U.S. patent application number 13/598154 was filed with the patent office on 2012-12-20 for testing lumenectomy samples for markers of non-vascular diseases.
This patent application is currently assigned to TYCO HEALTHCARE GROUP LP. Invention is credited to John B. Simpson, Angela Soito.
Application Number | 20120322688 13/598154 |
Document ID | / |
Family ID | 38235243 |
Filed Date | 2012-12-20 |
United States Patent
Application |
20120322688 |
Kind Code |
A1 |
Soito; Angela ; et
al. |
December 20, 2012 |
TESTING LUMENECTOMY SAMPLES FOR MARKERS OF NON-VASCULAR
DISEASES
Abstract
Lumenectomy material is tested to determine the presence or
likelihood of a condition of a patient. The lumenectomy material is
in the form of at least one continuous tissue strand collected in
vivo from an inner surface of a body lumen of the patient. The
presence of at least one marker of a disease is determined. The
disease may be hypertension, hyperlipidemia, depression, obesity,
metabolic syndrome, insulin resistance, kidney damage, or diabetes.
The patient is identified as having or as likely to develop the
disease if a marker of the disease is identified in the lumenectomy
material of the patient.
Inventors: |
Soito; Angela; (Oakland,
CA) ; Simpson; John B.; (Woodside, CA) |
Assignee: |
TYCO HEALTHCARE GROUP LP
Mansfield
MA
|
Family ID: |
38235243 |
Appl. No.: |
13/598154 |
Filed: |
August 29, 2012 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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13362249 |
Jan 31, 2012 |
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13598154 |
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13167767 |
Jun 24, 2011 |
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13362249 |
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11356460 |
Feb 17, 2006 |
7989207 |
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13167767 |
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Current U.S.
Class: |
506/9 ; 435/29;
435/6.11; 435/6.12; 435/7.1; 435/7.92; 600/567 |
Current CPC
Class: |
A61B 10/0233 20130101;
Y10T 436/25 20150115; G01N 33/68 20130101; A61B 17/22 20130101 |
Class at
Publication: |
506/9 ; 600/567;
435/7.92; 435/7.1; 435/29; 435/6.11; 435/6.12 |
International
Class: |
A61B 10/02 20060101
A61B010/02; C12Q 1/68 20060101 C12Q001/68; C40B 30/04 20060101
C40B030/04; G01N 33/53 20060101 G01N033/53; G01N 21/64 20060101
G01N021/64 |
Claims
1. A method for diagnosing a disease in a patient, the method
comprising: a) collecting a tissue sample from a lumen of a body of
said patient in a manner sufficient to ensure that the structure of
the collected tissue sample retains the actual in vivo tissue
structure; b) performing a test on said sample to obtain test
results, wherein said test results in the identification of at
least one marker of a disease selected from the group consisting of
hypertension, hyperlipidemia, depression, obesity, metabolic
syndrome, insulin resistance, kidney damage, and diabetes; and c)
diagnosing said patient for said disease based on said test
results, wherein the disease is selected from the group consisting
of hypertension, hyperlipidemia, depression, obesity, metabolic
syndrome, insulin resistance, kidney damage, and diabetes.
2. The method according to claim 1, wherein said sample is
collected by a catheter.
3. The method according to claim 2, wherein said catheter comprises
a housing and said housing comprises an aperture for collecting
said tissue sample.
4. The method according to claim 3, wherein the catheter further
comprises a blade.
5. The method according to claim 4, wherein the blade is translated
via the aperture.
6. The method according to claim 5, wherein said aperture is
elongated and further comprises a cutting window.
7. The method according to claim 6, wherein said tissue sample
comprises a lumenectomy material.
8. The method according to claim 7, wherein said lumenectomy
material is removed from an inner surface of a body lumen.
9. The method according to claim 8, wherein the catheter is
employed in such a manner that it planes across the inner surface
of the body lumen.
10. The method according to claim 9, wherein the planing action of
the catheter results in the collection of said lumenectomy material
within the aperture.
11. The method according to claim 10, wherein the lumenectomy
material collected comprises at least one continuous tissue strand
having a substantially consistent depth and width.
12. The method according to claim 5, wherein translation of the
blade results in the collection of the tissue sample, and further
wherein the tissue sample comprises a lumenectomy material.
13. The method according to claim 10, wherein the amount of said
lumenectomy material collected ranges from about 1 mg to about 2000
mg.
14. The method according to claim 10, wherein the length of the
lumenectomy material ranges from about 2.0 mm to about 10 cm.
15. The method according to claim 14, wherein the length of the
lumenectomy material ranges from about 2.0 mm to about 0.5 cm.
16. The method according to claim 10, wherein the length of the
lumenectomy material is longer than 10 cm.
17. The method according to claim 1, wherein the markers comprises
one or more of a member selected from the group consisting of a
DNA, a protein, and a RNA.
18. The method according to claim 1, wherein the test further
results in the identification of an increased or decreased level of
the marker as compared with a non-disease condition.
19. The method according to claim 1, wherein the test further
results in the identification of the presence or absence of the
marker.
20. The method according to claim 1, further comprising the
collection of the tissue sample from a plurality of sites within
said lumen of the patient's body.
Description
CROSS-REFERENCES TO RELATED APPLICATION
[0001] This application is a continuation of U.S. patent
application Ser. No. 13/362,249, filed Jan. 31, 2012, which is a
continuation of U.S. patent application Ser. No. 13/167,767, filed
Jun. 24, 2011, now abandoned, which is a continuation of U.S.
patent application Ser. No. 11/356,460, filed Feb. 17, 2006, now
U.S. Pat. No. 7,989,207 B2, issued Aug. 2, 2011, the contents of
each of which are hereby incorporated by reference herein.
TECHNICAL FIELD OF THE INVENTION
[0002] This invention is related to the area of disease diagnosis
and prognosis. In particular, it relates to testing for disease
markers in lumenectomy samples, such as samples from a blood
vessel.
BACKGROUND OF THE INVENTION
[0003] Cardiovascular disease frequently arises from the
accumulation of atheromatous material on the inner walls of
vascular lumens, particularly arterial lumens of the coronary and
other vasculature, resulting in a condition known as
atherosclerosis. Atherosclerosis occurs naturally as a result of
aging, but may also be aggravated by factors such as diet,
hypertension, heredity, vascular injury, and the like. Atheromatous
and other vascular deposits restrict blood flow and can cause
ischemia which, in acute cases, can result in myocardial
infarction. Atheromatous deposits can have widely varying
properties, with some deposits being relatively soft and others
being fibrous and/or calcified. In the latter case, the deposits
are frequently referred to as plaque. One conventional treatment
for cardiovascular disease is the use of stents. Endoluminal stents
are commonly used to treat obstructed or weakened body lumens, such
as blood vessels and other vascular lumens. Once deployed in the
blood vessel, the stent can remain in the body lumen where it will
maintain the patency of the lumen and/or support the walls of the
lumen which surround it. One factor impeding the success of stent
technology in endoluminal treatments is the frequent occurrence of
in-stent restenosis, characterized by proliferation and migration
of smooth muscle cells within and/or adjacent to the implanted
stent, causing reclosure or blockage of the body lumen.
[0004] Atherosclerosis and restenosis can be treated in a variety
of ways, including drugs, bypass surgery, and a variety of
catheter-based approaches which rely on intravascular debulking or
removal of the atheromatous or other material occluding a blood
vessel. Of particular interest to the present invention, a variety
of methods for cutting or dislodging material and removing such
material from the blood vessel have been proposed, generally being
referred to as atherectomy procedures. Atherectomy catheters
intended to excise material from the blood vessel lumen generally
employ a rotatable and/or axially translatable cutting blade which
can be advanced into or past the occlusive material in order to cut
and separate such material from the blood vessel lumen. In
particular, side-cutting atherectomy catheters generally employ a
housing having an aperture on one side, a blade which is rotated or
translated by the aperture, and a balloon to urge the aperture
against the material to be removed.
[0005] Although atherectomy catheters have proven very successful
in treating many types of atherosclerosis and in-stent restenosis,
improved atherectomy catheters and methods are continuously being
pursued. For example, many currently available side-cutting
atherectomy catheters have difficulty in capturing occluding
material in the cutting aperture. To facilitate material capture,
the cutting aperture is frequently elongated to increase the area
into which the material can penetrate. Such elongation typically
requires an equivalent lengthening of the cutter housing. Since
most cutter housings are rigid, such lengthening makes it more
difficult to introduce the distal end of the catheter through
tortuous regions of the vasculature.
[0006] Another shortcoming of many currently available atherectomy
catheters is that they typically require a balloon positioned
opposite the cutting window to urge the cutting window into contact
with occluding material. Such balloons, however, unduly increase
the size of the distal portion of the catheter. Even with the
balloon, the amount of material that can be removed by conventional
atherectomy catheters is limited by the size of the cutting window.
Other disadvantages of some catheters include cutting elements with
less than ideal hardness, inadequate storage space within the
catheter for containing removed material, sub-optimal guide wire
lumens, and/or the like. In addition, the available atherectomy
catheters generally provide material insufficient in quantity
and/or quality for testing by many histological, array, proteomic
or other biochemical or molecular methods. For example, in one
report a device and method available to the artisan collected less
than about 50 mg of tissue. (Safian et al., Circulation 82: 305-307
(1990)). This amount of material is not typically enough to carry
out more than one test, or is insufficient to successfully carry
out a number of diagnostic tests available to the physician or
researcher.
[0007] Recently atherectomy catheters have been developed which can
access small, tortuous regions of the vasculature and remove
atheromatous and other occluding materials from within blood
vessels and stents in a controlled fashion. In particular, these
atherectomy catheters facilitate capturing and invagination of
atheromatous materials. Particularly, these catheters are capable
of in vivo capturing and removing of continuous tissue strands of
sufficient quantity and quality for testing in vitro. These
catheters and methods for their use are adaptable for use in a
variety of body lumens, including but not limited to coronary and
other arteries.
[0008] There is a continuing need in the art to develop new methods
for accurate and early assessments of disease states and incipient
or imminent disease states.
SUMMARY OF THE INVENTION
[0009] One aspect of the invention provides a method of determining
the presence or likelihood of a condition of a patient. A
lumenectomy material comprising at least one continuous tissue
strand collected in vivo from an inner surface of a body lumen of a
subject is tested for the presence of at least one marker of a
disease selected from the group consisting of hypertension,
hyperlipidemia, depression, obesity, metabolic syndrome, insulin
resistance, kidney damage, and diabetes. The patient is identified
as having or as likely to develop the disease if a marker of the
disease is identified in the lumenectomy material of the
subject.
[0010] This and other embodiments which will be apparent to those
of skill in the art upon reading the specification provide the art
with methods for detection, diagnosis, and prognosis of
diseases.
DETAILED DESCRIPTION OF THE INVENTION
[0011] The inventors have developed methods for testing for the
presence or likelihood of certain diseases. Rather than testing for
certain disease makers in serum, for example, the present methods
test for disease markers in lumenectomy samples, such as
artherectomy samples.
[0012] Diseases which can be evaluated using the method of the
invention include, but are not limited to, hypertension,
hyperlipidemia, depression, obesity, diabetes, insulin resistance,
metabolic syndrome, kidney disease, and kidney damage. Lumens from
which the test sample can be harvested include blood vessels, such
as the coronary artery, the gastrointestinal tract, such as the
intestine, airways, such as the bronchi and the trachea, tear
ducts, mammary ducts, kidney tubules, ureters, bladders, urethras,
vas deferens, epididymis, and fallopian tubes.
[0013] Lumenectomy catheters which can be used to collect the
samples of the present invention are described in U.S. application
publication no. 20050177068, the disclosure of which is expressly
incorporated herein. Other lumenectomy catheters which provide
sufficient material for testing may also be used. In certain
embodiments the amount of material collected can be about 1 mg to
about 2000 mg, more typically the amount of material can be about 1
mg to about 100 mg, about 100 mg to about 200 mg, about 200 mg to
about 300 mg, about 300 mg to about 400 mg, about 400 mg to about
500 mg, about 500 mg to about 600 mg, about 600 mg to about 700 mg,
about 700 mg to about 800 mg, or about 800 mg up to about 2000
mg.
[0014] The material excised from the body lumen will vary in length
and will depend on the catheter configuration, the type of material
removed, the body lumen, and the like. However, in certain
embodiments, the material will be in the form of continuous strands
that have a substantially consistent depth and width of tissue
cuts. The material is typically longer than the length of the
cutting window (but it may be shorter), and typically has a length
of at least about 2.0 mm, although the length may be between about
0.5 cm up to about 10 cm or longer in length. Advantageously, the
planing action of the catheter provides a material tissue structure
that reflects the actual in vivo tissue structure, and provides
information about larger portions of the disease state of the body
lumen.
[0015] Markers which can be tested are any for which an association
has been established between the marker and the disease or imminent
onset of the disease. Markers can be, for example, proteins,
enzymes, or RNAs. The marker can be the presence or absence of a
substance or an increased or decreased level of the substance. The
material collected from the body lumen is typically a continuous
strip of tissue that may be longer than the cutting window of the
lumenectomy catheter. This material can provide a sufficient amount
of sample material of a quality and quantity that can be used for
one or more of genomic screening, DNA hybridization, RNA
hybridization, gene expression analysis, PCR amplification,
proteomic testing, drug efficacy screening, protein marker
detection, DNA marker detection, RNA marker detection, histological
testing, histopathology, cytopathology, cell and tissue type
analysis, biopsy, or the like. In addition, the material collected
may be sufficient in amount and quality for testing for one or more
of the presence of a DNA, an RNA, or a protein marker.
[0016] Generally the markers may be in the category of apoptotic
markers, cell cycle proteins, transcriptional factors,
proliferative markers, endothelial growth factors, adhesion
molecules, cytokines, chemokines, chemokine receptors, inflammation
markers, coagulation factors, fibrinolytic factors, oxidative
stress related molecules, extracellular matrix molecules,
interleukins, growth factors, glycoproteins, proteoglycans,
cell-surface markers, serum markers, or immune factors. Other types
of markers which are established as associated with the diseases
may be used as well.
[0017] Specific markers which may be used include C-reactive
protein, interleukin-6, and/or intracellular adhesion molecule-1
for depression; angiotensin II, aldosterone, and/or atrial
natriuretic factor for hypertension; tissue factor pathway
inhibitor, plasminogen activator inhibitor-1, triglycerides, and/or
apolipoprotein B for hyperlipidemia; triglycerides for insulin
resistance; low density lipoprotein, Remnant-like
particles-cholesterol and/or triglycerides for diabetes;
triglyceride-rich lipoproteins for kidney damage. Other markers as
are known in the art and which are associated with specific
diseases can be used as well, without limitation.
[0018] Particular types of tests that can be carried out
successfully on the excised lumenectomy material removed by the
methods of the present invention include, but are not limited to,
enzyme histochemistry, immunohistology, immunocytochemistry,
immunoassays, immunofluorescent assays, immunoprecipitation assays,
ELISA, flow cytometry, fluorescent activated cell sorting,
radioimmunochemistry, electrophoresis, two-dimensional gel
electrophoresis, Western blotting, protein sequencing, mass
spectrometry, proteomic analysis, and protein microarray analysis.
Further, Nothern blotting, RNase protection assays, in situ
hybridization assays, DNA microarray testing, reverse transcription
polymerase chain reaction PCR (RT-PCR), Southern blotting, DNA
sequencing, PCR amplification, single strand conformational
polymorphism assays, single strand polymorphism (SNP) assays, and
serial analysis of gene expression (SAGE) assays can be
successfully carried out with the lumenectomy material compositions
collected by the disclosed methods.
[0019] Prior to testing the harvested material, the material can
optionally be placed in a preserving agent, a tissue fixative, or a
preparation agent compatible with a particular test to be run.
Agents known in the art for preserving, fixing or preparing the
material for later use include, for example, saline, heparinized
saline, liquid nitrogen, formalin, a membrane lysis agent, an RNA
or DNA preparation agent, and the like. The material can be
collected in a single access or can be collected in multiple
translumenal accesses in the same patient. Further the material is
typically at least one substantially consistent, continuous strip
of material that maintains the structure of the material as it was
removed from the inner surface of the lumen of the patient. Also,
sample material can be collected from one, two, or more sites in
the same or a different body lumen of a patient.
[0020] The lumenectomy catheters can achieve selective plaque
excision, i.e., they can specifically target diseased areas. Thus
the samples are enriched in disease markers, relative to serum
samples, in which disease markers are diluted with other substances
from non-diseased tissues. Nonetheless, serum testing may be
performed in conjunction with the lumenectomy evaluation, and the
results used, for example, to confirm each other.
[0021] The above disclosure generally describes the present
invention. All references disclosed herein are expressly
incorporated by reference. A more complete understanding can be
obtained by reference to the following specific examples which are
provided herein for purposes of illustration only, and are not
intended to limit the scope of the invention.
REFERENCES
[0022] The disclosure of each reference cited is expressly
incorporated herein.
[0023] Yu H. et al., Hypertension 2000; 35:135
[0024] Raij, L., Hypertension, 2001; 37:767
[0025] Tomiyama, H., et al., Hypertension, 2005; 45:997
[0026] Guo, X., et al., Hypertension, 2005; 45:799
[0027] Sarnak, M. et al., Hypertension, 2003; 42:1050
[0028] Cassidy, A., et al., Circulation, 2005; 111:1877-1882
[0029] Empana, J. P., et al., Circulation, 2005; 111:2299-2305
[0030] Bolterman, R. et al., Hypertension, 2005, doi:
10/1161/01.HYP.0000174602.59935.D5
[0031] Preston, R., et al., Hypertension, 2003; 41:211
[0032] Zitoun, D., et al., Arteriosclerosis, Thrombosis, and
Vascular Biology. 1996; 16:77-81
[0033] Sijbrands, E., et al., Arteriosclerosis, Thrombosis, and
Vascular Biology. 1999;19:2722
[0034] Mar, R., et al., Circulation Research. 2004; 94:993
[0035] Twickler, T. B., et al., Circulation. 2004;109:1918-1925
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