Clinical Chemistry

273 Pages·2007·6.78 MB·English

April 1 2007, Volume 53, Issue 4 , pp.543-806

Editorials:

Glen L. Hortin
A New Era in Protein Quantification in Clinical Laboratories: Application of
Liquid Chromatography-Tandem Mass Spectrometry
Clin Chem 2007 53: 543-544.

Current Issues in Laboratory Medicine:

Curtis A. Parvin and Sanford Robbins, III
Evaluation of the Performance of Randomized versus Fixed Time Schedules
for Quality Control Procedures
Clin Chem 2007 53: 575-580. Published online February 22, 2007;
10.1373/clinchem.2006.083311

Molecular Diagnostics and Genetics:

Peng Hou, Zaozao Chen, Meiju Ji, Nongyue He, and Zuhong Lu
Real-time PCR Assay for Ultrasensitive Quantification of DNA-Binding
Proteins
Clin Chem 2007 53: 581-586. Published online February 8, 2007;
10.1373/clinchem.2006.077503
Claudia Langebrake, Kalle Günther, Jürgen Lauber, and Dirk Reinhardt
Preanalytical mRNA Stabilization of Whole Bone Marrow Samples
Clin Chem 2007 53: 587-593. Published online February 8, 2007;
10.1373/clinchem.2006.078592

Constance L.H. Lo, Shea Ping Yip, Peter K.C. Cheng, Tony S.S. To, Wilina W.L. Lim,
and Polly H.M. Leung
One-Step Rapid Reverse Transcription–PCR Assay for Detecting and Typing
Dengue Viruses with GC Tail and Induced Fluorescence Resonance Energy
Transfer Techniques for Melting Temperature and Color Multiplexing
Clin Chem 2007 53: 594-599. Published online February 22, 2007;
10.1373/clinchem.2006.077446
Wolfgang Lalouschek, Georg Endler, Martin Schillinger, Kety Hsieh, Wilfried Lang,
Suzanne Cheng, Peter Bauer, Oswald Wagner, and Christine Mannhalter
Candidate Genetic Risk Factors of Stroke: Results of a Multilocus
Genotyping Assay
Clin Chem 2007 53: 600-605. Published online February 22, 2007;
10.1373/clinchem.2006.073494
Natale Scaramozzino, Audrey Ferrier-Rembert, Anne-laure Favier, Corinne
Rothlisberger, Stéphane Richard, Jean-Marc Crance, Hermann Meyer, and Daniel Garin
Real-Time PCR to Identify Variola Virus or Other Human Pathogenic
Orthopox Viruses
Clin Chem 2007 53: 606-613. Published online March 1, 2007;
10.1373/clinchem.2006.068635

Evidence-Based Laboratory Medicine and Test
Utilization:

Robert H. Christenson
National Academy of Clinical Biochemistry Laboratory Medicine Practice
Guidelines for Utilization of Biochemical Markers in Acute Coronary
Syndromes and Heart Failure
Clin Chem 2007 53: 545-546. Published online March 23, 2007;
10.1373/clinchem.2006.079749
NACB WRITING GROUP MEMBERS, Fred S. Apple, Robert L. Jesse, L. Kristin
Newby, Alan H.B. Wu, Robert H. Christenson, NACB COMMITTEE MEMBERS,
Robert H. Christenson, Fred S. Apple, Christopher P. Cannon, Gary Francis, Robert
Jesse, David A. Morrow, L. Kristin Newby, Jan Ravkilde, Alan B. Storrow, Wilson Tang,
Alan H.B. Wu, IFCC COMMITTEE ON STANDARDIZATION OF MARKERS OF
CARDIAC DAMAGE (C-SMCD) MEMBERS, Fred S. Apple, Robert H. Christenson,
Allan S. Jaffe, Johannes Mair, Jordi Ordonez-Llanos, Franca Pagani, Mauro Panteghini,
Jillian Tate, and Alan H.B. Wu
National Academy of Clinical Biochemistry and IFCC Committee for
Standardization of Markers of Cardiac Damage Laboratory Medicine
Practice Guidelines: Analytical Issues for Biochemical Markers of Acute
Coronary Syndromes
Clin Chem 2007 53: 547-551. Published online March 23, 2007;
10.1373/clinchem.2006.084715

NACB WRITING GROUP MEMBERS, David A. Morrow, Christopher P. Cannon,
Robert L. Jesse, L. Kristin Newby, Jan Ravkilde, Alan B. Storrow, Alan H.B. Wu, Robert
H. Christenson, NACB COMMITTEE MEMBERS, Robert H. Christenson, Fred S.
Apple, Christopher P. Cannon, Gary Francis, Robert L. Jesse, David A. Morrow, L.
Kristin Newby, Jan Ravkilde, Alan B. Storrow, Wilson Tang, and Alan H.B. Wu
National Academy of Clinical Biochemistry Laboratory Medicine Practice
Guidelines: Clinical Characteristics and Utilization of Biochemical Markers
in Acute Coronary Syndromes
Clin Chem 2007 53: 552-574. Published online March 23, 2007;
10.1373/clinchem.2006.084194

Hemostasis and Thrombosis:

Boris T. Ivandic, Evangelos Giannitsis, Philipp Schlick, Peter Staritz, Hugo A. Katus,
and Thomas Hohlfeld
Determination of Aspirin Responsiveness by Use of Whole Blood Platelet
Aggregometry
Clin Chem 2007 53: 614-619. Published online March 1, 2007;
10.1373/clinchem.2006.081059

Proteomics and Protein Markers:

Erwin H.J.M. Kemna, Harold Tjalsma, Vladimir N. Podust, and Dorine W. Swinkels
Mass Spectrometry–Based Hepcidin Measurements in Serum and Urine:
Analytical Aspects and Clinical Implications
Clin Chem 2007 53: 620-628. Published online February 1, 2007;
10.1373/clinchem.2006.079186
Christian Melle, Günther Ernst, Niko Escher, Daniel Hartmann, Bettina Schimmel,
Annett Bleul, Heike Thieme, Roland Kaufmann, Klaus Felix, Helmut M. Friess, Utz
Settmacher, Merten Hommann, Konrad K. Richter, Wolfgang Daffner, Horst Täubig,
Thomas Manger, Uwe Claussen, and Ferdinand von Eggeling
Protein Profiling of Microdissected Pancreas Carcinoma and Identification
of HSP27 as a Potential Serum Marker
Clin Chem 2007 53: 629-635. Published online February 15, 2007;
10.1373/clinchem.2006.079194
Amelie Plymoth, Claes-Göran Löfdahl, Ann Ekberg-Jansson, Magnus Dahlbäck, Per
Broberg, Martyn Foster, Thomas E. Fehniger, and György Marko-Varga
Protein Expression Patterns Associated with Progression of Chronic
Obstructive Pulmonary Disease in Bronchoalveolar Lavage of Smokers
Clin Chem 2007 53: 636-644. Published online February 15, 2007;
10.1373/clinchem.2006.076075

John F. Timms, Elif Arslan-Low, Aleksandra Gentry-Maharaj, Zhiyuan Luo, Davy
T’Jampens, Vladimir N. Podust, Jeremy Ford, Eric T. Fung, Alex Gammerman, Ian
Jacobs, and Usha Menon
Preanalytic Influence of Sample Handling on SELDI-TOF Serum Protein
Profiles
Clin Chem 2007 53: 645-656. Published online February 15, 2007;
10.1373/clinchem.2006.080101
Minna A. Korolainen, Tuula A. Nyman, Paula Nyyssönen, E. Samuel Hartikainen, and
Tuula Pirttilä
Multiplexed Proteomic Analysis of Oxidation and Concentrations of
Cerebrospinal Fluid Proteins in Alzheimer Disease
Clin Chem 2007 53: 657-665. Published online February 8, 2007;
10.1373/clinchem.2006.078014

Cancer Diagnostics:

Heather L. Beyer, Ryan D. Geschwindt, Curtis L. Glover, Ly Tran, Ingegerd Hellstrom,
Karl-Erik Hellstrom, M. Craig Miller, Thorsten Verch, W. Jeffrey Allard, Harvey I. Pass,
and Niranjan Y. Sardesai
MESOMARKTM: A Potential Test for Malignant Pleural Mesothelioma
Clin Chem 2007 53: 666-672. Published online February 8, 2007;
10.1373/clinchem.2006.079327
Olga P. Bondar, David R. Barnidge, Eric W. Klee, Brian J. Davis, and George G. Klee
LC-MS/MS Quantification of Zn- 2 Glycoprotein: A Potential Serum
Biomarker for Prostate Cancer
Clin Chem 2007 53: 673-678. Published online February 22, 2007;
10.1373/clinchem.2006.079681

Lipids, Lipoproteins, and Cardiovascular Risk Factors:

Gregory T. Jones, Andre M. van Rij, Jennifer Cole, Michael J.A. Williams, Emma H.
Bateman, Santica M. Marcovina, Meiying Deng, and Sally P.A. McCormick
Plasma Lipoprotein(a) Indicates Risk for 4 Distinct Forms of Vascular
Disease
Clin Chem 2007 53: 679-685. Published online February 15, 2007;
10.1373/clinchem.2006.079947
Yoosoo Chang, Seungho Ryu, Eunju Sung, and Yumi Jang
Higher Concentrations of Alanine Aminotransferase within the Reference
Interval Predict Nonalcoholic Fatty Liver Disease
Clin Chem 2007 53: 686-692. Published online February 1, 2007;
10.1373/clinchem.2006.081257

Renke Maas, Friedrich Schulze, Jens Baumert, Hannelore Löwel, Khatera Hamraz,
Edzard Schwedhelm, Wolfgang Koenig, and Rainer H. Böger
Asymmetric Dimethylarginine, Smoking, and Risk of Coronary Heart
Disease in Apparently Healthy Men: Prospective Analysis from the
Population-Based Monitoring of Trends and Determinants in Cardiovascular
Disease/Kooperative Gesundheitsforschung in der Region Augsburg Study
and Experimental Data
Clin Chem 2007 53: 693-701. Published online February 22, 2007;
10.1373/clinchem.2006.081893

Drug Monitoring and Toxicology:

Frank T. Peters, Nele Samyn, Thomas Kraemer, Wim J. Riedel, and Hans H. Maurer
Negative-Ion Chemical Ionization Gas Chromatography–Mass Spectrometry
Assay for Enantioselective Measurement of Amphetamines in Oral Fluid:
Application to a Controlled Study with MDMA and Driving Under the
Influence Cases
Clin Chem 2007 53: 702-710. Published online March 1, 2007;
10.1373/clinchem.2006.081547

Endocrinology and Metabolism:

Santica Marcovina, Ronald R. Bowsher, W. Greg Miller, Myrlene Staten, Gary Myers,
Samuel P. Caudill, Scott E. Campbell, Michael W. Steffes for the Insulin Standardization
Workgroup
Standardization of Insulin Immunoassays: Report of the American Diabetes
Association Workgroup
Clin Chem 2007 53: 711-716. Published online February 1, 2007;
10.1373/clinchem.2006.082214
Kristina Anna Strnadová, Margareta Holub, Adolf Mühl, Georg Heinze, Rene
Ratschmann, Hermann Mascher, Sylvia Stöckler-Ipsiroglu, Franz Waldhauser, Felix
Votava, Jan Lebl, and Olaf A. Bodamer
Long-Term Stability of Amino Acids and Acylcarnitines in Dried Blood
Spots
Clin Chem 2007 53: 717-722. Published online February 1, 2007;
10.1373/clinchem.2006.076679
Henri Déchaud, Anne Denuzière, Sabina Rinaldi, Julien Bocquet, Hervé Lejeune, and
Michel Pugeat
Age-Associated Discrepancy between Measured and Calculated Bioavailable
Testosterone in Men
Clin Chem 2007 53: 723-728. Published online February 22, 2007;
10.1373/clinchem.2006.077362

Antoon J.M. Janssen, Frans J.M. Trijbels, Rob C.A. Sengers, Jan A.M. Smeitink,
Lambert P. van den Heuvel, Liesbeth T.M. Wintjes, Berendien J.M. Stoltenborg-
Hogenkamp, and Richard J.T. Rodenburg
Spectrophotometric Assay for Complex I of the Respiratory Chain in Tissue
Samples and Cultured Fibroblasts
Clin Chem 2007 53: 729-734. Published online March 1, 2007;
10.1373/clinchem.2006.078873

Automation and Analytical Techniques:

John Middleton and Jeffrey E. Vaks
Evaluation of Assigned-Value Uncertainty for Complex Calibrator Value
Assignment Processes: A Prealbumin Example
Clin Chem 2007 53: 735-741. Published online February 15, 2007;
10.1373/clinchem.2006.081174
Johanna E.M. Groener, Ben J.H.M. Poorthuis, Sijmen Kuiper, Mariette T.J. Helmond,
Carla E.M. Hollak, and Johannes M.F.G. Aerts
HPLC for Simultaneous Quantification of Total Ceramide,
Glucosylceramide, and Ceramide Trihexoside Concentrations in Plasma
Clin Chem 2007 53: 742-747. Published online March 1, 2007;
10.1373/clinchem.2006.079012
Duncan C.S. Talbot, Richard M. Ogborne, Tony Dadd, Herman Adlercreutz, Geoff
Barnard, Susanne Bugel, Fortune Kohen, Sandra Marlin, Jerry Piron, Aedin Cassidy, and
Jonathan Powell
Monoclonal Antibody-Based Time-Resolved Fluorescence Immunoassays for
Daidzein, Genistein, and Equol in Blood and Urine: Application to the
Isoheart Intervention Study
Clin Chem 2007 53: 748-756. Published online February 22, 2007;
10.1373/clinchem.2006.075077

Clinical Immunology:

Santosh K. Ghosh, Thomas A. Gerken, Keith M. Schneider, Zhimin Feng, Thomas S.
McCormick, and Aaron Weinberg
Quantification of Human ß-Defensin-2 and -3 in Body Fluids: Application
for Studies of Innate Immunity
Clin Chem 2007 53: 757-765. Published online February 22, 2007;
10.1373/clinchem.2006.081430

Other Areas of Clinical Chemistry:

Andrew S. Levey, Josef Coresh, Tom Greene, Jane Marsh, Lesley A. Stevens, John W.
Kusek, Frederick Van Lente for Chronic Kidney Disease Epidemiology Collaboration
Expressing the Modification of Diet in Renal Disease Study Equation for
Estimating Glomerular Filtration Rate with Standardized Serum Creatinine
Values
Clin Chem 2007 53: 766-772. Published online March 1, 2007;
10.1373/clinchem.2006.077180
Markus Herrmann, Omid Taban-Shoma, Ulrich Hübner, Anette Pexa, Heiko Kilter,
Natalia Umanskaya, Rainer Hans Straub, Michael Böhm, and Wolfgang Herrmann
Hyperhomocysteinemia and Myocardial Expression of Brain Natriuretic
Peptide in Rats
Clin Chem 2007 53: 773-780. Published online February 15, 2007;
10.1373/clinchem.2006.077859

Technical Briefs:

Zia Fazili, Christine M. Pfeiffer, and Mindy Zhang
Comparison of Serum Folate Species Analyzed by LC-MS/MS with Total
Folate Measured by Microbiologic Assay and Bio-Rad Radioassay
Clin Chem 2007 53: 781-784. Published online February 1, 2007;
10.1373/clinchem.2006.078451
Hsiao-Mei Wiedmeyer, Kenneth S. Polonsky, Gary L. Myers, Randie R. Little, Carla J.
Greenbaum, David E. Goldstein, and Jerry P. Palmer
International Comparison of C-Peptide Measurements
Clin Chem 2007 53: 784-787. Published online March 1, 2007;
10.1373/clinchem.2006.081570
Ulrike Haug, Timo Hillebrand, Peter Bendzko, Michael Löw, Dietrich Rothenbacher,
Christa Stegmaier, and Hermann Brenner
Mutant-Enriched PCR and Allele-Specific Hybridization Reaction to Detect
K-ras Mutations in Stool DNA: High Prevalence in a Large Sample of Older
Adults
Clin Chem 2007 53: 787-790. Published online February 22, 2007;
10.1373/clinchem.2006.078188
Christina Dahl, Karen Grønskov, Lars A. Larsen, Per Guldberg, and Karen Brøndum-
Nielsen
A Homogeneous Assay for Analysis of FMR1 Promoter Methylation in
Patients with Fragile X Syndrome
Clin Chem 2007 53: 790-793. Published online January 26, 2007;
10.1373/clinchem.2006.080762

Letters to the Editor:

Birger Mensel, Ulrike Wenzel, Markus Roser, Jan Lüdemann, and Matthias Nauck
Considerably Reduced Centrifugation Time without Increased Hemolysis:
Evaluation of the New BD Vacutainer® SSTTMII Advance
Clin Chem 2007 53: 794-795.
Helen L. Bailey and Emily M. Chan
Liposomal Amphotericin B Interferes with the Phosphorus Assay on the
Synchron LX 20 Analyzer
Clin Chem 2007 53: 795-796.
Fiona M.F. Lun, Rossa W.K. Chiu, Tak Y. Leung, Tse N. Leung, Tze K. Lau, and Y.M.
Dennis Lo
Epigenetic Analysis of RASSF1A Gene in Cell-Free DNA in Amniotic Fluid
Clin Chem 2007 53: 796-798.
Mariasilvia Tommasi and Silvia Raspanti
Comparison of Calcitonin Determinations by Polyclonal and Monoclonal
IRMAs
Clin Chem 2007 53: 798-799.
Stanley F. Lo, Bernadine Jendrzejczak, and Basil T. Doumas
Total or Neonatal Bilirubin Assays in the Vitros 5,1 FS: Hemoglobin
Interference, Hemolysis, Icterus Index
Clin Chem 2007 53: 799-800.
Geralyn Lambert-Messerlian, Christina Bandera, Elizabeth Eklund, Andrew Neuhauser,
and Jacob Canick
Very High Inhibin A Concentration Attributed to Heterophilic Antibody
Interference
Clin Chem 2007 53: 800-801.
Sarah Molyneux, Michael Lever, Christopher Florkowski, and Peter George
Plasma Total Coenzyme Q9 (CoQ9) in the New Zealand Population:
Reference Interval and Biological Variation
Clin Chem 2007 53: 802-803.
Etienne Cavalier, Pierre Delanaye, Jean-Marie Krzesinski, and Jean-Paul Chapelle
Analytical Variation in Plasma Renin Activity: Implications for the
Screening of Primary Aldosteronism
Clin Chem 2007 53: 803-804.
Katherine Duxbury, Louise Gallagher, and Brian Keevil
The Impact of Simultaneous Measurement of Testosterone and
Androstenedione in Women with Suspected Androgen Excess
Clin Chem 2007 53: 804-805.

Book, Software, and Web Site Reviews:

Roland Valdes, Jr
An A-Z Guide to Pharmacogenomics. Michael G. Catania. Washington DC:
AACC Press, 2006, 58 pp., $24 ($19 AACC members), softcover. ISBN 1-
59425-047-2.
Clin Chem 2007 53: 806.
Emily S. Winn-Deen
Pharmacogenomics, Second Edition. Werner Kalow, Urs B. Meyer, and
Rachel F. Tyndale, eds. Boca Raton, FL: Taylor & Francis Group, 2005, 696
pp., $199.95, hardcover. ISNB 1-57444-878-1.
Clin Chem 2007 53: 806.

Corrections:

Correction
Clin Chem 2007 53: 805.

A New Era in Protein Quantification in Clinical Laboratories:
Application of Liquid Chromatography-Tandem Mass Spectrometry

In this issue of Clinical Chemistry, Bondar and coworkers
at the Mayo Clinic report on development of a quantita-
tive liquid chromatography-tandem mass spectrometry
(LC-MS/MS) assay for zinc-�2-glycoprotein (1). The assay
described may be more notable for the approach em-
ployed rather than for the specific analyte. Unlike most
current clinical laboratory assays of proteins, the ap-
proach used does not rely on the specificity of antibodies
for capture and detection. Instead, the assay described by
Bondar et al. cleaves the protein into small peptides by
proteolysis with trypsin. By use of LC-MS/MS, one of the
peptide fragments released from zinc-�2-glycoprotein is
ratioed vs a stable isotope-labeled form of the same
peptide. The method serves as an example of an approach
to protein quantification that does not require specific
antibody reagents and may be broadly applicable.
The instrument used for this analysis, an LC-triple
quadrupole mass spectrometer, is an increasingly com-
mon tool in the clinical laboratory. Its range of applica-
tions now includes routine assays for (a) detecting inborn
errors of metabolism, (b) monitoring therapeutic drugs,
and (c) quantifying steroid and thyroid hormones. The
technology provides high selectivity and high throughput
in a clinical laboratory environment. MS/MS usually
offers high specificity, even in complex sample matrices,
through selection of a specific precursor ion in the first
mass analyzer and selection of a specific fragment ion
formed during passage of the precursor ion through a
collision cell. Experience analyzing therapeutic drugs and
hormones in blood shows the ability of the method to
measure components down to nanomole per liter concen-
trations. Considering that each of the 30 most abundant
plasma proteins usually has concentrations well over 1
�mol/L (2), many proteins are likely to be sufficiently
abundant for analysis by this technique in unfractionated
specimens. Low abundance proteins, with concentrations
�1 nmol/L, however, are likely to require some form of
fractionation or concentration, such as immunocapture of
the target protein or peptide (3).
The report by Bondar et al. (1) is but one of numerous
reports describing the application of LC-MS/MS to the
quantification of proteins for research purposes. Most of
these studies have described approaches for relative
quantification by use of differential isotopic labeling of
paired specimens (4). A number of reports describe the
absolute quantification of proteins through use of stable
isotope-labeled internal standard peptides (3, 5–8). Such
internal standards can readily be prepared, either by
chemical synthesis or by in vitro translation. Most of the
applications developed in research laboratories, however,
have relied on capillary LC, nanospray interfaces, and ion
trap or other types of mass spectrometers not commonly
found in clinical laboratories (3, 4, 6–8). These LC-
MS/MS techniques may be more challenging to apply as
routine analytical techniques than the LC-MS/MS ap-

proaches commonly applied in clinical laboratories. Al-
though the report by Bondar et al. (1) conceptually does
not break new ground in its analytical approach, it does
illustrate how quantitative analysis of proteins by LC-
MS/MS is becoming a practical technique for clinical
laboratories to implement, using equipment that currently
is applied to other clinical analyses.
There has been some question about how new technol-
ogies developed for proteomic analysis will impact the
clinical laboratory (2, 9–11). Profiling of intact peptides or
proteins by 2-dimensional electrophoresis or matrix-
assisted laser desorption time-of-flight mass spectrome-
ters serves as a discovery tool for top-down proteomics.
Chromatographic separations of proteolytic digests of
proteins analyzed by ion trap or Fourier-transform ion
cyclotron resonance mass spectrometers offer approaches
for bottom-up proteomics. These approaches, however,
present substantial challenges for routine clinical applica-
tion and for achieving the usual standards of clinical
laboratory practice (12). In contrast, multiple reaction
monitoring in LC-MS/MS, using triple-quadrupole mass
spectrometers, is a proven clinical laboratory technique
for quantitative analysis of molecules in complex matrices
such as serum and plasma. Application of this technique
to protein analysis shows promise for providing high
accuracy and analytical specificity, and should be readily
adaptable to simultaneous multiplex analysis of many
proteins. The one major limitation of this technique, from
the standpoint of proteomic analysis, is that it is a targeted
approach, which requires foreknowledge of which pro-
teins to analyze. This characteristic can be a drawback
from the standpoint of marker discovery, but not neces-
sarily from the standpoint of a clinical assay, for which
analytes preferably are known entities.
It is becoming increasingly evident that new technolo-
gies evolving from proteomics research are not simply of
academic or research interest. LC-MS/MS employing
multiple reaction monitoring is one example of a new
technology for protein analysis that is likely to have
substantial practical impact in clinical laboratories. One of
the most immediate consequences of the application of
this technology is the development of new reference
methods to standardize protein assays. Two recent exam-
ples are restandardization of laboratory measures of he-
moglobin A1c (13) and C-peptide (14). This approach is
likely to be applied progressively to standardization of a
wider range of protein assays, such as for urine albumin
using a recently described LC-MS/MS technique (15).
Because LC-MS/MS measures the abundance of only one
peptide segment of a protein, expression of the abundance
of this peptide in units of molarity rather than mass/
volume generally is more appropriate, and it may be
possible to develop chemically-synthesized peptides that
can serve as reference materials for standardization of
protein assays. Finally, the ability to measure the concen-

Editorial

Clinical Chemistry 53, No. 4, 2007
543

tration of any protein of sufficient abundance, without the
need for purified reference preparations or specific anti-
bodies, should accelerate the discovery and application of
measurements
of
additional
proteins
for
diagnostic
applications.

References
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Glen L. Hortin

Department of Laboratory Medicine
National Institutes of Health,
Building 10, Room 2C-407,
Bethesda, MD 20892
Fax [phone]
E-mail