BIOE 301

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BIOE 301

• Lecture Four

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Special Guest

• Dr. Bob Parkerson, Baylor College of Medicine
• Co-director of the International Health Track for
  MD students
• Established WHO Collaborating Center for Family
  Community Medicine
• Shoulder to Shoulder

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BIOE in the News

• Ethics Lancet Study Faked!
• http//www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd
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• http//www.npr.org/templates/story/story.php?story
  Id5165566
• Single pill for HIV
• http//www.npr.org/templates/story/story.php?story
  Id5163844
• Packaging Malaria Drugs
• http//www.npr.org/templates/story/story.php?story
  Id5164602

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Summary of Lecture 3

• Developing World
• HIV/AIDS
• Unintentional injuries
• Cardiovascular diseases
• Tuberculosis
• Developed World
• Unintentional injuries
• Cardiovascular diseases
• Cancer
• Self-inflicted injuries

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Overview of Lecture 4

• What are the major health problems worldwide?
• Leading causes of mortality for ages 45-59
• Developed world
• Developing world
• Global health challenges

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Leading Causes of Mortality Ages 45-60

• Developing World
• Cardiovascular diseases,
• Cancer (malignant neoplasms),
• Unintentional injuries, and
• HIV/AIDS
• Developed World
• Cardiovascular diseases,
• Cancer (malignant neoplasms),
• Unintentional injuries, and
• Digestive Diseases

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Ischemic Heart Disease
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CABG PTCA
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Cerebrovascular Disease Stroke

• Abrupt onset with focal neurologic deficit
• Usually mini-event or warning signs
• 5-20 transient ischemic attacks
• Reversible ischemia
• 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

• Causes of stroke
• 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

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Cerebrovascular Disease Diagnosis

• History
• Exam
• Imaging
• CT Scan
• MRI
• CT/MR Angiography

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Cerebrovascular Disease Treatment

• Thrombolysis
• Rehabilitation
• Experimental
• Angioplasty
• Heparin
• Coumarin
• Aspirin

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Cancer, Ages 45-59

• Cancer kills 1.5 million people aged 45-59 each
  year throughout the world each year
• Lung cancer
• 263,000/year deaths in this age group
• Stomach cancer
• 185,000 deaths/year
• Liver cancer
• 179,000 deaths/year
• Breast cancer
• 148,000 deaths/year

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Cancer

• Tumor
• Abnormal mass of tissue
• Growth exceeds that of normal tissue
• Purposeless and preys on host
• Types of Tumors
• Benign
• Malignant
• Only malignant tumors can spread (Metastasize)

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Microscopic Appearance
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2004 Estimated US Cancer Deaths
Men290,890
Women272,810
25 Lung bronchus 15 Breast 10 Colon
rectum 6 Ovary 6 Pancreas 4 Leukemia
3 Non-Hodgkin lymphoma 3 Uterine
corpus 2 Multiple myeloma 2 Brain/ONS 24
All other sites
Lung bronchus 32 Prostate 10 Colon
rectum 10 Pancreas 5 Leukemia 5 Non-Hodgkin 4
lymphoma Esophagus 4 Liver intrahepatic 3bil
e duct Urinary bladder 3 Kidney 3 All other
sites 21
ONSOther nervous system. Source American Cancer
Society, 2004.
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Differentiation and Anaplasia

• Benign tumors
• Well differentiated
• Malignant tumors
• Range from well to poorly differentiated
• Hallmarks of anaplasia
• Cells and nuclei show pleomorphism
• Cells contain abundant DNA, coarse, clumped
  chromatin
• Large NC ratio (11) rather than (14)
• Large nucleoli
• Large of mitoses
• Dysplasia
• Precancerous condition in epithelial tissue
• Anaplastic cells in epithelium
• Dysplasia does not always progress to cancer

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Carcinogensis

• Carcinogenesis
• Result of non-lethal genetic damage
• Tumor masses result from the clonal expansion of
  a single progenitor cell that has incurred
  genetic damage

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Biology of Tumor Growth

• Natural hx of most cancers has 4 phases
• Malignant transformation in target cell
• Growth of transformed cells
• Local invasion
• Distant metastases

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Fig 7.33 The Metastatic cascade Neoplasia
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Tissue Invasion

• Metastasis causes 90 of cancer death
• How do tumors invade
• Detach from primary tumor
• Degrade surrounding matrix
• Migrate

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Importance of Cancer Screening
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Lung Cancer Epidemiology

• United States
• 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
• Smoking
• Actively increases relative risk 13X
• Passively increases relative risk 1.5X

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Lung Cancer Clinical Manifestations

• Signs and symptoms
• Coughing, wheezing, difficulty breathing,
  recurrent pneumonia
• Diagnosis
• Screening
• Trials of CXR, sputum cytology, NOT SUCCESSFUL
• Diagnostic
• CXR
• CT directed biopsy
• Bronchoscopically directed biopsy
• Staging concept of localized vs. distant disease

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Lung Cancer Treatment

• Localized
• Small Possibly surgery
• Large Chemo or XRT surgery
• Metastatic
• Chemo XRT

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Digestive Diseases

• Worldwide, 456,000 people aged 45-59 die each
  year from digestive diseases
• Cirrhosis of the liver
• Kills 250,000 people each year between the ages
  of 45 and 59

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Liver

• Largest organ in the body
• Metabolizes fat and glucose
• Helps remove toxic substances from blood
  Produces
• Bile to help absorb fats
• Proteins that regulate blood clotting
• Immune agents
• Loss of liver function can produce severe disease
  and death

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Liver Microscopic Organization
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Cirrhosis

• Normal liver is replaced with scar tissue as a
  result of chronic injury, interfering with liver
  function
• Causes of cirrhosis
• Chronic alcoholism
• Viral hepatitis infection
• Symptoms of cirrhosis
• 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.

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Leading Causes of Death
Ages 15-44 HIV/AIDS Unintentional injuries
Cardiovascular diseases Tuberculosis Unintention
al injuries Cardiovascular disease
Cancer Self-Inflicted Injuries  
Ages 0-4 Perinatal conditions Lower respiratory
infections Diarrheal diseases Malaria Perinatal
conditions Congenital anomalies Lower respiratory
infections Unintentional injuries  
Ages 45-59 Cardiovascular diseases Cancers
Unintentional injuries HIV/AIDS Cardiovascular
diseases Cancer Unintentional injuries
Digestive Diseases  
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Leading Causes of Death
Ages 15-44 HIV/AIDS Unintentional injuries
Cardiovascular diseases Tuberculosis Unintention
al injuries Cardiovascular disease
Cancer Self-Inflicted Injuries  
Ages 0-4 Perinatal conditions Lower respiratory
infections Diarrheal diseases Malaria Perinatal
conditions Congenital anomalies Lower respiratory
infections Unintentional injuries  
Ages 45-59 Cardiovascular diseases Cancers
Unintentional injuries HIV/AIDS Cardiovascular
diseases Cancer Unintentional injuries
Digestive Diseases  
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New World of Global Health

• Bill and Melinda Gates Foundation
• Pledged 6 billion since 1999 to global health
  issues
• Roughly the same as the WHO budget during the
  same time
• Global Fund to Fight AIDS, TB and Malaria
• 8.6 billion to 128 countries launched in 2002
• Presidents Emergency Plan for HIV/AIDS Relief,
  2004
• 15 billion

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Challenges Faced

• Countries struggle with procurement policies,
  hard to convert to drugs
• Shortages of trained health care workers
• http//www.npr.org/templates/story/story.php?story
  Id4987628
• Corruption
• Lack of coherent approach

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What is a grand challenge?

• Scientific or technical innovation that
• Removes a critical barrier to solving an
  important health problem in developing world
• High likelihood of global impact and feasibility
• Different than
• Simple statement of a big problem in global
  health
• HIV/AIDS, malnutrition, lack of access to medical
  care, lack of resources
• Meant to
• Direct investigators to specific breakthrough
  that provides solution to a significant health
  problem(s)

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Global Health Challenges

• 200 million medical research initiative
• 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?story
  Id939533

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Call for Grand Challenges

• Call For Ideas I (May 2003)
• 1048 submissions from scientists and institutions
  in 75 countries
• Scientific Board heard proposals (August 2003)
• Problem
• Roadblock (obstacle to progress)
• Challenge
• List of potential benefits

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Goals and Grand Challenges

• Seven Long Range Goals
• 14 Grand Challenges
• Heavily oriented toward infectious disease
• 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)

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Goals and Grand Challenges

• Improve childhood vaccines
• 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
• 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

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Goals and Grand Challenges

• Control insects that transmit infectious disease
• 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
• Improve nutrition to promote health
• GC9-Create a full range of optimal bioavailable
  nutrients in a single staple plant species
• Improve drug treatment of infectious disease
• GC10-Discover drugs and delivery systems that
  minimize the likelihood of drug-resistant
  organisms

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Goals and Grand Challenges

• Cure latent and chronic infections
• 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
• 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

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Grand Challenge Proposals

• NIH issued request for proposals to address
  challenges
• Grants of up to 20M over five years or less
• http//www.grandchallengesgh.org/

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Summary of Lecture Four

• Developing World
• Cardiovascular diseases,
• Cancer (malignant neoplasms),
• Unintentional injuries, and
• HIV/AIDS
• Developed World
• Cardiovascular diseases,
• Cancer (malignant neoplasms),
• Unintentional injuries, and
• Digestive Diseases

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Assignments Due Next Time

• HW 4