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BIOE 301 Lecture Four 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 BIOE in the News Ethics – Lancet Study Faked! Single pill for HIV 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 Developing World 1. 2. 3. 4. 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 What are the major health problems worldwide? Leading causes of mortality for ages 45-59 Developed world Developing world Global health challenges Leading Causes of Mortality Ages 45-60 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 Ischemic Heart Disease CABG PTCA Cerebrovascular Disease: Stroke Abrupt onset with focal neurologic deficit Usually mini-event or warning signs Reversible ischemia 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 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 Cerebrovascular Disease: Diagnosis History Exam Imaging CT Scan MRI CT/MR Angiography Cerebrovascular Disease: Treatment Thrombolysis Rehabilitation Experimental Angioplasty Heparin Coumarin Aspirin Cancer, Ages 45-59 Cancer kills 1.5 million people aged 45-59 each year throughout the world each year Lung cancer Stomach cancer 185,000 deaths/year Liver cancer 263,000/year deaths in this age group 179,000 deaths/year Breast cancer 148,000 deaths/year Cancer Tumor Types of Tumors: 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 Benign tumors Malignant tumors Range from well to poorly differentiated Hallmarks of anaplasia: 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 Precancerous condition in epithelial tissue Anaplastic cells in epithelium Dysplasia does not always progress to cancer 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 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 Fig 7.33 – The Metastatic cascade Neoplasia Tissue Invasion Metastasis causes 90% of cancer death How do tumors invade: 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 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 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 Lung Cancer: Treatment Localized Small: Possibly surgery Large: Chemo or XRT + surgery Metastatic: Chemo + XRT 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 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 Liver – Microscopic Organization 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. 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 Bill and Melinda Gates Foundation Global Fund to Fight AIDS, TB and Malaria 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 $15 billion 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 ?storyId=4987628 Corruption Lack of coherent approach 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) 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 ?storyId=939533 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 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) 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 Goals and Grand Challenges Control insects that transmit infectious disease Improve nutrition to promote health 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 GC10-Discover drugs and delivery systems that minimize the likelihood of drug-resistant organisms 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 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/ 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