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W O R L D ’ S C L I N I C A L L A B O R AT O RY N E W S L E A D E R
ISSN 1068-1760
Vol. 30 No. 4 • 6-7/ 2013
Diagnostic Blood Test for
Fibromyalgia Developed
C
ytokine-producing activity of
immune cells of fibromyalgia
(FM) patients has led to the development of a commercial blood test.
The very real biological condition
of FM takes an average of three to
five years for someone with the illness to get an accurate diagnosis as
hitherto there was no diagnostic
Noninvasive Prenatal Test Screens
Blood for Chromosomal Abnormalities
P
hysicians will have access to a
new noninvasive prenatal test,
which uses cell-free fetal DNA in
circulating maternal blood.
The test, called Panorama, uses
cell-free fetal DNA in circulating
maternal blood to screen for chromosomal abnormalities associated
with trisomy 21 (Down syndrome),
novel molecular diagnostic
platform with high sensitivity
and specificity has been developed
for the early detection of the Chikungunya virus (CHIKV).
Chikungunya has reemerged as
an important arboviral infection of
global health significance and
because of lack of a vaccine and
Cont’d on page 33
Cont’d on page 8
Image: Courtesy of Georgetown University Hospital
A
cutting-edge technology has
been developed that can successfully screen human blood for
disease markers that may hold the
key to better diagnosing and understanding of puzzling health conditions, including autoimmune diseases. The technology accurately
identified human blood markers for
blood test that tracks
fragments of DNA shed
by dying tumor cells could
be used to monitor how well
patients are responding to
cancer treatment, as well as
provide a non-invasive alternative to biopsies in advanced breast cancer.
A
Cont’d on page 4
INSIDE
Image: A cluster of breast cancer
cells showing visual evidence of
programmed cell death
See article on page 13
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A
Process Offers Potential
for New Biomarkers
Blood Test Tracks
Response to Cancer
Treatment
I
Rapid Molecular Test
for Chikungunya Virus
trisomy 18 (Edwards syndrome), trisomy 13 (Patau syndrome) and
monosomy X (Turner syndrome).
Panorama can be used as early as
the ninth week of pregnancy.
In December 2012, the American
Congress of Obstetricians and Gynecologists (ACOG) issued a medical
opinion stating that cell-free fetal
Cont’d on page 6
V
DAILY CLINICAL LAB NEWS
Fully-Automated von Willebrand
Factor Assay Panel Released
he HemosIL AcuStar
VWF assay panel offers the first fully-automated
chemiluminescent system
to use recombinant technology, allowing greater precision than platelet-based
tests.
T
Clinical News . . . . . . . 4-60
IFCC News . . . . . . . . . . . 61
EFLM Corner . . . . . . . . . .66
Product News . . . . . 22-46
Technical Literature 58, 60
Industry News . . . . . . . . .68
International Calendar . 69
PUBLISHED IN COOPERATION WITH
See article on page 4
Prostate Cancer Test
Closer to Clinical Trial
A
Novel Biomarker Detects
Deadly Lymphoma
A
breakthrough urine biomarker for
prostate cancer will soon be available which will signal a significant step
forward in the battle against prostate
cancer. A protein called Engrailed-2
(EN2) is made by prostate cancers and
secreted into urine where it can easily
be detected in a small urine sample
novel diagnostic test accurately
identifies patients who have a
new type of deadly intestinal lymphoma that is particularly common in
Asia. The test will have an immediate
impact on patient care, with doctors
now able to diagnose patients accurately and tailor more effective treatment
Cont’d on page 4
Cont’d on page 8
International Federation
of Clinical Chemistry
and Laboratory Medicine
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LabMedica
Process Offers Potential for New Biomarkers
cont’d from cover
neuromyelitis optica (NMO), a rare autoimmune disorder resembling multiple sclerosis that can result in
blindness and paralysis, by substituting antibodybinding targets with biologically unnatural molecules
called peptoids.
Scientists at Scripps Research Institute (Jupiter,
FL, USA; www.scripps.edu) identified several peptoids that bound exclusively to antibodies in NMO
patient blood serum and not healthy patients or
patients with similar diseases, including multiple
sclerosis (MS), lupus, Alzheimer’s disease (AD) and
narcolepsy. At least one of the peptoids bound to an
antibody that is well known to be associated with
NMO.
The team used the chemical library screening
technology to identify a synthetic peptoid that
binds anti-Aquaporin 4 (AQP4) antibodies in the
serum of NMO patients. After processing the
serum, slides were scanned on a GenePix 4200AL
microarray
scanner
(Molecular
Devices;
Sunnyvale, CA, USA; www.moleculardevices.com)
by using the 488/635 nm laser at 100% power and
a 500-photomultiplier-tube gain.
The investigators screened 100,000 peptoids using
a second-generation bead-based screening approach
that yielded several peptoid ligands for the antigenbinding site of anti-AQP4 antibodies. They showed in
a small preliminary study that the use of a small panel
of these peptoids allows one to distinguish between
NMO patient serum and serum from healthy controls
or patients with MS, AD, narcolepsy, and lupus with
high accuracy.
Thomas Kodadek, PhD, the senior author of the
study, said, “We find disease biomarkers differently
than anyone else. This enables new disease biomarker detection. Additionally, by using these peptoid hits
to ‘fish’ for disease-specific antibodies, the system
enables disease-specific antibody detection without
first knowing the antibodies’ natural binding targets.”
The study was published on March 21, 2013, in the
journal Chemistry & Biology.
Fully-Automated von Willebrand Factor Assay Panel Released
fully automated von Willebrand Factor assay has
been released in Europe and international territories
as a European CE in vitro diagnostic (IVD) Mark product
under the European Directive on in vitro Diagnostic
Medical Devices but not currently [US FDA] 510(k)
cleared. A product of Instrumentation Laboratories
(Bedford, MA, USA; www.instrumentationlaboratory.
com/ilww), the fully automated HemosIL AcuStar VWF
assay panel, designed exclusively for use on the ACL
AcuStar Hemostasis Testing System, includes HemosIL
AcuStar VWF Antigen (VWF:Ag) and HemosIL AcuStar
VWF Ristocetin Cofactor (VWF:RCo) Activity assays.
HemosIL AcuStar VWF:RCo is the first fully automated, chemiluminescent assay to use recombinant technology, allowing full automation and greater precision than
platelet-based tests. It meets guidelines on VDF investigation and enhances accuracy versus manual methods.
Chemiluminescence offers an enhanced linearity range to
quantify extremely low levels of VWF concentrations.
Like all reagents on the ACL AcuStar System,
HemosIL AcuStar VWF assays are ready-to-use, cartridge-based and offer results in 30 minutes – ondemand, 24/7. This is the third specialty assay panel
A
commercialized on the ACL AcuStar system. Previously
introduced panels include Antiphospholipid Syndrome
and Heparin-Induced Thrombocytopenia.
“With the ACL AcuStar Hemostasis Testing System,
our goal is to automate complex assays and offer
enhanced efficiency and sensitivity where it matters
most,” said Remo Tazzi, Director of Hemostasis
Marketing at IL. “Our new HemosIL AcuStar VWF
assays achieve this, allowing clinicians to make quicker
and more effective patient care decisions.”
VDF is an acquired or inherited bleeding disorder,
caused by a qualitative or quantitative defect of the
VWF protein. Whereas hemophilia mainly affects
males, VDF is not gender-specific. The disease affects
over 1% of the worldwide population and occurs in
1/100–100,000 people with hemophilia. Acquired
VDF can be associated with serious autoimmune problems (e.g., rheumatoid arthritis, systemic lupus erythematosus, and specific types of kidney failure or cancers)
and may develop with no underlying conditions.
Certain kinds of VDF may remain undiagnosed because
symptoms can be mild. Prompt diagnosis and classification are necessary for optimal therapeutic management.
Prostate Cancer Test Closer to Clinical Trial
cont’d from cover
from men, allowing faster testing that could save lives
and offer the potential for huge cost savings. The
University of Surrey (Guildford, UK; www.surrey.ac.uk)
where the test was originally developed has signed a
worldwide nonexclusive agreement with international
diagnostic specialist Zeus Scientific (Raritan, NJ, USA;
www.zeusscientific.com) to develop and market its
breakthrough urine biomarker, EN2. Urinary EN2 levels can be measured by an enzyme-linked immunosorbent assay and higher EN2 levels correlated with the
stage of the tumor.
In a joint statement, the University and the Prostate
Project Charity (Godalming, UK; www.prostate-project.
org.uk) who jointly funded the research, said: “This is
the news we have all been waiting for. In two years of
extensive trials in the USA and Europe, EN2 has consis-
tently outperformed the 30-year-old prostate-specific
antigen (PSA) test proving itself to be twice as effective
at finding prostate cancer. Its accuracy has never been in
doubt, but it has proved difficult to bulk test urine samples using conventional assay technology. Now, Zeus
Scientific, one of the leaders in this field is confident it
can overcome the problems and bring EN2 to market.”
Hardev Pandha MD, PhD, professor of Medical
Oncology at the University of Surrey, said, “The
University of Surrey is looking forward very much to
working with Zeus to introduce EN2 as a novel diagnostic test for prostate and bladder cancers. Our tests
have shown that levels of EN2 correlate strongly with
disease volume. Knowledge of disease volume may
help urologists assess whether the patient has a small
volume of disease that may be safely and actively monitored or a larger volume that needs to be treated.”
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Diagnostic Blood Test Developed for Fibromyalgia
cont’d from cover
blood test to definitively confirm the disorder. The
blood test was developed in conjunction with a
study that identified unique immunologic patterns
in fibromyalgia patients. Scientists at the
University of Illinois at Chicago (UIC; IL USA;
www.uic.edu) measured plasma cytokine levels in
a group of 110 patients with a diagnosis of FM
and determined responses to mitogen challenges
of their peripheral blood mononuclear cells
(PBMC). The cytokine levels of these patients
were then compared with those in a group of 91
matched healthy controls.
A custom panel of antibody-conjugated beads
for measuring eight human cytokines (BioRad
Laboratories; Hercules, CA, USA; www.biorad.com) was used in the assay. The investigators
that cytokine levels of stimulated PBMC cultures
of healthy control subjects were significantly
increased as compared to matched nonstimulated
PBMC cultures. In contrast, the concentrations of
most cytokines were lower in stimulated samples
from patients with FM compared to controls.
The FM Test is the first test to objectively diagnose fibromyalgia via a simple blood test, with
results usually available in one week or less. The
FM Test was developed by EpicGenetics (Santa
Monica, CA, USA; www.epicgtx.com), and will
cost USD 744. The FM test is a multibiomarkerbased assay, which comprises immune system
white blood cell chemokine and cytokine patterns. Patients with fibromyalgia have a significantly dysregulated pattern regarding these proteins. Test results are based upon a 1-100 scoring
system, with fibromyalgia patients having scores
of 50 and above. The FM Test is more than 93%
sensitive and by comparison, the rheumatoid
arthritis blood test is only 65% sensitive.
Bruce S. Gillis, MD, MPH, the founder of
EpicGenetics, said, “The result was the discovery
of a major set of differences in cell-mediated
immunity in the fibromyalgia group versus the
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healthy patient, and this discovery was opposite to
what was anticipated. Specifically, while
fibromyalgia patients are often considered to be
‘hyper/overactive responders,’ we identified that
the fibromyalgia patients had a depressed and dysregulated immune system.” The original study the
test was based on was published on December
17, 2012, in the journal BMC Clinical Pathology.
Image: The FM test is designed to diagnose
fibromyalgia via a simple blood test (Photo courtesy
of EpicGenetics).
Novel Biomarker Identifies
Deadly Lymphoma
cont’d from cover
strategies to improve prognosis. Clinical scientists at
Singapore General Hospital (Singapore; www.
singhealth.com.sg) studied 60 patients with suspected epitheliotropic intestinal T-cell lymphoma (EATL
Type II) from nine different centers from 1999 to
2012. The median age at presentation was 58 years
(range: 23 to 83 years) with male predominance
(male–female ratio 2.6:1). The disease, almost
unheard of before 2008, has been classified as an
alternative type of enteropathy-associated T-cell lymphoma (EATL Type I), a disease common in
Caucasians and associated with celiac disease.
Immunohistochemical analysis of paraffin-embedded tumor sections was performed with a variety of
antibodies using the BONDMAX automated staining
machine (Leica Microsystems; Wetzlar, Germany;
www.leica-microsystems.com). Interphase fluorescence in situ hybridization (FISH) was performed
using the C-MYC break-apart and chromosome 8 centromeric probes (Abbott Laboratories; Abbott Park, IL,
USA; www.abbott.com) and FISH ancillary kit (DAKO
A/S; Glostrup, Denmark; www.dako.com).
The team has identified a novel biomarker,
known as megakaryocyte-associated tyrosine kinase
(MATK), and developed a diagnostic test that
enables clinicians to diagnose accurately patients
suffering from this type of lymphoma. Requests for
this test have come in from around the world,
including China and the USA. The disease was characterized by extensive nuclear expression of MATK
in 87% and in 88% there was usually a CD8+
CD56+ cytotoxic phenotype, there was frequent
aberrant expression of CD20 in 24%.
Lim Soon Thye, MD, a consultant oncologist and
senior author, said, “Our investigation has an immediate impact on the care we can provide to patients
with this rare but very aggressive intestinal lymphoma. With an accurate diagnosis, we can treat
our patients better and improve overall survival.”
The study was published on March 12, 2013, in the
journal Leukemia.
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Molecular Test Rapidly Detects Chikungunya Virus
cont’d from cover
effective treatment, rapid diagnosis plays an
important role in early clinical management of
patients. Scientists at the National University of
Singapore (Singapore; www.nus.edu.sg) collected
a total of 42 serum samples from 22 CHIKVinfected patients and 20 from uninfected individuals, to evaluate the clinical sensitivity and specificity of the developed test. All of the serum samples were validated using a real-time reverse transcriptase polymerase chain reaction (RT-PCR)
detection assay targeting the CHIKV envelope
glycoprotein1 gene.
The molecular test uses 2,7-diamino-1,8-naphthyridine derivative (DANP)-labeled cytosinebulge hairpin primers to amplify the nsP2 region
of the CHIKV genome, followed by measurement
of the fluorescence emitted from DANP-primer
complexes after PCR. RT-PCR was performed
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using the C1000 thermal cycler (Bio-Rad;
Hercules, CA, USA; www.bio-rad.com). Samples
were assayed after optimization with CHIKV
genomic RNA using AccessQuick Reverse
Transcription-PCR kit (Promega; Madison, WI,
USA; www.promega.com).
The detection limit of the assay was 0.01
plaque-forming units per reaction of CHIKV. The
primers were highly specific in detecting CHIKV,
without any cross-reactivity with the panel of
RNA viruses validated in the study. The feasibility
of the DANP-coupled hairpin RT-PCR for clinical
diagnosis was evaluated using clinical serum samples from CHIKV-infected patients, and the specificity was 100% and the sensitivity was 95.5%.
The authors concluded that the novel DANPcoupled hairpin RT-PCR technology is a simple,
rapid, and cost effective detection method for
CHIKV. The results from a patient sample evalua-
LMI-07-13 108
tion have indicated high clinical sensitivity and
specificity of this method. The method can be a
useful tool for rapid detection of CHIKV during
outbreaks or as a point-of-care molecular assay for
acute-phase patient serum samples in many parts
of the world. The study was published in the
March 2013 issue of the Journal of Molecular
Diagnostics.
Molecular Diagnostic Alliance
to Target Developing World
T
wo companies are collaborating to develop novel
molecular diagnostics (MoDx) for autoimmune,
cancer, and infectious diseases, among others.
Seegene (Seoul, Korea; www.seegene.com) and
Selventa (Cambridge, MA, USA; www.selventa.com)
together are developing MoDx for underserved diagnostic markets including autoimmune, cancer, and
infectious diseases. The synergistic combination of
Selventa’s Systems Diagnostics (SysDx) multi-omic
analytics platform and Seegene’s TOCE and DPO
multiplex polymerase chain reaction (PCR) technology should result in new MoDx that accelerate the
adoption of personalized medicine in major classes of
disease.
SysDx analyzes a holistic range of a patient’s
molecular information (e.g., genomic, epigenomic,
transcriptomic, proteomic, metabolomic, and electronic medical record information) to identify a panel
of “multi-omic” biomarkers that can accurately diagnose a patient’s disease and response or nonresponse
to a specific therapy. By leveraging multiplexing technology, SysDx’s multi-omic biomarker approach will
be the basis for a range of high value MoDx.
SysDx testing is a progression from “single-omic
tests that today are largely limited to the analyses of
genetic aberrations in a patient’s disease. As the
molecular drivers of disease are intertwined across
thousands of interrelated biochemical pathways, it is
vital that a diagnostic be able to test for a more comprehensive set of disease-relevant biomarkers.
Quantitative TOCE (qTOCE) technology provides
real-time simultaneous detection and quantification
of multiple targets in a single channel (“one channel–many targets”). This technology can work with
any qPCR instrument to differentiate as many as 7
targets per channel from a single sample, in a single
reaction. qTOCE enables multiplex assay development across a wide range of applications, including
high-multiplex quantitative real-time PCR and highly
selective mutational analysis.
“We are excited to collaborate with Seegene, a
leading molecular diagnostic technology innovator,”
said Dr. David de Graaf, president and CEO, Selventa.
“Seegene’s world-class detection technology and
assay development in combination with our SysDx
platform can result in a wide range of novel MoDx
with high clinical utility.”
Dr. Jong-Yoon Chun, founder, CTO and CEO of
Seegene added, “Selventa’s SysDx platform is a breakthrough approach to biomarker identification that has
the potential to vastly improve patient diagnosis and
care,” said “Our multiplex PCR technology detecting
a wide range of SysDx-derived biomarkers can facilitate better patient diagnostics, improved patient care,
and reduced healthcare costs.”
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Test Aids Diagnosis of Preeclampsia
test with high sensitivity and specificity level helps diagnosis of early onset
preeclampsia.
The triage placental growth factor
(PLGF) test is a fluorescence immunoassay,
which, when used in conjunction with a
Triage Meter enables the quantitative
determination of PLGF in ethylenediaminetetraacetic acid (EDTA) anticoagulated plasma samples. Together with other
diagnostic and clinical information, the test
aids in the diagnosis of preeclampsia.
The Alere (Linz, Austria; www.
alere.com) Triage PLGF test can provide a
PLGF level from a maternal plasma specimen in just 15 minutes. The Triage MeterPro is a portable fluorescence instrument used to measure the results of the
Triage tests from Alere. The Triage
MeterPro can be used in a laboratory or in
a point-of-care setting. It
uses a Class 1 laser as a light
source. Light from the laser
hits a test device that has
been inserted in the meter.
This causes the fluorescent
dye in the test device to give
off energy. The more energy
the fluorescent dye gives off,
the stronger the signal.
The current criteria for
defining preeclampsia (raised
A
Image: A study shows
that the Triage PLGF,
which measures the
placental growth factor
(PLGF), can quantify
risk in women when
preeclampsia is detected
(Photo courtesy of Alere).
blood pressure and protein in urine) are
nonspecific, appear late in the development
of the disease, and result in over diagnosis
because of their poor specificity.
On December 15, 2011, the Lancet
published an editorial online that highlights
the fact that many maternal deaths in the
UK are associated with substandard care
and are potentially preventable. The article
suggests that it is the failure to diagnose or
appropriately manage preeclampsia, which
is the most common cause of maternal
death.
Preeclampsia is a serious and potentially
fatal condition that arises in pregnancy,
usually in the second or third trimester.
The exact cause is unknown but it is
thought to be related to a problem with the
placenta. The nonspecificity of signs and
symptoms contribute to making clinical
diagnosis a significant challenge, this represents a high risk to both mother and child.
Prof. Christopher Redman, emeritus professor of Obstetrics at John Radcliffe
Hospital (Oxford, United Kingdom; www.
oxfordradcliffe.nhs.uk) commented, “A reliable and specific test that aids in the diagnosis of those aspects of the preeclampsia syndrome that jeopardize the safety of mother
and/or unborn baby would be invaluable.
Alere Triage PLGF is a major advance in the
assessment for preterm disease.”
Automated Microscope Alerts
Diagnosticians to Possible Cell Anomalies
n automated microscope system
runs its own tests and alerts
diagnosticians to possible cell anomalies.
The Ikonisys (New Haven, CT,
USA; www.ikonisys.com) system
consists of three parts: a robotic handling apparatus, the reagents needed
to run the tests, and image processing
software to identify problematic proteins or chromosomes.
To use the Iconoscopes microscope system, the lab technician
merely needs to load slides with the
cell samples, introduce the reagent
that will make abnormal cells fluoresce, place up to 25 slides into a cassette, slide the cassette into the
machine, and push a button. The
robotic handling system will remove
each slide one by one and scan the
cells to see which ones are abnormal.
The machine tells the technician
which cells looked suspicious, and he
can then spend a couple minutes
checking only those.
Petros Tsipouras, professor of biology at the University of Athens
(Greece; www.uoa.gr) and Ikonisys
chairman and CEO, said that the sys-
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tem could lead to a noninvasive alternative to amniocentesis or chorionic
villus sampling to check fetuses for
chromosomal abnormalities that
could indicate Downs Syndrome.
The system could also look for
cancer cells shed by a tumor and circulating in the bloodstream, even
when the tumor is too small to
image. Such a test could be a useful
backup to the prostate specific antigen (PSA) tests given to men to look
for prostate cancer and would cut
down on unnecessary biopsies
The company has begun marketing the automated system, starting
with a test for bladder cancer and
another for abnormalities on amniocytes that would indicate birth
defects. It plans to introduce another
test, based on a third-party reagent,
to look for signs of breast cancer.
Ikonisys has launched a clinical
laboratory for its rare-cell-based tests.
Under Food and Drug Administration
(FDA; Silver Spring, MD, USA;
www.fda.gov) “home brew” rules,
the company can use its tests inhouse before it receives FDA
approval to sell to others.
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Test Diagnoses and Monitors
Thyroid Cancer After Surgery
new laboratory test for the
diagnosis and lifelong monitoring of medullary thyroid cancer
patients after thyroid surgery, was
launched globally (except in the
US). Elevated concentrations of
calcitonin in the blood are associated with the onset of this type of
cancer.
The new test is an important
component of medical assessment
especially when the patient’s symptoms are not specific. When performed alongside further examinations, the calcitonin test supports
final clinical clearance. Patients
can be treated at an earlier stage
with greater chances of success.
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Roche (Basel, Switzerland; www.
roche/com) developed the Elecsys
Calcitonin assay and launched it
for patients with nonspecific
tumors of the thyroid. “The development of new laboratory tests for
cancer management reflects our
key goal of diagnostic solutions
that support healthcare professionals with clear, actionable information and can thus contribute to
increasing patient survival,” said
Roland Diggelmann, COO, Roche
Diagnostics.
When performed alongside further examinations, the calcitonin
test supports final clinical clearance.
Patients can be treated at an earlier
stage with greater chances of success. The test also expands Roche’s
portfolio for improved thyroid management. Designed for use on
Roche’s cobas modular analyzer
platform, the immunoassay Elecsys
Calcitonin offers healthcare professionals an integrated solution for
accurate diagnosis and reliable
patient monitoring, significantly
improving medical decision-making
and treatment planning.
Image: The Elecsys Calcitonin assay is designed for cancer detection and monitoring of patients with nonspecific tumors of the thyroid (Photo courtesy of the
Mayo Foundation).
Biofluid Ribonucleic Acid
Isolation Kit Launched
n isolation kit for the extraction
of small ribonucleic acid (RNA)
from serum, plasma, urine and other
biofluids has been specifically optimized for such applications. The new
biofluids kit allows scientists to
obtain high quality microRNA from
virtually all types of biofluids in just
45 minutes and the workflow is completed in six simple steps without the
use of hazardous chemicals such as
phenol and chloroform.
The miRCURY RNA Isolation Kit –
Biofluids (Exiqon; Vedbaek, Denmark; www.exiqon.com) is optimized
to work with company’s highly sensitive miRCURY LNA Universal real-time
microRNA polymerase chain reaction
(qPCR) platform. The Isolation Kit is
ideal for use with urine samples together with Exiqon’s Toxicology Focus
microRNA PCR Panels, and for serum
and plasma samples with the
Serum/Plasma Focus microRNA PCR
Panels, or indeed any of the almost
2,000 prevalidated qPCR microRNA
assays available. The Isolation Kit –
Biofluids can be used with a centrifuge
or a vacuum manifold is provided in
pack sizes of 10 and 50 units.
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The company offers a complete
range of PCR products for microRNA
analysis, which includes ready-to-use
panels for genome-wide screening of
human, mouse and rat microRNAs,
numerous focus panels, the fully flexible Pick & Mix panels, spike-in kits,
cDNA synthesis and PCR Master Mix
kits, as well as unique qPCR data
analysis software. Customers that
have identified novel microRNAs can
take advantage of Exiqon’s proprietary LNA chemistry and unique
design algorithm through easy-to-use
online tool for high quality design of
custom microRNA qPCR assays.
Henrik M. Pfundheller, Senior Vice
President Sales and Marketing at
Exiqon, said, “Our customers want
fully integrated systems that allow
highly robust and sensitive microRNA
profiling in difficult samples such as
blood and urine, and we deliver the
solution with this new kit. We have
not only optimized the protocols to
ensure the highest yield in the market
but have also made sure that the sample does not contain any inhibitors
which may jeopardize the downstream PCR analysis.”
LabMedica International
June-July/2013
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LabMedica
for daily laboratory medicine news click to www.labmedica.com
Blood Test Tracks Response
to Cancer Treatment
blood test that tracks fragments of DNA shed by dying tumor cells could
be used to monitor how well patients are responding to cancer treatment. In women with advanced breast cancer, the blood test could provide a
noninvasive alternative to biopsies, and help adapt treatment to individual
patients and the progress of disease.
A team of scientists at the Cancer Research Institute (Cambridge, UK;
www.cancerresearchuk.org) compared circulating tumor DNA against the
two other well-known biomarkers, cancer antigen 15-3 (CA 15-3), and circulating tumor cells, to assess disease progress in 30 women being treated
for advanced metastatic breast cancer. Serial blood samples were collected
between April 2010 and April 2012 at intervals of three or more weeks.
Sequencing was performed on DNA from breast cancer specimens and
matched normal tissue specimens, with the use of one or both of two methods: tagged-amplicon deep sequencing
for the gene encoding the phosphatidylinositol- 4,5-bisphosphate 3-kinase, catalytic subunit alpha protein (PIK3CA)
and for the gene encoding for tumor
protein p53 (TP53) or paired-end
whole-genome sequencing. The scientists measured the levels of CA 15-3 in
50 L aliquots of plasma by means of the
ADVIA Centaur immunoassay system
(Siemens Healthcare; Erlangen, Germany; www.siemens.com).
The team compared the three sets of
biomarker results with computed tomography (CT) scans to see if changes in the
biomarkers matched up with changes in
the cancer. They found that out of the
three biomarkers the circulating tumor
DNA gave the most accurate real time
picture of changes taking place in the
body. They successfully detected tumor
DNA in 29 of the 30 women (97%),
while circulating tumor cells were
detected in 26 of the 30 (87%) and CA
15-3 was detected in 21 of 27 (78%).
VISIT US AT:
Carlos Caldas, MD, FMedSci, co-lead
author said, “We can use blood samples
to track how breast cancer is progressing
as fragments of DNA are shed by cancer
Booth: 1916
cells when they die, meaning they can
be detected in blood samples using sensitive new sequencing techniques. The
levels of tumor DNA are telling us how
the cancer is responding to treatment.”
Circulating tumor DNA represents a
“liquid biopsy” alternative, allowing sensitive and specific serial sampling to be
performed during the course of treatment. The study was published on
March 13, 2013, in the journal New
England Journal of Medicine (NEJM).
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Image: A cluster of breast cancer cells
showing visual evidence of programmed
cell death (Photo courtesy of Annie
Cavanagh, Wellcome Images).
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LabMedica
Image Cytometry Measures
Mononuclear Cell Concentration
rapid fluorescence-based image cytometry
system has been utilized for brightfield and
fluorescence imaging analysis of cellular characteristics.
The viability and concentration of isolated
peripheral blood mononuclear cells (PBMCs) are
traditionally measured by manual counting with
trypan blue (TB) using a hemacytometer, but red
blood cell (RBC) contamination can be an issue.
Scientists at the Nexcelom Bioscience
Laboratories, (Lawrence, MA, USA; www.nexcelom.com) compared their Cellometer Vision
instrument with both manual counting and automatic method for accurately measuring the concentration of PBMCs in prepared blood samples.
Fifteen freshly isolated samples were stained
with acridine orange and propidium iodide
(AO/PI) to identify RBC contamination. The five
different methods were manual counting of TBstained PBMCs in hemacytometer; manual
counting of PBMCs in brightfield images; manual counting of acetic acid lysing of RBCs with TBstained PBMCs; automated counting of acetic
acid lysing of RBCs with PI-stained PBMCs; and
AO/PI dual staining method.
Each of the 15 samples measured was categorized into low, medium, or high RBC contamination. Five samples showed less than 10% of RBC
contamination, six samples showed 10% to 40%
of RBC contamination, and four samples showed
RBC contamination greater than 40%. The total
particles counted in brightfield increased due to
the addition of RBCs, while AO/PI staining
showed consistent measurement of PBMCs,
which again demonstrated the robustness of the
method despite RBC contamination. Although
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inherent RBC contaminants may have existed in
the sample, the purpose was to observe the
increasing difference between fluorescently
stained nucleated cells and total brightfield cell
count including RBCs.
The authors concluded that fluorescencebased image cytometry can be utilized to eliminate the RBC-induced error in patient samples,
which can improve accuracy and efficiency of
PBMC measurement. Cellometer image cytometry has also demonstrated fluorescence-based cell
population analysis such as apoptosis detection,
cell cycle, as well as surface marker labeling. The
system can be used to perform immunophenotyping of collected PBMCs, and can quickly characterize incoming patient samples, further simplifying PBMC characterization protocol. The study
was published in the February 2013 issue of the
Journal of Immunological Methods.
Image: The Cellometer Vision instrument, designed
for measuring the concentration of PBMCs in prepared blood samples (Photo courtesy of Nexcelom
Bioscience Laboratories).
Semiconductor-Based Sequencing
Achieves Rapid Cancer Genotyping
enotyping platforms should provide rapid turnaround times and work effectively with limited amounts DNA even when it is of poor quality. A
method that combines highly multiplexed polymerase chain reaction (PCR) with semiconductorbased sequencing has been described that works
well with formalin-fixed, paraffin-embedded (FFPE)
tissue specimens that often yield low quality DNA.
Scientists at the Knight Cancer Institute
(Portland, OR, USA; www.ohsu.edu) have described
semiconductor-based sequencing of DNA from FFPE
specimens using a single-tube, multiplexed panel of
190 amplicons targeting 46 cancer genes. A validation set of 45 FFPE tumor specimens containing 53
point mutations previously identified with a mass
spectrometry-based genotyping platform, along with
19 indels ranging from 4 to 63 base pairs (bp), was
used to evaluate assay performance.
The investigators used as little as 10 ng of input
DNA, with as average read depths of 2,000 times,
which can be obtained in 48 hours, with more than
95% of the reads on target. With a mutant-allele
ratio cutoff of 8%, they were able to achieve 100%
sensitivity and 95.1% specificity of point mutation
detection. All indels were visible by manual inspec-
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tion of aligned reads; 6/9 indels were equal to or
greater than 12 bp in length were detected by the
variant caller software either exactly or as mismatched nucleotides within the indel region.
Indels are a special mutation class, usually defined
as a mutation resulting in a co-localized insertion
and deletion and a net gain or loss in nucleotides.
Nineteen known insertions and deletions were
all visible on manual inspection of aligned reads,
although only two were identified exactly by the
variant caller software. It is expected that manual
inspection will be needed to evaluate common gene
regions known to harbor large indels, such as in the
v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) and the epidermal growth factor receptor (EGFR). Notably, 27 variants were
observed in genes that had not previously been tested in these samples, and all were confirmed.
The authors concluded that the rapid turnaround time and low input DNA requirements
make the multiplex PCR and semiconductor-based
sequencing approach a viable option for mutation
detection in a clinical laboratory. The study was
published in the March 2013 issue of the Journal of
Molecular Diagnostics.
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Study: Microscopic Hematuria an
Unreliable Indicator of Bladder Cancer
study found that microscopic hematuria does
not necessarily mean cancer, and has led to a
new model to predict renal and bladder cancer
risk better.
Blood found in urine that cannot be seen by the
naked eye does not necessarily indicate the presence of cancer, according to a Kaiser Permanente
Southern California (Gardena, CA, USA; www.
kaiserpermanente.org) study published in the
January 11, 2013, online version of the journal
Mayo Clinic Proceedings. Tests routinely done on
patients with this condition could be avoided and
has led to the creation of a screening tool to better
diagnose certain types of cancers.
The study examined the electronic health
records of more than 4,000 patients with microscopic hematuria who were members of Kaiser
Permanente health plans in Southern California,
Northern California, and the Pacific Northwest
between January 2009 and August 2011. The
study found that an extremely small proportion
of patients with microscopic hematuria were
subsequently discovered to have cancer. Among
the 4,414 patients who were evaluated for the
condition, only 2.3% were diagnosed with bladder cancer and only 0.2% had a pathologically
confirmed diagnosis of renal cancer.
Pathology reports were reviewed for all
patients with cancer diagnoses. A total of 50 can-
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cers (44 bladder and 6 renal)
were confirmed in the test
cohort and 61 cancers (56
bladder and 5 renal) in the validation cohort. In the test
cohort, 5 of 55 neoplasms
were benign on the final
pathology report, and 1
patient with a 1.7-cm, enhancing renal lesion elected close
observation and was counted
as having stage T1 cancer. In
the validation cohort, 56 of 59
bladder cancers were confirmed as were 5 of 7 renal
cancers (2 renal lesions were benign hemorrhagic
renal cysts). The overall cancer detection rate was
1.9% in the test cohort (50 of 2630 patients) and
3.4% for the validation cohort (61 of 1784 patients).
Overall, 100 bladder cancers were diagnosed
among 4414 patients evaluated (2.3%), and only
11 renal cancers were pathologically confirmed
(0.2%).
It is probable that patients with microscopic
hematuria, especially those under 50 years of age
and with no history of gross hematuria, may not
benefit from further evaluation, and therefore
could avoid routine tests that contain unnecessary
risks such as radiation exposure from CT scans
and invasive endoscopy.
“This study provides scientific data that confirms what others have suspected – that microscopic hematuria is an unreliable indicator of
renal or bladder cancer,” said study lead author
Ronald K. Loo, MD, and regional chief of urology
for the Southern California Permanente Medical
Group. “This suggests that a large number of follow-up examinations of patients with asymptomatic microscopic hematuria, which often
includes radiologic and invasive procedures, could
be safely avoided.”
Image: A bladder cancer cell (Photo courtesy of the
CDC).
High-Tech Blood Test
Predicts Premature Birth Risk
blood test that predicts preterm
birth harvests exosomes from
a blood sample and looks for a specific biomarker fingerprint that indicates a high risk for preterm birth,
even in women with no known risk
factors.
NX PharmaGen (Louisville, KT,
USA; www.nxpharmagen.com) has
conducted early studies with maternal serum samples using its
NeXosome Preterm Birth Assay. Two
cohorts were balanced for age and
subjects were asymptomatic with no
known risk factors, such as hypertension, twins, or gestational diabetes. The average age was 28. In
the study, a preterm birth was before
34 weeks and after 37 weeks was
full-term.
As early as 15 weeks, the test
could detect a risk for preterm birth.
NX PharmaGen’s initial human studies also suggest the test could be used
for early detection, sub-typing/staging, drug receptor presence/absence,
and recurrence monitoring for cancer, including lung cancer, ovarian
cancer, and brain cancer.
“If you harvest exosomes and
open them up and look at their con-
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tent, the protein content of a term
pregnancy looks very different from a
preterm pregnancy,” commented
Brian Brohman, co-founder and chief
business officer of NX Pharmagen.
The initial benefit of the
NeXosome Preterm Birth Assay will
allow doctors to move a patient from
normal OBGYN care to a fetal medicine specialist.
“This is a tool to tell doctors
where they should be spending extra
time,” Brian Brohman said. “If you
can extend the pregnancy on knowledge of a risk, you can save lots of
money.”
Next steps for NX PharmaGen are
assay optimization and validation.
Brian Brohman said that it is too early
to know which regulatory path the
company will take: Clinical Laboratory Improvement Amendments a
laboratory-developed test (CLIA LDT)
and an US Food and Drug
Administration (FDA; Silver Spring,
MD, USA; www.fda.gov) approval.
The company is seeking patents
on the biomarker pattern that indicates a high risk of premature birth
and the method of harvesting exosomes from a blood sample.
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LabMedica
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Rapid Tuberculosis Detection
Test Endorsed by Experts
diagnostic test for tuberculosis (TB) that can
accurately and quickly detect both TB and
drug-resistant strains has been authorized by leading experts in the field.
The diagnostic accuracy of the Xpert MTB/RIF
test can provide timely advice for clinicians and
policymakers in countries where TB is a major
public health problem and where drug resistance
further complicates efforts to control TB.
Scientists from the Cochrane Infectious
Diseases Group, McGill University (Montreal,
QC, Canada; www.mcgill.ca) and the Foundation
for Innovative New Diagnostics (FIND; Geneva,
Switzerland; www.finddiagnostics.org), analyzed
data from 18 studies involving a total of 7,816
people, with most studies being carried out in
low- and middle-income countries. Their analysis
showed that when Xpert MTB/RIF test is being
used as a replacement for smear microscopy for
1,000 people being screened, of whom 150 have
TB, the test picks up 132 of the 150 cases (88%)
and falsely diagnoses 17 (2%) with TB.
Where the Xpert test is being used as a replacement for culture-based drug susceptibility testing,
it is also able to detect the equivalent of 141 out
of 150 cases (94%) of rifampicin resistance. When
Xpert is used as a follow-on test, after conventional smear microscopy has already produced a negative result, it picks up 101 out of 150 cases
(67%). As smear-negative TB is not picked up by
smear microscopy because microscopy cannot
detect small numbers of bacteria, Xpert picked up
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67% of this group that would have
been missed by microscopy.
The authors concluded that when
the Xpert assay is used as an initial
diagnostic test for TB detection and
rifampicin resistance detection in
patients suspected of having TB,
multi-drug-resistant (MDR)-TB, or
human immunodeficiency virus
(HIV)-associated TB, it is both sensitive and specific. Xpert may also be
valuable as an add-on test following
microscopy for patients who have previously been found to be smear-negative. An Xpert result that is positive for
rifampicin resistance should be carefully interpreted and take into consideration the risk of MDR-TB in a given
patient and the expected prevalence
of MDR-TB in a given setting. The
Xpert MTB/RIF test is manufactured
by Cepheid Inc. (Sunnyvale, CA, USA;
www.cepheid.com).
Karin Weyer, DSc, Coordinator,
Laboratories, Diagnostics and Drug
Resistance at the World Health Organization
(WHO; Geneva, Switzerland; www.who.int) said,
“This Cochrane Review provides high quality evidence that reinforces WHO’s endorsement of this
test. Recent price reductions have greatly facilitated rollout of this technology with 1.4 million test
cartridges and over 200 GeneXpert instruments
for the rapid detection of TB and rifampicin resistance will be distributed in 21 countries with a
high burden of TB.” The review was published on
January 31, 2013, in the Cochrane Library.
Image: The Xpert MTB/RIF test for the detection of
tuberculosis (Photo courtesy of Cepheid).
Digital PCR Chosen to Develop Leukemia Test
general method called “limiting dilution polymerase chain reaction (PCR)” was developed
for quantifying PCR targets. This method was subsequently used for the quantification of marker
mutations in acute leukemia.
By diluting DNA samples so that only one or two
copies per well were present and then amplifying
those copies with PCR, scientists were able to
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detect two copies of leukemic DNA against a background of 160,000 normal genomes.
The team then reported that the outcome of
acute leukemia can be predicted by measuring the
response to treatment using limiting dilution PCR
to quantify the leukemic cells at high sensitivity.
Prof. Alec Morley and his lab at Flinders University
and Medical Center in Adelaide (SA, Australia;
LMI-07-13 120
www.flinders.sa.gov.au) then used real-time quantitative PCR (qPCR) to develop a highly sensitive
method for isolating and quantifying the chromosomal translocation that is typically associated with
chronic myelogenous (or myeloid) leukemia
(CML), also known as chronic granulocytic
leukemia (CGL), a cancer of the white blood cells.
It is a form of leukemia characterized by the
increased and unregulated growth of predominantly myeloid cells in the bone marrow and the accumulation of these cells in the blood.
Because the translocation point for each patient
is different in CML, real-time PCR conditions may
vary from patient to patient and may therefore produce different results. Therefore, real-time PCR
conditions may vary from patient to patient and
may therefore produce different results. The lab has
now returned to digital PCR.
Monoquant (www.monoquant.com.au), a company associated with Flinders University, used BioRad’s (Hercules, CA, USA; www.bio-rad.com)
QX100 system to refine the new clinical test for
CML. Not only does the instrument offer high sensitivity but also removes variability in amplification
efficiency that results from using patient-specific
PCR primers, a traditional sticking point for the US
Food and Drug Administration (FDA; Silver Spring,
MD, USA; www.fda.gov). Monoquant hopes the
results from the QX100 system will fast-track the
FDA approval process for its test.
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PRODUCT NEWS
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AUTOMATED OSMOMETER
BENCH-TOP ANALYZER
BIOCHEMISTRY ANALYZER
Advanced Instruments
Beckman Coulter
BioSystems
AUTOMATED
CLINICAL ANALYZER
The A2O fully automated unit offers
ease of use and walk-away operation. Key features include 20-sample
capacity, direct primary tube sampling, liquid level detection, positive
sample identification, bidirectional
data interface, and intuitive software
control package.
The UniCel DxH 600 cellular analysis system features high-quality
results, improved first-pass accuracy, and automatic rerun and reflex
testing. The analyzer is designed for
mid- to high-volume labs, and is
intended to help reduce overall manual review rates and processes.
The BA400 analyzer is designed to
offer enhanced performance for labs
looking to achieve the highest efficiency with optimal operative cost.
Key features include 88 refrigerated
positions with internal barcode reader, and 135 positions for samples,
controls, and standards.
The Biolis 50i is designed to measure 480 tests per hour, or 580 tests
per hour with ISE. Key functions of
the system include HbA1c automatic
preparation, clot detection, and dedicated ISE probe.
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Test Predicts Harmful
Breast Cancer Mutations
multiple gene expression-profile test is able to predict the
presence of harmful breast cancer
type 1 (BRCA1) or BRCA2 gene
mutations in otherwise healthy
women carrying the mutation.
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Women with a mutation in their
BRCA1 or BRCA2 gene have a significantly increased risk for developing breast cancer or ovarian cancer,
and for many of those at risk the disease may develop at an early age.
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Scientists at the Hadassah
Hebrew University Medical Center
(Jerusalem, Israel; www.hadassah.
org.il) obtained fresh blood samples
from proven BRCA1 or BRCA2
mutation carriers and mutation-negative women. All subjects were
healthy women between ages 25
and 50 years, with no personal history of cancer. The test was carried
out on leucocytes from the blood
samples donated by nine healthy
women with a mutated BRCA1
gene and eight healthy women with
a mutated BRCA2 gene. The investigators extracted the total ribonucleic acid (RNA) from these cells and
compared it to the total RNA from
identically treated white blood cells
from 10 healthy, noncarrier women.
About 1,500 genes were differentially expressed between carriers
and noncarriers. The list was narrowed down to 18 genes that were
the most significantly differentiated
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between the two groups of women.
The final narrowing was done with
a validation study of a model using
21 of the newly identified genes and
five control genes to predict the risk
for carrying a mutation. The blood
samples used were from an independent group of 40 women who
were carriers of mutated BRCA1
and/or BRCA2 and 17 noncarrier
women. The model had a sensitivity
of 95% and a specificity of 88%.
Asher Y. Salmon, MD, the senior
author and a breast cancer specialist,
said, “In wealthy societies, it can
become a screening tool for identifying individuals with a very high susceptibility for carrying a mutation,
and full sequencing can be reserved
only for them. In societies in which
sequencing is not feasible, this test
can substitute for it with a very high
accuracy rate.” The study was published on January 22, 2013, in the
journal Cancer Prevention Research.
Image: Israeli researchers at Hadassah Medical Center have developed a test
that can predict if healthy women are at a significant risk of developing breast or
ovarian cancer. Using a blood test, the researchers were able to identify the presence of a harmful mutation, which may trigger those types of cancers in women
(Photo courtesy of Jspace).
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Rapid Malaria Test Assessed for Field Use
apid diagnostic tests (RDT) for malaria infections could replace light microscopy in poor
resource locations as their ease of use and accuracy are improved.
Although light microscopy (LM) is the gold
standard for malaria diagnosis it is not available in
many outlying health facilities, it is time consuming, requires highly trained personnel, and needs
careful preparation and application of reagents to
ensure quality results.
Scientists at the University of Gondar (Ethiopia;
www.uog.edu.et) collected blood samples from 254
patients suspected to have malaria at a health center in Northwestern Ethiopia in the late malaria
transmission-peak season from November 2011 to
December 2011. The male to female ratio was
1.57:1, while the mean age of the participants was
21.4 years with an age range of 5 months to 75
years. Most of the participants were from rural areas
of the district. The samples were examined immediately by light microscopy (LM) and the RDT.
The overall parasite positivity using LM was
104 (40.9%): 40 (15.7%) for Plasmodium falciparum, 58 (22.8%) for P. vivax, and 6 (2.4%) had
R
Technique Catalogs
Lymphoma-Linked Genetic
Variations
novel approach has been devised to sort out random mutations in genes associated with lymphoma, and the proteins produced by the genes could
be tested to see how they performed.
Antigen receptor signaling to nuclear factor of
kappa light polypeptide gene enhancer in B-cells (NFκB), is essential for normal lymphocyte activation, but
is dysregulated in several types of lymphoma.
Scientists at Johns Hopkins School of Medicine
(Baltimore, MD, USA; www.hopkinsmedicine.org)
made copies of the caspase recruitment domain family, member 11 (CARD11) gene in a way that made
random mutations likely. The CARD11 protein plays
a key role in signaling the presence of infection,
which leads infection-fighting white blood cells to
grow and divide.
The investigators then used the faulty copies to
make mutant proteins, and tested the ability of those
proteins to trigger the signaling reaction that is
CARD11’s specialty. This allowed them to find to
which mutations increased the protein’s activity and
by how much and this information could then be
compared to emerging data about CARD11 mutations
found in human lymphomas. They noted that
CARD11 is part of the NF- κB signaling pathway, a
target of some cancer therapies.
Joel Pomerantz, PhD, an associate professor in the
Johns Hopkins School of Medicine’s Institute for Cell
Engineering, and senior author of the study said “Our
goal was to correlate various mutations with potential
to promote lymphoma. We imagine eventually being
able to correlate response to a particular therapy with
a particular mutation.” The cancers called lymphomas, affect about 75,000 patients in the United
States of America each year. The study was published
in the January 2013 issue of the journal Molecular
and Cellular Biology (www.mcb.asm.org).
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mixed infections. The CareStart RDT gave an
overall parasite positivity of 100 (39.4%) with 50
(19.7%) for P. falciparum, 24 (9.5%) for P. vivax,
and 26 (10.2%) for mixed infections. Difference
in detection of P. falciparum parasites using either
the LM or the RDT was insignificant, but difference in detection of P. vivax using the LM and
RDT was found to be significant.
The CareStart Malaria COMBO Test kit (Diasys
Ltd.; New York, NY, USA; www.diasys.com) is a
three-band RDT detecting histidine-rich protein 2
(HRP-2) and PAN-lactate dehydrogenase (pLDH),
yielding results in 20 minutes. The test has an
overall sensitivity of 95% and specificity of 94.2%.
The sensitivity and specificity for mixed infections
and non-falciparum malaria was slightly less. The
authors concluded that the CareStart RDT test
showed good sensitivity and specificity with an
excellent agreement to the reference light
microscopy. The RDT could therefore be used in
place of microscopy, which in poor set-ups cannot
be used routinely. The full study is available since
in November 2012 in the Malaria Journal
Image: Red blood cells infected with Plasmodium
falciparum, the cause of malaria (Photo courtesy of
Visual Photos).
LabMedica
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Image: The LSM 700 laser
scanning microscope
(Photo courtesy of
Carl Zeiss Microscopy).
New Confocal Laser
Microscope Introduced
laser-scanning microscope sets a new standard for confocal microscopy. It offers maximum performance at a practical price.
The LSM 700 Laser Scanning Microscope
from Carl Zeiss Microscopy LLC (Oberkochen, Germany; www.zeiss.com/micro),
offers microscopy solutions and systems for
research, routine, and industrial applications. In
addition, Carl Zeiss Microscopy markets
microscopy systems for the clinical market, as
well as optical sensor systems for industrial and
pharmaceutical applications offers innovative
solutions for image analysis with good sensitivity and quality at an attractive price/performance
ratio. The fields of application extend from simple routine to multidimensional images.
LSM 700 can be utilized both at individual
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workstations and in user groups. The microscope has a small footprint, which makes it
suitable for small rooms. The fields of application extend from simple routine to multidimensional images in biomedical research.
High flexibility in both application and system structure is the outstanding feature of the
LSM 700. The ZEN 2009 software from Carl
Zeiss makes its operation very clear and easy
to learn allowing intuitive use even by firsttime users. Complex methods are easy to control and the user has a clear overview of the
experiment at all times. The system can be
combined with a large number of microscope
stands and tailored to the personal requirements of each user. This makes it ideal as an
entry-level system for confocal microscopy.
Enzyme May Lead
to Better TB Test
n enzyme has been identified that will trigger
the rapid breakdown of several Mycobacteria,
which could lead to better tests for the deadly
tuberculosis infection.
The current bacterial culture test for tuberculosis infections is highly accurate but time-consuming, taking up to several weeks, while the diagnostic process called nucleic acid-based amplification
(NAA) faces difficulty in breaking open, or lysing
bacteria.
Scientists at University of Pittsburgh Graduate
School of Public Health (PA, USA; www.
publichealth.pitt.edu) show that exposure to an
enzyme called esterase from Mycobacterium smegmatis hydrolyzes the ester linkage of trehalose dimycolate in vitro, which triggers the rapid and efficient
lysis of Mycobacterium tuberculosis, Mycobacterium bovis, and Mycobacterium marinum.
A rapid and efficient lysis of trehalose dimycolate hydrolase (TDMH) exposed M. tuberculosis,
and a subsequent release of nucleic acids (NA)
offered a unique opportunity to use this enzyme for
achieving more sensitive detection in a nucleic acid
amplification assay for the diagnosis of tuberculosis
(TB). The nucleic content in the supernatant of
TDMH-exposed bacilli started to increase within 30
minutes of exposure, and it peaked at around 60
minutes.
Treatment of samples with TDMH prior to the
amplification reaction facilitated the NA detection
in 37 samples, a highly significant improvement in
the numbers of positive detection. The investigators also demonstrated that this quick lysis of M.
tuberculosis improved its detection at lower density.
Anil Ojha, PhD, an assistant professor and senior
author of the study said, “Tuberculosis is a huge
public health burden. Clearly, controlling the infection is heavily dependent upon an effective diagnosis. Discovery of enzyme-based mycobacteria lysis
has the potential to increase the sensitivity of
NAA.” The study was published on January 4,
2013, in the Journal of Biological Chemistry.
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June-July/2013
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Immune Response Predicts Predisposition to Burkitt Lymphoma
n important association has been identified
between Plasmodium falciparum (Pf) malaria
and endemic Burkitt Lymphoma (eBL) that may
help identify young children who are more susceptible.
The evolving complexity and heterogeneity of
the humoral immune response to the deadliest of
malarial parasites is possibly a key component for
risk of developing eBL in young children who reside
in malaria endemic areas of Equatorial Africa.
Scientists at George Washington University
(Washington DC, USA; www.gwu.edu) developed,
optimized, and standardized an extensive panel of
serological tests of recombinant Pf antigens representing several stages of the parasite lifecycle
assayed in more than 700 cases and control samples
from young children. The children were domiciled
in Pf malaria endemic areas of Ghana, had eBL, and
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were matched with children of the same age, sex,
and of the same village who did not have eBL.
The team used an immunomics approach to
their antibody response to Pf malaria. This enabled
different statistical and epidemiological associations
to be made between a range of antibody response to
Pf malaria antigens and eBL, establishing a pattern
of immune responses rather than a single immune
response, identifying the children who are at risk for
developing eBL. The results of study showed a significant increase in the risk of developing eBL in
young children who had a distinct pattern of antibody responses to several different recombinant Pf
malaria antigens, including some antigens, which
are vaccine candidates. Of special note, the study
also found a significant decreased risk of eBL in
children with antibodies to SE36, a vaccine candidate protein that has been associated with lower
risk of malaria in epidemiological studies. Endemic
Burkitt Lymphoma is a cancer of the lymphatic system in children affecting in particular their B-lymphocytes.
Jeffrey Bethony, PhD, who was the senior author
of the study, said, “Plasmodium falciparum malaria
has long been suspected as an important trigger to
Epstein Barr virus-associated lymphoma of very
young children living in Equatorial Africa. Our study
adds to this literature, explaining that it is not simply the presence or absence of Pf malaria infection,
but the breath and complexity of the antibody
response to malaria that may be the true indicating
factor for who develops endemic Burkitt Lymphoma
and who does not.” The study was presented at the
54th Annual Meeting of the American Society of
Hematology held December 8-11, 2012, in Atlanta
(GA, USA; www.hematology.org).
Blood Test for Autism Outperforms Existing Genetic Tests
blood test for autism spectrum disorders
(ASDs) presents evidence that abnormal
immunologic activity affecting brain development may help explain some of autism’s origins.
The blood test was described on December 5,
2012, in the online open access journal PLOS
ONE. It is based on a large, gene-chip investigation and it could enable early diagnosis of autism
in about two thirds of patients before clear symptoms start to appear at 5 years, the average age of
diagnosis in the US.
Sek Won Kong, MD, of the Boston Children’s
Hospital Informatics Program (CHIP; Boston,
MA, USA; www.chip.org), is the leader of a team
of investigators who analyzed blood samples from
66 male patients with ASDs, and compared them
with 33 age-matched boys without ASDs. They
studied RNA signatures using microarrays and
discovered differences in gene activity, or expression between the two groups.
Analyzing the blood samples, Dr Kong and colleagues flagged 489 genes as having distinct
expression patterns in the ASD group, and narrowed this to a group of 55 genes that correctly
identified or ruled out autism in 76% of samples.
They validated their findings in a second group of
104 male and female patients with ASDs and 82
controls, achieving an overall classification accuracy of 68%.
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The 55 genes whose expression was altered
suggest more than one path to what we know as
autism. Based on their genetic signatures, subjects with ASDs clustered into four subgroups
marked by changes in different biological pathways.
“It’s clear that no single mutation or even a
single pathway is responsible for all cases,” said
Dr Kohane. “By looking at this 55-gene signature,
which can capture disruptions in multiple pathways at once, we can say with about 70 percent
accuracy, ‘this child does not have autism,’ or
‘this child could be at risk,’ putting him at the
head of the queue for early intervention and evaluation. And we can do it relatively inexpensively
and quickly.”
Most current theories of autism focus on disordered synapses but, Dr. Kohane speculates that
brain development in autism may be impaired by
abnormal immune responses to infections and
other stressors, during infancy or prenatally.
Boston Children’s Hospital has licensed the
gene signature approach exclusively to SynapDx
(Southborough, MA, USA; www.synapdx.com).
It can potentially diagnose autism far more often
than the genetic tests currently available. Current
tests look for variety of autism-related mutations
but altogether, the known mutations account for
fewer than 20% of autism cases.
mRNA Assay Offers Applications
in Clinical Biomarker Discovery
n mRNA quantitative assay is a simple, highthroughput, reproducible method, that offers
a wide range of applications in clinical biomarker
discovery and molecular testing to target personalized medicine.
The assay employs simple filtration of blood to
capture leukocytes prior to extraction and purification of mRNA. This eliminates interference by
the large amount of red blood cells in whole
blood, and enables sensitive detection of changes
in mRNA levels. The system adopts a 96-well
microplate format, making it suitable for simultaneous processing of multiple samples. The drug
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response of an individual is simulated in a test
tube by using whole blood samples stimulated
with the drug. This system successfully brought a
new “ex vivo” concept, which measures in vivo
response in an in vitro assay and makes it possible
to predict drug efficacy.
With this system, Hitachi Chemical (Tokyo,
Japan; www.hitachi-chem.co.jp/english) plans to
conduct contract test services for pharmaceutical
companies to find novel biomarkers and select
subjects for clinical trials by predicting drug efficacy. It eventually aims to utilize the system as a
companion diagnostic.
LabMedica International
June-July/2013
26
LabMedica
for daily laboratory medicine news click to www.labmedica.com
Assay Detects Minimal Residual
Disease in Blood Based Cancers
clinical assay measures minimal
residual disease (MRD) in a range
of blood-based cancers that will help
doctors more effectively determine
effectiveness of treatments, monitor
patient remission status, and personalize future treatments.
Adaptive Biotechnologies (Seattle,
WA, USA; www.adaptivebiotech.com),
a provider of next-generation sequencing assays for the adaptive immune system, has launched clonoSEQ, a clinical
assay that measures minimal residual
disease (MRD) in a range of blood-based
cancers that is significantly more sensitive than today’s most common pathology tests.
Minimal residual disease refers to
small numbers of leukemic cells that
remain in the patient during treatment
or after treatment when the patient is in
remission. The number of these residual cells may be, in some cases, correlated with the risk of relapse. Knowledge of MRD can influence clinical
care and increase cure rates.
Adaptive has extensive experience
applying its MRD assay for research in
centers
worldwide,
and
has
instituted quality control measures to
markedly improve the accuracy and
sensitivity of MRD testing as well as
simplify data reporting to make comprehension easier and quicker for
hematologists.
The company developed a set of
immune receptor templates to eliminate polymerase chain reaction (PCR)
amplification bias. It has instituted a
systematic chain of custody to handle
customer samples. Its bioinformatics
platform enables the measurement of
MRD as a ratio of the malignant clone
to the total number of nucleated cells in
a blood sample as well as to the lineagerelated cells.
The launch of clonoSEQ follows
demonstration by Adaptive Biotechnologies, in collaboration with the Fred
Hutchinson Cancer Research Center
and the University of Washington
department of laboratory medicine, that
clonoSEQ detected minimal residual
disease in nearly twice the number of
patients with T-lineage acute lymphoblastic leukemia/lymphoma (TALL) than flow cytometry. The study
was published in the May 2012 journal
Science Translational Medicine.
Future plans for clonoSEQ include the development and distribution
of a proprietary kit that would allow for
the assay to be performed in point-ofneed clinical pathology laboratories.
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LabMedica International
June-July/2013
Image: ClonoSEQ is a set of CLIAstandardized assays developed by
Adaptive for highly sensitive (approximately 106) detection of Minimal Residual
Disease (MRD) in leukemia and lymphoma patients. The assay focuses on Tcell receptor or B-cell receptor (Ig)
Complementarity Determining Region 3
(CDR3) chains. The nucleotide sequences that encode the CDR3 regions
are generated by site-specific recombination between genomic variable (V), diversity (D), and joining (J) region gene segments (Photo courtesy of Adaptive
Biotechnologies).
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Coagulation Test
Correlates Protein Concentration
for Plasma Cell Dyscrasia
Diagnosis of Prostate
Cancer Uses Oncogene
Molecular Signature
diagnostic test distinguishes
patients with clinically relevant
prostate cancer from normal
prostate in men with elevated
prostate-specific antigen (PSA) levels.
The team worked with three
oncogenes previously associated
with poorer outcomes in prostate
cancer: c-Myc , Ha-Ras, and v-Src.
Led by Richard G. Pestell, MD, PhD,
director of the Kimmel Cancer
Center (KCC; Philadelphia, PA,
USA; www.kimmelcancercenter.org)
and the chair of the department of
cancer biology at Thomas Jefferson
University (Philadelphia, PA, USA;
www.jefferson.edu) the team reported their preclinical findings from a
blinded, retrospective analysis of over
350 patients in the November 30,
2012, edition of Cancer Research.
The test, the team claims, is
superior to several previously published gene tests and to the Gleason
scale, which is the rating given to
prostate cancer based upon its
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microscopic appearance and currently used to help evaluate the
prognosis of men with the disease.
The oncogene-specific prostate cancer molecular signatures were recapitulated in human prostate cancer
and validated in distinct populations
of patients as a prognostic and diagnostic test. In addition, the team
demonstrated how the isogenic
prostate cancer cell lines metastasized in immune-competent mice.
“Identification of gene signatures
in breast cancer has allowed for a
deeper understanding of the disease,
and this paper moves us steps closer
to being able to follow a similar trajectory with prostate cancer. Today,
such an understanding and a formidable testing ground for new therapies is lacking for this disease,” Dr.
Pestell said. “With this new oncogene-specific prostate cancer molecular signature, we have a valuable
prognostic and diagnostic resource
that could help change the way we
manage and treat prostate cancer.”
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bnormal screening coagulation
tests are frequently observed in
asymptomatic patients with multiple
myeloma and other plasma cell neoplasms.
Prothrombin time (PT), activated
partial thromboplastin time (APTT)
and fibrinogen activity have been
linked with clinical history and disease parameters in patients with
plasma cell dyscrasia.
Scientists at the University of
Arkansas for Medical Sciences (Little
Rock, AR, USA; www.uams.edu)
studied coagulation tests in a total of
252 patients. Of these, 79 patients
(31%) had abnormal routine screening coagulation test results. An isolated prolonged PT of greater than
15 seconds was found in 62 patients
(25%), and 10 patients had prolonged PT and APTT (4%).
Prothrombin time, APTT, and fibrinogen activity were analyzed on the
STA-R Evolution, using PT reagent
Neoplastine CI PLUS and APTT
reagent STA-PTT A, all products of
Diagnostica Stago (Parsippany, NJ,
USA; www.stago-us.com). Fibrinogen activity was determined by measuring the clotting time of diluted plasma in the presence of excess thrombin with a reference range of
197–447 mg/dL. The quantitation of
monoclonal proteins was performed
by separating serum proteins using
capillary electrophoresis with direct
protein detection by UV absorbance
at 200 nm.
An isolated prolonged PT was the
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most common abnormal coagulation
test found in 25% of the patients. A
prolonged PT was more frequently
observed in 157 patients with the
multiple myeloma compared to the
34 monoclonal gammopathy of
undetermined significance (MGUS)
patients or other diagnostic categories of plasma cell dyscrasia. There
were no differences immunoglobulin
isotype in 62 patients with isolated
prolonged PT compared to the 173
patients with normal screening coagulation tests. Fibrinogen activity was
significantly lower in patients with
prolonged PT although there was no
correlation between fibrinogen activity and PT. Serum M protein concentrations were significantly greater in
patients with prolonged PT and were
positively correlated with PT. Serum
M protein concentrations were significantly elevated in patients with
prolonged PT compared to patients
with normal PT and were positively
correlated with PT values.
The authors concluded that there
was an association between disease
severity and prolonged PT in that
patients with multiple myeloma
were more likely to have prolonged
PT than patients with other plasma
cell neoplasms. Of the factors examined, the monoclonal protein level
was significantly higher in patients
with isolated prolonged PT and correlated with PT. The study was published on December 7, 2012, in the
International Journal of Laboratory
Hematology.
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June-July/2013
28
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Hemocytometers Evaluated for
Peritoneal Fluid Cell Counts
he diagnostic performance of different automated hemocytometers for white blood cell (WBC) enumeration of peritoneal fluids was compared with manual microscopy analysis.
The term ascites is conventionally
used for designating the accumulation
of fluid in the peritoneal cavity and the
presence of elevate numbers of WBCs
and polymorphonucleated leukocytes
(PMNs) is pivotal to diagnose spontaneous bacterial peritonitis (SBP).
Scientists at the Academic Hospital
of Parma (Italy; www.ao.pr.it) analyzed 100 peritoneal fluids with manual microscopy and five automated
hemocytometers. Manual microscopic analysis was carried out using
Nageotte and Fuchs-Rosenthal chambers after staining with Turk’s and
May-Grünwald–Giemsa reagents.
The five automated counters were
the XE-2100 and XE-5000 (Sysmex;
Kobe, Japan; www.sysmex.com); the
Advia 2120 (Siemens; Erlangen
Germany; healthcare.siemens.com);
the BC-6800 (Mindray; Mahwah, NJ,
USA; www.mindray.com); and the
Abbott Sapphire (Abbott Park, IL,
USA; www.abbottdiagnostics.com).
The XE-2100 is a flow cytometer,
using forward-scattered and side-scattered light, whereas the WBC differential entails a specific nucleic acid
dye to measure the cells by side-fluorescent light and side-scattered light.
The analysis of WBC as performed on
the XE-5000 is with a flow cytometry
technique by means of a semiconductor laser and fluorescent measurement.
For manual microscopy the mean
values in the 100 peritoneal fluids
was 873 WBC/mm3, compared to
943 WBC/mm3 for the XE-2100 and
741 WBC/mm3 for XE-5000. For the
Advia 2120, the mean was 741
WBC/mm3, while for the BC-6800 it
was 938 WBC/mm3 and 782
WBC/mm3 for the Sapphire. There
were no significant differences
between the different counts and
therefore correlations were highly significant. The agreement between
manual analysis and flow cytometry
at the diagnostic threshold for septic
peritonitis with a count equal to or
greater than 1000 WBC/mm3, was
99% for XE-2100, XE-5000, Advia
2120, BC-6800 and 96% for
Sapphire.
The authors concluded that used
for routine analysis of body fluids the
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LabMedica International
June-July/2013
five hemocytometers tested display
acceptable performance for routine
screening of peritoneal fluid. Higher
correlations with manual microscopy
were found for the two Sysmex analyzers although those of the Advia
2120, BC-6800 and Sapphire were
still excellent. The study was published in the January 2013 issue of
the journal Clinical Biochemistry.
Image: The XE-5000 automated analyzer (Photo courtesy of Sysmex).
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Whole Genome Sequencing Better at Tracing TB Outbreaks
study revealed that a new form of genetic
testing of the bacteria that cause tuberculosis (TB) provides better information on TB transmission and thus allows tracing of TB outbreaks
more accurately than the current standard tests.
A team of experts from public-health institutions, research institutes, and universities in
Germany and France led by Stefan Niemann
from the Forschungszentrum Borstel (Borstel,
Germany; www.fz-borstel.de) compared the
results of the two types of tests on 86
Mycobacterium tuberculosis isolates from a TB
outbreak in the German states Hamburg and
Schleswig-Holstein (overall 2301 TB cases have
been investigated in the study period from 1997
to 2010).
They found that the new test, based on the
sequencing of the respective whole genomes
(i.e., whole genome sequencing, WGS) provided
more accurate information on clustering and
temporal spread of the pathogen than the standard tests, which are based on the analysis of
small genome regions (classical genotyping).
Importantly, while standard tests were not able
to distinguish the strains involved, WGS-based
analyses revealed that only a particular clone
started spreading at the onset of the outbreak,
suggesting that subtle differences in the genome
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might influence the success of pathogen transmission.
“Only genome based investigations allowed
us to trace the spread of M. tuberculosis with
the resolution needed to visualize transmission
patterns correctly,” said Dr. Andreas Rötzer, first
author of the study.
Genotyping of M. tuberculosis strains is usually used to detect TB outbreaks and guide tracing contacts of TB cases. However, standard
genotyping analyses only tiny parts of the
genome, and may therefore not be able to distinguish between closely related strains spreading
in distinct transmission chains. This was confirmed by this study: WGS-based typing discriminated better the different strain variants
involved in the outbreak, was in better agreement with information on known contacts
between the patients, and allowed the investigators to more precisely follow the spread of clones
over space and time.
Based on the genome sequencing data, the
authors were also able to estimate that the
genome of M. tuberculosis evolves in its natural
host population (infected individuals) at a slower
mutation rate than other bacterial pathogens
(0.4 mutations per genome per year). This measure of the bacterium’s mutation rate will be use-
ful to trace future outbreaks and estimate when
and via which individual they originated.
An additional advantage of WGS compared to
standard genotyping is that WGS allows the
identification of mutations of bacterial genes
causing antibiotic resistance mutations and variations in virulence genes. This is especially
important as M. tuberculosis strains that are
resistant to the most potent drugs are increasingly emerging in several world regions and rapid
detection of resistance is crucial for successful
treatment.
The costs of whole genome analysis based on
Next Generation Sequencing are declining;
therefore, this test could soon become the standard method for identifying transmission patterns and rates of infectious disease outbreaks.
In addition, the authors state: “We envision
that the progressive effective implementation of
WGS for Public Health and medical diagnostics
will also be accelerated by the broader distribution of more accessible and flexible sequencing
machines, and upcoming bioinformatics developments to facilitate quick and relevant interpretation of the resulting data by the clinical and medical staff.”
The study was published in PLOS Medicine
on February 12, 2013.
Serological Assay Assessed
for Dyspepsia Patients
commercial panel of assays provides an algorithm, which indicates stomach health and the function
of the gastric mucosa. The assay,
known as GastroPanel, is performed
with a simple blood test that can be
used to assess the condition of the gastric mucosa and to confirm the diagnosis of hypochlorhydria and indicate
whether the changes in the mucosa
are due to a chronic inflammatory
condition.
The scientists at Quest Diagnostics
(Heaton, UK; www.questdiagnostics.com) have used GastroPanel to
examine 181 patients whose ages
ranged from 19 to 75 years, with a
median of 41 years. Of these, 105
(60.7%) were Japanese, 53 (30.6%)
were European, and the remaining
15 (8.7%) were an assortment of ethnicities. Of particular note among the
Japanese group was the receipt of
samples from 23 husband and wife
couples. GastroPanel evaluates for
pepsinogen I and II, gastrin 17, and
antibodies to Helicobacter pylori
infection, but does not identify the
organism.
Of the 181 samples tested by the
GastroPanel (Biohit Oyj; Helsinki,
Finland; www.biohithealthcare.com),
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115 (68.4%) showed no abnormalities in the samples and were reported
as normal function of gastric mucosa.
Thirty-six samples (20.7%) were positive for H. pylori alone and a report
was issued with a recommendation
to return to their doctor and start an
appropriate course of antibiotics. The
remaining 30 samples showed a
range of abnormal results. Only 27
(14.9%) patients were over 50 years
of age, 18 of which were reported as
normal, four were positive for H.
pylori alone, four showed increased
pepsinogen I levels and the last sample, from a 51-year-old Japanese
woman, was positive for both H.
pylori and pepsinogen I.
The authors concluded that the
GastroPanel assay can be used to
diagnose H. pylori infection and
atrophic gastritis, and to estimate the
risks associated with these conditions. Approximately half of the gastroscopies performed show healthy
gastric mucosa and therefore the
GastroPanel assay could save the
patient from unnecessary discomfort
and also reduce unnecessary healthcare costs. The study was published
in December 2012 in the British
Journal of Biomedical Science.
LMI-07-13 130
LabMedica International
June-July/2013
30
LabMedica
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Solid Media Used to
Isolate Leptospira
solation of Leptospira, from clinical samples and testing of antimicrobial susceptibility are difficult and time-consuming. Pathogenic
Leptospira are slow-growing Gram-negative spirochetes and a new
solid medium that facilitates more-rapid growth of these organisms has
been developed.
Microbiologists at the Mahidol University (Bangkok, Thailand;
www.mahidol.ac.th) developed the new solid medium, called LVW
agar, by testing the effects of combinations of ingredients and incubation conditions. All recipes contained three core ingredients and a variable concentration of two additional ingredients. A total of 109 pathogenic Leptospira isolates were used during the development and evaluation of the new solid medium and Etest, which is well-established
method for antimicrobial resistance
testing, antibiotic susceptibility testing
in microbiology laboratories around the
world.
The medium was developed by
evaluating the effects of numerous factors on the growth rate of a strain of
Leptospira interrogans. These included the type of base agar, the concentration of rabbit serum (RS), and the concentration and duration of carbon dioxide incubation during the initial period
of culture. The highest growth rate of
this strain was achieved using a Noble
agar base supplemented with 10% RS
and named LVW agar, with an initial
incubation at 30 °C in 5% CO2 for two
days prior to continuous culture in air
at 30 °C.
These conditions were used to
develop the Etest for three species, L.
interrogans, L. kirschnerii, and L.
borgpetersenii. The minimum inhibitory concentrations (MICs) were read on
day seven for all samples. The validated
Etest methodology was performed for
109 Leptospira isolates with five
antimicrobial drugs, penicillin G, doxycycline, ceftriaxone, cefotaxime, and
chloramphenicol. The MIC90 values
were as follows: penicillin G, 0.064
units/mL; doxycycline, 0.19 μg/mL;
cefotaxime, 0.047 μg/mL; ceftriaxone,
0.5 μg/mL; and chloramphenicol, 2
μg/mL.
Leptospirosis is a zoonotic disease
that has a worldwide distribution but
has the greatest impact on health in
developing countries, where it is often
grossly under recognized. The authors
concluded that LVW agar that enables
rapid growth, isolation of single
colonies, and simple antimicrobial susceptibility testing for Leptospira species
will become widely used in diagnostic
microbiology laboratories, but especially in resource-limited settings. The
study was published in the January
2013 issue of the journal Antimicrobial
Agents and Chemotherapy.
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Image: Leptospira interrogans bacterium
(Photo courtesy of Science Photo
Library).
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LabMedica International
June-July/2013
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PRODUCT NEWS
To receive prompt and free information on products, log on to
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HEMOGLOBIN
MEASUREMENT DEVICE
qPCR MACHINE
Ceragem
The DA7600 qPCR is designed for
ease of use, accuracy, and user reliability. The system is considered
ideal for laboratories and test centers that require both enhanced performance and cost-effectiveness.
The Cera-Chek Hb Plus is designed
to accurately measure hemoglobin
levels with as little as 1 μL of blood
within five seconds. The detection
strips are divided into a grip part and
a detecting part, to avoid the possibility of blood contamination.
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Daan Gene
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CLINICAL
CHEMISTRY SYSTEM
PROTEIN ANALYZER
ELITech Group
The Nephstar is a bench-top nephelometric analyzer for rapid quantitative measurements of specific proteins in blood or urine samples. Key
benefits include automatic calibration and blanking, temperature-controlled reaction chamber, and results
available in three minutes or less.
The Selectra ProM is designed for
primary, STAT or backup testing
needs, and offers a throughput of up
to 266 tests per hour. The system
requires minimal maintenance, and
offers an effective use of consumables to reduce operating costs.
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Urinary Enzyme Levels Correlate with Prediabetic Plasma Glucose
rinary N-acetyl-β-D-glucosaminidase (NAG) excretion is increased in patients with impaired glucose tolerance (IGT).
During the oral glucose tolerance
test (OGTT) the plasma glucose, urine
glucose, and insulin levels correlate
strongly with urinary NAG levels in
prediabetic subjects.
Scientists at the Nippon Medical
School (Tokyo, Japan; www.nms.ac.jp)
performed OGTTs on 33 men and 47
women, aged 18 to 79 years, who
were not yet diagnosed with diabetes
mellitus (DM), and in whom HbA1c
levels were equal to or greater than
6.8%. The study was carried out from
December 2005 through August
2010.
Urinary NAG levels were measured
spectrophotometrically with sodio-
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metacresolsulfonphthaleinyl- N-acetylβ-D-glucosaminide as a substrate
(NAG assay kit, Shionogi & Co.; Osaka,
Japan; www.shionogi.co.jp). Urinary
glucose levels and serum creatinine
(Cr) levels were measured with enzymatic assays. The serum levels of cystatin C were measured with the N
Latex Cystatin C kit (Siemens Healthcare Diagnostics, Inc., Marburg, Germany; www.medical.siemens.com)
and the fully automated particle-enhanced nephelometric immunoassay.
Forty-two subjects had normal glucose tolerance (NGT), 31 had impaired
glucose tolerance (IGT), and seven had
DM. NAG levels were significantly
higher in subjects with DM and in subjects with IGT than in subjects with
NGT. Urinary NAG in the DM group
was 8.53 ± 4.96 U/g UCr, which was
LMI-07-13 132
elevated compared to the NGT group,
which ranged from 5.40 ± 3.82 U/g
UCr. The IGT group’s range was 6.60
± 2.88 U/g UCr, which was also significantly higher than the nondiabetic
group. The NAG level was positively
correlated with plasma glucose levels
at 120 minutes of the OGTT and was
associated with the glycemic status of
prediabetic patients.
The authors concluded that that the
urinary excretion of NAG with other
urinary enzymes in the prediabetic
state is an appropriate biomarker for
screening for prediabetic renal dysfunction. Their results suggest that postprandial hyperglycemia is an independent factor that causes renal tubular
damage in prediabetes patients. The
study was published on November 9,
2012, in the Journal of Clinical
Laboratory Analysis.
Rapid Malaria Diagnostic
Test Evaluated in Asia
apid diagnostic tests (RDT) for
malaria have been brought into
field operations to supplement and in
some cases replace the gold standard of
light microscopy.
Although attempts have been made
to augment or even replace microscopic diagnosis of malaria with enzymelinked immunosorbent assays (ELISA),
real time, and conventional polymerase chain reactions (PCR), these
are not feasible in the field.
Scientists at the International Centre for Diarrhoeal Disease Research,
Bangladesh (ICDDR,B; Dhaka, Bangladesh; www.icddrb.org) collected
whole blood samples from 372 febrile
patients referred for malaria diagnosis
by clinicians from May 2009 to
December 2010. The samples were
assayed by a newly available RDT and
were compared to microscopy adjusted with nested PCR as the gold standard. DNA extraction for the PCR was
prepared using QiaAmp blood mini-kit
(Qiagen; Hilden, Germany; www.
qiagen.com) from preserved whole
blood. Other PCR reagents were obtained from New England BioLabs Inc.;
R
Ipswich, MA, USA; www.neb.com).
The RDT device evaluated was the
Onsite (Pf/Pan) RDT produced by
CTK Biotech Inc. (San Diego, CA,
USA; www.ctkbiotech.com) which has
the ability to detect Pan-specific lactate
dehydrogenase (pLDH) and Plasmodium falciparum specific histidine-rich
protein 2 (HRP-2). Of these 372
patients, 229 (61.6%) tested positive
for malaria infection detected by
microscopy and nested PCR. The
OnSite (Pf/Pan) RDT was 94.2% sensitive and 99.5% specific for P. falciparum diagnosis and 97.3% sensitive
and 98.7% specific for P. vivax diagnosis. Sensitivity varied with differential
parasite count for both malaria species.
The authors concluded that the
OnSite (Pf/Pan) RDT, a lateral flow
chromatographic immunoassay, performed satisfactorily in standard laboratory conditions. It can be utilized for
diagnosis of symptomatic malaria as
well as to discriminate falciparum
malaria infection from vivax malaria in
endemic areas and during outbreaks.
The study was published on December
12, 2012, in the Malaria Journal
LabMedica International
June-July/2013
32
LabMedica
for daily laboratory medicine news click to www.labmedica.com
Noninvasive Prenatal
Test Screens Blood for
Chromosomal Abnormalities
cont’d from cover
DNA testing is one option that can be used as a primary screening test in women
at increased risk of aneuploidy. It may also be offered as a follow-up test for
women with a positive first-trimester or second-trimester screening test result.
The noninvasive prenatal test has been developed and validated by Natera,
Inc. (San Carlos, CA, USA; www.natera.com). Physicians will be able to forward
specimens for testing to Natera’s Clinical Laboratory Improvement Amendments
(CLIA)-certified laboratory. The test will be made available to physician clients of
Quest Diagnostics (Madison, NJ, USA; www.questdiagnostics.com) in certain
regions in March and nationwide in the United States in April 2013.
A “low risk” Panorama test result indicates a lower likelihood that a pregnancy is affected. With this information, a
woman may consider, in consultation
with her physician and results of other
medical assessments, whether to pursue or forgo invasive diagnostic testing,
which carries a slight risk of miscarriage. A “low risk” Panorama result
does not guarantee an unaffected pregnancy.
“Cell-free fetal DNA testing is a significant advance in prenatal screening,” said Charles Strom, MD, PhD,
senior medical director, genetics, Quest
Diagnostics Nichols Institute. “By offering physicians and women access to
Panorama, Quest Diagnostics is delivering on its commitment to provide
clinically important innovations aligned
with guideline-based care.”
Natera is a leading genetic testing
company that has developed a proprietary bioinformatics-based technology
(NATUS) to deliver accurate and comprehensive high-throughput testing for
reproductive indications from minute
quantities of DNA. Natera operates a
CLIA-certified laboratory in San Carlos
(CA, USA) providing a host of preconception and prenatal genetic testing
services.
Image: The Panorama test is designed to
screen for chromosomal abnormalities,
such as trisomy 21 (Photo courtesy of the
Global Down Syndrome Foundation).
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LAB SYSTEMS
BIOCHEMISTRY ANALYZER
Hitachi Aloka Medical
Horron XLH Medical Electronics
The LabFLEX3500 Series is a variety of systems that can be configured by combining functional modules to suit the needs, size, and
operational methods of facilities. The
systems also allow for the configuration of a transport option for specific
layout and conditions of a facility.
The semiautomatic biochemistry
analyzer features multicolor touch
screen operation and intelligent software options. Both flow cell and
cuvette can be used, and the system
can display real-time reaction graph,
and print out QC reports.
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CHEMILUMINESCENCE
IMMUNOASSAY SYSTEM
CHEMISTRY ANALYZER
SNIBE
The URIT-8021A features durable
syringes to ensure accuracy and
precision, along with an auto-washing system to reuse cuvettes. Other
benefits include automatic stop/
alarm, liquid level protection, collision protection, and a throughput of
200 tests per hour.
The Maglumi 600 features options
such as three modes of operation,
sample loading for up to 16 sample
tubes, four reagents on board, and
clot detection. The system is considered ideal for IVD, with a throughput
of up to 180 tests per hour with first
results available in only 12 minutes.
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Blood Test Identifies Mortality
Risk for Trauma Patients
simple, inexpensive blood test performed on
trauma patients upon admission can help
doctors easily identify patients at greatest risk of
death.
A computerized tool that combines factors like
age, gender, and common blood tests known as
the complete blood count (CBC) and the basic
metabolic profile (BMP) can determine an individual’s mortality risk is now available to physicians.
Scientists at the Intermountain Medical Center
(Salt Lake City, UT, USA; http://intermountain
healthcare.org) studied 9,538 patients and discovered that some trauma patients are far more likely to die than others were, regardless of the severity of their original injuries. The Intermountain
Risk Score is a computerized tool and has been
helpful in evaluating individuals with medical
problems like heart failure or chronic pulmonary
disease. The benefit of the tool had not been tested for trauma patients hospitalized due to an accident or traumatic injury, rather than an underlying condition.
The Intermountain Medical Center used the
tool to categorize patients according to high, mod-
A
erate, and low risk levels.
Some surprising findings
emerged as high-risk men
were nearly 58 times more
likely to die within a year than
low-risk men were. Men with
a moderate risk were nearly
13 times more likely to die
than those with low risk.
High-risk women were 19
times more likely to die within a year than low-risk women
were, and women with moderate risk were five
times more likely to die than those with low risk.
Sarah Majercik, MD, an Intermountain
Medical Center surgeon, said, “As surgeons, we
don’t often use all of the CBC results in evaluating a patient who needs surgery for a bleeding
spleen or after a motor vehicle accident. There
are certain values, such as hemoglobin, hematocrit, and platelets that we scrutinize closely as
part of good clinical care, but then other parts,
such as the red blood cell distribution width
(RDW) that we pay no attention to at all in the
acute setting. These factors are generally overlooked, even though they are part of the CBC
that every trauma patient gets when he or she
arrives in the emergency room.” The study was
presented on January 18, 2013, at the 27th annual Scientific Session of the Eastern Association for
the Surgery of Trauma held in Phoenix (AZ, USA;
www.east.org).
Image: Amber Vance, a medical laboratory scientist,
works on a complete blood count panel at
Intermountain Medical Center (Photo courtesy of
Ravell Call, Deseret News).
Novel Immunoassay Evaluated for Cardiac Troponin
he analytical performance of an immunoenzymometric assay for the cardiac troponin (cTnI)
has been appraised and compared with other
methods. The test is a two-site immunoenzymometric assay, which uses a combination of two
monoclonal antibodies, respectively directed to
41–49 and 87–91 amino acids of the cTnI peptide
chain, and the ternary troponin ITC complex as a
calibration antigen.
Scientists at the Fondazione Toscana G.
Monasterio (Pisa, Italy; www.ftgm.it) evaluated the
assay in 452 healthy individuals of which 326 were
males and 126 were female. The median age was
45 years with a range between 17 to 76 years. The
study participants were recruited from laboratory
T
staff, blood donors, or voluntary subjects, included
in screening programs for preventive medicine.
The immunoenzymometric assay for the cTnI
evaluated in the study was the Tosoh ST AIA-PACK
cTnI 3rd-Generation, and it uses the automated
AIA-2000 platform (Tosoh Corporation, Tokyo,
Japan; www.tosoh.com). The third-generation AIAPack assay for cTnI showed an improved analytical
sensitivity and reproducibility, especially at very
low cTnI concentrations compared to the previous
second-generation AIA-Pack assay. The values of
the third-generation assay were a limit of detection
(LoD) at 8.7 ng/L and the limit of quantitation
(LoQ) at 100 ng/L. The LoD and 10% LoQ values
of the second-generation assay reported previously
were 38 ng/L and 130 ng/L, respectively.
The third-generation AIA-Pack Tosoh assay for
cTnI showed a very close agreement throughout all
the working range with the Access AccuTnI
Beckman–Coulter method (Beckman Coulter, Inc.,
Fullerton, CA, USA; www.beckmancoulter.com).
Close concordance was also demonstrated between
the cTnI measured by Tosoh methods and those of
cTnT measured with ECLIA Roche method (Roche
Diagnostics, Mannheim, Germany; www.roche.
com). The authors concluded that their results imply
that the third generation AIA-Pack assay is suitable
for the clinical evaluation of patients with cardiac diseases. The study was published in the January 2013
issue of the journal Clinica Chimica Acta.
LabMedica International
June-July/2013
34
LabMedica
for daily laboratory medicine news click to www.labmedica.com
DNA Test Detects Mutations
Across Multiple Genes
he first multigene DNA sequencing test that
can help predict cancer patients’ responses to
treatment has been launched in the United
Kingdom.
The test uses the latest DNA sequencing techniques to detect mutations across 46 genes that
may be driving cancer growth in patients with
solid tumors and the presence of a mutation in a
gene can potentially determine which treatment a
patient should receive.
Scientists at the Oxford Biomedical Research
Center (UK; www.oxfordbrc.nihr.ac.uk) launched
the DNA test for the UK National Health Service
(NHS; London, UK; www.nhs.uk). The number of
genes tested marks a step change in introducing
next-generation DNA sequencing technology into
the NHS, and heralds the arrival of genomic medicine with whole genome sequencing of patients
just around the corner.
The test costs around GBP 300 and could save
significantly more in drug costs by getting patients
on to the right treatments straightaway, reducing
harm from side effects as well as the time lost
before arriving at an effective treatment. The test
is run on a next generation sequencing platform
called the Ion Personal Genome Machine (Life
Technologies Corporation, Carlsbad, CA, USA;
T
www.lifetechnologies.com). The
test and accompanying software
have been substantially modified
as requested by the Oxford team to
fulfill diagnostic standards in their
laboratory.
The scientists have carried out
tests and comparisons to verify the
robustness of the technique with
cancer biopsies direct from patients.
The team compared the new 46gene test against conventional techniques for 80 consecutive cancer
biopsies in the hospital laboratory’s
workflow. The next-generation DNA sequencing
method detected all the mutations the conventional method did. It also detected new mutations the
conventional method did not, and detected mutations present at much lower levels in the samples.
The time taken for the 46-gene test also fitted into
the standard turnaround time for samples at the laboratory. The test requires a very small amount of 5
ng of DNA, an advantage when working with clinical samples that are typically limited in quantity.
Jennifer Taylor, MD, of the Wellcome Trust
Center for Human Genetics (Oxford, UK;
www.well.ox.ac.uk) said, “We wanted a test that
would use the latest DNA sequencing techniques
to detect a wide range of mutations in a wide
range of genes. The test should be able to cover
more cancers and more treatments, all for a similar cost to conventional methods. It’s a significant
step change in the way we do things. This new 46
gene test moves us away from conventional methods for sequencing of single genes, and marks a
huge step towards more comprehensive genome
sequencing in both infrastructure and in handling
the data produced.”
Image: The Ion Personal Genome Machine (Photo
courtesy of Life Technologies).
Biomarkers Found for Metastatic Breast Tumor Cells
ome breast tumor circulating cells in the bloodstream are marked by a constellation of biomarkers that identify them as those destined to metastasize
in the brain.
Sophisticated techniques have been used to test
samples of circulating breast tumor cells to identify
and characterize the biomarkers that are the signature of the cells destined to seed the brain with a
deadly spread of cancer.
Scientists at Baylor College of Medicine (Houston,
TX, USA; www.bcm.edu) collected blood samples
from 38 patients with metastatic or nonmetastatic
breast cancer. Isolated peripheral blood mononuclear
cells (PBMCs) were separated, analyzed, and sorted
with the BD FACSAria II 3Laser high-speed sorting
S
flowcytometer (Becton Dickinson; Franklin Lakes,
NJ, USA; www.bd.com ). The circulating tumor cells
were cultured and injected into animals. Total ribonucleic acid (RNA) from the PBMCs was amplified by
real time polymerase chain reaction.
The biomarkers identified by the scientists included human epidermal growth factor receptor 2
(HER2+), epidermal growth factor receptor (EGFR),
heparanase (HPSE) and Notch1, a single-pass transmembrane receptor. Together, these four proteins,
previously known to be associated with cancer metastasis, spell out the signature of circulating tumors cells
that travel to the brain. The scientists did not find evidence of the epithelial cell adhesion molecule
(EpCAM). The study not only identifies a novel signa-
ture of circulating tumor cells, it shows the limitations
of currently approved platforms used to identify cancer in this way. Analyzing such cells can help scientist
understand how the disease spreads, which may be
an initial step in developing new methods of treating
metastatic disease.
Dario Marchetti, PhD, professor of pathology and
lead author said, “We don’t claim that these biomarkers are the only important ones. We hope to find novel
markers in brain metastasis that will make diagnosis
and monitoring even more targeted.” The investigators are also trying to find ways to link these circulating tumor cells back to the signature of the original or
primary tumor. The study was published on April 10,
2013, in the journal Science Translational Medicine.
Flow Cytometry Assay Measures NK Cell Function
eripheral blood natural killer (NK) cell function
in healthy adults has been assessed using the
target-induced NK loss (TINKL) assay.
The TINKL assay is a sensitive flow cytometrybased assay for measuring NK cell function; its clinical application has been evaluated and the activity
measured, which is independent of the number of
NK cells in the assay.
Immunologists at The Canberra Hospital
(Garran, ACT, Australia; www.canberrahospital.
act.gov.au) collected blood from 70 healthy adult
male, and 53 healthy female volunteers. Their
mean age (± standard deviation) was 38 ± 11 years,
ranging from 19 to 65 years. Venous blood was collected in vacutainers containing ethylenediaminetetraacetic acid (EDTA), and samples were processed
within 24 hours. Peripheral blood mononuclear
P
35
LabMedica International
June-July/2013
cells (PBMC) were isolated, cryopreserved, and
stored in liquid nitrogen. On the day prior to assay,
PBMC were thawed and maintained in culture
overnight.
The TINKL assay, conducted using NK-sensitive
erythroleukaemic cell K562, was used to measure
natural killing, and the NK-resistant Raji B lymphoblastoid cell in the presence of the CD20 monoclonal antibody Rituximab was used to measure
antibody-dependent killing. Peripheral blood NK
cell function measured by the TINKL assay was
assessed in repeated samples of 123 healthy adults.
The PBMC were assayed in 21 trials over a
three-month period. NK loss was 31% ± 10%
(range 7% to 55%) as a consequence of natural
killing, and 39% ± 10% (range 14% to 64%) as a
consequence of antibody-dependent killing. The
variation in NK cell function in the population
measured by the TINKL assay is greater than can
be accounted for by interexperimental variability.
The intraexperimental coefficient of variation
(CV) was on average 11% for natural killing and
3% for antibody-dependent killing, compared to
14% and 9% respectively for the interexperimental variation.
The authors concluded that their data provides
additional information on the TINKL assay relevant
to testing NK cell function in a clinical setting. The
intra-experimental variability and the inter-experimental variability of the assay have been quantified,
and the large range in NK cell function in a population of healthy donors is now chronicled. The study
was published on April 6, 2013, in the Journal of
Immunological Methods.
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Blood Protein Detects Higher
Risk of Cardiovascular Event
blood protein is able to detect higher risk of
cardiovascular events in people with chest
pain originating from heart disease.
Higher levels of pregnancy-associated plasma
protein A (PAPP-A) is associated with an increased
risk of cardiovascular events in people with cardiac chest pain that developed as a result of heart
disease and/or coronary artery disease.
Scientists at the University of Tubingen
(Germany; www.uni-tuebingen.de) conducted a
study of 2,568 patients to determine if the presence of PAPP-A could help predict cardiovascular
events. The study included patients who visited
hospital with cardiac chest pain between
December 2007 and April 2009. Serum PAPP-A
values were analyzed using an automated
immunofluorescent assay (Kryptor PAPP-A,
Thermo Fisher Scientific, BRAHMS GmbH;
Hennigsdorf, Germany; www.thermoscientific.
com).
More than half (52%) of patients had stable
angina and the remaining 48% had acute coronary
syndrome. The normal serum value for men and
A
Image: Pregnancy-associated plasma protein-A
(PAPP-A) is a protein produced by both the embryo
and the placenta, and is associated with an
increased risk of cardiovascular events (Photo courtesy of TheVisualMD).
nonpregnant women is less than 14 mIU/L.
Serum levels in patients who had cardiovascular
events in the three months following initial hospital admission, such as a heart attack, myocardial
infarction, stroke or death, were higher at 62 ±
156 mIU/L, compared with those who did not at
21 ± 23 mIU/L. The optimal prognostic cutoff
value was a PAPP-A level of 34.6 mIU/L.
Stephan von Haehling MD PhD, a coauthor
from the Charité Medical School (Berlin,
Germany; www.charite.de), said, “PAPP-A
remained a significant independent predictor of
major cardiovascular events and remained the
strongest predictor of major cardiovascular events
when we restricted the analysis to patients with
stable angina, and when we restricted it to
patients with acute coronary syndrome.” The
authors concluded that higher levels of serum
PAPP-A were independently associated with an
increased short-term risk of cardiovascular events
in patients presenting with cardiac chest pain. The
study was published on March 18, 2013, in the
journal Canadian Medical Association Journal.
Genetic Markers Predict Alzheimer’s Disease
buildup of certain proteins in the brain and
spinal fluid has an increased likelihood of people developing Alzheimer’s disease.
Mutations identified in certain genetic regions
influence the levels of these protein accumulations
and this may help identify people most at risk of
developing Alzheimer’s disease well before they
show signs of cognitive decline.
A group of scientists collaborating with those at
Washington University School of Medicine (St.
Louis, MO, USA; www.wustl.edu) measured the
proteins tau, ptau, and Aβ42 in cerebrospinal fluid
(CSF) in 1,269 individuals. The mean age at enrollment was 78.5 years and 30.9% were male. At the
last evaluation, 24.9% met clinical diagnostic crite-
A
ria for AD and 21.8% had mild cognitive impairment. The samples were genotyped using Illumina
chips (San Diego, CA, USA; www.illumina.com).
A genetic region identified by the group includes
the Alzheimer’s disease gene triggering receptor
expressed on myeloid cells 2 (TREM2), which
encodes a cellular receptor and other genes in
TREM2’s family, including Trem-like transcript 1
protein (TREML2). Alison Goate, PhD, of the
Washington University School of Medical School,
said, “Tau is an important biomarker of neurodegeneration in Alzheimer’s disease, present as insoluble aggregates in the brain and as soluble protein
in the cerebrospinal fluid. We have identified several genes that influence the levels of soluble tau in
the cerebrospinal fluid, and we show that one of
these genes also influences risk for Alzheimer’s disease, rate of cognitive decline in Alzheimer’s disease, and density of tangle pathology in the brain.”
Carlos Cruchaga, PhD, the first author of the
study said, “Interestingly, although these genes are
similar, the associations of TREM2 and TREML2
with cerebrospinal fluid tau levels were in the opposite direction, one associated with risk for
Alzheimer’s disease and the other protective.” The
authors concluded that using a genome-wide association study they were able to identify the risk variants for Alzheimer’s disease by measuring the levels
of tau in the CSF. The study was published on April
4, 2013, in the journal Neuron.
Blood Test Confirms Negative Mammography, Detects Missed Cancer
rapid, accurate, and cost-effective blood test
measures disease-specific autoantibodies to
detect the presence of breast cancer.
The Octava Pink breast cancer test is produced
by Eventus Diagnostics (EventusDx, Miami, FL,
USA; Ora, Israel; www.eventusdx.com). The company plans to commercialize its products in collaboration with corporate partners in the US, Europe,
and Asia. Octava Pink is intended for confirmatory
use in women who have received negative mammography results. The National Cancer Institute
(NCI; Frederick, MD, USA; www.cancer.gov) estimates that screening mammograms miss about 20%
of breast cancers that are present at the time of the
procedure, leading to false negative results. Studies
suggest that the Octava Pink test accurately confirms true negative mammography results, while
identifying the presence of cancer in more than half
of the cases when the mammography result is a false
negative and cancer is actually present.
EventusDx is partnering with breast cancer spe-
A
cialists in Italy and Israel to make Octava Pink available on a pilot basis. The Octava technology has
been verified in clinical trials in over 800 women
conducted at major cancer centers in Israel, Italy,
and the US.
“We developed Octava Pink to address a serious
shortcoming of mammography – the high rate of
false negative results,” said Prof. Benjamin Piura,
MD, FRCOG, CMO of EventusDx and professor
emeritus of obstetrics and gynecology at BenGurion University of the Negev. “The Octava technology has demonstrated encouraging specificity
and sensitivity levels in multisite clinical testing in
over 800 women. We expect that Octava Pink will
identify at least half of all breast cancers in women
who were mistakenly given negative mammography results, while providing welcome reassurance
to women whose negative results are accurate.”
Octava Pink can also address core needle breastbiopsy results that are false negatives, estimated at
about 5% of biopsies. Confirming negative biopsy
results with Octava Pink should detect at least half
of those cases where cancer is actually present, triggering additional diagnostic testing and treatment
when appropriate. Octava Pink may also be useful
to physicians caring for women who will not or
cannot receive mammograms.
EventusDx has received the CE mark designation for the Octava Pink breast cancer test.
“Receiving CE marking for Octava Pink is an important milestone for our company,” said Alon Hayka,
president of EventusDx in Israel. “Octava Pink is
designed to reassure women with true negative
mammograms and to enable earlier diagnosis and
treatment of breast cancer in women receiving false
negative results.”
Eventually EventusDx intends to apply its technology to develop blood tests for the detection of
additional cancers, including lung, colon, prostate,
and ovarian cancers. The company plans to commercialize its products in collaboration with corporate partners in the US, Europe, and Asia.
LabMedica International
June-July/2013
38
LabMedica
for daily laboratory medicine news click to www.labmedica.com
Mobile Device Performs
Laboratory-Quality HIV Testing
low-cost mobile device has been
engineered that combines cell phone
and satellite communication technologies
with fluid miniaturization techniques and
performs all essential enzyme-linked
immunosorbent assay (ELISA) functions.
The device combined the portability of
mobile technology with the detection
potential of enzyme-linked antibodies to
create a fully automated and portable
microfluidic device dubbed the “mChip,”
and has been tested in an African setting.
A team of scientists including those
at Columbia University (New York, NY,
USA; www.columbia.edu) who invented the device assessed its ability to perform serodiagnostic testing for human
immunodeficiency virus (HIV) in a
field setting and synchronize the
results in real time with electronic
health records. They tested serum,
plasma, and whole blood samples collected in Rwanda and on a commercially available sample panel made of
mixed antibody titers.
The handheld apparatus, which is a
mobile microfluidic chip for immunoassay on protein markers (mChip) device,
captures the essential functions of
ELISA as performed by pipetting
robots, microplate readers, desktop
computers, and communication hardware. The device does not need gridbased power and is sufficiently low in
cost and energy consumption to be
suitable for resource-limited settings.
ELISA is the most sensitive and commonly used laboratory diagnostic for
HIV, and historically has taken hours
and sometimes days to provide a result.
The mChip device, however, produces
a result in just 15 minutes.
To explore the performance of the
mChip device on coinfected samples,
the team evaluated the HIV accuracy of
the mChip device on 167 Rwandan
patient samples. Also, 100 plasma samples from Rwandan patients were tested for hepatitis B and C (HBV and
HCV), as well as 67 serum samples
from patients who were also tested for
syphilis and herpes simplex virus (HSV2). Despite the high prevalence of viral
hepatitis, 99 positive for HBV and/or
HCV in the sample set and the substantial number of sexually transmitted
infections, 31 positive for syphilis
and/or HSV-2, the diagnostic sensitivity of the mChip device was high at
100%, as was the diagnostic specificity
at 99%, with only two false positives.
Samuel K. Sia, PhD, a bioengineer
and the senior author of the study,
referring to the data repository that
doctors can access, said, “Now, with a
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LabMedica International
June-July/2013
single push of a button, there is automation not only from the sample to the
result, but to the synchronization of data
to the cloud. This automation is very
important because it minimizes user error
and user variability. The real power is that
one finger prick can give you multiple
rapid test results, making it cheaper and
more convenient.” The cost of the device
is estimated at USD 100. The study was
published on January 17, 2013, in the
journal Clinical Chemistry.
Image: Prof. Sam Sia’s mobile device speeds up diagnostic testing for
HIV and more. It can easily be used in remote areas around the world.
The mChip mobile device is on the left, with a satellite communication
modem on the right (Photo courtesy of Columbia Engineering).
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HbA1c TEST
VENTED ENCLOSURES
LAB DETECTION SYSTEM
RAPID HIV TEST
Abbott Diagnostics
Air Science
Curetis
The ARCHITECT clinical chemistry
Hemoglobin A1c (HbA1c) test is
designed to help physicians in diagnosing and monitoring diabetes, as
well as identify patients at risk for
developing diabetes. The assay is
designed for use on the ARCHITECT c8000 and c4000 systems.
The series of vented enclosures provide containment of airborne particulates during manipulation and transfer of potent compounds. Features
include turbulent-free airflow pattern,
custom sizes, HEPA-filter technology, ductless design, and an easy-tochange filtration system.
The Unyvero system is designed for
the detection of a broad panel of
bacteria and antibiotic resistances
from a single sample in one run. The
versatile system processes a disposable cartridge, providing the necessary reagents to complete the
analysis from sample to result.
Diagnostic Automation/Cortez
Diagnostics
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The OneStep HIV 1&2 Serum/WB/
Plasma RapiCard InstaTest is a single-use device for qualitative detection of antibodies to HIV in blood,
serum, and plasma samples. The
test offers a specificity of 100% and
a sensitivity of 99.4%.
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Novel Test Diagnoses
Malaria in Returning Travelers
novel, single-amplification polymerase chain
reaction (PCR) assay has been used to diagnose malaria among travelers returning from
endemic areas.
A practical single-round amplification
Plasmodium-genus-specific PCR assays has been
designed that is based on primers targeting the
18S locus and the mitochondrial genome with
sensitivity and specificity equal to nested PCR.
Tropical disease specialists at the Haukeland
University Hospital (Bergen, Norway; www.
helse-bergen.no) carried out a retrospective study
of whole blood samples from a cohort of 132 fever
patients with potential imported primary or recurrent malaria between 2006 and 2011. The samples had been previously analyzed for malaria parasites on Giemsa-stained, thin and thick slides by
experienced microscopists. Three PCR assays,
two genus-specific and one species-specific, were
assessed in the cohort of patient samples. The
mitochondrial PCR products were sequenced in
both directions.
Among the 135 samples assayed, 28 were
A
defined as malaria positive by at least two of
the methods among microscopy and the
three different genus-specific PCR assays.
The new mitochondrial PCR was 100% sensitive detecting all 28 positives. At the
threshold dilution 0.5 parasites/μL, the sensitivity of the mitochondrial PCR was 97%,
that of the single-round, 18S PCR was 93%,
and the reference-nested 18S was PCR 87%.
Both single-round amplification assays identified all malaria positives diagnosed by nested
PCR that had a sensitivity of 96%.
Sequencing of the genus-specific mitochondrial PCR products revealed different
single nucleotide polymorphisms that allowed
species identification of the 28 sequences with following distribution; 20 were Plasmodium falciparum, 6 were P. vivax, 1 was P. ovale, and 1 P.
malariae. The microscopists had missed two infections detected by all PCR assays.
The authors concluded that the design of PCR
programs with suitable parameters and optimization resulted in simpler and faster single-round
amplification assays. Both the sensitivity and
specificity of the novel mitochondrial PCR was
100% and proved equivalent to the reference
nested PCR. Sequencing of genus-specific mitochondrial PCR products could be used for species
determination. The study was published on
January 22, 2013, in the Malaria Journal.
Image: Plasmodium falciparum, the malaria-causing
parasite (Photo courtesy of the CDC).
Prenatal Testing with Cell-Free DNA Demonstrated Clinical Benefit
oninvasive prenatal testing (NIPT) has clinical
benefit over conventional prenatal screening
tests, and at a price point of USD 795, NIPT
demonstrated cost savings to the healthcare system.
An analytic model was used to compare NIPT
for trisomy 21, which causes Down syndrome,
against conventional prenatal screening with first
trimester combined or integrated screening for the
US population. Modeling was based on a 4 million
pregnant women cohort in the US. While NIPT is
not as comprehensive as a karyotype, it does not
carry a risk of pregnancy loss.
This is the first study to evaluate the economic
impact of NIPT in a high-risk pregnancy population
as recommended by the American Congress of
N
Obstetricians and Gynecologists (ACOG) and the
Society for Maternal Fetal Medicine (SMFM). As
compared to conventional prenatal screening, NIPT
detected 65%–85% more cases of trisomy 21,
reduced invasive procedures by over 95%, and in
turn, reduced over 99% of unnecessary fetal loss.
The study appeared online on January 28, 2013, in
the Journal of Maternal-Fetal and Neonatal
Medicine.
“The clinical advantages of implementing noninvasive prenatal testing into clinical practice are
becoming increasingly clear and this model quantifies the benefit,” said Dr. Aaron Caughey, senior
author of the study and chair of Obstetrics and
Gynecology at Oregon Health and Sciences
University (Portland, OR, USA; www.ohsu.edu).
“One of the most striking findings is that NIPT can
be cost saving to the US healthcare system at the
appropriate price. Few, if any, new technologies can
demonstrate both clinical and cost benefit. NIPT
represents a healthcare advance to achieve the
Triple Aim of improved quality, better access, and
lower costs.”
Produced by molecular diagnostics company
Ariosa Diagnostics, Inc. (San Jose, CA, USA;
www.ariosadx.com) the Harmony Prenatal Test
equips pregnant women and their healthcare
providers with reliable information to make decisions regarding their health, without creating
unnecessary stress or anxiety.
LabMedica International
June-July/2013
40
for daily laboratory medicine news click to www.labmedica.com
LabMedica
Prostate Cancer Genetic
Tests Predicts Prognosis
iagnostic and prognostic genetic tests have been developed to
better predict prostate cancer survival outcomes and distinguish clinically relevant cancers.
The diagnostic test distinguished
patients with clinically relevant
prostate cancer from normal
prostate in men with elevated
prostate-specific antigen (PSA) levels, and prognostic tests separate out
men who died of prostate cancer
versus those who lived.
Scientists at the Kimmel Cancer
Center (Philadelphia, PA, USA;
www.kimmelcancercenter.org) performed a retrospective analysis of
over 350 patients using an oncogene-specific prostate cancer molecular signature, based on studies carried out in mice. They worked with
three oncogenes previously associated with poorer outcomes in prostate
cancer: avian myelocytomatosis
viral oncogene homolog (c-Myc),
Harvey rat sarcoma viral oncogene
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41
LabMedica International
June-July/2013
homolog (Ha-Ras), and sarcoma
(Schmidt-Ruppin A-2) viral oncogene homolog (v-Src).
Canonical analysis was performed using the c-Myc-specific
genes that were also found to be differentially expressed between tumor
and normal samples in two human
prostate datasets. The first canonical
variable, resulting from this analysis,
was used to discriminate tumor
from normal samples in each human
prostate dataset. The oncogene-specific prostate cancer molecular signatures were repeated and validated
in distinct populations of patients as
a prognostic and diagnostic test for
human prostate cancer. The c-Myc
gene copy number is increased in up
to 30% of cases at the preneoplastic
stage in patients with prostatic
intraepithelial neoplasia. Specifically
the tests identified men whose outcome was fatal on average after 30
months.
Richard G. Pestell, MD, PhD, the
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senior investigator of the study said,
“This oncogene signature shows further value over current biomarkers
of prediction and outcomes. Such a
signature and cell line may also
enable the identification of targets
for therapies to better treat prostate
cancer, which takes the lives of over
27,000 men a year. With this new
oncogene-specific prostate cancer
LMI-07-13 141
molecular signature, we have a
valuable prognostic and diagnostic
resource that could help change the
way we manage and treat prostate
cancer.” The study was published
online on November 30, 2012, in
the journal Cancer Research.
Image: Scanning electron micrograph
(SEM) of prostate cancer cells (Photo
courtesy of David McCarthy / SPL).
LabMedica
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CHEMISTRY ANALYZER
LAB INFORMATION SYSTEM
PROSTATE CANCER TEST
Dirui Industrial
McKesson Provider Technologies
MDxHealth
Orphee
The CS-T240 auto-chemistry analyzer features a multiple-function
sample and reagent disk, as well as
a 60 nm probe, liquid level detection,
and collision protection. Other benefits include stable performance,
LIS/HIS interface, and a throughput
of up to 240 tests per hour.
The Horizon Lab 13.5 is a standalone lab information system with an
EHR module certification for meaningful use stage 2. The system is
designed as an integrated, enterprise-wide solution that works for all
lab settings, and can be adapted to
any healthcare setting.
The ConfirmMDx genetic test is
designed to differentiate prostate
cancer-free men from those who
may be harboring occult cancer. The
ConfirmMDx, combined with PSA
and other risk factors, is intended to
improve the diagnosis of prostate
cancer and avoid repeat biopsies.
The Mythic 22 OT features a TFT
color touch screen, built-in numeric
keyboard, 22 parameters, two
curves, and one scattergram. The
system offers enhanced technology,
requires a sample volume of less
than 17 μL, and can process up to
50 samples per hour.
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HEMATOLOGY ANALYZER
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Quantification of Marker Mutations in Acute Leukemia
imiting dilution polymerase chain reaction
(PCR) was developed for quantifying PCR targets. This method was used for the quantification of
marker mutations in acute leukemia.
By diluting DNA samples so that only one or two
copies per well were present and then amplifying
those copies with PCR, Prof. Morley and his team
at Flinders University and Medical Center
(Adelaide, SA, Australia; www.flinders.sa.gov.au)
were able to detect two copies of leukemic DNA
against a background of 160,000 normal genomes.
L
The team discovered that the outcome of acute
leukemia can be predicted by measuring the response
to treatment using limiting dilution PCR to quantify
the leukemic cells at high sensitivity. Subsequently
Prof. Morley’s Lab used real-time quantitative polymerase chain reaction (qPCR) to develop a highly sensitive method for isolating and quantifying the chromosomal translocation that is typically associated
with Chronic Myelogenous Leukemia (CML).
Monoquant (Adelaide, SA, Australia; www.
monoquant.com.au), a company associated with
Flinders University, used the Bio-Rad (Hercules,
CA, USA; www.bio-rad.com) QX100 system to
refine the new clinical test for CML. Not only does
the instrument offer high sensitivity, it also removes
variability in amplification efficiency that results
from using patient-specific PCR primers, a traditional sticking point for the US Food and Drug
Association (FDA; Silver Spring, MD, USA;
www.fda.gov). Monoquant hopes the results from
the QX100 system will fast track the FDA approval
process for its test.
Hepatitis C Point-of-Care Tests Highly Accurate
oint-of-care tests (POCTs) for the diagnosis of
hepatitis C (HCV) have a high level of accuracy
and may help increase screening rates for this disease. Convenient, quality-assured, antibody-based
rapid diagnostic tests (RDTs) and POCTs could facilitate preliminary screening, although they cannot
differentiate between acute and chronic infections
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and their rapid turnaround time limits loss to follow-up and facilitates early associations.
Although both diagnostic test types are rapid,
RDTs require special equipment, such as centrifuges
and refrigerators, whereas POCTs eliminate the need
for electricity and are more robust at high temperatures, thus offering additional opportunities to
LMI-07-13 142
expand screening. A meta-analysis carried out by scientists at McGill University Health Center
(Montreal, QC, Canada; www.muhc.ca) reviewed
19 studies conducted between 1992 and 2012 that
screened for HCV in adults. All the studies had evaluated the diagnostic accuracy of POCTs and RDTs
that screen for HCV in oral fluid, whole blood,
serum, or plasma. The investigators found that
POCTs had the highest sensitivity for whole blood at
98.9% and serum or plasma also at 98.9%. The RDTs
of serum or plasma had the next-highest sensitivity of
98.4%, followed by POCTs of oral fluid at 97.1%.
Specificity of POCTs of whole blood and serum or
plasma was also high, at 99.5% and 99.7%, respectively. The specificity of RDTs of serum or plasma followed, at 98.6%, and then the specificity of POCTs of
oral fluid, at 98.2%. The authors notes that because
the tests evaluated in this meta-analysis detected antibodies to HCV, these POCTs could not differentiate
between acute and chronic infections and could not
detect infection within three months of exposure.
The authors concluded that given the convenience of POCTs and their rapid turnaround time,
these results show great potential for expanded
first-line screening for hepatitis C infection and
demonstrate the utility of blood-based singleton
POCTs and of multiplex POCTs designed to provide
integrated HIV and HCV screening of at-risk populations. The study was published on October 16,
2012, in the journal Annals of Internal Medicine.
LabMedica International
June-July/2013
42
LabMedica
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Genetic Test Reveals Predisposition for Abnormal Blood Clotting
he non-O ABO blood type is the most
important risk factor for venous thromboembolism, making up 20% of inferred risk for
the condition. Individuals with an A or B blood
type have an increased risk of venous thromboembolism or blood clots in their veins and
myocardial infarction compared with individuals with O blood type.
A retrospective study was carried out by scientists at the Copenhagen University Hospital
(Denmark; www.rigshospitalet.org) who looked
at data on 66,001 people who had been followed for 33 years from 1977 through 2010 to
determine whether ABO blood type is associated with an increased risk of venous blood clots
in the general population. They determined
ABO genotype from single nucleotide polymorphisms (SNP) in the ABO gene. The genotypes
T
were validated by sequencing.
The scientists also measured the following
using standard hospital assays: plasma levels of
total cholesterol, low-density lipoprotein cholesterol, high density lipoprotein cholesterol,
platelets, mean platelet volume, leukocytes,
coagulation factors (II, VII, X), international normalized ratio, activated partial thromboplastin
time, high-sensitivity C-reactive protein and
complement C3.
The team found that the risk increased when
ABO blood type was combined with factor V
Leiden R506Q genotype or prothrombin
G20210A genotype. These genetic mutations
were associated with an increased risk of
venous thromboembolisms. This finding confirms the conclusion of other studies. The scientists also found an 11-fold increased risk of
venous thromboembolism for people with the
prothrombin G20210A mutation. The population attributable risk of venous thromboembolism was 20% for ABO blood type, 10% for
factor V Leiden R506Q and 1% for prothrombin
G20210A.
Børge G. Nordestgaard, MD, DMSc, a coauthor of the study said, “We found an additive
effect of ABO blood type on risk of venous
thromboembolism when combined with factor
V Leiden R506Q and prothrombin G20210A;
ABO blood type was the most important risk factor for venous thromboembolism in the general
population.” The authors concluded that ABO
blood type should be considered for inclusion in
genetic screening for thrombophilia. The study
was published February 4, 2013, in the
Canadian Medical Association Journal.
Molecular Blood Test
Detects Colorectal Cancer
molecular blood test that identifies changes in
DNA associated with colorectal cancer is now
available in the United States.
The test is designed to aid the detection of colorectal cancer, the third leading cause of cancerrelated deaths, but only 40% of cases are diagnosed
in early stages, due to low screening rates.
The new test is based on DNA methylation of the
Septin9 gene, a proprietary biomarker associated
with colorectal cancer that was identified by
Epigenomics AG (Frankfurt, Germany; www.
epigenomics.com). Epigenomics has demonstrated
in more than a half dozen peer-reviewed studies
involving approximately 3,000 specimens of
patients with diagnosed colorectal cancer and of
healthy control subjects that methylated Septin9 in
blood plasma indicates an increased likelihood of
colorectal cancer.
Epigenomics is sponsoring a multicenter clinical
study named PRESEPT in collaboration with
Quest Diagnostics (Madison, NJ, USA; www.quest
diagnostics.com) and other organizations to evaluate
the Septin9 biomarker’s performance for colorectal
cancer screening in screening-guideline-eligible individuals who have not been diagnosed with colorectal cancer. Quest Diagnostics is the first commercial
laboratory in the USA to offer a laboratory-developed
test based on the Septin9 biomarker.
Jon R. Cohen, MD, senior vice president and
chief medical officer of Quest Diagnostics said,
“Early detection rates are dismally low, largely
because many patients find existing tests and procedures invasive or unpleasant. Our ColoVantage colorectal cancer test, which is based on Septin9, has
yet to be clinically validated as a screening test.
Rather, it may promote further evaluation in patients
who have resisted testing in the past or as an adjunct
to existing procedures.” ColoVantage was validated
in multiple studies and achieved an overall 70% sensitivity and 89% specificity. ColoVantage has successfully detected cancer at all stages. Patients who test
positive for methylated Septin9 should be further
evaluated for the presence of colorectal cancer.
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June-July/2013
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Cancer Tissue Handling Needs Freezing Adaption
raditional specimen handling methods for
diagnosing cancer are hampering the introduction of genetic sequencing technology as a
routine laboratory procedure. Tumor tissue
obtained through a biopsy is fixed in formalin, and
embedded in paraffin for microscopic viewing,
but the chemical mixture damages DNA, so
sequencing tissue processed in this way can be difficult, if not impossible.
Scientists at the Scripps Translational Science
Institute (La Jolla, CA, USA; www.scripps.edu)
have suggested that a better alternative is to routinely freeze a portion of the specimen, which
retains the tissue’s genetic coding while preserving it for future analysis. In order to have enough
tissue to freeze, larger or additional biopsy samples may be required, especially when using min-
T
imally invasive needle biopsy procedures.
Although complete genetic evaluations of tumors
might require higher sample-storage costs and a
more invasive biopsy procedure, most patients
would likely agree to that option if it translates
into a better diagnosis and possible treatment.
Evidence of such benefit should come from randomized clinical trials that compare detailed
genetic evaluation of tumor tissue with the current standard of care for cancer patients.
Genetically guided cancer therapy is an established procedure for the treatment of malignancies. This is especially true where identifying
mutations by genotyping of the human epidermal
growth factor receptor 2 gene (HER2) in breast
cancer or the proto-oncogene B-Raf gene (BRAF)
in melanoma, may alter the chemotherapeutic
regime. The level of crucial detail is only possible
with whole genome and exome sequencing from
frozen tissue.
Eric J. Topol, MD, a cardiologist and one of the
authors, said, “Deciding how best to obtain tumor
samples and how best to process them for whole
genome or exome sequencing is a pivotal yet
unresolved issue with several layers of complexity. We need to completely rethink the way we
have collected and stored cancer tissue samples
for decades. It’s becoming increasingly clear that
obtaining an accurate map of a tumor’s DNA can
be the key to determining the specific mutations
that are driving a person’s cancer, how best to
treat it and how likely it is to recur.” The article
was published on January 2, 2013, in the Journal
of the American Medical Association (JAMA).
Cell Block Technique Detects
Low Frequency Abnormal Cells
ifferent cell block techniques have been compared for the detection of low
frequency abnormal cells and representative sampling with simple sedimentation. Automated cell block systems rapidly create paraffin-embedded cell
blocks by using vacuum filtration to deposit a layer of cells on a filter and infiltrate those cells with reagents and paraffin.
Scientists at Hologic Inc (Marlborough, MA, USA; www.hologic.com)
compared three cell block systems using a novel tracer-cell model consisting
of epidermoid carcinoma (CaSki) cells (American Type Culture Collection;
Manassas, VA, USA; www.atcc.org). The cells were prestained in solution
with hematoxylin and serially diluted in a background of pooled clinical
serous effusion specimens and quantified using a hemocytometer. Ten replicates diluted cells were processed using each cell block method, and the
resulting blocks were cut to produce two slides from each block. The slides
were deparaffinized, counterstained with eosin, cover-slipped, and screened
for the presence of tracer cells.
Tracer cells were identified on the initial slides for 20 of 40 simple sedimentation cell blocks, 21 of 40 in Richard-Allan HistoGel cell blocks (Thermo
Scientific, Waltham, MA, USA; www.thermoscientific.com), and 25 of 40
Hologic’s Cellient cell blocks. All three methods showed representative sampling in 100% of the blocks made from the 100 tracer/mL specimen. With
blocks made from the 10 tracer/mL specimen, simple sedimentation,
HistoGel, and Cellient showed 90.0%, 80.0%, and 100% representative sampling, respectively. Representative sampling at the 1 tracer/mL dilution was
10.0% for simple sedimentation and 30% for
HistoGel and Cellient. At the 0.1 tracer/mL dilution, only Cellient showed representative sampling.
The study was published on January 3, 2013, in
the journal Pathology and Laboratory Medicine
International.
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for daily laboratory medicine news click to www.labmedica.com
Abnormal Protein Potential Biomarker for ALS and FTD
dentification of abnormal protein may help
diagnose and treat Amyotrophic lateral sclerosis
(ALS), or Lou Gehrig’s disease and frontotemporal
dementia (FTD).
Investigators have discovered an abnormal protein that first forms as a result of genetic abnormalities and later builds up in the brains of many
patients with either disease. These investigators
are beginning to recognize ALS and FTD as part of
a spectrum disorder with overlapping symptoms.
By analyzing brain tissue from patients with
ALS or FTD, Dr. Petrucelli, chair of neuroscience
at Mayo Clinic in Florida (Jacksonville, FL, USA;
www.mayoclinic.org/jacksonville) and his team
discovered that the abnormal protein, which they
call C9RANT, is generated as a result of repeat
expansions of nucleotides in the noncoding region
of the C9ORF72 gene. These expansions are the
most common cause of ALS and FTD. “Simply
put, an error in the highly regulated cellular
process through which proteins are generated
causes the abnormal production of C9RANT,”
explained Dr. Petrucelli.
The scientists discovered the protein
I
C9RANT after creating a novel antibody to specifically detect it. The ability to detect C9RANT in
individuals’ cerebrospinal fluid (CSF) may provide
a valuable diagnostic and prognostic tool for identifying patients carrying the C9ORF72 repeat
expansion and for then tracking the progression of
the disease in these at-risk individuals.
Amyotrophic lateral sclerosis (ALS), or Lou
Gehrig’s disease, and frontotemporal dementia
(FTD) are devastating neurodegenerative diseases
with no effective treatment. “Although it remains
to be shown whether C9RANT is causing the cell
death or toxicity associated with disease symptoms, our discovery offers a potential target to prevent neuronal loss in patients carrying the
C9ORF72 repeat expansion,” said Dr. Petrucelli.
These studies were reported online in the
February 12, 2013 Cell Press journal Neuron.
The investigators described an abnormal protein
that first forms as a result of genetic abnormalities
and later builds up in the brains of many patients
with ALS or FTD.
Image: Immunohistochemistry of postmortem tissue
reveals neuronal inclusions of C9RANT in the brains
of patients with c9FTD/ALS (Photo courtesy of
Neuron, Ash et al.).
Biotherapy
Monitoring Kits Expand
Theranostic Range
ew additions for two biotherapy monitoring kits
are now available in all EU countries. Theradiag
(Marne-la-Vallée, France; www.theradiag.com) a
company specializing in theranostic and in vitro diagnostics, has obtained a CE mark for two new biotherapy monitoring kits; Tocilizumab (anti-IL6R) and
Rituximab (anti-CD20) that further expand the Lisa
Tracker range. The company now offers a range of
seven blood test kits providing comprehensive multiparameter diagnosis solutions to monitor patients
with autoimmune and inflammatory diseases.
Rituximab is also used to treat hematological cancers.
Michel Finance, CEO of Theradiag, said, “These
two new monitoring kits expand our theranostic
range to cancerology and show that we are on track
to meet our roadmap targets. The Lisa Tracker range
is a unique diagnostic tool, which enables physicians
to tailor treatments and optimize patient care. This
new CE mark outlines our expert know-how in our
lines of innovative proprietary diagnostic products
and their sale in international markets.”
Theradiag innovates and develops theranostic
tests (combining treatment and diagnosis) that measure the efficiency of biotherapies in the treatment of
autoimmune diseases, cancer, and AIDS. Theradiag
is thus participating in the development of “customized treatment,” which favors the individualization of treatments, the evaluation of their efficiency,
and the prevention of drug resistance. The company
markets the Lisa-Tracker range (CE marked), which
is a comprehensive multiparameter diagnosis solution for patients with autoimmune diseases treated
with biotherapies. Theradiag is also developing new
diagnostic markers thanks to its microRNA platform,
which will allow specific biomarkers to be identified
in order to guide therapy and will be first applied to
the treatment of AIDS.
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June-July/2013
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PRODUCT NEWS
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ELISA KIT
HEMOGLOBIN PHOTOMETER
VERIFICATION ASSAYS
DIAsource ImmunoAssays
EKF Diagnostics
Streck
Trinity Biotech
The 1,25-Dihydroxy-Vitamin D
ELISA kit is a complete assay for the
extraction of 1,25-Dihydroxy-Vitamin
D, followed by quantitation by an
enzyme-linked immunoassay. Key
features include accurate results,
reduced hands-on time, and fast
turnaround time.
The STAT-Site M Hgb is a batteryoperated, portable analyzer that provides fast results and precise hemoglobin analysis in seconds using a
single drop of fingerstick blood. Key
features include reduced personnel
training, reliability, and low required
user maintenance.
The Retic-Chex Linearity assays
with instrument-specific values for
reticulocyte percentages verify the
accuracy of hematology instruments. The Retic-Chek Linearity is
assayed for the Sysmex XN-series
and is available in five-level sets with
3.0 mL plastic cap-pierceable vials.
The TrinLab D2 is designed for lower
volume EIA, and offers an innovative
system, increased security, and
easy-to-use intuitive software. The
system is available with applications
for CAPTA and MarDx infectious disease, as well as autoimmune ELISA
reagents.
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ELISA AUTOMATION SYSTEM
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Molecular Blood Test Diagnoses Herpes Simplex Virus Infection
olymerase chain reaction (PCR)
is now the test of choice for identifying central nervous system infection caused by herpes simplex virus
(HSV).
A longitudinal review of HSV PCR
testing at two pediatric academic
medical centers in the USA determined the clinical features of children positive for serum HSV through
PCR testing. Scientists at the University of Texas Southwestern Medical Center (Dallas, TX, USA; www.
utsouthwestern.edu) in collaboration
with others carried out a retrospective review of all patients who had a
serum HSV PCR test at the participating institutions from 2005 to 2010.
The study focused on children with
one positive blood HSV PCR test and
reviewed their charts for demograph-
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ic, clinical, and other data. They
defined a neonatal HSV infection as
occurring before 42 days of age.
More than 700 patients received
blood HSV PCR testing during the
study period. Of those children, 294
were infants younger than 42 days
old. A positive HSV PCR test was
found in 45 patients (6.1%), 21 of
whom were infants. Of these infants,
approximately 25% were diagnosed
with skin, eye, and mouth HSV disease; another 25% were diagnosed
with central nervous system HSV disease; and approximately 50% had disseminated HSV disease. One third of
the neonatal HSV patients in this
study died. For two of those infants,
the blood HSV PCR was the only positive HSV test. In another four children, the blood HSV PCR was the
LMI-07-13 146
first test that was positive.
Among the 24 older children with
positive blood HSV PCR tests, 50%
were immunocompromised. Another
29% suffered from atopic dermatitis.
Mucocutaneous lesions were much
more common, occurring in 92% of
these older children and 13% of the
older children died. In four of the
older children, the blood HSV PCR
was the only positive test, and it was
the first positive test in another seven
of these children, all of whom had
vesicular lesions that would have
clinically suggested an HSV diagnosis.
The authors concluded that HSV PCR
testing on serum samples can be a
useful adjunct in the diagnosis of
HSV, especially among young infants
who are much less likely than older
children to have mucocutaneous
lesions. The study was published in
the August 2012 edition of the
Journal of Pediatrics.
Serum Albumin Levels
Predict Pneumonia Severity
he prognostic value of serum
albumin levels in hospitalized
adults with community-acquired
pneumonia has been evaluated.
When serum albumin levels are
measured within 24 hours of admission to the hospital, they can be correlated with the outcome of patients
with community-acquired pneumonia (CAP).
Scientists at the University Hospital of Bellvitge (Barcelona, Spain;
www.bellvitgehospital.cat) carried
out a prospective cohort of adults
with CAP requiring hospitalization
from 1995 through 2011. Serum
albumin results were obtained from
the central laboratory database and
were determined by a molecular
absorption spectrometry utilizing
bromocresol green. Pathogens in
blood, normally sterile fluids, sputum, and other samples were investigated using standard microbiological
procedures. Serum albumin levels
were measured within 24 hours of
admission. The primary end point
was 30-day mortality.
T
During the study period, 3,463
patients with CAP required hospitalization. The median value of albumin
was 31 g/L. As levels of serum albumin decrease, the risk of complications
significantly
increased.
Decreased albumin levels were also
significantly associated with prolonged time to reach clinical stability,
prolonged hospital stay, intensive
care unit (ICU) admission, the need
for mechanical ventilation, and 30day mortality. Hypoalbuminemia was
documented in 1,307 (37.7%)
patients, whose serum albumin was
less than 30 g/L.
The authors concluded that
hypoalbuminemia is frequent among
hospitalized patients with CAP. Low
serum albumin levels within 24
hours of hospital admission are significantly associated with increased risk
of complications and poor outcome
from CAP. Serum albumin is an
objective and good prognostic marker
in hospitalized adults with CAP. The
study was published on December
31, 2012, in the Journal of Infection.
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Genetic Test Identifies Small but Deadly Lung Cancers
novel genetic test can help identify small
but aggressive lung tumors associated with
poor survival.
The test can identify highly aggressive lung
cancer at a very early stage and the results may
help physicians decide on which chemotherapy
treatment is suitable for patients with aggressive
tumors.
Scientists at the University of California, San
Francisco (UCSF; CA, USA; www.ucsf.edu)
working with colleagues from California and
China, conducted an international validation
study of the newly available genetic test in small
tumors likely to be detected by the new lung
cancer computed tomography (CT) screening
A
Increasing Antigen
Levels Predicts Aggressive
Prostate Cancer
guidelines. They studied 269 patients who
underwent lung surgery to remove aggressive,
non-small-cell lung tumors that were smaller
than 2 cm in size. Aggressive tumors usually
form, grow, and spread quickly, but theses
tumors had not yet spread to the lymph nodes.
The investigators found overall postsurgical
survival rates of 83%, 69%, and 52% in low-,
intermediate-, and high-risk groups, respectively. Similar results were found in analyzing
tumors sized 1 cm or smaller. Early detection of
lung tumors through low-dose computed tomography (CT) screening, combined with a reliable
test that can identify highly aggressive tumors
that benefit from individualized treatments, will
help decrease the mortality rate from lung cancer, the leading cancer killer of men and women
in the USA, according to the American Cancer
Society (Atlanta, GA, USA; www.cancer.org).
Johannes Kratz, MD, from the UCSF said,
ongitudinal measures of prostate specific antigen (PSA) improve the accuracy of aggressive
prostate cancer detection when compared with a
single measurement of PSA alone.
As a rule, the higher the PSA level in the blood,
the more likely a prostate problem is present, but
many factors, such as age, race, and noncancerous
conditions can affect PSA levels.
Scientists from Kaiser Permanente (Pasadena,
CA, USA; www.kaiserpermanente.org) collaborating with others, retrospectively examined the electronic health records of 219,388 men ages 45 and
older who had at least one PSA measurement,
while some had at least three PSA measurements.
This cohort was followed from January 1, 1998, to
December 31, 2007, for the development of biopsy-confirmed prostate cancer.
The annual percent changes in total serum PSA
levels were estimated using linear mixed models.
The accuracy of prostate cancer prediction was
assessed for prostate cancer overall and for aggressive disease with a Gleason score equal to or
greater than seven, and was compared with that of
a single measure of PSA level using area under the
receiver-operating characteristic curves.
The study found that annual percent changes in
PSA more accurately predicted the presence of
aggressive prostate cancer when compared to single measurements of PSA alone, but only marginally improved the prediction of prostate cancer overall. The men in the cohort showed a mean change
of 2.9% in PSA levels per year and the rate of
change in PSA increased modestly with age.
Lauren P. Wallner, PhD, MPH, the study lead
author, said, “The results of this study could provide clinicians with a better prostate cancer preventive strategy that could help differentiate
between men with an aggressive form of the disease and those who have slow growing, indolent
cancer that may not necessarily merit treatment.
Our study demonstrates that repeated measurements of PSA over time could provide a more accurate, and much needed detection strategy for
aggressive forms of prostate cancer.” The study
was published on January 15, 2013, in the British
Journal of Urology International.
“We have known for a number of years that
patients with aggressive early stage lung cancers
identified by molecular prognostic tests benefit
from additional therapy. Imagine receiving the
news from your doctor that despite undergoing
surgery for your tiny one-centimeter lung cancer, you still have a 25% chance of dying in the
next five years. Now, instead of telling these
patients we have nothing more for them, we
can offer this test which reliably identifies
whether they have highly aggressive tumors.”
He added, “This new genetic test is immediately available to clinicians via a CLIA-approved
testing laboratory, and it’s a tool that patients
can ask their physicians about today, not sometime in the future.” The study was presented at
the 49th Annual Meeting of The Society of
Thoracic Surgeons held 26-30 January, 2013 in
Los Angeles (CA, USA; www.sts.org).
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Gene Found for Common
Form of Epilepsy
gene mutation linked to the
most common form of epilepsy
has been found that could in the
future lead to a genetic test for the
condition. The use of exome
sequencing detected the gene for
autosomal dominant familial focal
epilepsy with variable foci (FFEVF),
which is notable because family
members have seizures originating
from different cortical regions.
A team of scientists working with
those at University of South
Australia (Adelaide, SA, Australia;
www.unisa.edu.au) studied about
90 families where two members had
epilepsy. The exomes of individuals
were independently sequenced both
in Australia and in The Netherlands.
The coding sequences were
enriched using the SureSelect
Human All Exon 50Mb kit (Agilent
Technologies; Santa Clara, CA, USA;
www.agilent.com). After sequence
A
capture and amplification, fragments
were sequenced using a SOLiD v4
instrument (Applied Biosystems;
Mulgrave, VIC, Australia; www.
appliedbiosystems.com.au).
The results showed that a gene
called DEP domain-containing 5
(DEPDC5) causes focal epilepsy in
about 12% of families in which only
two people have focal epilepsy. This
high frequency establishes DEPDC5
mutations as a common cause of
familial focal epilepsies. As well as
opening new opportunities for diagnosing epilepsy, the scientists
believe their discovery will also lead
to better-targeted treatments.
The identification of DEPDC5 as
the gene underlying FFEVF substantially advances understanding of the
pathogenesis of epilepsy by implicating another new gene pathway. Apart
from enabling the diagnosis of FFEVF
through molecular testing, these find-
ings also enable strategies to be
devised to improve prognosis through
tailored treatment targeting DEPDC5.
Ingrid E. Scheffer, MD, professor
and pediatric neurologist, of the
Florey Neuroscience Institute (Melbourne, VIC, Australia; www.florey.
edu.au) said, “This discovery is paradigm shifting, if you have focal
epilepsy and there is no cause
known, then this gene should be tested to look for a mutation.” The study
was published on March 31, 2013,
in the journal Nature Genetics.
Image: The SureSelect Human AllExon V5 and V5 + UTRs are designed
for next-generation sequencing and
produce exome samples ready for
sequencing the next day (Photo courtesy of Agilent Technologies).
Project Focuses on Discovery of Early Cancer in Women
cientists are focusing on the early detection of
breast and ovarian cancer with the goal of
developing a test to identify tumor markers present
in blood and link these markers to the presence of
cancer. Partners in the project called EpiFemCare,
include GATC Biotech (Constance Germany, www.
gatc-biotech.com), which will manage sample processing, i.e., the DNA isolation from serum and the
reduced representation bisulfite sequencing from
serum derived DNA. This method analyses DNA
methylation in normal and tumor DNA.
In addition, 6 institutions from 5 European countries combining clinical, scientific, and industrial
expertise will add a new dimension to the treatment
of cancer in women. The USD 7.8 million project
S
from the European Commission will develop and test
new methods for screening, diagnosing, and personalizing treatment of breast and ovarian cancer.
“We are proud of being a partner within the
development of a DNA-based blood test that promotes new ways of diagnosing and treating patients
with breast or ovarian cancer. The processing of
samples in our ISO 17025 certified Genome &
Diagnostic Center is one of our key competences,”
commented Peter Pohl, CEO of GATC Biotech AG.
The collaborative project is led by Prof. Martin
Widschwendter from the Department of Women’s
Cancer at the University College London (United
Kingdom; www.instituteforwomenshealth.ucl.ac.uk).
Collaborators include Charles University (Prague,
Czech Republic), Ludwig Maximilians University
(Munich, Germany), and companies with expertise in
epigenetics and next generation screening (GATC
Biotech, Germany), managing, and analyzing the
large volumes of data created by these experiments
(Genedata; Switzerland).
Implementation of successful screening programs
has dramatically reduced the number of women
dying from cervical cancer. Similarly, the EpiFemCare
project aims to reduce the number of women who
receive a diagnosis of breast or ovarian cancer when
that cancer is already advanced by 50%, also reduce
the number of women who receive unnecessary longterm chemotherapy by 50%, and reduce the number
of women dying from these female cancers by 20%.
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Blood-Based Biomarkers Diagnose Parkinson’s Disease
bjective and measurable biomarkers to
improve Parkinson’s Disease (PD) diagnostics would be advantageous during its earlier
stage, prior to the motor onset phase.
Blood-based circulating micro ribonucleic acid
(miRNA) biomarkers for PD are quantifiable, as it
is known that miRNAs detected in various cells
and tissues can also be found in biofluids such as
blood plasma and serum.
Scientists at the Van Andel Institute (Grand
Rapids, MI, USA; www.vai.org) obtained the global miRNA expressions in plasma from an initial
discovery set of 32 PD patients and 32 normal
controls. They identified nine pairs of PD-predictive classifiers and 13 most differentially
expressed miRNAs as potential biomarkers to discriminate PD patients from normal controls.
The team used a quantitative real-time polymerase chain reaction technique (qRT-PCR) to
O
validate and evaluate the performance of these
biomarkers. The study subjects were all recruited between January 2006 and November 2009.
Total RNA that included miRNAs was isolated
from plasma using the TRI reagent RT-blood protocol (Molecular Research Center, Cincinnati,
OH, USA; www.mrcgene.com). RNA samples
were processed, labeled, and hybridized onto
microarrays.
The investigators identified nine pairs of PDpredictive classifiers and 13 most-differentially
expressed miRNAs as potential biomarkers to discriminate PD patients from normal controls. The
combination of biomarkers that achieved the
highest predictive performance was applied to
another set of 42 PD patients and 30 controls
from the same clinical site. A new, independent
validation set of samples from 30 PD patients
from a different clinical site showed lower bio-
marker performance.
Sok Kean Khoo, PhD, the senior author said,
“The ideal biomarker should be minimally invasive, cost efficient, quantifiable, reproducible, specific, and sensitive. Biofluids such as plasma could
provide an ideal resource for development of such
desirable biomarkers. This is a proof-of-concept
study to demonstrate the feasibility of using plasma-based circulating miRNAs. The hypothesis
that miRNA expression changes are associated
with the neurodegenerative disease process,
either directly or as part of positive feedback
loops, is emerging rapidly. This study opens new
opportunities to the exploration of circulating
miRNAs for diagnostic, prognostic, and therapeutic interventions for PD and possibly other neurodegenerative diseases.” The study was published in the December 2012 issue of the Journal
of Parkinson’s Disease.
Blood Calcium Levels
Linked to Ovarian Cancer
igh blood calcium levels might
predict ovarian cancer, the most
fatal of the gynecological cancers.
Many ovarian cancers express
parathyroid hormone-related protein,
which acts to raise calcium levels in
serum, which may be a biomarker for
ovarian cancer.
Cancer epidemiologists at Wake
Forest Baptist Medical Center (Winston-Salem, NC, USA; www.wake
health.edu) measured total and ionized serum calcium levels using ionspecific electrodes. They were pHadjusted because the protein binding
of calcium is affected by pH; ionized
calcium in blood is commonly corrected to standard pH. Serum samples were collected as part of Third
National Health and Nutrition
Examination Surveys (NHANES III)
between 1988 and 1994 from two
nationally representative prospective
cohorts.
Eleven ovarian cancer deaths
were observed over 95,556 personyears of follow-up through December
31, 2006, representing 137,404
ovarian cancer deaths in the United
States of America. The range in total
serum calcium in cases was 2.14–
2.44 mmol/L and for ionized serum
calcium was 1.17–1.31 mmol/L.
The normal reference range for total
serum calcium is approximately
2.17–2.52 mmol/L and 1.12–
1.32 mmol/L for ionized serum calcium. In the second cohort, there
were eight ovarian cancer cases in
over 31,089 person-years of followup. The range of total serum calcium
was 1.98–2.93 mmol/L. The rela-
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tive hazard for fatal ovarian cancer
was 1.52 per 0.1 mmol/L increase in
total serum calcium and 2.44 per 0.1
mmol/L increase in ionized serum
calcium.
Gary G. Schwartz, PhD, the lead
author of the study, said “One
approach to cancer biomarker discovery is to identify a factor that is differentially expressed in individuals with
and without cancer and to examine
that factor’s ability to detect cancer in
an independent sample of individuals.” His coauthor added, “Everyone’s got calcium and the body regulates it very tightly. We know that
some rare forms of ovarian cancer are
associated with very high calcium, so
it’s worth considering whether more
common ovarian cancers are associated with moderately high calcium.”
The authors concluded that this
biomarker, the higher levels of calcium in serum, were significantly positively associated with the risk of
ovarian cancer in two prospective
cohorts. The principal limitation of
this study is the small number of
cases. Conversely, the study has several strengths: it is prospective, uses
population-based data from two
nationally representative cohorts,
and is the first to study ionized
serum calcium. The existence of
stored sera from sample sets of
women with and without ovarian
cancer should facilitate the confirmation or refutation of the association between serum calcium and
ovarian cancer. The study was published January 9, 2013, in the journal Gynecologic Oncology.
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Mast Cell Biomarker Predicts Severity of Dengue
protein produced by mast cells in the
immune system may predict which people
infected with dengue virus will develop lifethreatening complications.
Dengue virus (DENV) spread by mosquitoes,
infects as many as 390 million people worldwide
each year, and is a significant health issue in tropical areas of the world including parts of Latin
America and Asia, and health professionals in
Florida have reported cases in recent years.
Scientists at Duke University (Durham, NC,
USA; www.duke.edu) working with their colleagues at Duke-National University of Singapore
(www.duke-nus.edu.sg) investigated the role of
mast cells in attacking dengue virus in humans,
and identified a biomarker derived from the mast
A
cells, that appeared to predict the most severe
cases of the disease in human patients.
Samples used for the investigation were derived
from patients who ranged in age from 18 to 77
years, with a mean of 40 years; 42% of samples
were obtained from females, and 58% from males.
Dengue positive samples were determined based
on physician diagnosis as well as molecular tests
including reverse transcriptase polymerase chain
reaction (RT-PCR) for viral ribonucleic acid (RNA).
The dengue fever (DF) and dengue hemorrhagic
fever (DHF) patient sera used in this study were previously determined to be positive for serotypes 1, 2,
or 3 by RT-PCR using the OneStep RT-PCR Kit
(Qiagen; Valencia, CA, USA; www.qiagen.com).
Enzyme-linked immunosorbent assay (ELISA) kits
for the human mast cell biomarker chymase, a serine protease, were obtained from Antibodies-Online
(Atlanta, GA, USA; www.antibodies-online.com).
Patients that were diagnosed with DF or DHF
showed chymase levels in serum obtained during
the acute phase of infection were significantly
higher than levels in the serum of either healthy
controls or individuals with fever that were DENV
negative by RT-PCR. DF patients displayed an
increase in serum chymase that was approximately 10 times higher than in healthy individuals or
DENV-negative patients while, in DHF patients,
chymase levels 30 times higher than healthy controls were detected.
The study was published on April 30, 2013, in
the journal eLife.
Antinuclear Antibodies Detected by Automated Immunofluorescence
ntinuclear and anticytoplasmic antibodies are
important diagnostic markers for systemic
rheumatic diseases and autoimmune hepatitis.
The diagnostic performance of automated systems for image acquisition and interpretation of
indirect immunofluorescence-based tests for antinuclear antibodies are increasingly being used.
Scientists at the Catholic University Leuven
(Leuven, Belgium; www.kuleuven.be) measured by
automated indirect immunofluorescence 268 consecutive samples submitted to the laboratory for
antinuclear antibody testing. Included in the study
were in 231 patients with a systemic rheumatic disease at the time of diagnosis, 143 blood donors,
134 patients with chronic fatigue syndrome, and
A
133 diseases controls whose diagnosis of systemic
rheumatic disease was excluded.
Antinuclear antibodies were detected by Zenit
G-Sight (A. Menarini Diagnostics, Florence, Italy;
www.menarinidiagnostics.it), an automated system
for image acquisition and interpretation of indirect
immunofluorescence-based tests. The automated
fluorescence microscope uses a light-emitting diode
(LED) light source with a 450–490 nm bandwidth
and is equipped with a motorized precision stage
for up to five slides and a Charged Coupled Device
(CCD) color camera.
Image acquisition by G-Sight was of high quality
and the accuracy of pattern assignment was limited. There was a significant correlation between
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automated estimation of fluorescence intensity,
known as the probability index of positivity and
end-point titer. Probability index interval specific
likelihood ratios for systemic rheumatic disease
increased with increasing level of positivity probability.
Probability indexes were higher with the transfected mitotic human epithelioid (Hep-2000) cell
substrate (Immunoconcepts; Sacramento, CA,
USA; www.immunoconcepts.com) than with the
human epithelial cell (Hep-2) substrate. The probability indexes reached a plateau at titer 160 with
the Hep-2000 substrate.
The study was published on January 16, 2013,
in the journal Clinica Chimica Acta.
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Flow Cytometry Evaluated for Cord Blood Differentials
he potential of flow cytometry to analyze and
to report leukocyte differentials on cord blood
to be used for hematopoietic stem cells has been
evaluated.
Currently, the reference method for white
blood cell (WBC) is the microscopic manual
count, but international standards advise that
potential donor blood is tested for total nucleated
cell count, nucleated red blood cell count
(nRBCs), total number of CD34 cells, viability or
potency as measured by viable CD34 cells.
Colony-forming unit assays, microbial cultures,
and finally a complete blood count with WBC differential are also advisable.
Hematologists at the Centre Hospitalier
Universitaire (CHU; Rennes, France; www.
chu-rennes.fr) analyzed 161 cord bloods between
November 2010 and February 2011. WBC differentials were determined for each sample, by a cell
counter, a manual method, and the flow cytome-
T
try using an antibody cocktail. WBC differential
includes the count of neutrophils, eosinophils,
basophils, lymphocytes, monocytes, immature
granulocytes, and blasts cells.
All samples were analyzed on the HematoFlow
platform (Beckman Coulter, Miami, FL, USA;
www.beckmancoulter.com) within 12 hours of
collection. This platform is built around Beckman
Coulter’s FP1000 cell preparator, along with their
FC500 five-color flow cytometer. The antibody
cocktail used was another Beckman Coulter product called the CytoDiff.
A good correlation was obtained for neutrophils, lymphocytes, and immature granulocytes
when the manual method was compared to the
flow cytometry, but was weaker for eosinophils
and even lower for monocytes and basophils. The
flow cytometry method employed allowed the
identification of 12 cell subtypes (neutrophils,
eosinophils, basophils, B lymphocytes, T-non-cyto-
toxic and T cytotoxic/Natural Killer (NK) lymphocytes, CD16 negative monocytes and CD16 positive monocytes, immature granulocytes, B blasts,
T blasts and non-B-non-T blasts) within a single
panel of antibodies and a minimal volume of 50
μL of blood.
The authors concluded that the flow differential has some drawbacks such as the cost of
CytoDiff reagent, but this can be balanced by the
reduction in technician time required for manual
counting and the use of a standardized product.
The flow cytometry appears as a technique completely adapted to provide a WBC differential on
a cord blood sample. The additional cell subset
counts offered in the same turn-around-time
would probably be exploited in the near future to
better characterize the engraftment potential.
The study was published in the February 2013
issue of the International Journal of Laboratory
Hematology.
Leukocyte Ratio
Predicts Ulcerative
Colitis Severity
lood neutrophil-to-lymphocyte (N/L) ratio is an
indicator of the overall inflammatory status of
the body, and an alteration in N/L ratio may be
found in ulcerative colitis (UC) patients.
An optimal test has not yet been developed for
UC and therefore the adjunctive use of additional
blood markers may add a significant advantage for
predicting disease severity and achieving diagnostic
precision.
Medical scientists at Erciyes University (Kayseri,
Turkey; www.erciyes.edu.tr) enrolled 26 UC
patients, 18 males and 8 females, and 28 healthy
controls, 10 males and 18 females in the study.
Complete blood counts, erythrocyte sedimentation
rates (ESR), and C-reactive protein levels (CRP)
were established for both patients and controls. The
white blood count (WBC), neutrophil, and lymphocyte counts were recorded, and the N/L ratios
were calculated from these parameters. The median disease duration in UC patients was 2.75 years.
The N/L ratios of patients with active UC were
significantly higher at 3.85 ± 2.71 than those of
inactive UC at 2.40 ± 1.05 and controls at 1.77 ±
0.68 were. The optimum N/L ratio cut-off point
for active UC was 2.47. There was no significant
difference between inflammation parameters, disease extension, and disease activity. The other
inflammation markers such as ESR and CRP were
also higher in the patients with active UC.
The authors concluded that in patients with
UC, the N/L ratio is strongly associated with
active disease. Unlike many other noninvasive
markers of UC, the N/L ratio is inexpensive and
readily available. Although the accuracy of the
N/L ratio for detecting active UC is suboptimal,
the ratio is an easily derived measure that might, in
combination with other markers, assist in identifying patients at increased risk of active and severe
disease. The study was published in the January
2013 issue of the Journal of Clinical Laboratory
Analysis.
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Molecular Immunoassay Diagnoses Melioidosis
elioidosis is caused by the
Gram-negative
bacterium
Burkholderia pseudomallei for
which the standard test growing it
on microbiological culture media,
which requires at least 3 to 4 days to
obtain a result, hindering successful
treatment of acute disease.
Where the seroprevalence of
antibodies to B. pseudomallei is relatively low, serology is a potentially
advantageous addition to culture in
the diagnosis of melioidosis and
serology would be very effective in
diagnosing travelers and military
personnel returning from endemic
tropical areas.
Scientists at James Cook University (Douglas, Australia; www.
M
jcu.edu.au) developed an enzymelinked immunosorbent assay
(ELISA) and a quantitative immunopolymerase chain reaction (PCR)
assay capable of detecting melioidosis-specific antibodies. They demonstrated their validity with indirect haemagglutination assay
(IHA)-negative sera from patients
with melioidosis. A total of 10 serum samples from three IHA-positive and three IHA-negative melioidosis patients were tested along
with sera from six healthy controls.
To verify the assays, the scientists
used various techniques including
immunoblotting, indirect peroxidase-conjugated protein G ELISA,
and indirect terminus utilization
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substance (Tus) DNA replication terminator sites (Ter)-lock immunoPCR. Both the latter systems Both
systems were based on the detection of immunoglobulin G (IgG) by
protein G conjugated to a signal generation system consisting of either
the enzymatic activity of peroxidase
or a quantitative PCR (qIPCR) readout in the case of Tus and the TTlock-T DNA probe. All patient sera,
including that collected at presentation and in subsequent follow-up
collections, reacted against the B.
pseudomallei antigenic fraction in
both the G-peroxidase ELISA and
TT-lock qIPCR format. Individual
negative control sera from six
healthy controls did not react
against the B. pseudomallei antigenic fraction in either assay.
The authors concluded that
although the indirect TT-lock
qIPCR system is slightly slower
than the ELISA format, it requires
the least amount of serum and
would be advantageous when multiple testing is required for the confirmation of disease. The ability to
detect antibodies in patient sera
that were persistently IHA negative
is very promising, indicating that
both immunoassay formats will be
ideal for the rapid and reliable diagnosis of melioidosis in patients in
nonendemic regions. The study
was published in the February
2013 edition of the journal
Diagnostic Microbiology and
Infectious Disease.
Image: Burkholderia pseudomallei,
the causative agent of melioidosis
(Photo courtesy of Dennis Kunkel
Microscopy).
Antibodies to Carbamylated Proteins
Provide Insight into Rheumatoid Arthritis
Booth: 2034
etection of antibodies to carbamylated proteins (anti-CarP) is
an important advance in the diagnosis
of Rheumatoid Arthritis (RA).
A study published in 2012 by a
team at Leiden University Medical
Center (LUMC; Leiden, The Netherlands; www.lumc.nl) in Proceedings of the National Academy of
Sciences of the United States of
America (PNAS) showed that
Immunoglobulin G (IgG) and IgA
antibodies recognizing carbamylated
antigens were present in about 50%
of RA patients. Anti-CarP antibodies
recognize homocitrulline and are
therefore distinct from anticitrullinated protein antibodies (ACPA), including anti-cyclic citrullinated peptide
(anti-CCP), a biomarker commonly
used to diagnose RA. Anti-CarP IgG
and IgA were detected in 16% and
30% of ACPA negative RA patients
respectively. Additionally, anti-CarP
antibodies were shown to be predictive of a more severe course of disease
as measured by radiological progression in ACPA negative RA patients.
LUMC and Inova (San Diego, CA,
USA; www.inovadx.com) have
announced the completion of an
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exclusive, worldwide license agreement for technology developed at
LUMC to detect antibodies to carbamylated proteins (anti-CarP). “The
detection of autoantibodies in sera of
RA patients has provided important
insight into the processes that initiate
and drive RA. Since anti-CarP antibodies can also be detected in a subgroup of patients for whom so far no
serological markers were available
we believe this may provide new
insight into the pathogenesis of
RA,”said Dr. Leendert Trouw, assistant professor at LUMC.
Prof. Tom Huizinga, head of the
department of Rheumatology at
LUMC added “With new treatment
options at hand it is now possible to
apply early and aggressive treatment. Understanding which patients
would benefit most from such an
intervention is important to maximize efficiency, and detection of
anti-CarP antibodies may identify
such patients.”
The LUMC is part of the Dutch
Federation of University Medical
Centers (NFU). The NFU is a collaboration of the eight University Medical
Centers of the Netherlands.
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Hepatitis C Immunoassays Evaluated
apid anti-hepatitis C (HCV)
immunoassays can assist and
identify chronically infected patients
who are unaware of their status.
The performance characteristics
of three premarket anti-HCV
immunoassays have been evaluated
and compared for their sensitivity
and specificity.
Scientists at the US Centers of
Disease Control (CDC; Atlanta, GA,
USA; www.cdc.gov) examined six
different studies that used lateral flow immuno-chromatographic
assay devices for testing serum, finger stick blood, and oral fluid from
three manufacturers. Active HCV
infection was determined by quantitative nucleic acid testing (NAT)
which detects the presence of HCV
ribonucleic acid (RNA).
The three immunoassays used in
the studies were from Chembio (Medford, NY, USA; www.
chembio.com); MedMira (Halifax,
R
NS, Canada; www.medmira.com);
and OraSure (Bethlehem, PA, USA;
www.orasure.com). Overall sensitivity and specificity was highest
when serum specimens were compared to finger stick and oral fluid
samples. The sensitivity of the
OraSure test was higher that of the
Chembio or MedMira assays.
False negative and false positive
results occurred with all assays and
specimens. OraSure had the least
number of false negative at 0% to
6%, while the MedMira assay yielded the largest proportion of false
negatives. In two studies, false negatives were associated with human
immunodeficiency viral infections.
In one study, the OraSure assay outperformed the conventional enzyme
immunoassay (EIA).
The authors concluded that antiHCV tests detect both current and
past infection, but cannot differentiate between them. Patients who are
positive with a rapid anti-HCV test
should also be tested with NAT,
which is more expensive and labor
intensive. The authors note that a
quantitative antigen assay Architect
HCV Ag (Abbott, Abbott Park, IL,
USA; www.abbott.com), which is
performed on an automated platform is available in Europe. This
assay is also less expensive and does
not require the intensive labor of the
NAT, but is less sensitive. The study
was published on December 7,
2012, in the journal Antiviral
Therapy.
Image: The OraQuick test for detection of the Hepatitis C virus (HCV)
(Photo courtesy of OraSure Technologies).
Microbiological Molecular
Assay Analyses Heart Valve Tissue
ositive heart valve (HV) culture
is a major criterion for the diagnosis of infective endocarditis, but is
poorly sensitive compared with
molecular assays.
Molecular methods applied
directly to HV tissue have shown
promise in negative-culture infective
endocarditis and sequencing of the
gene encoding 16S ribosomal ribonucleic acid (rRNA) is an accurate
means of identifying microorganisms
and, offers sensitive and rapid diagnosis.
Scientists at the Central University
Hospital at Limoges (CHU; France;
www.chu-limoges.fr) applied a twostep broad-range polymerase chain
reaction (PCR) and a specific realtime PCR to HV samples and compared the results with those of serologic tests and conventional microbiological methods. This study examined HV samples excised from 31
patients with definite endocarditis
based on Duke’s modified criteria,
between January 1, 2002, and
December 31, 2007. The aortic valve
was affected in 15 cases and the
mitral valve in 16 cases.
Two broad-range PCR methods
were applied to the 31 HV samples.
The first was a real-time (RT-PCR)
method, followed by a conventional
end-point PCR that was applied to
HV samples on which the first PCR
was negative. Five specific RT-PCR
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procedures were also used in order to
identify Bartonella spp., Tropheryma
whipplei, Chlamydophila pneumoniae, Mycoplasma pneumonia, and
Coxiella burnetii. Blood cultures
were positive in 23 cases.
The RT-PCR was positive in 11 of
the 23 patients with blood culturepositive endocarditis. All the
sequencing results matched the
blood culture results to the genus
level at least. Seven culture-negative
HV specimens gave an amplification
product, sequencing of which identified Streptococcus mutans in one
patient and Streptococcus anginosus
in another patient. Streptococcus
gallolyticus was found three patients
and Staphylococcus epidermidis in
two patients. Specific PCR identified
one T. whipplei, which was also
identified by conventional end-point
PCR.
The authors concluded that the
strategy of combining the two-step
broad-range PCR methods improved
the sensitivity of the molecular
method from 38.7% to 58%. Their
results confirm that blood culture is
still the gold standard for the diagnosis of infective endocarditis, but does
show that molecular methods
applied to HV can be useful when
blood culture is negative. The study
was published January 12, 2013, in
the journal Diagnostic Microbiology
and Infectious Disease.
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Saliva Gland Test Proposed
for Parkinson’s Diagnosis
bnormal proteins associated with Parkinson’s
are consistently found in the submandibular
salivary glands, under the lower jaw. Therefore,
testing a portion of a person’s saliva gland may be
a way to diagnose Parkinson’s disease.
Scientists from the Mayo Clinic Arizona
(Phoenix, AZ, USA; www.mayoclinic.org/arizona) performed a study of 15 people with an
average age of 68 who had Parkinson’s disease for
an average of 12 years, responded to Parkinson’s
medication, and did not have known salivary
gland disorders. Biopsies were taken of two different salivary glands: the gland under the lower jaw
and the minor salivary glands in the lower lip. The
biopsied tissues were stained and reviewed for
evidence of the abnormal Parkinson’s protein.
In four of the initial lower jaw biopsies, while
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researchers were still perfecting the technique,
not enough tissue was available to complete the
tests. The abnormal Parkinson’s protein was
detected in nine of the 11, or 82%, of the patients
with enough tissue to study.
“While still under analysis, the rate of positive
findings in the biopsies of the lower lip glands
appears to be much lower than for the lower jaw
gland. This study provides the first direct evidence
for the use of lower jaw gland biopsies as a diagnostic test for living patients with Parkinson’s disease,” said study author Charles Adler, MD, PhD,
with the Mayo Clinic Arizona and a Fellow of the
American Academy of Neurology. “This finding
may be of great use when needing tissue proof of
Parkinson’s disease, especially when considering
performing invasive procedures such as deep
brain stimulation surgery or gene therapy.”
The investigators intend to present the study at
the American Academy of Neurology’s 65th annual meeting in San Diego (CA, USA), March 16-23,
2013.
Image: Anatomical illustration of human salivary
glands (Photo courtesy of PR Science).
Genetic Markers Associated with
Early Cancer-Specific Mortality
n analysis has found that the loss or amplification of particular DNA regions contributes to
the development of prostate cancer.
Novel effectors and markers of localized but
potentially life-threatening prostate cancer (PCa)
have been identified by evaluating chromosomal
copy number alterations (CNAs) in tumors from
patients who underwent prostatectomy. A team of
scientists at Wake Forest School of Medicine
(Winston-Salem, NC, USA; www.wakehealth.edu)
used a method that can detect these genetic
changes in cells from prostate tumors from 125
patients who underwent radical prostatectomy
between 1988 and 2004. A second cohort included 103 prostatectomy patients who were treated
between 2002 and 2008 with a median follow-up
of approximately five years most of whom had a
less aggressive form of PCa.
CNAs in tumor DNA samples from 125 patients
in the discovery cohort who underwent prostatectomy were assayed with high-resolution Affymetrix 6.0
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single-nucleotide polymorphism microarrays (Santa
Clara, CA, USA; www.affymetrix.com) and then
were analyzed using the Genomic Identification of
Significant Targets in Cancer (GISTIC) algorithm.
The investigators found that changes in 20 gene
regions were likely to contribute to prostate cancer
development and changes in seven of the 20
regions were linked with early death from prostate
cancer. Patients whose cancer cells had a loss of the
gene that encodes for phosphatase and tensin
homolog protein (PTEN) and an amplification of the
gene that encodes for myelocytomatosis viral oncogene homolog (MYC) were more than 50 times as
likely to die from prostate cancer than other
patients who had similarly staged tumors and
prostate-specific antigen levels at the time of diagnosis. Analyses of 333 tumors from additional
patients confirmed the link between PTEN and
MYC and prostate cancer lethality.
The study was published on April 22, 2013, in
the journal Cancer.
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Diagnostic Test Rapidly
Detects Candida
nano-inspired platform has been developed
that detects DNA from five of the most common Candida species found in patient blood.
The diagnostic platform based on T2 magnetic
resonance, which is capable of sensitive and rapid
detection of fungal targets in whole blood in
approximately three hours, or up to 25 times faster
than the current gold standard of blood culture.
A scientific team led by those from Brown
University (Providence, RI, USA; www.brown.edu)
studied the use of a novel diagnostic method based
on T2 magnetic resonance (T2MR) to diagnose candidemia. The T2Candida assay uses blood-compatible polymerase chain reaction (PCR) to amplify
Candida DNA, which then binds to superparamagnetic nanoparticles coated with a complementary
DNA strand. The binding event causes the nanoparticles to cluster, which changes the sample’s T2MR
signal.
The investigators tested both Candida-spiked
and patient samples and were able to rapidly, accurately, and reproducibly detect five Candida species
within human whole blood with a limit of detection as low as one colony forming units (CFU)/mL
and a time-to-result of approximately three hours.
Spiked samples showed 98% positive agreement
and 100% negative agreement between T2MR and
blood culture. Clinical samples demonstrated similar concordance with blood culture with the important distinction that T2MR was able to identify
Candida species in the presence of antifungals,
whereas blood culture could not.
The T2MR diagnostic platform is a product of
T2Biosystems (Lexington, MA, USA; www.
t2biosystems.com) and using this system the scientists were able to detect down to three CFU/mL of
C. albicans and C. tropicalis and even lower limits
of detection for C. krusei, C. glabrata, and C. parapsilosis. From 24 patients’ whole-blood samples,
they were able to correctly identify the 8 candidemic patients, without any false-positive readouts from
blood samples that contained bacteria.
The study was published on April 24, 2013, in
the journal Science Translational Medicine.
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Plants Provide Diagnostic Reagent for West Nile Virus
method has been developed for testing for
West Nile Virus (WNV), using plants to
produce biological reagents for detection and
diagnosis.
A plant expression system has been investigated for protein production due to its low-cost and
high-scalability nature and its ability to make
appropriate posttranslational modifications.
Scientists at Arizona State University
(Tempe, AZ, USA; www.asu.edu) explored the
feasibility of using plant transient expression
systems to produce two groups of protein
reagents that are required for the detection and
diagnosis of WNV infection. One was a recombinant antigen derived from the domain III
(DIII) of WNV envelope (E) protein and the second, a monoclonal antibody (mAb E16) that
specifically recognizes WNV DIII.
High expression levels of both reagents were
A
observed in two kinds of plants: Nicotiana benthamiana, which is a close relative of tobacco,
and lettuce. The two reagents may be readily
purified to greater than 95% and retain their
native functionality and specificity. The binding
specificity of plant-derived E16 at various concentrations of this mAb were incubated with
either DIII of WNV or DIII of Dengue virus
serotype 2 (DENV-2) that was immobilized on
an enzyme linked immunosorbent assay (ELISA)
plate. A mammalian cell-culture-derived E16
and a generic human immunoglobulin G (IgG)
(Southern Biotech, Birmingham, AL, USA;
www.southernbiotech.com) were used as the
positive and negative control, respectively.
The binding to WNV DIII increased with the
concentration of lettuce or N. benthamianaderived E16 in the reaction in a similar manner as
the mammalian cell-derived E16 positive control.
In contrast, none of the E16s showed specific
binding to DIII of DENV-2. The negative control,
a generic human IgG, showed no specific binding
to either WNV or DENV-2 DIII. These results indicate that the specific avidity for WNV DIII is
retained by the plant-derived E16s. This high
specificity makes it a valuable reagent in obtaining
unambiguous diagnostic results for detecting
WNV and WNV infection.
Qiang Chen, PhD, the senior author said,
“Our test will improve the accuracy of diagnosis, leading to the proper treatment of patients
affected by WNV. The plant-derived monoclonal
antibody we examined is not only low-cost, but
highly specific for WNV antigen and does not
recognize antigens from other flaviviruses.” The
study was published in the October 2012 issue
of the Journal of Biomedicine and Biotechnology.
Genetic Mutations Identified
for Cowden Syndrome
wo new genes have been identified that are associated with
Cowden syndrome (CS), an underdiagnosed condition that carries high
risks of breast, thyroid, and other
cancers.
The discovery of these genes will
promote diagnosis and clinical management of CS while also assisting in
predictive genetic testing and genetic
counseling for a disease that is difficult to recognize and is characterized
by small, noncancerous growths.
Scientists at the Cleveland Clinic
(Cleveland, OH, USA; www.clevelandclinic.org) performed genetic
sequencing on DNA from individuals
with CS who have none of the
known genetic alterations associated
with CS. State-of-the-art technology
was used to identify a high prevalence of mutations in the phosphatidylinositol-4,5-bisphosphate 3kinase, catalytic subunit alpha
(PIK3CA) and the alpha serine/threonine-protein kinase (AKT1) genes,
which are involved in cancer-related
signaling pathways.
Germline mutations in the phosphatase and tensin homolog (PTEN)
gene were found to cause 85% of CS
when data from tertiary academic
centers was analyzed. However,
prospective data from the community over the last 12 years has revealed
a 25% PTEN mutation frequency.
PTEN is the phosphatase that has
been implicated in a heritable cancer
syndrome and subsequently in multiple sporadic cancers and developmental processes.
The investigators found that 8 of
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91 (8.8%) unrelated CS individuals
without germline PTEN mutations
carried 10 germline PIK3CA mutations and 2 (2.2%) had AKT1 mutations. These mutations result in significantly increased phosphorylation
of AKT on the activation residue
Thr308 (P-Thr308-AKT) and increased cellular phosphatidylinositol (3,4,5)-triphosphate (PIP3).
These results suggest that PIK3CA
and AKT1 are CS susceptibility
genes.
Charis Eng, MD, PhD, who is the
Founding Director of the Lerner
Research Institute’s Genomic Medicine Institute (Cleveland, OH, USA;
www.lerner.ccf.org) said, “Geneenabled risk assessment and management begins with the identification of
all the genes that, when mutated,
account for as many or all the individuals with a particular syndrome, in
this case CS. We started with only
PTEN, and now we know that succinate dehydrogenase complex, subunit B, iron sulfur (SDHB/D), killin,
p53-regulated DNA replication
inhibitor (KLLN), PIK3CA, and AKT1
account for CS. Each also brings differing risks of breast, thyroid, and
other cancers, and so this discovery
directly aids genetic counseling and
clinical management.” Cowden syndrome is a rare autosomal dominant
inherited disorder characterized by
multiple tumor-like growths called
hamartomas and an increased risk of
certain forms of cancer. The study
was published on December 13,
2012, in the American Journal of
Human Genetics.
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Automated Workstation Screens Urine Before Culture
utomated systems have been developed to
screen urine in order to eliminate those in
which a culture is highly unlikely to yield clinically relevant results. A flow cytometry system that
quantifies urine elements associated with urinary
tract infection (UTI) has recently added a new element, the detection of “all small particles” (ASP) to
improve the sensitivity of the assay.
Scientists at the Veterans Affairs Medical Center
(Houston, TX, USA; www.houston.va.gov) evaluated
1,000 urine specimens submitted consecutively that
had a urine culture and urinalysis ordered on the
same day. Specimens were tested for leukocyte
esterase and nitrite with a chemistry dipstick analyzer and for white blood cells (WBC), ASP, bacteria,
and yeast with an automated urinalysis system.
Urinary samples were also tested on bacterial culture
plates.
There were 893 samples from male patients,
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and 107 from females. There were 123 specimens
from patients with indwelling urinary catheters. Of
the 1,000 specimens evaluated 604 (60.4%) were
culture positive at any level, that is equal to or
greater than 103 colony forming units (CFU)/mL.
Two combinations of results available on the iQ200
Workstation (Iris Diagnostics; Chatsworth, CA,
USA; www.irisdiagnostics.com) were assessed for
sensitivity, specificity, and negative predictive value
(NPV). One method assessed leukocyte esterase,
WBCs, nitrite, and the presence of few or more
bacteria or yeast, a combination chosen to reflect
the current parameters combination of manual urinalysis strips and standard microscopy. The other
method assessed WBCs, the presence of few or
more bacteria or yeast, and an ASP count of greater
than 10,000, thus eliminating the redundancy of
biochemical markers and focusing on the microscopic elements available on the iQ200.
The iQ200 Workstation is used in combination
with the Aution Max AX-4280 chemistry dipstick
analyzer (Arkray; Edina, MN, USA; www.
arkrayusa.com). The scientists found that the dipstick
analysis added no advantage in a laboratory with
microscopy. Although specificities were generally
low, between 65.6% and 70.1%, the goal for screening samples is high sensitivity and NPV. The NPV
approached 95% in comparison to the gold standard,
but was further improved to greater than 99% when
compared to the ordering clinician’s diagnosis or an
expert review that assessed the indications in the
record that a UTI was present. The authors concluded that ASP did not enhance specificity, sensitivity, or
NPV. The iQ200 Workstation performed well by any
standard, thus providing a reliable system by which
to improve the use of laboratory resources. The study
was published in the January 2013 issue of the journal Diagnostic Microbiology and Infectious Disease.
Biomarkers Identified for Acute Kidney Injury Risk
wo biomarkers have been discovered for the
early assessment of acute kidney injury (AKI)
that can be easily measured in urine.
The two novel biomarkers can detect affected
patients roughly 12 to 36 hours earlier than current
tests for adult patients and have been subsequently
validated using a clinical assay and compared to
existing markers of AKI.
Scientists at the Mayo Clinic (Rochester, MN,
USA; www.mayoclinic.org ) led a multicenter study
to evaluate nearly 340 biomarkers to find the two
with the highest correlation to kidney injury risk. In
the discovery phase, they enrolled 522 adults in
three distinct cohorts including patients with sepsis, shock, major surgery, and trauma and examined
over 300 markers. In the validation study, they
enrolled 744 adult subjects with critical illness and
without evidence of AKI at enrollment. The final
analysis cohort was a heterogeneous sample of 728
T
critically ill patients.
Paired urine and blood samples were collected
at enrollment and up to 18 hours later by standard
methods and centrifuged. Biomarkers were measured with single or multiplexed immunoassays
using standard enzyme-linked immunosorbent
assays (ELISA). The platforms used were the
Luminex 200 (Luminex; Austin, TX, USA; www.
luminexcorp.com); the MSD SECTOR Imager 6000
(Meso Scale Discovery; Gaithersburg, MD, USA;
www.mesoscale.com), or the Astute140 Meter
(Astute Medical; San Diego, CA, USA; www.
astutemedical.com). The two biomarkers with the
highest correlation to kidney injury risk were the
Insulin Growth Factor Binding Protein-7 (IGFBP-7)
and Tissue Inhibitor of Metalloproteinases-2 (TIMP-2).
The investigators also examined the performance of urine TIMP-2 and IGFBP7 compared to various other markers including urine kidney-injury
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marker-1 (KIM-1) and urine neutrophil gelatinaseassociated lipocalin (NGAL) in terms of discrimination between AKI of different severities and various
non-AKI conditions including chronic kidney disease. Unlike existing markers, TIMP-2 and IGFBP7
showed clear separation between AKI and non-AKI
conditions.
The authors concluded that urine insulin-like
growth factor-binding protein 7 (IGFBP7) and tissue
inhibitor of metalloproteinases-2 (TIMP-2) are new
biomarkers for AKI and perform better than existing
markers for predicting the development of moderate
or severe AKI within12 hours of sample collection.
The risk for major adverse kidney events, such as
death, dialysis, or persistent renal dysfunction within 30 days, was elevated sharply for [TIMP2]•[IGFBP7] above 0.3 and doubled when values
were greater than 2.0. The study was published on
February 6, 2013, in the journal Critical Care.
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Real-Time PCR Instrument Designed
for Clinical Diagnostic Laboratories
Real-Time polymerase chain reaction (PCR)
instrument can perform numerous diagnostic
functions, including pathogen detection, gene
expression analysis, SNP genotyping, copy number analysis, mutation detection, micro-RNA and
other noncoding RNA analysis, and high-resolution melt analysis.
Life Technologies Corp. (Carlsbad, CA, USA;
www.lifetechnologies.com) has launched its
Applied Biosystems QuantStudio Dx Real-Time PCR
instrument. The instrument is CE-in vitro diagnostic
(IVD) marked for use in Europe and represents a significant extension of Life Technologies’ product
offerings in the diagnostics arena.
The instrument is being released with CEmarked Quidel Molecular Assay for Clostridium
difficile for detection of hospital-acquired infec-
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tions. Additional Quidel Molecular infectious disease applications are currently under development
and will be available in 2013, including an
Influenza A + B Assay, a Human metapneumovirus
(hMPV) + respiratory syncytial virus (RSV) assay,
and a herpes simplex virus 1 and 2, and varicella
zoster virus (chicken pox and shingles) assay.
The instrument’s touch screen, reagent, sample
tracking, and Laboratory Information Management
Systems (LIMS) interface are simple to use, and flexible. Easily interchangeable thermal cycling blocks
accommodate 96- or 384-well plates and a proprietary qPCR microfluidics card, which can perform
48 tests on eight samples simultaneously without
the need for liquid-handling robots. The card can
also be used to design and implement custom tests.
Two software options are available on the
instrument. The QuantStudio Dx Software runs in
vitro diagnostic (IVD) tests in a secure mode with
preset run and analysis parameters, while the
QuantStudio Test Development Software enables
development of custom tests and supports clinical
research projects.
Image: The QuantStudio Dx real-time PCR instrument for molecular diagnostics (Photo courtesy of
Life Technologies).
Pathogenic Yeasts Quantified by Flow Cytometry
flow cytometric, single-stain approach to quantify Candida albicans has been investigated as
an alternative to the standard viable plate count. In
clinical settings, viable plate counts (VPC) are used
to determine the patient’s microbial load, but it is
labor intensive, time consuming, and only allows
detection of those organisms that readily grow on
solid media.
Microbiologists at the University of Antwerp
(Belgium; www.ua.ac.be) investigated a singlestain, flow cytometric approach for the enumeration of viable C. albicans cells. This single-stain
strategy is based on the differences in the fluorescence intensity between viable and nonviable cells.
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In this study, the cells with an intact membrane are
considered alive, while the cells with a damaged
membrane are defined as dead.
Cell samples were stained with TO-PRO-3
iodide (TP3; Molecular Probes, OR, USA;
www.invitrogen.com) which has a peak excitation
at 642 nm with emission at 661 nm. All flow
cytometry (FCM) studies were performed using a
FACSCalibur flow cytometer (BD Biosciences, NJ,
USA; www.bdbiosciences.com) equipped with a
red diode laser (excitation at 633 nm) and a band
pass filter measuring red fluorescence (FL4; range
653–669 nm). Molecular Probes’ CountBright
absolute counting beads were added to the samples
as an internal standard to calculate the exact volume analyzed by the flow cytometer.
The authors concluded that the FCM quantification of viable cells using TP3 is a good alternative
for the more time consuming and labor-intensive
VPC. In comparison to other FCM techniques, this
single-stain procedure is simple to apply and costeffective since only one dye needs to be added.
Moreover, the unique excitation/emission profile
of TP3 allows the application of additional dyes to
assess other cellular parameters with minimal spectral overlap. The study is planned for publication in
print on February 15, 2013, in the Journal of
Microbiological Methods.
Test Assists Risk Assessment, Early Detection of Lung Cancer
simple physician-ordered blood test aids in risk
assessment and the early detection of lung
cancer in high-risk patients. The test detects the
body’s immune response, in the form of autoantibodies (or immuno-biomarkers), to antigens produced by solid-tumor cells.
A panel of tumor antigens is selected for their
involvement in the development of lung cancer.
Autoantibodies form and circulate in the body at all
stages of the disease including Stages I and IIA, which
are the earliest stages of lung cancer. Their measurement may signify the presence of cancerous cells.
Early CDT-Lung has been approved by the New
York State Department of Health. Utilizing a simple
blood specimen, the test is directed at patients with
a high risk of developing lung cancer, including
heavy smokers, those exposed to suspect environmental conditions, and patients with a CT nodule
under surveillance. The availability of EarlyCDTLung by Enzo Clinical Labs (New York, NY, USA;
www.enzo.com) is the result of an agreement with
its developer, Kansas-based Oncimmune (De Soto,
KS, USA; www.oncimmune.com). The agreement
provides for Enzo to be the only clinical laboratory
located within its marketing area to make the test
available to physicians.
The new diagnostic test that assists in risk assessment and early detection of lung cancer is being
made available to physicians in the New York met-
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June-July/2013
ropolitan market as well as New Jersey and Eastern
Pennsylvania. Enzo is the only clinical laboratory
making the test available in those areas.
Enzo Clinical Labs is a full service clinical reference laboratory. The company combines the extensive testing capabilities of a large laboratory with the
convenience and personalized service of a local one.
Enzo was one of the area’s first laboratories to be
awarded the College of American Pathologists (CAP)
accreditation. This award indicates that Enzo passed
a rigorous series of inspections more sophisticated
than those mandated by licensing authorities.
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TECHNICAL
LITERATURE
F R E E S E RV I C E • S E RV I C E G R AT U I T • K U N D E N D I E N S T G R AT I S • S E RV I C I O G R AT U I TO • S E RV I Z I O G R AT U I TO
MASS
SPECTROMETERS
RENAL
FUNCTION ASSAY
DETECTION KITS
DOA
SCREEN CUP
POC TESTS
D-tek
HemoCue
PRODUCT
CATALOG
Healgen
The latest glucose
point-of-care (POC)
tests are developed for
professional use, deliver lab-accurate results,
and are approved for
diagnosing
various
forms of diabetes.
Products available include variable- and
fixed-volume pipettes,
pipette tips, pipette
controllers, dispensers,
syringes, stands and
accessories.
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AB Sciex
Dako
The 3200MD series is
designed as a combination of dependability,
high performance, accuracy, and throughput, offering a costeffective lab solution
for IVD.
The Cystatin C assay
offers fast and early
detection of reduced
renal function, and provides essential information for patient management.
The BlueDot/BlueDiver
Dot kits are designed
for the detection of
myositis/sclerodermarelated antibodies in
human serum, with 12
different target antigens covered in one
test.
The one-step drugs of
abuse (DOA) screen
test cup offers simple
and hygienic operation, and accurate
results for testing of
any combination of 16
different drugs.
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Handheld Mobile Device Checks Patients’ HIV Status
handheld mobile device can check patients’
HIV status with just a finger prick, and synchronize the results in real time with electronic health
records (EHRs). The technology takes a step toward
providing remote areas of the world with diagnostic
services traditionally available only in centralized
healthcare settings.
In a new study, a team including Curtis D. Chin,
PhD, and Yuk Kee Cheung, PhD, designed a device
that captures all the essential functions of enzymelinked immunosorbent assays, the most commonly
used laboratory diagnostic for HIV. The authors show
that the device performs laboratory-quality HIV testing in 15 minutes using finger-pricked whole blood.
The study appears online in the 2013 edition of the
American Association for Clinical Chemistry
(www.aacc.org) journal Clinical Chemistry.
The device also detects weakly positive samples,
and uses cellphone and satellite networks to automatically synchronize test results with patient health
A
records from anywhere in the world. Because of the
real-time data upload, this mobile device will allow
policymakers and epidemiologists to monitor disease
prevalence across geographical regions quickly and
effectively. This could improve effectiveness in allocating medications to different communities, and
patient care in general.
Of the 34 million people infected with HIV
worldwide, 68% of them live in sub-Saharan Africa,
with South and Southeast Asia bearing the second
greatest burden of disease. Many HIV-infected people in these regions are unable to be tested or treated because they cannot easily travel to centralized
healthcare centers. This creates an extreme economic burden on already-poor nations, with the
epidemic estimated to cause a 1.5% annual loss in
gross domestic product each year for the worst
affected countries. It has also created 16.6 million
AIDS orphaned children who have lost one or both
parents to the disease.
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Plasma Proneurotensin
Levels Predict Breast Cancer
simple blood test for the determination of
proneurotensin (pro-NT) shows promise as a
starting point for the prevention of breast cancer.
The test will be available in Europe beginning in
the second quarter of 2013.
Sphingotec GmbH (Hennigsdorf, Germany;
www.sphingotec.de/corporate-information) will
launch the blood test, Sphingotest pro-NT, for the
early prediction of breast cancer in women. The
new test detects the release of the satiety hormone
neurotensin and is applicable to all female individuals, regardless of genetic predispositions. Data
demonstrating that determination of proneurotensin levels offers a substantial advantage in prediction of breast cancer was recently published in
the October 10, 2012, Journal of the American
Medical Association (JAMA).
Neurotensin is a satiety hormone, released in
gastrointestinal tract. The major stimulus for neurotensin production is fat. Breast cancer-cell growth
is stimulated by neurotensin. Because neurotensin
is a very unstable peptide, Sphingotec uses the stable precursor hormone proneurotensin as a surrogate biomarker for neurotensin. High levels of
proneurotensin correspond with a three-fold risk of
developing breast cancer or a recurrence of breast
cancer.
“Sphingotec will offer a simple blood test that
can be used by gynecologists, family doctors and
clinical laboratories for women to quantify their
individual risk to develop breast cancer,” said Dr.
Andreas Bergmann, CEO of Sphingotec GmbH.
“We are confident this test will impact current prevention and early recognition programs for breast
cancer and ultimately breast cancer incidence as
well.”
Sphingotec GmbH is a biotechnology company
that aims to reduce incidence of severe diseases
like cancer and diabetes by identification of susceptibility factors. The company explores biomarkers
that are susceptibility factors for the development
of severe diseases and provides starting points for
prevention strategies.
A
LabMedica International
June-July/2013
58
LabMedica
for daily laboratory medicine news click to www.labmedica.com
Test Being Developed to Diagnose Mild Cognitive Impairment
utoantibody biomarkers in the blood can
potentially be used to diagnose early stages of
Alzheimer’s and Parkinson’s diseases.
A grant of USD 799,800 from the Osteopathic
Heritage Foundation at the University of Medicine
and Dentistry of New Jersey-School of Osteopathic
Medicine (Stratford, NJ, USA; http://som.
umdnj.edu) will help expand earlier research conducted by Robert Nagele, PhD, director of the
Biomarker Discovery Center (at the University). Dr.
Nagele’s published research includes recent findings that identify specific autoantibody biomarkers
in the blood for early diagnosis of Alzheimer’s and
Parkinson’s diseases.
The funded project will pursue three specific
goals: to identify a small number of autoantibody
A
biomarkers that can accurately (90% or higher)
diagnose MCI cases caused by early stage
Alzheimer’s disease; to verify the accuracy rate with
a larger scale study; and to construct and test a diagnostic kit that is maximally accurate for the broadest possible MCI patient population. If successful,
the study will then apply for final US Food and
Drug Administration (FDA; Silver Spring, MD,
USA; www.fda.gov) approval of the test.
Current approaches to MCI diagnosis rely on
physical, neurological, and psychiatric examinations,
laboratory tests, and a thorough review of the
patient’s medications and medical history. Recently,
great attention has been given to using neuroimaging
technologies to detect structural changes in the brain
before symptoms appear. However, these approaches
require expensive equipment and technology and
can require hospital visits, the injection of radioactive
compounds, and the availability of radiologists with
advanced training in these techniques.
While current treatments for Alzheimer’s cannot
stop the progression of the disease, several medications are capable of significantly enhancing brain
performance and alleviating symptoms. A number of
promising drugs are also currently under development and in clinical trials for the treatment of early
Alzheimer’s disease. An easy-to-administer blood
test for MCI would give pharmaceutical companies
a way to identify patients for clinical trials who are
at a very early stage of their disease and give
researchers a nearly immediate way to monitor the
effectiveness of medications under examination.
Dye Checks Heparin Levels in Blood
cientists have developed a dye
that provides a quick and accurate method of checking heparin levels in the blood. The modified dye,
which has excellent sensing capacity
for heparin, pinpoints the anticoagulant’s level in human serum and has
the potential to work more quickly
than existing clinical methods for
doing this. Because the dye can rapidly detect heparin levels, the scientists
have named it “Mallard Blue,” (the
same shade as the livery of the A4
Pacific Mallard, which holds the
world speed record for a steam loco-
S
motive).
Heparin is an important anticoagulant, which has a significant role in
major surgery. The scientists in the
department of chemistry at York
University
(Toronto,
Canada;
www.yorku.com) studied biological
systems to discover how the dye
would bind heparin even in highly
competitive human serum.
In the laboratory, the scientists
modified existing dyes, which previously could not bind with heparin successfully under these challenging conditions. The scientists in the depart-
ment of chemistry at York used inspiration from biological systems to allow
the dye to bind heparin even in the
highly competitive human serum. The
modified dye, which has excellent
sensing capacity for heparin pinpoints
the anticoagulant’s level in human
serum and has the potential to work
more quickly than existing clinical
methods for doing this. The work was
published in the online edition of
February 13, 2013, Journal of the
American Chemical Society.
The York scientists worked with a
team led by Sabrina Pricl at the
University
of
Trieste
(Italy;
www.units.it), who used high-level
computer modeling to understand
precisely how Mallard Blue binds to
heparin so strongly.
The next stage in this work will
involve the incorporation of this new
dye into a device for simple bedside
read-out of heparin levels in blood.
Vigorous Mixing May Effect Blood Results
he effect of tube mixing techniques on the quality of diagnostic blood specimens collected in vacuum tube systems by venipuncture
has been evaluated.
The accurate mixing of blood in
tubes with anticoagulant- or clot activator additives is essential for their
effectiveness and may influence the
reliability of test results and thereby
affect the diagnostic outcome, the follow-up, and the therapeutic management of patients.
Clinical biochemists at the University of Verona (Italy; www.univr.it) collected blood from 100 volunteers for
routine coagulation, immunochemistry, and hematological testing from
April 1, 2012, to May 1, 2012. The
blood was put into six vacuum tubes:
two 3.6 mL vacuum tubes containing
0.4 mL of buffered sodium citrate; two
3.5 mL vacuum tubes with clot activator and gel separator; and two 3.0 mL
vacuum tubes containing dipotassium ethylenediaminetetraacetic acid
(K2EDTA). All vacuum tubes, each of
one additive type were processed
through two different procedures.
The standard procedure was blood
specimens in K2EDTA- or sodium citrate-vacuum tubes were gently
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59
LabMedica International
June-July/2013
inverted five times whereas the specimens in tubes with clot activator and
gel separator were gently inverted
ten times. The second procedure consisted of all the blood specimens were
shaken up vigorously during three to
five seconds independently of the
additive type inside the tubes.
Routine hematology, clinical
chemistry, and immunochemistry
and coagulation tests were performed. The results of the investigation for all the parameters showed
that no significant differences were
detected between the standard procedures versus the vigorous mix. Only
a visual alteration with the presence
of foam on the top was shown by all
the tubes mixed vigorously before
centrifugation.
The vacuum tubes used were manufactured by Terumo Europe (Heverlee, Belgium; www.terumo-europe.
com). The authors concluded that primary blood tubes vigorous mixing
does not promote laboratory variability and suggest that similar evaluation
should be done using other brands of
vacuum tubes by each laboratory manager. The study was published in the
February 2013 issue of the journal
Clinical Biochemistry.
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F R E E S E RV I C E • S E RV I C E G R AT U I T • K U N D E N D I E N S T G R AT I S • S E RV I C I O G R AT U I TO • S E RV I Z I O G R AT U I TO
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The latest immunochromatographic test
is intended for the
diagnosis of infectious
diseases such as Norovirus, Rotavirus, and
rota-adeno in stool
samples.
The RIDA GENE kits
diagnose gastrointestinal infections, hospitalacquired infections,
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Spectroscopy Aids Breast Cancer Diagnosis
S
TOR Y
IBU APPL
R
T
DIS ED TO
IT
INV
iffuse reflectance spectroscopy
collects and analyzes light after it
has interacted with the sample and this
gives a unique spectrographic signature.
This special type of spectroscopy
has been used locate calcium deposits
during a biopsy and could greatly
improve the accuracy of diagnosing
breast cancer.
A team from Massachusetts
Institute of Technology (Cambridge,
MA, USA; www.mit.edu) and Case
Western
Reserve
University
(Cleveland, OH, USA; www.case.edu)
have investigated whether diffuse
reflectance spectroscopy can help to
diagnose breast cancer. They examined
203 tissue samples within minutes of
their removal from 23 patients. Each
sample could be one of three types,
each with its own spectrographic signature. It could be healthy, it could
contain lesions with no microcalcifications, or it could contain lesions with
microcalcifications.
Diffuse reflectance and Raman
spectroscopic measurements were performed using a portable, compact clinical system. This instrument contains a
xenon flash lamp (370–740 nm) to
obtain diffuse reflectance spectra, and
a diode laser (830 nm) for Raman excitation. For spectral acquisition, the
probe was gently brought into contact
with the tissue specimen and the spectra were collected with room lights off.
Spectra were recorded from multiple
tissue sites of interest from each tissue
core as well as from several cores in
each biopsy, and thus the number of
collected spectra varied from patient to
patient. By analyzing these patterns,
the team produced a computer algorithm that showed a success rate of
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97% in identifying tissue with microcalcifications.
Normally a radiologist takes X-rays
from three different angles to locate
the tiny calcium deposits, then inserts
a needle into the tissue and removes
up to 10 tissue samples. A pathologist
then tests these samples to see if they
contain microcalcifications, but in 15%
to 25% of cases, it is not easy to locate
and take a tissue sample accurately,
resulting in an inconclusive diagnosis.
This means the patient has to have
more X-rays and undergo more invasive surgery to retrieve further samples.
Maryann Fitzmaurice, MD, PhD,
cosenior
author,
said,
“Microcalcifications are most often
seen in breast tumors, but they can
also occur, albeit rarely, in other types
of cancer. If they don’t get them on the
first pass, they usually don’t get them
at all. It can become a very long and
arduous procedure for the patient,
with a lot of extra X-ray exposure, and
in the end they still don’t get what
they’re after, in one out of five patients.
James Tunnell, PhD, an associate
professor at the University of Texas
(Austin, TX, USA; www.utexas.edu),
who not involved in the study
describes the study as a “good first
step” toward a system that could have
a big impact on breast cancer diagnosis. “This technology can be integrated
into the system that is already used to
take biopsies. It’s a very simple technology that can get the same amount of
accuracy as more complicated systems.” The study was published online
on December 24, 2012, in the journal
Proceedings of the National Academy
of Sciences of the United States of
America (PNAS).
LabMedica International
June-July/2013
60
Edited by Tahir Pillay MBChB, PhD, FRCPath(Lon), FCPath(SA)
IFCC members may send news to: Tahir Pillay MBChB, PhD, Head, Dept of Chemical Pathology,
Faculty of Health Sciences, University of Pretoria, Private Bag Bag x323, Arcadia, 0007, South Africa
Tel: (27) 012-319-2114; Fax: (27) 328 6000; Email: [email protected]
NEWS
MESSAGE FROM THE PRESIDENT
by Dr. Graham Beastall, President, IFCC
Reflections on
EuroMedLab Milan 2013
his year is a busy one for IFCC Regional Congresses—in Milan (Europe), Cape Town (Africa),
Bali (Asian Pacific), and Lima (Latin America). The first
of these took place from May 19–23, in the impressive
new Milano Congressi (MiCo) convention center,
which claims to be the largest in Europe.
For IFCC, the Milan experience started a few days before the congress as all
IFCC Divisions and many IFCC Committees, Task Forces and Working Groups
chose to hold meetings in association with EuroMedLab. This made for a convivial
atmosphere in the buildup to the congress.
The congress itself started with a
spectacular concert from a full symphony orchestra and a large choir. This set
the tone for the congress as the cultural
attractions of Milan were shown to great
effect during the week, culminating in a
final gathering in the huge 15th century
Castello Sforza, which is located at the
heart of the city.
The scientific program was excellent
with a wide range of relevant topics considered in plenary lectures, symposia,
educational workshops, and posters. A
particular feature of the congress was
the large choice of industry-sponsored
workshops which were available each
afternoon and which were of a high standard and well attended.
The exhibition was fully subscribed
and very busy. It was great to see some
new IFCC Corporate Members exhibiting for the first time. All the exhibitors
should be happy with the number of visitors they encountered.
The numbers at the congress give a
fair reflection of its success. There were
almost 5,000 registered delegates from
more than 100 different countries. In
addition, there were another 2,000 visitors to the exhibition. It was especially
pleasing to see so many young scientists and so many delegates from developing countries. The organization was
impeccable and the overwhelming opinion is that it was a great success.
Thanks go to Mauro Panteghini and the
excellent organizing team that he led.
For IFCC and EFLM (the Regional
Federation in Europe) EuroMedLab
Milano was a showcase event that
demonstrated the importance of laboratory medicine to healthcare. All attendees will have found something at the
congress to help them improve the quality of the service that they provide to
their users. In addition, all attendees will
have made new friends and shared in
the international family of IFCC.
T
IFCC OFFICE
Via Carlo Farini 81, 20159 Milan, ITALY
Tel: (39) 02-6680-9912 • Fax: (39) 02-6078-1846
E-mail: [email protected] • Web: www.ifcc.org
Office Hours: 9.00-13.00 and 14.00-18.00
Staff Members: Paola Bramati, Silvia Cattaneo,
Silvia Colli-Lanzi
61
LabMedica International
June-July/2013
Photo: A scene from the opening
ceremony of EuroMedLab 2013
News from the World of the International
Federation of Clinical Chemistry and Laboratory Medicine
Visit www.ifcc.org for more information
NEWS
Catalan Society Expands Activity
by Joan Nicolau, Editor, In Vitro Veritas
n March 2012, the Catalan Association for Clinical
Laboratory Sciences organized the 10th Catalan
Congress of Clinical Laboratory Sciences.
Other activities of the association included:
Translation to Catalan of “Terminology in
Analytical Measurement. Introduction to VIM 3,”
which was published on the website;
Meeting topic: “How to write a scientific paper”;
Course on “Statistics applied to the Clinical
Laboratory Sciences”;
Course on “Update on the Clinical Laboratory
Sciences”;
Organization of the Course on Benchmarking;
Publication of articles related to the Clinical
Laboratory Sciences in the online journal of the
Association, In vitro veritas;
Authorship of the “Guide for the internal quality
control of ordinal quantity measurements with
control materials,” also found on the website.
I
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10th Congress of the Catalan Association
for Clinical Laboratory Sciences
The 10th Congress was held during March 1-3,
2012, in Manresa (Spain). The program included
several topics: recent advances in the diagnostics of
diabetes mellitus, tuberculosis and allergy, genetics,
bone metabolism, tumor markers, laboratory informatics, and prenatal screening, as well as the optimization of economic resources in the clinical labo-
ratory.
Lectures and round table discussions were held and posters
were displayed during the
Congress, which were discussed in one of the sessions.
The meeting attracted around
two hundred participants from
all over the Catalan autonomous
region of Spain. The language
used was Catalan, an official
language of the country. Several
companies related to the field
had exhibits of the latest diagnostic products and laboratory
technology.
The social program included a visit to the medieval
Monastery of Saint Benet – the Photo: Dr. Mari Cruz Pastor, President of the Congress (left), Dr. Jaume
venue of the Congress, and a Miró, President of the ACCLC (third from the right), and Dr. Jaume Trapé,
General Coordinator of the Congress (right).
gala dinner.
Since its foundation in 1996,
the ACCLC has organized a Congress every two 28-29, in Barcelona. The main objective of this
years to discuss current topics and promote the Symposium was to debate the impact molecular
genetics has on the organization of clinical laboratoquality practice of clinical laboratory sciences.
ries and its evolution in the next future. Experts from
7th European Symposium
several countries attended. The official languages of
The VII European Symposium was held under the the Symposium were Catalan, Spanish, and English,
IFCC auspices and the IUPAC sponsorship on May with simultaneous translation of the debates.
Khosrow Adeli Named New Editor-in-Chief of the Journal
“Critical Reviews in Clinical Laboratory Sciences”
r. Khosrow Adeli, PhD, FCACB, DABCC, who currently chairs
the IFCC Communications and Publications Division, was
appointed as Editor-in-Chief of Critical Reviews in Clinical
Laboratory Sciences in 2013, to succeed John R. Burnett. Critical
Reviews in Clinical Laboratory Sciences is a leading publication
in laboratory medicine, ranking 2/32. Dr. Adeli is currently the
head and full professor of Clinical Biochemistry at the Hospital for
Sick Children and the Departments of Biochemistry, and
Laboratory Medicine & Pathobiology at the University of Toronto
in Toronto (Canada). He is the Director of the Point of Care
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Testing program at the Hospital for Sick Children in Toronto. Dr.
Adeli is a fellow of the Canadian Academy of Clinical Biochemistry
and a diplomate of the American Board of Clinical Biochemistry.
Dr. Adeli served as the Editor-in-Chief of the Clinical Biochemistry
journal for 7 years (1999–2006). He is an editorial board member
of the Clinical Biochemist Reviews. He served (2006–2010) as
the president of COMACC, the Commission on Accreditation in
Clinical Chemistry, a North American organization responsible for
accreditation of clinical chemistry training programs in the USA
and Canada.
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News from the World of the International
Federation of Clinical Chemistry and Laboratory Medicine
Visit www.ifcc.org for more information
NEWS
Nominations Invited for Triennial
IFCC Distinguished Awards to Be
Presented at IFCC-WorldLab 2014
by Howard Morris, IFCC vice president,
Chairman, IFCC Awards Committee
s you are aware, the IFCC confers several distinguished awards to scientists and clinicians who
work in clinical chemistry and laboratory medicine or
related disciplines. These triennial awards are the
highest honors that our federation can bestow to colleagues worldwide in recognition of their outstanding
achievements, to publicize their exceptional research
and other contributions that have improved medical
and healthcare, and to stimulate and encourage
other scientists to accelerate their efforts in advancing clinical chemistry and laboratory medicine.
A
On behalf of IFCC and its Awards Committee, I am
pleased to call for nominations for the following seven
IFCC distinguished awards for presentation at the
IFCC Congress in June 2014, Istanbul (Turkey).
These seven awards for 2014 are listed below and a
more detailed description of them including the former
honorees can be found on the IFCC website at:
www.ifcc.org/about-us/2014-ifcc-awards
IFCC Distinguished Clinical Chemist Award,
sponsored by Beckman Coulter;
IFCC-Henry Wishinsky Award for Distinguished
•
•
International Services, sponsored by Siemens;
IFCC Award for Distinguished Contributions in
Education, sponsored by Abbott Diagnostics;
IFCC-Abbott Award for Significant Contributions
in Molecular Diagnostics, sponsored by Abbott
Diagnostics;
IFCC Distinguished Award for Laboratory Medicine and Patient Care, sponsored by Unilabs;
IFCC-Robert Shaffer Award for Outstanding
Achievements in the Development of Standards
for Use in Laboratory Medicine, sponsored by
NIST-CLSI;
IFCC-Young Investigator Award, sponsored by
IFCC.
Nominations are welcome from the President or
National Representative of the nominees’ national
society, which should be a full member of the IFCC.
Each nomination should contain (1) a statement as
to the reasons for nomination, (2) a full CV of the
nominees including a bibliography, and (3) other letters of support (optional). They should be sent to Ms.
Colli-Lanzi of the IFCC Office ([email protected]).
The closing date for receipt of nominations is
November 30, 2013.
Please do not hesitate to write to Ms. Colli-Lanzi
or me ([email protected]) if you have
any queries.
The IFCC Awards Committee 2012-2014: Chair:
H. Morris (AU); Members: J.C. Forest (CA); M.
Jouma (SY); L. Lai (MY); R. Sierra-Amor (MX); G.
Sypniewska (PL).
•
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Ukrainian Society Elects
New Executive Board
by Dr. Igor Mishunin, PhD, Board Member,
National Representative for IFCC & EFLM
he Ukrainian Society of Clinical Laboratory
Diagnostics’ (USCLD) new Executive Board was
elected at the society’s annual meeting:
Dr. Valeryj Dejev, President;
Prof. Adel Rudenko, Head of Board;
Dr. Kateryna Osipchuk, Board Member, Treasury;
Dr. Igor Mishunin, Board Member and National
Representative for IFCC & EFLM;
Prof. Danylo Gluzman, Board Member;
Dr. Sergey Verevka, Board Member;
Prof. Zoltan Fabry, Board Member;
Prof. Tetiana Gavrylenko, Board Member.
T
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New Executive Council
Takes Over at Pakistan Society
he new executive council has been elected by the
members of Pakistan Society of Chemical
Pathologists (PSCP) for the 2013–2015 term. Prof.
Dilshad Ahmed Khan, Dr. Sameena Ghayur, and
Prof. Rizwan Hashim have been elected President,
Vice President and Secretary / Treasurer respectively for this term and they will be the national representatives. Their contact details are shown hereunder:
T
•
Prof. Dilshad Ahmed Khan: President
[email protected]
•
Dr. Sameena Ghayur: Vice President
[email protected]
•
Prof. Rizwan Hashim: Secretary/Treasurer
[email protected]
LabMedica International
June-July/2013
64
News from the World of the International
Federation of Clinical Chemistry and Laboratory Medicine
Visit www.ifcc.org for more information
NEWS
Vietnamese Society to
Mark 50th Anniversary
with Jubilee Conference
in September
by Prof. Dr. Hoang Van Son,
Executive Committee of the VACB, National
Representative of the VACB to the IFCC
he Vietnamese Association of
Clinical Biochemists (VACB) celebrates the 50th Anniversary of its
foundation this year, 2013.
The Foundation Congress was
held on June 1, 1963, at the Viet-Xo
Huu nghi Hospital (Hospital of
Vietnam-Soviet Union Friendship) in
Hanoi, under the decision of the
Minister of Health Dr. Pham Ngoc
Thach. The VACB is working within
the framework of the Vietnam General
Medical Association (VGMA).
The first VACB President was Dr.
of Pharmacy Tran Thi An, Head of
Department of Biochemistry of the
University of Medicine and Pharmacy
of Hanoi. The official journal of the
VACB, the Medical Biochemistry,
appeared in 1963, 50 years ago.
During 50 years of development, the
Vietnamese Association of Clinical
Biochemists has been progressing,
expanding rapidly in the Health care
system for the Vietnamese people.
Nowadays, there are 18 Professors
and A/Professors, many Philosophy
Doctors of Medicine, of Pharmacy,
hundreds of bachelors working in the
many Universities of Medicine, of
Pharmacy, numerous Hospitals in
Hanoi, Ho-Chi-Minh City, and in 63
provinces. In other institutions, there
are additional VACB members.
The VACB comprises a number of
Societies: Society of Clinical
Biochemistry of Hanoi and Northern
T
Provinces, Society of Clinical
Biochemistry of Ho-Chi-Minh City
and Southern Provinces, Society of
Clinical Biochemistry of Center of
Vietnam,
Branch
Society
of
Molecular Biology, Branch Society of
Proteomics, Branch Society of
Immunology and Allergology, Branch
Society of Toxicology.
Numerous advanced techniques
in Molecular Biology, Enzymology,
Immunology, Oncology, Proteomics,
Endocrinology, Toxicology, POCT,
etc. have been implemented in the
last years of the 20th century and in
this century. There are four High
Schools for technicians that have
been training many technicians,
especially for the hospitals. The
Departments of Biochemistry of the
Universities of Medicine are important incubators for PhD theses. Many
studies have appeared in the
International Congresses and in
some international medical Journals.
The VACB has been a member of
the IFCC since 1989 and a member of
the APFCB since 1990; International
cooperation has been flourishing since
that time. Thanks to the precious support of the IFCC, the APFCB, the IATDMCT, of some Associations such as
the Australasian Association of Clinical
Biochemists (AACB), the French
Society of Clinical Biology (SFBC),
and the VACB has implemented the
QA and QC Programs successfully, as
Photo: The senior members of the Vietnamese Association of Clinical Biochemists
(VACB), half of them have attended the Founding Congress of the VACB.
well the IFCC Professional Exchange
Program: five VACB members have
been trained in Hong Kong, Australia,
and Sweden.
The VACB has organized 10
National Congresses and 2 or 3
Scientific Conferences every year.
Prof. Dr. Hoang Bich Ngoc is
working as the current VACB
President; General Secretary: Prof,
Dr. Pham Thien Ngoc; National
Representative of the VACB to the
IFCC: Prof. Dr. Hoang Van Son.
The Jubilee 50 Anniversary Meeting
will be organized on September 6–7,
2013, in Hanoi, together with the
Scientific Conference.
The VACB wishes to meet international colleagues in this important
event. You are welcome!
IFCC Welcomes New Corporate Members
Instrumentation
Laboratory
Instrumentation Laboratory (IL, USA),
founded in 1959, is a worldwide developer, manufacturer, and distributor of in
vitro diagnostic instruments, related
reagents, and controls for use primarily
in hospitals and independent clinical
laboratories. Company product lines
include Critical Care systems, Hemostasis systems, and Information Management systems. IL’s GEM product
offerings, part of the Critical Care line,
include the GEM Premier 4000 analyzer with Intelligent Quality Management
(iQM), GEM Premier 3500, GEMweb
Plus Custom Connectivity, and complimentary products GEM PCL Plus, a
portable coagulation analyzer the
ACL TOP Family of Hemostasis
Testing Systems, fully automated,
high-productivity analyzers, including
the ACL TOP 700, ACL TOP 700 LAS,
65
LabMedica International
June-July/2013
ACL TOP 700 CTS, ACL TOP 500
CTS, and ACL TOP 300 CTS. IL also
offers the ACL AcuStar, ACL ELITE,
other Hemostasis analyzers, and the
HemosIL line of reagents. IL is based
in Bedford (MA, USA; www.ilus.com).
Shanghai Zhicheng
Biological Technology
Shanghai Zhicheng is an innovative
Chinese company devoted to manufacturing and marketing in vitro diagnostic
(IVD) tests for use in clinical laboratories. The company has been focusing
on promoting the quality of their products by serious and pragmatic R&D,
and strict QC according to ISO 13485
and ISO 9001 since its foundation by
Mr. Wanghui in 1995. Company products are distributed to more than 1,000
laboratories in China under the the
well-known brand of “DENUO.” Web:
www.shzhicheng.com
LINKXPRESS COM
LMI-07-13 165
EFLM CORNER
European Federation of Clinical
Chemistry and Laboratory Medicine
Edited by Dr. Bernard Gouget
Milan 2013: In the Wild World
of Laboratory Medicine
by Dr. Bernard Gouget
SFBC-EFLM Representative; IFCC Treasurer;
Secretary General, International Francophone Federation
of Clinical Biology and Laboratory Medicine (FIFBCML)
ilan, the capital of Lombardy, is the largest industrial city
of Italy with diverse industrial sectors. It is a magnetic
point for designers, artists, photographers, and models. Milan
has an ancient city center with high and interesting buildings
and palazzos, which is why so many people from all over the
world want to see the city of glamour. The week of May 19,
2013, Milan was the city of Lab Medicine: an interdisciplinary
scientific platform bringing specialists in Laboratory Medicine
with an academic, clinical, and industrial background together.
EuroMedlab Milano 2013, which represents the most important European congress in the field of Lab Medicine, was a
very successful event. According the Emmezeta statistics, the
number of delegates attending for one or more days was
4,706 from 101 countries. Delegates from outside Europe
accounted for 20%. Attendees younger than 35 years of age
were 393 (8%). The 82 major exhibitors covered an area of
3,500 m2. Two hundred outstanding international speakers
contributed to the high scientific level of the 5 plenary sessions
and 23 symposia that related to a specific disease or pathophysiologic conditions combining clinical laboratory, research,
and future development with their own clinical experience.
Forty-five educational workshops were organized in close collaboration with diagnostic companies and the delegates presented 1,239 posters.
Thank you Prof. Mauro Panteghini, president of EML
Milano 2013, and congratulation to the congress organizing
committee, scientific program committee, SIBioC team and
MZ congress organizing secretariat staff for this outstanding
scientific and cultural program, it was a wonderful opportunity to meet old and new friends with the common interest in
promoting the added value of Lab Med. It was also a good
opportunity to visit the city of Milano. Many participants visited
the Duomo and Santa Maria delle Grazie, which is one of the
most famous churches in Milan—a Dominican convent included in the UNESCO World Heritage sites list. The church is
famous above all for the mural of the Last Supper by Leonardo
da Vinci, which is situated inside the refectory of the convent.
The cultural and social evening at the Castello Sforzesco on
Wednesday night was an extraordinary experience. Before the
luxurious Italians buffets, it was possible to visit the Sforza
Castle museum open until late for EuroMedLab guests and to
admire the Michelangelo’s statue named Pieta Rondanini, the
sculpture on which Michelangelo worked until six days prior to
his death, on February 18, 1564. At the end of the evening, the
show of the flying acrobats “Sonics” was simply breathtaking.
During the EFLM general assembly, Athens was choosen
to organize EuroMedlab 2017. Congratulations to Alexander
Halliassos and the Greek delegation. It is also important
to congratulate the newly elected members of the EFLM
Executive Board and thank the outgoing members of the
EFLM EB, Volunteer leadership and is often underappreciated. Thank you all as well!
After Milan, it is a big challenge to organize such a sustainable, high level and dynamic forum. Together with Prof.
Joelle Goudable and Prof. Philippe Gillery on behalf of the
French Society of Clinical Biology (SFBC) and of the
Congress Organizing Committee, it is a great pleasure to
invite both academics and specialists in Lab Medicine and
partners to attend the 21st IFCC-EFLM European Congress
of Clinical Chemistry and Laboratory Medicine (EuroMedLab
Paris 2015). This unique event, including the Journées
Internationales de Biologie (JIB) 2015, will be held in Paris
(France), on June 21-25, 2015 in the Palais des Congrès de
Paris, one of the French capital’s legendary venues. In 1789,
it was the French revolution, EuroMedlab Paris 2015 will be
the “Revolution in Lab Medicine” linking scientific and other
evidence to shape tomorrow’s development in the field of Lab
Medicine and global health placing the patient at the heart of
all our efforts and discussions.
M
Photo: Dr. Bernard Gouget launching
EuroMedLab Paris 2015 at the closing
ceremony of EuroMedLab 2013.
LabMedica International
June-July/2013
66
EFLM CORNER
European Federation of Clinical
Chemistry and Laboratory Medicine
French Society of Clinical Biology (SFBC):
A Review of Scientific Activities
by Véronique Ducros, Jean-Philippe Lavigne, Sylvain Lehmann, for the Scientific Committee
he SFBC, which was founded in
1942, regroups nearly 1,000
members working in private or public
medical laboratories. Programs and
activities of the SFBC are intended to
enable medical biologists and laboratory specialists to operate efficiently
with a high standard of professional
and technical competence improving
the quality of care and benefits for
the patient by providing a clear vision
of the key role of clinical chemistry
and laboratory medicine.
The Scientific Committee (SC)
aims are to establish and to improve
the standards for scientific, clinical,
and technical aspects of best laboratory practices. SC plays also an important role in bridging basic science,
applied science, and clinical care.
Formal links are established with
research institutions, regulatory bodies, and other national clinical societies
in specific fields (hematology, nephrology, endocrinology, and the like).
A key task of the SC deals with
the creation and the monitoring of
multidisciplinary working groups
(WG). They are composed of experts
in the different area of clinical biology
and their goal is to provide to the
community, updated information on
specific subjects, recommendations,
and guidelines taking into account
the needs of the patients and practitioners, as well as public health
issues. The topics of the WG originate from both the members of the
SBFC and the SC.
Summary of the activities of the different WG are available on the website of the SFBC (www.sfbc.asso.fr). A
more complete access to the work of
the working groups (constitution of
groups, reports, manuscript, etc.) is
available for SFBC members. This
article provides a synthetic vision of
the different groups, their work, and
their contribution as follows:
Accreditation requirements for
Clinical Laboratory: This WG is
devoted to developing recommendations for implementing the required
ISO 15189 in all French medical laboratories. These recommendations
T
•
are compiled in three recently published guides for certification.
Laboratory automation and
standardization: This WG aims to
prepare technical guides and standardized description for analytical
systems, robotics, computerization,
and automation of medical biology
laboratories. Their conclusions are
published in the form of detachable
leaflet, the last one focusing on
“Middleware.”
Toxicology management in emergency unit: This WG updated and
outlined the different protocols for
extraction and chromatography techniques implemented to carry out toxicological screening (in serum and
urine) in case of severe poisoning.
They are also at the origin of a common QC, which can be used by most
laboratories dealing with toxicology.
Monitoring of blood glucometers:
This new WG was designed to assess
different readers of blood glucose and
discussed how to deploy them in hospitals, their monitoring (QC), and their
use based on the current recommendations in endocrinology.
Place of mass spectrometry in
clinical biology: This new WG aims at
reviewing the interest and limits of
mass spectrometry in different fields:
clinical chemistry, bacteriology, toxicology, et al. It will provide information on the future of the technique
and its compatibility with accreditation requirements.
Pharmacogenomics and predictive medicine: This WG is intended to
review the available pharmacogenomic applications for different clinical applications (e.g., cytochromes
and VKORC1 isoforms in anticoagulant treatments). Two main areas of
interest are emerging within the WG:
the Next Generation Sequencing and
pharmacogenetics-pharmacogenomics and its applications in the
clinic.
Level of Evidence (LOE) of
pros-tate cancer biomarkers: This
WG is studying the LOE of two
groups of biological markers (serum:
PSA and derivatives; urinary: PCA3
•
•
•
•
•
•
Society Name Change:
“SIBioC – Laboratory Medicine”
uring its most recent general
assembly on April 15, 2013, an
amendment to the scientific society’s
by-laws was ratified by the board and
the full membership. While leaving the
glorious SIBioC acronym unchanged,
they changed the society’s name to
“SIBioC – Laboratory Medicine” (The
Italian Society of Clinical Biochemistry
and Clinical Molecular Biology).
As with the previous change that led
the IFCC to become the “International
Federation of Clinical Chemistry and
Laboratory Medicine,” this change
responds to a recommendation from
D
67
LabMedica International
June-July/2013
the European Federation of Clinical
Chemistry and Laboratory Medicine
(EFLM) inviting all members to start
including laboratory medicine in their
title.
This request is the logical consequence of last year’s decision by
EFLM member societies on the most
appropriate descriptive name for our
profession: “specialists in laboratory
medicine.” This is the first stage in a
two-step process to enable us to
progress toward recognition of the profession under a European commontraining framework.
and fusion genes) in early diagnosis,
support, assessment of aggressiveness and their best uses in humans
over 40 years.
Fetal alcohol syndrome: This
group is working on diagnostic practices and biological markers currently
used for monitoring of maternal pregnancy alcohol and screening/diagnosis of fetal impairment in utero and at
birth.
Natriuretic peptides: This WG
has two objectives: review the interest and the use of these analytes in
clinical practice; perform an analytical assessment of the BNP/NTproBNP assays.
CSF biomarkers in Alzheimer’s
disease: This WG will review the use
of the most relevant biomarkers in
the diagnosis of Alzheimer’s disease.
It will also help to standardize the
preanalytical phase between laboratories and to implement internal and
external quality controls.
New Troponin assays use in emergency unit: This new WG will
assess the interest of the new
Troponin kits and will propose recommendations for their best use in
emergencies.
•
•
•
•
Biomarkers of vascular calcification in kidney disease: This group will
compare the interest of the new emerging biomarkers of the vascular risk in
the chronic renal insufficiency (FGF23,
Klotho, OPG/RANKL/TRAIL, and others) and will propose recommendations for kidney disease and mineral
metabolism disturbances follow-up.
Urinary biomarkers of renal
function: The WG will review the literature to compare the urinary biomarkers of renal dysfunction.
Analytical aspect will be also
addressed through a multisite evaluation that will focus on the limit of
detection and eventually on the clinical interest.
The SC task is also to select and
validate the national candidate for the
international working groups (IFCC,
EFLM, et al). It is also involved in the
organization of scientific events and
in particular the annual scientific
meeting of the SFBC. Finally, the SC
participates in the selection of annual
SFBC Award recipients of clinical
chemists or laboratory scientists who
work in the field of clinical chemistry,
laboratory medicine, and clinical laboratory science.
•
INDUSTRY NEWS
EKF Diagnostics Launches Division
for Molecular Cancer Diagnostics
KF Diagnostics (Cardiff, UK;
www.ekfdiagnostics.com), a
worldwide manufacturer of point-ofcare (POC) diagnostic tools, organ
injury biomarkers and assays, has
launched a new division focusing on
molecular and companion diagnostics. The company will develop the
technologies for cancer gene detection through its recent acquisition of
the UK-based 360 Genomics.
EKF Molecular has been set up to
offer products with the potential to
change current DNA extraction and
detection practices, allowing EKF to
address the surging companion diagnostics market.
EKF Molecular’s lead product,
PointMan, is a real-time PCR technology that provides sensitive detection for cancer mutations. PointMan
is effective in amplifying the
sequence of interest while suppressing amplification of the wild type.
The resulting sample is enriched for
the mutation thus offering high sensitivity in a variety of sample types.
EKF Molecular expects to follow the
launch of PointMan with additional
E
products later this year. Xtract, the
second product in EKF’s range,
offers users in the pharmaceutical,
academic, and diagnostic sectors a
quicker, less expensive, and automatable platform for DNA extraction technology.
Julian Baines, CEO of EKF, said,
“Companion diagnostics, is a situation where everyone wins: patients
get better diagnosis which leads to
better treatments and survival rates;
doctors see increased patient safety
and can make better informed decisions about treatments; healthcare
providers and insurance companies
will see better patient outcomes
through reduced costs and pharmaceutical companies will be able to
gain easier regulatory approval and a
quicker time to market for their
drugs.”
EKF Diagnostics Holdings plc specializes in the development, production, and worldwide distribution of
POC blood analyzers for use in the
detection and management of diabetes, anemia, lactate and kidney
related diseases.
Life Technologies Buys
Korean Distributor
ife Technologies Corp. (Carlsbad,
CA, USA; www.lifetechnologies.
com) announced the acquisition of an
instrument distributor Life Science
Korea (LSK; Seoul, Republic of Korea;
www.lgls.com).
LSK has been Life Technologies’' primary instrument distributor since 1994
and holds distribution rights to Applied
Biosystems products, including nextgeneration sequencing instruments,
Sanger sequencing systems, forensics,
and polymerase chain reaction (PCR)
products. LSK serves more than 1,000
customers in academia, government,
pharmaceutical, biotech, hospitals, and
applied markets. Under the acquisition
terms, the LSK name will become part
of Life Technologies Korea. No other
terms of the deal were announced.
The combination of LSK and Life
L
Technologies will continue to build a
strong Life Technologies brand in Korea
to stimulate fast and sustainable growth
and be well positioned to take advantage of Korea’s focus on developing
biotechnology. In the past five years,
South Korea has shown solid growth in
the biotechnology industry and with
the Korean government's Bio-vision
2016 initiative, it is expected that the
country will continue to invest heavily
in the life sciences industry.
Life Technologies is a global
biotechnology company with portfolio of 50,000 end-to-end solutions
secured by more than 5,000 patents
and licenses that span the following
biologic spectrum-scientific exploration, molecular diagnostics, 21st
century forensics, regenerative medicine, and agricultural research.
Ventana and Barco in Alliance
for Digital Pathology Viewing
entana Medical Systems, Inc.
(VMSI; Tucson, AZ, USA; www.
ventana.com), member of the Roche
Group, has announced the signing of
a worldwide agreement with healthcare imaging expert Barco, Inc.
(Kortrijk, Belgium; www.barco.com)
to provide Barco's leading diagnostic
and clinical review display systems
for use with Ventana’s “Virtuoso”
image and workflow management
system, offering a turnkey solution
that provides consistent whole slide
image viewing with efficiency.
The advantages of medical grade
displays over commercial off-the-shelf
monitors include enhanced contrast;
V
color accuracy and sharpness; prolonged image stability over time; and
the ability to calibrate the screen for
optimal viewing. Barco's Coronis
Fusion 4MP DL diagnostic color display and MDRC-2124 wide-screen
clinical monitor offer these capabilities and more for precise, high confidence viewing. Barco's system supports effortless and precise panning
and zooming on whole slide images.
Moreover, the display system
includes Barco's MediCal Awe, an
automated, real-time calibration system that provides high image quality
and consistency across the screen for
the life of the display.
Analytik Jena Acquisition
Focuses on Sepsis Diagnostics
nalytik Jena (Jena, Germany;
w w w. a n a l y t i k - j e n a . d e / e n )
acquired all the assets of the insolvent
company SIRS-lab GmbH (Germany,
www.sirs-lab.de). SIRS-Lab, a company that develops molecular diagnostics
methods and testing systems for lifethreatening infections such as sepsis,
filed for insolvency in December 2012.
Analytik Jena AG, which will also
obtain the entire range of product
expertise, including more than 50
patents and 10 employees at the Jena
site, will be entering the worldwide
growth market of sepsis diagnostics,
continuing the development work
and expertise of SIRS-Lab in this field.
Analytik Jena in its stronger focus on
routine diagnostics will work more
closely with hospital and clinical part-
A
ners in the process.
SIRS-Lab was founded in 2000 as
a spin-off of the Friedrich Schiller
University at the Jena Sepsis
Competence Center by a team of scientists. The aim of the scientists was
to combat the high mortality rate
associated with sepsis (blood poisoning). With the product LOOXSTER,
the company developed a patented
technology for concentrating bacterial and fungal DNA in diagnostic samples. This product is used in VYOO,
the CE marked product for sepsis
diagnostics. SIRS-Lab was also developing a gene expression product
(SIQNATURE) to indicate the body’s
immune response to an infection. A
related test developed by SIRS-Lab is
almost ready for the market.
LabMedica International
June-July/2013
68
INTERNATIONAL CALENDAR
For a free listing of your event, or a paid
advertisement in this section, contact:
International Calendar • LabMedica
P.O.Box 802214, Miami FL 33280-2214, USA
Fax: 1-954-893-0038 • E-mail: [email protected]
Yellow-highlighted listings are available
at US$ 300 for a one-year period.
Please mail check with your event’s
details to above address.
ASHG 2013 - Annual Meeting of the American
Society of Human Genetics. Oct 22-26; Boston,
Massachusetts, USA; Web: www.ashg.org
7th National Congress of Clinical Laboratory.
Oct 23-25; Bilbao, Spain; Web: www.labclin2013.es
APFCB 2013 - 13th Cong. Asian-Pacific Fed.
for Clinical Biochemistry. Oct 27-30; Bali,
Indonesia; Web: http://apfcbcongress2013.org
COLABIOCLI 2013 - XXI Congreso LatinoAmericano de Bioquimica Clinica. Oct 29-Nov
1; Lima, Peru; Web: http://colabiocli-lima2013.org
NOVEMBER 2013
AUGUST 2013
FIME 2013. Aug 7-9; Miami Beach, FL, USA;
Web: www.fimeshow.com
26th Annual Meeting of the Association of
Medical Laboratory Immunologists (AMLI).
Aug 10-13; Savannah, GA, USA; Web:
www.amli.org
ISEH 42ND Annual Scientific Meeting. Aug 2225; Vienna, Austria; Web: https://iseh.site-ym.com
42nd ISEH Annual Scientific Meeting - Society
for Hematology and Stem Cells. Aug 22-25;
Vienna, Austria; Web: https://iseh.site-ym.com
25th European Congress of Pathology.
Aug 31-Sep 4; Lisbon, Portugal; Web: www.
esp-congress.org
SEPTEMBER 2013
AABB Annual Meeting & CTTXPO Advancing Trasfusin and Cellular Therapies
Worldwide. Sep 1-4; Denver, CO, USA; Web:
www.aabb.org
25th National Congress of Biochemistry of the
Turkish Biochemical Society (TBD). Sep 3-6;
Izmir, Turkey; Web: www.biyokimyakongresi.org
AACB 51st Annual Scientific Conference of
Australasian Association
of
Clinical
Biochemists. Sep 16-19; Gold Coast, QLD,
Australia; Web: www.aacb.asn.au
ASCP 2013 - American Society for Clinical
Pathology Annual Meeting. Sep 18-21; Chicago
IL, USA; Web: www.ascp.org/ascp2013
52nd Annual ESPE Meeting - European Society
of Paediatric Endocrinology. Sep 19-22; Milan,
Italy; Web: www.jointmeeting2013.org
AACC 2013 - Annual Meeting, American
Association for Clinical Chemistry. Sep 20-25;
Houston, TX, USA; Web: www.aacc.org
2nd Croatian Congress of Laboratory
Diagnostics. Sep 21-25; Sibenik, Croatia; Web:
http://hlu.hr
47th Brazilian Congress of Clinical Pathology /
Laboratory Medicine. Sep 22-25; Sao Paulo,
Brazil; Web: www.cbpcml.org.br
MipTec Conference & Exhibition 2013. Sep 2426; Basel, Switzerland; Web: www.miptec.ch
ExpoMedical 2013. Sep 25-27; Buenos Aires,
Argentina; Web: www.expomedical.com.ar
BCLF 2013 - 21st Annual Meeting, Balkan
Clinical Laboratory Federation. Sep 25-28;
Budva, Montenegro; Web: http://bclf2013.org
61st Annual Scientific Meeting of the American
Society of Cytopathology. Nov 8-12; Orlando,
FL, USA; Web: http://cytopathologymeeting.org
The 13th Euroconference on Clinical Cell
Analysis. Nov 12-14; luxembourg, luxembourg;
Web: www.escca.eu
Analytica Anacon India 2013. Nov 12-14;
Mumbai, India; Web: www.analyticaindia.com
JIB 2013 - Journées Internationales de Biologie.
Nov 13-15; Paris, France; Web: www.jib-sdbio.fr
Pathology Update 2013: State-of-the-Art
Diagnostic Approaches to Surgical Pathology.
Nov 13-16; Montreal, Quebec, Canada; Web:
www.ascp.org
Association for Molecular Pathology (AMP)
Annual Meeting 2013. Nov 14-16; Phoenix, AZ,
USA; Web: www.amp.org
39th Annual Meeting of the American Society
for Histocompatibility and Immunogenetics
(ASHI). Nov 18-22; Chicago, IL, USA; Web:
www.ashi-hla.org
MEDICA 2013. Nov 20-23; Düsseldorf,
Germany; Web: www.medica.de
India Lab Expo 2013. Nov 21-23; Hyderabad,
India; Web: www.indialabexpo.com
DECEMBER 2013
California Society of Pathologists 66th Annual
Convention. Dec 3-7; San Francisco, CA, USA;
Web: www.calpath.org/events.php
55 Annual American Society of Hematology
(ASH) Meeting and Exposition. Dec 7-10; San
Diego, CA, USA; Web: www.hematology.org
Annual Meeting of the American Society for
Cell Biology. Dec 14-18; New Orleans, LA,
USA; Web: www.ascb.org/meetings/index.cfm
JANUARY 2014
Arab Health / Arab MedLab 2014. January;
Dubai, UAE; Web: www.arabhealthonline.com
The British Fertility Society - BFS Annual
Meeting. Jan 8-9; Sheffield, UK; Web:
www.britishfertilitysociety.org.uk
Protein Purification & Recovery - Cambridge
Healthtech Institute’s Sixth Annual Meeting.
Jan 13-14; Palm Springs, CA, USA; Web:
www.chi-peptalk.com
SLAS 2014, Society of Laboratory Automation
and Screening. Jan 18-22; San Diego, CA, USA;
Web: www.slas2014.org
OCTOBER 2013
MARCH 2014
9th EFLM Symposium for Balkan Region. Oct
3-5; Belgrade, Serbia; Web: www.dmbj.org.rs
APCCB 2013 - 13th Congress of the AsiaPacific Federation for Clinical Biochemistry
and Laboratory Medicine. Oct 6-9; Bali,
Indonesia; Web: www.apccb2013.org
BIOTECHNICA 2013. Oct 8-10; Hannover,
Germany; Web: www.biotechnica.de
69th Annual Meeting of the ASRM - American
Society for Reproductive Medicine. Oct 12-17;
Boston, Massachusetts, USA; Web: www.asrm.org
39th Annual Symposium and Congress of the
National Society for Histotechnology (NSH).
Oct 12-15; Providence, RI, USA; Web: www.histoconvention.org
CAP 2013 – The Pathologists’ Meeting College of American Pathologist. Oct 13-16;
Kissimmee, FL, USA; Web: www.cap.org
Analytica China 2013. Oct 16-18; Shanghai,
China; Web: www.analyticachina.com
World Vaccine Congress 2014. Mar 24-26;
Washington, DC, USA; Web: www.terrapinn.com
69
LabMedica International
June-July/2013
APRIL 2014
Experimental Biology 2014. Apr 26-30; San
Diego, CA, USA; Web: http://experimental
biology.org
Biomarkers & Diagnostics World Congress
2014. Apr 30-May 2; Philadelphia, PA, USA;
Web: www.biomarkerworldcongress.com
MAY 2014
16th European Congress of Endocrinology. May
3-7; Wroclaw, Poland; Web: www.ece2014.org
EuroPRevent - European Society of Cardiology.
May 8-10; Amsterdam, Netherlands; Web: www.
escardio.org
ECCMID 2014 – 24rd Eur. Cong. of Clin.
Microbiology & Infectious Diseases. May 1013; Barcelona, Spain; Web: www.congrex.ch
LabMedica International
Vol. 30 No. 4 • 6-7/ 2013
ADVERTISING INDEX
Inq.No.
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143
147
157
150
111
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155
130
126
163
162
127
172
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142
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Page
77 Elektronika . . . . . . . . . . . .49
9th EFLM Symposium . . . . . .67
AACC . . . . . . . . . . . . . . . . . . .61
AB Sciex . . . . . . . . . . . . . . . .43
Advanced Instruments . . . . . .47
Agappe . . . . . . . . . . . . . . . . .57
Airclean . . . . . . . . . . . . . . . . .50
Autobio . . . . . . . . . . . . . . . . . .11
BCLF 2013 . . . . . . . . . . . . . . .68
Biomerica . . . . . . . . . . . . . . . .55
Bioporto . . . . . . . . . . . . . . . . .30
Bioron . . . . . . . . . . . . . . . . . .26
Brand . . . . . . . . . . . . . . . . . . .63
Caretium . . . . . . . . . . . . . . . .62
Carolina . . . . . . . . . . . . . . . . .27
Cellavision . . . . . . . . . . . . . . .72
Ceragem . . . . . . . . . . . . . . . .52
Ceragem . . . . . . . . . . . . . . . .53
Cytognos . . . . . . . . . . . . . . . .42
DAAN Gene . . . . . . . . . . . . . .28
DAS . . . . . . . . . . . . . . . . . . . .12
DiagCor . . . . . . . . . . . . . . . . .44
DIALAB . . . . . . . . . . . . . . . . .41
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Diagnostica Stago . . . . . . . . . .9
DIRUI . . . . . . . . . . . . . . . .24-25
DSI . . . . . . . . . . . . . . . . . . . . .62
EKF . . . . . . . . . . . . . . . . . . . .31
ELITech Group . . . . . . . . . . . . .2
Erba . . . . . . . . . . . . . . . . . . . . .7
EuroLabFocus 2014 . . . . . . .66
Globe Scientific . . . . . . . . . . .10
Greiner Bio-One . . . . . . . . . . .39
Hecht, Karl . . . . . . . . . . . . . . .56
Hitachi Aloka Medical . . . . . . .8
iCubio . . . . . . . . . . . . . . . . . . .32
IDS . . . . . . . . . . . . . . . . . . . . .71
IFCC Worldlab 2014 . . . . . . .64
Inova . . . . . . . . . . . . . . . . . . .19
Instrumentation Laboratory . .23
JIB 2013 . . . . . . . . . . . . . . . . .69
LabMedica.com . . . . . . . . . . . .6
Lee Co., The . . . . . . . . . . . . .58
Master Diagnostica . . . . . . . .20
Medix Biochemica . . . . . . . . .14
MIPTEC 2013 . . . . . . . . . . . .69
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WAMA . . . . . . . . . . . . . . . . . .33
145
West Medica / Vision . . . . . . .45
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