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Research Interests
Pulmonary embolism:
Since 1999, my work has focused on screening, risk
stratifying, and treatment of pulmonary embolism. I have focused on PE
because of its importance to society, and also because of the
fascinating physiology that occurs with PE. I have investigated the role
of using the alveolar deadspace (estimated using capnometry and arterial
PaCO2) plus a whole-blood D-dimer to screen for PE. At Carolinas Medical
Center (CMC), we use a combination of a decision rule that I derived and
the deadspace/D-dimer in what we term the “PE rule out” procedure. We
use this procedure approximately three times each day in the ED as part
of real practice. To advance my ideas, together with my business
partner, Mr. Michael Sinsheimer, I co-founded BreathQuant Medical
Systems, a company dedicated to noninvasive diagnosis (see
www.breathquant.com). Our company has patented and tested a breath-based
device and signal processing algorithm that uses expired CO2
and O2 to estimate alveolar deadspace from PE (US patent
issued). The proprietary name of this device is the CarboximeterTM
(US trademark pending). We have acquired $6MM in private funding to
build an FDA-approved carboximeter for the evaluation of dyspneic
patients. Additionally, we developed and are marketing a novel method of
assessing pretest probability of PE that uses a technique that I
invented known as computer-assisted, database-derived attribute matching
(US patent pending). I have an NIH R42 grant designed to advance this
technology. In follow-up to my published work on the use of an ECG
scoring system and pulse oximetry, I have a funded NIH RO1 grant
designed to provide clinicians with simple clinical criteria to predict
right ventricular strain on echocardiography and long-term
cardiopulmonary disability after PE. To help discover mechanisms of
persistent pulmonary hypertension after PE, we are examining the impact
of nonmalignant thrombophilia on the prognosis of PE. In the laboratory,
I have developed rat models of PE to allow us to measure the role of
inflammation on vascular reactivity during and pulmonary vascular
remodeling during pulmonary vascular occlusion. We hope to link the
inflammatory response to the presence of persistent pulmonary
hypertension in treated PE in rats and in humans. We are currently using
2-D electrophoresis to resolve plasma proteins in effort to discover a
protein liberated in the alveolar epithelial fluid and in the blood
under conditions of lung ischemia.
Education
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Bachelor of Science,
Major: Biochemistry, Minor: English
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Virginia Polytechnic
Institute and State University
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Blacksburg, Virginia,
1982-1986
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Doctor of Medicine
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Medical College of
Virginia
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Richmond, Virginia, 1986-1990
Selected Recent Publications
1. Custalow CB, , Thornton LR, Omalley P, Barbee RW,
Grattan RM, Lopaschuk GD, Watts JA, Kline JA. Role of fatty acids
in the recovery of heart function during resuscitation from hemorrhagic
shock. Shock, 15:231-238, 2001.
2. Heffner AC, Kline JA. Role of the
peripheral intravenous catheter in false-positive D-dimer testing.
Academic Emergency Medicine, 8: 103-106, 2001.
3. Courtney DM, Sasser H, Pinkus C, Kline JA.
Pulseless electrical activity with witnessed arrest as a predictor of
sudden death from pulmonary embolism in outpatients. Resuscitation,
49:265-272, 2001.
4. Norris BL, Patton WC, Rudd JN, Schmitt CM,
Kline JA. Pulmonary dysfunction in patients with femoral shaft
fractures treated with intramedullary nailing. Journal of Bone and
Joint Surgery, 83:1162-1168, 2001.
5. Sullivan DM, Watts JA, Kline JA.
Biventricular dysfunction after acute pulmonary embolism in the rat.
Journal of Applied Physiology 90:1648-1656, 2001.
6. Kline JA, Israel EG, Michelson EA, O’Neil
BJ, Plewa MC, Portelli DC. Diagnostic accuracy of a bedside D-dimer and
alveolar deadspace measurement for rapid exclusion of pulmonary embolism
(a multicenter study), JAMA 285:761-798 [See correspondence,
below. Paper featured in The Charlotte Observer local section March
14,2001]
7. Daniel KR, Courtney DM, Kline JA.
Assessment of cardiac stress from massive pulmonary embolism with
12-lead electrocardiography. Chest. 120:474-481, 2001.
8. Watts JA, Grattan RM, Whitlow BS, Kline JA.
Activation of Poly (ADP-ribose) in severe hemorrhagic shock and
resuscitation. American Journal of Physiology – Gastrointestinal &
Liver Physiology. 281(2):G498-506, 2001.
9. DeBehnke D, Kline JA, Shih R. Research
Fundamentals: Choosing and appropriate journal, manuscript preparation,
and interaction with editors. Academic Emergency Medicine
8:844-850, 2001.
10. Courtney DM, Kline JA. Identification of
pre-arrest clinical characteristics of fatal Pulmonary Embolism.
Academic Emergency Medicine.8:1136-1142, 2001.
11. Kline JA, Nelson RD,
Jackson RE, Courtney DM. Criteria for the safe use of D-dimer testing in
emergency department patients with suspected pulmonary embolism: A
multicenter United States study. Annals of Emergency Medicine.
37:144-152, 2002.
12. Moore CL,
Rose GA, Arrowood JA. Sullivan DM, Tayal VS, Kline JA.
Determination of left ventricular function in hypotensive emergency
department patients by emergency physician echocardiography.
Academic Emergency Medicine. 9:186-193, 2002.
13. Courtney DM, Watts JA, Kline JA. End
Tidal CO2 is reduced during hypotension and cardiac arrest in
a rat model of massive pulmonary embolism. Resuscitation.
53:83-91,2002
14. Custalow CB, Kline JA, Marx JA, Baylor
MR. Emergency department resuscitative procedures: animal laboratory
training improves procedural competency and speed Academic Emergency
Medicine 9:575-596, 2002.
15. Fesmire FM, Kline JA, Wolf SJ. Clinical
Policy: Critical issues in the evaluation and management of adult
patients presenting with suspected pulmonary embolism.
Annals of
Emergency Medicine, 41 (2):257-269, 2002.
16. Roshon MR, Kline JA, Thornton LR, Watts
JA. Cardiac UCP2 Expression and myocardial oxidative metabolism during
acute septic shock in the rat. Shock, 19(6):570-576, 2003
17. Richman PB, Wood J,
Kasper DM, Collins JM, Petri RW, Field AG, Cowles DN, Kline JA.
Contribution of indirect computed tomography venography to computed
tomography angiography of the chest for the diagnosis of thromboembolic
disease in two U.S. emergency departments. Journal of Thrombosis
and Haemostasis, 1(4):652-657, 2003
18. Jones A, Watts JA, Younger JG, Kline JA,.
Inhibition of Prostaglandin Synthesis During Experimental Massive
Pulmonary Embolism in the Rat. American Journal of Physiology
284: L1072-L1081, 2003
19. Kline JA, Wells PS. Methodology for a
Rapid Protocol to Rule-Out Pulmonary Embolism in the Emergency
Department. Annals of Emergency Medicine,
42(2):266-275, 2003.
20. Watts JA,
Kline JA. From Bench to Bedside: the role of mitochondrial medicine
in the pathogenesis and treatment of cellular injury. Academic
Emergency Medicine 10(9): 985-997, 2003.
21.
Wilson JS, Rushing GR, Johnson BL,
Kline JA, Back MR, Bandyk DF.
Dichloroacetate
Increases Skeletal Muscle Pyruvate Dehydrogenase Activity During Acute
Limb Ischemia. Journal of Vascular and Endovascular Surgery
37(3):T1-5, 2003
22. Wilson, JS,
Rushing, G, Johnson, BL, Kline JA, Parker, JL, Bowser, AN,
Bandyk, DF. The Effects of Dichloroacetate in a Rabbit Model of Acute
Hind Limb Ischemia and
Reperfusion.
Journal of American College of Surgeons, 197(4)591-5, 2003
23.
Kline JA, Cowles DN, Courtney DM, Newgard CE, Jackson RE. Use of
Pulse Oximetry to Predict Short-term Mortality in Hemodynamically Stable
Patients with Pulmonary Embolism in the Emergency Department.
American Journal of Medicine, 115(3):203-208, 2003
24.
Jones AE,
Tayal VS, Kline JA. Focused Training
of Emergency Medicine Residents in Goal-Directed Echocardiography: A
Prospective Study. Academic Emergency Medicine,
10(10):1054-1058, 2003
25. Jones AE,
Kline JA. Availability of technology to evaluate for pulmonary
Embolism in Academic Emergency Departments in the United States.
Journal of Thrombosis Haemostasis, 1(10)2240-2, 2003
26. Brown MD,
Kline JA, Nelson RD, Lau J.
Turbidimetric D-dimer in the diagnosis of pulmonary embolism: A
Meta-Analysis. Clinical Chemistry, 49:1846-1853, 2003
27. Zagorski J,
Debelak J, Gellar M, Watts JA, Kline JA. Chemokines Accumulate
in the Lungs of Rats with Severe Pulmonary Embolism Induced By
Polystyrene Microspheres. Journal of Immunology (Inflammation)
171(10):5529-36, 2003
28.
Jones AE, Stiell IA, Spaite DW, Nesbit L, Hasan N, Watts B, Kline JA.
Non-traumatic pre-hospital hypotension predicts in hospital
mortality. Annals of Emergency Medicine, 43:106-113, 2004
29. Watts JA,
Kline JA, Thornton LR, Grattan RM, Brar SS. Metabolic dysfunction
and depletion of mitochondria in hearts of septic rats. Journal of
Molecular Cellular Cardiology 36:141-150, 2004.
30. Richman PB, Courtney DM, Friese J, Matthews J,
Field A, Petri R, Kline JA. Prevalence and significance of non-thromboembolic
findings on chest computerized tomography angiography performed to
rule-out pulmonary embolism-A multi-center study of 1025 emergency
department patients. Academic Emergency Medicine, 11: 642-647,
2004
31. Jones AE, Tayal VS, Sullivan DM, Kline JA.
Randomized controlled trial of immediate versus delayed goal-directed
ultrasound to identify the cause of nontraumatic hypotension in
emergency department patients. Critical Care Medicine,
32:1703-1708, 2004.
32. Kline JA, Mitchell AM, Kabrhel C,
Richman PB, Courtney DM. Clinical criteria to prevent unnecessary
diagnostic testing in emergency department patients with suspected
pulmonary embolism. J. Thrombosis Haemostasis, 2:1247-1255, 2004.
[see commentary]
33. Kline JA,
Johnson CL, Webb WB, Runyon MS.
Prospective study of clinician-entered
research data in the Emergency Department using an Internet-based system
after the HIPAA Privacy Rule BMC Medical Informatics
and Decision Making 2004, 4:17
34. Kline JA, Webb WB, Jones AE, Hernandez
J. Impact of a rapid rule-out protocol for pulmonary embolism on the
rate of screening, missed cases, and pulmonary vascular imaging in an
urban U.S. emergency department. Annals of Emergency Medicine,
44:490-503, 2004.
35. Jones AE, Fitch M, Kline JA. Severity of
emergency department hypotension predicts adverse hospital outcome.
Shock 22(5):410-4, 2004
36. Brown MD, Vance SJ, Kline JA. An
emergency department guideline for the diagnosis of pulmonary embolism:
An outcome study. Academic Emergency Medicine, 12:20-25, 2005.
37. Engoren M, Plewa MC, O’Hara D, Kline JA
Evaluation of capnography using a genetic algorithm to predict arterial
partial pressure of carbon dioxide. Chest 127: 579-584, 2005.
38. Kline JA, Novobilski AJ, Kabrhel C,
Richman PB, Courtney DM, Derivation and validation of a Bayesian network
for the diagnosis of pulmonary embolism. Ann Emerg Med
45:282-290, 2005.
39. Courtney DM, Kline JA. Prospective use
of a prediction rule to identify pulmonary embolism as likely cause of
outpatient cardiac arrest. Resuscitation 65(1):57-64,
2005.
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