NMR, and structure-function studies to define distance parameters of critical functional groups of sLe(x). This sLe(x) pharmacophore was used to search a three-dimensional data base of chemical structures. Compounds that had a similar spatial relationship of functional groups were tested as inhibitors of selectin binding. Glycyrrhizin, a triterpene glycoside, was identified and found to block selectin binding to sLe(x) in vitro. We substituted different sugars for the glucuronic acids of glycyrrhizin and found the L-fucose derivative to be the most active in vitro and in vivo. A C-fucoside derivative, synthesized on a linker designed for stability and to more closely approximate the original sLe(x) pharmacophore, resulted in an easily synthesized, effective selectin blocker with anti-inflammatory activity.

    Title Evidence for Competitive Intramolecular Trimethylsilyl Rearrangement to Oxygen and Sulfur in Beta-trimethylsilylethylthiolesters.
    Date February 1994
    Journal Rapid Communications in Mass Spectrometry : Rcm
    Title Educating Medical Students. Assessing Change in Medical Education--the Road to Implementation.
    Date July 1993
    Journal Academic Medicine : Journal of the Association of American Medical Colleges
    Title Medical Education in the United States and Canada Revisited.
    Date July 1993
    Journal Academic Medicine : Journal of the Association of American Medical Colleges
    Title Protective Action of Zinc Against Cobalt-induced Testicular Damage in the Mouse.
    Date April 1993
    Journal Reproductive Toxicology (elmsford, N.y.)
    Excerpt

    The purpose of this study was to determine if toxic effects of cobalt on the murine testis could be prevented by zinc, an essential metal for spermatogenesis. CD-1 male mice were administered one of the following in their drinking water: 1) 400 ppm CoCl2, 2) 800 ppm ZnCl2, 3) 400 ppm CoCl2 + 800 ppm ZnCl2, or 4) distilled water. After 13 weeks, animals were sacrificed and testes were excised, weighed, and processed for histologic study. Comparison of testicular weights revealed no difference between the control and zinc-treated groups, while there was a small but significant reduction in the zinc/cobalt-treated group, and a large reduction in the cobalt-treated group. Histologic evaluation of testes confirmed the degenerative effects of cobalt, as well as the normal morphology in the zinc-treated group. Furthermore, 90% of the animals in the zinc/cobalt-treated group exhibited complete or partial protection as demonstrated by tubular morphology. This study indicates that zinc prevents cobalt-induced testicular damage.

    Title Histopathology of Testes from Mice Chronically Treated with Cobalt.
    Date May 1992
    Journal Reproductive Toxicology (elmsford, N.y.)
    Excerpt

    Effects of cobalt on murine testes were evaluated by light and electron microscopy. Continuous exposure of male mice to cobalt (400 ppm) via drinking water over a 13-week period resulted in a reproducible, sequential pattern of seminiferous tubule degeneration. Initial changes involved vacuolation of Sertoli cells and formation of abnormal spermatid nuclei. This was followed by the presence of multinucleated cells and sloughing of cells. Sertoli cells phagocytosed degenerating cells. Continued degeneration resulted in shrinkage of tubules with the accumulation of "calcified" necrotic debris in some. Sertoli cells were the last surviving cells. As degenerating tubules shrank, peritubular areas became highly disorganized. Myoid cell shapes became irregular, and basal laminae became highly folded. Endothelial cells of testicular vessels were thickened in areas and contained vesiclelike structures. Leydig cell morphology was normal but interstitial areas appeared hypercellular. The possible interactions of cobalt with iron and zinc, essential metals for spermatogenesis, are discussed.

    Title Effects of Acute and Chronic Exposure to Cobalt on Male Reproduction in Mice.
    Date May 1992
    Journal Reproductive Toxicology (elmsford, N.y.)
    Excerpt

    Chronic exposure of male mice to cobaltous chloride dramatically affected their reproductive potential, while acute administration had minimal effects. Acute exposure, followed by evaluation weekly over a 7-week period, revealed no significant changes in epididymal sperm concentration or testicular weight. However, small but significant decreases in fertility at weeks 2 and 3 of the study were observed. Sperm motility was depressed only during the first week of the study. In chronic studies, cobalt affected fertility in a time- and dose-dependent manner. There was a decrease in testicular weight, epididymal sperm concentration, and fertility. Sperm motility was also depressed. Serum testosterone levels were dramatically increased in cobalt treated animals, while FSH and LH serum levels were normal. It appears that cobalt is directly or indirectly interfering with spermatogenesis and with local regulatory mechanisms in testosterone synthesis.

    Title The Intramolecular Migration of a Trimethylsilyl Group Located Alpha to a Sulfone in Substituted Cyclohexyl Systems.
    Date April 1992
    Journal Rapid Communications in Mass Spectrometry : Rcm
    Excerpt

    The intramolecular migration of a trimethylsilyl moiety alpha to a sulfone group of some modified cyclohexyl ring systems is investigated. The large difference in the relative abundance of this rearrangement ion for similar compounds is related to the stability of the protonated species.

    Title Computer Databases of Medical School Curricula.
    Date February 1992
    Journal Academic Medicine : Journal of the Association of American Medical Colleges
    Excerpt

    As the pace of curriculum reform in medical education has accelerated during the past decade, so too have demands on curriculum managers to supply increasingly detailed information about the curriculum. In response, a number of schools have joined together to begin work on designs for computer databases of the curriculum. The authors describe three of the most mature curriculum database prototypes, developed by groups at the medical schools of the University of North Carolina at Chapel Hill (UNC), The University of Maryland, and the University of Miami. All three groups have employed relational database management systems to organize information about each "instructional unit" in the preclinical curriculum, including a set of keywords defining the major concepts presented. The keywords are indexed to a controlled vocabulary, either the Medical Subject Headings (MeSH) or a MeSH derivative. The UNC database also employs a textfile management system to provide users with an overview of the entire curriculum. Future work will focus on identifying a suitable controlled vocabulary; capturing content in greater contextual detail; incorporating alternative learning formats, such as problem-based learning; creating links between content items and examination questions; and capturing information generated by student-patient interactions in clinical settings. As a result of recent collaboration with the Association of American Medical Colleges, work to define a prototype national database has begun and a consortium of interested schools is addressing further development activities.

    Title Use of Deoxyribonucleic Acid (dna) Fingerprints for Identity Determination: Comparison with Traditional Paternity Testing Methods--part Ii.
    Date February 1991
    Journal Journal of Forensic Sciences
    Excerpt

    Six red blood cell (RBC) antigen systems, coupled with human lymphocyte antigen (HLA) phenotyping, were used to establish paternity on 28 mother/child/alleged-father trios. Samples were subsequently examined using the deoxyribonucleic acid (DNA) fingerprinting test with the multilocus Jeffreys DNA probes 33.6 and 33.15. In 27 of 28 paternity cases, the DNA fingerprinting test results supported and enhanced the results of RBC and HLA typing by resolving disputed paternity cases conclusively. One discrepancy between conventional serological methods and DNA analysis is discussed.

    Title Use of Deoxyribonucleic Acid (dna) Fingerprints for Identity Determination: Comparison with Traditional Paternity Testing Methods--part I.
    Date February 1991
    Journal Journal of Forensic Sciences
    Excerpt

    A study involving comparison of the deoxyribonucleic acid (DNA) finger-printing test with traditional methods used for paternity testing is presented. Samples from 191 cases were tested for a series of blood group and polymorphic protein markers. DNA "fingerprints" were then obtained for all samples using the multilocus probes 33.6 and 33.15. The results of DNA fingerprinting correlated well with those of traditional methods and proved to be informative in cases where traditional methods yielded inconclusive or insufficient results.

    Title The Value of Preliminary Traction in the Treatment of Congenital Dislocation of the Hip.
    Date September 1990
    Journal The Journal of Bone and Joint Surgery. American Volume
    Excerpt

    In forty-one children who had forty-seven congenitally dislocated hips, the results of attempted closed reduction with general anesthesia, but without preliminary traction, were studied. Twenty (43 per cent) of the hips could not be reduced closed, and an open reduction was needed. After the reduction, all of the involved hips were immobilized in the so-called human position (marked flexion and slight abduction). At a minimum follow-up of two years, osteonecrosis of the femoral head had developed in only two hips (4 per cent). Patients who were more than one year old when the hip was reduced had a higher incidence of osteonecrosis of the femoral head and were more likely to need reconstructive procedures later. Patients who were more than eighteen months old at the time of the attempted closed reduction were more likely to need an open reduction of the hip. Treatment of congenital dislocation of the hip in young children remains an extremely complex problem. It has not been clearly established that the use of preliminary traction decreases the incidence of osteonecrosis of the femoral head or improves the outcome of treatment. In our experience, uncomplicated (non-teratological, postnatal) congenital dislocation of the hip has been safely treated with either open or closed reduction without preliminary traction in patients who were younger than two years old, provided that the reduction could be obtained without excessive force.

    Title Multiple Sites of Action of the Vitamin D Endocrine System: Fsh Stimulation of Testis 1,25-dihydroxyvitamin D3 Receptors.
    Date March 1990
    Journal Journal of Steroid Biochemistry
    Excerpt

    1,25-Dihydroxyvitamin D [1,25(OH)2D] receptors exist in numerous unexpected tissues. These include, for example, rat lung, heart, testis, and uterus, but not prostate and bladder. The issues of 1,25(OH)2D effects on and receptor location in the testis were addressed by (a) physiological and pharmacological manipulations of tubule cell types and (b) histological examination of testes of vitamin D-deficient rats. FSH treatment in hypophysectomized adult rats increased 1,25(OH)2D receptor levels by 135% (P less than 0.01). Busulfan treatment reduced testis receptor levels by 35% (P less than 0.05) after 35 days (maximum effect), and the effect was reversed after recovery (85 d). Cryptorchidism for 5 or 50 days resulted in modest (33%, P less than 0.05) or substantial (79%, P less than 0.001) reductions in receptor levels. Only the FSH treatment and 50 days cryptorchidism reduced receptor levels in the residual tissue. The testes of vit. D-deficient rats showed incomplete spermatogenesis and degenerative changes. Although interpretation is complicated by the intricate communication among testis cell types, these data suggest that the Sertoli cell is a primary site of action of 1,25(OH)2D in the testis. Moreover, these data indicate that 1,25(OH)2D receptor function in the testis relates to germ cell division/maturation, although this may be an indirect effect via the Sertoli cells.

    Title The Source of Relaxin in Pregnant Syrian Hamsters.
    Date April 1988
    Journal Endocrinology
    Excerpt

    Serum immunoreactive relaxin (IR) was measured on days 8, 10, and 14 of gestation in intact and ovariectomized (day 8 of pregnancy) hamsters. In intact hamsters, IR increased from 3-4 ng/ml on day 8 to 20 ng/ml by day 14 of pregnancy. After ovariectomy on day 8, pregnancy failed, and IR decreased rapidly to 0.29 ng/ml on day 14. However, when pregnancy was maintained in ovariectomized hamsters by daily injections of 0.1 microgram 17 beta-estradiol and 4 mg progesterone, serum IR rose to levels similar to those in intact hamsters on days 10 and 14 of pregnancy (i.e. 15 and 20 ng/ml, respectively). Placentas were obtained from other groups of hamsters on days 11, 14, and 15 of pregnancy and homogenized for bioassay by the classical guinea pig pubic symphysis palpation bioassay. Homogenates of placentas obtained on days 14 and 15 contained, respectively, 4 and 10 micrograms eq porcine relaxin/serum relaxin/g fresh tissue. The placenta, rather than the ovary, appears to be the source of during pregnancy in the hamster.

    Title Absence of Relaxin Immunostaining in the Male Reproductive Tracts of the Rat and Mouse.
    Date July 1986
    Journal The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society
    Excerpt

    By use of the biotin-avidin immunohistochemical method and a homologous antiserum as the primary antiserum, relaxin immunostaining was absent in the testes, prostate, seminal vesicles, and epididymides of the rat. Relaxin immunostaining was also lacking when anti-porcine relaxin serum was employed as the primary antiserum. Furthermore, immunohistochemical studies for relaxin localization in the reproductive tract of the male mouse using both anti-rat and anti-porcine relaxin sera also revealed an absence of the hormone in the reproductive system of this species. Although this study suggests that immunoreactive relaxin is absent in the male reproductive tracts of both the rat and mouse, it raises some questions concerning the reports in the literature of the presence of relaxin-like substances in the male reproductive tracts of other species. These reports are discussed in relation to our current results.

    Title Spinal Arthrodesis for Spinal Deformity Using Posterior Instrumentation and Sublaminar Wiring. A Preliminary Report of 100 Consecutive Cases.
    Date April 1986
    Journal International Orthopaedics
    Excerpt

    One hundred consecutive patients with spinal deformity due to various diagnoses were treated by posterior spinal arthrodesis with instrumentation and multiple sublaminar wires. Both the Harrington and Luque rodding systems were used. A total of 1128 wire loops were passed. No patient developed paraparesis or paraplegia, but three had transient sensory disturbance. There were no cases of broken rods or wires. Forty-five of the patients had no postoperative support. This worked well for neuromuscular scolioses, but for idiopathic scoliosis there was a disturbing loss of correction in many cases. Fusion to the sacrum was best accomplished with the "Galveston" technique, other methods having a high rate of pseudarthrosis. The main benefits appeared to be the ability to stabilize neuromuscular patients without the use of external immbolization, and the correction of thoracic lordosis.

    Title Immunocytochemical Studies of Relaxin in Ovaries of Pregnant and Cycling Mice.
    Date May 1985
    Journal The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society
    Excerpt

    Immunocytochemical staining for relaxin in ovarian sections of pregnant mice from day 11 through day 18 of gestation revealed that only corpora lutea (CL) of pregnancy are stained. Evaluation of serial sections of ovaries from a day 16 pregnant mouse revealed that the only luteal structures present are CL of pregnancy. The number of CL present in each ovary equaled the number of implantation sites in each related horn (7 on the right side and 8 on the left side). These large CL varied in shape, being round in some profiles to very elongate in others. All CL were immunochemically stained for relaxin using the peroxidase-antiperoxidase method of L. Sternberger (Immunocytochemistry, 2nd ed. Wiley, New York, 1979). The intensity of the strain varied from cell to cell within each CL. Small luteal structures that were observed to be immunochemically stained for relaxin were demonstrated to represent the periphery of CL of pregnancy. No luteinized follicles were observed and interstitial cells and follicles were not immunochemically stained in any of the day 16 serial ovarian sections or in any of the ovarian sections from pregnant mice on the other days of gestation studied. CL of previous cycles were not observed to be present in the ovaries at days 15, 16, or 18 of gestation. However on day 14 and before, CL of previous cycles were observed and they did not exhibit any relaxin immunostaining. Immunocytochemical studies using the biotin-avidin system revealed that no relaxin immunostaining could be demonstrated in the ovaries of cycling mice at any stage of the estrous cycle. In conclusion, this study revealed that the only ovarian structures demonstrating relaxin immunocytochemical staining in the mouse were CL of pregnancy.

    Title Pregnant Mouse Corpora Lutea: Immunocytochemical Localization of Relaxin and Ultrastructure.
    Date November 1984
    Journal Biology of Reproduction
    Excerpt

    Relaxin was localized in corpora lutea of pregnant mouse ovaries by using the unlabeled antibody peroxidase-antiperoxidase technique and a highly specific rabbit antirat relaxin serum. Relaxin immunostaining was first observed in luteal cells located at the periphery of corpora lutea on Day 10 of gestation. The number of relaxin immunostained cells and the intensity of the stain gradually increased to reach a maximum between Days 16 and 18 of gestation. While a few luteal cells were specifically stained for relaxin on Day 1 postpartum, no luteal cells were stained on Day 2 postpartum. Ultrastructural studies of luteal cells from pregnant mouse ovaries revealed the presence of a distinct electron-dense, membrane-bound granule population, which was first observed on Day 12 of gestation. The granules increased in number to reach a maximum between Days 16 and 18 of gestation, and were absent by Day 2 postpartum. The appearance and disappearance of this granule population closely paralleled the relaxin immunostaining in the luteal cells. We suggest that the granules may be the subcellular sites of relaxin storage in the pregnant mouse ovary.

    Title Ultrastructural Localization of Relaxin Immunoreactivity in Corpora Lutea of Pregnant Rats.
    Date May 1984
    Journal Endocrinology
    Excerpt

    Relaxin was localized in cells of corpora lutea of pregnant rats at the ultrastructural level using a highly specific antirat relaxin serum and the unlabeled peroxidase-antiperoxidase technique. Electron-dense, membrane-bound granules (maximum diameter, 270 nm), which are present in luteal cells during the last third of gestation, were the only inclusions that were immunochemically stained. The number of granules observed in the luteal cell cytoplasm varied from cell to cell within a particular section. Furthermore, in the granule-rich luteal cells, the granules appeared in clusters. This study establishes that these electron-dense granules represent the subcellular sites of relaxin localization within luteal cells of pregnant rats.

    Title Herpes: Coping and Caring--a Total College Health Program.
    Date May 1984
    Journal Journal of American College Health : J of Ach
    Title Bioassay of Porcine Relaxin Components by in Vitro Inhibition of Rat Uterine Contractions.
    Date February 1984
    Journal Endocrinology
    Excerpt

    Isolation of porcine relaxin by the procedure of Sherwood and O'Byrne has resulted in three, slightly different relaxin molecules which differ in the length of their B chains. The purpose of this study was to determine if a difference in biological activity exists among the three relaxin forms as determined by the in vitro inhibition of spontaneous rat uterine contractions. Uterine segments from estrogen-primed, virgin rats were suspended in Locke's solution in a siliconized, water-jacketed organ bath at 37 C. After regular contractions were established, the minimum concentration of each relaxin component necessary to cause total inhibition was determined. Total inhibition for all three relaxin components was obtained at a chamber concentration of 0.2-0.36 U/ml. Thus, no difference in biological activity exists among the three relaxin forms as demonstrated by the rat uterine inhibition bioassay.

    Title Preparation for the Teaching Role in Residencies: an Elective for Medical Students.
    Date December 1982
    Journal Journal of Medical Education
    Title A Required Internal Medicine Preceptorship.
    Date May 1982
    Journal Journal of Medical Education
    Title A Logbook System for Monitoring Student Skills and Experiences.
    Date November 1981
    Journal Journal of Medical Education
    Title Abortion After Roe and Doe: a Proposed Statute.
    Date March 1979
    Journal Vanderbilt Law Review
    Title Pathology of Listeriosis.
    Date March 1966
    Journal Journal of the National Medical Association
    Title Differences In Leucyl-transfer Rna's And Synthetase In Soybean Seedlings.
    Date
    Journal Proceedings of the National Academy of Sciences of the United States of America
    Excerpt

    Charged leucyl-transfer RNA (leucyl-tRNA) of soybean cotyledons can be fractionated into six radioactive peaks on a Freon column. Four leucyl-tRNA peaks are observed with the homologous hypocotyl system. Hypocotyl synthetase preparations only slightly acylate the other two leucyl-tRNA's (species 5 and 6). Further, leucyl-tRNA(5 and 6) of the hypocotyl are present in small amounts in comparison to the cotyledon. Therefore, the rate-limiting quantities of synthetase and tRNA(5 and 6) obtained from the hypocotyl prevent the detection of these two species of tRNA when a homologous hypocotyl system is used. To measure the relative amounts of hypocotyl tRNA's, the cotyledon synthetase preparation is employed. Preliminary results show that 6-benzyladenine increases the acylation of leucyl-tRNA(5 and 6) and decreases acylation of tRNA(1) in the hypocotyl. Synthetase preparations from cytokinin-treated plants are not significantly affected.


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