EEMB 50 Non Infectious Diseases
EEMB 50 Non Infectious Diseases
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EEMB50 Non Infectious Diseases April 07 2014 Lecture 4 A War on Cancer Was a massive failure Nixon signed a 16 billion cancer bill in 1971 There has been much decrease in death rate since then Incidence The of new cases of a disease occurring in a given population over a certain period of time NOT A GIVEN Many decreases in ling cancer have been due to the decrease in smoking but not because of new treatments that put an end to cancer The technology and medicine has grown since the time of the bill and so beating cancer is now a more realistic goal because we know its chemistry and more about it Most cancers cannot be cured but can be controlled History Case 45 4500 yrs ago scribe wrote down the studies of Imhotep and people recognized cancer and its difference to other diseases They knew that nothing could be done to treat patients with cancer Doctors linked cancer with civilization because prior to industrialization there weren t as many cases of cancer Hippocrates 460370 BC Carcinos Greek for crab FOR HARD TUMORS Onkos Greek for mass burden FOR MALIGNANT TUMORS Hippocrates proposed the FOUR HUMORS and Gala later expanded on it which explained some of the causes of diseases and ways of restoring balance They proposed that the body was composed of four body uids the 4 humors balance between them determined the health of an individual Imbalance caused illness 1 Blood 2 Phlegm 3 Black bile 4 Yellow bile Excess of black or yellow bile could lead to disease and black bile in particular was associated with cancer and depression Remedy was too remove excess and restore balance Ex in ammation is a good sign of healing but they believed they had to remove excess blood and so would open the skin and let the blood ow out Galen proposed cancer was amasses black bile that could not escape and so that caused the lumps to form The best practice for 2000 yrs was to do nothing Surgery did not cure cancer and so they did not perform any Surgeries that Were performed were done in a speedy manner because there Was no anesthesia but the cause of infection and germs later led to their death faster than the actual cancer would have killed them Rudolf Virchnow 1821 1902 Was a German doctor who discovered leukemia in a patient who had a milky White substance in his blood and proposed the cell theory John Bennett also contributed to the discovery of leukemia and described the blood as being spoiled Cell Theory All living things are composed of cells and cell products and cells only arise from other cells Cell types 1 Hyertrophy an increase in the size of the cells but not number 2 Hyperplasia an increase in the number of cells 3 Pathological Hyperplasia an increase in the number of cells caused by a disease Cancer is a pathological hyperplasia because it causes abnormal increase in numbers of cells and is caused by a disease EEMB 50 Non Infectious Diseases April 09 2014 Lecture 5 How Cancer Works 0 Cancer pathological hyperplasia an increase in the number of cells caused by disease 1 Can cause large masses to invade other tissues 2 All cancers have this fundamental characteristic 0 Chemicals can cause cancers 0 X rays were a major source of radiation and doctors as well as patients were getting cancers from this 0 Chimney sweepers also got cancers from the chemicals in the chimneys that they would rub up against for long periods as they cleaned and many times they were naked 0 Percival Dotts was a scientist who demonstrated that a cancer may be caused by an environmental carcinogen like in the chimney sweepers 0 How can something that kills cells lead to the increased number of cells seen in cancer 0 Mutation A change in the genetic material 0 Carcinogen An agent that can cause cancer they are mutagens 1 Chemistry 2 Radiation 3 Viruses 4 Hereditary The Ames Test asses the mutagenic potential of chemical compounds and sees if it is cancerous Oncogene a gene that has the potential to cause cancer if mutated 1 cancer causing virus is the Rous Sarcoma RSV Discovered by Reyton Rous in a chicken 2 competing theories Cancer is caused by viruses 1 Infectious the downside 2 Curable upside Cancer is caused by mutation 1 Non infectious 2 Cure seems further away 1970 SRC gene identified as first tumor causing gene oncogene It was also found in 1976 that the SRC gene is everywhere But it is slightly different to that found in viruses SRC acts as a marker that latches onto proteins and triggers cell division but for the SRC found in viruses it goes into overdrive cell division Proto Oncogene A normal gene that can become an oncogene due to mutations or increased expression Cancer is caused when a proto oncogene becomes mutated and becomes an oncogene EEMB 50 Non Infectious Diseases April 11 2014 Lecture 6 How cancer works part 2 Oncogene a gene that has the potential to cause cancer Tumor suppressor gene gene that suppresses the development of oncogenes 1 Discovered after oncogenes 2 Some stop reprod In a cell with mutated DNA or cell suicide 3 Requires that both genes since we have two to be mutated Two hit hypothesis for most tumor suppressor genes both copies have to be mutated before their function is lost It is known or often called the gene for cancer It can be inherited or sporadic but 2 things will need to happen if it is sporadic or inherited for the genes to both become mutated and lose their function Ex is the BRCA 2 gene for breast cancer 1 You already have one mutated copy but to get the bc you need two Apoptosis programmed cell death 2 Part of the cell cycle because they don t live forever 3 Those cells with mutated DNA will die or kill themselves Cancer cells are those cells that have forgotten how to die 4 Buy cancer cells avoid this because they stop growing before they reach maturity and so they never kill themselves if they are mutated 5 They don t become specialized and their ability to divide increases and less likely to kill itself while those who do become specialized lose ability to divide Dysplasia abnormality of development These differences in cells can be observed when searching for cancer in tissue because the abnormal cells loom irregular and small while the healthy specialized cells look more normal Benign Tumor A tumor that lacks the ability to invade neighboring tissue or distant tissue mestasize and is self limited and becomes dangerous once it has access to its own blood supply Cancer involves the corruption of multiple systems Angiogenesis formation of a new blood vessels When cells need a new blood supply and become stressed they release a hormone signal that forms new vessels Some cancerous cells are able to release this signal but not all and this can lead to their evasion of cell death This is a sort of dividing line between a malignant tumor and a benign tumor Some drugs such as AVASTIN stop blood vessels from growing and help the tumor from spreading and growing while also potentially shrinking away some of the vessels already there It is very expensive however and it side effects along with the condition of life of the person would cause a problem but with cancer screening we can sometimes remove those tumors that don t spread Also because of the stages of cancer cells we usually find them too late and there are already tumors spreading all over the body Most cancers can also metastasize Metastasis spread of cancer from one organ to another EX Malignant tumors a tumor that has the ability to invade neighboring tissue or distant tissue KEY FACTS ABOUT CANCER 1 Cancer cells DO NOT need to discover anything new 2 A cell must suffer MULTIPLE mutations to become cancerous 3 Genes for cancer usually involve the loss of one copy of a gene that PREVENTS cancer EEMB 50 NON Infectious Diseases April 13 Lecture 7 Cancer Screening Caner is a series of steps not a single event Tumors need to learn how to grow through the formation of new blood sources vessels avoid cell death and mutate both tumor suppressor genes Leonard Hay ick demonstrated that a population of normal fetal cells in a cell culture can only divide between 40 to 60 times before they die This is because of the Hay ick method which is the explanation as to why cells stop dividing after a certain point 1 Telomeres shorten at every division and lead to programmed senescence and acting as a check on cancer 2 Telomeres are caps on chromosomes that help them retain their form shape without unwinding 3 Each time a cell replicates the telomere gets shorter reaching the point where the cell eventually dies 4 Some cancers are able to avoid this by producing telomerase which prevents telomeres shortening it rebuilds the telomere so there is no limit to how many times a cell can replicate 5 All cells have the ability to do this but they do not 6 This evolved many think as a check on cancer and as an explanation to one of the things that cause aging in humans HeLa Cells came from a woman named Henrietta Lacks who died of cervical cancer in 195 1 1 Cells taken from her tumor are among the oldest and most common cells used 2 They are believed to be immortal because they are the longest living line of human cells 3 Aggressive cell line growing line Once a caner is malignant and starts growing out of control has its own blood supply and begins to spread it becomes very dangerous They have exponential growth as they begin to multiply For a cancer to be detected it takes about 10quot 9 cells but by that time many that cancer will already spread or it may be too late to remove Cancer cells start to slow down cell growth rate as it starts to become resource limited and is spreading to much of the body as it is competing with the host Metastatic cancer vs nonmetastatic cancer 1 M cancer is harder to remove and more complicated treatments used to treat it 2 NM cancer is less dangerous to remove and after removal it is more likely that the cancer did not have time to spread elsewhere throughout the body BUT STILL CHANCE OF DEATH FROM A NM CANCER How cancer kills Infection before antibiotics were available 1 Cancer cells have a chaotic growth rate and are able to grow faster than blood cells some may die and become infected 2 There are blood vessels that can also be growing faster than the tumors themselves and lead to bleeding infection Loss of function 1 Some cancers can grow so large in organs like the kidney or liver that there is not enough organ left to do its function organ failure death 2 Ex with brain cancer loss of a small fraction can lead to death because in this example parts that are in control of breathing die Disrupt homeostasis 1 Homeostasis is the ability of an organism to maintain internal equilibrium by adjusting its physical processes 2 Example Bone cancer releases excess Calcium into the blood that it cannot be regulated anymore 3 People can literally waste away as the cancer changes the bodies equilibrium Competition for resources 1 When a cancer is competing with your body for resources that it becomes so large you have to fight against it 2 Rarely seen today because of medical advances and detection of cancers Metastatic Cancer 1 Because it travels to other parts of your body there is a high risk it can spread to vital organs making surgeries more complicated and dangerous 2 Detecting cancer early is incredibly important before it metastasizes because then it can be surgically removed and possibly cured 3 Cancer control reduce risks discourage people from smoking and screening to catch cancers early and have a better and higher chance of curing it Cancer Screening some are very useful some not useful and some even potentially dangerous 1 CT Scan Lung Cancer and all sorts used to scan for many cancers smokers over the age of 50 are rec to take the scan CT Scans are expensive and there is a lot of advertising to promote it Do Not do it unless you are sure you have high risks because many times the outcomes of the tests are more dangerous than the actual cancer could have caused 2 PSA Test Prostate Cancerit is a chemical test that tests for high levels of the chemical it used to be recommended annually for men over 50 but that has declined over the yrs 3 Pap Smear Cervical Cancer cytological test for women over 21 and done every 3 5 yrs the test examines the shape and the form of specific cells to see for irregularities 0 CT Scans and lung cancer 0 Lung cancer is one of the most common and with a low survival rate after detection 0 Spiral CT Scan X Ray computed tomography 1 Get slices of your body as the machine moved down your body it is on a circular track that spins done in 30 seconds and is also able to detect how much x rays penetrate into your body 2 It detects the cancers the size of an eraser smaller than anything we could have been able to visually see before 3 Typically the tumors of this size in our lungs would be asymptomatic and would have not metastasized yet and in theory would be considered curable 4 Problem with these scans are that they detect cancers that would potentially be dangerous or deadly to you this would lead to identification as a cancer patient and be given treatment for cancers that would not hurt you while the side effects of the medicine would harm you 5 Screening is only worthwhile if it can detect and cure cancers that have ultimately killed people 6 Detecting cancers that haven t shown symptoms is in a way pointless and dangerous as the radiation given from these scans can actually cause you cancers that will be dangerous and metastasize 7 The risks of treatment also come with risks 0 Ex In Lung Cancer removal of tumors in the lungs surgically can be messy and risky and even come with a mortality rate of 25 0 Overdiagnosis false positive a false positive result of a tumor that will never cause death but is treated a cancer 0 A Good Screening program cures cancers that would otherwise kill people 0 Bad Screening program cures cancers that would not kill people 0 Overscreening diagnoses many people with a positive result and sent to secondary test 0 Lead time bias Leam about cancer sooner so think that ur survival rate increases but in reality it is the same than that of a person who would have not known about it and still lived same amount of time as the treated person ex in Lung cancer 0 Once Cancer turns too deadly it is too late to cure and removal of lung may be deadly 0 We start the clock sooner and we do not want to do this 0 Solution 1 Be able to distinguish tumors that will never become dangerous and ones that Will but this is difficult as Well because it all depends on mutation and We do not know which will become lethal and which will not EEMB 50 NON Infectious Diseases Lecture 8 April 16 2014 Cancer Screening and Viruses Types of Cancer screen 1 Visual 2 Tactile feeling 3 Imaging looking inside the body 4 Fluid Very few of the human body can be seen so we use screening to see inside By the time a doctor machine can detect a cancer the cancer may already be too big and deadly X Rays are used to but they themselves are dangerous because they cause cancers too after too much exposure from the radiation PSA Testing comes with problems and has begun to fall out of favor Normally PSA chemicals can go into bloodstream but with Prostate cancer more PSA can leak into blood because the cells are disorganized Prostate testing was recommended for men over the age of 40 50 The problem with over diagnosis of Prostate cancer is that only a small number of these tumors will turn dangerous and this test detects all EVEN those which are NOT dangerous Deciding to treat all may come with side effects worse than the non dangerous cancer would have caused It is recommended but the benefits do not outweigh the harmful effects Doctors order the test in order to cover themselves from possible future dangerous cancer cases that might arise and so send patients to take test anyway People abide to take these tests because they are not aware of how many benign tumors they have in their bodies and as they get older the chance of finding a tumor is higher Imaging Technology 1 Leading to more diagnosis of cancers but little effect on what matters 2 Too much over diagnosis but not seeing more deaths because they remain the same because even those with nondeadly tumors are being identified as patients Cytological Screening 1 Pap Smear falls under this category 2 Pap Smear named after George Papanicolau who collected samples of cells from the reproductive tracts of guinea pigs and women and in a woman who had cervical cancer noticed abnormal cells 3 He studied these cells and suggested that these cells taken from Women s reproductive tracts could be used to detect cervical cancer 4 It was a useful technique that could detect cervical cancer at an early stage and by the 1950 s was being widely used 5 This cervical cancer screening is very effective and saves the lives of about 35000 Women every year 6 It is successful because this 0 Causes of Cervical Cancer 1 Associated with viruses 2 HPV Human Papillomavirus is picky about which cells it will infect in the human body they have specific ecological niches Within the human body 3 HPV 16 AND 18 are associated with Cervical cancer and affect the mucosal membrane of the human reproductive tract and attacks the basal cells through skin then infects the cells 4 It is a very narrow region which can become infected and can be detected early with a pap smear 0 Pap Smear is a good screen because 1 it requires a limited search area 2 done repeatedly 3 visual search 0 Cervical Cancer is the 2nd highest death for Women 0 It needs to be done regularly to prevent so many deaths 0 Some cancer screening may be harmful pointless or even recommended for everyone 0 The association with HPV can be helped through the use of vaccines 0 HPV is a sexually transmitted disease so there is controversy about giving young girls ages 9 12 the vaccine 0 Gardasil is a vaccine that prevents cervical cancer if taken before becoming sexually active 0 In a trial those who Were given a placebo resulted in 41 infected with HPV and 9 Without signs of cancer 0 Those who received the vaccine resulted with a 00 for both infection and signs of cancer 0 Social controversy arose because many thought that giving young girls this vaccine would encourage them to become sexually active because they would be protected 0 For cells to become cancerous they must 1 Mutate 2 Mutate both gene suppressor genes 3 Avoid natural cell death and metastasize 0 Viruses and Cancer 0 What causes cancer 1 Some chemicals 2 Some Virusesl bacteria 3 Radiation 4 Hereditary 0 Not appropriate to talk about Viruses causing cancer 1 Only 1 of Women infected with HPV will develop cervical cancer 2 90 of Women with CC are infected with HPV 3 So the Virus doesn t CAUSE in all women EEMB 50 NON Infectious Diseases Lecture 9 April 18 2014 Cancer Risks and Cancer Clusters an epidemic of anxiety Many headlines in media about the risks of cancer but the actual dangers are actually lower Over last 1520 yrs The Worst carcinogens have been identified 1 Ex Smoking causing lung cancer 2 Chemicals that caused cancer when Workers Were in contact with them chimney and steel Workers Press likes to dramatize the risks Many studies suggest that many things like yogurt and coffee can cause cancer 1 The relative risks they give are from 13 risk and instill fear into society Human studies of cancer risks would be unethical and on animas would be hard to interpret Some studies and surveys 2 Electromagnetic Fields and Leukemia in children Source of Worry and doubt for many people 3 Used the phone numbers of people to ask Whether they lived in certain areas and Whether they had small children 4 These were biased because of economic reasons poorer families would not have a phone and if they did they would be less likely to participate in the survey 5 Many of the poorer families would be more likely to live in these areas and outside in uences such as drinking and smoking during pregnancy would in uence these results When people identify with cancer they remember and think more about how and Why they got cancer Oral contraceptives and breast cancer 1 Case control studies suggest a link biased 2 Cohort studies do not find a link Cancer Clusters there is a lack of them We find cancers and then see Where they are They are used to describe a greater number of cancers in a particular area Most are just a feature of random clustering that are expected normally Some clusters are created when people don t look at cancers but not at a range of them so they assume there must be a cluster in that area Diet is also a cause of cancer There have been studies that suggest specific foods cause or help fight against cancer O 1 2 3 4 5 6 7 8 9 People do not think of that fact that because some chemicals do kill cancer in petridishes they will also not harm some healthy cells surrounding cancerous cells Obesity is associated with many cancers because it causes the release of certain hormones which in uence cell division and cause changes in the body Alcohol is also a cause of cancer especially kidney In some countries there is a cancer that is most prominent these can be seen as clusters and people think they might be hereditary to the native people of those countries But this is not true because if they move the majority have the same type of cancer prominent to the area to which they moved to Ex in Austria Skin Cancer is the most prominent cancer While in the US it is Colon Cancer Key Cancer Facts Carcinogens are mutagens Cancer is not a single disease Cells do not need to discover anything new to become cancerous A cell must suffer multiple mutations to become cancerous Cancer cells can be immortal Cancer detected early is often cured Cancer that has metastasized is very hard to treat Most cancers detected by screening would never become dangerous Overdiagnosis carries risks of side effects and even death 10 Most large cancer risks Were discovered years ago 11 Small cancer risks are very hard to distinguish from nothing 12 Cancer clusters are exceedingly rare EEMB 50 Lecture 10 April 21 2014 The Human Heart An Owner s Manuel Fun Facts 1 72 beats per min 2 100000 beats per day 3 35 million beats per year 4 3 billion beats per lifetime Heat disease is only slightly ahead of cancer Majority of hearts that fail don t follow our owner s manual Smoking high blood pressure and other causes lead to heart failure and other problems with the heart Our idea of the heart shape deals With love People think some animal hearts resemble human hearts The heart has four different chambers the LR Ventricles and LR atriums The Left Ventricle is more muscular than the right because it pumps blood to the body and therefore requires more strength to do so Blood coming from the body goes to the right atrium then Ventricle which will pump it to the lungs and become oxygen rich The blood then goes to the left atrium and into left Ventricle Where it will be pumped to the body Arteries carry blood away from the heart going to the lungs and body oxygen poor blood Veins carry blood to the heart oxygen rich blood The heart has Valves and they are needed to ensure blood moves in one direction and it doesn t ow back from where it came from The AV Valves separate the atrium and Ventricles When the semilunar Valves close they produce the second heart beat after AV Valves close Systole contraction of the heart muscle Diastole relaxation of the heart muscle When the heart is contracting it is working the hardest because it is pumping blood to the body When they Ventricles are relaxed they are being filled with blood before they begin pumping Heart Valves can fail Heart murmur blood ows back to atrium and the Valve is swinging around This makes the heart less efficient and the heart works harder When you go to the doctor and they cuff your arm they do not listen to your heart but to the sound caused by the high blood pressure after the cuff is released slowly The heart has an intemal pacemaker that initiates the electrical signaling between the chambers of the heart without the intervention of the Nervous System Each electrical signal begins in the sinus node and then continues to the atria Ventricular node The combined contraction of the atria and Ventricles is the heartbeat The body can control heart beat by changing the membrane potential and altering the permeability of cells to certain ions A hole in the heart refers to a hole between the 2 Ventricles and is also known as Ventricular Septal Defect It results in a oxygen poor blood from the right Ventricle to mix with oxygen rich blood in the left Ventricle this blood owing through the lungs causes an extra noise known as a heart murmur EEMB 50 Lecture 11 April 23 2014 The Human Heart How it Fails 0 Holes within the heart Ventricular Septum 0 We evolved from animals with 2 chamber hearts 0 Advantages of a 4 chambered heart 1 Efficient gas exchange 2 High oxygen efficiency 3 Can contain two different pressures within our two systems 0 Blood doesn t stay in the heart it is always passing 0 Heart is supplied with blood from arteries Coronary arteries which surround the heart like a crown 0 Vast majority of heart problem deaths are caused by problems that begin in coronary arteries which interferes with the blood supply to the heart itself 0 Angina is chest pain that is associated with poor blood ow to the heart 0 Edward Jenner was a doctor who noticed angina while he practiced autopsies because doctors would perform their own autopsies and would learn this way 0 Plaque is buildup on and in the vessel walls and cause angina 1 These blockages can cause the angina and if blockages are more severe fatal heart attacks can occur 0 Ischemia is a restriction in blood supply to tissues causing a shortage of oxygen and glucose 2 This is very serious for your tissue like the brain and the heart because they start to die off within minutes 3 It is seen as a holding checking 4 Virchow discovered Ischemia and how it will affect tissues when they are active vs when they are not 5 When a tissue is active it is using a lot of oxygen but when it is not getting the blood supply the tissue will become distressed 6 When the brain and heart are oxygen deprived their cells will begin to die within minutes 2 to 3 for less active tissues it will take more time 7 Coronary arteries are important in supplying oxygen and blood to tissues so when there is restriction from plaque and ischemia the heart is affected greatly 0 Ischemic heart disease 0 Coronary artery disease 0 Coronary heart disease 0 Atherososcierosis thickening of the artery wall as a result of the accumulation of fatty materials The plaque actually builds in and not really on the Wall The fattening of the wall causes the angina because the blood cannot ow to heart which causes you to feel pain When these burst there forms a clot and some of these clots escape and break off and go into the bloodstream Heart attacks Impulse sinus node then atrioventricular node Ventricular fibrillation v fib are uncoordinated contractions of the ventricles and there is twitching instead of pumping of blood Vfib cardiogenic shockinadequate blood supply due to heart failure asystole at lineno electrical activity in the heart Single event requires obstruction of large portion of arteries for a heart attack A defibrillator is a procedure in which an electrical device gives an electric shock to the heart and helps establish normal contraction rhythms it is like a restart that helps the pacemaker start beating normally again CPR can also help to restart the heart beat after it has stopped but it must be done correctly and the right amount of pressure must be utilized Series of heart failure 1 Chronic congestive heart failure enough of the heart has been damaged that with each beat it can t supply enough blood to the body 2 There is then uid in the lungs and body parts and this causes swellings 3 It is like a slow drowning death EEMB 50 April 25 2014 Lecture 12 Mending a Broken Heart 0 Fixing what is broken 1 Angioplasty and stents 2 Coronary artery bypass surgery 3 Valve replacement 4 Pacemakers 5 Heart transplants 0 Plaque never goes away 0 How do you fix an artery with plaque that blocks blood ow 0 Scraping would not work because it is not on the wall it in in the wall 0 Angioplasty is the technique of mechanically widening narrowed or arteries that are obstructed 1 Balloon angioplasty the procedure of passing an empty and narrowed balloon on guide wire known as a balloon catheter through narrowed locations It is then in ated enough for blood to be able to pass through It is a problem though because one the balloon is removed the openings narrow again Stents is a small mesh tube that is used for widening narrow arteries It is placed in an artery and keeps the ow of blood moving Stent implantations have been proven to not help after results were compared of those patients who had and did not have stents 7 Patients like stents however because they don t have to change their eating habits or exercise routine 39gtP 0 Coronary artery bypass surgery 1 Much more invasive technique used to reduce risk of death from by Coronary Artery disease and ease pain of angina it is an open heart surgery 2 It consist of taking a healthy artery or vein from the body and connecting it stitching grafting to the blocked coronary artery 3 The grafted artery bypasses goes around the blocked portion of the artery and creates a new path for oxygen rich blood to ow to the heart muscle 4 During this surgery the heart is never stopped only slowed down 0 Valve replacement 1 We can have mechanical or biological valves 2 Mechanical valves last 20 30 years but require lifelong blood thinners 3 Biological heart valves do not require blood thinners but only last 1015 years 0 Pacemakers 1 Deal with the electrical problems of the heart not the plumbing 2 They are now implanted into the chest 0 Heart transplants 1 Are necessary after a series of heart attacks chronic congestive heart failure 2 Christiaan Barnard was the first doctor to perform the first heart transplant surgery in 1967 3 Lewis Washkansky was the first man to receive a heart transplant but died days after due to infection in his lungs 4 However supply does not exceed demand of hearts Opt in only those who have given explicit consent are potential donors People do not really get around to it and so many people want to change it so that more people on the waiting list have more opportunities to get a heart Opt out anyone who has not refused consent is a potential donor In some countries organs can be bought but there are ethical debates on that issue People must be on a waiting list in areas close to them there can t be a national waiting list because organs only last certain amount of hours outside of the body Some people have suggested Xenotransplants Xenotransplants using animal organs as transplants for humans A line of pigs in particular has been developed Whose hearts do not have markers that will make our body reject them There are ethical issues with this along with animal rights Violations EEMB 50 Lecture 13 April 28 2013 Number Needed to Treat Treatment and prevention of heart disease Best and Worst of health care l resurrection during a sudden heart attack 2 diagnosis 3 defibrillators can be implanted in people 4 drugs very rapidly alleviate pain from the heart ex blood thinners drugs that Widen coronary arteries The Worst are resuscitating during chronic congestive heart failure People can barely even move around The problem is not that we can t do anything for them but that we can Doing it again and again and again until they succumb It is also incredibly expensive The quality of life for a patient with congestive heart failure will be loW poor Only with a heart transplant will they have a better quality of life Older people are not on top of the list however and they are the ones with the most heart problems and other organ failures POLST is a good approach in improving end of life care in the US it encourages doctors to speak with their patients to create specific medical orders to be taken by health care Workers during a medical crisis It basically for a patient to decide What they Want in the case that they are near death Over time the health care system Has currently tried to reduce the number of cases prevention rather than treatment People who present data to people 1 Pharmaceutical companies selling more drugs so they promote the use of drugs even if they are not that that great 2 HMO reducing costs 3 Public Health officer improving health of society Fundamental Axiom in preventative medicine a large number exposed to a small risk may generate many more cases than a small number of people exposed to a large risk This re ects a change in the health care system focusing more on the people in a path towards a disease than those already with the disease Pre hypertension for example leads to screening which then leads to the possible prescription of medication to prevent heart problems later Problems with Overdiagnosis 1 Costs 2 Hassle 3 Stress 4 Side effects As definitions of abnormal elevated levels of cholesterol move towards the mean many people begin to fall into the abnormal group Pharmaceutical companies then see those people as more customers for their drugs Number Needed to Treat the number of patients needed to be treated for one to benefit NNT 1Absolute risk reduction Absolute risk reduction control group event rate experimental group event rate EEMB 50 April 30 2014 Lecture 14 Blood Pressure Cholesterol and Salt NNT stats for lots of preventative medicine is large but doesn t make it useless Blood pressure is easy to measure regulation of blood pressure is complicated and there is greater pleasure from an increase in cardiac output and increase in tissue resistance Example exercising The amount of blood doesn t increase but the beats do The arteries dilate for easier blood ow and this causes blood pressure to fall It can increase when the artery is narrow and more blood goes through Pulse pressure the difference between systolic and diastolic blood pressures Low weak most commonly caused from an output from heart caused by significant lack of blood High can be caused mainly by a stiffening of the arteries less exible resistance increases they can stiffen from atherosclerosis or aging Stiff arteries cause an increase in blood and systolic pressure This is a natural process that occurs as everyone ages and also by an accumulation of calcium in the artery walls High blood pressure is problematic 1 Link between strokes and atherosclerosis because atherosclerosis can cause high blood pressure but it can also be caused by stiffening arteries as you age The genesis from this plaque can be cholesterol but it is not known but we associate it because of causation and correlation Cholesterol is an essential part of our cells and are the precursors for many other compounds and the body also makes its own Cholesterol is manufactured in the liver is in the food we eat 80 of the cholesterol in our body comes from our own body while 20 comes from our food Statins block an enzyme used in synthesis of cholesterol and lowers cholesterol production because we can t produce it and alters our ability to get it from our food There is good and bad cholesterol and it can be an indicator of heart disease Cholesterol needs to be transported via the blood to our cells but it cannot dissolve so lipoproteins carry them to our cells The high density lipoproteins also carry cholesterol but that one which is known as bad cholesterol from the arteries back to the liver to be denatured Salt high sodium dietwas thought to cause increased blood pressure and heart disease There is very little evidence that lowering Sodium would show benefits If you already have blood pressure it does not help 0 Some of these low sodium diets are not helpful EEMB 50 Lecture 16 2014 Stroke Treatment Stroke Damage 2 different types of strokes 1 Ischemic obstruction blocks blood ow to part of brain 2 Hemorrhagic stroke weakened vessel wall ruptures causing bleeding in the brain There is damage from burst pressure damage and further obstruction Hemorrhagic strokes are more deadly and damaging in additional ways but less likely The burst is damaging and blood accumulation puts pressure on the brain and other veins plus brain cant swell because of the skull The neurons of the brain begin to die if the blood supply isn t retumed to your brain There is a range of susceptibility some neurons die within minutes and others take hours Damage through a stroke takes hours it is not quickly The sooner victim gets medical intervention the sooner they can return blood to the brain so less function of the brain can be lost Someone taken quickly taken to the hospital with an Ischemic stroke is given blood thinners to help blood ow better For Hemorrhagic strokes we want the opposite because blood is owing out and we want blood to begin clotting the rupture instead of thinning it It is important to classify the type of stroke a patient comes in with and that is why they are given brain scans 1 MRI scan 2 CT Scan These have been improved and are preferred over X rays because X rays are not direct pictures from the body but are a measure of the emission of rays that make it through dense matter Pooled blood shows up as an opaque white color and this is how we know it is a hemorrhagic stroke needs to be cleaned and clotted as soon as possible Ischemic strokes kill brain cells and so the dead cells appear more dense Veins all over the brain are affected during a stroke Each hemisphere of the brain has its own blood supply supplied by 3 large arteries Blocks can happen in any of the arteries but most of the time it happens in the middle cerebral artery blockage occurs there Depending on which artery is affected and which hemisphere the outcome of the stroke will be different for each person Hemiplegia paralysis on one side of the body Left brain hemisphere right side of body Right brain hemisphere left side of body The hemisphere that s affected will affect the opposite side of the body Recognizing someone is having a stroke 1 F face for control of facial muscles 2 A arm to see if arms will droop when raised 3 S speech to see if they have slurred speech or use correct Words 4 T time to call an ambulance Aneurism a blood filled balloon like bulge in the wall of a blood vessel in the brain is a stroke Waiting to happen They can be clipped or can be embolized 0 A catheter can be used to take out the clot 0 When it is coiled it is sealed off with a wire it is far less invasive than clipping which involves brain surgery EEMB 50 Lecture 17 May 9 2014 Stroke Risk Factors and Meta Analysis A silent stroke stroke that does not show any outward symptoms Smoking large risk factor Smoking damages cells lining blood Vessels and change ratios of HDL and LDL Makes blood more likely to clot Reduces oxygen carried because hemoglobin has Carbon Monoxide rather than Oxygen which makes the heart work harder as it tries to pump blood to the body Strokes and gender risk men have about 33 percent more strokes than women Men and women have different mortality rates from strokes strokes affect men and women at different ages Meta analysis a statistical technique for combining the findings from multiple independent studies Established criteria based on study designed Forest plots way to Visually present the results summed up as a risk ratio of meta analysis Rows in an individual study present are in chronological order Vertical lines represent zero effect The box size represents sample size in each study The mean of the results is calculated and plotted as a diamond the larger the diamond the bigger the mean Large studies will tend to be close to the mean while small studies will Vary more It is important that we look for the meta analysis of studies to see if they are beneficial or how successful they are EEMB 50 May 12 2014 lecture 18 Lung Function Lung diseases leading to high death rates in developing countries because of increased air pollution solid fuel use in homes and very high smoking rates Smoking decreased in the US but not in developing countries because the tobacco industry in those countries has no restraints and adults and even children smoke in those countries There were many misconceptions about the lungs from the Greeks and the Romans 1 They believed that blood ow was only in one Way 2 Food was converted to blood in the liver 3 Blood ow from right side of the heart to the left 4 Pulmonary artery supplied fuel to the lungs 5 Lungs primarily was a cooling organ They had no idea of the functions of the lungs Da Vinci came closer to understanding the mechanics of the lungs but he still thought they were for cooling William Harvey was allowed dissections of human corpses Through them he gained proof of the continuous circulation of the blood and he hypothesized that blood ows Within a closed system circuit But he still did not know What the lungs did Joseph Priestly discovered Oxygen Heinrich Magnus measured the concentration of gases going into and leaving the lungs Blood leaving the lungs had more Oxygen and less Carbon Dioxide and the blood entering the lungs had less Oxygen but more Carbon Dioxide Lungs are poorly evolved as good as they need to be Vital capacity the maximum amount of air a person can expel from the lungs after a maximum inhalation Vital Capacity goes down with age because of the gradual stiffening of tissue Alveoli final branching of the respiratory tree and the primary gas exchange units of the lungs Lots of elasticity in the alveoli and the system Strength brings blood to very close contact with air you bring in Weakness because of very thin Wall alveoli are very sensitive and damaged easily Damage to alveoli l Invading microbes 2 Inhaled particulate matter 3 Immune system response to above Mucus is Vital and there are cells that align airways leading to alVeoli all produce mucus to capture dust dirt and pathogens The mucus escalator moves up and out of the lungs by cilia cells It is a Vital system in the lungs that trap dust from going to alVeoli breakdown in escalator means an infection in the respiratory tract and excessive mucus production like when you have a cold Cilia cells stop Working because of smoke and can increase mucus production If the mucus isn t of the correct consistency this can lead to cystic fibrosis EEMB 50 May 14 2014 Lecture 19 Lung Disease Thin film of water surrounds Alveoli and they are very moist Surfactant is needed in the alveoli in order for the surface tension between the alveoli to allow them to move and allow gas exchange if this did not happen you would not be able to breathe because your lungs cannot absorb the Oxygen A few weeks before babies are born they begin to produce surfactants but some premature babies do not have them and that is why they have difficulty breathing and are placed in incubators or are given surfactants Chronic Obstructive Pulmonary Disease COPD a progressive disease that affects the lungs restricting airways and making it difficult to breathe Emphysema and Chronic Bronchitis are both diseases of causes that are very similar and are considered COPDs With Emphysema alveoli are selfdestructing possibly by the immune system 1 There is decreased area for gas exchange as membranes break down and there is a loss of elasticity because there are small ruptures begin to make larger ruptures 2 Patients with emphysema are usually referred to as pink puffer and are usually barrel chested are short of breath and get a pink ush 3 They get this appearance because they are working quite hard trying to breath Treatment 1 It is irreversible 2 Slow progression by removing irritants like smoke 3 Supplemental Oxygen 4 Lung transplant but few patients were enough to survive surgery and advancements in stem cell treatments can better give more people to have lung transplants Bronchitis develops in the Bronchioles and there are two forms acute and chronic 1 Bronchitis is an in ammation of the bronchial tubes which carry air to and from the lungs People with Bronchitis often cough up thickened mucus 2 Acute Bronchitis is very common because it usually develops from a cold pathogens or other respiratory infections It can last a few weeks and then the in ammation will leave Chronic Bronchitis is more serious and results from smoking It lasts forever and there is permanent damage to the bronchioles after exposure to the smoking lung irritants There is a constant irritation or in ammation of the lining of the bronchial tubes and there is hyperplasia of mucus producing cells so there is lots of mucus now 3 This causes the cough and there is poor gas exchange low Oxygen levels in the blood and high Carbon Dioxide 4 People with Bronchitis can t respond by breathing more rapidly because bronchioles are narrow and it would only tire you out 5 Patients with Chronic Bronchitis are known as blue bloaters because there as the lungs fail to provide blood with Oxygen to organs and tissues like the heart they become stressed 6 There is wheezing coughing of mucus and septum production Treatments for Chronic Bronchitis include 1 Bronchodilators which relax muscles around the airways 2 Steroids to reduce in ammation Oxygen therapy to help with shortness of breath Because of the uid accumulation in the lings they are very susceptible to infections Asthma is also a chronic long term lung disease that in ames and also narrows the airways making it very difficult to breathe It is caused by genetics environmental triggers and leads to muscular constriction of the airways and the cells in the airways may also produce more mucus than usual There is medication that causes smooth muscle relaxation All these diseases could be solved from having a lung transplant however there is donor shortage the transportation of organs without damage lung rejection patients may be too weak to survive the surgery EEMB 50 May 16 2014 Lecture 20 Industrial Diseases Also known as occupational diseases Apt double meaning since it became a metaphor for strikes and other actions from unions Unions did not always play a positive role in health conditions of its workers Bemardino Ramazzini 16331714 was interested in diseases that workers had as a result of their job or occupation He said that occupation was a vital clue in medical evaluation He was the father of occupational medicine The Industrial Revolution brought an explosion of occupational diseases 1 Led workers to do the same task for hours a day for days after days 2 Because of this they had a longer exposure time things that might not be healthy for longer than before An example would be hat makers of the early 1900 s who had high exposure to Mercury components They had a long exposure to the Mercury and this resulted in their Nervous system being affected and causing them to not have control of their movements Many miners also had diseases that were as a result of the exposure to chemicals The unions never did anything about this issue however and so many workers were in danger In 1970 Nixon signed the Occupational Safety and Health Act whose main goal was to ensure that employers provide employees with an environment free of hazards such as exposure to toxic chemicals and unsanitary conditions Pneumoconiosis Miners lung Black lung 1 Resulted after long term exposure and inhalation of coal dust 2 The lungs are damaged when the walls of the alveoli are in amed and the lung stiffens from scarring of the tissue and leads to an inability of the lungs to function 3 It takes decades for it to progress to a very disabling stage 4 Prior to WWII miners still mined by hand but afterwards coal mines became mechanized and led to 2 associated changes 5 Because there was more productivity profits also went up 6 As productivity went up so did the coal dust and increased the exposure and deaths of miners inhaling the dust 7 For decades workers unions did nothing to decrease this exposure because productivity was so high 8 Coal miners themselves had to begin rallying and pressing for legislation 9 The Black Lung Benefits Act regulated levels of dust in the mines that the miners Were exposed to and provided benefits to those miners with black lung who are disabled and gives X ray screenings to test for the health of the Workers 10 The cases of black lung Went down for a time period but then they began to come back 0 Black lung has begun to reappear due to powerful mining equipment which has increased productivity and raising levels of dust 0 Shifts have become longer because more machines are doing the laborious Work and this increases their exposure to dust 0 Profits are more in uential however and regulations are not as efficient as in the l970 s 0 Asbestosis 1 6 7 Asbestos is a natural mineral that forms long thin microscopic fibers that are resistant to fire heat and chemicals and do not conduct electricity it is mined and used in different industries When it is processed it is more dangerous than when it is mined The individual crystal can be very small and fragment into smaller and smaller parts fibers to the point that they remain in the air for a long period and are easily inhaled They reach down deep in your lungs to the alveoli and stay there for many years It causes scarring in your lungs and making it hard to breathe and for Oxygen to get into the blood and your alveoli become damaged There needs to be long term exposure and usually takes decades to develop It can also act as a carcinogen of lung cancer 0 How does inert mineral cause cancer 1 2 There are 3 hypothesis Tangles chromosomes because some crystals are so small they interfere with chromosomes and cause mutations In ammatory response Releases lots of compounds that can cause hyperplasia and increase the number of cells being produced Concentrates other carcinogens and smoking increases these chances EEMB 50 Lecture 21 May 19 2014 Diabetes The Pissing Evil Like all previous diseases diabetes covers a number of different disorders Disorders have in common that they are related to insulin problems 2 million new cases of diabetes per year Increase in US not due to aging population There is a 13 chance a child will get diabetes It is not just a first world problem of developed countries Hippocrates and Galen on the subject of diabetes 1 Hippocrates did not say anything about it 2 Galen said it was a very rare disease that he had observed only twice The Greeks and Romans 1 Said it was very rare 2 Causes frequent urination 3 An unquenchable thirst 4 Diabetes from Greek word to pass through The middle ages called it the pissing evil because there was frequent urination and after doctors tasted the urine they said it was sweet urine and that was diagnostic of Diabetes Thomas Willis 16211675 diabetes was a diabetes mellitus in which there is high sugar levels in the blood Diabetes began to increase after industrialization and urbanization In New York in the late 19th century there were few people diagnosed with diabetes but going into the 20th century those numbers began growing slowly and people started to take notice The pancreas produces a substance that regulates blood sugar levels glucose Frederick Banting discovered Insulin It was previously known that the pancreas secreted a substance from its islets of Langerhans but with damage to them it was not released Initially they thought that grinding a pancreas and injecting it would cure diabetes but that did not work Banting was able to separate the substance from the pancreas and named it insulin Insulin was developed in 1923 as a treatment Insulin was obtained for a long time from animals like pigs and cows It began to be made synthetically in 1964and in 1987 it was bioengineered Before Banting s treatment they would starve diabetics by controlling their diets and regulate sugar levels in the urine This was very brutal for adults but especially children because they would be starved The death rates of diabetics Also did not go down Insulin also began to only work on some patients but not all because there are two types There is the 1 insulin sensitive which was thought to affect the younger population 2 insulin insensitive resistant which was more common but not confined to the elderly Many people blamed the industrializing of cities and introduction of machinery because people began to do less physical labor and were siting all the time They also blamed unhealthy nonexercising people EEMB 50 Lecture 22 May 21 2014 Diabetes Biology Diabetes has been around for a long time it was rare at first but then rose There is an association with urbanization and increased cases of diabetes It is usually diagnosed by thirst and sweet urine Carbohydrate digestion 1 Carbohydrates are taken up by the body and broken down to Glucose which is the energy that the body needs 2 They circulate in the blood until they are taken up by the cell membranes 3 Glucose uptake is facilitated by glucose protein transporters which are activated by Insulin sometimes there are more or less of these transport proteins 4 Insulin receptors on the surface of the cells signal molecule which facilitates glucose to enter the cell The release of insulin from the pancreas is determined by blood glucose levels so after a meal there is usually high levels of glucose in the blood and insulin is released This keeps blood glucose at a good range Glucose builds up in blood because of lack of insulin or ineffective response to insulin Why is sugar in your blood a problem 1 Effect on kidneys it is progressive and eventually leads to kidney failure 2 Can get a transplant dialysis and those may lead to death U 39gt Kidneys play a role in filtration in the removal of Waste Kidneys maintain bodily homeostasis reabsorption The nephron is the basic structural unit of the kidney with an arterial coming in and out the one coming in is wider than the one going out The high pressure forces small molecules out of the blood this happens in Bowman s Capsule The body selectively chooses which compounds to take back up in like Glucose energy and usually takes this back up again and is taken back into the bloodstream Due to osmosis when the filtrate concentration is too high Water is taken up and you become dehydrated so this accounts for the thirst With diabetes 1 Too much glucose to be reabsorbed in filtrate 2 Glucose pulls Water into filtrate 3 Blood ow to kidneys is reduced to prevent Water loss 4 Overtime this leads to ischemia and cell death and kidney failure 0 Type 1 diabetes is considered an autoimmune disease and autoimmune diseases often involve genetics the immune system and pathogen exposure 0 Type 1 Diabetes 1 2 Previously known as insulin sensitive diabetes and juvenile onset diabetes Had been known it had a genetic component and genes were linked to diabetes are genes linked to the immune system One theory is that autoimmune diseases are provoked by prior exposure to pathogens and so White blood cells attack insulin coming from the islets of Langerhans Treatments for Diabetes 1 include Glucose monitoring permitted by patients themselves tight control Pancreas transplant which is not highly recommended because there is a 10 chance of dying and the organ might be rejected by the body and there is a 60 chance of no more diabetes which is not very high EEMB 50 May 23 2014 lecture 23 Diabetes and epigenetics 0 Type 1 diabetes review 1 Caused by a lack absence of insulin production and can be remediated by artificial insulin and patients can be trusted to regulate their levels of insulin and inject the appropriate amounts to themselves 2 It is an autoimmune disease but genetics and the environment are also important 3 Treatments a new pancreas pros and cons 60 chance of no more diabetes and 10 chance of death 4 Shortage of donors 5 Type 1 diabetes is no longer a fatal disease so the risks like surgery may outweigh the benefits 0 Type 2 diabetes 1 Insulin resistance a decreased ability of some cells of the body to respond to insulin or when the body is resistant to the insulin produced 2 Buildup of sugar same as in type 1 but a much more chronic disease and insulin injections don t help because the body is resistant to it 3 Cells begin to lose insulin receptors overtime due to long exposure to insulin or not responding to signal correctly 4 Why does this happen 5 Such long exposure to insulin overtime is caused by ones diet causing high glucose levels in our blood 0 Insulin resistance is the body s way of saying no more sugar leading to lots of glucose in the blood 0 Treatments for Type 2 Diabetes 1 Diet and exercise because it makes your cells want sugar 2 Low carb diets can help 3 Some drugs are only short term fixes 0 Problems with Type 2 Diabetes 0 Drugs are only short term fixes and at some point the pancreas itself will begin to start failing 0 Largely but not entirely a lifestyle disease hence the association between obesity and diabetes 0 Pre diabetes fasting blood sugar levels problems of Overdiagnosis and treatments 0 Epigenetics the study of changes in gene expression caused by mechanisms other than changes in the underlying DNA sequence Lamarck proposed that as you use or not use certain body parts they pass those on to their offspring Darwin proposed that the traits that We already have and are used and have a benefit for the animal or person in their environment are passed down This relates to the idea that our ancestors were limited in their resources and so their bodies were adapted to low levels of sugar and so recent lifestyles encourage much higher levels of sugar in their blood because there is more food and fattier foods available This may be one reason as to why our body s cells now become resistant to insulin after long exposure to glucose in the blood There is also the Thrifty Phenotype hypothesis in which a pregnant Woman can modify the development of her unborn child such that it will be prepared for survival in an environment in which resources are likely to be short resulting in thrifty phenotype This hypothesis can affect persons three generations after such like grandmother mother and you This can lead to greater risks for the fetus later in life if they are in an environment in which they are not limited in their resources and they have high glucose levels EEMB 50 May 28 2014 Lecture 24 Alzheimer s disease First described by Dr Alois Alzheimer in 1907 Most common cause of dementia in the elderly Extensive pathology senile plaques and neurofibrillary tangles Average length between diagnosis and death is 8 years Prevalence in individuals over the age of 88 No there is no treatment but there may be early diagnosis Key cellular differences between normal a normal and an Alzheimer s brain 1 Extensive neural cell death 2 Two abnormal pathological features in the brain 3 Amyloid plaques deposits outside the cell and neurofibrillary tangles tangled fibers inside the brain 4 There is a predominance of these things on the hippocampus which is where many of a person s cognitive abilities are controlled and processed 5 It begins in the hippocampus but then it begins to spread throughout the brain What are the plaques and the tangles made of Amyloid plaques AB which are small fragments of a large protein called APP Neurofibrillary tangles tau of an abnormal form because it was not properly phosphorylated Strategies to determine Causation and Mechanism 1 Genetic strategies to determine causation we need to identify molecular villains 2 Biochemical strategies to work out molecular mechanisms Two general classes of Alzheimer s disease 1 Familial Alzheimer s inherited l 3 of all cases early onset usually 30 50 years of age and not a single gene disorder AD is linked to chromosomes 1 14 and 21 2 Sporadic AD not inherited 97 of all cases usually at age of 60 and above Genetic analysis of AD and related dementias 1 Mutations genetic errors in the action of the following genes cause AD 2 APP a parent of AB 3 Presenilin 1 and 2 PS1 amp PS2 4 Mutations in the Tau gene How do genetic errors in APP relate neuronal cell death and dementia 1 APP is a transmembrane protein in neurons 2 It is normally cleaved by an enzyme secretase but with AD there is an abnormal cleavage of APP which leads to an excess of amyloid accumulation Inherited 3 make too much AB peptide because either APP or enzyme that cleaves it is not functioning properly Sporadic 97 no mutations but for some reasons AB accumulates So excess AB leads to plaques and eventually loss of cognitive ability There are protein misfolding diseases that are associated with neurodegenerative diseases Are there any genetic risk factors associated with these sporadic cases H Apolipoprotein E ApoE 2 A cholesteroltriglyceride regulation cardiovascular system 3 ApoE2 ApoE3 and ApoE4 alleles 4 ApoE4 is the bad one big increase in risk of AD 5 One of ApoE s normal functions is to promote AB degradation ApoE4 is not nearly as good as ApoE2 and ApoE3 at doing this HYPOTHESIS if they could increase ApoE levels or activity in cells then that should degrade AB faster thereby reducing AB levels and reducing damage What is needed to test this hypothesis 1 A drug that increases the level or activity of ApoE and ideally doesn t do anything bad 2 An Alzheimer s model system to test the drug because it can t be tested on humans 3 We want to see if increasing ApoE reduces AB levels and if it does anything to the Alzheimer s symptoms such as the cognitive abilities that began to change 0 4 The drug that was used was already in the market and FDA tested Bexarotene Targeretin which increases levels of ApoE protein levels by activating transcription of the ApoE gene 5 Good things about this drug are that it is administered orally and crosses blood brain barriers The model were genetically engineered mice who had elevated levels of AB leading to behavioral symptoms such as loss of ability to learn and memory Resulted in decreased levels of AB within hours and plaque levels also declined Within days and the most important thing is that the mice regained their cognitive abilities that they had lost The same results are not however guaranteed to be the same for humans EEMB 50 May 30 2014 Lecture 25 The Placebo Effect Placebo a substance or treatment containing no medication or therapeutic value given to reinforce a patients expectations to get well A placebo doesn t just have to be a pill it can also be a surgery an injection even buttons and they can be any color Placebos are far from a modern invention and have been seen and used throughout medicine s history Most medicine was based on the placebo effect because doctors had a limited access to certain technology and drugs that are available today It was also used by traditional healers and it worked because people believed in their healing abilities and powers this is the placebo Why do you get better after visiting the doctor healer or shaman 1 doctor helped you 2 you believed in the doctor s power to heal you placebo due to the fact that your mind believes this but it was not caused by anything the doctor actually did 3 you get better anyway color and shape and what type of placebo it is affects its outcome and effectiveness Henry Beecher was an Army surgeon during WWII and at one point his supply of Morphine ran out and he had to give fake injections but they worked the same as the Morphine would have because it had the same results like the easing of pain and when wounded soldiers were taken into surgery they felt no pain during the process He came back to the United States after the war and wrote a paper in which he said that it was important to test medical drugs with the existence of the placebo effect in mind This would show that a drug is better than a placebo and this led to a bill about requirements for drugs to be tested to be better than placebos It was not until 1962 that the bill was passed due to the effects that Thalidomide had on pregnant women s children It caused appalling deformities on the children and 60000 children were affected Dr Frances Kelsey was an FDA member and she was responsible for the non use of the same drug in the US Soon after there was a bill passed in both houses that required new drugs would be tested through adequate and well controlled studies carried out by experts It ensured that the medications we take are safe and effective The Dietary supplement and health education act 1994 defines a dietary supplement as product and so medication that is sold as a dietary supplement doesn t have to go through the FDA testing because it is a herbal supplement and considered food There is no safety requirement but they must put a label on the bottle which states that the FDA does not guarantee these results and that the product does not cure any diseases Many people still buy these supplements and although some like Airbome have been proven not to prevent or protect from what they advertise and believe that they will get the results Where would we expect a placebo to be effective 1 Placebo getting powerless attributed just getting better anyway to the placebo effect and overestimating the numbers researchers got carried away with the true effect of placebos How does it work Pain grossly simplified The body responds to in ammation and blood clotting with the brain increasing the signal for the release of Prostaglandins which give us the perception of pain and lead us to stop doing what we are doing The brain releases endorphins to dampen down pain there are addictive drugs like opium morphine and others which signal this release and make you feel better just like medicine does It is this release that makes you feel better and aspirins work with lowering prostaglandins Placebos work because the faster that you calm down the faster your brain releases endorphins and this makes you feel better Because you have less pain and you think you are getting cured or treatment your body does it naturally Pharmaceutical companies via advertisements set up peoples expectation towards a drug to go up by associating it with positive images An example would be Prozac and Zoloft People might ask why not take them if they work 2 They are medication and have side effects and possible conditions that can affect you in life later 3 Placebo is better because you don t get the same consequences EEMB 50 June 2 2014 Lecture 26 Accidental Death 5th leading cause of death in the US Accidental poisoning is the leading cause of accidental death in the United States They are poisoned by prescription drugs that pharmaceutical companies make and are prescribed by doctors Opioids are painkillers that are the main type of drug that cause overdoses and they are extremely addictive and there is a linear response in the more drugs that are taken in the pain is reduced and a euphoric feeling is induced After a certain dosage there is a lower heart rate and slower supply of blood to the heart and body overdose When you stop taking them your body feels strange because it was already used to the drug and after you stop it does not know how to react Two examples of addictive painkillers are Opium and Morphine are highly addictive 1 Opium is a dried latex from the opium poppy it is a mixture of many compounds 2 Morphine is the main active compound in opium and it is itself a single compound Analgesic a substance that relieves pain 3 important properties 1 Highly addictive 2 Give a euphoric feeling 3 Relieve pain Morphine was used in the army but use on the general public was not really permitted Diacetylmorphine Heroin was produced during the 185 0 s by the Bayer pharmaceutical company of Germany to take the place of Morphine and was marketed as a treatment for some infectious diseases as well as a remedy for Morphine addiction It was a more efficient way of getting Morphine into a person and it became a prescription drug but was then banned due to its addictive nature Vicodin and OxyContin can also become addictive if they are taken within the guidelines but many people take them for addiction Toxic effect TD50 is the dose required to produce a toxic effect in 50 of the population Therapeutic effect ED50 is the dose required to produce a therapeutic effect The therapeutic ratio Index is the toxic dose divided by the effective dose TD50ED50 Heroin was once legal but it has become illegal due to its addictive nature and it has begun to be seen used and sold in the streets illegally 0 There was a tendency for the main users of this drug to be blacks but over the years the majority of heroin users are now young White and suburban and are taking becoming addicted to prescription drugs EEMB 50 Lecture 27 June 04 2014 Overview Healthcare The OECD is an organization where governments of 34 democracies and other market economic countries work with one another to promote economic growth prosperity and sustainable development The United States is the country in the world which spends the most on healthcare 3 trillion but do we get value for the money All the amount that we spend is not resulting in meaningful healthcare End of life options are important and it was considered that doctors should be able to talk to and inform their older patients about things like a living will and advance directive This idea was transformed into a death panel idea and taken out of the health care plan for the miscommunication but it would have played an important role in giving people better quality of life when they are in certain medical situations rather than suffering in pain In Holland euthanasia is legal and if doctors believe a patient is better suited not living they can end their life Evidence based medicine is an important way of seeing which treatments and studies offer the right solution or if they are reliable It is more than choosing studies but rather systematic reviews of evidence For example if you want to get screened but are not sure you can go on the website US Preventative task force which gives you their recommendation based on evidence on past studies The Fundamental Axiom in preventative Medicine a large number of people exposed to a small risk may generate many more cases than a small number of people exposed to a large risk They also recommend whether you should take a certain drug based on its prevention of what you are taking it for NNT com focuses mainly on therapies and bases its summaries of evidence based medicine They claim to be We are a group of physicians that have developed a framework and rating system to evaluate therapies based on their patientimportant benefits and harms as well as a system to evaluate diagnostics by patient sign symptom lab test or study The Cochrane Collaboration is an independent non profit organization composed of doctors and researchers and others who use meta analysis and forest plots to give viewers a result of trials and other health care information Dow they work 0 You can check any current clinical trials or search anything on different studies and find their current information at c1inica1trialsgoV EEMB 50 Lecture 28 June 06 2014 Overview and Review 0 Smoking leads to many of the leading diseases killing people like lung cancer ischemic heart diseases and other cancers 0 How to live longer and healthier l 2 3 Don t smoke Eat a sensible diet important for diabetes cancer and heart disease Exercise fights thickening of arteries lower blood pressure and it makes your cells need more fuel thus reducing your risk of diabetes Be careful of painkillers and alcohol there are drugs and operations that treat symptoms but they don t cure the underlying causes like exercise and eating healthy can they also limit the quality of life of a person 0 Cerebrovascular diseases etiology 1 7 There are four types of strokes transient ischemic attack silent stroke ischemic and hemorrhagic stroke Ischemic and hemorrhagic strokes are the most dangerous Ischemic strokes The physical blockage of blood ow to an area of the brain causing brain cells in the area to die Hemorrhagic stroke When a blood vessel bursts in the brain Blood accumulates and compresses the surrounding brain tissue this type of stroke is twice as deadly Thrombus Formation of a blood clot inside a blood vessel Embolism Lodging of a travelling blood clot an embolus at a site distant to origin Vast majority of strokes affect one side of the brain therefore body 0 Cure Treatments aneurisms need to be treated or clipped off clamped off not actually cut so it isolates it and prevents it from blowing up 0 They can also surgically be stuffed with a coil or wire and these reduce the buildup of plaque 0 Etiology of COPD A progressive disease that affects the lungs restricting airways and making it difficult to breathe l 2 Bronchitis An in ammation of the mucus membranes of the bronchi Emphysema An obstructive lung disease caused by the destruction of the walls of the alveoli Symptoms differ because the pink puffer is the patient with emphysema because since his alveoli are severely damaged he breathes rapidly trying to get as much air as he can but it is not very helpful They get a pink ushed appearance and become barrel chested 4 With bronchitis the blue bloater has no solution by breathing in more air because their airways are constricted and this leads to poor oxygenation of the heart and the buildup of uid They also wheeze a lot 0 Cure treatment not much and once there is damage to the alveoli it is not repairable Lung transplant Rare and the survival rate is 5 years 0 Etiology of Diabetes 1 Type 1 diabetes insulin sensitive A form of diabetes that results from the autoimmune destruction of the insulinproducing cells of the pancreas Type 2 diabetes insulin resistant A form of diabetes that is characterized by high blood glucose caused by the lack of sensitivity of cells to insulin With diabetes Too much glucose to be reabsorbed Glucose pulls Water in to filtrate Blood ow to kidneys is reduced to prevent Water loss Over time this leads to ischemia and cell death Cure treatment type 1 can be controlled through the administration of artificial insulin that patients inject themselves with when they measure their glucose levels and they are too high Type 2 managed and cured by diet and exercise because cells can start to respond again and accept the insulin they produce already
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