Bio

Clinical Focus


  • Anatomic Pathology
  • Pathology

Academic Appointments


Administrative Appointments


  • Associate Chair for Education, Stanford University School of Medicine - Pathology (2004 - Present)

Professional Education


  • Residency:Brigham and Women's Hospital Harvard Medical School (1985) MA
  • Internship:Brigham and Women's Hospital Harvard Medical School (1983) MA
  • Medical Education:Yale University School of Medicine (1982) CT
  • Board Certification: Anatomic Pathology, American Board of Pathology (1986)
  • Fellowship:Stanford University School of Medicine (1986) CA

Research & Scholarship

Current Research and Scholarly Interests


Autopsy pathology.

Medical informatics in pathology: structured reports; diagnostic coding.

Orthopedic pathology: implanted prosthetic materials.

Medical education: case-based learning in pathology; the use of glass slides, images and specimens in pathology; faculty development (teaching improvement) in the basic medical sciences.

Teaching

2013-14 Courses


Publications

Journal Articles


  • Best Cases from the AFIP Fatal 2009 Influenza A (H1N1) Infection, Complicated by Acute Respiratory Distress Syndrome and Pulmonary Interstitial Emphysema RADIOGRAPHICS Guo, H. H., Sweeney, R. T., Regula, D., Leung, A. N. 2010; 30 (2): 327-333

    View details for DOI 10.1148/rg.302095213

    View details for Web of Science ID 000275622400003

    View details for PubMedID 20068001

  • Pathological evidence of Wolman's disease following hematopoietic stem cell transplantation despite correction of lysosomal acid lipase activity BONE MARROW TRANSPLANTATION Gramatges, M. M., Dvorak, C. C., Regula, D. P., Enns, G. M., Weinberg, K., Agarwal, R. 2009; 44 (7): 449-450

    View details for DOI 10.1038/bmt.2009.57

    View details for Web of Science ID 000270933000007

    View details for PubMedID 19308038

  • Features of hemolysis due to Clostridium perfringens infection INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY Boyd, S. D., Mobley, B. C., Regula, D. P., Arber, D. A. 2009; 31 (3): 364-367

    Abstract

    Infection by Clostridium perfringens can be an unsuspected cause of hemolysis in emergency room patients. Historically, this condition has been associated with wound contamination and other tissue infections. We report the case of an autistic patient who presented to our emergency department with a distended abdomen and hemolysis of unknown etiology. The patient had no history of recent surgery. Exploration of the abdomen revealed a hepatic abscess. Blood cultures tested culture positive for C. perfringens. We present images demonstrating the salient features of the peripheral blood smear in cases of this uncommon but deadly cause of hemolysis.

    View details for DOI 10.1111/j.1751-553X.2007.01018.x

    View details for Web of Science ID 000265407400013

    View details for PubMedID 18177433

  • Using a statistical natural language Parser augmented with the UMLS specialist lexicon to assign SNOMED CT codes to anatomic sites and pathologic diagnoses in full text pathology reports. AMIA ... Annual Symposium proceedings / AMIA Symposium. AMIA Symposium Lowe, H. J., Huang, Y., Regula, D. P. 2009; 2009: 386-390

    Abstract

    To address the problem of extracting structured information from pathology reports for research purposes in the STRIDE Clinical Data Warehouse, we adapted the ChartIndex Medical Language Processing system to automatically identify and map anatomic and diagnostic noun phrases found in full-text pathology reports to SNOMED CT concept descriptors. An evaluation of the system's performance showed a positive predictive value for anatomic concepts of 92.3% and positive predictive value for diagnostic concepts of 84.4%. The experiment also suggested strategies for improving ChartIndex's performance coding pathology reports.

    View details for PubMedID 20351885

  • Continuous Intramedullary Polymer Particle Infusion Using a Murine Femoral Explant Model JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS Ortiz, S. G., Ma, T., Regula, D., Smith, R. L., Goodman, S. B. 2008; 87B (2): 440-446

    Abstract

    In vitro models are important investigative tools in understanding the biological processes involved in wear-particle-induced chronic inflammation and periprosthetic osteolysis. In the clinical scenario, particles are produced and delivered continuously over extended periods of time. Previously, we quantified the delivery of both polystyrene and polyethylene particles over 2- and 4-week time periods using osmotic pumps and collection tubes. In the present study, we used explanted mice femora in organ culture and showed that continuous intramedullary delivery of submicron-sized polymer particles using osmotic pumps is feasible. Furthermore, infusion of 2.60 x 10(11) particles per mL (intermediate concentration) of ultrahigh molecular weight polyethylene (UHMWPE) for 2 weeks and 8.06 x 10(11) particles per mL (high concentration) UHMWPE for 4 weeks both yielded significantly higher scores for bone loss when compared with controls in which only mouse serum was infused.

    View details for DOI 10.1002/jbm.b.31122

    View details for Web of Science ID 000260355000017

  • Database upload service for image files http://uploadservice.sourceforge.net Regula, D. 2006
  • Specimen Photography for Canon Powershot http://specimenphoto.sourceforge.net Regula, D. 2006
  • Proinflammatory mediator expression in a novel murine model of titanium-particle-induced intramedullary inflammation JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS Warme, B. A., Epstein, N. J., Trindade, M. C., Miyanishi, K., Ma, T., Saket, R. R., Regula, D., Goodman, S. B., Smith, R. L. 2004; 71B (2): 360-366

    Abstract

    Wear debris from total joint replacement prostheses is implicated in periprosthetic osteolysis and implant loosening. The pathophysiology of this biological process remains unclear. Animal models of particle-induced osteolysis have proven useful in the study of specific tissue responses to wear debris. However, existing in vivo murine models of particle-mediated inflammation do not permit analysis of cortical bone degradation. This study describes a murine model of particle disease using an intramedullary rod in the mouse femur to parallel the clinical situation. The model consists of placing a 10-mm-long Kirschner wire retrograde in both femurs of C57b1/6 male mice via a medial parapatellar arthrotomy. Phagocytosable titanium particles were also implanted unilaterally to replicate generation of wear debris. Mice were sacrificed at 2, 10, and 26 weeks and whole femurs were cultured for 72 h. Levels of interleukin-6, monocyte chemotactic protein-1, and macrophage colony stimulating factor were assayed by ELISA. Transverse histological sections, at the level of the implant, were taken and stained with hematoxylin and eosin (H&E). Results demonstrated increased expression of proinflammatory mediators at 2 weeks in femora with rod and particles compared to femora with rods alone. Destruction of the endosteum was evident at 2, 10, and 26 weeks in the femora with titanium. This novel murine model of particle-induced intramedullary inflammation may facilitate cost-effective genetic studies and offers investigators a simple, clinically relevant intramedullary model to readily examine the pathogenesis of particle-mediated periprosthetic osteolysis.

    View details for DOI 10.1002/jbm.b.30120

    View details for Web of Science ID 000224846700018

  • A pilot study of faculty development for basic science teachers ACADEMIC MEDICINE Skeff, K. M., Stratos, G. A., Bergen, M. R., Regula, D. P. 1998; 73 (6): 701-704

    Abstract

    Relatively little research has focused on faculty development methods that assist basic science teachers to improve their instructional skills. This study was designed to assess the effectiveness for basic science faculty of a faculty development seminar series that had been previously shown useful for clinical teachers.The Stanford Faculty Development Program's seminars on clinical teaching were adapted for basic science instruction. Eight pathology faculty participated in a series of nine small-group seminars designed to provide teachers with knowledge of a framework for analyzing teaching and identifying areas for improvement, and skill-based training in specific teaching behaviors. Each seminar included (1) brief lectures, (2) review of videotaped reenactments of teaching interactions, (3) role-play exercises with videotape review, and (4) formulation of personal and departmental teaching goals.Program evaluation included multiple measures: participant self-assessment, student ratings of the participants, and blinded ratings of pre- and post-seminar videotapes of participants' classroom teaching. All measures indicated a positive effect of the intervention.Faculty development programs have significant potential to enhance basic science instructors' teaching effectiveness.

    View details for Web of Science ID 000074383900028

    View details for PubMedID 9653410

  • Polyethylene and titanium alloy particles reduce bone formation - Dose-dependence in bone harvest chamber experiments in rabbits ACTA ORTHOPAEDICA SCANDINAVICA Goodman, S., Aspenberg, P., Song, Y., Regula, D., Lidgren, L. 1996; 67 (6): 599-605

    Abstract

    Particles similar to those generated from joint replacements affect net bone formation within the Bone Harvest Chamber in rabbits. Whether these effects depend on the concentration of particulate materials is unknown. In this study, we performed a histomorphologic and morphometric analysis of net bone formation in the Bone Harvest Chamber in the presence of different concentrations of phagocytosable particles of high density polyethylene and titanium 6-aluminum 4-vanadium alloy. Chambers were implanted in 9 mature New Zealand white rabbits bilaterally. Concentrations of 10(6), 10(7) and 10(8) polyethylene particles/mL, and 10(8) and 10(9) particles/ mL of titanium alloy in 1% sodium hyaluronate carrier were implanted for 3-week periods in sequence in each of the chambers. 3-week control periods in which nothing was implanted in the chamber were included between the treatments. Increasing concentrations of polyethylene particles were associated with a more marked foreign body response and fibrosis. Net bone formation for the three polyethylene doses was reduced by 11%, 21% and 33% of controls, respectively. For titanium alloy, net bone formation was reduced by 8% and 56% of controls, for concentrations of 10(8) and 10(9) particles/mL, respectively. Our findings suggest possible adverse effects of wear debris on net bone formation and bony remodeling in the prosthetic bed, when concentrations of specific particles reach critical local levels.

    View details for Web of Science ID A1996WD77200015

    View details for PubMedID 9065075

  • Targeted disruption of the mouse beta 1-adrenergic receptor gene: Developmental and cardiovascular effects PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Rohrer, D. K., Desai, K. H., Jasper, J. R., Stevens, M. E., Regula, D. P., Barsh, G. S., Bernstein, D., Kobilka, B. K. 1996; 93 (14): 7375-7380

    Abstract

    At least three distinct beta-adrenergic receptor (beta-AR) subtypes exist in mammals. These receptors modulate a wide variety of processes, from development and behavior, to cardiac function, metabolism, and smooth muscle tone. To understand the roles that individual beta-AR subtypes play in these processes, we have used the technique of gene targeting to create homozygous beta 1-AR null mutants (beta 1-AR -/-) in mice. The majority of beta 1-AR -/- mice die prenatally, and the penetrance of lethality shows strain dependence. Beta l-AR -/- mice that do survive to adulthood appear normal, but lack the chronotropic and inotropic responses seen in wild-type mice when beta-AR agonists such as isoproterenol are administered. Moreover, this lack of responsiveness is accompanied by markedly reduced stimulation of adenylate cyclase in cardiac membranes from beta 1-AR -/- mice. These findings occur despite persistent cardiac beta 2-AR expression, demonstrating the importance of beta 1-ARs for proper mouse development and cardiac function, while highlighting functional differences between beta-AR subtypes.

    View details for Web of Science ID A1996UW79200098

    View details for PubMedID 8693001

  • EFFECTS OF PARTICULATE HIGH-DENSITY POLYETHYLENE AND TITANIUM-ALLOY ON TISSUE INGROWTH INTO BONE HARVEST CHAMBER IN RABBITS JOURNAL OF APPLIED BIOMATERIALS Goodman, S., Aspenberg, P., Song, Y., Doshi, A., Regula, D., Lidgren, L. 1995; 6 (1): 27-33

    Abstract

    The purpose of this study was to determine whether small, phagocytosable particles of titanium alloy (Ti) and high-density polyethylene (HDPE) have an adverse effect on bone ingrowth. The bone harvest chamber (BHC) was implanted bilaterally in the proximal tibial metaphysis of six mature rabbits. The BHC has a transverse 1-mm wide pore providing a continuous canal through the chamber for tissue ingrowth. After an initial 6-week period for osseointegration of the BHC, the contents of the canal were harvested repeatedly at 3 weekly intervals. This could be done with the chamber in place, without disturbing its exterior surface or the surrounding bone. The carrier solution, 1% sodium hyaluronate (Healon) was implanted first. In subsequent implantations, Healon was mixed with particles of HDPE or Ti averaging 4.7 +/- 2.1 and 3.0 +/- 2.6 microns, respectively. The contralateral chamber was left empty and served as a control. The chambers were harvested repeatedly, alternating experimental and control sides. The sections from the control side, and those containing Healon alone demonstrated extensive trabecular bone in a fibrovascular stroma. The sections containing Ti alloy particles were qualitatively and quantitatively similar to the control sections and those containing Healon, except for the presence of small black granules of Ti alloy, dispersed in the fibrovascular stroma or phagocytosed by scattered macrophages. The sections containing HDPE particles were infiltrated and engulfed by mononuclear and multinuclear histiocytic cells in a highly fibrous stroma. The majority of the multinucleated cells present were interpreted as being foreign body giant cells.(ABSTRACT TRUNCATED AT 250 WORDS)

    View details for Web of Science ID A1995QH69800004

    View details for PubMedID 7703535

  • EPSTEIN-BARR VIRUS-ASSOCIATED NATURAL-KILLER LARGE GRANULAR LYMPHOCYTE LEUKEMIA HUMAN PATHOLOGY Gelb, A. B., VANDERIJN, M., Regula, D. P., CORNBLEET, J. P., Kamel, O. W., Horoupian, D. S., Cleary, M. L., Warnke, R. A. 1994; 25 (9): 953-960

    Abstract

    We describe the first case of an Epstein-Barr virus (EBV)-associated natural killer-large granular lymphocyte (NK-LGL) leukemia in the United States to the best of our knowledge. A 29-year-old woman of Japanese descent developed EBV infection after a blood transfusion as indicated by a rise in serum antibody titers. Peripheral blood and bone marrow aspirate smears demonstrated increased LGLs. Flow cytometry showed that these cells expressed NK-associated surface antigens. Cytogenetic analysis of the bone marrow aspirate showed two distinct but related clones with multiple copies of a modified 7 marker chromosome. Death followed colonic perforation. Findings at necropsy included bone marrow lymphocytosis and erythrophagocytosis, a mononucleosis-like lymphadenitis, atypical hepatitis with a mixed, predominantly T-cell infiltrate, interstitial pneumonitis, and multiorgan system vasculitis with perforation of the transverse colon. Epstein-Barr virus transcripts were identified in lymphocytes infiltrating liver and peripheral nerve by in situ hybridization. In addition, Southern blot analyses showed monoclonal bands superimposed on oligoclonal ladders of EBV termini in liver and lymph node. The identical episomal form of EBV was found in the bone marrow, lymph node, and liver. No immunoglobulin (Ig), T-cell receptor beta, or T-cell receptor gamma chain gene rearrangements were identified. These studies support the hypothesis that the LGL population was a neoplastic EBV-related clonal proliferation of NK cells.

    View details for Web of Science ID A1994PG35800018

    View details for PubMedID 8088773

  • EFFECTS OF AN ISOGENIC ZN-METALLOPROTEASE-DEFICIENT MUTANT OF LEGIONELLA-PNEUMOPHILA IN A GUINEA-PIG PNEUMONIA MODEL MOLECULAR MICROBIOLOGY Moffat, J. F., Edelstein, P. H., Regula, D. P., Cirillo, J. D., Tompkins, L. S. 1994; 12 (5): 693-705

    Abstract

    To determine the effects, if any, of the Zn-metalloprotease on virulence of Legionella pneumophila infection, an isogenic mutant deficient in protease (encoded by the proA gene) was tested in an Acanthamoeba cell model, in guinea-pig macrophages, and in a guinea-pig pneumonia model. The cloned proA gene was completely inactivated by insertion of a kanamycin-resistance cassette into the protease gene of L. pneumophila AA100. This mutated gene was then introduced into the L. pneumophila chromosome by allelic exchange to form the isogenic ProA- mutant AA200. AA200 showed no difference in its ability to enter, survive, or grow in Acanthamoeba and explanted guinea-pig macrophages; neither light nor electron microscopy revealed morphological differences in the eukaryotic cells infected with the protease mutant or the wild-type strains. The proA gene was found to be expressed in L. pneumophila during intracellular growth in amoebae by measuring the light produced from a truncated luxC gene fusion with the proA promoter. Virulence of the protease mutant was attenuated when tested in a guinea-pig model of infection employing the intratracheal inoculation method. AA200 was slower to cause death, grew to lower numbers in the lungs, resulted in less necrotic debris and a larger macrophage infiltrate, and was more likely to be found in association with macrophage vacuoles than the parent strain. Although deletion of the protease was not sufficient to completely abolish virulence in a guinea-pig model, the mutation caused a delay in the lethal effects of L. pneumophila and attenuated the infection.

    View details for Web of Science ID A1994NP48400002

    View details for PubMedID 8052122

  • Autopsy findings after coronary rotational atherectomy. The American journal of cardiovascular pathology van de Rijn, M., Regula, D. P., Billingham, M. 1990; 3 (4): 301-304

    Abstract

    We describe the findings at autopsy in a patient who underwent Rotablator atherectomy of the right coronary artery. During the procedure, the artery became occluded. Despite attempts to reopen the vessel with balloon angioplasty and emergency coronary artery bypass grafting, the patient developed irreversible cardiac failure and expired 2 days after the Rotablator procedure. At autopsy, the right coronary artery was found to be occluded by thrombus. No evidence of dissection or perforation of the vessel wall was seen. Small intramyocardial arteries and arterioles, downstream from the treated vessel, were embolized by pulverized atheroma.

    View details for PubMedID 2129571

  • NODULAR AND DIFFUSE TYPES OF LYMPHOCYTE PREDOMINANCE HODGKINS-DISEASE NEW ENGLAND JOURNAL OF MEDICINE Regula, D. P., Hoppe, R. T., Weiss, L. M. 1988; 318 (4): 214-219

    Abstract

    The nodular form of lymphocyte predominance Hodgkin's disease has been shown to be immunophenotypically distinct from the histologically diffuse form and from other types of Hodgkin's disease. We undertook a clinicopathological study of 73 cases to determine whether any clinical differences between the nodular and diffuse subtypes could be discerned. Patients with the diffuse form (n = 41) tended to have a course similar to that of other types of Hodgkin's disease; there were few relapses and only two deaths due to Hodgkin's disease. In contrast, patients with the nodular form (n = 32) had significantly more relapses, which were independent of stage or treatment and equally distributed up to 10 years after initial therapy. Despite the frequent relapses, patients with the nodular form had an indolent course, and there was only one death due to Hodgkin's disease. There were seven fatal second cancers and two non-neoplastic treatment-related deaths, equally distributed between the nodular and diffuse groups. We conclude that nodular lymphocyte predominance Hodgkin's disease may have important clinical as well as immunophenotypic differences from other forms of Hodgkin's disease, and that patients with this condition should be followed carefully because of the possibility of late relapse.

    View details for Web of Science ID A1988L784400004

    View details for PubMedID 3336412

Conference Proceedings


  • Multiresolution browsing of pathology images using wavelets Wang, J. Z., Nguyen, J., Lo, K. K., Law, C., Regula, D. BMJ PUBLISHING GROUP. 1999: 430-434

    Abstract

    Digitized pathology images typically have very high resolution, making it difficult to display in their entirety on the computer screen and inefficient to transmit over the network for educational purposes. Progressive zooming of pathology images is desirable despite the availability of inexpensive networking bandwidth. An efficient progressive image resolution refining system for on-line distribution of pathology image using wavelets has been developed and is discussed in this paper. The system is practical for real-world applications, pre-processing and coding each 24-bit image of size 2400 x 3600 within 40 seconds on a Pentium II PC. The transmission process is in real-time. Besides its exceptional speed, the algorithm has high flexibility. The server encodes the original pathology images without loss. Based on the image request from a client, the server dynamically generates and sends out the part of the image at the requested scale and quality requirement. The algorithm is expandable for medical image databases such as PACS.

    View details for Web of Science ID 000170207300089

    View details for PubMedID 10566395

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