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BME 301
Lecture Three
Review of Lecture Two
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Developing countries
Leading causes of mortality: ages 15-44
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Developing world
1.
2.
3.
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HIV/AIDS
Road Accidents
Interpersonal violence
Developed world
1.
2.
3.
Road accidents
Self-inflicted injuries
Interpersonal violence
Overview of Lecture 3
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What are the major health problems
worldwide?
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Leading causes of mortality by age
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Developed world
Developing world
Global health challenges
Leading Causes of Mortality Ages 45-60
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Developing World
1.
2.
3.
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Heart Disease - ARF
Cerebrovascular Disease
Tuberculosis
Developed World
1.
2.
3.
Heart Disease – IHD
Respiratory Cancers
Cerebrovascular Disease
Epidemiology: ARF
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United States
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Developing countries
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1940: mortality was 20.6/100,000 population
1982: mortality was 2.2/100,000 population
Occasionally outbreaks in localized areas of
US (Salt Lake City, Pittsburgh in the 1980s)
Still a significant health problem
15-20 million new cases a year
Risk factors
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Low standard of living
Crowding
ARF – Clinical Course
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Begins with group A strep infection
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“strep throat” resolves (NOT SERIOUS)
Small group (3%) of propel go on to develop
rheumatic fever (CAN BE VERY SERIOUS)
Cause not fully understood
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Heightened immunologic reactivity to
streptococcal antigens; makes antibodies that
are cross-reactive to human tissue antigens
Individual develops autoimmune reaction
induced by strep infection
ARF – Clinical Course
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Initial attack
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1-5 weeks after strep throat
infection
Migratory polyarthritis and fever
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One joint after another becomes
painful and swollen for a few days
and then gets better
Carditis – inflammation of lining of
the heart, can induce heart
arrythmias. Usually heals
Prognosis for first attack is
usually quite good, 1% die
ARF – Clinical Course
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Subsequent attacks
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Increased vulnerability to reactivation of
disease with subsequent strep infections
Same symptoms with each attack
Carditis worsens with each attack
Heart valves are frequently deformed (mitral)
Hear failure develops after decades
Long Term Consequences: ARF
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Healing of rheumatic valvitis can lead to
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valvular stenosis
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and/or regurgitation
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Heart pumps against a closed valve with stenosis
heart pumps against an open valve with regurgitation
Can lead to heart failure
Can lead to death
My Uncle Gene
Treatment: ARF
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Treat first strep throat infection with
penicillin
Treat other manifestations
symptomatically
Prophylactic long term anti-strep therapy
given to anyone who has had RF
Ischemic Heart Disease:
Epidemiology
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United States
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11 million people have coronary artery disease
Causes more deaths, disability and economic cost
than any other illness
Risk factors
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Positive family history
Diabetes
Hyperlipidemia
Hypertension
Smoking
Ischemic Heart Disease: Pathogenesis
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Atherosclerosis
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Causes a decrease in myocardial perfusion
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Stable angina
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Typically a 50-60 yo man or 65-75 yo woman
Heaviness, pressure, squeezing, smothering or choking
Localized to chest
Lasts 1-5 minutes
Radiates to left shoulder and both arms
Unstable angina
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Patients with angina that is:
 New onset and severe and frequent
 Accelerating
 Angina at rest
Ischemic Heart Disease: Diagnosis
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Usually made by history
Physical exam may reveal other disorders
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Lipid disorders
Hypertension
Diabetes
Testing
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EKG
Stress Testing
Coronary arteriography
http://www.columbiasurgery.org/divisions/cardiac/im
ages/novartis_207B.jpg
Ischemic Heart Disease: Treatment
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Medical management
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Nitrates
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Increase myocardial oxygen supply, systemic
vasodilation
Beta blockers
Inhibit increases in heart rate and contractility
 Decrease myocardial oxygen demand
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Calcium channel agonists
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Coronary vasodilators
CABG
PTCA
CABG
PTCA
Cerebrovascular Disease: Epidemiology
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Third leading cause of death in the US
Most prevalent neurologic disorder
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Morbidity
Mortality
Cerebrovascular Disease: Stroke
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Abrupt onset with focal neurologic deficit
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Usually mini-event or warning signs
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Reversible ischemia
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5-20% transient ischemic attacks
Some lasting 24-72 hours
Completed stroke
Maximal deficit within hours
 Often patient awakens with completed stroke
 Usually preceded by TIA Progressive stroke
 Ischemia worsens min. to min. or hour to hour
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Cerebrovascular Disease: Pathogenesis
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Causes of stroke:
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Blood vessel supplying the brain is blocked
Thrombosis (clot in vessel)
Embolism (clot breaks off and lodges in blood
vessel in brain)
Vasoconstriction or spasm
Venous collapse
Cerebrovascular Disease: Diagnosis
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History
Exam
Imaging
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CT Scan
MRI
CT/MR Angiography
Cerebrovascular Disease: Treatment
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Thrombolysis
Rehabilitation
Experimental
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Angioplasty
Heparin
Coumarin
Aspirin
Lung Cancer: Epidemiology
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United States
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99,000 males die per year
78,000 females die per year
Five year survival: 14%
Only 15% of patients are diagnosed with
localized disease
Risk factors
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Smoking
Actively: increases relative risk 13X
 Passively: increases relative risk 1.5X
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Lung Cancer: Clinical Manifestations
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Signs and symptoms
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Coughing, wheezing, difficulty breathing,
recurrent pneumonia
Diagnosis:
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Screening:
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Trials of CXR, sputum cytology, NOT SUCCESSFUL
Diagnostic:
CXR
 CT directed biopsy
 Bronchoscopically directed biopsy
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Staging: concept of localized vs. distant disease
Lung Cancer: Treatment
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Localized
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Small: Possibly surgery
Large: Chemo or XRT + surgery
Metastatic:
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Chemo + XRT
Tuberculosis: Epidemiology
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Reported cases:
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3.8 million new cases per year reported to WHO
90% occur in developing world
Probably underreported
Likely 9 million new cases per year
 3 million deaths per year (98%) in developing world
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Tuberculosis: Pathogenesis
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Bacterial infection of the lungs
Drug susceptible TB is curable
If untreated, results in death in 5 years in
half of all cases
Tuberculosis: Clinical Manifestations
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Primary disease
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Results from initial infection
Usually occurs in children
Lesion in lower or middle lungs
Heals spontaneously, may leave calicified scar
Secondary disease
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Endogenous reactivation of latent infection
May involve massive amounts of lung
1/3 of patients: cavity formation liquefied
necrosis spills into airway pneumonia
 2/3 of patients: spontaneous remission chronic,
progressively debilitating course ‘consumption’
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Tuberculosis: Clinical Manifestations
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Symptoms
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Fever
Night sweats
Weight loss
Weakness
Coughs (productive with bloody sputum)
Tuberculosis: Diagnosis
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CXR
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Shows nodules
Sputum culture
Tuberculosis: Treatment
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Chemotherapy with streptomycin
Four new drugs available for oral therapy
NPR Story: TB and AIDS
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http://www.npr.org/rundowns/segment.php?
wfId=1520699
Global Health Challenges
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$200 million medical research initiative
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Grand challenges in global health
Bill and Melinda Gates Foundation
Encourage scientific and technological
solutions to diseases that disproportionately
affect the developing world
Announced in January 2003
What is a grand challenge?
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Scientific or technical innovation that:
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Removes a critical barrier to solving an important
health problem in developing world
High likelihood of global impact and feasibility
Different than:
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Simple statement of a “big problem” in global health
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HIV/AIDS, malnutrition, lack of access to medical care, lack
of resources
Meant to:
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Direct investigators to specific breakthrough that
provides solution to a significant health problem(s)
Call for Grand Challenges
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Call For Ideas I (May 2003)
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1048 submissions from scientists and
institutions in 75 countries
Scientific Board heard proposals (August
2003)
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Problem
Roadblock (obstacle to progress)
Challenge
List of potential benefits
Goals and Grand Challenges
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Seven Long Range Goals
14 Grand Challenges
Heavily oriented toward infectious disease
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Infectious diseases account for the most
profound discrepancies between advanced
and developing economies
Causes of infectious diseases are well-known
Can more easily formulate technical and
scientific obstacles to progress
Results reported in Science (Oct 17, 2003)
Goals and Grand Challenges
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Improve childhood vaccines
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GC1-Create effective, single dose vaccines that can be
used soon after birth
GC2-Prepare vaccines that do not require refrigeration
GC3-Develop needle-free delivery systems for
vaccines
Create new vaccines
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GC4-Devise reliable tests in model systems to
evaluate live attenuated vaccines
GC5-Solve how to design antigens for effective
protective immunity
GC6-Learn which immunological responses provide
protective immunity
Goals and Grand Challenges
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Control insects that transmit infectious disease
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Improve nutrition to promote health
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GC7-Develop a genetic strategy to deplete or
incapacitate a disease-transmitting insect population
GC8-Develop a chemical strategy to deplete or
incapacitate a disease-transmitting insect population
GC9-Create a full range of optimal bioavailable
nutrients in a single staple plant species
Improve drug treatment of infectious disease
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GC10-Discover drugs and delivery systems that
minimize the likelihood of drug-resistant organisms
Goals and Grand Challenges
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Cure latent and chronic infections
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GC11-Create therapies that can cure latent infections
GC12-Create immunologic methods that can cure
chronic infections
Measure disease and health status accurately in
economically in poor countries
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GC13-Develop technologies that permit quantitative
assessment of population health status
GC14-Develop technologies that allow assessment of
individuals for multiple conditions or pathogens at
point-of-care
Next Steps
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NIH issues request for proposals to
address challenges
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Grants of up to $20M over five years of less
Due June 2004
Awards in October 2004
Summary of Lecture Three
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Leading causes of mortality: ages 45-60
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Developing World
1.
2.
3.
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Developed World
1.
2.
3.
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Heart Disease - ARF
Cerebrovascular Disease
Tuberculosis
Heart Disease – IHD
Respiratory Cancers
Cerebrovascular Disease
Global health challenges
Assignments Due Next Time
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WA2
Poll on Global Attitudes