Transcript Lecture 4

BIOE 301
Lecture Four
Special Guest

Dr. Bob Parkerson, Baylor College of Medicine
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Co-director of the International Health Track for
MD students
Established WHO Collaborating Center for Family
& Community Medicine
Shoulder to Shoulder
BIOE in the News
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Ethics – Lancet Study Faked!
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Single pill for HIV
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http://www.ncbi.nlm.nih.gov/entrez/query.fcgi
?cmd=Retrieve&db=PubMed&list_uids=16226
613&dopt=Abstract
http://www.npr.org/templates/story/story.php
?storyId=5165566
http://www.npr.org/templates/story/story.php
?storyId=5163844
Packaging Malaria Drugs

http://www.npr.org/templates/story/story.php
?storyId=5164602
Summary of Lecture 3
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Developing World
1.
2.
3.
4.
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HIV/AIDS
Unintentional injuries
Cardiovascular diseases
Tuberculosis
Developed World
1.
2.
3.
4.
Unintentional injuries
Cardiovascular diseases
Cancer
Self-inflicted injuries
Overview of Lecture 4
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What are the major health problems
worldwide?
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Leading causes of mortality for ages 45-59
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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.
4.
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Cardiovascular diseases,
Cancer (malignant neoplasms),
Unintentional injuries, and
HIV/AIDS
Developed World
1.
2.
3.
4.
Cardiovascular diseases,
Cancer (malignant neoplasms),
Unintentional injuries, and
Digestive Diseases
Ischemic Heart Disease
CABG
PTCA
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
Cancer, Ages 45-59
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Cancer kills 1.5 million people aged 45-59
each year throughout the world each year
Lung cancer
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Stomach cancer
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185,000 deaths/year
Liver cancer
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263,000/year deaths in this age group
179,000 deaths/year
Breast cancer
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148,000 deaths/year
Cancer
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Tumor
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Types of Tumors:
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Abnormal mass of tissue
Growth exceeds that of normal tissue
Purposeless and preys on host
Benign
Malignant
Only malignant tumors can spread
(Metastasize)
Microscopic Appearance
2004 Estimated US Cancer Deaths*
Lung & bronchus
32%
Prostate
10%
Colon & rectum
Men
290,890
Women
272,810
25%
Lung & bronchus
15%
Breast
10%
10%
Colon & rectum
Pancreas
5%
6%
Ovary
Leukemia
5%
6%
Pancreas
Non-Hodgkin
lymphoma
4%
4%
Leukemia
3%
Esophagus
4%
Non-Hodgkin
lymphoma
Liver & intrahepatic
bile duct
3%
3%
Uterine corpus
2%
Multiple myeloma
Urinary bladder
3%
2%
Brain/ONS
Kidney
3%
All other sites
21%
ONS=Other nervous system.
Source: American Cancer Society, 2004.
24%
All other sites
Differentiation and Anaplasia
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Benign tumors
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Malignant tumors
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Range from well to poorly differentiated
Hallmarks of anaplasia:
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Well differentiated
Cells and nuclei show pleomorphism
Cells contain abundant DNA, coarse, clumped chromatin
Large NC ratio (1:1) rather than (1:4)
Large nucleoli
Large # of mitoses
Dysplasia
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Precancerous condition in epithelial tissue
Anaplastic cells in epithelium
Dysplasia does not always progress to cancer
Carcinogensis
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Carcinogenesis:
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Result of non-lethal genetic damage
Tumor masses result from the clonal expansion
of a single progenitor cell that has incurred
genetic damage
Biology of Tumor Growth
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Natural hx of most cancers has 4 phases:
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Malignant transformation in target cell
Growth of transformed cells
Local invasion
Distant metastases
Fig 7.33 – The Metastatic cascade
Neoplasia
Tissue Invasion
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Metastasis causes 90% of cancer death
How do tumors invade:
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Detach from primary tumor
Degrade surrounding matrix
Migrate
Importance of Cancer Screening
Five-Year Relative Survival Rates by Stage at Diagnosis
Relative Survival Rate (%)
100
90
80
70
60
Local
50
40
Regional
Distant
30
20
10
0
Colon &
Rectum
Melanoma
Oral Cavity
Urinary
Bladder
Uterine Cervix
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
Digestive Diseases
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Worldwide, 456,000 people aged 45-59
die each year from digestive diseases
Cirrhosis of the liver
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Kills 250,000 people each year between the
ages of 45 and 59
Liver
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Largest organ in the body
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Metabolizes fat and glucose
Helps remove toxic
substances from blood
Produces:
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Bile to help absorb fats
Proteins that regulate blood
clotting
Immune agents
Loss of liver function can
produce severe disease
and death
Liver – Microscopic Organization
Cirrhosis
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Normal liver is replaced with scar tissue as a
result of chronic injury, interfering with liver
function
Causes of cirrhosis:
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Chronic alcoholism
Viral hepatitis infection
Symptoms of cirrhosis:
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Exhaustion, loss of appetite, nausea, vomiting blood,
weakness, weight loss, and abdominal pain.
Patients bruise and bleed easily and become highly
sensitive to medicines with increasing loss of liver
functions.
Leading Causes of Death
Ages 0-4:
Perinatal conditions
Lower respiratory infections
Diarrheal diseases
Malaria
Ages 15-44:
HIV/AIDS
Unintentional injuries
Cardiovascular diseases
Tuberculosis
Ages 45-59:
Cardiovascular diseases
Cancers
Unintentional injuries
HIV/AIDS
Perinatal conditions
Congenital anomalies
Lower respiratory infections
Unintentional injuries
Unintentional injuries
Cardiovascular disease
Cancer
Self-Inflicted Injuries
Cardiovascular diseases
Cancer
Unintentional injuries
Digestive Diseases
BY SPECIFIC DISEASE
Ages 0-4
Cause of Disability
Lower respiratory infections
Diarrhoeal diseases
Low birth weight
Malaria
Birth asphyxia and birth trauma
Measles
Protein-energy malnutrition
Congenital heart anomalies
Pertussis
HIV/AIDS
Total DALYs
Total Population
DALYs Rate
Ages 15-44
Cause of Disability
HIV/AIDS
Unipolar depressive disorders
Tuberculosis
Road traffic accidents
Violence
Self-inflicted injuries
Schizophrenia
Bipolar disorder
Alcohol use disorders
Hearing loss, adult onset
Total DALYs
Total Population
DALYs Rate
Developing Countries
% of Total
# DALYs
DALYs
14.3%
60,236,694
13.2%
55,543,335
10.7%
44,997,007
10.0%
42,244,474
7.9%
33,133,613
18,618,263
4.4%
3.5%
14,718,970
3.1%
12,851,427
12,264,915
2.9%
2.9%
12,181,146
420,827,539
536,962,742
78.4%
Developing Countries
% of Total
# DALYs
DALYs
59,382,428
13.3%
35,978,376
8.1%
19,848,813
4.5%
19,151,250
4.3%
14,923,499
3.3%
12,189,495
2.7%
12,074,350
2.7%
10,977,659
2.5%
10,664,330
2.4%
9,186,758
2.1%
445,613,527
2,312,272,679
19.3%
Cause of Disability
Low birth weight
Congenital heart anomalies
Birth asphyxia and birth trauma
Lower respiratory infections
Diarrhoeal diseases
Iodine deficiency
Mental retardation, lead-caused
Meningitis
Down syndrome
Asthma
Total DALYs
Total Population
DALYs Rate
Developed Countries
% of Total
# DALYs
DALYs
1,337,103
10.3%
1,327,944
10.2%
1,310,241
10.1%
1,138,923
8.8%
537,438
4.1%
495,378
3.8%
467,625
3.6%
367,281
2.8%
367,109
2.8%
259,845
2.0%
13,003,994
81,206,312
16.0%
Unipolar depressive disorders
Alcohol use disorders
Road traffic accidents
Self-inflicted injuries
Violence
Bipolar disorder
Drug use disorders
Schizophrenia
Ischaemic heart disease
Hearing loss, adult onset
Developed Countries
% of Total
# DALYs
DALYs
10,484,105
13.7%
6,308,519
8.3%
3,804,331
5.0%
3,144,909
4.1%
2,285,286
3.0%
2,209,104
2.9%
2,037,084
2.7%
1,944,628
2.5%
1,916,252
2.5%
1,523,616
2.0%
Total DALYs
Total Population
DALYs Rate
76,416,610
597,682,683
12.8%
Cause of Disability
Leading Causes of Death
Ages 0-4:
Perinatal conditions
Lower respiratory infections
Diarrheal diseases
Malaria
Ages 15-44:
HIV/AIDS
Unintentional injuries
Cardiovascular diseases
Tuberculosis
Ages 45-59:
Cardiovascular diseases
Cancers
Unintentional injuries
HIV/AIDS
Perinatal conditions
Congenital anomalies
Lower respiratory infections
Unintentional injuries
Unintentional injuries
Cardiovascular disease
Cancer
Self-Inflicted Injuries
Cardiovascular diseases
Cancer
Unintentional injuries
Digestive Diseases
Violence
Self-inflicted injuries
Schizophrenia
Bipolar disorder
Alcohol use disorders
Hearing loss, adult onset
Total DALYs
Total Population
DALYs Rate
Ages 45-59
Cause of Disability
Ischaemic heart disease
Cerebrovascular disease
Cataracts
Unipolar depressive disorders
Chronic obstructive pulmonary disease
Hearing loss, adult onset
HIV/AIDS
Tuberculosis
Vision disorders, age-related
Diabetes mellitus
Total DALYs
Total Population
DALYs Rate
14,923,499
12,189,495
12,074,350
10,977,659
10,664,330
9,186,758
3.3%
2.7%
2.7%
2.5%
2.4%
2.1%
445,613,527
2,312,272,679
19.3%
Developing Countries
% of Total
# DALYs
DALYs
12,050,270
7.6%
10,212,640
6.4%
9,735,678
6.1%
8,374,876
5.3%
7,287,981
4.6%
6,891,572
4.3%
6,703,167
4.2%
6,504,260
4.1%
4,787,811
3.0%
4,045,375
2.5%
159,380,182
600,316,766
26.5%
Violence
Bipolar disorder
Drug use disorders
Schizophrenia
Ischaemic heart disease
Hearing loss, adult onset
Total DALYs
Total Population
DALYs Rate
2,285,286
2,209,104
2,037,084
1,944,628
1,916,252
1,523,616
3.0%
2.9%
2.7%
2.5%
2.5%
2.0%
76,416,610
597,682,683
12.8%
Ischaemic heart disease
Cerebrovascular disease
Unipolar depressive disorders
Hearing loss, adult onset
Trachea, bronchus, lung cancers
Chronic obstructive pulmonary disease
Osteoarthritis
Cirrhosis of the liver
Diabetes mellitus
Alcohol use disorders
Developed Countries
% of Total
# DALYs
DALYs
5,286,352
11.3%
3,123,891
6.7%
3,006,141
6.4%
1,884,097
4.0%
1,770,453
3.8%
1,762,640
3.8%
1,545,250
3.3%
1,438,096
3.1%
1,388,386
3.0%
1,086,926
2.3%
Total DALYs
Total Population
DALYs Rate
46,615,959
254,600,864
18.3%
Cause of Disability
New World of Global Health
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Bill and Melinda Gates Foundation
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Global Fund to Fight AIDS, TB and Malaria
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Pledged $6 billion since 1999 to global health
issues
Roughly the same as the WHO budget during
the same time
$8.6 billion to 128 countries launched in 2002
President’s Emergency Plan for HIV/AIDS
Relief, 2004
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$15 billion
Challenges Faced
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Countries struggle with procurement
policies, hard to convert $$ to drugs
Shortages of trained health care workers
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http://www.npr.org/templates/story/story.php
?storyId=4987628
Corruption
Lack of coherent approach
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)
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
http://www.npr.org/templates/story/story.php
?storyId=939533
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
Grand Challenge Proposals
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NIH issued request for proposals to
address challenges
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Grants of up to $20M over five years or less
http://www.grandchallengesgh.org/
Summary of Lecture Four

Developing World
1.
2.
3.
4.

Cardiovascular diseases,
Cancer (malignant neoplasms),
Unintentional injuries, and
HIV/AIDS
Developed World
1.
2.
3.
4.
Cardiovascular diseases,
Cancer (malignant neoplasms),
Unintentional injuries, and
Digestive Diseases
Assignments Due Next Time

HW 4