Biomedical subjects

C Bruce Alexander

Publications and source records attributed to C Bruce Alexander.

12 recordsLinked to original sources

PubMed2006

Curriculum content and evaluation of resident competency in clinical pathology (laboratory medicine): a proposal.

Ten years have passed since the Graylyn Conference Report on Laboratory Medicine Clinical Pathology training was issued. Over that period, the Accreditation Council for Graduate Medical Education substantially revised the requirements for training programs; the American Board of Pathology amended both the requirements and the periods needed for certification; and the discipline itself, along with the broader discipline of pathology, evolved significantly. Recently, a curriculum proposal in anatomical pathology was published as a potential template to be used by training programs to help meet these new and evolving needs. Toward the same end, the Academy of Clinical Laboratory Physicians and Scientists has now developed a template for a curriculum in clinical pathology (laboratory medicine), taking into account newly designated and revised areas of residency core competency, the alterations in training requirements promulgated by the Accreditation Council for Graduate Medical Education and American Board of Pathology, and the rapidly developing nature of the discipline itself. The proposed clinical pathology curriculum defines goals and objectives for training, provides guidelines for instructional methods, and gives examples of how outcomes can be assessed. This curriculum is presented as a potentially helpful outline for use by pathology residency training programs.

Clinical Competence↗

PubMed2006

Pathology graduate medical education (overview from 1926 to 2005).

Postgraduate training of pathologists in the United States dates from 1926. From 1926 to 1936, certification was developed as a measure of competence for the public. In 2000, competence was redefined by the Accreditation Council for Graduate Medical Education (ACGME) Outcome Project for all physicians-in-training as mastering "the six competencies." These consist of (1) patient care, (2) medical knowledge, (3) practice-based learning and improvement, (4) interpersonal and communication skills, (5) professionalism, and (6) systems-based practice. The Outcome Project emerged in parallel with the American Board of Medical Specialties' Maintenance of Certification Project for all physicians. Outcome measures and benchmarks are the methods by which competence in medical practice will be measured for the public. Trends in pathology graduate medical education previously reported in 2001 (Hum Path 2001;32[7]:671-676) are updated through 2005 and reviewed. Demographic data regarding number and size of programs, curricula initiatives for pathology, changes in assessment, and outcomes information on certificates issued are discussed. Factors shaping pathology residency training are reviewed, as well as future trends that will impact training curricula.

Certification↗

PubMed2006

Curriculum content and evaluation of resident competency in clinical pathology (laboratory medicine): a proposal.

Ten years have passed since the Graylyn Conference Report on Laboratory Medicine/Clinical Pathology training was issued. Over that time period, the Accreditation Council for Graduate Medical Education (ACGME) substantially revised the requirements for training programs, the American Board of Pathology (ABP) amended both the requirements and the time periods needed for certification, and the discipline itself, along with the broader discipline of pathology, evolved significantly. Recently, a curriculum proposal in anatomic pathology was published as a potential template to be used by training programs to help meet these new and evolving needs. Toward the same end, the Academy of Clinical Laboratory Physicians and Scientists has now developed a template for a curriculum in clinical pathology (laboratory medicine), taking into account newly designated and revised areas of residency core competency, the alterations in training requirements promulgated by the ACGME and ABP, and the rapidly developing nature of the discipline itself. The proposed clinical pathology curriculum defines goals and objectives for training, provides guidelines for instructional methods, and gives examples of how outcomes can be assessed. This curriculum is presented as a potentially helpful outline for use by pathology residency training programs.

Clinical Competence↗

PubMed2006

Curriculum content and evaluation of resident competency in clinical pathology (laboratory medicine): a proposal.

Ten years have passed since the Graylyn Conference Report on Laboratory Medicine/Clinical Pathology training was issued. During that period, the Accreditation Council for Graduate Medical Education (ACGME) substantially revised the requirements for training programs, the American Board of Pathology (ABP) amended the requirements and the time needed for certification, and the discipline itself along with the broader discipline of pathology, evolved significantly. Recently, a curriculum proposal in anatomic pathology was published as a potential template to be used by training programs to help meet these new and evolving needs. Toward the same end, the Academy of Clinical Laboratory Physicians and Scientists has developed a template for a curriculum in clinical pathology (laboratory medicine), taking into account newly designated and revised areas of residency core competency, the alterations in training requirements promulgated by the ACGME and ABP, and the rapidly developing nature of the discipline itself The proposed clinical pathology curriculum defines goals and objectives for training, provides guidelines for instructional methods, and gives examples of how outcomes can be assessed. This curriculum is presented as a potentially helpful outline for use by pathology residency training programs.

Clinical Competence↗

PubMed2005

Loss of fibroblast Thy-1 expression correlates with lung fibrogenesis.

Fibroblasts consist of heterogeneous subpopulations that have distinct roles in fibrotic responses. Previously we reported enhanced proliferation in response to fibrogenic growth factors and selective activation of latent transforming growth factor (TGF)-beta in fibroblasts lacking cell surface expression of Thy-1 glycoprotein, suggesting that Thy-1 modulates the fibrogenic potential of fibroblasts. Here we report that compared to controls Thy-1-/- C57BL/6 mice displayed more severe histopathological lung fibrosis, greater accumulation of lung collagen, and increased TGF-beta activation in the lungs 14 days after intratracheal bleomycin. The majority of cells demonstrating TGF-beta activation and myofibroblast differentiation in bleomycin-induced lesions were Thy-1-negative. Histological sections from patients with idiopathic pulmonary fibrosis demonstrated absent Thy-1 staining within fibroblastic foci. Normal lung fibroblasts, in both mice and humans, were predominantly Thy-1-positive. The fibrogenic cytokines interleukin-1 and tumor necrosis factor-alpha induced loss of fibroblast Thy-1 surface expression in vitro, which was associated with Thy-1 shedding, Smad phosphorylation, and myofibroblast differentiation. These results suggest that fibrogenic injury promotes loss of lung fibroblast Thy-1 expression, resulting in enhanced fibrogenesis.

Animals↗

PubMed2003

Pulmonary transplantation for advanced bronchioloalveolar carcinoma.

BACKGROUND: No effective therapy is currently available for the diffuse stage of bronchioloalveolar carcinoma. OBJECTIVE: We tested the hypothesis that total lung replacement with standard lung transplantation techniques would provide curative therapy. METHODS: Nine patients aged 31 to 58 years with bronchioloalveolar carcinoma were entered in the study. Five patients initially had bilateral diffuse tumor. Four patients had recurrence in the contralateral lung after pulmonary resection. RESULTS: Between 1993 and 1998, all 9 patients underwent transplantation (2 single-lung and 7 bilateral transplants, 1 reoperative single-lung transplant, and 1 reoperative bilateral transplant). Two patients had mediastinal node metastasis (level 7) at the time of transplantation, and 1 of these had a frankly invasive adenocarcinoma. Of the 8 patients with pure bronchioloalveolar carcinoma, 6 had recurrent pulmonary tumor after transplantation. In 2 of these patients the tumor was localized and could be resected with left lower lobectomy in one case and left pneumonectomy in the other. One is alive 89 months after transplantation; the other died 82 months after transplantation. Four other patients had a diffuse pattern of pulmonary recurrence. Two died of progressive pulmonary failure; 1 of these had retransplantation with recurrence. A third patient died of cerebral edema shortly after bilateral retransplantation. The other patient is alive with recurrence 39 months after transplantation and has bronchiolitis obliterans. Two patients without recurrence are well with unrestricted performance levels 87 and 76 months after transplantation. CONCLUSIONS: Transplantation produces a powerful palliative outcome in patients with advanced bronchioloalveolar carcinoma, but the recurrence rate is high. Transplantation for this indication remains controversial.

Adenocarcinoma, Bronchiolo-Alveolar↗

PubMed2003

Pelvic trauma in rapidly fatal motor vehicle accidents.

OBJECTIVE: To study the incidence and nature of pelvic fractures in rapidly fatal automobile accidents. DESIGN: Retrospective. SETTING: County Medical Examiner's Office. PATIENTS: The files of 255 consecutive motor vehicle accident fatalities examined at the Jefferson County Coroner/Medical Examiner's office (study period 1996-1998) were reviewed. We correlated this information with our previous findings, derived from a review of 392 such cases (study period 1994-1996). RESULTS: Approximately 25% of decedents involved in rapidly fatal automobile accidents sustained pelvic fractures. In 93% of the cases, postmortem radiographs were available and suitable for scoring according to the Orthopaedic Trauma Association nomenclature. The distribution of pelvic fractures by type was type A, 16%; type B, 32%; and type C, 52%, with the most common pelvic fracture being type C1 (26%). Additionally, pedestrians and motorcyclists were twice as likely to sustain a pelvic fracture, and the severity of pelvic fracture type seemed to correlate with increasing speed of the automobile. No correlation between drug use or direction of impact and incidence or type of pelvic fracture was observed. Compared with published studies on survivors of automobile accidents, our data suggest that pelvic injuries may tend to be more severe in victims who do not survive to hospitalization. CONCLUSIONS: Our data indicate that current estimates about the mortality of pelvic fractures may be faulty due to exclusion of victims who fail to survive to hospitalization. This series suggests that an appreciation of the full spectrum of pelvic ring disruptions requires collaboration between orthopaedic surgeons and forensic pathologists.

Accidents, Traffic↗

PubMed2002

Nitric oxide-dependent generation of reactive species in sickle cell disease. Actin tyrosine induces defective cytoskeletal polymerization.

The intermittent vascular occlusion occurring in sickle cell disease (SCD) leads to ischemia-reperfusion injury and activation of inflammatory processes including enhanced production of reactive oxygen species and increased expression of inducible nitric-oxide synthase (NOS2). Appreciating that impaired nitric oxide-dependent vascular function and the concomitant formation of oxidizing and nitrating species occur in concert with increased rates of tissue reactive oxygen species production, liver and kidney NOS2 expression, tissue 3-nitrotyrosine (NO(2)Tyr) formation and apoptosis were evaluated in human SCD tissues and a murine model of SCD. Liver and kidney NOS2 expression and NO(2)Tyr immunoreactivity were significantly increased in SCD mice and humans, but not in nondiseased tissues. TdT-mediated nick end-label (TUNEL) staining showed apoptotic cells in regions expressing elevated levels of NOS2 and NO(2)Tyr in all SCD tissues. Gas chromatography mass spectrometry analysis revealed increased plasma protein NO(2)Tyr content and increased levels of hepatic and renal protein NO(2)Tyr derivatives in SCD (21.4 +/- 2.6 and 37.5 +/- 7.8 ng/mg) versus wild type mice (8.2 +/- 2.2 and 10 +/- 1.2 ng/mg), respectively. Western blot analysis and immunoprecipitation of SCD mouse liver and kidney proteins revealed one principal NO(2)Tyr-containing protein of 42 kDa, compared with controls. Enzymatic in-gel digestion and MALDI-TOF mass spectrometry identified this nitrated protein as actin. Electrospray ionization and fragment analysis by tandem mass spectrometry revealed that 3 of 15 actin tyrosine residues are nitrated (Tyr(91), Tyr(198), and Tyr(240)) at positions that significantly modify actin assembly. Confocal microscopy of SCD human and mouse tissues revealed that nitration led to morphologically distinct disorganization of filamentous actin. In aggregate, we have observed that the hemoglobin point mutation of sickle cell disease that mediates hemoglobin polymerization defects is translated, via inflammatory oxidant reactions, into defective cytoskeletal polymerization.

Actins↗

PubMed2002

Spatial mapping of pulmonary and vascular nitrotyrosine reveals the pivotal role of myeloperoxidase as a catalyst for tyrosine nitration in inflammatory diseases.

Nitrotyrosine (NO(2)Tyr) formation is a hallmark of acute and chronic inflammation and has been detected in a wide variety of human pathologies. However, the mechanisms responsible for this posttranslational protein modification remain elusive. While NO(2)Tyr has been considered a marker of peroxynitrite (ONOO(-)) formation previously, there is growing evidence that heme-protein peroxidase activity, in particular neutrophil-derived myeloperoxidase (MPO), significantly contributes to NO(2)Tyr formation in vivo via the oxidation of nitrite (NO(2)(-)) to nitrogen dioxide (.NO(2)). Coronary arteries from a patient with coronary artery disease, liver and lung tissues from a sickle cell disease patient, and an open lung biopsy from a lung transplant patient undergoing rejection were analyzed immunohistochemically to map relative tissue distributions of MPO and NO(2)Tyr. MPO immunodistribution was concentrated along the subendothelium in coronary tissue and hepatic veins as well as in the alveolar epithelial compartment of lung tissue from patients with sickle cell disease or acute rejection. MPO immunoreactivity strongly colocalized with NO(2)Tyr formation, which was similarly distributed in the subendothelial and epithelial regions of these tissues. The extracellular matrix protein fibronectin (FN), previously identified as a primary site of MPO association in vascular inflammatory reactions, proved to be a major target protein for tyrosine nitration, with a strong colocalization of MPO, NO(2)Tyr, and tissue FN occurring. Finally, lung tissue from MPO(-/-) mice, having tissue inflammatory responses stimulated by intraperitoneal zymosan administration, revealed less subendothelial NO(2)Tyr immunoreactivity than tissue from wild-type mice, confirming the significant role that MPO plays in catalyzing tissue nitration reactions. These observations reveal that (i) sequestration of neutrophil-derived MPO in vascular endothelial and alveolar epithelial compartments is an important aspect of MPO distribution and action in vivo, (ii) MPO-catalyzed NO(2)Tyr formation occurs in diverse vascular and pulmonary inflammatory pathologies, and (iii) extracellular matrix FN is an important target of tyrosine nitration in these inflammatory processes.

Animals↗

PubMed2002

Competency-based residency training in pathology: challenges and opportunities.

The Accreditation Council for Graduate Medical Education (ACGME) is requiring that all medical specialties adopt a new paradigm for residency education: competency-based residency education. Competency-based education includes not only the acquisition of knowledge and the demonstration of safe medical practice, but also competency in practice-based learning, practice improvement, interpersonal skills and communication, professionalism, and an awareness of pathology's role in a larger health care system. Implementation of this new training program will require new educational resources and the implementation of new faculty and resident skills and incentives.

Competency-Based Education↗

PubMed2002

Analysis of the incidence of pelvic trauma in fatal automobile accidents.

Pelvic fractures are frequent complications of motor vehicle accidents, and motor vehicle accidents are the most common cause of pelvic fracture. Although pelvic fractures are associated with considerable morbidity and mortality, there has traditionally been no attempt to grade or classify pelvic fractures during postmortem examination. The authors performed a retrospective study of cases examined at the Jefferson County Coroner/Medical Examiner Office from 1994 to 1996, reviewing investigative reports and autopsy findings. Radiographs were examined for the presence and Tile type of pelvic fracture. Pelvic fractures were identified in 88 of 392 cases (23%). In most (89%), the pelvic fracture was readily classified according to Tile type on the basis of radiographs and the inferred mechanism of injury. This study indicates that current estimates of the mortality of pelvic fractures are low because of the exclusion of individuals who do not survive to hospitalization. Furthermore, pelvic fractures in rapidly fatal motor vehicle accidents tend to be more severe than fractures in individuals who have a significant interval of survival. The presence and classification of pelvic fractures may be readily determined by radiographs in most cases. The Tile classification scheme is easy to apply and has important implications in the comparison of study groups.

Accidents, Traffic↗

PubMed2000

Protein nitration, metabolites of reactive nitrogen species, and inflammation in lung allografts.

This study investigated nitration and chlorination of epithelial lining fluid (ELF) proteins in patients (n = 29) who had undergone lung allotransplantation. We assayed lung lavage nitrotyrosine (NT) and chlorotyrosine (CT) by HPLC. We measured NT, nitrate (NO(3)(-)), and nitrate (NO(2)(-)) in bronchoalveolar lavage fluid (BALF) and total nitrite (NO(2)(-) + NO(3)(-)) in serum of another group of lung transplant patients (n = 82). In the first group (n = 29), percent nitration of tyrosines (Tyr) (NT/total Tyr x 100) in BALF proteins was: patients, 0.01 (0.00-0.12)%; median (25th-75th% confidence interval), and control subjects 0.01 (0.00-0.02)%. CT (CT/ total Tyr x 100) occurred only in the patients' BALF: 0.01 (0. 00- 0.02)%. In the second group (n = 82), nitrotyrosine (NT) was detected by ELISA in the BALF of patients: 9 (0-41) pmol/mg pro and control subjects: 28 (26-33). Total nitrite (NO(2)(-) + NO(3)(-)) in BALF of the patients: 3.3 (1.9-5.1) microM significantly exceeded that in control subjects: 1.3 (0.8-1.3) microM; p = 0.0133. Serum nitrite also was significantly higher in patients: 37 (26-55) microM than control subjects: 19 (17-20) microM; p = 0.0037. Airway inflammation in transbronchial biopsies (B score) correlated with NT in BALF (p = 0.0369). Lung transplants have increased airway concentrations of reactive nitrogen species (RNS) metabolites. NT, a marker of peroxynitrite (ONOO(-)), is related to the degree of airway inflammation in lung transplants.

Adult↗