Emeritus Faculty - University Medical Line, Pathology
Member, Point of Care Resource Committee, College of American Pathologists (2011 - 2013)
Chair, Publications Committee, Society of Pediatric Pathology (2012 - 2015)
Task Force on Paediatric Laboratory Medicine, International Federation Clinical Chemistry (2011 - 2013)
Chair, Pediatric Maternal Fetal Division, American Association of Clinical Chemistry (2012 - 2013)
Honors & Awards
Outstanding Speaker Award, American Association of Clinical Chemistry (2011)
Outstanding Speaker Award, American Association of Clinical Chemistry (2012)
16th Annual Roger Boeckx Memorial Lecture, Childen's National Medical Center, Washington D.C. (2012)
Current Research and Scholarly Interests
Pediatric Hematopathology, Pediatric Laboratory Medicine and Pathology
- Laboratory diagnostic tools for personalized fetal medicine and improving neonatal outcomes. Clinical biochemistry 2014; 47 (9): 702-703
Fetal Laboratory Medicine: On the Frontier of Maternal-Fetal Medicine
2012; 58 (2): 337-352
Emerging antenatal interventions and care delivery to the fetus require diagnostic support, including laboratory technologies, appropriate methodologies, establishment of special algorithms, and interpretative guidelines for clinical decision-making.Fetal diagnostic and therapeutic interventions vary in invasiveness and are associated with a spectrum of risks and benefits. Fetal laboratory assessments are well served by miniaturized diagnostic methods for blood analysis. Expedited turnaround times are mandatory to support invasive interventions such as cordocentesis and intrauterine transfusions. Health-associated reference intervals are required for fetal test interpretation. Fetal blood sampling by cordocentesis carries substantial risk and is therefore performed only when fetal health is impaired, or at risk. When the suspected pathology is not confirmed, however, normative fetal data can be collected. Strategies for assurance of sample integrity from cordocenteses and confirmation of fetal origin are described. After birth, definitive assessment of prenatal environmental and/or drug exposures to the fetus can be retrospectively assessed by analysis of meconium, hair, and other alternative matrices. A rapidly advancing technology for fetal assessment is the use of fetal laboratory diagnostic techniques that use cell-free fetal DNA collected from maternal plasma, and genetic analysis based on molecular counting techniques.Developmental changes in fetal biochemical and hematologic parameters in health and disease are continually delineated by analysis of our collective outcome-based experience. Noninvasive technologies for fetal evaluation are realizing the promise of lower risk yet robust diagnostics; examples include sampling and analysis of free fetal DNA from maternal blood, and analysis of fetal products accessible at maternal sites. Application of diagnostic technologies for nonmedical purposes (e.g., sex selection) underscores the importance of ethical guidelines for new technology implementation.
View details for DOI 10.1373/clinchem.2011.166991
View details for Web of Science ID 000300303700007
View details for PubMedID 22205694
Diagnostic Laboratory Technologies for the Fetus and Neonate with Isoimmunization
SEMINARS IN PERINATOLOGY
2011; 35 (3): 148-154
Maternal-fetal blood group incompatibility is common but less commonly results in hemolytic disease of the fetus and newborn (HDFN). HDFN is associated with greater peak bilirubin, at an earlier age, and for longer duration than other causes of hyperbilirubinemia. It poses a substantial risk for kernicterus and accounts for the majority of exchange transfusions for hyperbilirubinemia. Advances in diagnosis and management are described, from identification of the alloimmunized pregnancy by maternal ABO and Rh typing, antibody screen (indirect Coombs test), identification and titration; laboratory evaluation of the maternal-fetal unit with a critical maternal antibody titer to prompt fetal antigen status determination; assessment of fetomaternal hemorrhage by conventional Kleihauer-Betke testing or by flow cytometric methodology; to antenatal management of isoimmunization and fetal status assessments using the systems of Liley, Queenan, and serial Doppler fetal middle cerebral artery peak velocity measurements. The utility of laboratory diagnostics in the approach to hemolysis in the neonate, including hematology, chemistry, and peripheral blood smear review, is reviewed. The goal of management, to deliver a healthy infant at or near term, is attained for the majority of cases using current modalities; future directions include noninvasive genotyping of fetal blood from maternal serum to fully eliminate RhD alloimmunization and HDFN; and development of prophylaxis and intervention strategies for non-RhD alloimmunizations for which immune globulin is currently unavailable.
View details for DOI 10.1053/j.semperi.2011.02.009
View details for Web of Science ID 000292057900008
View details for PubMedID 21641488
- Fetal health assessment in utero by laboratory technologies: Clinical benefits, risks and controversies 12th International Congress of Pediatric Laboratory Medicine (ICPLM) PERGAMON-ELSEVIER SCIENCE LTD. 2011: 460–62
- Critical values for the maternal-fetal unit, fetus, infant, child and adolescent: Bilirubin reporting practice in North American Children's Hospitals as a paradigm for critical value reporting assessment 12th International Congress of Pediatric Laboratory Medicine (ICPLM) PERGAMON-ELSEVIER SCIENCE LTD. 2011: 483–84
- Diagnostic Test Sample Volume: How Much Is Too Much?: Leveraging Point-of-Care Testing to Reduce Sample Volumes, Iatrogenic Anemia, and Transfusion Requirement in Adult Populations Point of Care The Journal of Near-Patient Testing and Technology 2011; 10 (4): 157-162
Teaching pediatric laboratory medicine to pathology residents
ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE
2006; 130 (7): 1031-1038
Laboratory data are essential to the medical care of fetuses, infants, children, and adolescents. However, the performance and interpretation of laboratory tests on specimens from these patients, which may constitute a significant component of the workload in general hospitals and integrated health care systems as well as specialized perinatal or pediatric centers, present unique challenges to the clinical pathologist and the laboratory. Therefore, pathology residents should receive training in pediatric laboratory medicine.Children's Health Improvement through Laboratory Diagnostics, a group of pathologists and laboratory scientists with interest and expertise in pediatric laboratory medicine, convened a task force to develop a list of curriculum topics, key resources, and training experiences in pediatric laboratory medicine for trainees in anatomic and clinical pathology or straight clinical pathology residency programs and in pediatric pathology fellowship programs.Based on the experiences of 11 training programs, we have compiled a comprehensive list of pediatric topics in the areas of clinical chemistry, endocrinology, hematology, urinalysis, coagulation medicine, transfusion medicine, immunology, microbiology and virology, biochemical genetics, cytogenetics and molecular diagnostics, point of care testing, and laboratory management. This report also includes recommendations for training experiences and a list of key texts and other resources in pediatric laboratory medicine.Clinical pathologists should be trained to meet the laboratory medicine needs of pediatric patients and to assist the clinicians caring for these patients with the selection and interpretation of laboratory studies. This review helps program directors tailor their curricula to more effectively provide this training.
View details for Web of Science ID 000238984300019
View details for PubMedID 16831030
Reduction in red blood cell transfusions using a bedside analyzer in extremely low birth weight infants.
Journal of perinatology
2005; 25 (1): 21-25
Preterm infants typically experience heavy phlebotomy losses from frequent laboratory testing in the first few weeks of life. This results in anemia, requiring red blood cell (RBC) transfusions. We recently introduced a bedside point-of-care (POC) blood gas analyzer (iSTAT, Princeton, NJ) that requires a smaller volume of blood to replace conventional Radiometer blood gas and electrolyte analysis used by our neonatal intensive care unit (NICU). The smaller volume of blood required for sampling (100 vs 300-500 microl), provided an opportunity to assess if a decrease in phlebotomy loss occurred and, if so, to determine if this resulted in decreased transfusions administered to extremely low birth weight (ELBW) infants.We hypothesized that the use of the POC iSTAT analyzer that measures pH, PCO(2), PO(2), hemoglobin, hematocrit, serum sodium, serum potassium and ionized calcium would result in a significant decrease in the number and volume of RBC transfusions in the first 2 weeks of life.A retrospective chart review was conducted of all inborn premature infants with birth weights less than 1000 g admitted to the NICU that survived for 2 weeks of age during two separate 1-year periods. Blood gas analysis was performed by conventional laboratory methods during the first period (designated Pre-POC testing) and by the iSTAT POC device during the second period (designated post-POC testing). Data collected for individual infants included the number of RBC transfusions, volume of RBCs transfused, and the number and kind of blood testing done. There was no effort to change either the RBC transfusion criteria applied or blood testing practices.The mean (+/-SD) number of RBC transfusions administered in the first 2 weeks after birth was 5.7+/-3.74 (n=46) in the pre-POC testing period to 3.1+/-2.07 (n=34) in the post-POC testing period (p<0.001), a 46% reduction. The mean volume of RBC transfusions decreased by 43% with use of the POC analyzer, that is, from 78.4+/-51.6 ml/kg in the pre-POC testing group to 44.4+/-32.9 ml/kg in the Post-POC testing group (p<0.002). There was no difference between the two periods in the total number of laboratory blood tests done.Use of a bedside blood gas analyzer is associated with clinically important reductions in RBC transfusions in the ELBW infant during the first two weeks of life.
View details for PubMedID 15496875
Imaging cell death with radiolabeled annexin V in an experimental model of rheumatoid arthritis
JOURNAL OF NUCLEAR MEDICINE
2002; 43 (10): 1359-1365
Rheumatoid arthritis is associated with chronic synovial inflammation due to the abnormal accumulation of macrophages and autoreactive T lymphocytes in joints. The autoreactive cells cause an inflammatory proapoptotic response to self-antigens resulting in eventual bone, cartilage, and soft-tissue loss and destruction. The goal of our study was to determine the timing and intensity of apoptosis in joints using 99mTc-labeled annexin V, an in vivo marker of apoptosis, in a murine model of immune arthritis.We used 99mTc-annexin V and autoradiography to study the extent and severity of apoptosis in the front and rear paws of DBA/1 mice with type II collagen-induced rheumatoid arthritis.Compared with control values (n = 10), there was a significant (P < 0.002) nearly 3-fold increase in uptake of 99mTc-annexin V in the front foot pads, rear toes, rear foot pads, and heels at the time of maximal extremity swelling as determined by serial caliper measurements at 4 wk after inoculation with type II bovine collagen (n = 9). The front toes had a 5- to 6-fold increase in uptake compared with control values (P < 0.001). Histologic analysis revealed only scattered rare lymphocytes in the periarticular soft tissues, without joint destruction. Dual autoradiography with 125I-bovine serum albumin as a control showed that 99mTc-annexin V localization was specific. Treatment with methylprednisolone for 1 wk (n = 8) at 4 wk after immunization with type II collagen decreased 99mTc-annexin V uptake by 3- to 6-fold compared with control values (P < 0.002).99mTc-annexin V can detect collagen-induced immune arthritis and its response to steroid therapy before joint destruction.
View details for PubMedID 12368374
Pediatric laboratory medicine - Current challenges and future opportunities
AMERICAN JOURNAL OF CLINICAL PATHOLOGY
2002; 117 (5): 683-690
The practice of pediatric laboratory medicine involves unique challenges related to development, nutrition, growth, and diseases during different periods of infancy, childhood, and adolescence. This article discusses key aspects of pediatric laboratory medicine faced by clinical pathologists, clinical laboratory scientists, and clinicians, including point-of-care testing, preanalytic variables, analytic factors, age-specific reference intervals, esoteric laboratory tests, clinical impact, andfuture opportunities. Although challenging, pediatric laboratory testing offers many opportunities for improved patient care, clinical- and laboratory-based research, and education.
View details for Web of Science ID 000175305600001
View details for PubMedID 12090415
- Pathological case of the month - Primary bone lymphoma: Diffuse large B-cell type ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE 2001; 155 (3): 409-410
Hematologic values and appearances in the healthy fetus, neonate, and child
CLINICS IN LABORATORY MEDICINE
1999; 19 (1): 1-?
Morphologic and laboratory aspects of diagnostic pediatric hematology are reviewed, including developmental hematopoiesis in normal fetal blood, the principal morphologic features unique to examination of pediatric blood samples, special preanalytic considerations for the laboratory, and important analytic interferences common in the pediatric setting.
View details for Web of Science ID 000080605900002
View details for PubMedID 10403073
LACK OF EFFECT OF PROPHYLACTIC AEROSOLIZED PENTAMIDINE ON THE DETECTION OF PNEUMOCYSTIS-CARINII IN INDUCED SPUTUM OR BRONCHOALVEOLAR LAVAGE SPECIMENS
ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE
1993; 117 (5): 493-496
Two independent studies were undertaken to determine the effect of prophylactic treatment with aerosolized pentamidine on the laboratory diagnosis of Pneumocystis carinii pneumonia in individuals at risk for or with the acquired immunodeficiency syndrome. The first study was a retrospective analysis to determine the effect of prophylactic treatment with aerosolized pentamidine on the diagnostic yield and sensitivity of detection of P carinii in induced sputum specimens. The results of examinations of 110 induced sputum specimens from patients who had not received aerosolized pentamidine were compared with the findings in 57 specimens from patients who had. There was no statistically significant difference between the two groups for the diagnostic yield in induced sputum specimens (48% vs 47%) or in bronchoalveolar lavage fluid specimens subsequently obtained from patients with nondiagnostic induced sputum examinations (33% vs 37%). The sensitivity of induced sputum specimens for identifying P carinii was 76% to 78% for patients who had not received aerosolized pentamidine and 71% to 75% for patients who had received the drug. The second study was a prospective comparison of 118 bronchoalveolar lavage fluid specimens to determine the effect of prophylactic treatment with aerosolized pentamidine on the number of organisms present. One hundred eighteen bronchoalveolar lavage fluid specimens were quantitatively examined and scored according to the number of clumps of P carinii present. No statistically significant difference was seen in the number of clumps of P carinii found in specimens from patients who had received aerosolized pentamidine vs the number of clumps found in specimens from patients who had not. In conclusion, prophylactic treatment with aerosolized pentamidine had no effect on (1) the diagnostic yield and sensitivity of detection of P carinii in induced sputum specimens or (2) the number of organisms detected in bronchoalveolar lavage fluid specimens obtained from individuals at risk for or with the acquired immunodeficiency syndrome.
View details for Web of Science ID A1993LA78700010
View details for PubMedID 8489338
DISAPPEARANCE OF EOSINOPHILS FROM BRONCHOALVEOLAR LAVAGE FLUID AFTER PATIENT EDUCATION AND HIGH-DOSE INHALED CORTICOSTEROIDS - A CASE-REPORT
HEART & LUNG
1993; 22 (3): 235-238
Inhaled steroid therapy is being emphasized in the treatment of asthma but requires patient adherence to regular dosing regimens and skilled inhalation techniques for treatment to be effective. If used correctly, high-dose inhaled corticosteroids may eradicate specific types of inflammatory cells from the airway, whereas use of systemic corticosteroids in chronic asthma may not significantly reduce airway inflammation or clinical symptoms. We report a case in which reduction in inflammatory cells in the airway was confirmed by bronchoalveolar lavage after individual patient education, training in self-monitoring, and treatment with inhaled corticosteroids. Clinical symptoms were reduced after conversion of this patient from systemic to inhaled corticosteroids.
View details for Web of Science ID A1993LD53600007
View details for PubMedID 8491659
EFFECT OF AEROSOLIZED PENTAMIDINE PROPHYLAXIS ON THE CLINICAL SEVERITY AND DIAGNOSIS OF PNEUMOCYSTIS-CARINII PNEUMONIA
AMERICAN REVIEW OF RESPIRATORY DISEASE
1992; 146 (4): 844-848
To determine if the use of aerosolized pentamidine prophylaxis decreases the clinical severity or the sensitivity of diagnostic tests for Pneumocystis carinii pneumonia (PCP), we conducted a retrospective matched cohort comparison study of patients admitted to San Francisco General Hospital with PCP from August 1, 1989, to June 30, 1990. Patients who had received pentamidine prophylaxis during at least the 2 months prior to the diagnosis of PCP were matched with patients who had not received the drug. Matching was based on the number of prior episodes of PCP, sex, age, and risk factors for human immunodeficiency virus infection. As markers of clinical severity, we chose alveolar-arterial oxygen difference, serum lactate dehydrogenase levels, outpatient versus inpatient treatment, length of hospitalization, length of intravenous anti-pneumocystis treatment, development of respiratory failure, in-hospital mortality, and chest radiographic appearance. Although, of the 27 matched pairs identified, significantly fewer of the pentamidine cohort were treated as inpatients, and significantly more of this cohort had upper lobe dominant disease on chest radiograph, we found no other significant differences between markers of clinical severity for the two cohorts. In addition, we found no significant differences in the rate of sputum or bronchoalveolar lavage positivity for P. carinii between the two cohorts. We conclude that, although hospitalization is less common in patients with a history of prophylactic pentamidine use, aerosolized pentamidine prophylaxis does not decrease the clinical severity or the sensitivities of sputum induction or bronchoalveolar lavage as diagnostic tests for PCP.
View details for Web of Science ID A1992JR47100006
View details for PubMedID 1416408
TOXOPLASMA-GONDII PNEUMONITIS IN PATIENTS INFECTED WITH THE HUMAN-IMMUNODEFICIENCY-VIRUS
ARCHIVES OF INTERNAL MEDICINE
1992; 152 (5): 1073-1077
Pulmonary toxoplasmosis is a rarely recognized opportunistic infection in immunocompromised patients. A few case reports have described pulmonary toxoplasmosis in human immunodeficiency virus-infected patients in association with Toxoplasma gondii central nervous system disease. We encountered six cases of pulmonary toxoplasmosis in human immunodeficiency virus-infected patients who presented with a protracted febrile illness, respiratory symptoms, and an abnormal chest roentgenogram in the absence of neurologic findings. No clinical or roentgenographic features distinguished T gondii pneumonitis from more common opportunistic pulmonary infections. As the acquired immunodeficiency syndrome epidemic progresses, the presenting illnesses have evolved. Toxoplasma gondii must be considered a potential cause of pulmonary disease during the evaluation of human immunodeficiency virus-infected patients with respiratory symptoms.
View details for Web of Science ID A1992HU61600026
View details for PubMedID 1304722
CLINICAL AND PATHOLOGICAL FEATURES OF BACILLARY PELIOSIS HEPATIS IN ASSOCIATION WITH HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION
NEW ENGLAND JOURNAL OF MEDICINE
1990; 323 (23): 1581-1586
Peliosis hepatis is characterized by cystic, blood-filled spaces in the liver and is seen in patients with chronic infections or advanced cancer and as a consequence of therapy with anabolic steroids. Cutaneous bacillary angiomatosis is a bacterial infection that occurs in patients with human immunodeficiency virus (HIV) infection; its histologic appearance is that of a pseudoneoplastic vascular proliferation.We studied liver tissue from eight HIV-infected patients with peliosis hepatis, two of whom also had cutaneous bacillary angiomatosis. For comparison we examined tissue from four patients who had peliosis hepatis without HIV infection. Tissues were examined histologically on routine sections and with special stains and electron microscopy.The histologic features seen in peliosis hepatis associated with HIV infection, but not in the four cases unrelated to HIV infection, were myxoid stroma and clumps of a granular purple material that on Warthin-Starry staining and electron microscopy proved to be bacilli. The bacilli, which could not be cultured, were morphologically identical to those found in the skin lesions of cutaneous bacillary angiomatosis. The clinical courses of two of the patients with this "bacillary peliosis hepatis" indicate that it responds to antibiotic treatment.HIV-associated bacillary peliosis hepatis is an unusual, treatable opportunistic infection, probably caused by the same organism that causes cutaneous bacillary angiomatosis. Our failure to find bacilli in non-HIV-associated cases implies that other pathogenetic mechanisms may also be responsible for peliosis hepatis.
View details for Web of Science ID A1990EK69600002
View details for PubMedID 2233946