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00 FMP 08 Week 8 Intro Pages Sunday, February 10, 2008 7:19 PM

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01 SCHAFFER 2008 Diagnosis and Etiology of Depression 2x3 Sunday, February 10, 2008 7:18 PM

• Sadness = healthy, normal condition that everyone feels • Depression = medical condition

Briefly describe how sadness is different from depression? List 5 signs that indicate the presence of depression?(7)

ie. The thoughts that one has affects one's mood and thereby makes one depressed

• Have to differentiate sadness from depression • Remember that depression lasts for weeks or months

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Dysthymia is a mood disorder that falls within the depression spectrum. Not considered to be as severe as major depression, dysthymic disorder is generally thought to be a chronic depression. According to the APA, DSM-IV (2000), two or more of six possible symptoms must be present for a diagnosis of dysthymia. These symptoms include poor appetite or overeating, insomnia or hypersomnia, low energy or fatigue, low self-esteem, poor concentration or difficulty making decisions, and feelings of hopelessness [Hersen, M., Turner, S. M., & Beidel, D. C. (Eds.). (2007). Pasted from <http://en.wikipedia.org/wiki/Dysthymia>

In order to diagnose someone with a major depressive episode (MDE), there are 3 major diagnostic criteria according to DSM IV; what are they? In order to diagnose someone with a major depressive episode (MDE), there they must have 5 or more of which symptoms during a 2 week period? (list 5, there's a total of 9) List 4 diagnoses that are associated with MDE's(6)?

List 3 medical conditions that can lead to a mood disorder due to a general medical condition?(5) Name 2 vitamin deficiencies that can cause a mood disorder?

â&#x20AC;˘ All the following have established links with depression

Eg. Of having melanoma vs. brain tumor and cancer secondary to latter but can't really justify it being secondary to the former (skin cancer) since not directly linked

What is substance-induced MDE? List 2 ways you can be more assured of a substance-induced MDE diagnosis; ie. There are 3 criteria that must be met to confirm substanceinduced MDE, list 2?

Give examples of 3 substances that can lead to substanceinduced MDE?(4)

â&#x20AC;˘ Eg. If someone loses a job, excessive if spend next week in bed

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T/F: Adjustment Disorder with Depressed Mood is diagnosed in patients with a mental illness/disorder? What is Adjustment Disorder with depressed mood? How many months within the onset of a stressful event must depression occur and after how many months must it resolve in order to be diagnosed with Adjustment Disorder with Depresed Mood?


List 4 diagnostic criteria for Dysthymia?(5)

How is major depressive disorder diagnosed? In diagnosing dysthymia, the patient should "never be without symptoms for…" what period of time?

• Population was randomly sampled ○ Women experience depression more frequently than men ○ Highest in youngest age group of 15-24 ○

No significant gender differences found in geriatric populations

Depression CAN be a chronic condition!

• 50% of time patients have low grade depressive symptoms • Followed depressive patients for 12 years • What they did: each week over 12 years classified the intensity of the depressive symptoms (as colored above)

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T/F: Major depressive disorder occurs more frequently in the elderly (+60 years old) than in those less than 60 years old? Within the course of Major Depressive Disorder, what is the mean duration of an untreated Major Depressive Episode? The mean number of lifetime episodes for someone who suffers from Major Depressive Disorder is __ to __? T/F: According to the Canadian Community Health Survey, women over 64 are significantly more likely to suffer from depression than men over 64? T/F: According to the Canadian Community Health Survey, the highest rate of Major Depressive Disorder was amongst the 15-24 year old age group? T/F: According to the Canadian Community Health Survey, women are overall more likely to suffer from depression compared to men? 50% of those with Major Depressive Disorder have onset before the age of ___? T/F: True depression is NOT a chronic condition but is by definition acute episodes of depressive symptoms?


1 (prior to age 11)

How much of the variance in the incidence of depression is accounted for by life events?

(higher in women)

List 6 risk factors for depression?(8)

8 • So if you go through large groups of patients histories, only 10% is actually associated with stressors; most people are not experiencing a period of depression after stressful events • So if any one of us developed dpression in the next month, we'd be able to go back and identify some stressor that we could link with that depression; so there's stress but also vulnerability for people to develop depression

• If a child experiences loss of parent especially before age of 11, then increased risk for depression

List 3 neurotransmitters involved in depression?(3) Biochemically, what is the response to anti -depressants that target norepinephrine? How are serotonin levels linked to precipitating the symptoms of depression? Do antidepressants increase or decrease dopamine levels? Do antidepressants work by upregulating or downregulating betaadrenergic receptors (thereby influencing norepineprhine)?

What is the effect of untreated depression on hippocampal volume? What happens to blood flow to the attention/cognition areas of the brain in depression versus blood flow to the vegetativeautonomic areas of the brain?

• On y axis: total hipp vol.; x axis days of untreated depression •

Showed that longer pts untreated for, smaller the hipp'l vol was

• So some neurotoxicity associated with depression • One of the other features of the anti -depressants is that they increase Brain Derived Neurotropic Factor (BDNF) and regeneration of hippocampus (in animal models) • brain derived neurotropic factor ○ Now looking for stem cells that will increase proliferation of stem cells in the hippocampus

• Looking at blood flow in the brain; work done at UofT; found that the blue, the upper part was dec. blood flow and the lower part was inc. blood flow • If looked at as a mean, patients who were depressed had decreased blood flow and believed to be associated with some cognitive difficulties • Increased blood flow in the limbic system (ie. Amygdala, associated with anxiety and fear) • Patients with depression also had lower hippocampal volume

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What did the Dunedin Multidisciplinary Health and Development Study reveal regarding genetics and depression in S/S genotyped individuals?

• Found that treatment reveresed the blood flow; top is areas in which blood flow increased in brain and bottom areas that • Looking at dorsolateral prefrontal cortex

Probability experiencing MDE (major depressive episode) increased in S/S

• Dunedin study: looked at serotonin system ○ S= short allele ○ L=long allele

At 2,3,4 stressful life events, begin to see separation

What did the Dunedin Multidisciplinary Health and Development Study reveal regarding maltreatment, serotonin transporter gene promoter region genotypes, and propensity to experience depression?

• In same group looked at maltreatment during childhood

• If you look at the genotype, those who had the L/L, even if they experienced trauma as a child, much less likely to experience depression

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Brain derived neurotrophic factor Tuesday, February 12, 2008 8:53 AM

Brain-derived neurotrophic factor From Wikipedia, the free encyclopedia Jump to: navigation, search Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor found in the brain and the periphery. It is a protein that acts on certain neurons of the central nervous system and the peripheral nervous system that helps to support the survival of existing neurons and encourage the growth and differentiation of new neurons and synapses. In the brain, it is active in the hippocampus, cortex, and basal forebrain—areas vital to learning, memory, and higher thinking. BDNF was the second neurotrophic factor to be characterized after nerve growth factor (NGF). Although the vast majority of neurons in the mammalian brain are formed prenatally, parts of the adult brain retain the ability to grow new neurons from neural stem cells in a process known as neurogenesis. Neurotrophins are chemicals that help to stimulate and control neurogenesis, BDNF being one of the most active. Mice born without the ability to make BDNF suffer developmental defects in the brain and sensory nervous system, and usually die soon after birth, suggesting that BDNF plays an important role in normal neural development. Despite its name, BDNF is actually found in a range of tissue and cell types, not just in the brain. It is also expressed in the retina, the CNS, motor neurons, the kidneys, and the prostate.

Contents [hide] • • • • • • • •

1 Effects of stress and BDNF's link in depression 2 Mechanism of action for BDNF 3 Other diseases associated with low BDNF levels 4 High BDNF levels 5 Epilepsy 6 References 7 External links 8 Further reading

[edit] Effects of stress and BDNF's link in depression Exposure to stress and the stress hormone corticosterone has been shown to decrease the expression of BDNF in rats, and leads to an eventual atrophy of the hippocampus if exposure is persistent. Similar atrophy has been shown to take place in humans suffering from chronic depression. In addition, rats bred to be heterozygous for BDNF, therefore reducing its expression, have been observed to exhibit similar hippocampal atrophy, suggesting that an etiological link between the development of depressive illness and regulation of BDNF exists. On the other hand, the excitatory neurotransmitter glutamate, voluntary exercise, caloric restriction, intellectual stimulation, and various treatments for depression (such as antidepressants and electroconvulsive therapy) strongly increase expression of BDNF in the brain, and have been shown to protect against this atrophy. [citation needed]

[edit] Mechanism of action for BDNF BDNF binds at least two receptors on the surface of cells which are capable of responding to this growth factor, TrkB (pronounced "Track B") and the LNGFR (for "low affinity nerve growth factor receptor", also known as p75). TrkB is a receptor tyrosine kinase (meaning it mediates its actions by causing the addition of phosphate molecules on certain tyrosines in the cell, activating cellular signaling). There are other related Trk receptors, TrkA and TrkC. Also, there are other neurotrophic factors structurally related to BDNF: NGF (for Nerve Growth Factor), NT-3 (for Neurotrophin-3) and NT-4 (for Neurotrophin-4). While TrkB mediates the effects of BDNF and NT-4,TrkA binds and is activated by NGF, and TrkC binds and is activated by NT-3. NT-3 binds to TrkA and TrkB as well, but with less affinity. The other BDNF receptor, the LNGFR, plays a somewhat less clear role. Some researchers have shown the LNGFR binds and serves as a "sink" for neurotrophins. Cells which express both the LNGFR and the Trk receptors might therefore have a greater activity - since they have a higher "microconcentration" of the neurotrophin. It has also been shown, however, that the LNGFR may signal a cell to die via apoptosis - so therefore cells expressing the LNGFR in the absence of Trk receptors may die rather than live in the presence of a neurotrophin.

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[edit] Other diseases associated with low BDNF levels Various studies have shown possible links between low levels of BDNF and conditions such as depression, schizophrenia, Obsessive-compulsive disorder, Alzheimer's disease, Huntington's disease, Rett syndrome, and dementia, though it is still not known whether these levels represent a cause or a symptom. [citation needed]

[edit] High BDNF levels High levels of BDNF and Substance P have been found associated with increased itching in eczema [1].

[edit] Epilepsy Epilepsy has also been linked with polymorphisms in BDNF. Given BDNF's vital role in the development of the landscape of the brain, there is quite a lot of room for influence on the development of neuropathologies from BDNF. Levels of both BDNF mRNA and BDNF protein are known to be up-regulated in epilepsy (Gall C, et.al. 1991). BDNF modulates excitatory and inhibitory synaptic transmission by inhibiting GABAA-receptor mediated post-synaptic currents. This provides a potential reason for the observed up-regulation.

[edit] References 1. ^ 'Blood chemicals link' to eczema [1]

[edit] External links • • • •

BDNF and Alzheimer's Disease- What's the Connection? New Clue to Huntington's May Lead to Treatment New Findings May Support Soy-Dementia in Men Low BDNF activity promotes resilience

[edit] Further reading • Gall C, Lauterborn J, Bundman M, Murray K, Isackson P (1991). "Seizures and the regulation of neurotrophic factor and neuropeptide gene expression in brain". Epilepsy Res. Suppl. 4: 225-45. PMID 1815605. • Jones KR, Fariñas I, Backus C, Reichardt LF (1994). "Targeted disruption of the BDNF gene perturbs brain and sensory neuron development but not motor neuron development". Cell 76 (6): 989-99. PMID 8137432. • Arévalo JC, Waite J, Rajagopal R, et al (2006). "Cell survival through Trk neurotrophin receptors is differentially regulated by ubiquitination". Neuron 50 (4): 549-59. doi:10.1016/j.neuron.2006.03.044. PMID 16701206. • Yamada K, Nabeshima T (2004). "Brain-derived neurotrophic factor/TrkB signaling in memory processes.". J. Pharmacol. Sci. 91 (4): 267-70. PMID 12719654. • Pang PT, Lu B (2005). "Regulation of late-phase LTP and long-term memory in normal and aging hippocampus: role of secreted proteins tPA and BDNF.". Ageing Res. Rev. 3 (4): 407-30. doi:10.1016/j.arr.2004.07.002. PMID 15541709. • Hashimoto K, Koizumi H, Nakazato M, et al. (2005). "Role of brain-derived neurotrophic factor in eating disorders: recent findings and its pathophysiological implications.". Prog. Neuropsychopharmacol. Biol. Psychiatry 29 (4): 499-504. doi:10.1016/j.pnpbp.2005.01.007. PMID 15866349. • Tsai SJ (2007). "Increased central brain-derived neurotrophic factor activity could be a risk factor for substance abuse: Implications for treatment.". Med. Hypotheses 68 (2): 410-4. doi:10.1016/j.mehy.2006.05.035. PMID 16824691. • Bath KG, Lee FS (2006). "Variant BDNF (Val66Met) impact on brain structure and function.". Cognitive, affective & behavioral neuroscience 6 (1): 79-85. PMID 16869232. • Nair A, Vaidya VA (2006). "Cyclic AMP response element binding protein and brain-derived neurotrophic factor: molecules that modulate our mood?". J. Biosci. 31 (3): 423-34. PMID 17006024. Pasted from <http://en.wikipedia.org/wiki/Brain-derived_neurotrophic_factor>

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Food and Your Moods Tuesday, February 12, 2008 8:52 AM

by Julia Ross, author of The Diet Cure Are you an emotional basket case who can't get by without comfort food? If you had more strength, could you power through your problems without overeating? Should you feel ashamed of yourself for needing emotional sustenance from foods? No! I hope to help you understand why you are using food as selfmedication. It's not because you are weak willed, it's because you're low in certain brain chemicals. You don't have enough of the brain chemicals that should naturally be making you emotionally strong and complete. HealthyPlace.com Video Eating Behavior Modification Strategies for Overweight Adults and Children Medical Approaches to Weight Loss These brain chemicals are thousands of times stronger than street drugs like heroin. And your body has to have them. If not, it sends out a command that is stronger than anyone's willpower: "Find a druglike food or a drug, or some alcohol, to substitute for our missing brain chemicals. We cannot function without them!" Your depression, tension, irritability, anxiety, and cravings are all symptoms of a brain that is deficient in its essential calming, stimulating, and mood-enhancing chemicals.

Why Are Your Natural Mood-Enhancing Chemicals Sometimes Deficient? Something has interfered with your body's ability to produce its own natural brain drugs. What is it? It's obviously not too unusual, or there wouldn't be so many people using food to feel better, or taking Prozac for depression relief. Actually, there are several common problems that can result in your becoming depleted in your feel-good brain chemicals, and none of them is your fault! You may have inherited deficiencies. We are learning more all the time about the genes that determine our moods and other personality traits. Some genes program our brains to produce certain amounts of mood-enhancing chemicals. But some of us inherited genes that undersupply some of these vital mood chemicals. That is why some of us are not emotionally well balanced and why the same emotional traits seem to run in families. If your mother always seemed to be on edge, and had a secret stash of chocolate for herself, it should come as no surprise that you, too, need foods like candy or cookies to calm yourself. Parents who have low supplies of naturally stimulating and sedating brain chemicals often produce depressed or anxious children who use food, alcohol, or drugs as substitutes for the brain chemicals they desperately need. Prolonged stress "uses up" your natural sedatives, stimulants, and pain relievers. This is particularly true if you have inherited marginal amounts to begin with. The emergency stores of precious brain chemicals can get used up if you continually need to use them to calm yourself over and over again. Eventually your brain can't keep up with the demand. That's why you start to "help" your brain by eating foods that have druglike effects on it. Regular use of druglike foods such as refined sugars and flours, and regular use of alcohol or drugs (including some medicines), can inhibit the production of any of your brain's natural pleasure chemicals. All of these substances can plug into your brain and actually fill up the empty places called receptors, where your natural brain drugs - the neurotransmitters - should be plugging in. Your brain senses that the receptors are already full, so it further reduces the amounts of neurotransmitters that it produces. As the amounts of these natural brain chemicals drop (remember, they can be thousands of times stronger than the hardest street drugs), more and more alcohol, drugs, or druglike foods are needed to fill newly emptied brain slots. This vicious circle ends when these substances you ingest are unable to "fill the bill" any longer. Now your brain's natural mood resources, never fully functional, are now more depleted than they ever were, and you still crave your mood-enhancing drugs - whether it's sugar or alcohol and cocaine. You may be eating too little protein. In fact, you almost certainly are if you've been dieting or avoiding fatty foods, many of which are high in protein, too. Your brain relies on protein - the only food source of amino acids - to make all of its mood-enhancing chemicals. If you are not getting enough protein, you won't be able to manufacture those crucial chemicals. A little later in this chapter and in chapter 18, you'll learn about complete and incomplete proteins, and what is "enough" protein for you. Simply put, eating the equivalent of three eggs, a chicken breast, or a fish or tofu steak at every meal might get you enough protein to keep your brain in repair.

The Physical Cause of Emotional Eating In the late 1970s, I was the supervisor of a large San Francisco alcoholism treatment program. Our clients were very serious about getting sober, and we gave them the most intensive treatment available anywhere. Yet they could not stop drinking. Eighty to ninety percent relapse rates were standard then,

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anywhere. Yet they could not stop drinking. Eighty to ninety percent relapse rates were standard then, and still are, in the alcohol and drug addiction fields. As I studied these heartbreaking relapses, I began to see a pattern. Our clients had stopped drinking, but they had quickly developed a heavy addiction to sweets. Sugar is almost identical to alcohol biochemically. Both are highly refined, simple carbohydrates that are instantly absorbed, not needing digestion (complex carbs, like whole grains, need time to be digested). Both sugar and alcohol instantly skyrocket blood sugar levels and temporarily raise levels of at least two potent mood chemicals in the brain. This high would be followed by a low, of course. So, just as when they were using alcohol, our clients who had switched to eating large amounts of sugar were moody, unstable, and full of cravings. Since alcohol usually works even faster than sugar does, at some point, caught in a particularly low mood, they would break down and have a drink to get some relief. One drink would become a full-blown relapse. In 1980, when I became the director of the program, I began hiring nutritionists to help solve this disturbing relapse problem. They suggested to our clients that they quit eating sweetened foods, foods made from refined (white) flour, and caffeine, and that they eat more whole grains and vegetables. Unfortunately, these nutritional efforts didn't pay off. For reasons that we understood only later, our clients just couldn't stop eating the sweets and starches that eventually led them back to alcohol. For six years we struggled for a solution, then, in 1986, we found one. The solution came from Dr. Joan Mathews Larson, the director of a nutritionally oriented alcoholism treatment center in Minneapolis, Minnesota. This brilliant pioneer, the author of Seven Weeks to Sobriety, introduced me to a technique that was quickly eliminating her alcoholic clients' cravings and raising her center's long-term success rate from 20 percent to 80 percent! The technique involved the use of specific amino acids that could rapidly feed the addicted brain exactly the type of protein that it needed to naturally fill up its empty mood-chemical sites. The results were spectacular. No longer did alcoholic clients need sweets or alcohol to feel good! Amino acid therapy revolutionized the work at our clinic, too, dramatically raising our success rates with alcohol and drug-addicted clients. Moreover, we were able to successfully treat clients with other addictions as well. In fact, our most spectacular successes were with food-addicted clients. Ninety percent of the compulsive overeaters we have treated with amino acid therapy have been freed from their food cravings within forty-eight hours.

Using Amino Acids to End Emotional Eating When psychological help does not clear up emotional eating, we need to look at the four brain chemicals - neurotransmitters - that create our moods. They are: 1. dopamine/norepinephrine, our natural energizer and mental focuser 2. GABA (gamma amino butyric acid), our natural sedative 3. endorphin, our natural painkiller 4. serotonin, our natural mood stabilizer and sleep promoter If we have enough of all four, our emotions are stable. When they are depleted, or out of balance, what we call "pseudo-emotions" can result. These false moods can be every bit as distressing as those triggered by abuse, loss or trauma. They can drive us to relentless overeating. advertisement

For some of us, certain foods, particularly ones that are sweet and starchy, can have a druglike effect, altering our brains' mood chemistry and fooling us into a false calm, or a temporary energy surge. We can eventually become dependent on these druglike foods for continued mood lifts. The more we use them, the more depleted our natural mood-enhancing chemistry becomes. Substituting amino acid supplements for these drug foods can have immediate and dramatic effects. Toni, a 26-year-old Native American, was referred to our clinic because she was exhausted, profoundly depressed, anxious and suffering lifelong trauma from the physical and emotional violence of her family. Toni drank alcohol and ate sweets to cope. She went regularly to her scheduled counseling sessions but was unable to rouse herself to communicate with her counselor. She had volunteered to come to Recovery Systems, hoping that a new approach would help. Toni had already been through three longterm treatment programs for alcohol addiction. Clearly, she was motivated to solve her problem. When we saw Toni's condition, the nutritionist and I conferred and decided to give her amino acids on the spot. I asked her to tell me one thing: What was the worst thing she was experiencing at that moment? She said "I'm sooooo tired." Her slumped body and still, dull eyes confirmed this. Our goal? To treat her lack of energy and depression by raising her levels of the neurotransmitter norepinephrine, the body's natural energizer. We gave her our smallest dose - 500 milligrams of Ltyrosine. While we waited and hoped for an effect, I spoke about how and why amino acids can be helpful. After about ten minutes, Toni said, "I'm not tired anymore." "Great!" I said. And then I asked my next question: "What is the worse thing you are experiencing, now that your energy is better?" She answered by bending over and grasping herself around the stomach. "I'm really uptight." We then gave Toni the smallest dose of GABA - 100 milligrams - a natural Valium-like chemical along with 300 milligrams of L-taurine. We suspected that together these supplements would help relieve her tension and allow her to relax - and they did. She stretched her legs out in front of her and then stood up,

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tension and allow her to relax - and they did. She stretched her legs out in front of her and then stood up, got a glass of water, and went to the bathroom. While she was gone, her counselor came in and happened to tell me that Toni was in a lot of emotional pain because of the chronic alcoholic violence in her family. When her family members drank alcohol, they all became different people, vicious and cruel. And they had never been able to stay away from alcohol. When Toni returned, I asked her, "Can we give you something to help you endure the emotional pain that you are in?" She said yes, so I gave her a supplement containing 300 milligrams DL-phenylalanine and 150 milligrams L-glutamine. (DL-phenylalanine is the amino acid used to alleviate emotional pain.) In ten minutes I asked Toni how she was feeling, and she smiled and said, "Just right." I was incredulous. How could these small amounts really be helping her? Our European American clients usually need two to four times as much of each type of amino acid to get such dramatic effects. I asked if she would like any more of any of the aminos I had already given her for energy, relaxation, or pain relief. Her answer: "Just right," and a shake of her head. By this time Toni's eyes were sparkling. Weeks later her counselor reported that by continuing with the amino acids she had first used in our office, Toni was actually talking for the first time in their counseling sessions, and was being praised at work, was being noticed for the first time by men, and was staying sober and sugar-free.

Mood Foods: How Amino Acids Feed Your Brain The four key mood chemicals (neurotransmitters) are made of amino acids. There are at least twenty -two amino acids contained in protein foods. High-protein foods, such as fish, eggs, chicken, and beef, contain all twenty-two, including the nine amino acids that are considered essential for humans. Other foods, such as grains and beans, have some but not all of the essential nine aminos, so they need to be carefully combined to provide a complete protein (for example, rice and beans, or corn and nuts). If you are eating three meals a day, each meal including plenty of protein (most people with eating and weight problems are doing neither), your positive moods and freedom from cravings can be maintained. But most people need to kick-start the brain's repair job, using certain key amino acids. This will allow you to actually enjoy eating protein and vegetables instead of cookies and ice cream. After a few months, you will be getting all the aminos you need from your food alone and won't need to take amino acids as supplements any longer. Restoring depleted brain chemistry sounds like a big job - but it isn't. Three of the four neurotransmitters that color all your moods are made from just a single amino acid each! Because biochemists have isolated the key amino acids, you can easily add the specific ones that may be deficient. These "free form" amino acids are instantly bioavailable (in other words they are predigested), unlike protein powders from soy or milk, which can be hard to absorb. Hundreds of research studies at Harvard, MIT, and elsewhere (some of which date back to the early part of this century) have confirmed the effectiveness of using just a few targeted amino acid "precursors" to increase the key neurotransmitters, thereby eliminating depression, anxiety, and cravings for food, alcohol and drugs.

Stopping Carbohydrate Cravings It may sound impossible, but you can stop your food cravings almost instantly with just one amino acid supplement. Any absence of fuel for your brain's functions is perceived correctly by your body as a code red emergency. Powerful biochemical messages then order you to immediately eat refined carbohydrates to quickly fuel your brain. There are only two fuels that the brain can readily use: 1. glucose, which is blood sugar made from sweets, starches, or alcohol 2. L-glutamine, an amino acid available in protein foods (or as a supplement, carried in all health food stores). L-glutamine reaches the starving brain within minutes and can often immediately put a stop to even the most powerful sweet and starch cravings. The brain is fueled by L-glutamine when glucose levels drop too low. Don't be intimidated by the strong effects of supplementation. Lglutamine is a natural food substance; in fact, it's the most abundant amino acid in our bodies. It serves many critical purposes: stabilizing our mental functioning, keeping us calm yet alert, and promoting good digestion.

Restoring Energy and Focus When your brain is adequately fueled with its back-up emergency supplies of L-glutamine, you are ready to rebuild your four key neurotransmitters, starting with dopamine/norepinephrine, your natural caffeine. Without this natural brain stimulant, you can be slow and tired and have a hard time concentrating. You don't sparkle and can't stay on track mentally. It's hard to get things done and you can feel dull and sometimes just want to stay in bed. Your physical as well as your mental energy drops without adequate norepinephrine. The amino acid that provides this jet-fuel is the nutritional powerhouse L-tyrosine. Ltyrosine produces thyroid hormones and adrenaline as well as well as norepinephrine. Like L-glutamine, L-tyrosine goes to work in minutes to perk you up.

Enhancing Your Ability to Relax The next key mood-enhancing chemical is GABA (gamma amino butyric acid), our natural Valium. GABA acts like a sponge, soaking up excess adrenaline and other by -products of stress and leaving us relaxed. It seems to drain the tension and stiffness right out of knotted muscles. GABA can even smooth out seizure activity in the brain. My colleague, Elliot Wagner, a specialist in drug detox, taught me that GABA

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can even give relief to heroin addicts going through the severe anxiety of early withdrawal. Think what it can do for garden variety stress and uptightness!

When Food is Comfort More Info You May Be Depressed! What Do You Do Now? Food and Your Moods Recovering from Compulsive Overeating - Binge Eating Chocolate is My Kryptonite: Feeding Your Feelings For many people, overeating helps compensate for a depletion of the natural pain relievers, the endorphins. Life's pain can be unendurable without adequate amounts of these buffer chemicals. Some of us (for example, those of us from alcoholic families) may be born with too little natural pain tolerance. We are overly sensitive to emotional (and sometimes physical) pain. We cry easily. Like our alcoholic parents, we need something to help us endure our daily lives, which seem so painful. Others of us use up too much endorphin through trauma and stress. We just run out, especially if we were born short on endorphins to begin with. When our comfort chemicals run low, many of use turn to comfort foods. If you need food as a reward and a treat, or to numb your feelings, your natural pleasure enhancers, the pain-killing endorphins, are probably in short supply. Foods that elevate your endorphin activity can easily become addictive. If you "love" certain foods, those foods are firing a temporary surge of endorphins. Euphoria, joy, the "runner's high" - these are all feelings produced by endorphins. Some people have so much natural endorphins that they smile all the time and get great pleasure from everyday life. Of course, we all endure suffering and loss. But, with enough endorphins, we can bounce back. For anorectics and bulimics, the trauma of starving and vomiting can trigger an addictive endorphin high, because trauma of any kind can set off an automatic burst of soothing endorphins. You may know of people who felt no pain for hours after a terrible physical injury. Runners don't get their big endorphin high until they have run past "the wall of pain." At that point, they have run too far!

Raising Serotonin, Our Natural Prozac Low serotonin can be the easiest deficiency of all to develop. Very few foods are high in the amino acid tryptophan, which is the only nutrient that the body can use to make serotonin. According to a 1997 Lancet study, tryptophan is one of the first nutrients to be depleted by weight -loss dieting. If, in addition to dieting, you inherited low serotonin levels and experience a lot of stress, your levels can fall low enough to set off a major eating disorder or serious emotional disturbances. Restoring your serotonin levels can be a life-or-death matter. Suicides and violent crimes are closely associated with deficiencies of serotonin. The sometimes fatal obsessions and self-hate of bulimics and anorectics are clearly linked to low serotonin levels as well. Do you have any obsessions that might be caused by low serotonin levels? The women I have worked with who report obsessive behavior tend to be "neat-niks" and suffer from negative obsessing about their physical appearance, while the men are often "neat-freaks," although they also complain about troubling sexual fantasies they can't stop. As we all know, anorectics (who are low in serotonin) are driven to obsessive control of their food intake. Obsessive fears and phobias are common among people with low serotonin levels. It may be a difficult adjustment for you to begin to see symptoms like control, fear, and low self-esteem as biochemical problems, not just psychological ones. But the success of drugs like Prozac has already alerted us to the biochemical nature of many symptoms that don't respond to psychological help alone. Drugs like Prozac are called serotonin reuptake inhibitors (SSRIs) because they keep whatever serotonin we have active. But they do not actually provide additional serotonin. For this reason, most people using SSRIs often continue to have some low-serotonin symptoms. Before there were SSRIs, the pharmaceutical compound L-tryptophan was commonly used to increase serotonin levels. For more than twenty years, psychiatrists and health food stores enthusiastically recommended it for relieving depression and food cravings and normalizing sleep without side effects. Many people found that their symptoms were eliminated permanently after only a few months of L-tryptophan use. In 1989, a series of bad batches of L-tryptophan, which filled forty people and made many more very sick, prompted the Food and Drug Administration (FDA) to stop all U.S. sales. One Japanese company, Showa Denko, had produced all of these batches, which, it was found, were contaminated because they had eliminated three filter systems that they'd been using for years - just why they chose to take away these safety filters is a question that remains unanswered. Showa Denko has never made tryptophan again. Despite evidence that no other manufacturer has ever made a problem batch, the FDA recommended for years that L-tryptophan not be used as a supplement. (Interestingly, they have made no effort to stop the sale of infant formulas, most of which contain added L-tryptophan.) With L-tryptophan unavailable, drugs like Prozac, Zoloft, and Redux have become our primary tools for combating the crippling symptoms of low serotonin. Unfortunately, these drugs provide only temporary and incomplete benefits, and often have uncomfortable or dangerous side effects. Fortunately, in 1996, many compounding pharmacies began providing L-tryptophan again, by physician prescription, and a new version of tryptophan called 5HTP (5-hydroxytryptophan) became available over the counter in 1998 without FDA opposition. In 2000, Lidtke Technologies Corporation of Phoenix, Arizona, made Ltryptophan available through health professionals without prescription. Look for other supplement suppliers to follow suit, as the FDA has never formally banned the sale of this essential amino acid.

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suppliers to follow suit, as the FDA has never formally banned the sale of this essential amino acid. Whatever mood-enhancing brain chemicals you have in short supply, they can be replenished quickly, easily, and safely.

Tryptophan Depletion: The Path to Depression, Low Self-esteem, Obsession and Eating Disorders Serotonin, perhaps the most well known of the brain's four key mood regulators, is made from the amino acid L-tryptophan. Because few foods contain high amounts of tryptophan, it is one of the first nutrients that you can lose when you start dieting. A new study shows that serotonin levels can drop too low within seven hours of tryptophan depletion. Let's follow this single essential protein (there are nine altogether) as it becomes more and more deeply depleted by dieting. To see how decreased levels of even one brain nutrient might turn you toward depression, compulsive eating, bulimia, or anorexia. In his best seller, Listening to Prozac, Peter Kramer, M.D., explains that when our serotonin levels drop, so do our feelings of self-esteem, regardless of our actual circumstances or accomplishments. These feelings can easily be the result of not eating the protein foods that keep serotonin levels high. As their serotonin-dependent self-esteem drops, girls tend to diet even more vigorously. "If I get thin enough, I'll feel good about myself again!" Tragically, they don't know that they will never be thin enough to satisfy their starving minds. Extreme dieting is actually the worst way to try to raise self-esteem because the brain can only deteriorate further and become more self-critical as it starves. More and more dieters worldwide are experiencing this miserable side effect of weight reduction on the brain. When tryptophan deficiency causes serotonin levels to drop, you may become obsessed by thoughts you can't turn off or behaviors you can't stop. Once this rigid behavior pattern emerges in the course of dieting, the predisposition to eating disorders is complete. Just as some low-serotonin obsessivecompulsives wash their hands fifty times a day, some young dieters may begin to practice a constant, involuntary vigilance regarding food and the perfect body. They become obsessed with calorie counting, with how ugly they are, and on how to eat less and less. As they eat less, their serotonin levels fall farther, increasing dieters' obsession with undereating. As their zinc and B vitamin levels drop low as well, their appetite is lost. This can be the perfect biochemical setup for anorexia. What so many therapists and others have observed as the central issue of "control" in anorexia often comes down to this: just as vitamin C deficiency (scurvy) results in an outbreak of red spots, do does tryptophan (and serotonin) deficiency result in an outbreak of the obsessive-compulsive behavior that we call "control." There may be psychological elements in the picture, too, but a low-serotonin brain is ill equipped to resolve them.

Source: excerpted with permission from The Diet Cure: The 8-Step Program to Rebalance Your Body Chemistry and End Food Cravings, Weight Problems, and Mood Swings-Now, by Julia Ross. Read this transcript with Dr. Kathleen DesMaisons, author of "Potatoes Not Prozac". She discusses how sugar addiction can affect your mood.

RELATED LINKS AND INFO Triumphant Journey: A Cyberguide To Stop Overeating Compulsive Overeating: Dealing With The Feelings and How To Treat It Starting an Exercise Program: The Right Time Is Now Mind/Body Medicine for Treating Depression Prayer May Heal Depression What Dr. Andrew Weil Recommends for Treating Depression Symptoms Depression Treatment Overview depression treatments: alternative ~ antidepressants ~ ect emdr ~ therapy ~ self-help ~ transcranial magnetic stimulation vagus nerve stimulation Pasted from <http://www.healthyplace.com/Communities/Depression/treatment/alternative/food_moods.asp>

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01 SCHAFFER 2008 Diagnosis and Etiology of Depression Sunday, February 10, 2008 7:16 PM

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02 SCHAFFER 2008 Biological Treatment of Depression 2x3 Sunday, February 10, 2008 7:19 PM

How did trends in the outpatient treamtent of depression change between 1987 and 1997 in the US?

• Data coming from canadian community health survey; what's the chance in the last 12 months that you actually saw someone with that condition • So only about a third of the people with one of these conditions got any help with these symtpoms ○ General rule is family practitioners: they go to their family doctor most frequently to report psychiatric conditions ○ Next up the list is psychiatrists but only 12% chance; most are family physicians •

• So in 1987, if they did go to family physician/psyhciatrist then only 35% chance would be given meds • Now closer to 80%! • So there's been a shift to more medical treatment

Acute treatment aims to remove all signs and symptoms of the current episode of depression and to restore psychosocial and occupational functioning (a remission). A remission (absence of symptoms) may occur either spontaneously or with treatment. If the patient improves significantly, but does not fully remit with treatment, a response i s declared. If the symptoms return and are severe enough to meet syndromal criteria within 6 months following remission, a relapse (return of sy mptoms of the current episode) is declared.

Continuation treatment is intended to prevent this relapse. Once the patient has been asymptomatic for at least 4 to 9 months following an episode, recovery from the episode is declared. At recovery, continuation treatment may be stopped. For those with recurrent depressions, however, a new episode (recurrence) may occur months or years later.

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What is the difference between the goals of acute, continuation, and maintenance treatment with respect to treating depression?


recurrent depressions, however, a new episode (recurrence) may occur months or years later.

Maintenance treatment is aimed at preventing a new episode of depression and may be prescribed for 1 year to a lifetime, depending on the likelihood of recurrences. Pasted from <http://www.mentalhealth.com/bookah/p44-d2a.html>

How long does the acute phase of antidepressant treatment last? How long does the maintenance phase of antidepressant treatment last? How long does the continuation phase of antidepressant treatment last? Every patient treated for depression needs to go through at least which 2 phases of treatment? Give 3 examples of TCA antidepressants? How do TCA antidepressants work? Why are SSRI's more sought after than TCAs? List 2 common side effects of TCAs? Give 2 examples of SNRIs? Give 2 examples of SSRIs? What is the generic name of Celexa? What is the generic name of Prozac? What is the generic name of Effexor? What is the generic name of Zoloft? What is the generic name of Paxil? How do SSRIs work? How do SNRIs work? Which is the MOST toxic in overdose: SSRIs, TCAs, SNRIs?

• 3 stages when prescribing ○ Acute: treat depression quickly ○ Continuation: treatment to prevent relapse  Every patient treated for depression needs to have the acute and continuation ○ Maintenance: only required for some patients

SNRIs: Allow for more noradrenaline in the synaptic cleft

• Patients can take lots of ssri's but not have anything happen to them

• Older TCA's; came out in 60's no brand names because came out in 60's; so all generic; used in areas not just related to psychiatry or depression • Amitriptyline used for chronic pain; high doses good anti-depressive effects

How does Buproprione (Wellbutrin) work? Buproprion (Wellbutrin), at high doses, has which common side-effect? What is the generic name for Remeron?

How do MAOI antidepressants work? List 2 common side effects of MAOIs?(3) What is the mechanism of action of Mirtazapine? List 2 common side-effects of Mirtazapine (Remeron)?(3) List 2 common side-effects of Buproprion (Wellbutrin)? Give an example of a reversible MAOI antidepressant and another example of an irreversible MAOI antidepressant? Tyramine ingestion while taking MAOIs can cause ___? Why should tripants (used in the treatment of migraines) not be taken with MAOI

• Eg. Tyramine: precursor for dopamine; found in many foods including tofu and cheese ○ If you're on a MAOI antidpressant and not able to break doewn the dopamine, get all sorts of side effects in peripehery leading to hypertension and headaches secondary to HTN • Lots of mao-a and mao-b in the gut • Drug-drug interactions: many other meds will also increase levels serotonin and NE: eg. Migraine meds (triptans) • Get serotonin syndrome with increasing serotonin levels • Any kind of aged foods, meat, fish, fermented projets • Wellbutrin: inhibits reuptake of dopamine; issues: increased risk of seizures especially at higher doses

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increased risk of seizures especially at higher doses • Mirtazapine (remeron): alpha -2 adrenergic receptors: sit presynaptically Foods to be restricted or avoided because of a 'tyramine' reaction (high BP) 1. Cheeses. Some have very high levels of tyramine, especially ‘mature’ cheese types like Stilton, Brie and Camembert, Mozzarella; the 'smellier' it is the more tyramine it contains. A tw enty gram serving of a strong cheese could possibly raise the BP to a measurable extent (but not to a dangerous extent). Larger quantities become progressively more risky. Most modern supermarket processed cheese has low (to the extent of being completely safe) levels of tyramine; how ever tyramine levels are unpredictable, so it is risky to experiment because the w orst possible outcome, even if that is remote, is a ‘stroke’. We can say that 'ricotta' and 'cottage' cheese types are alw ays safe to eat. 2. Extracts such as ‘Vegemite’, ‘Promite’, 'Marmite', ‘Bovril’ must be avoided.Foods like soy sauce, 'tofu' and 'miso' are made in a similar w ay; ie by 'fermentation' of brew s containing proteins, so only small amounts can be safely eaten. Because the BP goes up in proportion to the amount of tyramine that is eaten, it is OK to have small quantities (see below for what 'small' really means). 3. Meat products are safe, but if they are not fresh, ie if they have been subject to decomposition by m icro-organisms, then they may be risky; eg liver pate (and similar meat or fish pastes) are perfectly safe if freshly made and properly refrigerated. But after a couple days left out at room temperature they could be risky. Similarly 'salami' and 'pepperoni' sausages, and dried meats, are usually OK but caution is w arranted. Liver that is near its' 'use by' date w hen purchased, and is then kept in a domestic fridge that is not cold enough, may possibly be risky. 4. Alcoholic drinks in true m oderation(two drinks in any six hour period) is very likely to be safe. Modern hygienic production methods w ill make excessive tyramine levels rare. Badly made or stored drinks may be risky, so avoid ‘home made’ w ines or beers. Bottled beer is almost certain to be safe; but avoid ‘live’ beers w hich may be available from 'boutique' producers. They can be distinguished by the sediment (of dead yeast) in the bottom and they are cloudy if shaken. Also ‘keg’ or 'tap' beers may sometimes have significant tyramine levels and are best avoided. 5. Sauerkraut can sometimes contain sufficient tyramine levelsto w arrant restriction (see below) and broad (fava) beans are OK but the bean pods should not be eaten. Other non-serious interactions that are not dangerous Many plant derived substances, eg 'herbs' and 'foods' like chocolate, coffee, and tea contain chemical compounds that act as 'drugs', eg stimulants like caffeine. These effect everyone but may have an exaggerated effect in those taking various sorts of antidepressant drugs, including MAOIs; they should be taken in moderation and avoided if they precipitate symptoms such as anxiety, jitteriness, agitation, poor sleep etc Pasted from <http://www.psychotropical.com/MAOIs_Information_full.shtml >

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antidepressants? Tyramine is the precursor for ___? Which type of anti depressant class has a high rate of drugdrug and drug-food interactions?

Basically, avoid any foods that have been acted on siginficantly by microorganisms, as these may contain dangerously high tyramine levels


List 4 factors that should influence your choice of which antidepressant to prescribe? What are two specific side effects of most antidepressants that you should warn patients about?

Many patients with depression also have anxiety 1. Patients with anxiety respond well to serotnonin and those that increase dopamine and NE, then worsen these symtpoms; so anxiety: go to SSRI meds 2. Avoid specific side effects: eg. Sexual side effects, major issue with SSRI's: want to avoid anti -dpresnts that increase serotonin levels; another eg: weigth gain 3. Comorbid conditions: eg. Anxiety: another: chronic pain: TCA's: also used for pain: so use TCA to kill two birds with one stone 4. Previous lack of response: if they've been on 5 SSRI's, and haven't tried a different class, then use another class!

Most remission occurs between 4 to 10 weeks

Difference between response vs. remission • Response: at least 50% improvement in depressive symptoms • Remission is the absence of depressive symptoms; about half to two thirds will have good response to first antidprsnt that go on but the remission, ony about 37% will actually remit; after the 4th trial, about two-thirds

• Idea of these mediations is to get you back to who you are • Common question: Aren't these meds addictive?

• So weeks 4,6,8,10 will start to see remission • @ 10 weeks effect begins to taper off

The precursor for dopamine, _____, is found in many foods, including cheese and tofu?

What percentage, approximately, of patients will RESPOND to treatment with a first line antidepressant? (nb. Asking for response, NOT remission) What is the difference between response and remission? MOST remissions from antidepressant use occur between ___ to___ weeks of use?

4 possibilities to if meds not working: 1. Review diagnosis/investigations; if still want to treat: a. Combine b. Increase dose or duration: so if someone comes in 4 weeks later, then we suggest continue on antidepressant for longer time c. Switch d. Add a second List 4 strategies one should follow if the medications prescribed for anti-depression aren't helping? What does it mean to 'augment' antidepressant medication with other medications? In using a 2nd medication for depression treatment, what is the principle that should be followed?

• Investigations: TSH, b12, blood count, tox screen, drug screen • Augmentation: meds that are not themselves antidpresents

• Lithium: augment • T3: when added to antid. Can boost effectiveness; lots of other examples

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c. Switch d. Add a second List 4 strategies one should follow if the medications prescribed for anti-depression aren't helping? What does it mean to 'augment' antidepressant medication with other medications? In using a 2nd medication for depression treatment, what is the principle that should be followed?

• Investigations: TSH, b12, blood count, tox screen, drug screen • Augmentation: meds that are not themselves antidpresents but if you add them to antid. Have antid. Effects (examples later, eg. lithium) • Combination: 2 actual genuine antid. meds

• Lithium: augment • T3: when added to antid. Can boost effectiveness; lots of other examples that can be added; • on the right are combinations we sometimes use; want to use anti -d that have complimentary mechanisms of action; DON'T WANT TO COMBINE TWO OF THE SAME MEDS THAT HAVE THE SAME MECH OF ACTION

List 3 categories of patients who would require maintenance treatment?(4)

• Gold standard treatment: combinations of antidepressent and psychotherapy

• •

• •

Remember 3rd phase of treatment: maintenance Recurrent: i f keep getting depressed, when not on meds, then have to start preventing by keeping on meds Never been s hown to be a ny l ong term morbidity associated with maintenance Ra mi fications of relapse too high: single mother husband left marriage; caring for two s mall children: CAS i nvolved; i f s he's the s ole provider then v. di fficult

Which other form of treatment should be added to antidepressant therapy to achieve an even better outcome? How are number of episodes of antidepressant treatment correlated with length of antidepressant treatment? T/F: A MINORITY of patients achieve remission from depression with FIRST line medication? T/F: Most medication choices have similar efficacy? A majority of depression patients achieve remission after how many medication trials?

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T/F: A MAJORITY of patients achieve remission from depression after TWO OR MORE medications?

• Phototherapy: for seasonal depression ○ UV-free ○ Has biological antidepressant effects

• • • •

Bilateral ECT: v. cotnroversial; been around for long time All major hospitlas with psych depts have ECT Can be life-saving Changed lots since 1920's 30's as see in moveies Apart from pharmaceutical therapy, list 2 other biological treatments for depression?(4)

• Repetitive transcranial: coil over left prefrontal cortex: magnetic field that stimultes activity in cortex underneath • Deep brain stimulation: used in neurology and being tried in psych: anterior cingulate hpyeractive in depression; prove dampens activity in anterior cingulate; not in family docs ofice but cutting edge in biological treatments

• Margaret trudeau: came out with struggles with depression

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02 SCHAFFER 2008 Biological Treatment of Depression Sunday, February 10, 2008 7:19 PM

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03 ZARETSKY 2008 Cognitive Therapy for Depression 2x3 Sunday, February 10, 2008 7:52 PM

Take home messages: ○ Cbt is an active, structured form of psychot. That is empirically validated and broad spectrum ○

CBT is as effective as meds for mild to moderate depression and more effective in reducing relapse

○ Cbt for depression ultiilizes behavioural activation and congitive restructuring techniques

• CBT: consdiered be gold standard for psychotherapy

• Like meds, psychotherapy can be said to have a mechanism of action and this can be specific or non-specific

List 3 non-specific mechanisms of action of psychotherapy? List 3 specific mechanisms of action of psychotherapy?

List 2 different forms of psychotherapy?(3)

• Se slide (new slide, not in these lectures)

Forms of Psychotherapy: ○ Psychodynamic therapy: focus on past and relationships ○ Interpersonal therapy: manualized supportive therapy - focuses on interpersonal problems of patient ○ Cognitive thereapy/CBT/behaviour therapy

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The cognitive model states that one's core beliefs in a situation influence which 3 factors?

• Cognitive model has a myriad of applications Eg. Of a thought: "I'm not a good lecturer"

Cognitive therapy is generally time limited to how many months (for uncomplicated depression or anxiety)? T/F: Cognitive therapy can be done individually but should not be done in groups?

• So what is COGNITIVE therapy? Distilled to its essence: 2 premises: 1. It's the thought that counts: it's your thinking that explains why you do certain things 2. Don't believe everything you think! Vis -a-vis dysfunctional thoughts • Goal of therapy: teach the patient to become their own therapist: we don't like patients to be in treatment for 40 years: not a good outcome to be in psychotherapy; that's why v. popular with patients; very empowering; structured and goal oriented; in every session actually have an agenda try to address the patients needs nad bigger goals of treatment • For uncomplicated depression or anxiety, over in 4 to 6 months

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What are the stages in the Cognitive Model of Depression?(hint: 5 linear steps before get to symptoms of depression)?

Different types of adversity that lead to...

NB: all of us have negative core beliefs but not all of us get depressed; therefore have to also have biology

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Give examples of how CBT is a structured therapy? • At the end of every session actually ask patient: what did you take from this session; actually want feedback about the session; very empowering for patient • Eg. Self help exercises: manual: mind over mood; self help mood; from greenberger and deretsky; taking patient through CBT step by step

What are the 6 steps in cognitive restructuring? List 5 cognitive distortions?(10)

Eg. Cognitive distortions: all or nothing thinking: you're either comptent or a failure

• Cognitive therapy more than just being supportive

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Which of the following is an example of Socratic questioning, in response to a student saying "I'm a complete failure" (there may be more than one right answer): 1. What makes you think you are a complete failure?; 2. Why are you being so hard on yourself?; 3. What would a good student do?; 4. Would a complete failure be able to get 75% on an exam?; 5. On a scale of 0-100%, where do you fall? Where do other people fall?

In a typical course of CBT for depression, organize the following session goals from earliest to latest: Goal setting, relapse prevention and termination, assessment and suitability, behavioural activation, use of an automatic thought record? Typical course: Assessment

--> goal setting --> behavioral activaiton --> ATR --> deeper core beliefs --> relapse prevention

â&#x20AC;˘ CBT focuses on skill deficits â&#x20AC;˘ Patient came in for presentation; came to cbt after 4 -5 years of psychotherapy

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T/F: CBT is as effective as medication for chronic depression? Give a few examples of comorbidities of depression? List 4 psychiatric conditions in which CBT is the gold standard? T/F: If you wish to start a patient on CBT, this SHOULD NOT be started mid-way through their medication course because of the inability to discern which is having a positive effect? T/F: CBT is NOT as effective as medication for more severe non-psychotic depression?


Give an example of how CBT can be used to maintain patients in remission more effectively than clinical case management?

Therefore a much higher proportion (close to 75%) of those who achieved remission REMAINED IN REMISSION using CBT as opposed to only approximately 15% with clinical case management.

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T/F: For chronic depression, there is no difference between using CBT alone versus using medication alone?

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Apart from depression, list 2 other common medical problems which CBT be used for?(5)

CBT and SRI treatment responsive OCD patients show similar decreased activitiy in which brain structure?

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T/F: CBT is as effective as medication for mild to moderate depression? T/F: CBT is MORE effective than medication in reducing relapses?

• SEE SLIDES MISSED IN HANDOUT LECTURE9 Take home messages: ○ Cbt is an active, structured form of psychot. That is empirically validated and broad spectrum ○

Is as effective as meds for mild to moderate depression and more effective in reducing relapse

○ Cbt for depression ultiilizes behavioural activation and congitive restructuring techniques

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04 SCHAFFER 2008 Introduction to Bipolar Disorder 2x3 Sunday, February 10, 2008 7:21 PM

What are the 2 criteria used to define bipolar disorder?

In diagnosing a manic episode, what are the 4 general categories? In diagnosing a manic episode, patients must experience 3 or more of which 7 symptoms?(just name 5)

Are depressive episodes necessary for the diagnosis of bipolar disorder?

• Eg. Patient had stopped a way for hurricanes to happen; put up wall! • Most specific symptom of mania: decreased sleep need, genuine; don't feel tired when wake up; just sleeping 2 hours • Increase in goal directed activity: washing dishes and renovating house at night

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A genuine manic episode generally lasts for at least how long? What is Bipolar Disorder Type II? According to the mood spectrum, what's the difference between bipolar type I and type II? List 3 criteria for hypomanic episodes?(6)

â&#x20AC;˘ Hypomani: 4 days â&#x20AC;˘ Mania: at least 1 week

Hypomania + Depression = ___?

List 3 symptoms that overlap between mania and depression?(6)

What are the 3 diagnostic criteria for a mixed episode? In diagnosing a mixed episode, criteria for BOTH a manic episode AND major depressive episode should be met for what minimum period of time?

What percentage of bipolar patients have recurrence? What are the two most common conditions that are comorbid with bipolar disorder?

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What is the most common age for the onset of bipolar disorder in males and females? The presence of mania, in Canada, is highest in which age group: 15-24, 25-64, or over 64?

The leading cause of mortality in patients with BD is due to ___?

T/F: Bipolar disorder is NOT caused by parents but CAN be reversed by will power?

T/F: Bipolar disorder MAY run in families? T/F: Patients with bipolar disorder do not actually have morphological abnormalities but they do have second messenger and mitochondrial dysfunction?

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BIPLOR DISORDER IS OFTEN MISDIAGNOSED!

Approximately ___% of depressed patients have bipolar disorder?

List 3 populations that are particularly at risk for bipolar disorder?(6)

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List 2 psychiatric disorders for which mood stabilizers are indicated for? T/F: Mood stabilizers DO NOT worsen mania or depression? Apart from mood stabilizers and antidepressants what are some other treatments for bipolar disorder? With respect to lithium levels, the treatment of mania or depression has a higher target blood level?

With respect to lithium administration, what is the range of dosages used to treat bipolar disorder? Would a higher target blood level of lithium be sought to treat acute mania or acute depression? Would a higher target blood level of lithium be sought to treat acute depression or for maintenance treatment of bipolar disorder? The administration of which anticonvulsant has a 1:1000 risk of ___ Syndrome? Divalproex and lamotrigine are both ___? Both anticonvulsants What is the generic name for Divalproex? What is Lamotrigine? Lamotrigine is primarily used for the treatment o f â&#x20AC;Ś? T/F: Valproic acid is primarily used to treat bipolar depression? The administration of which bipolar medication has a 1:1000 risk of StevensJohnson Syndrome? What does CANMAT stand for?

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Give 2 examples of atypical antipsychotics?(4) Atypical antipsychotics were originally introduced for the treatment of ___? Atypical antipsychotics are used more for the treatment of mania or bipolar depression?

Would lithium, olanzapine, and divalproex be appropriate combination therapy for the treatment of acute bipolar mania? The main side effects of the atypical antipsychotics are ___ risks, such as â&#x20AC;Ś(name 2)?(3)

Monotherapy for treatment of bipolar depression includes which 2 medications? List 2 popular combination therapies for the treatment of bipolar depression?(3) List a popular combination therapy for the treatment of acute bipolar mania?

For the pharmacological management of acute bipolar mania, which medications are commonly used for monotherapy? Long term lithium use has potential complications for which organ? Which of the following lead to weight gain (may be more than one right answer): atypical antipsychotics, anticonvulsants, lithium? Which of the following are potential complications of long-term mood stabilizer use: teratogenicity, glucose dysregulation, renal effects, liver problems, sexual dysfunction, dyslipidemia, weight gain? Sexual dysfunction is a prominent side effect of long-term use of which mood stabilizer? Which of the following are side effects of anticonvulsants: teratogenicity, glucose dysregulation, renal effects, liver probl ems, sexual dysfunction, dyslipidemia, weight gain? List 3 potential complications of long term mood stabilizer use?(7)

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T/F: Lamotrigine and Divalproex are indicated as combination therapy for the treatment of bipolar depression? Which category of longterm mood stabilizers has the highest risk of causing dyslipidemia? Which category of longterm mood stabilizers has the highest risk of causing teratogenicity? Which category of longterm mood stabilizers has the highest risk of causing sexual dysfuntion? Which category of longterm mood stabilizers has the highest risk of causing liver problems? Which category of longterm mood stabilizers has the highest risk of causing glucose dysregulation?


List 2 different psychosocial interventions for the maintenance phase of bipolar disorder?(4)

Olanzapine, risperidone, clozapine, and quetiapine are all examples of which class of medications?

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04 SCHAFFER 2008 Introduction to Bipolar Disorder Sunday, February 10, 2008 7:22 PM

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05 KAHAN 2008 Substance Abuse Key Concepts 2x3 Sunday, February 10, 2008 7:53 PM

List 3 factors that are correlated with the addictive potential of drugs?(5) List 3 ways in which you could make a drug less addictive?(5)

What is the primary difference between the reward pathway of cocaine compared to alcohol, nicotine and opioids?

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What are the 4 C's of addiction?

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The ____ and NMDA ____ are inhibited by alcohol?

Symptoms of alcohol withdrawal typically start how many hours after the last drink? Does tolerance to alcohol develop quickly or slowly? Alcohol inhibits which system in the brain? Tachycardia and vomiting are examples of complicated or uncomplicated signs of alcohol withdrawal?

Alcohol suppresses ___ and enhances ___ (both neurotransmitters)? Cessation of alcohol use leads to unopposed activity of which neurotransmitter?

How are the symptoms of uncomplicated alcohol withdrawal different from those of complicated alcohol withdrawal? Alcohol enhances ___, which is an inhibitory neurotransmitter and suppreses ___ which is a neuroexcitatory neurotransmitter?

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What are the psychiatric chronic effects of alcohol consumption? What are the CNS chronic effects of alcohol consumption? What are the hepatic chronic effects of alcohol consumption? What are the GI chronic effects of alcohol consumption? What are the cardiovascular chronic effects of alcohol consumption?

According to the Lowrisk Drinking Guidelines, how many drinks are low risk for the general population to have per day? According to the Lowrisk Drinking Guidelines, how many drinks are low risk for women to drink per week? According to the Lowrisk Drinking Guidelines, how many drinks are low risk for men to drink per week?

What is a standard drink for beer, wine, liquor (give quantities)?

Pasted from <http://images.google.com/images?um=1&hl=en&rls=com.microsoft%3Aen-us&q=acamprosate>

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As a laboratory marker for alcohol consumption, is MCV found to be depressed or elevated? What is the CAGE questionnaire? T/F: BOTH GGT and MCV are poor screening methods for excess alcohol use since both have low sensitivity AND specificity values?


What is the difference between the condition that Naltrexone is used to treat vs. Naloxone?

â&#x20AC;˘

Naloxone is a drug used to counter the effects of opioid overdose, for example heroin or morphine overdose. Naloxone is specifically used to counteract life -threatening depression of the central nervous system and respiratory system. Pasted from <http://en.wikipedia.org/wiki/Naloxone>

Naltrexone is an opioid receptor antagonist used primarily in the management of alcohol dependence and opioid dependence. Pasted from <http://en.wikipedia.org/wiki/Naltrexone>

List 2 medications that can be used to reduce drinking? What is the mechanism of action of Naltrexone? What is the mechanism of action of Acamprosate?

T/F: Nicotine can be both a relaxant AND a stimulant? What is the generic name of veranacline? Severe withdrawal from nicotine lasts approximately how many days?

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T/F: Nicotine replacement therapy is far SAFER than cigarette smoking? What is the mechanism of action of Champix? Approximately how long does it take for Buproprion to work?

Opioids act on which receptors?

Another name for endorphin receptors is ___ receptors?

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Physical symptoms of opioid withdrawal include â&#x20AC;Ś (name 2)? Are opioids safe in pregnancy (if not, why; what may they cause)? Are opioids effective for acute pain only, chronic pain only, or both? List 2 psychological symptoms of opioid withdrawal?(3) In using opioids, what's the difference in the rate of development of tolerance to psychoactive vs. analgesic effects?

Does methadone administration induce sedation? Another name for Suboxone is ___? Why can you not overdose on Buprenophine (Suboxone)? T/F: Buprenorphine is AS EFFECTIVE as methadone at 60-80 mg? What is the mechanism of action of buprenophine?

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Which of the following is a complication of cannabis use (may be more than one): poor social functioning, mania, delerium tremens, drug induced psychosis, cravings, fatigue and irritability, mood disorders? Cocaine blocks the presynaptic uptake of which 3 neurotransmitters? Usually a cocaine high is 20 minutes but with repeated use the euphoria only lasts for ___, followed by ___?

Another name for MDMA is ___? Give 2 examples of hallucinogens?(3) What are the withdrawal symptoms seen in withdrawal from hallucinogens? Which of the following is a complication of hallucinogen use (may be more than one): poor social functioning, mania, delerium tremens, drug induced psychosis, cravings, fatigue and irritability, mood disorders?

Another name for ecstasy is ___?

â&#x20AC;˘ Myoclonus: brief, involuntary twitching of a muscle or a group of muscles

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T/F: MDMA use may acutely lead to serotonergic syndrome? Which important neurotransmitter does MDMA (ecstasy) stimulate the release of? What are the components of serotonergic syndrome? T/F: The effects of MDMA may be temporarily decreased by treating with an SSRI? GHB stands for ___? GHB is a metabolite of ___? GHB use leads to ___ effects, like ___? Treatment for GHB use is ___? T/F: The withdrawal symptoms experienced in GHB withdrawal are similar to those experienced by withdrawal from hallucinogens? What are the withdrawal symtpoms in GHB withdrawal?


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06 RICHTER 2008 Anxiety Disorders 2x3 Sunday, February 10, 2008 7:54 PM

â&#x20AC;˘ Anxiety has physiological, cognitive, and behavioural components

How is anxiety differentiated from fear?

What is the approximate lifetime prevalence of anxiety disorders?

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List 2 core features of anxiety disorders? T/F: In chronic anxiety, patients' anxiety levels will dip to normal for a few days at most but will be above normal at a constant level most of the time?

List the 3 phases to a panic attack?

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(LECTURING ABOUT EACH OF THESE BELOW)

List 6 anxiety disorders?(11) In diagnosing a panic attack, patients must experience 4 or more of the following (list 5)?(13)

PANIC DISORDER What are the three related diagnoses for anxiety disorder?(ie. Panic disorder withâ&#x20AC;Ś, etc.) In order to be diagnosed with panic disorder, a patient must have both recurrent panics and one or more of which three symptoms? For the diagnosis of panic disorder patients must have symptoms for more than how long (ie. How many weeks or months)?

AGORAPHOBIA List typical situations in patients would experience agoraphobia? In agoraphobia, situations are ___, ___, or require the presence of ___? List 3 examples of agoraphobic situtations?

Agoraphobia is an anxiety disorder, often precipitated by

the fear of having a panic attack in a setting from which there is no easy means of escape. As a result, sufferers of agoraphobia may avoid public and/or unfamiliar places. In severe cases, the sufferer may become confined to their home, experiencing difficulty traveling from this "safe place."

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SPECIFIC PHOBIAS Are males or females more prone to panic disorders? What are the 4 major types of phobias? What is the gold standard treatment for phobias? The two major classes of pharmacotherapy for the treatment of phobias are ___ and ___?

SOCIAL ANXIETY DISORDER (SAD) What is social anxiety disorder?

The single most common mental disorder is ___?

List three subtypes of specific phobias? What is the difference between generalized and non-generalized social anxiety disorder? List 3 physical symptoms of social anxiety?(9)

Types of anxiolytics Anxiolytics are generally divided into two groups of medication, benzodiazepines and non-benzodiazepines.

• Benzodiazepines • Main article: Benzodiazepine Benzodiazepines are prescribed for short-term relief of severe and disabling anxiety. Common medications arelorazepam (Ativan), clonazepam (Klonopin), alprazolam (Xanax), and diazepam (Valium). Benzodiazepines may also be indicated to cover the latent periods associated with the medications prescribed to treat an underlying anxiety disorder. They are used to treat a wide variety of conditions and symptoms and are usually a first choice when short-term CNS sedation is needed. Longer term uses include treatment for severe anxiety and psychosis. There is a risk of withdrawal symptoms and rebound syndrome after continuous usage past two weeks. There is also the added problem of the accumulation of drug metabolites and adverse effects.

• Non-benzodiazepines See also: Nonbenzodiazepine Buspirone (BuSpar) is a serotonin 1A agonist. It lacks the sedation and the dependence associated with benzodiazepines and causes much less cognitive impairment. It may be less effective than benzodiazepines in patients who have been previously treated with benzodia zepines as the medication does not provide the sedation that these patients may expect or equate with anxiety relief.

• Barbiturates Barbiturates and meprobamate exert an anxiolytic effect linked to the sedation they cause. The risk of abuse and addiction is high. Many experts consider these drugs as obsolete for treating anxiety, although they may be valuable for the short term treatment of severe insomnia.

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â&#x20AC;˘ Herbal treatments Certain herbs, such as valerian, kava (Kava Kava), chamomile, Kratom, Blue Lotus extracts, Sceletium tortuosum (kanna) and bacopa monniera are reputed to have anxiolytic properties. With the exception of kava kava, only limited evidence exists for their efficacy.[1][2] Use of marijuana as an anxiolytic has seen promising results in regions where its practical study is possible, but its statusas a controlled substance in many countries make its study as such difficult. However a team from Brazil found cannabidiol to be an effective anti-psychotic and anxiolytic [3] 'CBD induced a clear anxiolytic effect and a patternof cerebral activity compatible with ananxiolytic activity (27). Therefore, similar to the data obtained in animal models, results from studies on healthy volunteers have strongly suggested an anxiolytic-like effect of CBD'. Pasted from <http://en.wikipedia.org/wiki/Anxiolytic>

OCD

For the diagnsosis of Social Anxiety Disorder, individuals older than 18 years must have SAD for a duration greater than ___ months? In diagnosing social anxiety disorder, it must not be related to any general medical condition, such as ___? Which two classes of meds are frequently used to treat performance anxiety?

What is the difference between obsessions and compulsions?

List a few obsessions related to OCD? List a few compulsions related to OCD?

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What are the 2 DSM-IV criteria for the diagnosis of OCD? T/F: Insight is usually absent in patients with OCD? OCD is frequently comorbid with other ___ disorders and ___?

PTSD

GENERALIZED ANXIETY DISORDER (GAD)

Buspirone is an anxiolytic agent and a serotonin receptor agonist belonging to the azaspirodecanedione class of compounds. Its structure is unrelated to those of the benzodiazepines, but it has an

For Generalized Anxiety Disorder to be diagnosed, worry must be present most days for greater than or equal to ___ months? What is the difference between acute stress disorder and PTSD? Pharmacologic treatment of Generalized Anxiety Disorder (GAD) may involve the use of which class of psychiatric medications? EMDR (eye movement desensitization and reprocessing) is indicated for the treatment of which disorder? For Generalized Anxiety Disorder to be diagnosed, there must be 3 or more of the following symptoms (list 4)?

efficacy comparable to diazepam in treating generalized anxiety disorder.[1][2] Pasted from <http://en.wikipedia.org/wiki/Buspirone>

ANXIETY DUE TO A GENERAL MEDICAL CONDITION Pharmacologic treatment for generalized anxiety disorder (GAD) may involve the use of which drugs (list 3)?

Is generalized anxiety disorder more prevalent in

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ANXIETY DUE TO A GENERAL MEDICAL CONDITION Pharmacologic treatment for generalized anxiety disorder (GAD) may involve the use of which drugs (list 3)?

Is generalized anxiety disorder more prevalent in males or females? Buspirone is a benzo or non-benzo?

SUBSTANCE-INDUCED ANXIETY DISORDER List 3 substances whos use can lead to substance-induced anxiety disorder?(4) Substance-Induced anxiety disorder may be associated with withdrawal from (which drugs) ___ or ___?

In Mowrer's two stage model of anxiety, which type of conditioning is required for the development of fear and which for the maintenance of fear?

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List the 3 major categories of neurotransmitters related to biogenic amines? GABA and glutamate are both examples of neurotransmitters that are biogenic amines, amino acids, or peptides? The neurobiology of anxiety involves which 3 major types of neurotransmitters? Cell bodies secreting majority of norepinephrine are located in the ___? Stimulation of the locus ceruleus leads ...?

Which are the two major nuclei on which serotonin has it's effects?

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GABA is the major (inhibitory/stimulatory) neurotransmitter? BZDP (benzo's), barbiturates, and alcohol all bind to which receptor of a major class of neurotransmitters? A high density of GABABZDP receptors are found in the ___, ___ an doccipital /frontal cortex? GABAA has allosteric binding sites for which major drugs (name 3)?

In the neuroanatomical model of anxiety, panic is thought to originate in the ___ and conditioned and unconditioned fear in the ___ and the ___? In the neuroanatomical model of anxiety, unconditioned fear is thought to originate in the ___ and conditioned fear in the ___? In the neuroanatomical model of anxiety, the limbic lobe is responsible for which type of anxiety? In the neuroanatomical model of anxiety, avoidance is mediated by which brain region? The major brain structures involved in OCD are the ___ and the ___?

T/F: Anxiety is CLEARLY genetic but it's also likely to be multifactorial? T/F: GABA has been implicated in both panic and ___? HPA axis dysfunction is prominently involved in which disorder?

â&#x20AC;˘ Neurotransmitters and Anxiety: Neurotransmitter

Anxiety Condition

NE

Panic

GABA

Panic, GAD

Serotonin

All anxiety disorders, especially OCD

Adrenergic, HPA axis PTSD

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T/F: CBT is the FIRST-LINE treatment for ALL anxiety disorders?

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Give examples of introceptive expsoures?

• •

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Imipramine, TCA (Imip) Placebo (PBO)


First-line treatment for GAD and SAD is ___? For all anxiety disorders EXCEPT GAD and SAD, ___ are indicated as first-line treatment?

T/F: In the treatment of anxiety disorders, benzo's are never first line treatment but they may be second line treatment? In the treatment of anxiety, when can you prescribe benzo's PRN?

BENZODIAZEPINES:

NEVER 1st OR 2nd

LINE TREATMENT FOR ANXIETY!

There's generally a ___ to ___ week lag in benefits from antidepressants and antianxiety medications?

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In the treatment of panic disorder, what are the indicated first and second line treatments? In the treatment of panic disorder, what are the indicated third line and third line/adjunctive treatments? T/F: MAOIs are indicated as second line treatment in the treatment of panic disorder? T/F: in addiiton to SSRIs, Venlafaxine is indicated as FIRST LINE treatment for panic disorder BUT NOT for social phobia?

â&#x20AC;˘ phenelzine sulfate: a monoamine oxidase inhibitor used as an antidepressant and in the prophylaxis of migraine; administered orally.

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â&#x20AC;˘ venlafaxine (Effexor) hydrochloride: an inhibitor of serotonin and norepinephrine reuptake, unrelated chemically to any other antidepressants, that potentiates neurotransmitter activity in the central nervous system; used as an antidepressant and antianxiety agent, administered orally.

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Buspirone is indicated as first line treatment for ___?


• CBT: FIRST LINE! • Generally treat anxiety disorders with SSRIs, benzo's

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06 RICHTER 2008 Anxiety Disorders Sunday, February 10, 2008 7:58 PM

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07 FMP 08 Week 8 Substance Abuse SEMINAR NOTES Sunday, February 10, 2008 7:55 PM

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Atenolol: a cardioselective 1-adrenergic blocking agent used in the treatment of hypertension and chronic angina pectoris and the prophylaxis and treatment of myocardial infarctionand cardiac arrhythmias; administered orally or intravenously.

• Prazosin hydrochloride: a quinazoline derivative with vasodilator properties, used as an oral antihypertensive.

• Hydrochlorothiazide: a thiazide diuretic, used for treatment of hypertension and edema; administered orally. It is often used in combination with a potassium-sparing diuretic.

• Enalapril: an angiotensinconverting enzyme inhibitor with antihypertensive and vasodilator actions. See also enalaprilat.

• 5oz of wine one standard drink • 12oz for beer

• So ask him about maximum amount; what's the most you would've had to drink in the last week or month?

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CAGE questionnaire is not a diagnostic test; just screening! T/F: The CAGE questionnaire is a good diagnostic test for diagnosing someone with alcoholism ONLY if males score 2/4 or higher and females score 1/4 or higher?

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Tolerance/withdrawal - physical depenence critera Psych dependence ○ Increased time spent using the substance getting using recovering from it ○ Using more than originally intended ○ Neglect of or giving up responsibilities related to home work social ○ Multiple unsuccessful attemps to cutdown ○ Contiiued use despite consequences secondary to the substance

• How do you treat severe alcohol withdrawal; use valium ○ Use diazepam loading protocol; one of the receptors that alcohol uses is the gabaergic receptors; when

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○ Contiiued use despite consequences secondary to the substance

• How do you treat severe alcohol withdrawal; use valium ○ Use diazepam loading protocol; one of the receptors that alcohol uses is the gabaergic receptors; when someone chornically drinking or alcohol dependent, then the immediate removal of all that alcohol will caause rebound excitatory consetllation of symptoms (sweating, seizures, etc.) so diazepam replaces alchool so that whatever left of gaabaergic symptoms prevents the onset of ○ Alcohol and diazepam crossreact; wait until they go into alcohol withdrawal; and then do CIWA based diazepam loading protocol; withdrawal symptoms scored out of 7 if score more than 10 then

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â&#x20AC;˘ Acetaminophen: the amide of acetic acid and paminophenol, having analgesic and antipyretic effects similar to aspirin but only weak antiinflammatory effects. Administered orally and rectally. Called also paracetamol.

â&#x20AC;˘ Cocaine: a crystalline alkaloid, obtained from leaves of Erythroxylon coca (coca leaves) and other Erythroxylon species, or by synthesis from ecgonine or its derivatives; used as a local anesthetic and vasoconstrictor applied topically to mucous membranes. Abuse of cocaine or its salts leads to dependence.

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Trazedone: when used in antidepressant doses makes people very sedated â&#x2014;&#x2039; Second generation antipsychotics also commonly used off label to help people sleep

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â&#x20AC;˘ Zyban (buproprion, or wellbutrin) also used to quit smoking; nicotine replacement therapy â&#x20AC;˘ Pharm'l and non-pharm'l therapy

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Seminar: Substance Abuse: A Case-Based Approach Thursday, March 06, 2008 5:51 PM

List what a standard drink is in terms of beer, wine, and liquor?

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In addition to asking how much a patient drinks on average per week and defining the size of the container of the type of alcohol they drink, which other important question should be asked to quantify alcohol consumption per week?

A 750 cc bottle of wine contains approximately how many standard drinks? An ounce contains approximately ___ cc's and a standard drink of wine contains about ___ oz?

What are the low risk drinking guidelines for men and women (ie. Maximum ___ standard drinks per week, or ___ drinks on any one day for men, â&#x20AC;Ś for women)?

T/F: Most of the cardiovascular benefits of alcohol can be obtained by drinking less than one drink per day and these benefits of reducing mortality from coronary artery disease are seconary to inhibition of platelet function and improvement in the lipid profile?

The CAGE questionnaire is scored as "positive" if men score higher than ___ out of 4 and women score higher than ___ out of 4?

T/F: Low Risk Drinking Guidelines recommend 14 standard drinks per week and three drinks MAXIMUM per day for MEN and 9 standard drinks per week and MAXIMUM 1 drink per day for WOMEN?

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If you suspect that a patient has an alcohol problem, which other questions, besides frequency and quantity of drinks per week and screening using the CAGE questionnaire, would you ask?

T/F: Problem drinkers DO experience alcohol withdrawal?

What is the definition of "alcohol dependence" (hint: 4 criteria, one of them being a type of dependence)?

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STRATEGIES TO AVOID INTOXICATION (7)

If someone is a problem drinker and you'd like to encourage them to recude their rate of drinking, what strategies can you recommend to help patients avoid intoxication (list 5)?(7) In tracking a problem drinker's progress over time, it may be helpful to order GGT and ___ at baseline and followup?

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What are the clinical features of alcohol dependence (list 3)?(5)

In treating alcohol withdrawal, diazepam is a good choice because it (list 3 reasons)?(5)

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Apart from an inpatient program, list 2 effective treatment plans that you can use for treating problem drinking? T/F: There is NO evidence that inpatient programs are more effective than outpatient in treating binge drinking and alcohol dependence? T/F: Naltrexone is a competitive beta-2 adrenergic antantagonist, and has been shown in several randomized trials to decrease the intensity and severity of binge drinking in alcohol dependent patients engaged in formal treatment programs? Another name for Naltrexone is ___? T/F: Naltrexone use reduces alcohol cravings? Why does Naltrexone use make it easier for patients to practise strategies learned in counselling to control excessive drinking habits? What is the mechanism of action of Naltrexone (ReVia) work?

___ is a clue that a patient on treatment for alcohol dependence may be relapsing?(3)

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Percocet is a combination of ___ and ___?

What are the clinical features of opioid withdrawal (list 2 objective signs and 2 subjective symptoms)? ( What is the time course of opioid withdrawal? The most common symptom of opioid withdrawal is ___? Insomnia and dysphoria may still be experienced for ___ after opioid withdrawal? For a patient experiencing alcohol withdrawal, which 3 other important questions would you ask on history?

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What is the mechanism of action of methadone? Methadone is an oral opioid ___ with a half-life of __ hours? Methadone is used in the treatment of patients who are physically and psychologically dependent on ___, such as ___ or high doses of other potent opioids such as ___ (just an example of one)? T/F: even if titrated carefully, methadone still causes drowsiness but this is a tolerated side-effect since it DOES relieve withdrawal and cravings, enabling patients to escape the biological compulsion to continue drug use? The 4 main components of methadone treatment are: (4)?

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What are the adverse effects of benzo's in the elderly? There is evidence that benzodiazepine use in the elderly increases the risk for â&#x20AC;Ś and the risk of â&#x20AC;Ś? Give an example of a long acting benzodiazepines (which, as a group, have been implicated in increasing the risk of falls and hip fractures in seniors)?

Benzo's increase risk of (5): 1. Falls and hip fractures in seniors, especially long-acting ones like diazepam and chlodiazepoxide 2. Confusion and impaired recall 3. MVA's 4. excerbate symptoms of depression 5. Potentially fatal hypoxia secondary to decreased respiratory drive in patients with sleep apnea and COPD

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How long does buproprion take to work? How effective is smoking cessation counselling? If someone has had a coronary event, how long should they wait before using a nicotine patch and gum?

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GHB is a structural analogue and metabolite of ___? __ and ___ characterize mild intoxication with GHB? What is the difference in symptoms experienced between mild intoxication with GHB and intoxication at higher doses? GHB can cause severe withdrawal syndrome similar to ___ withdrawal? GHB overdose is treated with Phenobarbital? GHB overdose at higher doses is characterized by which symptoms (name 3)? An 18 year old patient was brought in by ambulance to the emerg after his friends foundhim unresponsive in an after-hours night club. In the ambulance they gave him O2 and naloxone, to which he didn't respond. In the ER he was unresponsive to deep pain and was noted to have myoclonus and bradycardia and his O2 saturation was 80. After several hours he abruptly woke up, confused but otherwise well. What drug did he overdose on?

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Week 8 Review Questions Thursday, March 06, 2008 5:59 PM

FMP 2007 – 2008 Week 8 Review Questions Depression 1. What are the two “core” symptoms of a major depressive episode? 2. What are the other symptoms of depression? Classify them into two major categories. 3. What are the varieties of conditions associated with major depressive episodes? 4. What “general medical conditions” can cause depression? 5. What etiologic factors contribute to depression? 6. What brain anatomical changes are seen in some patients with depression? 7. What is the natural history of major depressive disorder? 8. What treatments in are available for depression? 9. What is psychotherapy? 10. What are the essential elements of cognitive behavioural therapy? 11. What kind of evidence supports the use of CBT? 12. What classes of medications are available to treat depression? 13. What are principles of the use of anti-depressants: a) How long to treat? b) Who needs maintenance treatment? c) How to treat refractory depression? 14. What neurotransmitter systems do these anti-depressants alter? 15. What are the major side effects of these anti-depressants? 16. What is the virtue of adding psychotherapy to anti-depressants? Bipolar disorder 17. What are the major features of a manic episode? 18. What is an expansive mood? 19. What is the natural history of bipolar disorder? 20. What is the difference between bipolar I and bipolar II? 21. What three medications or classes of medications are available for the treatment of mania? 22. What are the major side effects of each of these treatments? Substance abuse - general 23. What is meant by each of the following terms? a) Addiction b) Tolerance c) Withdrawal d) Physical dependence 24. What are the major drugs of abuse? 25. What is the meaning of the following terms: a) Dependence b) Withdrawal c) Tolerance d) Addiction Substance abuse - Ethanol 26. What are manifestations of alcohol withdrawal? 27. How should alcohol withdrawal be treated? 28. What are chronic effects of excessive alcohol use? 29. What are safe drinking limits for men, women and pregnant women? 30. What is a standard drink? 31. What is the meaning of the following strategies used in treatment of drug abuse, and give examples of each: a) Aversive therapy b) Agonist substitution c) Anti-craving therapy 32. What laboratory tests can be used to help indicate if someone is using ethanol to excess? 33. What is the CAGE questionnaire, and how should answers to it be interpreted? Substance abuse - Nicotine 34. What is the meaning of referring to nicotine as a chameleon drug? 35. What are features of nicotine withdrawal? 36. What three classes of drug are available to treat nicotine withdrawal? Substance abuse - Other 37. What are clinical features of opioid abuse?

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37. 38. 39. 40. 41.

What are clinical features of opioid abuse? What happens as a consequence of opioid withdrawal? How does methadone work to assist with opioid addiction management? What is buprenorphine? What are consequences of the abuse of each of the following: a) cocaine b) cannabis c) Gamma-hydroxy-butyrate d) Ecstasy e) Hallucinogens

Anxiety disorders 42. What are the diagnostic criteria for each of the following: a) Post-traumatic stress disorder b) Panic disorder c) Agarophobia d) Social anxiety disorder e) Generalized anxiety disorder f) Obsessive-compulsive disorder 43. What is a panic attack? 44. What general medical conditions can cause anxiety? 45. What is the preferred treatment for all anxiety disorders? 46. What medications are available for anxiety disorders? Which are first line? What is the role of benzodiazepines? Pasted from <https://portal.utoronto.ca/courses/1/Fall-2007-FMP211Y1-Y-LEC0101/content/_913877_1/FMP%202008%20week%2008%20review%20questions.doc? bsession=11327372&amp;bsession_str=session_id=11327372,user_id_pk1=501825,user_id_sos_id_pk2=1,one_time_token=>

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Dr. Schreiber Review Lecture Tuesday, February 19, 2008 Tuesday, February 19, 2008 11:16 AM What are the 4 C's of addiction? 1. What are the 4 C's of addiction? a. Consequences i. Person knows it's bad for them but they keep doing it anyway b. Control i. Loss of control c. Cravings! d. Compulsive use (over and over again) 2. What is the difference between tolerance and withdrawal and dependence? What is the difference a. Tolerance: between tolerance and i. Increased dose for same effect dependence? 1) need more of drug to get same effect b. Withdrawal i. Drug opposite effects without the drug c. Dependence i. In absence of continued substance use, get withdrawal symptoms ii. NB: addiction and dependence are not the same thing; we use lots of opiods in management of chronic cancer pain; average patient is dependetn on opiods with chronic cancer pain; 1) Addict means loss of control and cravings… 3. Alcohol Withdrawal a. What is uncomplicated alcohol withdrawal? You see someone who i. Autonomic "stuff"- Sweating, palpitations, ↑HR, ↑palpitations, ↑sweat, ↑tremor, anxiety you suspect has alcohol b. Moderate withdrawal - usually happens less than 48 hours withdrawal. He reports i. Hallucinations that he had a seizure 1) Classic: pink elephants that started with the 2) Often visual hallucinations; patients with schiz. Typically get auditory hallucinations arm then the whole ii. Generalized tonic clonic seizures body started to shake. 1) Eg. Question: see someone evidently alcohol withdrawal; says he had a seizure; started with Is this evidence of arm, then whole body started shaking; THIS IS NOT AN ALCOHOL WITHDRAWAL SEIZURE; alcohol withdrawal? should have no focal point if it's alcohol withdrawal seizure! c. Severe - within 3-5 days go completely nuts - quite high rate of mortality i. Delirium Tremens ii. Tachycardic, fever, severely impaired 4. What is the Treatment of choice for alcohol withdrawal? a. Benzo's - replace the sedating effect of the ethanol; want to use a drug that has a much longer half-life than alcohol In choosing a drug to treat alcohol i. Typically use Diazepam - (Valium) - longer halflife, about 36 hours withdrawal, the principle that you use is to 5. Standard drink: 13 grams of alcohol select one which has a much (longer/shorter) a. 12 oz beer half-life than alcohol? b. 5 oz wine What does the CAGE questionnaire stand c. 1.5 oz liquer for? What is the treatment for choice for alcohol Safe drinking limits: withdrawal? • Female: 2/day, 9 per week (smaller, less body water) Patient with moderate alcohol withdrawal • Male: 2 per day; 14 per week often have (auditory OR visual) • Pregnant Woman: 0 hallucinations? The half-life of diazepam is much longer than Men: 8 drinks per day for 10 years: 20% chance of cirrhosis alcohol, at around approximately ___ hours? • CAGE questionnaire ○ Cutdown? ○ Annoyed? ○ Guilty? ○ Eye-opener? • Two or more for men; one or more for women suggests drinking problem; just suggests you should explore further • 2 lab tests linked to alcohol intake: ○ GGT ○ ↑MCV

• 3 DRUGS SHOULD DEFINITELY KNOW: ○ Disulfiram: PAVLOVIAN! inhibits alcohol dehydrogenase; when acetaldehyde accumulates, it causes flushing, nausea; if person drinks then they'll get flushed and vomiting and start to associate with alcohol intake ○ Naltrexone - reduces cravings ○ Acamprosate - resduces withdrwal symptoms Acamprosate, also known by the brand name Campral®, is a drug used for treating alcohol dependence. Acamprosate is thought to stabilize the chemical balance in the brain that would otherwise be disrupted by alcoholism, possibly by blocking glutaminergic N-methyl-D-aspartate receptors, while gamma-aminobutyric acid (GABA) type A receptors are activated.[3] Reports indicate that acamprosate only works with a combination of attending support groups and abstinence from alcohol.[4] Certain serious side effects include allergic reactions, irregular heartbeats, and low or high blood pressure, while less serious side effects include headaches, insomnia, and impotence.[5] Acamprosate should not be taken by people with kidney problems or allergies to the drug.[6] Pasted from <http://en.wikipedia.org/wiki/Acamprosate>

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Suggest two lab tests for measuring baseline and follow up alcohol intake? A standar drink is approximately how many grams of alcohol?

Does MCV rise or fall with increased alcohol intake? Disulfiram inhibits which enzyme? What is the mechanism of action of Disulfiram? What is disulfiram used for the treatment of? Acamprosate reduces cravings OR withdrawal symptoms? Naltrexone reduces cravings OR withdrawal symptoms?


Pasted from <http://en.wikipedia.org/wiki/Acamprosate>

SMOKING 1. Nicotine replacement therapy - people relapse though; so may need to use Buproprion ○ Treatment: patch, gum, inhale 2. Buproprion a. Wen used for depression called Wellbutrin b. When for smoking: Zyban 3. Champix (Varenicline) a. Probably the most effective

Opioids: ○ Signs of overuse of opioids on physical exam include:  ↓HR  ↓RR  ↓pupils  ↓BP  ↓LoC (level of consciousness) ○ Withdrawal (remember: drug opposite effects)  Anxious, sweating, can't sleep, vomiting, diarrhea, muscle pain ○ How does methadone work?  LONG HALF-LIFE! ○ What is the antidote to opioid withdrawal? 

When used for depression, buproprion is called ___ whereas when it's used for smoking cessation, it's called ___? ___ is probably the most effective smoking cessation therapy available today? Another name for Varenicline is ___?

Withdrawl from opioids results in "drug opposite effects", which include … (list 3)?(6) What is the antidote to opioid withdrawal?

Naloxone! - one of the few drugs useful to memorize dose

□ Brand name is Narcan an opioid antagonist structurally related to oxymorphone, used in the diagnosis and treatment of opioid toxicity, to reverse opioid-induced respiratory depression, and as an adjunct in the treatment of hypotension associated with septic shock; administered parenterally.

○ Cocaine  What are the medical consequences of cocaine use? 1) Stroke 2) Intracerebral hemorrhage 3) Seizures 4) Severe HTN 5) MI 6) Arrhythmias (sympathetic agonist) 7) Rhabdomyolysis  Acute renal failure ○ Chronic Alcohol Use - Chronic complications  Liver 1) Fatty Liver 2) Alcoholic hepatitis 3) Cirrhosis 4) Hepatocellular Carcinoma - any cause of cirrhosis can lead to hepatocellular carcinoma  GI 1) Pancreatitis  Acute or chronic - BOTH can be triggered by alcohol  CVS 1) (contributes to) High blood pressure 2) Cardiomyopathy 3) Atrial fib  CNS 1) Dementia 2) Cerebellar atrophy 3) Ataxia 4) Neuropathy

List 3 medical consequences of cocaine use?(7) Chronic complications of alcohol use include …(list 1 per: liver, GI, CVS, CNS, )?(4)

List 2 CNS consequences of chronic alcohol consumption?(4)

List the 3 major neurotransmitters which have been shown to be out of balance in people with depression?

• 3 neurotransmitters messed up in people with major depression: 1. Serotonin 2. Dopamine 3. Norepinephrine

The hippocampus of patients TREATED for depression was shown to expand OR contract?

• Hippocampus: shown to expand in people treated for depression Criteria for major depressive episode: Have to have one or other of these two:  Depressed mood  Anhedonia □ Lack of interest/lack of pleasure  4 other symptoms that can be divided into 2 groups: □ Mental  Suicidal ideation  Decreased ability concentrate  Feeling worthless □ Physical  ∆ Sleep  ∆ Appetite/Weight  ∆ Psychomotor retardation  Fatigue • Almost every psychological diagnosis involves impairment in social or cognitive functioning

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• Almost every psychological diagnosis involves impairment in social or cognitive functioning DRUGS FOR DEPRESSION! ○ SSRIs i. Prozac □ Fluoxetine ii. Citalopram □ Celexa iii. Paroxetine □ Paxil iv. Citraline □ Zoloft v. Fluvoxamine □ Luvox ○ SNRIs  Venlafaxine □ Effexor - contributes to ↑HTN ○ Buproprion (DA) ○ Mirtazapine - works as an alpha 2 agonist, serotonin reuptake inhibitors

List 3 SSRIs? (below is just a partial list of 5) Another name for Zoloft is __? Another name for Citalopram is __? Another name for Citraline is __? Another name for Fluvoxamine is __? Another name for Paroxetine is __? Is Venlafaxine an SSRI or an SNRI? Another name for Venlafaxine is ___? What is the difference in the mechanism of action of Venlafaxine vs. Fluvoxamine?

 Mirtazapine: an antidepressant compound unrelated to any of the classes of antidepressants; administered orally.  ○ MAOI - monoamine oxidase inhibitors  What every doctor should know: interacts with certain foods, decongestants, meds, CAN TRIGGER HYPERTENSIVE CRISIS! So may cause ↑↑BP ○ TCA - 2 different names, same class  -ipramines  -

What is the mechanism of action of Mirtazapine? What is Mirtazapine used for?

MANIA! ○ ○ ○ ○ ○ ○

CORE SYMPTOM: Elevated euphoric or irritable mood that lasts for at least a week Sleep deprivation without fatigue ↑ speed of speech ↑speed thought ↑ pleasurable activities ↑ goal directed activity

Bipolar 2: ○ Not full extent of mania • List 3 types of mood stabilizers? 1. Lithium i. Causes impairment of renal water conservation and may contribute to renal failure 2. Anticonvulsants i. Carbamazepine ii. Valproate iii. Lamotragine 3. Antipsychotics i. Atypical (risperidone, olanzapine) □ Worst side effect: Leukopenia ↓WBC

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List 3 categories of mood stabilizers? Risperidone and olanazapine are both ___? An important side effect of lithium consumption is that it causes …? List 2 anticonvulsants that are used as mood stabilizers?(3)


Summary Week 8 Questions

01 SCHAFFER 2008 Diagnosis and Etiology of Depression 2x3 50% of those with Major Depressive Disorder have onset before the age of ___? Biochemically, what is the response to anti-depressants that target norepinephrine? Briefly describe how sadness is different from depression? Do antidepressants increase or decrease dopamine levels? Do antidepressants work by upregulating or downregulating beta-adrenergic receptors (thereby influencing norepineprhine)? Give examples of 3 substances that can lead to substance-induced MDE?(4) How are serotonin levels linked to precipitating the symptoms of depression? How is major depressive disorder diagnosed? How many months within the onset of a stressful event must depression occur and after how many months must it resolve in order to be diagnosed with Adjustment Disorder with Depresed Mood? How much of the variance in the incidence of depression is accounted for by life events? In diagnosing dysthymia, the patient should "never be without symptoms forâ&#x20AC;Ś" what period of time? In order to diagnose someone with a major depressive episode (MDE), there are 3 major diagnostic criteria according to DSM IV; what are they? In order to diagnose someone with a major depressive episode (MDE), there they must have 5 or more of which symptoms during a 2 week period? (list 5, there's a total of 9) List 2 ways you can be more assured of a substance-induced MDE diagnosis; ie. There are 3 criteria that must be met to confirm substance-induced MDE, list 2? List 3 medical conditions that can lead to a mood disorder due to a general medical condition?(5) List 3 neurotransmitters involved in depression?(3) List 4 diagnoses that are associated with MDE's(6)? List 4 diagnostic criteria for Dysthymia?(5) List 5 signs that indicate the presence of depression?(7) List 6 risk factors for depression?(8) Name 2 vitamin deficiencies that can cause a mood disorder? T/F: According to the Canadian Community Health Survey, the highest rate of Major Depressive Disorder was amongst the 15-24 year old age group? T/F: According to the Canadian Community Health Survey, women are overall more likely to suffer from depression compared to men? T/F: According to the Canadian Community Health Survey, women over 64 are significantly more likely to suffer from depression than men over 64? T/F: Adjustment Disorder with Depressed Mood is diagnosed in patients with a mental illness/disorder? T/F: Major depressive disorder occurs more frequently in the elderly (+60 years old) than in those less than 60 years old? T/F: True depression is NOT a chronic condition but is by definition acute episodes of depressive symptoms? The mean number of lifetime episodes for someone who suffers from Major Depressive Disorder is __ to __? What did the Dunedin Multidisciplinary Health and Development Study reveal regarding genetics and depression in S/S genotyped individuals? What did the Dunedin Multidisciplinary Health and Development Study reveal regarding maltreatment, serotonin transporter gene promoter region genotypes, and propensity to experience depression? What happens to blood flow to the attention/cognition areas of the brain in depression versus blood flow to the vegetative-autonomic areas of the brain? What is Adjustment Disorder with depressed mood? What is substance-induced MDE? What is the effect of untreated depression on hippocampal volume? Within the course of Major Depressive Disorder, what is the mean duration of an untreated Major Depressive Episode?

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02 SCHAFFER 2008 Biological Treatment of Depression 2x3 A majority of depression patients achieve remission after how many medication trials? Apart from pharmaceutical therapy, list 2 other biological treatments for depression?(4) Buproprion (Wellbutrin), at high doses, has which common side-effect? Every patient treated for depression needs to go through at least which 2 phases of treatment? Give 2 examples of SNRIs? Give 2 examples of SSRIs? Give 3 examples of TCA antidepressants? Give an example of a reversible MAOI antidepressant and another example of an irreversible MAOI antidepressant? How are number of episodes of antidepressant treatment correlated with length of antidepressant treatment? How did trends in the outpatient treamtent of depression change between 1987 and 1997 in the US? How do MAOI antidepressants work? How do SNRIs work? How do SSRIs work? How do TCA antidepressants work? How does Buproprione (Wellbutrin) work? How long does the acute phase of antidepressant treatment last? How long does the continuation phase of antidepressant treatment last? How long does the maintenance phase of antidepressant treatment last? In using a 2nd medication for depression treatment, what is the principle that should be followed? List 2 common side effects of MAOIs?(3) List 2 common side effects of TCAs? List 2 common side-effects of Buproprion (Wellbutrin)? List 2 common side-effects of Mirtazapine (Remeron)?(3) List 3 categories of patients who would require maintenance treatment?(4) List 4 factors that should influence your choice of which antidepressant to prescribe? List 4 strategies one should follow if the medications prescribed for anti-depression aren't helping? MOST remissions from antidepressant use occur between ___ to___ weeks of use? T/F: A MAJORITY of patients achieve remission from depression after TWO OR MORE medications? T/F: A MINORITY of patients achieve remission from depression with FIRST line medication? T/F: Most medication choices have similar efficacy? The precursor for dopamine, _____, is found in many foods, including cheese and tofu? Tyramine ingestion while taking MAOIs can cause ___? Tyramine is the precursor for ___? What are two specific side effects of most antidepressants that you should warn patients about? What does it mean to 'augment' anti-depressant medication with other medications? What is the difference between response and remission? What is the difference between the goals of acute, continuation, and maintenance treatment with respect to treating depression? What is the generic name for Remeron? What is the generic name of Celexa? What is the generic name of Effexor? What is the generic name of Paxil? What is the generic name of Prozac? What is the generic name of Zoloft? What is the mechanism of action of Mirtazapine? What percentage, approximately, of patients will RESPOND to treatment with a first line antidepressant? (nb. Asking for response, NOT remission) Which is the MOST toxic in overdose: SSRIs, TCAs, SNRIs? Which other form of treatment should be added to antidepressant therapy to achieve an even better outcome? Which type of anti-depressant class has a high rate of drug-drug and drug-food interactions? Why are SSRI's more sought after than TCAs?

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Why are SSRI's more sought after than TCAs? Why should tripants (used in the treatment of migraines) not be taken with MAOI antidepressants? 03 ZARETSKY 2008 Cognitive Therapy for Depression 2x3 Apart from depression, list 2 other common medical problems which CBT be used for?(5) CBT and SRI treatment responsive OCD patients show similar decreased activitiy in which brain structure? Cognitive therapy is generally time limited to how many months (for uncomplicated depression or anxiety)? Give a few examples of comorbidities of depression? Give an example of how CBT can be used to maintain patients in remission more effectively than clinical case management? Give examples of how CBT is a structured therapy? In a typical course of CBT for depression, organize the following session goals from earliest to latest: Goal setting, relapse prevention and termination, assessment and suitability, behavioural activation, use of an automatic thought record? List 2 different forms of psychotherapy?(3) List 3 non-specific mechanisms of action of psychotherapy? List 3 specific mechanisms of action of psychotherapy? List 4 psychiatric conditions in which CBT is the gold standard? List 5 cognitive distortions?(10) T/F: CBT is as effective as medication for chronic depression? T/F: CBT is as effective as medication for mild to moderate depression? T/F: CBT is MORE effective than medication in reducing relapses? T/F: CBT is NOT as effective as medication for more severe non-psychotic depression? T/F: Cognitive therapy can be done individually but should not be done in groups? T/F: For chronic depression, there is no difference between using CBT alone versus using medication alone? T/F: If you wish to start a patient on CBT, this SHOULD NOT be started mid-way through their medication course because of the inability to discern which is having a positive effect? The cognitive model states that one's core beliefs in a situation influence which 3 factors? What are the 6 steps in cognitive restructuring? What are the stages in the Cognitive Model of Depression?(hint: 5 linear steps before get to symptoms of depression)? Which of the following is an example of Socratic questioning, in response to a student saying "I'm a complete failure" (there may be more than one right answer): 1. What makes you think you are a complete failure?; 2. Why are you being so hard on yourself?; 3. What would a good student do?; 4. Would a complete failure be able to get 75% on an exam?; 5. On a scale of 0-100%, where do you fall? Where do other people fall? 04 SCHAFFER 2008 Introduction to Bipolar Disorder 2x3 A genuine manic episode generally lasts for at least how long? According to the mood spectrum, what's the difference between bipolar type I and type II? Apart from mood stabilizers and antidepressants what are some other treatments for bipolar disorder? Approximately ___% of depressed patients have bipolar disorder? Are depressive episodes necessary for the diagnosis of bipolar disorder? Atypical antipsychotics are used more for the treatment of mania or bipolar depression? Atypical antipsychotics were originally introduced for the treatment of ___? Divalproex and lamotrigine are both ___? For the pharmacological management of acute bipolar mania, which medications are commonly used for monotherapy? Give 2 examples of atypical antipsychotics?(4) Hypomania + Depression = ___? In diagnosing a manic episode, patients must experience 3 or more of which 7 symptoms?(just name 5) In diagnosing a manic episode, what are the 4 general categories? In diagnosing a mixed episode, criteria for BOTH a manic episode AND major depressive episode should

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be met for what minimum period of time? Lamotrigine is primarily used for the treatment o f â&#x20AC;Ś? List 2 different psychosocial interventions for the maintenance phase of bipolar disorder?(4) List 2 popular combination therapies for the treatment of bipolar depression?(3) List 2 psychiatric disorders for which mood stabilizers are indicated for? List 3 criteria for hypomanic episodes?(6) List 3 populations that are particularly at risk for bipolar disorder?(6) List 3 potential complications of long term mood stabilizer use?(7) List 3 symptoms that overlap between mania and depression?(6) List a popular combination therapy for the treatment of acute bipolar mania? Long term lithium use has potential complications for which organ? Monotherapy for treatment of bipolar depression includes which 2 medications? Olanzapine, risperidone, clozapine, and quetiapine are all examples of which class of medications? Sexual dysfunction is a prominent side effect of long-term use of which mood stabilizer? T/F: Bipolar disorder is NOT caused by parents but CAN be reversed by will power? T/F: Bipolar disorder MAY run in families? T/F: Lamotrigine and Divalproex are indicated as combination therapy for the treatment of bipolar depression? T/F: Mood stabilizers DO NOT worsen mania or depression? T/F: Patients with bipolar disorder do not actually have morphological abnormalities but they do have second messenger and mitochondrial dysfunction? T/F: Valproic acid is primarily used to treat bipolar depression? The administration of which anticonvulsant has a 1:1000 risk of ___ Syndrome? The administration of which bipolar medication has a 1:1000 risk of Stevens-Johnson Syndrome? The leading cause of mortality in patients with BD is due to ___? The main side effects of the atypical antipsychotics are ___ risks, such as â&#x20AC;Ś(name 2)?(3) The presence of mania, in Canada, is highest in which age group: 15-24, 25-64, or over 64? What are the 2 criteria used to define bipolar disorder? What are the 3 diagnostic criteria for a mixed episode? What are the two most common conditions that are comorbid with bipolar disorder? What does CANMAT stand for? What is Bipolar Disorder Type II? What is Lamotrigine? What is the generic name for Divalproex? What is the most common age for the onset of bipolar disorder in males and females? What percentage of bipolar patients have recurrence? Which category of long-term mood stabilizers has the highest risk of causing dyslipidemia? Which category of long-term mood stabilizers has the highest risk of causing glucose dysregulation? Which category of long-term mood stabilizers has the highest risk of causing liver problems? Which category of long-term mood stabilizers has the highest risk of causing sexual dysfuntion? Which category of long-term mood stabilizers has the highest risk of causing teratogenicity? Which of the following are potential complications of long-term mood stabilizer use: teratogenicity, glucose dysregulation, renal effects, liver problems, sexual dysfunction, dyslipidemia, weight gain? Which of the following are side effects of anticonvulsants: teratogenicity, glucose dysregulation, renal effects, liver problems, sexual dysfunction, dyslipidemia, weight gain? Which of the following lead to weight gain (may be more than one right answer): atypical antipsychotics, anticonvulsants, lithium? With respect to lithium administration, what is the range of dosages used to treat bipolar disorder? With respect to lithium levels, the treatment of mania or depression has a higher target blood level? Would a higher target blood level of lithium be sought to treat acute depression or for maintenance treatment of bipolar disorder? Would a higher target blood level of lithium be sought to treat acute mania or acute depression? Would lithium, olanzapine, and divalproex be appropriate combination therapy for the treatment of acute bipolar mania? 05 KAHAN 2008 Substance Abuse Key Concepts 2x3 Which of the following is a complication of hallucinogen use (may be more than one): poor social Week8 Page 278


Which of the following is a complication of hallucinogen use (may be more than one): poor social functioning, mania, delerium tremens, drug induced psychosis, cravings, fatigue and irritability, mood disorders? According to the Low-risk Drinking Guidelines, how many drinks are low risk for men to drink per week? According to the Low-risk Drinking Guidelines, how many drinks are low risk for the general population to have per day? According to the Low-risk Drinking Guidelines, how many drinks are low risk for women to drink per week? Alcohol enhances ___, which is an inhibitory neurotransmitter and suppreses ___ which is a neuroexcitatory neurotransmitter? Alcohol inhibits which system in the brain? Alcohol suppresses ___ and enhances ___ (both neurotransmitters)? Another name for ecstasy is ___? Another name for endorphin receptors is ___ receptors? Another name for MDMA is ___? Another name for Suboxone is ___? Approximately how long does it take for Buproprion to work? Are opioids effective for acute pain only, chronic pain only, or both? Are opioids safe in pregnancy (if not, why; what may they cause)? As a laboratory marker for alcohol consumption, is MCV found to be depressed or elevated? Cessation of alcohol use leads to unopposed activity of which neurotransmitter? Cocaine blocks the presynaptic uptake of which 3 neurotransmitters? Does methadone administration induce sedation? Does tolerance to alcohol develop quickly or slowly? GHB is a metabolite of ___? GHB stands for ___? GHB use leads to ___ effects, like ___? Give 2 examples of hallucinogens?(3) How are the symptoms of uncomplicated alcohol withdrawal different from those of complicated alcohol withdrawal? In using opioids, what's the difference in the rate of development of tolerance to psychoactive vs. analgesic effects? List 2 medications that can be used to reduce drinking? List 2 psychological symptoms of opioid withdrawal?(3) List 3 factors that are correlated with the addictive potential of drugs?(5) List 3 ways in which you could make a drug less addictive?(5) Opioids act on which receptors? Physical symptoms of opioid withdrawal include â&#x20AC;Ś (name 2)? Severe withdrawal from nicotine lasts approximately how many days? Symptoms of alcohol withdrawal typically start how many hours after the last drink? T/F: BOTH GGT and MCV are poor screening methods for excess alcohol use since both have low sensitivity AND specificity values? T/F: Buprenorphine is AS EFFECTIVE as methadone at 60-80 mg? T/F: MDMA use may acutely lead to serotonergic syndrome? T/F: Nicotine can be both a relaxant AND a stimulant? T/F: Nicotine replacement therapy is far SAFER than cigarette smoking? T/F: The effects of MDMA may be temporarily decreased by treating with an SSRI? T/F: The withdrawal symptoms experienced in GHB withdrawal are similar to those experienced by withdrawal from hallucinogens? Tachycardia and vomiting are examples of complicated or uncomplicated signs of alcohol withdrawal? The ____ and NMDA ____ are inhibited by alcohol? Treatment for GHB use is ___? Usually a cocaine high is 20 minutes but with repeated use the euphoria only lasts for ___, followed by ___? What are the 4 C's of addiction? What are the cardiovascular chronic effects of alcohol consumption?

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What are the cardiovascular chronic effects of alcohol consumption? What are the CNS chronic effects of alcohol consumption? What are the components of serotonergic syndrome? What are the GI chronic effects of alcohol consumption? What are the hepatic chronic effects of alcohol consumption? What are the psychiatric chronic effects of alcohol consumption? What are the withdrawal symptoms seen in withdrawal from hallucinogens? What are the withdrawal symtpoms in GHB withdrawal? What is a standard drink for beer, wine, liquor (give quantities)? What is the CAGE questionnaire? What is the difference between the condition that Naltrexone is used to treat vs. Naloxone? What is the generic name of veranacline? What is the mechanism of action of Acamprosate? What is the mechanism of action of buprenophine? What is the mechanism of action of Champix? What is the mechanism of action of Naltrexone? What is the primary difference between the reward pathway of cocaine compared to alcohol, nicotine and opioids? Which important neurotransmitter does MDMA (ecstasy) stimulate the release of? Which of the following is a complication of cannabis use (may be more than one): poor social functioning, mania, delerium tremens, drug induced psychosis, cravings, fatigue and irritability, mood disorders? Why can you not overdose on Buprenophine (Suboxone)? 06 RICHTER 2008 Anxiety Disorders 2x3 A high density of GABA-BZDP receptors are found in the ___, ___ an doccipital /frontal cortex? Are males or females more prone to panic disorders? Buspirone is a benzo or non-benzo? Buspirone is indicated as first line treatment for ___? BZDP (benzo's), barbiturates, and alcohol all bind to which receptor of a major class of neurotransmitters? Cell bodies secreting majority of norepinephrine are located in the ___? EMDR (eye movement desensitization and reprocessing) is indicated for the treatment of which disorder? First-line treatment for GAD and SAD is ___? For all anxiety disorders EXCEPT GAD and SAD, ___ are indicated as first-line treatment? For Generalized Anxiety Disorder to be diagnosed, there must be 3 or more of the following symptoms (list 4)? For Generalized Anxiety Disorder to be diagnosed, worry must be present most days for greater than or equal to ___ months? For the diagnosis of panic disorder patients must have symptoms for more than how long (ie. How many weeks or months)? For the diagnsosis of Social Anxiety Disorder, individuals older than 18 years must have SAD for a duration greater than ___ months? GABA and glutamate are both examples of neurotransmitters that are biogenic amines, amino acids, or peptides? GABA is the major (inhibitory/stimulatory) neurotransmitter? GABAA has allosteric binding sites for which major drugs (name 3)? Give examples of introceptive expsoures? How is anxiety differentiated from fear? HPA axis dysfunction is prominently involved in which disorder? In agoraphobia, situations are ___, ___, or require the presence of ___? In diagnosing a panic attack, patients must experience 4 or more of the following (list 5)?(13) In diagnosing social anxiety disorder, it must not be related to any general medical condition, such as ___? In Mowrer's two stage model of anxiety, which type of conditioning is required for the development of

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fear and which for the maintenance of fear? In order to be diagnosed with panic disorder, a patient must have both recurrent panics and one or more of which three symptoms? In the neuroanatomical model of anxiety, avoidance is mediated by which brain region? In the neuroanatomical model of anxiety, panic is thought to originate in the ___ and conditioned and unconditioned fear in the ___ and the ___? In the neuroanatomical model of anxiety, the limbic lobe is responsible for which type of anxiety? In the neuroanatomical model of anxiety, unconditioned fear is thought to originate in the ___ and conditioned fear in the ___? In the treatment of anxiety, when can you prescribe benzo's PRN? In the treatment of panic disorder, what are the indicated first and second line treatments? In the treatment of panic disorder, what are the indicated third line and third line/adjunctive treatments? Is generalized anxiety disorder more prevalent in males or females? List 2 core features of anxiety disorders? List 3 examples of agoraphobic situtations? List 3 physical symptoms of social anxiety?(9) List 3 substances whos use can lead to substance-induced anxiety disorder?(4) List 6 anxiety disorders?(11) List a few compulsions related to OCD? List a few obsessions related to OCD? List the 3 major categories of neurotransmitters related to biogenic amines? List the 3 phases to a panic attack? List three subtypes of specific phobias? List typical situations in patients would experience agoraphobia? OCD is frequently comorbid with other ___ disorders and ___? Pharmacologic treatment for generalized anxiety disorder (GAD) may involve the use of which drugs (list 3)? Pharmacologic treatment of Generalized Anxiety Disorder (GAD) may involve the use of which class of psychiatric medications? Stimulation of the locus ceruleus leads ...? Substance-Induced anxiety disorder may be associated with withdrawal from (which drugs) ___ or ___? T/F: Anxiety is CLEARLY genetic but it's also likely to be multifactorial? T/F: CBT is the FIRST-LINE treatment for ALL anxiety disorders? T/F: GABA has been implicated in both panic and ___? T/F: in addiiton to SSRIs, Venlafaxine is indicated as FIRST LINE treatment for panic disorder BUT NOT for social phobia? T/F: In chronic anxiety, patients' anxiety levels will dip to normal for a few days at most but will be above normal at a constant level most of the time? T/F: In the treatment of anxiety disorders, benzo's are never first line treatment but they may be second line treatment? T/F: Insight is usually absent in patients with OCD? T/F: MAOIs are indicated as second line treatment in the treatment of panic disorder? The major brain structures involved in OCD are the ___ and the ___? The neurobiology of anxiety involves which 3 major types of neurotransmitters? The single most common mental disorder is ___? The two major classes of pharmacotherapy for the treatment of phobias are ___ and ___? There's generally a ___ to ___ week lag in benefits from antidepressants and antianxiety medications? What are the 2 DSM-IV criteria for the diagnosis of OCD? What are the 4 major types of phobias? What are the three related diagnoses for anxiety disorder?(ie. Panic disorder withâ&#x20AC;Ś, etc.) What is social anxiety disorder? What is the approximate lifetime prevalence of anxiety disorders? What is the difference between acute stress disorder and PTSD? What is the difference between generalized and non-generalized social anxiety disorder? What is the difference between obsessions and compulsions?

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What is the difference between obsessions and compulsions? What is the gold standard treatment for phobias? Which are the two major nuclei on which serotonin has it's effects? Which two classes of meds are frequently used to treat performance anxiety? 07 FMP 08 Week 8 Substance Abuse SEMINAR NOTES T/F: The CAGE questionnaire is a good diagnostic test for diagnosing someone with alcoholism ONLY if males score 2/4 or higher and females score 1/4 or higher? Dr. Schreiber Review Lecture Tuesday, February 19, 2008 ___ is probably the most effective smoking cessation therapy available today? A standar drink is approximately how many grams of alcohol? Acamprosate reduces cravings OR withdrawal symptoms? An important side effect of lithium consumption is that it causes …? Another name for Citalopram is __? Another name for Citraline is __? Another name for Fluvoxamine is __? Another name for Paroxetine is __? Another name for Varenicline is ___? Another name for Venlafaxine is ___? Another name for Zoloft is __? Chronic complications of alcohol use include …(list 1 per: liver, GI, CVS, CNS, )?(4) Disulfiram inhibits which enzyme? Does MCV rise or fall with increased alcohol intake? In choosing a drug to treat alcohol withdrawal, the principle that you use is to select one which has a much (longer/shorter) half-life than alcohol? Is Venlafaxine an SSRI or an SNRI? List 2 anticonvulsants that are used as mood stabilizers?(3) List 2 CNS consequences of chronic alcohol consumption?(4) List 3 categories of mood stabilizers? List 3 medical consequences of cocaine use?(7) List 3 SSRIs? (below is just a partial list of 5) List the 3 major neurotransmitters which have been shown to be out of balance in people with depression? Naltrexone reduces cravings OR withdrawal symptoms? Patient with moderate alcohol withdrawal often have (auditory OR visual) hallucinations? Risperidone and olanazapine are both ___? Signs of overuse of opioids on physical exam include: ↓HR ↓RR ↓pupils ↓BP ↓LoC (level of consciousness) Suggest two lab tests for measuring baseline and follow up alcohol intake? The half-life of diazepam is much longer than alcohol, at around approximately ___ hours? The hippocampus of patients TREATED for depression was shown to expand OR contract? What are the 4 C's of addiction? What does the CAGE questionnaire stand for? What is disulfiram used for the treatment of? What is Mirtazapine used for? What is the antidote to opioid withdrawal? What is the difference between tolerance and dependence? What is the difference in the mechanism of action of Venlafaxine vs. Fluvoxamine? What is the mechanism of action of Disulfiram? What is the mechanism of action of Mirtazapine? What is uncomplicated alcohol withdrawal? Autonomic "stuff"- Sweating, palpitations, ↑HR, ↑palpitations, ↑sweat, ↑tremor, anxiety Week8 Page 282


Autonomic "stuff"- Sweating, palpitations, ↑HR, ↑palpitations, ↑sweat, ↑tremor, anxiety When used for depression, buproprion is called ___ whereas when it's used for smoking cessation, it's called ___? Withdrawl from opioids results in "drug opposite effects", which include … (list 3)?(6) You see someone who you suspect has alcohol withdrawal. He reports that he had a seizure that started with the arm then the whole body started to shake. Is this evidence of alcohol withdrawal? Seminar: Substance Abuse: A Case-Based Approach __ and ___ characterize mild intoxication with GHB? ___ is a clue that a patient on treatment for alcohol dependence may be relapsing?(3) A 750 cc bottle of wine contains approximately how many standard drinks? An 18 year old patient was brought in by ambulance to the emerg after his friends foundhim unresponsive in an after-hours night club. In the ambulance they gave him O2 and naloxone, to which he didn't respond. In the ER he was unresponsive to deep pain and was noted to have myoclonus and bradycardia and his O2 saturation was 80. After several hours he abruptly woke up, confused but otherwise well. What drug did he overdose on? An ounce contains approximately ___ cc's and a standard drink of wine contains about ___ oz? Another name for Naltrexone is ___? Apart from an inpatient program, list 2 effective treatment plans that you can use for treating problem drinking? For a patient experiencing alcohol withdrawal, which 3 other important questions would you ask on history? GHB can cause severe withdrawal syndrome similar to ___ withdrawal? GHB is a structural analogue and metabolite of ___? GHB overdose at higher doses is characterized by which symptoms (name 3)? GHB overdose is treated with Phenobarbital? Give an example of a long acting benzodiazepines (which, as a group, have been implicated in increasing the risk of falls and hip fractures in seniors)? How effective is smoking cessation counselling? How long does buproprion take to work? If someone has had a coronary event, how long should they wait before using a nicotine patch and gum? If someone is a problem drinker and you'd like to encourage them to recude their rate of drinking, what strategies can you recommend to help patients avoid intoxication (list 5)?(7) If you suspect that a patient has an alcohol problem, which other questions, besides frequency and quantity of drinks per week and screening using the CAGE questionnaire, would you ask? In addition to asking how much a patient drinks on average per week and defining the size of the container of the type of alcohol they drink, which other important question should be asked to quantify alcohol consumption per week? In tracking a problem drinker's progress over time, it may be helpful to order GGT and ___ at baseline and follow-up? In treating alcohol withdrawal, diazepam is a good choice because it (list 3 reasons)?(5) Insomnia and dysphoria may still be experienced for ___ after opioid withdrawal? List what a standard drink is in terms of beer, wine, and liquor? Methadone is an oral opioid ___ with a half-life of __ hours? Methadone is used in the treatment of patients who are physically and psychologically dependent on ___, such as ___ or high doses of other potent opioids such as ___ (just an example of one)? Percocet is a combination of ___ and ___? T/F: even if titrated carefully, methadone still causes drowsiness but this is a tolerated side-effect since it DOES relieve withdrawal and cravings, enabling patients to escape the biological compulsion to continue drug use? T/F: Low Risk Drinking Guidelines recommend 14 standard drinks per week and three drinks MAXIMUM per day for MEN and 9 standard drinks per week and MAXIMUM 1 drink per day for WOMEN? T/F: Most of the cardiovascular benefits of alcohol can be obtained by drinking less than one drink per day and these benefits of reducing mortality from coronary artery disease are seconary to inhibition of platelet function and improvement in the lipid profile? T/F: Naltrexone is a competitive beta-2 adrenergic antantagonist, and has been shown in several Week8 Page 283


T/F: Naltrexone is a competitive beta-2 adrenergic antantagonist, and has been shown in several randomized trials to decrease the intensity and severity of binge drinking in alcohol dependent patients engaged in formal treatment programs? T/F: Naltrexone use reduces alcohol cravings? T/F: Problem drinkers DO experience alcohol withdrawal? T/F: There is NO evidence that inpatient programs are more effective than outpatient in treating binge drinking and alcohol dependence? The 4 main components of methadone treatment are: (4)? The CAGE questionnaire is scored as "positive" if men score higher than ___ out of 4 and women score higher than ___ out of 4? The most common symptom of opioid withdrawal is ___? There is evidence that benzodiazepine use in the elderly increases the risk for â&#x20AC;Ś and the risk of â&#x20AC;Ś? What are the adverse effects of benzo's in the elderly? What are the clinical features of alcohol dependence (list 3)?(5) What are the clinical features of opioid withdrawal (list 2 objective signs and 2 subjective symptoms)? What are the low risk drinking guidelines for men and women (ie. Maximum ___ standard drinks per week, or ___ drinks on any one day for men, â&#x20AC;Ś for women)? What is the definition of "alcohol dependence" (hint: 4 criteria, one of them being a type of dependence)? What is the difference in symptoms experienced between mild intoxication with GHB and intoxication at higher doses? What is the mechanism of action of methadone? What is the mechanism of action of Naltrexone (ReVia) work? What is the time course of opioid withdrawal? Why does Naltrexone use make it easier for patients to practise strategies learned in counselling to control excessive drinking habits?

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00 FMP 2008 Week 9 Intro Material Friday, February 15, 2008

• Complete iterative testing for MCQ FMP2 online • Answer all questions for week objectives 8 and 9 • Create flashcard questions for weeks 8 and 9 lectures and also all past fmp and pbd

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Week 9 Review Questions Thursday, March 06, 2008 5:59 PM

FMP 2008 week 09 review questions

Liver enzyme abnormalities 1. What are the different patterns of liver to injury? 2. What are the elements of “fibrotest”? 3. What are the tests that actually assess liver function? 4. How can liver fibrosis be diagnosed? 5. What liver enzymes can have their level elevated in the setting of hepatitis? 6. What are enzymes of cholestasis? 7. What causes “mild” hepatitis with ALT > AST? Of AST > ALT? 8. What are genetic causes of liver disease, what are the clinical features of each, and how can they be treated? 9. Which causes of viral hepatitis are vaccine-preventable? 10. Which causes of chronic viral hepatitis are treatable? 11. What is non-alcoholic fatty liver? 12. What are 36 drug causes of hepatitis? (just kidding) 13. What is autoimmune hepatitis? 14. What causes severe hepatitis? (What constitutes “severe” in this context?) 15. What causes cholestasis? 16. What is primary sclerosing cholangitis? 17. What is primary biliary cirrhosis? Viral hepatitis 18. What are the 5 major types of viral hepatitis? 19. What are the clinical features and clinical course of hepatitis A? 20. How is hepatitis A transmitted? 21. How is hepatitis A managed? 22. Who should receive the hepatitis A vaccine? 23. How is hepatitis B transmitted? 24. What are clinical features of hepatitis B? 25. How is hepatitis B infection diagnosed? What is the relevance of tests for hepatitis B e antigen and antibody? 26. What are the serologic patterns of infection with hepatitis B that recovers, and that stays chronic? 27. Who should receive hepatitis B vaccine? 28. What are sequelae of chronic viral hepatitis? 29. What are the available treatments for chronic hepatitis B? 30. Who should receive treatment for chronic hepatitis B? 31. How is hepatitis C transmitted? 32. What is natural history of hepatitis C infection? 33. What is treatment of chronic hepatitis C? 34. What is hepatitis D? 35. What is hepatitis E? 36. What is hepatitis G? Esophageal disorders 37. What is dysphagia? 38. What are the major causes of dysphagia? 39. What is a reasonable algorithm for the diagnosis of dysphagia? 40. What is odynophagia? 41. List three treatments for achalasia. 42. What is the mechanism of GE reflux in most cases? 43. How can the diagnosis of reflux be confirmed? 44. What are the major complications of GE reflux? 45. What is esophagitis? 46. What is Barrett’s esophagus? 47. What is the key element of treatment of GE reflux? 48. What is the mechanism of parietal cell acid secretion? 49. List 5 proton pump inhibitors. Dyspepsia and peptic ulcer 50. What is dyspepsia? 51. What is the commonest cause of dyspepsia:

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51. What is the commonest cause of dyspepsia: a. Overall b. That has an organic basis 52. What are other important causes of dyspepsia? 53. What laboratory tests are appropriate for work-up of patients with dyspepsia? 54. What are the two major underlying causes of peptic ulcer disease? 55. What is Zollinger-Ellison syndrome? 56. What are complications of peptic ulcer disease? 57. What is H. Pylori? 58. What are complications of H. pylori? 59. How is H pylori treated? 60. What are the potential effects of NSAIDs on the GI tract? 61. Why do NSAIDs lead to peptic ulcer? 62. What is the best way to diagnose peptic ulcer disease? 63. List four categories of drugs that can heal a peptic ulcer without the use of antibiotics. What is the chief benefit of adding antibiotics to this regimen? Gastrointestinal bleeding 64. What are the major causes of upper GI bleeding? 65. What are three high risk unusual causes of upper GI bleeding? 66. What do the following terms mean? a. Hematemesis b. Melena c. Hematochezia 67. What is the natural history of bleeding due to peptic ulcer disease? 68. What are the prognostic factors related to overall outcome in patients with upper GI bleeding? 69. What is the general mortality rate in patients with upper GI bleeding due to peptic ulcer? 70. What are endoscopic findings that predict an adverse outcome in patients with upper GI bleeding due to peptic ulcer? 71. What are general supportive measures related to management of patients with upper GI bleeding? 72. What are specific therapeutic measures for patients with upper GI bleed due to peptic ulcer? 73. What are indications for surgery in patients with upper GI bleeding? 74. What leads to esophageal varices? 75. What are risk factors for bleeding among patients with esophageal varices? 76. What are adverse prognostic factors for bleeding esophageal varices? 77. What specific therapeutic modalities are available for bleeding varices? 78. What is octreotide? 79. What is TIPS? 80. What are major causes of lower GI bleeding? 81. What are the major investigative modalities available for lower GI bleeding? 82. What is a Meckel’s diverticulum? Acute pancreatitis 83. What are the two major causes of acute pancreatitis? 84. What are the additional important causes of acute pancreatitis? 85. What do patients with acute pancreatitis complain of? 86. What are the major physical findings in a patient with pancreatitis? 87. What laboratory tests are most helpful in the diagnosis of acute pancreatitis? 88. What are other causes of hyperamylasemia? 89. What imaging tests are helpful in diagnosis of acute pancreatitis and its complications? 90. What are the local complications of acute pancreatitis? 91. What are the major elements of treatment? 92. What is the role of endoscopy in the therapy of acute pancreatitis? Diarrhea 93. What causes acute diarrhea? 94. What causes chronic diarrhea? 95. What are major causes of bloody diarrhea? 96. What tests are appropriate in a patient with chronic diarrhea? Inflammatory bowel disease 97. What are the major differences in the histopathology of Crohn’s disease versus ulcerative colitis? 98. What are the locations of Crohn’s disease in the GI tract? 99. How does IBD present? 100. What are intestinal complications of IBD? 101. What are the extraintestinal manifestations of IBD? 102. What items are appropriate to consider in the differential diagnosis of the patient with suspected IBD?

103.

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103. 104. 105. 106. 107. 108. 109. 110. 111. 112. 113.

What factors on history, physical exam and lab testing contribute to the assessment of disease severity in a patient with IBD? What are the major treatment options for patients with Crohnâ&#x20AC;&#x2122;s and those with UC? What is infliximab? What is azathioprine? What is 5-ASA? What are adverse effects of corticosteroids? What is cyclosporine? What is budesonide? What is methotrexate? What are indications for surgery in patients with IBD?

Liver failure What are the pathologic features of cirrhosis? What are the causes of cirrhosis? What are the physical findings of cirrhosis? What are the laboratory test abnormalities seen in patients with cirrhosis? What are the elements of the Child-Pugh-Turcotte prognostic scale? What are the major complications of cirrhosis? What is the pathogenesis of cirrhotic ascites? What are the elements of management of cirrhotic ascites? What is a paracentesis? What are the major indications for liver transplantation? What is fulminant hepatic failure? What are symptoms associated with jaundice, and how do they help to differentiate the causes? What are major differences between Crohnâ&#x20AC;&#x2122;s disease and ulcerative colitis: a. Pathologically b. Clinically c. In terms of treatment 127. What are the major complications of portal hypertension? 128. How is spontaneous bacterial peritonitis: a. Diagnosed b. Treated 129. What are the indications for liver transplantation? 130. What are the clinical features of sclerosing cholangitis? 131. What is the pathogenesis of cirrhotic ascites? 132. What is a TIPS procedure?

114. 115. 116. 117. 118. 119. 120. 121. 122. 123. 124. 125. 126.

GI cancer screening

133. What is appropriate screening for: a. Colon cancer b. Esophageal cancer

Pasted from <https://portal.utoronto.ca/courses/1/Fall-2007-FMP211Y1-Y-LEC0101/content/_913894_1/FMP%202008%20week%2009%20review%20questions.doc? bsession=11327372&amp;bsession_str=session_id=11327372,user_id_pk1=501825,user_id_sos_id_pk2=1,one_time_token=>

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01 WONG 2008 Abnormal Liver Biochemistry and Function Saturday, February 16, 2008 5:55 PM

In the progression of fibrosis, does INR increase first or does Albumin drop first? How do the following factors rise and fall and in which order in the progression of liver fibrosis: Albumin, INR, Platelets, Bilirubin? When do you first start to experience symptoms from the progression of fibrosis (name after which of the following factors rises or falls): bilirubin, platelets, INR, albumin? T/F: Cirrhosis begins to occur soon after the start of symptoms secondary to the drop in platelets?

It takes a long time to get to liver cirrhosis

Not until losing 50-60% of liver that you start to get clinical signs, first platelets, then INR starts going up (by this time start to get sick); after that if ignore INR going up, then albumin drops, then finally at very end, they turn yellow (because of high bilirubin) THIS IS THE END STAGE OF LIVER DISEASE!

• Liver is unique in that there's regeneration • Everyone can donate the right lobe of your liver and within two weeks the right lobe will grow back!

T/F: you can donate the right lobe of your liver and within two weeks, it will grow back?

List 3 investigations you could use to diagnose fibrosis of the liver?

• Liver biopsy is the gold standard in the diagnosis of fibrosis! • Sound waves travel faster in a stiff liver than in a soft liver, called the Fibroscan; THE THING IN Europe now; coming to

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called the Fibroscan; THE THING IN Europe now; coming to Canada soon

Liver biopsy is the gold standard in the diagnosis of fibrosis!

GGT Bilirubin Alpha2 macroglobulin Apolipoprotein A1

Haptoblobulin

Fibrotest vs. Biopsy While primarily about Hyperlipidemia, this article verifies that FibroTest has been validated in chronic Hepatitis c. So, why are doctors still using biopsies??? Screening for Fibrosis with Non-invasive Biomarkers (Fibrotest) in Hyperlipidemic Patients Insulin resistance is a cause of liver disease that can lead to cirrhosis. Hyperlipidemic patients (HP) have multiple insulinresistance factors and frequent abnormal liver function tests. HP should be screened for significant liver fibrosis (bridging fibrosis: early F2, advanced F3, cirrhosis F4) but biopsy is inappropriate because of the high number of patients at risk. The aim of the current study was to use FibroTest, validated in chronic hepatitis C, B, alcoholic and non-alcoholic steatosis, to identify HP with F2F3F4. A consecutive cohort of HP, HCV-HBVneg, <50g alcohol/day, followed in a lipid center was analyzed. Fibrotest was retrospectively performed on frozen fasting sera (–80 C); a control group of blood donors was prospectively included. Fibrotest was performed blinded with security algorithms to identify high-risk of false negative/positive. Results Among 1,542 subjects, 40 (2.59%) were excluded using security algorithms, and 1,502 included: 50.3% female, median age 49yrs,957 HP and 545 controls. Among HP, 83.4% had cholesterol >=200mg/dl, 93.6% LDL-C >=100mg/dl, 17.5% triglycerides >=200mg/dl, 35.9% BMI >=27, 33% arterial hypertension, 31.8% insulinemia >=10mUI/ml and 13.7% glucose >=6mmol/L. GGT or ALT were elevated (>=50 IU/L) in 215 HP (22.5%). F2F3F4 were identified by Fibrotest in 25/957 (2.6%) HP, including 13 F2, 8 F3 and 4 F4 but in none (0%) of the 545 controls (P<0.0001). Among 25 HP with fibrosis, 19 had normal ALT, 14 normal GGT, 12 normal ALT and GGT, 4 elevated ALT and GGT and 9 elevated ALT or GGT. Factors associated (p<0.01) with fibrosis were higher age, BMI, triglycerides, uricemia, and insulinemia. In multivariate logistic regression, including alcohol consumption, insulinemia (P=0.003) and triglycerides (P=0.008) were the most significant risk factors. In HP with triglycerides >=200 mg/dl prevalence of fibrosis was 8.3% and 6.6% with insulinemia >=10mUI/ml. Conclusions Based on these results, the authors conclude, “Screening strategies for liver fibrosis are feasible with biomarkers in high-risk groups such as HP.” “Without such non-invasive strategies a liver biopsy would have been indicated in up to 22.5% of HP with elevated GGT or ALT and would have probably missed half of HP with fibrosis, who had normal GGT and ALT.” Biopredictive Department, Metabolism Unit, Biochemistry Department, Transfusion Unit, and Hepato-Gastroenterology Department,GHPS, Paris, France. 05/02/05 Reference M Munteanu and others. SCREENING FOR SIGNIFICANT FIBROSIS USING NON-INVASIVE BIOMARKERS (FIBROTEST) IN HYPERLIPIDEMIC PATIENTS (HP). Abstract 689. 40th EASL. April 13-17, 2005. Paris, France. Pasted from <http://www.hepatitis-central.com/mt/archives/2005/05/fibrotest_vs_bi.html>

Chronic liver diseases lead to fibrosis which can lead to the portal hypertension, changes in the liver architecture and may produce such an irreversible rearrangement of the circulation as to cause cirrhosis. These liver diseases can cause necrosis, collapse and scar formation which can also lead to fibrosis.

Cirrhosis is the end-stage progression of fibrosis, and is defined as characterized by irreversible scarring of the liver and impaired liver function. Pasted from <http://www.medhelp.org/posts/show/235680>

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What is the gold standard for the diagnosis of fibrosis?


What is the difference between fibrosis and cirrhosis?

Why is ultrasound not a good method for diagnosing mild fibrosis of the liver? Compared to a fibrotic liver, a normal liver will show increased or decreased echogenicity on ultrasound examination?

Fibroscan

A point system known as the Childâ&#x20AC;&#x2122;s-Pugh-Turcotte score (CPT score) has been devised to determine the severity of the cirrhosis. Depending on the total score, a patient is classified as Class A (early cirrhosis) through Class C (advanced cirrhosis).

Child-Pugh-Turcotte Criteria 1 Point

2 Points

3 Points

1. Albumin (g/dl)

>3.5

2.8-3.5

<2.8

2. Bilirubin (mg/dL)

<2

2-3

>3

3. Ascites

None

Minimal

Moderate

4. Encephalo-pathy

None

Grade 1-2 Grade 3-4

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A point system known as the Childâ&#x20AC;&#x2122;s-Pugh-Turcotte score (CPT score) has been devised to determine the severity of ___?


5. PT (sec prolonged) INR

<4 <1.7

4-6 <1.7-2.3

>6 >2.3

Class A: 5-6 points; Class B: 7-9 points; Class C: 10-15 points Pasted from <http://www.hcvadvocate.org/hcsp/articles/Herrera.html>

That was end-stage liver disease; nowadays we can intervene!

http://www.hcvadvocate.org/hcsp/articles/Herrera.html

What is the Child’s-PughTurcotte score used for? List 5 criteria measured to calculate a Child-PughTurcotte score?

List 2 enzymes which are released when the liver is damaged? List 3 potential complications of cirrhosis?(4)

• Surgeons came up with a score; realized back in 1950 that when you operate on someone with liver disease, they usually die on you; came up with 1 to 3 (mildly to highly abnormal) • Even if it wasn't a liver surgery, just the operation itself, with the addition of them having a bad liver, put them in group C at 80% risk of death within 30 days post surgery

• If patient has abnormal blood tests, want to know if have cirrhosis

Name 2 enzymes that are released when hepatocytes are damaged, but which DO NOT correlate with liver function? T/F: Though ALT and AST are markers of liver damage, they HAVE NO correlation with liver function?

ie. "How do we recognize liver injury?"

• Liver enzymes have NOTHING to do with liver function; tell you what's going on • How know if one problem with liver? There are proteins that are predominantly inside liver cells that only get released when there's damage; eg. In times of Hepatitis • Remember, if go out and play vigorous sports, ALT also found in muscle; AST found in cardiac muscle, skeletal muscle, and other tissues; EVEN LESS SENSTITIVE than ALT!

What do ALT and AST stand for? What does SGOT stand for? Which is less sensitive as a marker of liver damage: AST or ALT? Apart from being found in the liver, AST is also found in …(name 3 )? Apart from being found in the liver, ALT is also found in ___? ALT was formerly known as ___?

List 2 enzymes related to cholestasis?

Basically, high levels of ALP correlated with growth spurts; therefore: children/teens and pregnant women! • All the liver enzymes, upper limits of normal are 40 except for ALP (@105) • List of diseases that can cause the enzymes of cholestasis to rise • GGT NOT found in bone or placenta ○ GGT RARELY comes from kidney pancrease intestines prostate • Most blood tests are pretty stable with age except for ALP ○ Eg. Teenagerhigh; when settle down and stop growing, lower levels, at around 100 • Rememeber cholestasis is impaired bile flow

Medical Encyclopedia: ALP URL of this page: http://www.nlm.nih.gov/medlineplus/ency/article/003470.htm Alternative names Alkaline phosphatase Definition Alkaline phosphatase (ALP) is a protein found in all body tissues. Tissues with particularly high amounts of ALP include the liver, bile ducts, and bone. A blood test can be done to measure the level of ALP. See also: ALP isoenzyme test How the test is performed Blood is drawn from a vein, usually from the inside of the elbow or the back of the hand. The site is cleaned with

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The upper limits of the 4 major liver enzymes, GTT, ALP, AST, ALT, are all ___ except for ALP which has an upper limit of 105? AST was formerly known as ___?

Most blood tests are pretty stable with age except for which prominent enzyme related to cholestasis? Cholestasis refers to …? T/F: ALP levels are not stable with age, meaning that a growing teenager will have levels which will vary, and be lower than usual, compared to a non-growing adult? List 2 populations in which high levels of ALP are seen? List 3 other places in the body, apart from the liver, in which GGT is found?


Blood is drawn from a vein, usually from the inside of the elbow or the back of the hand. The site is cleaned with germ-killing medicine (antiseptic). The health care provider wraps an elastic band around your upper arm to apply pressure to the area and make the vein swell with blood. Next, the health care provider gently inserts a needle into the vein. The blood collects into an airtight vial or tube attached to the needle. The elastic band is removed from your arm. Once the blood has been collected, the needle is removed, and the puncture site is covered to stop any bleeding. How to prepare for the test You should not to eat or drink anything for 6 hours before the test, unless otherwise instructed by your doctor. Many drugs affect the level of alkaline phosphatase in the blood. Your health care provider may tell you to stop taking certain drugs before the test. Never stop taking any medicine without first talking to your doctor. • Allopurinol • Antibiotics • Anti-inflammatory medicines • Birth control pills • Certain arthritis drugs • Certain diabetes medicines • Chlorpromazine • Cortisone • Male hormones • Methyldopa • Narcotic pain medicines • Propranolol • Tranquilizers • Tricyclic antidepressants Why the test is performed This test is done to diagnose liver or bone disease, or to see if treatments for those diseases are working. It may be included as part of a routine liver function test. Normal Values The normal range is 44 to 147 IU/L (international units per liter).

GGT is found? T/F: GGT is NOT found in bone? ALP is also, in addition to being found in the liver, is found in ___ and ___? Out of the following enzyme blood tests, which is the LEAST stable with age: AST, ALP, ALT, GGT?

High levels of ALP are normally seen in children undergoing growth spurts and in pregnant women. Normal values may vary slightly from laboratory to laboratory. They also can vary with age and gender.

What abnormal results mean Higher-than-normal ALP levels may be due to: • Anemia • Biliary obstruction • Bone disease • Healing fracture • Hepatitis • Hyperparathyroidism • Leukemia • Liver disease • Osteoblastic bone cancers • Osteomalacia • Paget's disease • Rickets Lower-than-normal ALP levels (hypophosphatasemia) may be due to: • Malnutrition • Protein deficiency Additional conditions under which the test may be performed: • Alcoholic liver disease (hepatitis/cirrhosis) • Alcoholism • Biliary stricture • Giant cell (temporal, cranial) arteritis • Multiple endocrine neoplasia (MEN) II • renal cell carcinoma Update Date: 5/17/2007 Updated by: Benjamin W. Van Voorhees, MD, MPH, Assistant Professor of Medicine, Pediatrics and Psychiatry, The University of Chicago, Chicago, IL. Review provided by VeriMed Healthcare Network. Pasted from <http://www.nlm.nih.gov/medlineplus/print/ency/article/003470.htm>

A cholestatic pattern of liver enzyme abnormality refers mainly to high levels of which two liver enzymes? The diagnosis of viral hepatitis can be made via ___ and ___? T/F: fulminant liver failure is an unfortunate, common event in viral hepatitis?

In mild hepatitis is ALT higher than AST or the other way around? T/F: In mild hepatitis, ALT may be up to ALMOST 5 TIMES higher than AST? T/F: Non-alcoholic Fatty Liver can NEVER cause fulminant liver failure BUT it CAN LEAD TO cirrhosis? With which of the following causes of liver disease is fulminant liver failure possible (may be more than one): viral hepatitis, nonalcoholic fatty liver, medications and toxins, autoimmune hepatitis, alpha-1-antitrypsin deficiency? Vaccines are present against which hepatitis viruses?

ALP, AST, ALT, GGT: Liver Function Enzymes

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viruses? Do the majority or minority of patients with viral hepatitis experience fulminant liver failure? In hepatitis ___ and ___ there is no chronic infection? People diagnosed with metabolic disorder should also be suspected of having which liver disease?

Parenteral: [para- + enteral] not through the alimentary canal but rather by injection through some other route, such as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, or intravenous.

• Infection of liver with a virus that leads to damage; SOMETIMES can lead to cirrhosis

• Fulminant: [L. fulminare to flare up] sudden, severe; occurring suddenly and with great intensity. The first step in the treatment of liver disease secondary to medication use is to …? Cirrhosis secondary to nonalcoholic fatty liver disease develops over: days, weeks, months, years, decades? Onset of liver disease secondary to medications and toxins usually takes ____ (weeks, months, years) but can take up to ___ (weeks, months, years)? What does fulminant mean?

• Terrible disease; no way of making diagnosis short of a liver biopsy • Non-Alcoholic Fatty Liver associated with metabolic syndrome (and high BMI) • NEVER causes fulminant liver failure but IT CAN cause cirrhosis

• Usually get abnormal liver enzymes 1 to 2 months later; some 1 year later • Dose related: isoniazid (INH) and TB

T/F: the biggest culprit of medications causing liver disease are dermatologic medications?

• Biggest culprits are derm medications • People tend to forget about antibiotics; have cold, take penicillin or amoxicillin; • CAN cause fulminant failure • CAN cause cirrhosis but have to take drug for long time

Fulminant is any event or process which occurs suddenly, quickly and is intense and severe to the point of lethality , i.e, it has an explosive character. The word comes from Latin fulmināre, to strike with lightning. It is most used in medicine, and there are several diseases which have this adjective: • Fulminant liver failure • Fulminant colitis • Fulminant pre-eclampsia • Fulminant meningitis • Fulminant hepatic venous thrombosis (Budd-Chiari syndrome) Pasted from <http://en.wikipedia.org/wiki/Fulminant>

DON'T NEED TO Memorize THIS; JUST FYI Does autoimmune hepatitis have a male or female predominance? What is the difference between type 1 and type 2 autoimmune hepatitis? What is a potential treatment for autoimmune hepatitis that can prevent increased liver fibrosis? In autoimmune hepatitis, how long does it take for liver cirrhosis to develop? Hereditary causes of hepatitis tend to present earlier or later in life? Which of the following types of

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DON'T NEED TO Memorize THIS; JUST FYI Does autoimmune hepatitis have a male or female predominance? What is the difference between type 1 and type 2 autoimmune hepatitis? What is a potential treatment for autoimmune hepatitis that can prevent increased liver fibrosis? In autoimmune hepatitis, how long does it take for liver cirrhosis to develop? Hereditary causes of hepatitis tend to present earlier or later in life? Which of the following types of hepatitis does not have a specific diagnostic test: autoimmune hepatitis, hereditary hemochromatosis, alpha1-antitrypsin deficiency, viral hepatitis?

CAN cause fulminant liver failure and/or cirhosis

• Next talking about hereditary (genetic) diseases that are NOT very common but tend to present later in life; CAN'T cause fulminant liver failure but can cause cirrhosis; is age-related • Treatable by getting rid of iron; blood loss! Phlebotomy!

• No specific diagnostic tests for autoimmune hepatitis • Why tell people about this? ○ Not that uncommon ○ CANNOT prevent it because don't know what causes it; probably molecular mimicry

What is the treatment for hereditary hemochromatosis? Why? Apart from cirrhosis, symptoms of hemochromatosis can include…(list 3)? (hint: heart, skin, joints) • Commonest ones in northern europeans ("white" population): hemochromatosis: these people keep on absorbing iron their entire lives • Will cause cirrhosis with NORMAL liver enzymes • MUTATION IS NECESSARY BUT NOT SUFFICIENT; if you have the mutation, not necessarily have the disease; if have the disease, ALMOST CERTAINLY HAVE THE DISEASE!

• Protein misfolded! • VERY RARE!

List 3 non-hepatic sources of mild hepatitis where ALT < AST?

Wilson's Disease

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CAN cause fulminant liver failure and/or cirhosis

• Next talking about hereditary (genetic) diseases that are NOT very common but tend to present later in life; CAN'T cause fulminant liver failure but can cause cirrhosis; is age-related • Treatable by getting rid of iron; blood loss! Phlebotomy!

• No specific diagnostic tests for autoimmune hepatitis • Why tell people about this? ○ Not that uncommon ○ CANNOT prevent it because don't know what causes it; probably molecular mimicry

What is the treatment for hereditary hemochromatosis? Why? Apart from cirrhosis, symptoms of hemochromatosis can include…(list 3)? (hint: heart, skin, joints) • Commonest ones in northern europeans ("white" population): hemochromatosis: these people keep on absorbing iron their entire lives • Will cause cirrhosis with NORMAL liver enzymes • MUTATION IS NECESSARY BUT NOT SUFFICIENT; if you have the mutation, not necessarily have the disease; if have the disease, ALMOST CERTAINLY HAVE THE DISEASE!

• Protein misfolded! • VERY RARE!

List 3 non-hepatic sources of mild hepatitis where ALT < AST?

Wilson's Disease

• KNOW THIS ONE! REALLY RARE but genetic condition of an ATP responsible for transporting copper from one compartment of the cell to another • CAN CAUSE A FORM OF FULMINANT LIVER FAILURE ○ Tends to happen in young; late teenagers, early twenty year olds; NEED A TRANSPLANT RIGHT AWAY IF YOU RECOGNIZE THIS; it is actually treatable ○ SERUM COPPER is high in this ○ Usual trick: it's in the young; they usually already have cirrhosis; ○ SO  Hemolysis  Liver disease  Young □ = liver disease (secondary to WILSON'S DISEASE)

• IF AST higher than ALT, then indicates cirrhosis • Someone with hemolysis, muscle breakdown (myopathy, MI, muslce disease, etc., AST will be high; very non-specific)

• Kayser-Fleischer ring, a golden brown or green discoloration at the level of Descemet's membrane in the limbic region of the cornea, seen in Wilson's disease and other liver disorders.

ALCOHOL

Kayser-Flescher rings occur where? Kayser-Flescher rings are pathognomonic of which disease? Tetrathiomolibdate, Trientene, zinc, and penicillamine are all potential treatments for which disease? Since there is rapid deompensation in young Wilson's disease patients with cirrhosis, they should get an immediate ___?

Kayser-Fleischer ring in Wilson's disease.

○ Diagnosis is tricky because people don't answer truthfully; don't ask "do you drink" but rather "what do you drink"?! ○ How does it present?: urine eventually becomes very dark colour; start looking jaundiced; cycle of bouts of alcoholic hepatitis and jaundice and cold turkey, BUT THEY DON'T GET BETTER;

T/F: Alcoholic liver disease causes cirrhosis over the course of weeks and months instead of years/decades?

Mild hepatitis refers to

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○ Diagnosis is tricky because people don't answer truthfully; don't ask "do you drink" but rather "what do you drink"?! ○ How does it present?: urine eventually becomes very dark colour; start looking jaundiced; cycle of bouts of alcoholic hepatitis and jaundice and cold turkey, BUT THEY DON'T GET BETTER;

T/F: Alcoholic liver disease causes cirrhosis over the course of weeks and months instead of years/decades?

Mild hepatitis refers to ALT and/or AST being less than ___ x the limit of normal whereas severe hepatitits is defined as ALT and AST levels up to ___x the level of normal? List 6 causes of ACUTE, SEVERE hepatitis?

Eg. Case: Patient presents to emerg:  Drinker, repeated bouts of feeling unwell; when gets severe, RUQ pain, increase in neutrophils, WBC □ Will go down when stop drinking • Potentially treatable when sick; can give steroids • Alcoholic liver disease: CAN cause cirrhosis

What is a potential treatment for hepatitis secondary to chronic alcohol consumption?

What may be the cause of itchy skin in cholestasis?

• Memorize causes in yellow: causes of acute severe hepatitis! • Note alcohol NOT on the list; it's not the primary culprit if enzymes are really high; something else going on! JUST FYI; DON'T NEED TO MEMORIZE THIS

• In general, if ALP up alone, not the liver, but if both up, then likely the liver!

Gilbert's Sy ndrome: Jaundice typically appears during times of: ex ertion, stress, not eating, and infection. Pasted from <http://health.nytimes.com/health/guides/disease/gilberts -disease/overview.html>

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A patient's skin turns yellow in times of stress. The likely diagnosis is ___? Gilbert's syndrome is due to not being able to get rid of ___ efficiently? Gilbert's syndrome is a common cause of (choose one): isolated hyperbilirubinemia, autoimmune hepatitis, Kayser-Fleischer rings, liver cirrhosis, OR primary biliary cirrhosis ?

List 3 common causes of cholestasis?


List 3 hepatobiliary causes of elevated ALP? What is primary sclerosing cholangitis? Primary sclerosing cholangitisis diagnosed through ___? (Remember ALP released ma i nly 3rd tri mester placenta)

Primary Sclerosing Cholangitis (PSC)

Pasted from <http://www.clevelandclinic.org/health/health-info/docs/4100/4150.asp?index=13316&src=newsp>

In primary sclerosing cholangitis (PSC), the bile ducts inside and outside the liver become inflamed and scarred. As the scarring increases, the ducts become blocked. The ducts are important because they carry bile out of the liver. Bile is a liquid that helps break down fat in food. If the ducts are blocked, bile builds up in the liver and damages liver cells. Eventually, PSC can cause liver failure. Researchers do not know what causes PSC. Among the theories under investigation are the possible role of bacteria, viruses, and immune

system problems. PSC appears to be associated with ulcerative colitis, a type of inflammatory bowel disease. The disease usually begins between ages 30 and 60, but the disease can also arise during childhood. PSC is more common in men than women. PSC progresses slowly, so a person can have the disease for years before symptoms develop. The

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than women. PSC progresses slowly, so a person can have the disease for years before symptoms develop. The main symptoms are itching, fatigue, and jaundice, which causes yellowing of the eyes or skin. An infection in the bile ducts can cause chills and fever.

PSC is diagnosed through cholangiography, which involves injecting dye into the bile ducts and taking an x ray. Cholangiography can be performed as an endoscopic procedure (endoscopic retrograde cholangiopancreatography, ERCP), through radiology or surgery, or with magnetic resonance imaging (MRI) scans. Treatment includes medication to relieve itching, antibiotics to treat infections, and vitamin supplements, as people with PSC are often deficient in vitamins A, D, and K. In some cases, surgery to open major blockages in the common bile duct is also necessary. Liver transplantation may be an option if the liver begins to fail. Pasted from <http://digestive.niddk.nih.gov/ddiseases/pubs/primarysclerosingcholangitis/>

Primary biliary cirrhosis (PBC)

Primary biliary cirrhosis causes inflammation and scarring that destroy the small ducts within the liver, slowing and sometimes blocking the normal flow of bile, which is necessary for digestion.

Pasted from <http://www.mayoclinic.com/popupnowrap.cfm?objectid=A4E1A07F-2A5D-9994-E401906607352167&method=display_full>

Introduction Primary biliary cirrhosis is a disease in which the bile ducts in your liver are slowly destroyed. In primary biliary cirrhosis, the destruction of your bile ducts can cause harmful substances to build up in your liver and sometimes lead to irreversible scarring of liver tissue (cirrhosis). The cause of primary biliary cirrhosis remains unclear. Many experts consider primary biliary cirrhosis an autoimmune disease in which the body turns against its own cells, although it's likely that genetic and environmental factors also play a part. Primary biliary cirrhosis develops slowly. Medication can slow the progression of the disease, especially if treatment begins early.

Signs and symptoms Early-stage Although some people with primary biliary cirrhosis remain symptom-free for years after they're diagnosed, others experience fatigue, itching, dry eyes and dry mouth early in the disease: • Fatigue. This is the most common symptom of primary biliary cirrhosis. In general, energy levels are normal in the morning, but fall later in the day and don't improve with rest. Doctors haven't found any correlation between the degree of exhaustion and the severity of the illness. This means that people with mild primary biliary cirrhosis and those with more serious disease may be equally fatigued. • Itching. Another common symptom, itching (pruritis), is often most bothersome over your legs, arms and back. The severity of itching may change, often becoming worse at night and improving during the day. Nighttime itching can disturb sleep, making fatigue worse and sometimes leading to depression. The cause of this severe itching isn't clear. • Dry eyes and mouth (sicca syndrome). Sicca syndrome often occurs in people with other autoimmune disorders. It causes inflammation in the moisture-secreting glands of the eyes and mouth, resulting in the decreased production of tears and saliva. This can lead to difficulty swallowing, light sensitivity and corneal ulcers. Later stage As the destruction of bile duct and liver cells progresses, other signs and symptoms may develop, such as: • Jaundice. A common sign of advanced liver disease, jaundice turns your skin and the whites of your eyes yellow. The discoloration is due to high blood levels of bilirubin, a byproduct of the breakdown of the hemoglobin from old or damaged red blood cells. Normally, bile carries bilirubin out of the liver so that it can be excreted from your body. But as more bile ducts are destroyed and the flow of bile slows, bilirubin begins to build up in the blood and eventually becomes visible in your skin and eyes. • Hyperpigmentation. Inadequate bile flow increases the production of the skin pigment melanin. This causes your skin to become darker, even in areas that aren't exposed to the sun. Sometimes the deeper color isn't uniform, and your skin appears blotchy. • Swollen feet (edema) and abdomen (ascites). As liver damage progresses, your body begins to retain salt and fluids. At first, the excess water accumulates mainly in your feet and ankles, which tend to become more swollen late in the day. In time, fluid can also collect in your abdomen. • Cholesterol deposits (xanthomas). Your body uses bile as the main way of eliminating excess cholesterol. When disease interferes with this process, the amount of cholesterol in the blood increases. This can lead to the formation of fatty deposits in the skin around the eyes, the eyelids, or in the creases in the palms, soles, elbows, knees or buttocks. These raised, waxy growths usually don't appear until blood cholesterol reaches very high levels. Even then, not everyone with primary biliary cirrhosis develops them. • Digestive problems. Because bile is essential for the digestion and absorption of fats, primary biliary cirrhosis can cause intestinal problems. These include diarrhea and steatorrhea — greasy, badsmelling stools that result from poor fat digestion. Urinary tract infections. About one in five women with primary biliary cirrhosis experiences recurring

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smelling stools that result from poor fat digestion. Urinary tract infections. About one in five women with primary biliary cirrhosis experiences recurring urinary tract infections. The relationship between these infections and bile duct destruction isn't well understood. A few studies suggest that the same bacteria responsible for urinary tract infections may play a role in some cases of primary biliary cirrhosis.

Causes The exact cause of primary biliary cirrhosis isn't known, but it appears to be an immune system disorder that slowly destroys the bile ducts in your liver. Genetics and the environment also may play a role in this disease.

Risk factors The following factors may increase the risk of primary biliary cirrhosis: • Your sex. More than 90 percent of people with primary biliary cirrhosis are women. Immune system disorders in general affect far more women than men, but the reason for this isn't known. • Your age. Most people diagnosed with primary biliary cirrhosis are 35 to 60 years old. Although older adults can develop the disease, it is rare in children. • Family history. Primary biliary cirrhosis isn't hereditary, but having a family member with the disease increases your risk.

Screening and diagnosis Common tests Many people with primary biliary cirrhosis have no symptoms of the disease when they're diagnosed. Instead, doctors often become aware of a problem during routine blood tests or an evaluation for another condition. Several tests can help diagnose primary biliary cirrhosis, including: • Liver function tests. These blood tests check the levels of enzymes that may indicate liver disease in general and bile duct injury in particular. Certain liver enzymes are elevated in most people with primary biliary cirrhosis, especially alkaline phosphatase, which is produced in the bile ducts. • Ultrasound imaging. This noninvasive test uses high-frequency sound waves to create precise images of structures within the body, including the bile ducts. It's sometimes used to rule out other causes of bile flow blockage, such as gallstones or tumors. • Anti-mitochondrial antibodies (AMAs). Found in every cell, mitochondria are the prime energy producers of the body. Antibodies are proteins in the blood that help destroy bacteria and other harmful pathogens. Most people with primary biliary cirrhosis have anti-mitochondrial antibodies — antibodies that target enzymes in the mitochondria. These antibodies almost never occur in people who don't have primary biliary cirrhosis, even if they have other liver disorders. For that reason, a positive AMA test is considered a very reliable indicator of the disease. At the same time, a small percentage of people with primary biliary cirrhosis don't have AMAs. False-positive tests, which indicate a problem where none exists, also can occur. Because an AMA test isn't entirely foolproof, doctors usually perform a liver biopsy, which can definitively confirm the presence or absence of the disease. • Liver biopsy. In this test, a small sample of liver tissue (biopsy) is removed and examined in a laboratory, either to confirm the diagnosis or to determine the extent (stage) of the disease. Doctors withdraw the tissue through a small incision using a thin needle. Doctors may take more liver biopsies as time goes on to check the progression of the disease. • Magnetic resonance elastography (MRE). This relatively new test can help your doctor diagnose primary biliary cirrhosis and may help avoid the need for liver biopsy, which is more invasive. MRE technology works by combining traditional magnetic resonance imaging (MRI) with low-frequency sounds waves. The MRI component uses a magnetic field and radio waves to create clear and detailed cross-sectional images of your body, which show size and structure of your tissues and organs. The low-frequency sound waves then help reveal physical properties of those tissues and organs — such as tissue stiffness. Stiffness of your liver may indicate cirrhosis.

Complications As liver damage progresses, people with primary biliary cirrhosis may develop a number of serious problems, including: • Cirrhosis. The term "primary biliary cirrhosis" isn't entirely accurate because cirrhosis develops only in the last stages of the disease — often many years after diagnosis. Yet when it does occur, cirrhosis can be life-threatening because it interferes with the liver's ability to carry out essential functions. Cases of primary biliary cirrhosis are divided into four stages. The first stage — inflammation of the bile ducts — is the least serious, and stage 4 — cirrhosis — the most serious. Ongoing cirrhosis can lead to liver failure, which occurs when the liver is no longer able to function. • Increased pressure in the portal vein (portal hypertension). Blood from your intestine, spleen and pancreas enters your liver through a large blood vessel called the portal vein. Under normal circumstances, the pressure in this vein is considerably lower than the pressure in the arteries. But when scar tissue blocks normal circulation through the liver, blood backs up, much like water behind a dam, leading to increased pressure within the vein. And because blood doesn't flow normally through the liver, hormones, drugs and other toxins aren't filtered properly before entering the bloodstream. • Enlarged veins (varices). When circulation through the portal vein is slowed or blocked, blood may back up into other veins — mainly those in your stomach and esophagus. Sometimes veins also form around your navel and at the rectum. The blood vessels are thin walled, and increased pressure in the veins can cause bleeding in the upper stomach or esophagus. This is a life-threatening emergency that requires immediate medical care. • Liver cancer. The destruction of healthy liver tissue that occurs in cirrhosis greatly increases the risk of liver cancer, primarily hepatocellular carcinoma, which affects the hepatocytes, the main type of liver cell. • Weak bones (osteoporosis). Liver scarring interferes with the liver's ability to process vitamin D and calcium, both of which are essential for bone growth and health. As a result, weak, brittle bones and bone loss may be complications of late-stage primary biliary cirrhosis, and your doctor may order a bone density test to look for osteoporosis. • Vitamin deficiencies. A lack of bile affects the absorption of fats and of the fat-soluble vitamins A, D, E and K. This sometimes leads to deficiencies of these vitamins in advanced cases of primary biliary cirrhosis. Other complications In addition to bile duct and liver damage, people with primary biliary cirrhosis are likely to have other metabolic or immune system disorders, including:

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Thyroid disease. Thyroid problems not only are common in people with primary biliary cirrhosis, but often appear long before the bile duct damage is diagnosed. • CREST syndrome. This immune system disorder is a subset of scleroderma, a disease that leads to thickening, tightening and hardening of connective tissue. CREST syndrome can affect many body systems, including the blood vessels and esophagus, and sometimes the digestive tract, lungs and heart. People with primary biliary cirrhosis are more likely to have some, rather than all, of the signs and symptoms of CREST. • Raynaud's phenomenon. One of the components of CREST, this disorder is common in people with primary biliary cirrhosis. It occurs when small blood vessels (capillaries) spasm in response to cold or emotional stress, blocking the flow of blood. Although not everyone with Raynaud's experiences the same signs and symptoms during an attack, the areas of affected skin generally turn white before becoming blue, cold and numb. When circulation improves, the skin usually reddens and may throb or tingle. Attacks of Raynaud's may last from a few minutes to several hours and tend to become worse over time. • Rheumatoid arthritis. Some people with primary biliary cirrhosis have the aching joints that typify rheumatoid arthritis, another autoimmune disorder. Other people may have markers for rheumatoid arthritis in their blood but no signs or symptoms of the disease. •

Pasted from <http://www.mayoclinic.com/print/primary-biliary-cirrhosis/DS00604/METHOD=print&DSECTION=all>

Amyloidosis Introduction Amyloidosis is a rare and potentially fatal disease that occurs when substances called amyloid proteins build up in your organs. Amyloid is an abnormal protein usually produced by cells in your bone marrow that can be deposited in any tissue or organ. Amyloidosis can affect different organs in different people, and there are many types of amyloid. Amyloidosis frequently affects the heart, kidneys, liver, spleen, nervous system and gastrointestinal tract. The exact cause of amyloidosis is unknown, and there's no cure for amyloidosis. However, therapies are available to help you manage your symptoms and limit the production of amyloid protein.

Signs and symptoms

Purpura Around The Eyes

Some people with amyloidosis experience purpura — a condition where small blood vessels leak into the skin, causing purplish patches.

Enlarged Tongue An enlarged tongue (macroglossia) can be a sign of amyloidosis.

Pasted from <http://www.mayoclinic.com/print/amyloidosis/DS00431/METHOD=print&DSECTION=all>

Cholecystitis and Cholangitis • CHOLECYSTITIS: Infection or inflammation of the gallbladder, which collects and concentrates bile from the liver (Cholecystitis). • CHOLANGITIS: Infection or inflammation of the ducts that drain bile from the liver to the gallbladder (cholangitis). Pasted from <http://www.rxmed.com/b.main/b1.illness/b1.1.illnesses/cholecystitis_and_cholangitis.html>

Primary sclerosing cholangitis has a

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cholangitis has a (male/female) predominance while primary biliary cirrhosis has a (male/female) predominance? Which has a predominantly FEMALE predominance: Primary Biliary Cirrhosis OR Primary Sclerosing Cholangitis? Primary Sclerosing Cholangitis is associated with ___?

NEITHER PSC OR PBC lead to fulminant liver failure(also, both 10-20 year cirrhosis, neither prevenable)

ERCP and MRCP - When and Why

In both primary sclerosing cholangitis AND primary biliary cirrhosis, how long does it take, approximately, for liver cirrhosis to develop? Can EITHER primary sclerosing cholangitis OR primary biliary cirrhosis lead to fulminant liver failure? The progression of primary biliary cirrhosis is retarded through the use of ___?

• Not preventable because we have no idea what causes it!

• Just be aware meds can do this; JUST FOR REFERENCE!; don't have to memorize!

KNOW CAUSES OF SEVERE HEPATITIS • BE AWARE of liver function tests: INR, Albumin, Bilirubin: DO NOT tell you about the liver!

Out of the four enzymes below, which 2 would you test to further investigate hepatitis and which two for cholestasis: ALP, AST, ALT, GGT?

Eg. Can have Hep C but also hemochromatosis

• When see hepatitis: Fatty liver, alcohol, fatty liver from obese

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Name an uncommon cause of liver disease which, if caught, is very important to treat right away as it may be acutely fatal? List 3 biochemical disorders that are uncommon but important to know about in having a differential for liver disease? How do AST, ALT, and ALP levels manifest in hepatitis? How do AST, ALT, and ALP levels manifest in hepatitis? How do AST, ALT, and ALP levels manifest in cholestasis? How do AST, ALT, and ALP levels manifest in hepatitis List 3 medication classes that are associated with cholestasis?(5)

â&#x20AC;˘ Fluphenazine: the 2-trifluromethyl derivative of perphenazine, the most potent of the phenothiazine antipsychotic agents. â&#x20AC;˘ Imipramine: a tricyclic antidepressant of the dibenzazepine class, the first of the tricyclic antidepressants to be used.

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Alkaline Phosphatase and Gamma Glutamyltransferase Monday, March 31, 2008

David H. Vroon Zafar Israili Alkaline Phosphatase Definition Alkaline phosphatase (ALP) refers to a group of phosphomonoesterases that hydrolyze phosphate esters with optimum in vitro activity at a pH of 10. Enzyme activity is expressed in international units (IU), the amount of enzyme that catalyzes the conversion of 1 Îźmole of substrate per minute. Reference ranges vary widely with methodology; the most commonly used method produces a reference range of 35 to 125 IU per liter in an adult population. Intraindividual variation in ALP activity has been shown to vary considerably less than the interindividual variation included in reference ranges. Therefore comparison with preestablished values by the same method in an individual may be the most useful reference.

Technique Numerous methods utilizing different substrates and reaction conditions have been applied to measurement of ALP activity. The heterogeneity of methods presents problems with comparing results from different laboratories and often compromises the current application of data previously reported in the literature. Recent methodologic changes have emphasized the need for standardization and optimization of the assay. Readily hydrolyzed, self-indicating substrates that permit continuous monitoring under optimized reaction conditions are now preferred. Earlier methods (Bodansky, King, and Armstrong), which involved indirect quantitation of reaction products, are obsolete. The most widely used reference method utilizes 4-nitro-phenyl phosphate, a readily hydrolyzed, self-indicating ALP substrate introduced in 1946 by Bessey, Lowry, and Brock. The reaction rate is enhanced by removal of inhibitory phosphate and optimizing divalent cation (magnesium and zinc) concentrations.

Serum is the specimen of choice, although heparinized plasma can be used. Chelating anticoagulants, which remove the activator magnesium, are unacceptable. Since hemoglobin may interfere spectrophotometrically, in vitro hemolysis should be avoided. Assay within 4 hours of specimen colection is recommended; frozen specimens should be kept at room temperature for 12 hours prior to assay to assure complete enzyme reactivation. Basic Science Most human tissues contain ALP; kidney, liver, bone, intestine, reticuloendothelial tissue, and placenta are particularly rich sources. Enzymes derived from different tissues share catalytic properties, but differ in their chemical and physical characteristics. Three genetically determined forms have been described: intestinal, placental, and liver/bone/kidney/reticuloendothelial. Different molecular properties within these isoenzyme groups are probably the result of posttranslational modifications. Various methods have been used to separate organ-specific isoforms. None are entirely satisfactory, particularly in quantifying components of the liver/bone isoenzyme group. ALP activity in normal adult serum is derived predominantly from hepatic, osseous, and Week9 Page 24


ALP activity in normal adult serum is derived predominantly from hepatic, osseous, and reticuloendothelial sources. Physiologic bone growth in children increases serum activity to 2 to 5 times the levels observed in adults. Placental ALP causes 2-to 3-fold elevations during the second and third trimesters of normal pregnancy. Serum enrichment by intestinal isoenzyme may cause postprandial elevation, particularly in individuals with blood groups B or O who are also secretors of ABH blood group substance. A number of functions have been proposed. The location of hepatic ALP on the sinusoid membrane suggests involvement in transport function. Increased ALP synthesis is observed during cholestasis with increased bile acid concentration caused by intrahepatic or extrahepatic obstruction of the biliary tree. Bone ALP is probably involved with calcification, perhaps by hydrolyzing pyrophosphate, which inhibits mineralization. In hypophosphatasia, an inherited disorder with virtual absence of the bone ALP isoenzyme, there is histochemical evidence for deficient bone calcification. The intestinal isoenzyme appears to function in the transport of fatty acids, calcium, and phosphate. Clinical Significance The majority of sustained elevated ALP levels are associated with disorders of the liver or bone, or both. Therefore, these organ systems are of prime consideration in the differential diagnosis. A variety of primary and secondary hepatic conditions may be associated with elevated serum ALP levels. Since production is increased in response to cholestasis, serum ALP activity provides a sensitive indicator of obstructive and space-occupying lesions of the liver. The latter includes neoplastic (primary or metastic) and infiltrative diseases (granulomatous hepatitis). Bilirubin excretion is compromised only with extensive biliary obstruction or diffuse hepatic cell disruption; therefore, differential elevation of ALP relative to serum bilirubin provides an early indicator for obstructive or space-occupying conditions. Hepatic cell lesions are manifested by hyperbilirubinemia and dominant serum elevation of parenchymal enzymes, such as aminotransferases; ALP elevations may be only minimal. Diseases of bone associated with increased serum ALP are restricted to the presence of osteoblastic activity. Elevations are generally detectable prior to roentgenographic abnormalities. Neoplasms involving bone may be associated with marked serum elevations when lesions incite osteoblastic reaction, such as metastatic adenocarcinoma of the prostate. Conversely, osteolytic lesions such as occur within multiple myeloma are not associated with increased serum ALP activity. Metabolic bone diseases usually associated with serum enrichment by the bone isoenzyme include rickets, osteomalacia, and Paget's disease. Levels are usually normal in osteoporosis. Increased serum activity may be observed after bone fractures, rising after 1 week and persisting for up to 3 months. Elevated serum ALP occurring with neoplastic disease may be due to hepatic metastases, bone metastases, or direct contribution by neoplastic cells. Isoenzymes with physicochemical characteristics similar to the placental isoenzyme have been attributed to ectopic production by a variety of neoplasms; this apparently represents derepression of normally repressed fetoplacental genes. Clinically obscure elevations of ALP are commonly observed when multitest biochemical panels are performed on hospital populations. Because of the cellular distribution of ALP, increased serum activity may be caused by a wide variety of disorders involving multiple organs. Attempts to define organ source by isoenzyme study may be met with limited success because of technical limitations; accurate measurement of different isoenzymes contributing to total serum ALP activity is not currently possible. However, the presence of the intestinal or placental isoenzyme may be revealed by selected methods. Evaluation of an unexpectedly increased ALP should include the following: 1. Exclude physiologic causes. Is the patient pregnant or an actively growing child? Week9 Page 25


1. Exclude physiologic causes. Is the patient pregnant or an actively growing child? 2. Observe for the presence of clinical or biochemical clues to the origin of increased enzyme activity. Increased serum bilirubin or aminotransferase (either aspartate or alanine) activity suggests hepatic rather than bone origin. Disproportionate elevation of lactic dehydrogenase (LDH) relative to transaminase usually suggests nonhepatobiliary or multiorgan system disease. The association of elevated LDH, hypercalcemia, and hyperuricemia suggests metastastic neoplastic disease. 3. Is the elevation transient such as observed in various tissue reparative processes, healing bone fractures, or passive congestion of the liver? 4. Measurement of other enzymes such as 5â&#x20AC;˛-nucleotidase or gamma-glutamyltransferase may assist with identifying the hepatobiliary system as a source of elevated ALP since these enzymes are not significantly present in bone. 5â&#x20AC;˛-Nucleotidase is a highly specific but less sensitive indicator of hepatobiliary disease. Gamma glutamyltransferase is more sensitive; however, with the exception of its absence in bone and placenta, it is a less specific indicator of hepatobiliary disease than ALP. Gamma Glutamyltransferase

Definition Gamma glutamyltransferase (GGT) is one of a broad group of enzymes that catalyze the transfer of amino acids from one peptide to another amino acid or peptide. This enzyme is sometimes referred to as a "transpeptidase" but is more appropriately included in the amino acid transferase group. Specifically it catalyzes the transfer of a gamma glutamyl group to another acceptor. The reference range with most commonly used methods is 0 to 50 IU/L in males and 0 to 30 IU/L in females. Higher activity in males is probably caused by high enzyme concentration in prostatic tissue. Technique Self-indicating substrates with continuous reaction monitoring are preferred. Most commonly gamma-glutamyl-para-nitroanilide is used as substrate and glyclyglycine as acceptor. The substrate residue, para-nitroaniline, is directly measured by absorbance at 405 nm. The recently proposed reference method utilizes a carboxyl derivative of gamma-glutamyl-para-nitroanilide to enhance substrate solubility; higher levels of activity are observed with this substrate derivative. However, most laboratories use the unsubstituted substrate because of established clinical and laboratory experience. Serum is the specimen of choice; hemoglobin may interfere spectrophotometrically and hemolysis should be avoided. EDTA plasma is acceptable; other anticoagulants such as heparin, citrate, or oxalate may interfere with the reaction. Basic Science High concentrations of GGT are found in renal, prostatic, pancreatic, and hepatobiliary tissue; smaller amounts are found in all other tissues except muscle. A number of physiologic functions have been suggested. Involvement in amino acid transport and glutathione metabolism are most strongly indicated. Enzyme activity observed in serum is electrophoretically heterogeneous; however, true isoenzyme forms have not been defined, and fractionation has no clinical significance. Clinical Significance Hepatobiliary disease is the predominant source of increased serum GGT activity. Increases are associated with all forms of primary and secondary hepatobiliary disorders. Elevations are

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moderate (2 to 5 times reference) with diffuse hepatic cell injury due to toxic or infectious hepatitis. Cholestasis due to intrahepatic or extrahepatic biliary obstruction causes higher serum levels (5 to 30 times reference). Increases occur earlier and persist longer than ALP in cholestatic disorders. Since skeletal disease is not associated with increased serum activity, measurement of GGT is of clinical value in identifying the source of obscure ALP elevations. Levels in children after age 1 year and healthy pregnant women are within the usual adult reference range. Elevated serum levels of GGT are also found in alcoholics and patients receiving certain drugs, such as phenytoin or phenobarbital. This is probably the result of microsomal induction of enzyme activity. Serum measurement can be used to monitor alcoholic patients during therapy; abstinence from alcohol is associated with decrease in serum GGT activity. In addition, alcoholinduced hepatic cell injury may cause significantly higher serum levels than other causes of parenchymal disorders. Elevated GGT activity also occurs in patients with acute and chronic pancreatitis. Prostatic adenocarcinoma may be associated with increased serum levels. Therefore, although increases are absent with skeletal diseases, GGT activity should not be considered a highly specific indicator of hepatobiliary disease. References

Kaplan MM. Alkaline phosphatase. Gastroenterology 1972; 62: 452-68. (PubMed) Rosalki SB. Gamma-glutamyl transpeptidase. Adv Clin Chem 1975; 17: 53-107. (PubMed)

Wolf PL. Clinical significance of an increased or decreased serum alkaline phosphatase level. Arch Pathol Lab Med 1978; 102: 497-501. (PubMed) Pasted from <http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=cm.chapter.3148 >

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GGT Sunday, February 17, 2008 1:35 PM

Gamma-glutamyl transpeptidase Contents of this page: • Alternative Names • Why the Test is Performed • Definition • Normal Results • How the Test is Performed • What Abnormal Results Mean • How to Prepare for the Test • Risks • How the Test Will Feel • Considerations Alternative Names Gamma-GT; GGTP; GGT Definition Return to top Gamma-glutamyl transpeptidase is a test to measure the amount of the enzyme GGT in the blood. How the Test is Performed Return to top Blood is drawn from a vein on the inside of the elbow or the back of the hand. The puncture site is cleaned with antiseptic, and an elastic band is placed around the upper arm to apply pressure and restrict blood flow through the vein. This causes veins below the band to fill with blood. A needle is inserted into the vein, and the blood is collected in an air-tight vial or a syringe. During the procedure, the band is removed to restore circulation (blood flow). Once the blood has been collected, the needle is removed, and the puncture site is covered to stop any bleeding. For an infant or young child: The area is cleansed with antiseptic and punctured with a sharp needle or a lancet. The blood may be collected in a pipette (small glass tube), on a slide, onto a test strip, or into a small container. Cotton or a bandage may be applied to the puncture site if there is any continued bleeding. How to Prepare for the Test Return to top The health care provider may advise you to stop taking any drugs that can affect the test (see Special Considerations). For infants and children: The preparation you can provide for this test depends on your child's age and experience. For specific information regarding how you can prepare your child, see the following: • Infant test or procedure preparation (birth to 1 year) • Toddler test or procedure preparation (1 to 3 years) • Preschooler test or procedure preparation (3 to 6 years) • School age test or procedure preparation (6 to 12 years) • Adolescent test or procedure preparation (12 to 18 years) How the Test Will Feel Return to top When the needle is inserted to draw blood, some people feel moderate pain, while others feel only a prick or stinging sensation. Afterward, there may be some throbbing. Why the Test is Performed Return to top This test is used to detect diseases of the liver, bile ducts, and kidney. It is also used to differentiate liver or bile duct disorders from bone disease. GGT participates in the transfer of amino acids across the cell membrane, and in glutathione (an anti-oxidant) metabolism. High concentrations of GGT are found in the liver, bile ducts, and the kidney. GGT is measured in combination with other tests. In particular, the enzyme ALP is increased in liver and bile duct disease as well as in bone disease. GGT is elevated in liver and bile duct

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disease, but not in bone disease. So, a patient with an elevated ALP and a normal GGT probably has bone disease, not liver or bile ducts disease. Normal Results Return to top The normal range is 0 to 51 IU/L. Note: IU/L = international units per liter What Abnormal Results Mean Return to top Greater-than-normal levels of GGT may indicate: • Congestive heart failure • Cholestasis (congestion of the bile ducts) • Cirrhosis • Hepatitis • Liver ischemia (blood flow deficiency) • Liver necrosis • Liver tumor • Use of hepatotoxic drugs (drugs toxic to liver) Risks Return to top • Excessive bleeding • Fainting or feeling light-headed • Hematoma (bleeding under the skin) • Infection (a slight risk any time the skin is broken) • Multiple punctures to locate veins Considerations Return to top Drugs that can increase GGT levels include alcohol, phenytoin, and phenobarbital. Drugs that can decrease GGT levels include clofibrate and oral contraceptives (birth control pills). Veins and arteries vary in size from one patient to another and from one side of the body to the other. Obtaining a blood sample from some people may be more difficult than from others. Update Date: 1/22/2007 Pasted from <http://www.nlm.nih.gov/medlineplus/ency/article/003458.htm >

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Bilirubin Sunday, February 17, 2008 1:41 PM

Bilirubin Contents of this page: • Illustrations • Alternative Names • Definition • How the Test is Performed • How to Prepare for the Test

• Why the Test is Performed • Normal Results • What Abnormal Results Mean • Considerations

Illustrations

Blood test Alternative Names Return to top Total bilirubin; Unconjugated bilirubin; Indirect bilirubin; Conjugated bilirubin; Direct bilirubin Definition Return to top Bilirubin is a product that results from the breakdown of hemoglobin. Total and direct bilirubin are usually measured to screen for or to monitor liver or gallbladder problems. How the Test is Performed Return to top Blood is drawn from a vein (venipuncture) or capillary. The laboratory technician spins the blood in a centrifuge to separate the serum (liquid part) from the cells. The bilirubin test is done on the serum. How to Prepare for the Test Return to top Fast for at least 4 hours before the test. Your health care provider may instruct you to stop taking drugs that affect the test. Drugs that can increase bilirubin measurements include allopurinol, anabolic steroids, some antibiotics, antimalaria medications, azathioprine, chlorpropamide, cholinergics, codeine, diuretics, epinephrine, meperidine, methotrexate, methyldopa, MAO inhibitors, morphine, nicotinic acid, oral contraceptives, phenothiazines, quinidine, rifampin, salicylates, steroids, sulfonamides, and theophylline. Drugs that can decrease bilirubin measurements include barbiturates, caffeine, penicillin, and high-dose salicylates. Why the Test is Performed Return to top This test is useful in determining if a patient has liver disease or a blocked bile duct. Bilirubin metabolism begins with the breakdown of red blood cells. Red blood cells contain hemoglobin, which is broken down to heme and globin. Heme is converted to bilirubin, which is then carried by albumin in the blood to the liver. In the liver, most of the bilirubin is chemically attached to another molecule before it is released in the bile. This "conjugated" (attached) bilirubin is called direct bilirubin; unconjugated bilirubin is called indirect bilirubin. Total serum bilirubin equals direct bilirubin plus indirect bilirubin. Conjugated bilirubin is released into the bile by the liver and stored in the gallbladder, or transferred directly to the small intestines. Bilirubin is further broken down by bacteria in the intestines, and those breakdown products contribute to the color of the feces. A small percentage of these breakdown compounds are taken in again by the body, and eventually appear in the urine. Normal Results Return to top • Direct bilirubin: 0 to 0.3 mg/dL • Total bilirubin: 0.3 to 1.9 mg/dL Note: mg/dL = milligrams per deciliter Normal values may vary slightly from laboratory to laboratory. What Abnormal Results Mean Return to top Jaundice is the discoloration of skin and the sclera of the eye, which occurs when bilirubin accumulates in the blood at a level greater than approximately 2.5 mg/dL. Jaundice occurs because red blood cells are being broken down too fast for the liver to process. This might happen due to liver disease or bile duct blockage. If the bile ducts are blocked, direct bilirubin will build up, escape from the liver, and end up in the blood. If the levels are high enough, some of it will appear in the urine. Only direct bilirubin appears in the urine. Increased direct bilirubin usually means that the biliary (liver secretion) ducts are obstructed. Increased indirect or total bilirubin may indicate: • Crigler-Najjar syndrome •

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• Erythroblastosis fetalis • Gilbert's disease • Healing of a large hematoma (bleeding under the skin) • Hemolytic anemia • Hemolytic disease of the newborn • Physiological jaundice (normal in newborns) • Sickle cell anemia • Transfusion reaction • Pernicious anemia Increased direct bilirubin may indicate: • Bile duct obstruction • Cirrhosis • Dubin-Johnson syndrome (very rare) • Hepatitis • Intrahepatic cholestasis (buildup of bile in the liver) of many causes Additional conditions under which the test may be performed: • Biliary stricture • Cholangiocarcinoma • Cholangitis • Choledocholithiasis • Hemolytic anemia due to G6PD deficiency • Hepatic Encephalopathy • Idiopathic aplastic anemia • Idiopathic autoimmune hemolytic anemia • Immune hemolytic anemia (including drug-induced immune hemolytic anemia) • Secondary aplastic anemia • Thrombotic thrombocytopenic purpura • Wilson's disease Considerations Return to top Factors that interfere with bilirubin testing are: • Hemolysis (breakdown) of blood will falsely increase bilirubin levels • Lipids in the blood will falsely decrease bilirubin levels • Bilirubin is light-sensitive; it breaks down in light Update Date: 1/22/2007 Pasted from <http://www.nlm.nih.gov/medlineplus/ency/article/003479.htm >

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Alpha2 macroglobulin Sunday, February 17, 2008 1:35 PM

Alpha 2-macroglobulin Alpha-2 macroglobulin (abbreviated α2M or A2M) is a large plasma protein found in the blood. It is produced by the liver, and is a major component of the alpha-2 band in protein electrophoresis.

Contents [hide] • 1 Structure • 2 Function • 3 Disease • 4 References • 5 External links

Pasted from <http://en.wikipedia.org/wiki/Image:Fibrinolysis.png>

[edit] Structure Alpha-2 macroglobulin is compose of four identical subunits bound together by -S-S- bonds.

[edit] Function Alpha-2 macroglobulin is able to inactivate an enormous variety of proteinases (including serine-, cysteine-, aspartic- and metalloproteinases). Alpha-2 macroglobulin has in its structure a 35 aminoacid "bait" region. Proteinases binding and cleaving the bait region become bound to α2M. The proteinase-α2M complex is recognised by macrophage receptors and cleared from the system. It functions as an inhibitor of coagulation by inhibiting thrombin.[1] It functions as an inhibitor of fibrinolysis by inhibiting plasmin: Pasted from <http://en.wikipedia.org/wiki/Alpha_2-macroglobulin>

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Apolipoprotein A1 Sunday, February 17, 2008 1:41 PM

Apolipoprotein A1 Apolipoprotein A-I (ApoA-I) is an apolipoprotein. It is the major protein component of high density lipoprotein (HDL) in plasma. The protein promotes cholesterol efflux from tissues to the liver for excretion. It is a cofactor for lecithin cholesterolacyltransferase (LCAT) which is responsible for the formation of most plasma cholesteryl esters. ApoA-I was also isolated as a prostacyclin(PGI2) stabilizing factor, and thus may have an anticlotting effect. [1] Defects in the gene encoding it are associated with HDL deficiencies, including Tangier disease, and with systemic non-neuropathic amyloidosis.

Contents [hide] • 1 Activity associated with high HDL-C and protection from heart disease • 2 Role in other diseases • 3 Factors affecting ApoA-I activity • 4 References • 5 External links

[edit] Activity associated with high HDL-C and protection from heart disease As a major component of the high density lipoprotein complex ("good cholesterol"), ApoA-I helps to clear cholesterol from arteries. Five of nine men found to carry a mutation (E164X) who were at least 35 years of age had developed premature coronary artery disease.[2] One of four mutants of ApoA-I is present in roughly 0.3% of the Japanese population, but is found 6% of those with low HDL cholesterol levels. ApoA-I Milano is a naturally occurring mutant of ApoA-I, found in a family descended from a single couple of the 18th century. Described in 1980, it was the first known molecular abnormality of apolipoproteins.[3] Paradoxically, carriers of this mutation have very low HDL cholesterol levels, but no increase in the risk of heart disease. Biochemically, ApoA-I contains an extra cysteine bridge, causing it to exist as a homodimer or as a heterodimer with ApoA-II. However, the enhanced cardioprotective activity of this mutant (which likely depends on cholesterol efflux) cannot easily be replicated by other cysteine mutants. [4] Recombinant Apo-I Milano dimers formulated into liposomes can reduce atheromas in animal models by up to 30%.[5] ApoA-I Milano has also been shown in small clinical trials to have a statistically significant [6] effect in reducing (reversing) plaque build-up on arterial walls. In human trials the reversal of plaque build-up was measured over the course of five weeks.[6][7] APP018 (formerly D-4F), an 18-amino acid peptide (Ac-D-W-F-K-A-F-Y-D-K-V-A-E-K-F-K-E-A-F-NH2[8][9], using D-amino acids) that can be taken orally, was developed by Bruin Pharmaceuticals (a little-known company founded by Dr. Alan Fogelman, named after the UCLA Bruins [10][11]) and sold to Novartis for $200 million USD. The peptide and close variations thereof such as D-5F have been shown to elevate HDL-C and reduce atherosclerotic build-up in early animal data. The peptide has been tested with a variety of modifications, formulated with an excipient such as poly(lactideco-glycolide) (PLG), and formed into ProLease[12] drug-polymer microspheres. If all continues to go well it is expected to reach the pharmacy shelf around 2013. [13] • Apolipoprotein AI-CIII-AIV gene cluster Lately, two novel susceptibility haplotypes i.e. P2-S2-X1 and P1-S2-X1 have been discovered in ApoAI-CIII-AIV gene cluster on chromosme 11q23, who confer approximately threefold higher risk of coronary heart disease in normal [4] as well as non-insulin diabetes mellitus[5].

[edit] Role in other diseases A G/A polymorphism in the promoter of the ApoA-I gene has been associated with the age at which patients presented with Alzheimer disease.[14] Protection from Alzheimer disease by ApoA1 may rely on a synergistic interaction with alpha-tocopherol[15]. Amyloid deposited in the knee following surgery consists largely of ApoA-I secreted from chondrocytes (cartilage cells).[16] A wide variety of amyloidosis symptoms are associated with rare ApoA-I mutants. ApoA-I binds to lipopolysaccharide or endotoxin, and has a major role in the anti-endotoxin function of HDL.[17] • Apolipoprotein AI-CIII-AIV gene cluster Lately, two novel susceptibility haplotypes i.e. P2-S2-X1 and P1-S2-X1 have been discovered in ApoAI-CIII-AIV gene cluster on chromosme 11q23, who confer approximately threefold higher risk of coronary heart disease in normal [6] as well as non-insulin diabetes mellitus[7].

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as well as non-insulin diabetes mellitus[7]. In one study, a decrease in ApoA1 levels was detected in schizophrenia patients' CSF, brain and peripheral tissues.[18]

[edit] Factors affecting ApoA-I activity ApoA-I production is decreased by Vitamin D, and increased by a drug that antagonizes it. [19] Exercise or statin treatment may cause an increase in HDL-C levels by inducing ApoA-I production, but this depends on the G/A promoter polymorphism.[20]

[edit] References 1. ^ Yui Y, Aoyama T, Morishita H, Takahashi M, Takatsu Y, Kawai C (1988). "Serum prostacyclin stabilizing factor is identical to apolipoprotein A-I (Apo A-I). A novel function of Apo A-I". J. Clin. Invest. 82 (3): 803-7. PMID 3047170. 2. ^ Dastani Z, Dangoisse C, Boucher B, Desbiens K, Krimbou L, Dufour R, Hegele RA, Pajukanta P, Engert JC, Genest J, Marcil M (2006). "A novel nonsense apolipoprotein A-I mutation (apoA-I(E136X)) causes low HDL cholesterol in French Canadians". Atherosclerosis 185 (1): 127-36. PMID 16023124. 3. ^ Franceschini G, Sirtori M, Gianfranceschi G, Sirtori CR (1981). "Relation between the HDL apoproteins and AI isoproteins in subjects with the AIMilano abnormality". Metab. Clin. Exp. 30 (5): 502-9. PMID 6785551. 4. ^ Zhu X, Wu G, Zeng W, Xue H, Chen B (2005). "Cysteine mutants of human apolipoprotein A -I: a study of secondary structural and functional properties". J. Lipid Res. 46 (6): 1303-11. PMID 15805548. 5. ^ Chiesa G, Sirtori CR (2003). "Apolipoprotein A-I(Milano): current perspectives". Curr. Opin. Lipidol. 14 (2): 159-63. PMID 12642784. 6. ^ a b Apo A1-Milano Trial: Where are we now?. Cleveland Clinic. Retrieved on 2006-11-09. 7. ^ Cedars-Sinai Heart Center - Apo A-1 Milano. Cedars-Sinai Heart Center. Retrieved on 2006-11-09. 8. ^ Patent US 7,144,862 B2 9. ^ Patent WO2006 118805 10. ^ Matthew Herper, Forbes 07.11.05 "Novartis Enters 'Good Cholesterol' Battle." 11. ^ Fierce Biotech. "Bruin Pharmaceuticals." 12. ^ Bartus et al., 1998, Science 281:1161-2 [1] 13. ^ BioMarket Group AB, "Antidyslipidemics: market set for contraction as generics hit hard", October 4, 2006. 14. ^ Vollbach H, Heun R, Morris CM, Edwardson JA, McKeith IG, Jessen F, Schulz A, Maier W, Kölsch H (2005). "APOA1 polymorphism influences risk for early-onset nonfamiliar AD". Ann. Neurol. 58 (3): 436-41. PMID 16130094. 15. ^ Maezawa I, Jin LW, Woltjer RL, Maeda N, Martin GM, Montine TJ, Montine KS (2004). "Apolipoprotein E isoforms and apolipoprotein AI protect from amyloid precursor protein carboxy terminal fragment -associated cytotoxicity". J. Neurochem. 91 (6): 1312-21. PMID 15584908. 16. ^ Solomon A, Murphy CL, Kestler D, Coriu D, Weiss DT, Makovitzky J, Westermark P (2006). "Amyloid contained in the knee joint meniscus is formed from apolipoprotein A-I". Arthritis Rheum. 54 (11): 3545-50. PMID 17075859. 17. ^ Ma J, Liao XL, Lou B, Wu MP (2004). "Role of apolipoprotein A-I in protecting against endotoxin toxicity". Acta Biochim. Biophys. Sin. (Shanghai) 36 (6): 419-24. PMID 15188057. 18. ^ Huang JT, Wang L, Prabakaran S, Wengenroth M, Lockstone HE, Koethe D, Gerth CW, Gross S, Schreiber D, Lilley K, Wayland M, Oxley D, Leweke FM, Bahn S (2007). "Independent protein-profiling studies show a decrease in apolipoprotein A1 levels in schizophrenia CSF, brain and peripheral tissues". Mol Psychiatry. doi:10.1038/sj.mp.4002108. PMID 17938634. 19. ^ Wehmeier K, Beers A, Haas MJ, Wong NC, Steinmeyer A, Zugel U, Mooradian AD (2005). "Inhibition of apolipoprotein AI gene expression by 1, 25-dihydroxyvitamin D3". Biochim. Biophys. Acta 1737 (1): 16-26. PMID 16236546. 20. ^ Lahoz C, Peña R, Mostaza JM, Jiménez J, Subirats E, Pintó X, Taboada M, López-Pastor A (2003). "Apo A-I promoter polymorphism influences basal HDL-cholesterol and its response to pravastatin therapy". Atherosclerosis 168 (2): 289-95. PMID 12801612. Pasted from <http://en.wikipedia.org/wiki/Apolipoprotein_A1>

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Haptoblobulin Sunday, February 17, 2008 1:44 PM

Haptoglobin Haptoglobin (abbreviated as Hp) is a protein in the blood plasma that binds free hemoglobin released from erythrocytes with high affinity and thereby inhibits its oxidative activity. The haptoglobin-hemoglobin complex will then be removed by the reticuloendothelial system (mostly the spleen). In clinical settings, the haptoglobin assay is used to screen for and monitor hemolytic anemia

Contents [hide] • 1 Clinical significance • 2 Test order protocol • 3 Results interpretation • 4 Structure • 5 Miscellaneous Information • 6 Further reading • 7 External links

[edit] Clinical significance Since the reticuloendothelial system will remove the haptoglobin-hemoglobin complex from the body, haptoglobin levels will be decreased in hemolytic anaemias. In the process of binding hemoglobin, haptoglobin sequesters the iron within hemoglobin, preventing iron-utilizing bacteria from benefitting from hemolysis. It is theorized that because of this, haptoglobin has evolved into an acute phase protein.

[edit] Test order protocol Haptoglobin is ordered whenever a patient exhibits symptoms of anemia, such as pallor, weakness, orthostatic hypotension (positional changes in blood pressure) or shortness of breath along with physical signs of hemolysis, such as jaundice or dark-colored urine. The test is also commonly ordered as a hemolytic anemia battery which also includes a reticulocyte count and a peripheral blood smear. It can also be ordered along with a Direct Antiglobulin Test when a patient is suspected of having a transfusion reaction. Finally, it may be ordered in conjunction with a bilirubin.

[edit] Results interpretation A decrease in haptoglobin can support a diagnosis of hemolytic anemia, especially when correlated with a decreased RBC count, Hemoglobin, and Hematocrit, and also an increased reticulocyte count. If the reticulocyte count is increased, but the haptoglobin level is normal, this may indicate that cellular destruction is occurring in the spleen and liver, which may indicate a drug induced hemolysis, or a red cell dysplasia. The spleen and liver recognize an error in the red cells (either Drug coating the red cell membrane, or a dysfunctional red cell membrane), and destroy the cell. This type of destruction does not release hemoglobin into the peripheral blood, so the haptoglobin cannot bind to it. Thus, the haptoglobin will stay normal. If there are symptoms of anemia but both the reticulocyte count and the haptoglobin level are normal, the anemia is most likely not due to hemolysis, but instead some other error in cellular production, such as aplastic anemia Haptoglobin levels which are decreased but do not accompany signs of anemia may indicate liver damage, as the liver is not producing enough haptoglobin to begin with. As haptoglobin is indeed an acute phase protein, any inflammatory process (infection, extreme stress, burns, major crush injury, allergy, etc) may increase the levels of plasma haptoglobin.

[edit] Structure Haptoglobin is produced mostly by hepatocytes but also by other tissues: e.g. skin, lung, and kidney. Haptoglobin, in its simplest form, consists of two α- and two β-chains, connected by disulfide bridges. The chains originate from a common precursor protein which is proteolytically cleaved during protein synthesis. Hp exists in two allelic forms in the human population, so called Hp1 and Hp2; the latter one having arisen due to the partial duplication of Hp1 gene. Three phenotypes of Hp, therefore are found in humans: Hp1-1, Hp2-1, and Hp2-2. Hp of different phenotypes have been shown to bind hemoglobin with different affinities, with Hp2-2 being the weakest binder.

[edit] Miscellaneous Information Hp has been found in all mammals studied so far, some birds e.g. cormorant and ostrich but also, in its simpler form, in bony fish e.g. zebrafish. Interestingly, Hp is absent in at least some amphibians (Xenopus) and neognathous birds (chicken and goose).

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Pasted from <http://en.wikipedia.org/wiki/Haptoglobin>

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Fibroscan Sunday, February 17, 2008 1:51 PM 1: Am J Gastroenterol. 2007 Nov;102(11):2589-600. Epub 2007 Sep 10.

Links

FibroTest and FibroScan for the prediction of hepatitis C-related fibrosis: a systematic review of diagnostic test accuracy. Shaheen AA, Wan AF, Myers RP. Liver Unit, Division of Gastroenterology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada. BACKGROUND: The accurate diagnosis of hepatitis C virus (HCV)-related fibrosis is crucial for prognostication and treatment decisions. Due to the limitations of biopsy, noninvasive alternatives including FibroTest and FibroScan have been developed. Our objective was to systematically review studies describing the accuracy of these tests for predicting HCV-related fibrosis. METHODS: Studies comparing FibroTest or FibroScan versus biopsy in HCV patients were identified via an electronic search. Random effects meta-analyses and areas under summary receiver operating characteristics curves (AUC) were examined to characterize test accuracy for significant fibrosis (F2-4) and cirrhosis. Heterogeneity was explored using meta-regression. RESULTS: Twelve studies were identified, 9 for FibroTest (N = 1,679) and 4 for FibroScan (N = 546). In heterogeneous analyses for significant fibrosis, the AUCs for FibroTest and FibroScan were 0.81 (95% CI 0.78-84) and 0.83 (0.03-1.00), respectively. At a threshold of approximately 0.60, the sensitivity and specificity of the FibroTest were 47% (35-59%) and 90% (87-92%). For FibroScan (threshold approximately 8 kPa), corresponding values were 64% (50-76%) and 87% (80-91%), respectively. Methodological quality, the length of liver biopsy specimens, and inclusion of special populations did not explain the observed heterogeneity. However, the diagnostic accuracy of both measures was associated with the prevalence of significant fibrosis and cirrhosis in the study populations. For cirrhosis, the summary AUCs for FibroTest and FibroScan were 0.90 (95% CI not calculable) and 0.95 (0.87-0.99), respectively. CONCLUSIONS: FibroTest and FibroScan have excellent utility for the identification of HCV-related cirrhosis, but lesser accuracy for earlier stages. Refinements are necessary before these tests can replace liver biopsy. PMID: 17850410 [PubMed - indexed for MEDLINE] Pasted from <http://www.ncbi.nlm.nih.gov/pubmed/17850410>

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ALP, AST, ALT, GGT: Liver Function Enzymes Sunday, February 17, 2008 2:14 PM

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Wilson's Disease Sunday, February 17, 2008 2:16 PM

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ERCP and MRCP - When and Why Sunday, February 17, 2008 2:20 PM

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02 WONG 2008 Viral Hepatitis Saturday, February 16, 2008 5:56 PM

From PBD: 1- 09 02 Herpesviridae Mazzulli.pdf 2- 09 02 Herpesviridae Mazzulli.pdf

02 WONG ... Audio recording started: 9:06 AM Tuesday, February 19, 2008

Hepatitis A Is Hep A an RNA or DNA virus?

What' s the Incubation period (range and average) of Hep A? In which of the following age categories is jaundice frequently seen during a Hep A infection and in which is it a more rare occurrence: < 6 y.o., 6-14 y.o., > 14 years old? Case fatality of Hep A is highest in which age group? Name a complication of Hep A infection?

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If you suspect acute HAV infection, which antibody titre should you check and when?

List 3 ways in which Hep A can be transmitted?

T/F: Hep A infection CAN BE transmitted through blood exposure (ie. Injection drug use or transfusion)?

Recovery from Hep A infection in the majority of cases takes approximately ___ month(s)?

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Out of the following, which would be the most contagious (ie. Contain the most virions) in a Hepatitis A infected person: Serum, Stool/Feces, Saliva, Urine?

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Hepatitis B Which groups/ persons are at increased risk for infection by Hep A (name 3)?(5)

What' sthe Incubation period (range and average) of Hep B? Is jaundice secondary to Hep B infection seen more commonly in children < 5 y.o or >5 y.o.?

Less infectious infectious

infectious

Less infectious

Weeks after exposure Weeks after exposure

• NB: Total anti-HBc is ALWAYS high, in both patients with acute, spontaneous recovery AND chronic infection • Also, in both, IgM anti-HBc goes down quickly • Difference is in HBsAg: stays high in chronic; quickly decreases in acute

MARKER

USUAL SIGNIFICANCE

1. HBsAg

• Virus is present

2. Anti-HBs (surface antibody)

• Virus is usually cleared • Patient immune

3. HBeAg* (except for pre- • Active viral replication core mutant strains of • Ongoing liver disease HBV) • Patient infectious

4. Anti-HBe* (except for pre-core mutant strains of HBV)

• Viral replication reduced • Inactive liver disease (usually) • Less infectious

5. HBcAg

• Never detectable in serum

6. Anti-HBc (core antibody)

• Patient has come into contact with hepatitis B and may or may not still

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T/F: If a patient tests positive for HBsAg, they have a Hep B infection? T/F: If a patient tests positive for HBsAg, they have a Hep B infection? T/F: If a patient tests positive for HBsAg, they have a Hep B infection? T/F: If a patient tests positive for levels of Total anti-HBc, then you still CANNOT distinguish between whether the person has an acute or chronic Hep B infection? What is the difference between the levels of anti-HBs in acute vs. chronic Hep B infection? What is the difference between the temporal profile of HBsAg levels in acute vs. chronic Hep B infection? Symptoms of Hep B infection start approximately how many weeks after exposure?


antibody)

• hepatitis B and may or may not still be infected with the virus • Does not signify immunity

7. IgM anti-HBc (by routine commercially available assays)

• Signifies recent contact with hepatitis B

8. HBV-DNA (by routine commercially available assays)

• Active viral replication • Ongoing liver disease • Patient infectious

Pasted from <http://www.comeunity.com/adoption/health/hepatitis/smith.html>

Glossary

Hepatitis B: Liver disease caused by the hepatitis B virus (HBV). HBV is found in the blood of infected persons and is commonly transmitted through unprotected sex. Hepatitis B Immune Globulin (HBIG): A product available for prophylaxis against hepatitis B virus infection. HBIG is prepared from plasma containing high titers of anti -HBs and provides short-term protection (three to six months). a. Hepatitis B Core Ag (HBcAg): A core protein antigen of the hepatitis B virus not readily detectable in serum. It is an indicator of replicating hepatitis B virus. b. Hepatitis B Core Antibody (anti-HBc): Antibody to the hepatitis core antigen. Appears at the onset of symptoms in acute hepatitis B and persists for life. The presence of anti-HBc indicates previous or ongoing infection with HBV. c. Hepatitis B e Ab (anti-HBe): Antibody to HBeAg that indicates good probability of long lasting viral clearance. d. Hepatitis B e Antigen (HBeAg): Secreted product of the nucleocapsid gene of HBV found in serum during acute and chronic hepatitis B. Its presence indicates the virus is replicating and the infected individual is potentially infectious. e. Hepatitis B Surface Antibody (anti-HBs): The presence of anti-HBs is generally interpreted as indicating recovery and immunity from HBV infection. f. Hepatitis B Surface Antigen (HBsAg): A serologic marker on the surface of HBV. It can be detected in high levels in serum during acute or chronic hepatitis. Pasted from <http://www.hepatitisbhelp.com/hepatitis_b_glossary.html>

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• In the immune tolerant state Th2 is most active; Th1 and CD8 are minimal • In the immune clearance state, all Th2, Th1, and CD8 are active • In the inactive, carrier state, Th2 response is stronger

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Almost 1/5th of immigrants have Hep B!

List the 2 main populations in canada who are at risk for Hep B infection? T/F: Immigrants are screened for HIV, syphillis, and HBV BUT NOT TB? In which of the following body fluids are Hep B levels the highest (may be more than one): Urine, Vaginal Fluid, Serum, Saliva, Wound exudate, Saliva, Semen, Breast milk, Tears, Blood, Sweat, Feces? Untreated, chronic infection with HBV typically leads to ___ OR ___?

Is there a higher level of HBV via percutaneous and perinatal transmission or sexual transmission?

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List 4 drug classes that are available for the treamtent of HBV?

How long should interferon treatment for Hep B be given? List 4 group sof drugs that may be used to treat Hep B?

T/F: There is NO CURE for Hep B infection? What is the primary immune modulatory treatment for Hep B infection?

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Hepatitis C

Is it safe to BREASTFEED if a mother has an HCV infection? T/F: Perinatal transmission of HCV occurs less frequently in infants delivered vaginally (ie. NOT via C-section)?

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Hepatitis D What is the treatment for Hep C?

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Hepatitis D What is the treatment for Hep C?

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Classification

HDV is the only virus in the genus, Deltaviridae. HDV is not classified into a viral family because it is a unique virus depe ndent on HBV. HDV is a co-infection of HBV. The envelope of HDV particles contains the Hepatitis B surface antigen (HBsAg). The production and transmission of HDV is entirely dependent on HBV to provide HBsAg. Thus, HDV is considered a satellite virus of HBV. Unlike a classical satellite virus, however, HDV does not share sequence similarity with HBV, and it can replicate independently of HB V.

Clinical Features Symptoms and Incubation

Although variable, the clinical course of HDV is typically more severe than that of the other hepatitis viruses . After an incubation period of 3-7 weeks, nonspecific clinical symptoms, including fatigue, lethargy, nausea, and anorexia, begin and last for about 3-7 days. Viral replication is usually diminished during this phase. Jaundice occurs in the next phase of symptoms. Fatigue and nausea usually continue, and the serum bilirubin level becomes abnormal. At the same time, the infected person may have clay-colored stool and dark urine. This is evidence of the liver’s diminished ability to excrete bilirubin .

Diagnosis

Type D hepatitis should be considered in individuals who are HBsAg positive or who have evidence of recent HBV infection. The diagnosis for Hepatitis D infection is made following serologic tests for the virus. Total anti -HDV antibodies are detected by radioimmunoassay (RIA) or enzyme immunoassay (EIA) kits. To monitor ongoing HDV infection, reverse transcriptase polymerase chain reaction (RT-PCR) should be used. RT-PCR can detect 10 to 100 copies of the HDV genome in infected blood serum. Each of the markers of HDV infection, including IgM and IgG antibodies, disappears within months after recovery. In chronic H epatitis D infection, on the other hand, HDV RNA, HDAg, IgM anti-HD antibodies, and IgG anti-HD antibodies persist.

Outcomes

The outcome of disease depends on whether HDV is contracted as a co -infection or a superinfection. Co-infection: Co-infection occurs when both HDV and HBV are contracted simultaneously. This results in acute HDV and HBV infection. Depending on the relative amounts of HBV and HDV, one or two episodes of hepatitis occurs. Co -infections of HDV and HBV are usually acute and self-limiting infections. HBV/HDV co -infections cause chronic HDV infections in less than 5% of co -infected patients. Although clinical symptoms disappear, fatigue and lethargy may persist for weeks or months.

Picture from CDC Website

Superinfection: Superinfection occurs when chronic HBV carriers are infected with HDV . This leads to severe acute hepatitis and chronic Hepatitis D infection in 80% of the cases. Superinfection is associated with the fulminant form of viral hepatitis. Fulminant viral hepatitis, the most severe form of acute disease, is about ten times more common in HDV infections than in th e other types. It is characterized by hepatic encephalopathy that is manifested by changes in personality, disturbances in sleep, confusion, difficulty concentrating, and sometimes abnormal behavior and coma. The mortality rate of fulminant hepatitis is about 80%. C hronic hepatitis D infection progresses to liver cirrhosis in about 60 -70% of patients. Cirrhosis takes about 5-10 years to develop, but can appear two years after the onset of infection. Hepatocellular carcinoma occurs in chronically infected HDV patients with the same

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List the two steps in evaluating for HCV infection? In evaluating for HCV infection, if the patient has ALT and AST levels > 30, then …? In evaluating for HCV infection, if the patient has ALT and AST levels < 30, then …? IF ALT and AST are both < 30 and HCV PCR is negative, then what should be done in follow up to confirm no HCV infection? What 5 tests can you do to assess the severity of HCV infection?


frequency as in patients with ordinary HBV. Overall, the mortality rate for HDV infections lies between 2% and 20%, values ten times greater than the mortality rates for HBV.

Fulminant viral hepatitis, the most severe form of acute disease, is about ten times more common in HDV infections than in the other types.

Picture from CDC Website

Prevention and Treatment

Prevention of Hepatitis Delta Virus infection is based on prevention of HBV, as HDV requires the surface antigen of HBV to cause infection. There is no vaccine for HDV, but there is an effective vaccine for HBV. In order to prevent HDV -HBV co-infection, the HBV vaccine or post exposure prophylaxis (Hepatitis B Immune Globulin) can be used to prevent infection. The only way to prevent HBV HDV superinfection is to educate chronic HBV carriers about transmission and risky behaviors. HDV can be transmitted via bloo d exchange, sexual contact, sharing needles, and from mother -to-child. There is no specific treatment for HDV infections. Im m unosuppressiv e therapy has no positiv e clinical effect. Antiviral drugs, including Acyclovir, Ribavirin, Lamivudine, and synthetic analogs of thymosin have all proved ineffective. For infected patients, massive doses of a-interferon have caused disease remission, but most patients remained positive for HDV RNA whether or not there was improvement in disease conditions. The effect of interferon therapy seems to be indirect, perhaps via an effect on HBV or the immune response to the infection. Orthotopic liver transplantation has proven useful for treating fulminant acute and advanced chronic hepatitis D infections. Pasted from <http://www.stanford.edu/group/virus/delta/2005/>

â&#x20AC;˘

Orthotopic liver transplantation refers to a procedure in which a failed liver is removed from the patient's body and a healthy donor liver is transplanted into the same location. In this case, the liver donor is someone who has recently died. The procedure is the most common meth od used to transplant livers. Pasted from <http://www.emedicinehealth.com/liver_transplant/article_em.htm>

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How can Hep D infection be prevented? What is the treatment for Hep D infection?

jaundice

â&#x20AC;˘ Note how the titres of HDV RNA and HBsAg stay high, and also that ALT levels never go back down but oscillate at a higher level, indicative of liver compromise

Hepatitis E

Is Hep E an RNA or DNA virus?

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In Hep E infection, ALT reaches its peak approximately how many weks after exposure? Approximately how many week after Hep E exposure does the virus show up in stool? In Hep E infection, levels of (ALT or AST or ALP) reach their peak at approximately the same time as levels of (IgM anti -HEV or IgG anti-HEV) reach their peak?

Hepatitis G

Parenteral: [para- + enteral] not through the alimentary canal but rather by injection through some other route, such as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, or intravenous.

Effect of Hepatitis G Virus Infection on Progression of HIV Infection in Patients with Hemophilia Anthony E.T. Yeo, MD, MPH, PhD; Akihiro Matsumoto, MD, PhD; Michie Hisada, MD, ScD; James W. Shih, PhD; Harvey J. Alter, MD; James J. Goedert, MD, for the Multicenter Hemophilia Cohort Study* 20 June 2000 | Volume 132 Issue 12 | Pages 959-963 Background: Infection with hepatitis G virus (HGV), also known as GB virus C, is prevalent but is not known to be associated with any chronic disease. Infection with HGV may affect the risk for AIDS in HIV-infected persons. Objective: To compare AIDS-free survival in patients with and those without HGV infection during 16 years of follow up after HIV seroconversion. Design: Subanalysis of a prospective cohort study. Setting: Comprehensive hemophilia treatment centers in the United States and Europe. Patients: 131 patients with hemophilia who became HIV-positive between 1978 and 1985. Measurements: Age, CCR5 genotype, HIV and HCV viral loads, CD4+ and CD8+ lymphocyte counts, and 12-year AIDS-free survival by HGV positivity (viremia [RNA] or anti-E2 antibodies). Results: Compared with HGV-negative patients, the 60 HGV-positive patients (46%), including 22 who were positive for HGV RNA, had higher CD4+ lymphocyte counts (difference, 211 cells/mm 3 [95% CI, 88 to 333 cells/mm 3]) and 12-year AIDS-free survival rates (68% compared with 40%; rate difference, 1.9 per 100 person-years [CI, â&#x20AC;&#x201C;0.3 to 4.2 per 100 person-years]), despite similar ages and HIV viral loads. In multivariate proportional hazards models, risk for AIDS was 40% lower for HGVpositive patients independent of age, HIV and HCV viral loads, CD4 + and CD8+ lymphocyte counts, and CCR5 genotype. Conclusions: Patients with past or current HGV infection have higher CD4+

lymphocyte counts and better AIDS-free survival rates. The mechanism of this association is unknown. Pasted from <http://www.annals.org/cgi/content/full/132/12/959>

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T/F: Hepatitis G infection is actually NOT associated with liver infection? Hepatitis ___ and ___ are the major causes of end-stage liver disease and liver cancer? T/F: Hep G infection is associated with downregulation of which chemokine receptor that plays an important role in determining the progression of HIV infection? In HBV-HBD Superinfection, there is a high risk of ___? Which of the hepatitis viruses IS NOT associated with liver disease? How is Hepatitis G acquired?


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Thursday, March 27, 2008 12:45 AM

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Testing review of lecture Sunday, February 17, 2008 9:41 PM

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Past Hepatitis Lectures/Mentions

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03 LILLY 2008 Liver Failure Friday, February 15, 2008

Which is more common: cirrhosis or fulminant liver failure?

End Stage Liver Disease is marked by ___ and ___?

T/F: The lower the Child-Pugh Score, the better?

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• Budd-Chiari syndrome is the clinical picture caused by occlusion of the hepatic vein or inferior vena cava . It

presents with the classical triad of - abdominal pain - ascites - hepatomegaly • Examples of occlusion include thrombosis of hepatic veins and membranous webs in the inferior vena cava. The syndrome can be fulminant, acute, chronic, or asymptomatic. It occurs in 1 out of 100,000 individuals and is more common in females. Pasted from <http://en.wikipedia.org/wiki/BuddChiari_syndrome>

Cirrhosis

Compensation implies cirrhosis without complications. The complications that may develop include bleeding from varices (abnormal veins that form in the gullet), ascites, jaundice and encephalopathy (confusion, reduction in conscious level and coma). Cirrhosis of the liver can be 'compensated' or 'decompensated'.

Compensated cirrhosis may be managed with abstinence from alcohol and nutritional support as above.

Treatment of decompensated cirrhosis In patients with decompensated cirrhosis, specific treatments may be required to deal with the complications of the disease:

Bleeding varices Bleeding varices may need treatment by endoscope (a flexible camera which can be passed into the stomach) to destroy the abnormal veins in the wall of the gullet. Long-term treatment with tablets such as beta-blockers (eg propranolol) may reduce the risks of further bleeding. Patients with alcoholic cirrhosis often have a 'screening' endoscopy test to identify any varices before a bleed occurs. Where varices are found, treatment with beta-blockers has been shown to reduce the risk of a first bleed.

Ascites Ascites require a low salt diet, and reduction of fluid intake is often advised. Patients will usually be treated with diuretics (water tablets) and may require intermittent drainage of the fluid with a catheter or plastic drainage tube being inserted into the abdomen (paracent esis). In some cases these measures will be unsuccessful, and further interventions such as a liver transplant may be needed.

Encephalopathy Usually linked to additional stress on the body. This may include the use of inappropriate sedating or painkilling medicines, bleeding from the gullet or stomach, constipation, infections or abnormalities in the salts (electrolytes) in the blood. The main factor involved in c ausing the encephalopathy is an increase in ammonia levels in the brain. The treatment involves correcting the underlying problem, and treatment with lactulose (a liquid laxative). Lactulose decreases the production of ammonia in the gut and its absorption into the body. It lowers ammonia level s in the blood and may need to be taken long term to prevent recurrence of the encephalopathy.

Liver transplantation In some patients with cirrhosis, liver function continues to deteriorate despite abstinence from alcohol and they may be severely affected by complications. These individuals may need a liver transplant. But for patients to be considered for transplantation, they mus t: ○ have been abstinent from alcohol for six months. ○ have advanced liver disease with complications. ○ have no other organ damage. ○ have good social or family support. Approximately 85 per cent of appropriate patients reach the five-year survival rates following a transplant.

References Living in Britain - the 2001 general Household Survey. Department of Health. http://www.doh.gov.uk/public/livinginbritainsurvey.htm

Last updated 14.04.2004

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Pasted from <http://www2.netdoctor.co.uk/diseases/facts/alcliver.htm>

(5) 1

5

List 4 prognostic factors in cirrhosis? What is the difference between compensated and decompensated cirrhosis? How is decompensated cirrhosis managed?

Do patients with a ChildPugh Score of A or C have higher 1-year and 5-year survivals?

List 3 signs of decompensated cirrhosis?(4)

A synonym for decompensation, in the context of liver failure, is â&#x20AC;Ś?

HRS = Hepato-Renal Syndrome

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(5) 1

5

TIPS = Transjugular Intrahepatic Portosystemic Shunt.

List the 5 steps in the stepwise approach to the management of ascites?

The average western diet has approximately ___ - ___ meq of Na whereas a low salt diet has about ___ meq of Na?

fig 1: Portal hypertension before

the TIPS

procedure is performed. Portal hypertension causes blood flow to be forced backward, causing veins to enlarge and varices to develop across the esophagus and stomach from the pressure in the portal vein. The backup of pressure also causes the spleen to become enlarged.

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fig 2: After the TIPS procedure is performed. A radiologist makes a tunnel through the liver with a needle, connecting the portal vein (the vein that carries blood from the digestive organs to the liver) to one of the hepatic veins (the three veins that carry blood from the liver). A metal stent is placed in this tunnel to keep the track open. The shunt allows the blood to flow normally through the liver to the hepatic vein. This reduces portal hypertension, and allows the veins to shrink to normal size, helping to stop variceal bleeding.

Pasted from <http://www.clevelandclinic.org/health/health-info/docs/0200/0237.asp?index=4956&src=newsp>

Depicted is the procedure for performing TIPS. (a) A needle is passed under radiologic guidance from a hepatic vein into a major portal venous branch, and a guide wire is advanced through this needle. (b) A balloon is passed over the guide wire, creating a tract in the hepatic parenchyma. (c) An expandable stent is placed though this tract. (d) The effective result is a nonselective portosystemic shunt. Pasted from <http://www.heart-intl.net/HEART/011507/PortalHypertension.htm>

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Do recurrent bleeds occur in the majority of patients who have had at least one index variceal bleed secondary to cirrhosis?

What is the prevalence of cirrhosis in Hep C infection? The typical incubation period for Hep C is ___ to ___ weeks? Is cirrhosis or chronic infection more common as a clinical feature in Hep C infection?

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T/F: THE MAJORITY of deaths in HCV infection are liver-related?

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The most common adult indication for liver transplant is ___? The top two adult indications for liver transplantation are ___, ___ and ___?

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What is the definition of fulminant hepatic failure (include whether or not it's reversible and when the onset of encephalopathy should occur after appearance of first symptoms)? T/F: In fulminant hepatic failure, encephalopathy occurs 2 weeks after the onset of symptoms?

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05 KANDEL 2008 Dyspepsia and Peptic Ulcer Disease Friday, February 15, 2008

What is dyspepsia?

List 3 common causes of dyspepsia? List 3 uncommon causes of dyspepsia? List 3 rare causes of dyspepsia? Which 3 cancers are most commonly related to complaints of dyspepsia? Is cancer a common, uncommon, or rare cause of dyspepsia?

â&#x20AC;˘ See Giardia lamblia page, FMP Week 9, for an overview of Giardia lamblia

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What is giardia?

What is a helpful menomic in eliciting a history of pain?

Questions to ask: 3A + D ○

○ ○

Acid regurg? Age? Associated Sympx? Drugs (esp. NSAIDs)?

What are the 4 key questions to ask someone presenting with dyspepsia?

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Questions to ask: 3A + D ○ ○

○ ○

Acid regurg? Age? Associated Sympx? Drugs (esp. NSAIDs)?

What are the 4 key questions to ask someone presenting with dyspepsia? Out of the 4 questions that one should ask a patient with dyspepsia, which one is the only one which is correlated with a diagnosis?

Most patients who have dyspepsia should be investigated via (general tests/investigations) ___, ___, and ____? T/F: In trying to minimize the wastage of resources, only ONE blood test should be done for dyspepsia and that is Helicobacter serology?

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In ordering an ordinary workup for dyspepsia, which 4 lab investigations would you order?

In ordering a STELLAR workup for dyspepsia, which 5 lab investigations would you order in addition to: liver enzymes, CBC, creatinine, and glucose? List 2 complications of peptic ulcer disease?(3)

Patients with peptic ulcer disease commonly present with ___ and ___? Diagnosis of a peptic ulcer is made by ___?

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What should you do when presented with any gastric ulcer in order to rule out cancer?

List 2 common causes of peptic ulcer? List 3 RARE causes of peptic ulcer?

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The ONLY place where H. Pylori is found is in the ___ mucosa? T/F: ALL persons with H. pylori infection have gastritis, but only a minority will go on to develop a peptic ulcer and even fewer gastric cancer? The three drug regimen for the treatment of H. pylori infections usually includes a proton pump inhibitor plus the following two antibiotics: ___ AND (___ OR ___)?

Classes of Drugs used to Treat H. pylori

Drug Class

Drugs in the Class Antibiotics (+2) (usually amox. + clarith/metro) • Amoxicillin, • Clarithromycin, • Metronidazole, • Tetracycline

H2-Blockers

• • • •

Cimetidine (Tagamet), Famotidine (Pepcid), Nizatidine (Axid), Ranitidine (Zantac)

Proton Pump Inhibitors (PPIs) (-prazole's)

• • • • •

Esomeprazole (Nexium), Lansoprazole (Prevacid), Omeprazole (Prilosec), Pantoprazole (Protonix), Rabeprazole (Aciphex)

Cytoprotective Agents

• Bismuth subsalicylate, • Bismuth subcitrate potassium, • Sucralfate

Combination Products

• Helidac, • Prevpac, • Pylera

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• The primary goal of therapy for ulcers caused by H. pylori is to eradicate or destroy the bacteria. • To date, the most effective therapy for H. pylori are the three-drug regimens and four-drug regimens--specifically those regimens that contain a proton pump inhibitor (PPI) plus two antibiotics--since cure rates are typically higher with these therapies. Two -drug regimens tend to have a lower cure rate and should not be used, and four -drug regimens, while very effective,can be more complicated to take. Therefore, a three-drug regimen or possibly a pre-packaged, combination product is recommended as the most effective means of treating ulcers caused by H. pylori. • Combination products such as Helidac, Prevpac, and Pylera are effective in treating H. pylori-induced ulcers. Use of these products may help improve compliance with the treatment regimens but they are also more expensive treatment options. Additionally, no head-to-head trials have been performed between these comparative products to determine if one is superior to the other in terms of improving compliance or in curing the H. pylori infection. • Generally, you want to take a treatment regimen that provides at least an 80% cure rate (or eradication rate). The most effective treatment regimen contains a proton pump inhibitor (PPI), plus clarithromycin and either amoxicillin or metronidazole. • The duration of therapy needed is still controversial. Some doctors favor a 7 -day treatment regimen while others favor a 10 - to 14day treatment regimen. The shorter treatment duration may enhance compliance (which is important when treating a bacterial infection), but the longer treatment duration may have greater success in curing the infection (especially in persons who are compliant with taking their medications). If the first treatment attempt was not successful, a 14 -day treatment duration is needed. The American College of Gastroenterology recommends a 14 -day treatment duration. • The four-drug regimen consisting of a PPI, bismuth, metronidazole, and tetracycline (all taken for 2 weeks) is also highly effective . Pasted from <http://www.drugdigest.org/DD/Comparison/NewComparison/0,10621,550540 -21,00.html>

Most useful diagnostics for H. pylori infection are ___ and ___, though the most accurate is ___?

T/F: Disease secondary to H. pylori infection occurs years after the initial exposure and infection?

T/F: H. pylori infection can now be effectively eliminated with a single drug? T/F: Pathogen isolation NOT NECESSARY to diagnose someone with an H. pylori infection?

Is there a higher rate of dyspepsia or ulcer complications in patients who have adverse reactions to NSAIDs?

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Is there a higher rate of dyspepsia as a complication of NSAID use or ulcer formation?

Is dyspepsia a reliable indicator of an ulcer?

What is the effect of inhibition of cyclooxygenase by NSAIDS on prostaglandins levels? Do decreasing prostaglandin levels lead to increased or decreased levels of joint inflammatino and gastric cytoprotection?

T/F: Regarding complications of NSAID use, there is a 10x higher likelihood of dyspepsia complications compared to ulcer complications? How are arthritis and gastric mucosal stability related?

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Suppressing gastric acid prevents and heals peptic ulcers BUT ONLY WHILE â&#x20AC;Ś?

Oxyntic glands in the body and fundus of the stomach contain which 3 types of cells? List the 3 regions of the stomach? Pyloric glands in the antrum contain which 2 types of cells? Chief cells produce ___? Chief cells are located in the ___? Parietal cells produce ___ and ___? Parietal cells are located in the ___? G cells produce ___? G cells are located in the ___? Pepsinogen is secreted by ___ cells whereas gastrin is secreted by ___ cells? The cells which secrete pepsin are located in which region of the stomach? The cells which secrete gastrin are located in which region of the stomach? The cells which secrete HCL are located in which region of the stomach? Intrinsic factor is produced by ___ cells located in the ___ region of the somtach? Name a proton pump inhibitor?

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Intrinsic factor - lack of Intrinsic factor is a natural substance normally present in the stomach. It is essential to the digestion of vitamin B-12. â&#x2014;&#x2039; Lack of intrinsic factor leads to pernicious anemia and vitamin B-12 deficiency . Babies that are born without intrinsic factor cannot properly absorb vitamin B-12 starting around 6 months of age. The juvenile type of lack of intrinsic factor tends to manifest itself after the age of ten. Update Date: 2/6/2007

Pasted from <http://www.nlm.nih.gov/medlineplus/ency/article/001155.htm>

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Which is a more common cause of dyspepsia: Crohn's disease or pancreatitis?

What is the commonest cause of dyspepsia?

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What is functional dyspepsia?

The workup for dyspepsia includes which 3 tests (hint: one is a blood test)? Diagnosis of peptic ulcer is made by ___? T/F: The commonest cause of peptic ulcer disease is functional dyspepsia? T/F: The commonest cause of functional dyspepsia is peptic ulcer disease?

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Giardia lamblia Thursday, March 27, 2008

Giardia lamblia From Wikipedia, the free encyclopedia (Redirected from Giardia) Jump to: navigation, search Giardia lamblia

Giardia cell, SEM Scientific classification Domain: Eukaryota Phylum:

Metamonada

Order:

Diplomonadida

Family:

Hexamitidae

Genus:

Giardia

Species:

G. lamblia

Binomial name Giardia lamblia (Kunstler, 1882)

Parasite life cycle. Giardia lamblia (synonymous with Lamblia intestinalis and Giardia duodenalis) is a flagellated protozoan parasite that colonises and reproduces in the small intestine, causing giardiasis. The giardia parasite attaches to the epithelium by a ventral adhesive disc, and reproduces via binary fission [1]. Giardiasis does not spread via the bloodstream, nor does it spread to other parts of the gastro -intestinal tract, but remains confined to the lumen of the small intestine [2]. Giardia trophozoites absorb their nutrients from the lumen of the small intestine, and are anaerobes.

Contents [hide] â&#x20AC;˘ 1 Hosts

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• • • • • • • • • • •

1 Hosts 2 Life cycle 3 Manifestation of infection 4 Backcountry Water Sources 5 Prevention and Treatment 6 Microscopy 7 Research 8 History 9 References 10 See also 11 External links

[edit] Hosts Giardia affects humans, but is also one of the most common parasites infecting cats, dogs and birds . Mammalian hosts also include cows, beavers, deer, and sheep.

Life cycle Giardia infection can occur through 1. ingestion of dormant cysts in contaminated water, or 2. by the fecal-oral route (through poor hygiene practices). The Giardia cyst can survive for weeks to months in cold water [3], and therefore can be present in contaminated wells and water systems, and even clean-looking mountain streams, as well as city reservoirs, as the Giardia cysts are resistant to conventional water treatment methods, such as chlorination and ozonolysis. [3] Zoonotic transmission is also possible, and therefore Giardia infection is a concern for people camping in the wilderness or swimming in contaminated streams or lakes, especially the artificial lakes formed by beaver dams (hence the popular name for giardiasis, "Beaver Fever"). As well as water-borne sources, fecal -oral transmission can also occur, for example in day care centres, where children may have poorer hygiene practices. Those who work with children are also at risk of being infected, as are family members of infected individ uals. Not all Giardia infections are symptomatic, so some people can unknowingly serve as carriers of the parasite. The life cycle begins with a noninfective cyst being excreted with faeces of an infected individual. Once out in the environm ent, the cyst becomes infective. A distinguishing characteristic of the cyst is 4 nuclei and a retracted cytoplasm. Once ingested by a host , the trophozoite emerges to an active state of feeding and motility. After the feeding stage, the trophozoite undergoes asexual re plication through longitudinal binary fission. The resulting trophozoites and cysts then pass through the digestive system in the faece s. While the trophozoites may be found in the faeces, only the cysts are capable of surviving outside of the host. Distinguishing features of the trophozoites are large karyosomes and lack of peripheral chromatin, giving the two nuclei a ha lo appearance. Cysts are distinguished by a retracted cytoplasm. This protozoa lacks mitochondria, although the discovery of the presence of mitochodrial remnant organelles in one recent study "indicate that Giardia is not primitively amitochondrial and that it has retained a functional organelle derived from the original mitochondrial endosymbiont" [4]

Manifestation of infection Nomenclature for Giardia species are difficult, as humans and other animals appear to have morphologically identical parasite s. Colonisation of the gut results in inflammation and villous atrophy, reducing the gut's absorptive capability. In humans, infection is symptomatic only about 50% of the time, and protocol for treating asymptomatic individuals is controversial. [3]

Symptoms of infection

include (in order of frequency) diarrhoea, malaise, excessive gas (often flatulence or a foul or sulphuric tasting belch, which has been known to be so nauseating in taste that it can cause the infected person to vomit), steatorrhoea (pale, foul smelling, greasy stools), epigastric pain, bloating, nausea, diminished interest in food, possible (but rare) vomiting which is often violent, and weight loss.[3] Pus, mucus and blood are not commonly present in the stool. In healthy individuals, the condition is usually self-limiting, although the infection can be prolonged in patients who are immunocompromised, or who have decreased gastric acid secretion.[3] People with recurring Giardia infections, particularly those with a lack of IgA, may develop chronic disease. Lactase deficiency may develop in an infection with Giardia, however this usually does not persist for more than a few weeks, and a full recover y is the norm[citation needed]. Cats can be cured easily, lambs usually simply lose weight, but in calves the parasites can be fatal and often are not respon sive to antibiotics or electrolytes. Carriers among calves can also be asymptomatic. Dogs have a high infection rate, as 30% of the p opulation under one year old are known to be infected in kennels. The infection is more prevalent in puppies than in adult dogs. This p arasite is deadly for chinchillas, so extra care must be taken by providing them with safe water. Infected dogs can be isolated and trea ted, or the entire pack at a kennel can be treated together regardless. Kennels should also be then cleaned with bleach or other cleaning disinfectants. The grass areas used for exercise should be considered contaminated for at least one month after dogs show sig ns of infection, as cysts can survive in the environment for long periods of time. Prevention can be achieved by quarantine of infe cted dogs for at least 20 days and careful management and maintenance of a clean water supply.

Prevention and Treatment Treatment of drinking water for Giardiais not ordinarily indicated in wilderness regions, including much of the Sierra Nevada and other similar locations in North America. In many other areas frequented by hikers and campers, as well as places where many residents rely on untreated surface water, reliable prevention may involve filtration and/or chemical disinfection of available surface water, such as chlorination or ozonation. Normal concentrations of chlorine and ozone used in mass water treatment for most urban areas of the United States may not be adequate to kill all cysts. Giardia cysts are generally present in very small numbers in many such urban water supplies in th e United States. Yet typically these very common and very low concentrations in public water supplies are not a realistic health concern. Scooping water from the top of a stream or river is not an effective way to avoid Giardia. Filtering (<1µm pore) or boiling is

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Scooping water from the top of a stream or river is not an effective way to avoid Giardia. Filtering (<1µm pore) or boiling is

recommended for purification of drinking water in wilderness conditions. Giardia lamblia infection in humans is frequently misdiagnosed. Accurate diagnosis requires an antigen test or, if that is unavailable, an ova and parasite examination of stool. Multiple st ool examinations are recommended, since the cysts and trophozoites are not shed consistently. Human infection is conventionally treated with metronidazole, tinidazole or nitazoxanide. Although Metronidazole is the current firstline therapy, it is mutagenic in bacteria and carcinogenic in mice, so should be avoided during pregnancy. [3] One of the most common alternative treatments is berberine sulfate (found in Oregon grape root, goldenseal , yellowroot, and various other plants). Berberine has been shown to have an antimicrobial and an antipyretic effect. Berberine compounds cause uterine stimulation, and so should be avoided in pregnancy. High doses of berberine can cause bradycardia and hypotension. [5] Drug

Treatment duration

Possible Side Effects

Metronidazole 5-7 days

Metallic taste; nausea; vomiting; dizziness; headache; disulfiram-like effect; neutropenia

Tinidazole

Single dose

Metallic taste; nausea; vomiting; belching; dizziness; headache; disulfiram-like effect

Nitazoxanide

3 days

Abdominal pain; diarrhea; vomiting; headache; yellow-green discolouration of urine

Table adapted from Huang, White.. [3]

[edit] Microscopy

This picture shows multiple views of a single Giardia lamblia (intestinalis) cyst as imaged at different instrument settings by confocal microscopy.Bar = 10 micrometres. (A) is the cyst imaged by transmission (differential interference contrast), only. (B) is the cyst wall selectively imaged through use of fluorescent -labelled (TRITC) antibody that is cyst wall specific. (C) is the cyst imaged through use of carboxy fluorescein diacetate, a viability stain. (D) is a composite image of (B) and (C). (E) is a composite image of (A), (B), and (C). Under a normal compound light microscope, Giardia often looks like a "clown face," with two nuclei outlined by adhesive discs above dark median bodies that form the "mouth." Cysts are oval, have four nuclei, and have clearly visible axostyles.

[edit] Research Giardia alternates between two different forms — a hardy, dormant cyst that contaminates water or food and an active, disease-causing form that emerges after the parasite is ingested. National Institute of General Medical Sciences grantee Dr. Frances Gillin of the University of California, San Diego and her colleagues cultivated the entire life cycle of this parasite in the laboratory, and identified biochemical cues in the host's digestive system which trigger Giardia's life cycle transformations. [6][7] They also uncovered several ways in which the parasite evades the defences of the infected organism. One of these is by altering the proteins on its surface, which confounds the ability of the infected animal's immune system to detect and combat the parasite (called antigenic variation). Gillin's work reveals why Giardia infections are extremely persistent and prone to recur. In addition, these insights into Giardias biology and survival techniques may enable scientists to develop better strategies to understand, prevent, and treat giardia infections.

[edit] References 1. ^ Oxford textbook of Medicine, Fourth Edition, Volume 1. Oxford University Press pp759-760 2. ^ Harrison's Internal Medicine, Harrison's Online Chapter 199 Protozoal intestinal infections and trochomoniasis 3. ^ a b c d e f g Huang DB, White AC (2006). "An updated review on Cryptosporidium and Giardia". Gastroenterol. Clin. North Am. 35 (2): 291-314, viii. doi:10.1016/j.gtc.2006.03.006. PMID 16880067. 4. ^ Tovar J, León-Avila G, Sánchez LB, et al (2003). "Mitochondrial remnant organelles of Giardia function in iron -sulphur protein maturation". Nature 426 (6963): 172-6. doi:10.1038/nature01945. PMID 14614504. 5. ^ UpToDate (Lexi -Comp, Inc.) retrieved 28 August 2007 6. ^ Hetsko ML, McCaffery JM, Svärd SG, Meng TC, Que X, Gillin FD (1998). "Cellular and transcriptional changes during excystation of Giardia lamblia in vitro". Exp. Parasitol. 88 (3): 172-83. doi:10.1006/expr.1998.4246. PMID 9562420. 7. ^ Svärd SG, Meng TC, Hetsko ML, McCaffery JM, Gillin FD (1998). "Differentiation -associated surface antigen variation in the ancient eukaryote Giardia lamblia". Mol. Microbiol. 30 (5): 979-89. PMID 9988475. 8. ^ Ford, BJ The discovery of Giardia The Microscope 2005;53(4):148-153.

[edit] See also • 1998 Sydney water crisis

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• 1998 Sydney water crisis

[edit] External links • • • • • • •

GiardiaDB: The Giardia lamblia genome sequencing project Washington State Department of Health fact sheet on Giardia . Center for Disease Control fact sheet on Giardia Giardia article at MicrobeWiki Video of Giardia Life Cycle Giardia and the Sierra Nevada http://diarrhea.emedtv.com/giardia -lamblia/giardia-lambia.html

Pasted from <http://en.wikipedia.org/wiki/Giardia >

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Zollinger-Ellison syndrome Monday, March 31, 2008

Zollinger-Ellison syndrome, a

triad comprising

(1) intractable, sometimes fulminating, and in many ways atypical peptic ulcers ; (2) extreme gastric hyperacidity; and (3) gastrin-secreting, non-beta islet cell tumors of the pancreas, which may be single or multiple, small or large, benign or malignant. The gastrinoma sometimes occurs in sites (e.g., the duodenum) other than the pancreas. See also multiple endocrine neoplasia, type I. Pasted from <http://127.0.0.1:8080/rami?COMMAND=applyStylesheet(dor@doc.xsl,dor@s/12777451.pub)&sword=12785538 >

multiple endocrine neoplasia, type I, a variety that includes tumors of the anterior pituitary, parathyroid glands, and pancreatic islet cells in association with a high incidence of peptic ulcers and sometimes the Zollinger-Ellison syndrome; it is caused by a genetic abnormality on the long arm of chromosome 11. Called also Wermer's syndrome. Pasted from <http://127.0.0.1:8080/rami?COMMAND=applyStylesheet(dor@doc.xsl,dor@n/12561343.pub)&sword=12561395 >

Background nonâ&#x20AC;&#x201C;beta islet cell, gastrin-secreting tumor of the pancreas that stimulates the acid-secreting cells of the stomach to maximal activity, with consequent gastrointestinal mucosal ulceration. ZES may occur Zollinger-Ellison syndrome (ZES) is caused by a

sporadically or as part of an autosomal dominant familial syndrome called multiple endocrine neoplasia type 1 (MEN 1). The primary tumor is usually located in the duodenum, the pancreas, and abdominal lymph nodes, but ectopic locations have also been described (eg, heart, ovary, gall bladder, liver, kidney).

Pathophysiology The symptoms of ZES are secondary to hypergastrinemia, which causes hypertrophy of the gastric mucosa, leading to increased numbers of parietal cells and increased maximal acid output. Gastrin by itself also stimulates acid secretion, resulting in increased basal acid secretion. The large quantity of acid produced leads to gastrointestinal mucosal ulceration. It also leads to diarrhea and malabsorption. Malabsorption in ZES usually is multifactorial, being caused by direct mucosal damage by acid, inactivation of pancreatic enzymes, and precipitation of bile salts. ZES is sporadic in 75% of patients, while in the other 25% it is associated with MEN 1, an autosomal dominant condition characterized by hyperparathyroidism, pancreatic endocrine tumors, and pituitary tumors.

Frequency United States ZES occurs in approximately 0.1-1% of all patients with duodenal ulcers . Its frequency of occurrence is reported to be approximately the same as insulinoma, the most common functioning pancreatic endocrine tumor.

International Incidence is 1-3 cases per million patients per year in Sweden, 0.5 cases per million patients per year in Ireland, and 0.1-0.2 cases per million patients per year in Denmark.

Mortality/Morbidity Currently, the morbidity and mortality of ZES is low because of improved medical and surgical management of the disease. Fewer than 5% of patients develop a complication, such as abdominal perforation, gastric outlet obstruction, or esophageal stricture.

Race All races can be affected.

Sex A slight male predominance exists, with a male-to-female ratio of 1.3:1.

Age The mean age of onset of ZES is 43 years, with the patients with MEN 1/ZES presenting a decade earlier. Generally, a 5- to 7-year delay in diagnosis occurs. In a recent prospective study, fewer than 3% of patients were younger than 20 years, while 7% were older than 60 years at the time of disease onset.

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CLINICAL History A high index of clinical awareness is needed to make a diagnosis of ZES. • Abdominal pain is the most common symptom, present

in 75% of patients. Typically, it is located in the upper abdomen and mimics that of peptic ulcer disease. This symptom is reported more frequently by men and patients with the sporadic form of ZES.

• Of patients with ZES, 73% have diarrhea, and this is the most common symptom in patients who have MEN 1/ZES and in female patients. • The combination of diarrhea and abdominal pain is present in more than half the patients. • Heartburn is the third most common symptom, and this symptom mimics

gastroesophageal reflux disease (GERD). • Other symptoms include nausea, vomiting, gastrointestinal bleeding, and weight loss. Gastrointestinal bleeding frequently is due to ulceration in the duodenum and is the presenting symptom in 25% of patients. • In patients in whom MEN 1/ZES is suspected, a history indicative of nephrolithiasis, hypercalcemia, and pituitary disorders should be sought. A family history of nephrolithiasis, hyperparathyroidism, and gastrinoma also may be present.

Physical The findings of the physical examination may be normal. • Patients may be pale if presenting with gastrointestinal bleeding. • Jaundice may occur if the tumor compresses the common bile duct, although this presentation is very rare. • Epigastric tenderness may be present. • Dental erosions may be noted if symptoms consistent with GERD are present. • The presence of hepatomegaly suggests liver metastasis.

Causes • ZES is caused by a non–beta islet cell, gastrin-secreting tumor of the pancreas that stimulates the acidsecreting cells of the stomach to maximal activity, with consequent gastrointestinal mucosal ulceration. • ZES may occur sporadically or as part of MEN 1. Pasted from <http://www.emedicine.com/med/TOPIC2437.HTM>

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06 KANDEL 2008 Dysphagia and Gastro-esophageal Reflux Disease Friday, February 15, 2008

(5)

List 5 common causes of dyspepsia? List the 3 most common causes of dyspepsia?

H. pylori infection and NSAIDs are the two most common causes of ___?

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Which patients benefit most from proton pump inhibitors (list 4 types)?

There's a high correlation between helicobacter infection and which type of cancer?

Coagulopathy (aka.Bleeding disorders ) Definition Bleeding disorders are a group of conditions involving the body's blood clotting process. Such disorders can lead to heavy and prolonged bleeding after an injury. Causes Normal blood clotting involves as many as 20 different plasma proteins, which are known as blood clotting or coagulation factors. These factors act together with other chemicals to form a substance called fibrin that stops bleeding. Problems can occur when certain coagulation factors are low or missing. Bleeding problems can range from mild to severe. Some bleeding disorders are present at birth and are passed through families (inherited). Others develop during certain illnesses (such as vitamin K deficiency or severe liver disease), or treatments (such as the use of drugs to stop blood clots (anticoagulants) or the long-term use of antibiotics ). Bleeding disorders can also result from having poorly working or too few of the blood cells that promote blood clotting (platelets). These disorders can also be either inherited or picked up (acquired). The side effects of certain drugs often lead to the acquired forms. Symptoms • Abnormal menstrual bleeding • Bleeding into joints! • Excess bruising • Heavy bleeding • Nose bleeds Pasted from <http://www.nlm.nih.gov/medlineplus/ency/article/001304.htm>

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Pasted from <http://www.nlm.nih.gov/medlineplus/ency/article/001304.htm>

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DYSPHAGIA

What is achalasia? The diagnosis of achalasia is confirmed by a ____ test?

Is gastroscopy in a patient with achalasia found to be normal or abnormal?

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Scleroderma is a disease of abnormal ____ (HINT: a type of protein)? In Scleroderma, there is abnormal esophageal motility, namely, ABSENCE OF â&#x20AC;Ś and DECREASED â&#x20AC;Ś? Dysphagia can be due to a lower esophageal ____'s ring?

A Schatzki ring or Schatzki-Gary ring is a ring found in the lower part of the esophagus that can cause difficulty swallowing. The ring is made up of mucosal tissue (which lines the esophagus) or muscular tissue. [1] Patients with Schatzki rings can develop intermittent dysphagia (difficulty swallowing), or, more seriously, a completely blocked esophagus.

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Pasted from <http://en.wikipedia.org/wiki/Schatzki_ring>

CREST

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T/F: a diagnosis of dysphagia can be made by history alone?

How can you distinguish between mechanical and neuromuscular obstruction based on the type of food that causes dysphagia? If someone is deemed to have progressive mechanical obstruction, the next level in the diagnositic algorithm is to determine â&#x20AC;Ś? If someone is deemed to have progressive neuromuscular obstruction, the next level in the diagnositic algorithm is to determine â&#x20AC;Ś?

In the algorithmic approach to dysphagia, food that stops or "sticks" after being swallowed is suggestive of ___ dysphagia whereas a person who has difficulty initiating swallow has a condition suggestive of ___ dysphagia?

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Esophageal Stricture (peptic stricture) Article Last Updated: Jun 27, 2006

Background Disease processes that can produce esophageal strictures can be grouped into 3 general categories: (1) intrinsic diseases that narrow the esophageal lumen through inflammation, fibrosis, or neoplasia; (2) extrinsic diseases that compromise the esophageal lumen by direct invasion or lymph node enlargement; and (3) diseases that disrupt esophageal peristalsis and/or lower esophageal sphincter (LES) function by their effects on esophageal smooth muscle and its innervation. Many diseases can cause esophageal stricture formation. These include acid peptic, autoimmune, infectious, caustic, congenital, iatrogenic, medication-induced, radiation-induced, malignant, and idiopathic disease processes. The etiology of esophageal stricture can usually be identified using radiologic and endoscopic modalities and can be confirmed by endoscopic visualization and tissue biopsy. Use of manometry can be diagnostic when dysmotility is

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confirmed by endoscopic visualization and tissue biopsy. Use of manometry can be diagnostic when dysmotility is suspected as the primary process. CT scan and endoscopic ultrasound are valuable aids in the staging of malignant stricture. Fortunately, most benign esophageal strictures are amenable to pharmacological, endoscopic, and/or surgical interventions. Because peptic strictures account for 70-80% of all cases of esophageal stricture, peptic stricture is the focus of this article. A detailed discussion of possible benign and malignant processes associated with esophageal stricture and its management is beyond the scope of this article.

Pathophysiology Peptic strictures are sequelae of gastroesophageal reflux–induced esophagitis, and they usually originate from the squamocolumnar junction and average 1-4 cm in length. • Two major factors involved in the development of a peptic stricture are as follows: ○ Dysfunctional lower esophageal sphincter: Mean LES pressures are lower in patients with peptic strictures compared with healthy controls or patients with milder degrees of reflux disease. A study by Ahtaridis et al (1979) showed that patients with peptic strictures had a mean LES pressure of 4.9 mm Hg versus 20 mm Hg in control patients. LES pressure of less than 8 mm Hg appeared to correlate significantly with the presence of peptic esophageal stricture without any overlap in controls. ○ Disordered motility resulting in poor esophageal clearance: In the same study, Ahtaridis et al (1979) demonstrated that 64% of patients with strictures had motility disorders compared with 32% of patients without strictures. • Other possible associated factors include the following: ○ Presence of a hiatal hernia: Hiatal hernias are found in 10-15% of the general population, 42% of patients with reflux symptoms and no esophagitis, 63% of patients with esophagitis, and 85% of patients with peptic strictures. This suggests that hiatal hernias may play a significant role. ○ Acid and pepsin secretion: This does not appear to be a major factor. Patients with peptic strictures have been demonstrated to have the same acid and pepsin secretion rates as gender-matched and age-matched controls with esophagitis but no stricture formation. In fact, some authors believe that alkaline reflux may play an important role. ○ Gastric emptying: No good evidence suggests that delayed emptying plays a role. Pasted from <http://www.emedicine.com/med/TOPIC744.HTM>

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GERD stands for? Extra-esophageal symptoms of GERD include â&#x20AC;Ś (list 4)?

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The most accurate test for reflux is â&#x20AC;Ś?

24 hour esophageal pH monitor is the most accurate test for ___?

(Non-esophagitis reflux disease)

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List 3 esophageal complications of esophageal reflux?(5)

In barrett's esophagus there is metaplasia of the esophageal mucosa from ___ to ___? In barrett's esophagus there is increased risk of ___ of the lower esophagus? What is the suggested investigation in barrett's esophagus?

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In esophageal reflux, If nocturnal symptoms are present, what is a suggested nonpharmacological treatment that can alleviate

â&#x20AC;˘ Therefore less acidic intragastric contents are associated with better healing of esophagitis

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-prazole's:

What does NERD stand for? The efficacy of using a proton pump inhibitor is close to ___%?

Name 3 receptors on parietal cells which play an important role in gastric acid secretion?

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Stomach D cells make ___? Somatostatin decreases both ___ cell secretion of acid AND ___ cell secretion of gastrin? ___ and ___ affect parietal cells via ____ cells? What are ECL cells? Somatostatin is made by stomach ___ cells?

Reflux is due to transient relaxation of the â&#x20AC;Ś? 2 accurate indicators of reflux are ___ and ___?

Apart from prescription of proton pump inhibitors and elevating the head of the bed, what is another common nonpharmacological approach to treating reflux?

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Why may patients with pneumonia be more likely to be taking a proton pump inhibitor than a control group? Because pneumonia is one of the extraesophageal signs of reflux disease (also wheezing, laryngitis, cough). The PPI is therefore perhaps secondary to a diagnosis or less commonly, a prophylactic.

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Thursday, March 27, 2008 2:58 AM

Medical Encyclopedia: Scleroderma

URL of this page: http://www.nlm.nih.gov/medlineplus/ency/article/000429.htm Alternative names CREST syndrome; Progressive systemic sclerosis; Systemic sclerosis Definition Scleroderma is a widespread connective tissue disease that involves changes in the skin, blood vessels, muscles, and internal organs. Causes, incidence, and risk factors The cause of scleroderma is unknown. Persons with this condition have a build up of a substance called collagen in the skin and other organs. This build up leads to the symptoms associated with the disease. The disease usually affects people 30 to 50 years old. Women are affected more often than men. Risk factors are occupational exposure to silica dust and polyvinyl chloride. Symptoms • Blanching, blueness, or redness of fingers and toes in response to heat and cold (Raynaud's phenomenon) • Pain, stiffness, and swelling of fingers and joints • Skin thickening and shiny hands and forearm • Skin is hard • Tight and mask-like facial skin • Ulcerations on fingertips or toes • Esophageal reflux or heartburn Week9 Page 149


• Esophageal reflux or heartburn • Difficulty swallowing • Bloating after meals • Weight loss • Diarrhea • Constipation • Shortness of breath Additional symptoms that may be associated with this disease: • Wrist pain • Wheezing • Skin, abnormally dark or light • Joint pain • Hair loss • Eye burning, itching, and discharge Signs and tests Examination of the skin may show tightness, thickening, and hardening. Tests may include: • ESR • Rheumatoid factor • Antinuclear antibody • Urinalysis • Chest x-ray • Pulmonary function studies • Skin biopsy Treatment Drugs used to treat scleroderma include: • Nonsteroidal anti-inflammatory drugs (NSAIDs) • Corticosteroids Other treatments for specific symptoms may include: • Antacids for heartburn • Medications to treat Raynaud's phenomenon • Blood pressure medications (particularly ACE inhibitors) for high blood pressure or kidney problems • Medicines to improve breathing Treatment usually includes a combination of physical therapy and skin and joint protection techniques (for example, avoiding cold in the case of Raynaud's phenomenon). Support Groups See: Scleroderma - support group Expectations (prognosis) In most patients, the disease slowly gets worse. People who only have skin involvement have a better outlook. Death may occur from gastrointestinal, cardiac, kidney, or pulmonary (lung) involvement. Complications • Heart failure • Kidney failure • Pulmonary fibrosis • Pulmonary hypertension • Malabsorption Calling your health care provider Call for an appointment with your health care provider if: • You have symptoms of scleroderma • You have scleroderma and symptoms become worse or new symptoms develop Prevention There is no known prevention. Minimize exposure to silica dust and polyvinyl chloride. Update Date: 4/26/2007 Updated by: Steve Lee, DO, Rheumatology Fellow, Loma Linda University Medical Center, Loma Linda, CA. Review provided by VeriMed Healthcare Network.

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Pasted from <http://www.nlm.nih.gov/medlineplus/print/ency/article/000429.htm>

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Esophageal Manometry

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Hiatus Hernia

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07 STEINHART 2008 Inflammatory Bowel Disease Friday, February 15, 2008

IBD: a chronic recurrent, nonspecific inflammation of the GI tract • Have tendency go through relapses & remissions • No known cause: toxic insults (NSAIDS), and not due to bacteria

What is ulcerative colitis? What is crohn's disease?

• Exact cause of IBD not currently known • Main differences between Crohn's disease and UC: 1. UC, as colitis implies, is limited to the colon: Inflammation in UC refers to colon 2. CD can affect any part of the GI tract from mouth to anus and inflammation may be patchy; areas of inflammation may be separated from each other by areas of bowel

T/F: Crohn's disease can affect ANY part of the GI tract, from the mouth to the anus?

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Theory: IBD prone patients have failure to downregulate acute inflammation

What is thought to be the pathogenesis of IBD?

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Muscularis of the bowel wall is not inflamed and therefore no thickening of the bowel wall in UC

On Pseudopolyps The repeated cycle of ulceration, alternating with the deposition of granulation tissue during the healing phase, results in the development of raised areas of inflamed tissue that resemble polyps.

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However, these lesions are not neoplastic (i.e., true polyps), but inflammatory tissue, and are called pseudopolyps. They have no malignant potential. Pasted from <http://www.endoatlas.com/ib_uc_03.html>

â&#x20AC;˘ In UC there are NO skip lesions, meaning inflammation is continuous from the rectum proximally â&#x20AC;˘ In CD because the inflammation extends transmurally to the bowel wall the ulcers that occur will bleed and therefore and extend to adjacent bowel or skin and result in fistulas

Is it in Crohn's disease or Ucerative Colitis that skip lesions are found? Is it in Crohn's disease or Ucerative Colitis that non-caseating granulomas are found? Is it in Crohn's disease or Ucerative Colitis that the small bowel is involved? Is it in Crohn's disease or Ucerative Colitis where there is superficial inflammation? Is it in Crohn's disease or Ucerative Colitis where thereis transmural inflammation? What are the top 3 locations for Crohn's disease? The maximum incidence of UC and CD occurs between ___ and ___ years of age? The primary diagnostic sign of ulcerative colitis is ___? Is it in CD or UC that an abdominal mass MAY be present? Weight loss, signs of malnurtrition, and perianal disease are ALL MORE COMMON in ulcerative colitis or crohn's disease? T/F: The ONLY histologic feature that's histologic of ulcerative colitis is crypt distortion?

Which clinical feature(s) are most diagnostic of CD? Strictures, fistulas, and sepsis, are all common in UC or CD? Is the risk of malignancy increased in UC or CD? Is the risk of massive hemorrhage increased in UC or CD? T/F: perianal disease may or may not be present in UC but it is very commonly seen in CD?

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• Gross oversimplification of how patients can present

• These are chronic disorders so often have relapses; remission may be many months or many years; can also go into remission spontaneously • We don't know what the trigger(s) are for relapse or remission • Can also have chronic continuous

T/F: Toxic megacolon is a very rare complication of Crohn's Disease?

• With UC, important to point out that the hallmark is RECTAL BLEEDING • If someone says have UC but NEVER had blood in stool, have to questions the Dx; may be CD • Patients with UC typically don't get perianal disease • With UC no thickened loop of bowel or abdominal mass can detect • Abdominal pain inc. in CD may be secondary to obstruction, passage of contents through narrow area • Perianal disease more in CD rather than UC • 30% of patients with CD may have

Manifestations of IBD that occur outside the bowel

• Can ultimately lead to liver damage and cirrhosis List 4 extraintestinal manifestations of IBD?

• Toxic Megacolon: acute, severe form of colitis ○ Bowel wall becomes very thin in this situation • Fortunately not seen very often any more

So how do we make a diagnosis of Crohn's disease? What is the differential diagnosis of suspected jejunal + ileal inflammation, apart from CD? What is the differential diagnosis of suspected jejunal + ileal inflammation, apart from CD? What is the differential diagnosis of suspected jejunal + ileal inflammation, apart from CD? List 3 common intestinal complications of CD? Is Toxic Megacolon more associated with CD or UC?

Erythema Nodosum Background Erythema nodosum (EN) is an acute, nodular, erythematous eruption that usually is limited to the extensor aspects of the lower legs. Chronic or recurrent EN is rare but may occur. EN is presumed to be a hypersensitivity reaction and may occur in association with several systemic diseases or drug therapies, or it may be idiopathic. The inflammatory reaction occurs in the panniculus.

Pathophysiology EN probably is a delayed hypersensitivity reaction to a variety of antigens; circulating immune complexes have not been found in idiopathic or uncomplicated cases but may be demonstrated in patients with inflammatory bowel disease. Pasted from <http://www.emedicine.com/derm/topic138.htm>

Pyoderma Gangrenosum Background Pyoderma gangrenosum (PG) is an uncommon ulcerative cutaneous condition of uncertain etiology. PG was first described in 1930. It is associated with systemic diseases in at least 50% of patients who are affected. The diagnosis is made by excluding other causes of similar appearing cutaneous ulcerations, including infection, malignancy, vasculitis, collagen vascular diseases, diabetes, and trauma. Ulcerations of PG may occur after trauma or injury to the skin in 30% of patients; this process is termed pathergy. The 2 primary variants of PG are the classic ulcerative form, usually observed on the legs, and a more superficial variant known as atypical PG that tends to occur on the hands. Patients with PG may have involvement of other organ systems that

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known as atypical PG that tends to occur on the hands. Patients with PG may have involvement of other organ systems that manifests as sterile neutrophilic abscesses. Culture-negative pulmonary infiltrates are the most common extracutaneous manifestation. Other organs systems that may be involved include the heart, the central nervous system, the GI tract, the eyes, the liver, the spleen, bones, and lymph nodes. The prognosis of PG is generally good; however, recurrences may occur and residual scarring is common. Therapy of PG involves the use of anti-inflammatory agents, such as corticosteroids, and immunosuppressive agents.

Pathophysiology The pathophysiology of PG is poorly understood, but dysregulation of the immune system, specifically altered neutrophil chemotaxis, is believed to be involved. Pasted from <http://www.emedicine.com/derm/topic367.htm>

Toxic Megacolon Background

1. 2. 3.

Toxic megacolon is the clinical term for an acute toxic colitis with dilatation of the colon. The dilatation can be either total or segmental. A more contemporary term for toxic megacolon is simply toxic colitis, because patients may develop toxicity without megacolon. For purposes of this article, the term toxic megacolon is used, but either toxicity or megacolon can occur exclusively of each other. The hallmarks of toxic megacolon, a potentially lethal condition, are nonobstructive colonic dilatation larger than 6 cm and signs of systemic toxicity. Toxic megacolon was recognized in 1950 by Marschak et al. Jalan et al described the diagnostic criteria. The first criterion is radiographic evidence of colonic dilatation. The second criterion is any 3 of the following: fever (>101.5째F), tachycardia (>120), leukocytosis (>10.5), or anemia. The third criterion is any 1 of the following: dehydration, altered mental status, electrolyte abnormality, or hypotension.

Toxic megacolon was first thought to be a complication of ulcerative colitis. In fact, toxic megacolon may complicate any number of colitides, including inflammatory, ischemic, infectious, radiation, and pseudomembranous. The incidence of toxic megacolon is expected to increase due to the rising prevalence of pseudomembranous colitis. Colonic dilatation may be present in other conditions, such as Hirschsprung disease, idiopathic megacolon/chronic constipation, and intestinal pseudoobstruction (Ogilvie syndrome). However, these patients do not develop signs of systemic toxicity and, therefore, do not fall into the category of having toxic megacolon.

Pathophysiology Although the precise pathophysiology of toxic megacolon is unproven, several factors may contribute to its development and precipitation. Signs and symptoms of acute colitis may be present for as long as a week before dilatation develops. Often, triggering or predisposing factors can be identified. While the risk of toxic megacolon increases with the severity of colitis, rapid tapering or abrupt discontinuation of medications such as steroids, sulfasalazine, and 5-aminosalicylic acid may precipitate toxemia and dilatation. Medications that negatively impact bowel motility also are implicated in the development of toxic megacolon. These include, but are not limited to, anticholinergics, antidepressants, loperamide, and opioids. Procedures such as barium enema or colonoscopy may cause distension, may impair blood supply, or may exacerbate a microperforation and cause subsequent toxemia. In cases of uncomplicated colitis, the inflammatory response is confined to the mucosa. The microscopic hallmark of toxic megacolon is inflammation extending beyond the mucosa into the smooth-muscle layers and serosa. Myenteric plexus involvement is not consistent and probably does not contribute to dilatation. As inflammation progresses into the smooth-muscle layers of the colon, nitric oxide appears to be involved in the pathogenesis of toxic megacolon. Nitric oxide inhibits smooth-muscle tone and is generated by inflammatory cells such as neutrophils and macrophages in the inflamed portions of the colon. Studies performed by Mourelle et al. have shown increased amounts of inducible nitric oxide synthetase in the muscularis propria of patients with toxic megacolon. Inflammation and up-regulated nitric oxide synthetase are thought to increase local nitric oxide, which inhibits colonic smooth muscle and causes dilatation. Pasted from <http://www.emedicine.com/MED/topic1418.htm>

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More limited cf. CD but again depends on site of occurence

• If only rectum and sigmoid colon involved, then need consider venereal diseases

(with some erythema or redness of the mucosa)

In Ulcerative Colitis, if ONLY the rectum and sigmoid colon are involved, then you should consider which category of diseases?

List 4 signs/symptoms you would investigate in order to assess the severity of Ulcerative Colitis?(6) List 4 signs/symptoms you would investigate in order to assess the severity of Crohn's Disease?(6)

-- Tachycardi Which blood tests would you do (name 4) to conduct a disease severity assessment in IBD?(6)

In the disease severity assessment of IBD, which 2 neutrophil derived proteins can be measured in the feces because they are released by cells in inflammatory conditions?

Calprotectin and lactoferrin in the assessment of intestinal inflammation and organic disease Abstract

Calprotectin and lactoferrin are specific neutrophil-derived proteins, which can be measured in the feces because they are released by cells in inflammatory conditions. We evaluated the Background and aims

efficacy of calprotectin and lactoferrin in detecting organic disease as assessed by colonoscopy. Methods The study comprised 144 patients undergoing colonoscopy for lower gastrointestinal symptoms (abdominal pain, altered bowel habits, and bloody stools) (67), or inflammatory bowel disease activity, or surveillance for dysplasia (77). A single s tool sample was assayed for calprotectin and lactoferrin. The proportion of patients correctly diagnosed with each test and the relationship with endoscopic and histological findings were measured. Results Fecal excretion of calprotectin significantly correlated with the finding of colonic inflammation at endoscopy, both in ulcer ative colitis and in Crohn’s disease (p<0,001 and p<0,008, respectively), while lactoferrin excretion significantly correlated with histological inflammation (p=0.001 and p=0.009 respectively). Recommended cut-off values need to be adjusted in the inflammatory bowel disease group. Overall sensitivity, specificity, positive predictive value, and diagnostic efficacy were 78, 83, 86, and 80% for calp rotectin and 80, 85, 87, and 81% for lactoferrin, respectively. Conclusions Fecal calprotectin and lactoferrin appear to be equally recommendable as inflammatory disease markers in patients with lower gastrointestinal symptoms. Both tests are needed to accurately discriminate activity in inflammatory bowel disease pati ents. Keywords Calprotectin - Colon cancer - Crohn’s disease - Lactoferrin - Ulcerative colitis Pasted from <http://www.springerlink.com/content/r66601746q885863/>

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Pasted from <http://www.springerlink.com/content/r66601746q885863/>

Oldest drugs used for treatment; related to aspirin

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T/F: Since therapy must be individualized in IBD treatment based upon disease and patient factors, in many specific circumstances, there may NOT be an 'evidence base' available for treatments? For the induction and maintenance of treatment remission in BOTH UC and CD, which 2 drugs can be used? Corticosteroids and immunosuppressive agents can be used to induce remission in (CD or UC)? Antibiotics, ___ and methotrexate can be used to induce remission in (CD or UC)? Azathioprine, methotrexate, and infliximab can be used to induce remission in (CD or UC)? Corticosteroids and immunosuppressive agents can be used to induce remission in (CD or UC)? Which two drugs can be used to BOTH induce AND maintain remission in CD? Which drug, apart from sulphasalazine and 5ASA, can be used to maintain remission in BOTH CD and UC? List 3 drugs that can be used to induce remission in UC?(4) List 4 drugs that can be used to induce remission in CD?(6) List 4 drugs that can be used to maintain remission in CD?(5) List 3 drugs that can be used to maintain remission in UC?(4) T/F: There is NO role for antibiotics in Crohn's disease? Metronidazole can be used in (UC or CD) as a treatment option?


Avascular necrosis (AVN) is defined as cellular death of bone components due to interruption of the blood supply; the bone structures then collapse, resulting in bone destruction, pain, and loss of joint function. AVN is associated with numerous conditions and usually involves the epiphysis of long bones, such as the femoral and humeral heads and the femoral condyles, but small bones can also be affected. AVN of the jaw associated with bisphosphonate use was recently described. In clinical practice, AVN is most commonly encountered in the hip. Pasted from <http://www.emedicine.com/Med/topic2924.htm>

Budesonide is used to treat symptoms of stuffiness and runny nose due to allergies. Pasted from <http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a601030.html>

Newer Corticosteroids These newer corticosteroids are more rapidly metabolized than traditional corticosteroids, and they offer the promise of efficacy with fewer systemic side effects. The packaging of these agents in a pH-sensitive coating (similar to that used for 5-ASA preparations) offers the possibility of drug delivery to the small bowel and right colon with a minimum of side effects. Pasted from <http://www.aafp.org/afp/980101ap/botoman.html>

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(8) 1

5-ASA and sulphapyridine are both derivatives of ___? The two most important side-effects of corticosteroids to worry about in patients with IBD are ___ and ___?

Worry about the most!

8

What is budesonide? Budenoside has a high topical affinity for the ___ receptor? What is the advantage of using budenoside as opposed to conventional steroids? Azathioprine/6Mercaptopurine is indicated for ___ dependent or resistant disease (especially in (CD or UC)? In prescribing azathioprine/6mercaptopruine, which 2 blood tests should you order to monitor levels?

(ie. Broken down very quickly to inactive metabolites)

SKIPPED OVER; NOT USED VERY MUCH ANYMORE; MORE FOR HISTORICAL INTEREST

Interferes with folic acid metabolism

___ may reduce the immunogenecity of infliximab? T/F: Cyclosporine is sometimes used in maintenance therapy for UC?

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Methotrexate may reduce the immunogenecity of ___? Even though there is NO role for cyclosporine in maintenance therapy for UC, there MAY be a role for it in treating (which type of) CD or pyoderma gangrenosum?

List two indications for the use of infliximab in UC? List 3 indications for the use of infliximab in CD?(5)

List 3 potentially adverse outcomes relating to the use of biologics in the treatment of IBD?(4)

• REMICABE given as 3 treatments over 2 weeks; only treatment that's been shown to actually close these fistulas

SURGERY FOR TREATMENT OF IBD Indications

• Surgery is curative for patients with UC ○ Have to have an ileostomy or a pelvic pouch procedure (pouch fashioned out of remaining small intestine)

Indications

• In CD, surgery also an option ○ CD CAN come back in previously unaffected segments; NOT a curative procedure then

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List 3 indications for surgery in CD?(8) List 3 indications for surgery in UC?(7)


09 ROSSOS 2008 Pancreatitis Sunday, February 17, 2008

Difference between acute and chronic pancreatitis?

What are the endocrine and exocrine functions of the pancreas?

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Regarding the etiology of acute pancreatitis, the TWO MAJOR causes are ___ and ___?

Overall mortality for acute pancreatitis is ___ to ___%?

ERCP: Endoscopic Retrograde CholangioPancreatography

During an endoscopic retrograde cholangiopancreatography, a catheter is advanced through the endoscope and inserted into the pancreatic or biliary ducts. A contrast agent is injected into

these ducts and X-rays are taken to evaluate their caliber, length and course.

Narrowing, stones, and tumors in the ducts can be identified in the X-rays. Update Date: 5/8/2006 Pasted from <http://www.nlm.nih.gov/medlineplus/ency/imagepages/19564.htm>

(7) 1

7

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List 3 miscellaneous causes of acute pancreatitis (ie. Not alcohol, gallstones, idiopathic)?(5)


(early)

List 2 drugs which may cause druginduced pancreatitis via chronic accumulation of toxic metabolites?(3)

(months)

List 2 antimicrobial agents that may cause acute pancreatitis?(5)

List 7 groups of drugs that cause acute pancreatitis?

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What is the gold standard for establishing or excluding a CF diagnosis?

T/F: It IS NOT recommended that CFTR mutation screening be regularly performed in patients with pancreatitis?

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(7)

Release of lipase from the pancreas leads to which major systemic effect? Release of Phospholipase A2 from the pancreas leads to which major systemic effect? Release of complement from the pancreas leads to which major systemic effect? Release of thrombin from the pancreas leads to which

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the pancreas leads to which major systemic effect? Release of elastase, chymotrypsin, and kallikrein from the pancreas leads to which major systemic effect(s)? Fat necrosis secondary may occur secondary to the release of which major pancreatic enzyme?

How can you clinically diagnose acute pancreatitisâ&#x20AC;Ślist 5 ways?(5)

(Physical examination)

In actue pancreatitis, over the course of the first week of enzyme release, levels of which pancreatic enzyme are generally higher than amylase?

amylase

lipase

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of the first week of enzyme release, levels of which pancreatic enzyme are generally higher than amylase?

amylase

lipase

In which of the following causes of increased serum lipase will serum lipase actually be NORMAL (ie. NOT be raised): pancreastitis, parotitis, biliary stone, intestinal injury, tubo-ovarian disease, renal failure, macroamylasemia.

â&#x20AC;˘ So amylase levels are NORMAL in a. Parotitis, b. Tubo-ovarian disease, and c. Macroamylasemia

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In which of the following causes of increased levels of BOTH serum lipase AND amylase will levels of amylase and lipase actually be INCREASED: tubo-ovarian disease, renal failure, macoamylasemia, intestinal injury, pancreatitis, parotitis, biliary stone? In renal failure levels of serum amylase and lipase may be as high as ___ X normal?


serum amylase and lipase may be as high as ___ X normal?

Prognostic factors in acute pancreatitis include (name 2 general ones)? Examples of local complications secondary to acute pancreatitis include?

Overall mortality due to acute pancreatitis is about ___ to ___%?

How is BMI related to

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How is BMI related to prognosis of AP?

ERCP: Endoscopic Retrograde CholangioPancreatography

List 2 indications for early (48-72 hrs) ERCP in acute pancreatitis?

During an endoscopic retrograde cholangiopancreatography, a catheter is advanced through the endoscope and inserted into the pancreatic or biliary ducts. A contrast agent is injected into

these ducts and X-rays are taken to evaluate their caliber, length and course.

Narrowing, stones, and tumors in the ducts can be identified in the X-rays. Update Date: 5/8/2006 Pasted from <http://www.nlm.nih.gov/medlineplus/ency/imagepages/19564.htm>

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(5) 1 List 3 supportive therapies that can be offered in acute pancreatitis?(5)

5

Signs and symptoms of

(4) Pancreatitis is often caused by ___ or by ___? Symptoms of acute pancreatitis include â&#x20AC;Ś(list 4)?(5) When does acute pancreatitis become chronic? List 3 signs/symptoms of chronic pancreatitis?(4)

1

4

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09 ROSSOS 2008 Pancreatitis Friday, February 15, 2008

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11 FMP 2008 THURS GI MALIGNANCY Seminar Friday, February 15, 2008

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1. Think of ways to categorize it: anatomically, according to motor/neuro a. Motor ○ Rings: shasky rings: fibrotic rings; usually in lower esophageal area; webs that are in esophagus that can cause dysphagia b. Neuro ○ Achalasia - when you swallow fluid, LES relaxes; so failure to relax the LES; often these people have a lack of peristaltic waves in lower end of esophagus ○ Parkinson's disease, myasthenia gravis, GBS ○ If think of oropharyngeal transfer dysphagia, most commonly dysphagia in orpharyngeal area is due to stroke, parkinson's ms, lou gherig's disease; can also get webs, zenker's diverticulum In anatomy, Zenker's diverticulum, also pharyngoesophageal diverticulum, is a diverticulum of the mucosa of the pharynx, just above the cricopharyngeal muscle (i.e. above the upper sphincter of the oesophagus). Pasted from <http://en.wikipedia.org/wiki/Zenker's_diverticulum>

What is Zenker's diverticulum? Zenker's diverticulum typically occurs above which muscle? Pasted from <http://www.mayoclinic.org/images/zenkers-diverticulum-lg-bdy.jpg>

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Colorectal Cancer Screening in Elderly Patients Sunday, February 17, 2008 1:57 PM

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Esophageal Cancer Sunday, February 17, 2008 1:57 PM

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FMP2 Summary Of Notes