By M. Candela. Davenport College. 2018.

An important prin ciple central to metabolism is that the bodys basic unit is the cell cheap 10mg provera with visa. In turn generic provera 10mg on-line, each cell contains tiny organs, called organelles, that perform specic metabolic tasks. Discovery By Accident The work of a scientist is often likened to locking together the pieces of a jigsaw puzzle. Slowly and methodically, one by one, the pieces t together to make a pretty picture. The truth is, scientists dont have a puzzle box to know what the nished picture is supposed to look like. If you know the result of an experiment ahead of time, its not really an experiment. Being a scientist is hard work, but most researchers love the freedom to explore their curiosities. They test ideas methodically, nding answers to new problems, and every day brings a new challenge. Medicines By Design I Body, Heal Thyself 17 The cell is directed by a command center, the One important type of metabolism that occurs nucleus, where the genes you inherited from your constantly in our bodies is the reading and inter parents reside. These proteins personalized instruction manualare kept safe underlie the millions of chemical reactions that in packages called chromosomes. Proteins perform structural roles, cells has an identical set of 46 chromosomes, keeping cells shaped properly. Proteins also work 23 inherited from your mother and 23 from as enzymes that speed along chemical reactions your father. Metabolism they metabolizeeither break your bodys way of making energy and body down or activatehundreds of parts from food and watertakes place in every prescribed medicines and natural cell in every organ. Scientists who specialize ways of cellular signals make up metabolism, in pharmacogenetics (see page 8) have dis linking together all the systems that make covered that the human genetic code contains your body run. Her molecules called research has revealed that natural components prostaglandins of certain foods, including horseradish, oranges, (see page 21). River of Life Since blood is the bodys primary internal trans portation system, most drugs travel via this route. Medicines can nd their way to the bloodstream in several ways, including the rich supply of blood magical molecules that can make a clot form vessels in the skin. Blood is a rich child, the horror of seeing blood escaping your concoction containing oxygen-carrying red blood body through a skinned knee. You survived called plasma that contains clotting proteins, the scrape just ne because blood contains electrolytes, and many other important molecules. Skin plays an important role in preserving steps in the immediate care of a burn patient uid balance and in regulating body temperature took scientists decades to gure out, as they and sensation. Immune cells in skin help the body performed carefully conducted experiments on prevent and ght disease. Burn-induced 1980s, researchers doing this work developed skin loss can give bacteria and other microorgan the rst version of an articial skin covering called isms easy access to the nutrient-rich uids that Integra Dermal Regeneration Template, which course through the body, while at the same time doctors use to drape over the area where the allowing these uids to leak out rapidly. Today, Integra uid loss can thrust a burn or trauma patient into Dermal Regeneration Template is used to treat shock, so doctors must replenish skin lost to severe burn patients throughout the world. Two organ quick way to get a needed medicine to a diseased systems are particularly interesting to pharma organ, one of the biggest problems is getting the cologists: the nervous system (which transmits medicine to the correct organ. In many cases, electrical signals over wide distances) and the drugs end up where they are not needed and cause endocrine system (which communicates messages side effects, as weve already noted. These two systems are drugs may encounter many different obstacles key targets for medicines. Some medicines get lost when they stick tightly to certain proteins in the blood, effectively putting the drugs out of business. Skin consists of three layers, making up a dynamic network of cells, nerves, and blood vessels. Blood Vessel Nerve Hair Follicle Sweat Gland Fat 20 National Institute of General Medical Sciences No Pain, Your Gain Like curares effects on acetylcholine, the inter actions between another drugaspirinand metabolism shed light on how the body works. This little white pill has been one of the most widely used drugs in history, and many say that it launched the entire pharmaceutical industry. The bark of the willow tree contains a substance called salicin, a known antidote to headache and fever since the time of the Greek physician Hippocrates, around 400 B. Despite its usefulness dating back to ancient times, early records indicate that salicylate wreaked havoc on the stomachs of people who ingested this natural chemical. In the late 1800s, a scientic Salicylate Acetylsalicylate is the aspirin of today. Adding a chemical tag called an acetyl group (shaded yellow box, right) to a molecule derived from willow bark (salicy late, above) makes the molecule less acidic (and easier on the lining of the digestive tract), but still effective at relieving pain. Acetylsalicylate (Aspirin) Medicines By Design I Body, Heal Thyself 21 breakthrough turned willow-derived salicylate into a medicine friendlier to the body. Bayer scientist Felix Hoffman discovered that adding a chemical tag called an acetyl group (see gure, page 20) to salicylate made the molecule less acidic and a little gentler on the stomach, but the chemical change did not seem to lessen the drugs ability to relieve his fathers rheumatism.

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Arterioscle- An aneurysm is dened as an abnormal focal dilation of rosis in older patients is difcult to treat surgically buy provera 5mg without prescription, as an artery (see Table 2 purchase provera 10mg. A true aneurysm may be further subdivided stenoses or occlusions in medium-sized arteries into saccular in which there is a focal out-pouching suchastheiliac,femoralandrenalarteries;however, or fusiform where there is dilation of the whole cir- as patients often present late the disease may be too cumference of the vessel. A guide wire is inserted and then a bal- occurs following penetrating trauma when there is a loon fed over the wire and inated within the lesion. They may dissect and cut off blood critical ischaemia or severely limiting intermittent supply to tissue or rupture with resulting haemor- claudication, because failed grafting worsens symp- rhage. In addi- r Altered ow patterns predispose to thrombus forma- tion, most patients have other conditions such as tion, which may embolise to distal arteries or cause ischaemic heart disease, diabetes and cerebrovascu- occlusion at the site of the aneurysm. Abdominal aortic aneurysms may be found incidentally as a central expansile mass on examination or as calci- Sex cation on an X-ray. Patients may present with a dull, aching chronic or intermittent epigastric or back pain due to expansion. Geography Rupture causes a tearing epigastric pain that radiates Becoming more common in the developed world. More than half of aneurysms over 6 cm will rupture Pathophysiology within 2 years thromboembolism. The arterial wall becomes thinned and is replaced with brous tissue and stretches to form a dilated saccular or Investigations fusiform aneurysm. Suprarenal aneurysms have a much poorer prognosis with a high risk of renal impairment. Many patients have Management concomitant ischaemic heart disease or cerebrovascular r Ruptured abdominal aortic aneurysm is a surgical disease, which affects outcome. O negative blood may be required untilbloodiscross-matched,asbloodlosscanbemas- Denition sive. Aortic dissection is dened as splitting through the en- r Surgery at a specialist centre gives the best outcome, dothelium and intima allowing the passage of blood into but patients may not be t for transfer. In all cases there is degeneration of collagen r Asymptomatic small aneurysms should be managed and elastic bres of the media, known as cystic me- conservatively with aggressive management of hyper- dial necrosis. Trauma, including insertion of an arterial tension and other risk factors for atherosclerosis and catheter, is also a cause. Whilst surgical techniques remain There is an intimal tear, then blood forces into the aortic the standard treatment, increasingly endovascular wall, it can then extend the split further along the wall stenting techniques are being used that can be per- of the vessel. The most com- to make the diagnosis, particularly in haemodynami- mon site for these to start is at the point of the ductus cally unstable patients. They may extend as far down as the is required, and importantly hypertension should be iliac arteries. Intravenous Dissection classically presents with excruciating sudden -blockers, glyceryl trinitrate and hydralazine may all onset central chest pain, which may be mistaken for an be needed. The pain tends to be tear- ing, most severe at the onset and radiates through to cardiopulmonary bypass. Most patients are hypertensive at presenta- placed using a Dacron graft and the aortic valve re- tion. Hypotension suggests signicant blood loss, acute paired or replaced as necessary. Haemorrhage from descending aortic aneurysms may Asymptomatic thoracic aortic aneurysms found by cause dullness and absent breath sounds at the left lung screening, e. Complications Prognosis Dissection or formation of thrombus on the damaged Untreated thoracic aortic dissection results in 50% mor- endothelium may obstruct any branch of the aorta, tality within 48 hours. In all patients long-term strict and thus stroke, paraplegia (due to spinal artery in- blood pressure control is needed. Myocardial infarction may occasionally be due to dis- section involving the coronary arteries. Incidence r Chest X-ray may show a widened mediastinum: di- Commonest vascular emergency. Incasesofembolifurtherpost- of atrial brillation or post-infarction) or from ab- operative investigation is required to establish the source normal, infected or prosthetic heart valves. Hypo- Following assessment and resuscitation treatment in- volaemia or hypotension often precipitates complete volves the following: occlusion. Less commonly thrombosis may arise in r Heparintominimisepropagationofthrombus,invery non-atherosclerotic vessels as a result of malignancy, mild cases this will be sufcient. Loss of arterial blood supply causes acute ischaemia and r Acute occlusion with signs of severe ischaemia is irreversible infarction occurs if the occlusion is not re- treated with emergency surgery. Aftertheocclusionisrelievedthere mbectomy is usually performed with a Fogarty bal- maybesecondarydamageduetoreperfusioninjury. This loon catheter under local anaesthetic if possible, and is due to the production of toxic oxygen radicals, which complex cases may require arterial reconstruction. Clinical features Prognosis Patients present with a cold, pale/white and acutely Acute upper limb ischaemia tends to have a better prog- painfullimb,whichbecomesweakandnumbwithlossof nosis, as there is better collateral supply.

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Proc Natl Acad Sci cytokines upregulate inammation in response to peptidoglycan U S A 2009 purchase provera 2.5mg amex;106:15481553 cheap provera 10 mg without prescription. Rat hepatocytes and Kupffer cells interact to produce epigenetics in the actions of alcohol. J Cell Physiol 2007;213: expression in intestinal epithelial cells and its potential role in 286300. Gastroenterology 1997;112:2073 choline decient diet-induced nonalcoholic steatohepatitis mod- 2088. Mechanisms of alcohol-induced hepatic cell accumulation in mice and humans with alcoholic and nonal- brosis: a summary of the Ron Thurman Symposium. Hepatology 2004;39: stimulating factor induces proliferation of hepatic progenitors in 13901397. J Clin Gas- long-term outcome of severe alcohol-induced hepatitis treated troenterol 2004;38:292295. Current concepts and controversies in thionine in alcoholic liver cirrhosis: a randomized, placebo-con- the treatment of alcoholic hepatitis. J Hepatol 2010;52: review: glucocorticosteroids for alcoholic hepatitisa Cochrane 759764. Anabolic-androgenic steroids trial sequential analyses of randomized clinical trials. Propylthiouracil for alcoholic severe alcoholic hepatitis treated with steroids: early response liver disease. Hepatology 2007;45:1348 holic patients with cirrhosis of the liver: results of a controlled, 1354. In vitro steroid resis- versus corticoids alone: a multicentre, randomized, controlled tance correlates with outcome in severe alcoholic hepatitis. Ann Intern Med short-term survival in severe acute alcoholic hepatitis: a double- 1990;112:917920. Gastroenterology 2007;132:687 prednisolone for severe alcoholic hepatitis: a randomized con- 697. Pentoxifylline for rates alcoholic liver injury in a murine model of chronic-binge alcoholic hepatitis. The signicance of the in patients with severe alcoholic hepatitis is inefcient in non- complement system for the pathogenesis of age-related macular responders to corticosteroids. Graefes Arch Clin Exp Ophthalmol 2011;249:163 steroids with iniximab or placebo in severe alcoholic hepatitis: 174. Gastroenterology 2007; antiapoptotic caspase inhibitor, may lower aminotransferase 132:25332541. J Hepatol 2006;45: Institut dInvestigacions Biomdiques August Pi i Sunyer, Centro de 306320. In general, drug therapy is not indicated in managing diarrhea in children, although zinc supplementation Author Disclosure and probiotic use show promise. Drs Granado-Villar, Cunill-De Sautu, and Objectives After reading this article, readers should be able to: Granados have disclosed no nancial 1. Understand the importance of early feedings on the nutritional status of a child who commentary does has gastroenteritis. Fully understand that antidiarrheal agents are not indicated nor recommended in the an unapproved/ treatment of acute gastroenteritis in children. Recognize the role of vomiting in the clinical presentation of acute gastroenteritis. Introduction Acute gastroenteritis is an extremely common illness among infants and children world- wide. In developing countries, diarrhea is a common cause of mortality among children younger than age 5 years, with an estimated 2 million deaths each year. American children younger than 5 years have an av- erage of two episodes of gastroenteritis per year, leading to 2 million to 3 million ofce visits and 10% of all pediatric hospital admissions. Furthermore, approximately one third of all hospitalizations for diarrhea in children younger than 5 years are due to rotavirus, with an associated direct cost of $250 million annually. Stool patterns may vary among children; thus, it is important Abbreviations to note that diarrhea should represent a change from the norm. Vomiting followed by diarrhea may be the initial presentation in children, or vice versa. Recent medications and the childs Cryptosporidium immunization history also should be reviewed. The phys- Giardia lamblia ical examination should focus on identifying signs of de- Entamoeba histolytica Helminths hydration such as level of alertness, presence of sunken Strongyloides stercoralis eyes, dry mucous membranes, and skin turgor. Bacterial infections may result also divided patients into three groups: no signs of dehydra- in inltration of the mucosal lining of the small and large tion (<3%5%), some signs of dehydration (5%10%), and intestines, which in turn causes inammation. Furthermore, more obvious clinical signs of dehydration Assessment of Dehydration become apparent at 5% dehydration, and indications of Dehydration related to acute gastroenteritis is a major severe dehydration become evident when the uid loss reaches 9% to 10%.

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Classification of Gallbladder and Bile Duct Stones Two major types of gallstones exist (Table 2) provera 5 mg generic. Cholesterol stones are hard buy provera 10mg with mastercard, crystalline stones whose composition is more than 50% cholesterol, plus varying amounts of protein and calcium salts. Pigment stones are characterized by and acquire their colour from the insoluble pigment, calcium bilirubinate. Frequency of gallstone disease in different countries Very Common Common (10-30%) Intermediate (<10%) Rare (<0%) (30-70%) o American Indians o United States o United States o East Africa (whites) (blacks) o Sweden o Canada (whites) o Japan o Canada (Inuit) o Chile o Russia o Southeast Asia o Indonesia o Czechoslovakia o United Kingdom o Northern India o West Africa o United States o Australia o Greece o Southern Africa (Hispanics) o Italy o Portugal o Germany First Principles of Gastroenterology and Hepatology A. Classification of Gallstones Characteristic Cholesterol Pigment Black Brown o Composition - Pigment polymer - Calcium birubinate - Calcium salts (phosphates, - Calcium soaps carbonates) (palmitate, stearate) o Consistency - Crystalline - Hard - Soft, greasy o Location - Gallbladder (+/- - Gallbladder - Common Duct common duct) - Bile Ducts o Radiodensity - Lucent (85%) - Opaque (50%) - Lucent (100%) 1. Three key stages in cholesterol gallstone formation, expressed as a Venn diagram: 1. Pronucleating proteins (especially mucins) then precipitate cholesterol microcrystals (shown as two notched rhomboids); and finally 3. Impaired gallbladder emptying in the final stage results in stasis that allows the time for these microcrystals to be entrapped in a mucin gel, which aggregates and attracts other insoluble components of bile (such as bile pigment and calcium), and so becomes biliary sludge and evolves into overt gallstones. Shaffer 562 Cholesterol gallstones result primarily from an imbalance of the constituents of bile, aided by bile stasis. Bile is composed of three major organic molecules that are lipids: bile acids, phospholipids (phosphatidylcholine or lecithin) and cholesterol, in addition to its chief constituents: water and electrolytes. In the first stage of cholesterol gallstone formation, the liver secretes excess cholesterol, forming supersaturated bile that cannot be solubilized by bile salts and lecithin. Certain genetic factors affecting the canalicular transporters are likely responsible, eliciting their phenotypic effect through exposure to environmental factors like female sex hormones and obesity. With time and in the presence of pronucleating agents particularly mucin gel, cholesterol microcrystals precipitate out of solution the second stage. Mucin, a glycoprotein secreted by the gallbladder, then acts as a matrix scaffold for stone growth. The excessive cholesterol in bile also becomes incorporated into gallbladder smooth muscle, stiffens its sacroplasmic membranes, and so impairs signal transduction and contraction. In the third stage, gallbladder hypomotility and stasis facilitates retention, allowing the microcrystals to agglomerate and grow into overt gallstones. On abdominal ultrasound, biliary sludge is echogenic material that layers but unlike gallstones, sludge does not cast an acoustic shadow. Sludge develops in association with conditions causing gallbladder stasis, such as during pregnancy or total parenteral nutrition. Though frequently asymptomatic and prone to disappear, sludge in the gallbladder can evolve into overt stones, or may escape into the biliary tract producing biliary- type pain, cholecystitis or even pancreatitis. Risk factors for cholesterol gallstone formation are a family history (genetic), obesity/metabolic syndrome, female gender and aging. Certain ethnic groups such as First Nations persons are especially prone to cholelithiasis (Table 3). Mechanisms and clinical presentation for gallstone formation Cholesterol gallstones Black pigment stones Brown pigment stones Mechanisms o Excessive cholesterol o Chronic hemolysis o Stasis secretion o Altered bilirubin o Strictures metabolism o Excessive bilirubin excretion Associations Metabolic: o Cirrhosis o Infection o Family history o Cystic fibrosis o Inflammation o Obesity/Metabolic o Crohn disease syndrome o Advanced age o First Nations person o Female sex hormones o Aging First Principles of Gastroenterology and Hepatology A. Pigment Stones Black pigment stones constitute about 15% of gallstones found at surgery (cholecystectomy) in North America, These small, hard gallstones are composed of calcium bilirubinate as a polymer plus inorganic calcium salts (e. The basis for their formation is excessive (or abnormal) bilirubin excretion in bile. They tend to form in alcoholic patients, chronic hemolytic states and with old age. When ileal disease or loss causes bile salts to escape into the colon (especially the cecum) in large quantities, this biological detergent can then solubilize the bile pigment and return it via the portal vein to the liver. This creates an enterohepatic circulation for pigment material whose subsequent secretion into bile becomes excessive, creating black pigment stones. Brown pigment stones, soft and greasy, are composed of bilirubinate and fatty acids that respectively account for their color and slippery texture. These brown stones form in bile ducts associated with inflammation, infection (often from a stricture or tumor) or parasitic infestation (e. Bacteria and inflamed tissues release -glucuronidase, an enzyme that deconjugates bilirubin. The resultant free bilirubin then polymerizes and complexes with calcium to form calcium bilirubinate that precipitates in the bile duct system. Hydrolytic enzymes, acting on phospholipids, meanwhile produce fatty acids like calcium palmitate and stearate. Biofilm, a glycoprotein produced by bacteria as their glycocalyx, then agglomerates this pigment material, leading to brown stones.

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Then wiggle one finger order 2.5 mg provera with mastercard, then the other buy discount provera 2.5mg on line, then both, in all visual fields (or count fingers) Red pinhead test: test for colour sensitivity more sensitive than acuity (good for vague hemianopia). Blind spot = scotoma Hemianopia: Pituitary lesion bitemporal hemianopia (nasal retina affected). Upper temporal field in one eye is typically affected first Parietal lesion visual inattention 3, 4, 6: Seeing double. Often elderly have trouble looking up anyway Cover test: look at target, cover one eye, does other eye move? Use stick man drawn on tongue depressor Problems locating target (overshoot and come back) ? Test corneal reflex (early sign of lesion) patient looks up, use cotton wool on cornea (more sensitive than sclera) th Motor 5 : jaw opening in midline (tests pterygoids). Dont normally test taste 8: whispered voice at arms length, with patients eyes close. Observe sternomastoid and trapezius at rest for wasting, fasciculation, or dystonia. Always test neck extension if diffuse muscle weakness if abnormal indicates lesion above C1/C2 12: Hypoglossal nerve. Rapid passive movement maximal tone to start with, decreases suddenly as muscle is lengthened. Due to reflex contraction to muscle stretch Clonus: maintaining stretch (eg of ankle plantar flexors) further repetitive beating Power: compare between sides Test in position where patient has mechanical advantage: you shouldnt be able to win then if its normal Grade as follows: 0: no contraction 1: a flicker/trace of contraction 2: active movement with gravity eliminated 3: active movement against gravity but not against resistance 4: active movement against gravity and resistance, but reduced power (covers wide range can classify as mild, moderate or severe weakness) 5: normal power Motor exam of the arms: Observe arms at rest, then outstretched with eyes closed (check for drift non-specific test). Look st for wasting of 1 dorsal interosseus and abductor pollicis brevis Assess tone at elbow (flexion/extension and supination) and wrist (flexion/extension) with slow and rapid movements Arms (start at top and work down) Shoulder abduction (deltoid, C5, axillary nerve). Extended cocked wrist push it down Finger extension (extensor digitorum, C7). Look for atrophy of thenar eminence Motor Exam of the legs: Observation of legs: while standing, walking, lying down. Look for wasting of tibialis anterior and small muscles of feet Check for tone Check for clonus. Flex hip and knee to 45 degrees, externally rotate hip, rapidly dorsiflex foot and hold. Two or three beats of clonus may be normal if symmetrical Power in Legs (patient lying down): Hip flexion (ilio-psoas, L1-2, lumbar plexus). Push down on raised straight leg Hip extension (gluteus maximus, sciatic nerve, L5-S1). Often normally absent Leg (if no response, interlock fingers of both hands and pull just before tap) Patella (hold knees up) (L3/L4) Ankle (passively dorsiflex ankle) (S1). Not positive if withdrawal response (hip and knee flexion) due to over response Superficial Abdominal reflexes: Not tested routinely. Tires quickly Co-ordination Rapid alternating movements of hand: supinate and pronate hand rapidly (dysdiadokinesia) Finger-nose-finger test. Not too fast (may mask intention tremour) Heel-knee-shin test Heel-toe walking: tests midline cerebellar vermis Romberg: tests dorsal column sensory loss (ie proprioception). Rare in clinical practice Important syndromes including ataxia: Cerebellar haematoma: Sudden onset of progressive headache, vomiting, and inability to stand or walk. Decompressive surgery can be lifesaving th Wernickes Encephalopathy: Confusion, ataxia, nystagmus. Common with prolonged vomiting, poor nutrition, not confined to alcohol Sensory test Issue is where and why to test. Very easy to suggest to patient Common scenarios: Hemisensory loss: stroke, peripheral root and nerve lesion Glove or stocking: spinal chord lesion or peripheral neuropathy Get patient to close eyes. Dont try to completely map just test key boundaries Key Dermatomes: Stand on S1 Sit on S3 Groin: L1 Neuro-sensory 121 Umbilicus: T10 Nipple: T5 T2 meets C4 on line connecting axilla: should be clear difference across this line in any lesion between T2 and C4 Middle Finger: C7 Position sense: hold big toe by the sides, explain which way is up and down, then test. First sensation to go in progressive deterioration Pinprick: Use large safety pin and discard after use. More reliable than light touch if both damaged Temperature: Not usually done if pin prick done Light touch (cotton wool) Others (not routine): Two point discrimination Stereognosis: recognising objects by their feel (coin, key, etc). Normal hand first Graphaesthesia: write numbers on the hand Sensory inattention: touch sides separately and together which is being touched? Usually spinal chord lesion Muscle disease (rare): initial proximal pattern of weakness neck flexion, shoulder abduction, hip flexion Hemiparesis due to stroke: 1/day in Wellington (this one is not peripheral) Hand: Common Lesions: Ulnar neuropathy: Elbow compression weakness of finger but not thumb abduction. Sensory loss on little finger Median nerve compression in Carpal Tunnel Syndrome: weakness and wasting of abductor pollicis brevis, with numbness of palmar surface of fingers 1,2,3 and lateral 4. Tingling/pain which wakes at night C7 Radiculopathy: pain from neck, shoulder, arm and forearm. Weakness of elbow, wrist and finger extension C6 Radiculopathy: Weakens elbow flexion and wrist extension.

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