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Journey through the GI tract. Barb Bancroft, RN, MSN www.barbbancroft.com [email protected] Open wiiiiiiide…. Let’s take a journey through the GI tract with a few stops along the way…. The Teeth. Tooth loss and heart disease

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Journey through the gi tract l.jpg

Journey through the GI tract

Barb Bancroft, RN, MSN

www.barbbancroft.com

[email protected]


Open wiiiiiiide l.jpg
Open wiiiiiiide…

  • Let’s take a journey through the GI tract with a few stops along the way…


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The Teeth

  • Tooth loss and heart disease

  • Periodontal disease, subclinical vasculitis and coronary plaque development

  • State with the least teeth is the state with the most heart disease


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Oral bacteria and coronary artery disease

  • Specific periodontal pathogens are implicated

  • Enter the bloodstream via small ulcers that develop in the gum tissue of patients with periodontal disease

  • Contribute to plaque formation via inflammation; induce platelet aggregation and clot formation

  • 4 bacteria are implicated—Tannerella forsythia, Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, Treponema denticola.

  • Depending on the bacterial concentration, the increased risk of heart attack in persons with one or another of these bacteria ranges from 200-300 percent, compared to people with no evidence of the bacteria


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Floss

  • “Floss only the teeth you want to keep…”

  • MINUTIAE: On average, each person uses 54 feet of dental floss every month or about 1.5 feet of floss per day which equals 548 feet of floss in a year.


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Meth mouth

  • 22 y.o. meth user; snorted and/or injected meth x 2 years

  • Denied use of any other drugs

  • Drank 2-3 liters of carbonated drinks each day because of a dry mouth

  • How addicting is methamphetamine? Dopamine and addiction

  • (British Journal of Medicine 2006;333:156)


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Osteoporosis and tooth loss

  • Osteoporosis of the mandible and maxilla on dental X-rays—loss of trabecular bone

  • Women who do NOT take estrogen have fewer teeth


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Bites

  • The bite scale. The King of the Jungle, the African lion, has a bite force of only 940 pounds (427 kg). Hyenas register a 1,000-pound (454 kg) bite which explains why they might get the best of the African lion. Dusky sharks manage only 300 pounds (136 kg) of force.


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Bites

  • Labrador retrievers nip at your ankles with 125 pounds (57 kg) of force, only slightly surpassed by the infamous Mike Tyson, the heavyweight boxer, who chomped off Evander Holyfield’s ear with a force of 170 pounds (77 kg).

  • Had we lived in the day of the dinosaur, Tyrannosaurus Rex, the bite would have registered 3,011 pounds (1369 kg).

  • What about Petey the pit bull? Endorphins, L-tyrosine and dopamine


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Other human bites

  • Self-inflicted bites

  • Thumb-sucking

  • Seizures (can you swallow your tongue?)

  • Child abuse


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Gingival hypertrophy

  • Drugs—phenytoin (Dilantin), nifedipine (Procardia), cyclosporine

  • Leukemias—acute and chronic


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The immunocompromised patient

  • Candida albicans (inhaled steroids in asthmatics)

  • Diabetics with hyperglycemia

  • Fungal infections and TNF-α antagonists (infliximab/Remicade; adalimumab/Humira; certolizumab/Cemzia etanercept/Enbrel)

  • HSV-1, HSV-2

  • Kaposi’s sarcoma

  • HPV

  • HIV (TB)


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OPEN Wide

  • Aphthous ulcers and celiac disease

  • Mouth clues to vitamin deficiencies

  • Vitamin C—gingivitis, dental erosion

  • Vitamin B2 (riboflavin)—stomatitis, cheilosis, geographic tongue

  • Vitamin B3 (niacin), B6 (pyridoxine), B12 (cobalamin), folic acid (B9)—glossitis

  • Calcium (hypocalcemia)—numbness and tingling around the mouth**; tetany; Chvostek’s sign; Trusseau’s sign


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Say “ah”…

  • Soft palate and the uvula

  • Relationship of the pharyngeal musculature with CN IX (Glossopharyngeal) and X (Vagus)

  • Stroke patients

  • Swallowing

  • What is the hardest thing to swallow?


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Water…

  • Ya’ can’t size it, ya’ can’t shape it…


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Back to CN IX and X

  • The gag reflex

  • CN IX and X close off the nasopharynx

  • Head injured patients lose their gag reflex and have a high risk of aspiration pneumonia

  • Open your mouth and pant like a dog

  • “K, K, K, K, K”

  • uvula midline


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Causes of nasal speech

  • Cleft palate (folic acid!!)

  • Lou Gehrig’s (ALS) disease

  • Glossopharyngeal nerve palsy—(viral)

  • Guillain-Barré syndrome with bulbar onset (cranial nerve onset vs. ascending paralysis beginning with the longest nerves first—ie. the feet)

  • #1 cause of Guillain-Barré


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The “PRILS”

Muffled speech

Swollen lips, pharyngeal edema

Hives around the mouth

Highest risk patients?

Don’t forget the cough…

Drugs discovered because of a bite—Brazilian pit viper

Captopril (Capoten)

Enalapril (Vasotec)

Lisinopril (Prinivil, Zestril)

Perindopril (Aceon)

Moxepril (Univasc)

Benazepril (Lotensin)

Quinapril (Accupril)

Trandolapril (Mavik)

Ramipril (Altace)

Etc…

Diabetics, HBP, CHF, post-MI)

ACE inhibitors and angioedema


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Hoarseness

  • Vocal cords supplied by a branch of the vagus--recurrent laryngeal nerve

  • Causes of hoarseness? increased vocal cord thickness--testosterone, hypothyroidism, acromegaly, aneurysm of the thoracic aorta, lung cancer, and GERD—just to name a few

  • Hypothyroidism, large tongue, teeth indentations--♀ > ♂

  • Amyloidosis


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Salivary glands—parotid, sublingual, submandibular

  • Parotid gland—MUMPS (kids and vaccines)

  • Hypertrophy of the parotid gland in women with eating disorders (serum amylase will be elevated)

  • Acetylcholine innervates the salivary glands to produce saliva

  • Drugs to boost acetylcholine for patients w/ dry mouths—5 mg QID pilocarpine; cevimeline (Evoxac)

  • Artificial saliva?


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More on saliva

  • Sjögren’s syndrome (sicca)—autoimmune disease; may be primary or secondary to another autoimmune disease such as lupus

  • Saliva as innate defense--IgA

  • Taste and saliva—the elderly and anticholinergic drugs; stop the flow of saliva


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Drugs with anti-cholinergic properties

  • Amitryptyline (Elavil)

  • Doxepin (Sinequan)

  • oxybutynin (Ditropan)

  • Meclizine (Antivert)

  • Theophylline

  • Captopril (Capoten), nifedipine (Procardia)

  • Prednisolone

  • digoxin

  • dipyridamole (Persantine)

  • warfarin

  • Furosemide (Lasix)

  • isosorbide dinitrate (Isordil)


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More anticholinergic drugs

  • Codeine

  • Oxycodone

  • Fexofenadine (Allegra)

  • thioridazine (Mellaril)

  • Hydroxyzine (Atarax)

  • Loratadine (Claritin)

  • dicyclomine (Bentyl)

  • Cimetidine (Tagamet), ranitidine (Zantac)

  • benztropine (Cogentin)

  • trihexyphenidyl (Artane)

  • Diphenhydramine (Benadryl)

  • haloperidol (Haldol)


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Sublingual

  • Saliva and sublingual drugs—you need saliva to absorb sublingual drugs

  • NTG under the tongue to vasodilate the coronary arteries in patients with anginal chest pain

  • Jaundice and soft palate/sublingual mucosa


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How much saliva do you make a day? about 1 liter of saliva per day

How many times do you swallow in an hour? (70/200/10)

Swallowing is something we take for granted…spit in a cup!

Swappin’ saliva…chemistry? MHC complex

Speaking of saliva…


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Neurologic conditions per day

  • Parkinson disease

  • Low dopamine with a relative increase in acetylcholine

  • Relative increase in acetylcholine results in excess saliva and drooling


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You take swallowing for granted--until you have this sore throat…

  • Say ahhhhh…

  • Can you say “ouch”?

  • Can you say “I have a sore throat, and I can’t swallow…”

  • Group A beta hemolytic strep

  • Peritonsillar abscesses


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Enlarged tonsils throat…

  • EBV infection of tonsils

  • Waldeyer’s ring (tonsils and adenoids)

  • Kids and sleep apnea; kids, lack of sleep and growth hormon

  • Adults and sleep apnea? (hypertension, CAD in adults)

  • Behavior disorders? ADHD? In kids?

  • Non-Hodgkin’s lymphoma


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Oral signs of an eating disorder throat…

  • The frequent vomiting and nutritional deficiencies often associated with eating disorders can severely affect health

  • 89% of bulimic patients have signs of tooth erosion; over time, loss of tooth enamel can be considerable

  • Change in color, shape, length

  • Brittle, translucent, and sensitive to temperature

  • Swelling of salivary glands

  • Dry and cracked lips

  • Chronic dry mouth


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Oral cancers throat…

  • Causes? The usual suspects…

  • Tobacco, smoked, chewed, pipes, cigars, cigarettes, cigarillos

  • Alcohol?


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Cut back on the booze… throat…

  • Alcohol is on the list of “probable cause” for cancers of the colon, rectum and breast; “convincing cause” of cancers of the mouth and pharynx, larynx, esophagus, liver, and “possible cause” for lung cancer.


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The big surprise…Oral cancers and HPV throat…

  • HPV-16 and oral sex

  • mouth/throat cancer

  • Will the HPV vaccine (Gardisil) prevent this type of cancer if given early?


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Let’s move into the esophagus throat…

  • Hollow, highly distensible muscular tube that extends from the pharynx to the gastroesophageal junction at the level of T11 or T12 vertebra.

  • 10 to 11 cm in the newborn

  • 23 to 25 cm in the adult

  • A 2-4 cm segment just proximal to the anatomic esophagogastric junction, at the level of the diaphragm, is the LES, or lower esophageal sphincter


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GERD (gastroesophageal reflux disease) throat…

  • ACID is the bad guy

  • The Lower Esophageal Sphincter (LES) pressure

  • With GERD--decreased pressure in the lower esophageal sphincter due to drugs, nicotine, alcohol, fatty foods, peppermint, chocolate, citrus fruits and juices, increased pressure in stomach (late evening meal)

  • So, how about a pizza, cold beer and a cigarette before bedtime?

  • What drugs? Bronchodilators, NTG, tetracycline, quinidine, KCl, NSAIDS, Iron salts, bisphosphonates, Viagra and other ED drugs

  • Obesity


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What are non-drug ways to reduce GERD? throat…

  • Dietary changes?

  • A meta-analysis in the Archives of Internal Medicine revealed support for 2 measures:

  • Weight loss and head-of-bed elevation

  • Avoiding tobacco, alcohol, high-fat foods, and carbonated beverages was NOT shown to alleviate symptoms of GERD—even tho’ there is substantial evidence that consumption of these substances has an adverse impact on GERD


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Pharmacology of GERD throat…

  • Classic reflux sx (heartburn, reflux) have a + predictive value of 80%

  • Empiric therapy can be started without endoscopy, but endoscopy can only tell whether or not erosive esophagitis is present

  • PPIs (Proton Pump Inhibitors)—the “prazoles” are the mainstay of therapy in healing erosive esophagitis and treating symptoms of GERD

  • Omeprazole (Prilosec), lansoprazole (Prevacid), pantoprazole (Protonix), rabeprazole (Aciphex), and “the purple pill”—esomeprazole (Nexium)

  • Fastest acting—esomeprazole, rabeprazole, omeprazole, lansoprazole, pantoprazole


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Drugs to treat GERD throat…

  • MOA—Inhibition of the proton pump at the luminal surface of the stomach…especiallyafter a meal—work best when taken 30-60 minutes before breakfast or dinner

H+, Intrinsic Factor-B12

PPIs work here

Luminal surface

Parietal cell

Basilar surface

H2

H2 receptors

H2 blockers work here


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H throat…2 blockers

  • Work by blocking H2 receptors on basal surface of the parietal cell; work best when taken at night to reduce nocturnal histamine secretion and acid production

  • Cimetidine (Tagamet)*

  • Ranitidine (Zantac)

  • Famotidine (Pepcid)**

  • *drug interactions and side effects

  • **least drug interactions and side effects and most effective


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Has your patient been on the “prazoles” for longer than 5 years?

  • Check B12 levels in your patients…

  • The parietal cell that pumps acid also pumps out intrinsic factor (IF)

  • Intrinsic Factor is necessary for the absorption of B12 from food

  • If you stop pumping the acid into the stomach, you also stop pumping intrinsic factor for B12 absorption

  • Combine that with a decreased absorption of B12 over the age of 50 and you may have a B12 deficiency;

  • May also be caused by an autoimmune disease with antibodies against IF (pernicious anemia)

  • No acid, no calcium (elderly and patients on PPIs need to take calcium citrate for absorption)

  • No acid, no iron (check for iron deficiency anemia)


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Hematologic and neurologic symptoms of B12 deficiency 5 years?

  • Hematologic—megaloblastic anemia (big, immature RBCs)—MCV is greater than 120; also known as a macrocytic anemia

  • Neurologic—Cognitive dysfunction; Spinal cord dysfunction; peripheral neuropathy

  • The number 1 nutritional cause of dementia is B12 deficiency—is it reversible? Yes.

  • How can you supplement with B12?


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B12 supplementation 5 years?

  • Pill

  • Sublingual

  • Nasal

  • Injection

  • Need 6 mcg per day; take 1000 mcg by mouth/sublingual/nasal daily (1% via passive diffusion in stomach if you take B12 by mouth)

  • 1000 mcg/month via injection

  • Do not take over 3,000 mcg per day…the one dreaded side effect is:


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Barrett’s esophagus 5 years?

  • Complication of acid reflux (GERD)

  • Metaplasia of the lower third of the esophagus

  • What is metaplasia? The substitution of one adult cell for another adult cell

  • Usually a protective mechanism

  • Gastric epithelial cells have replaced squamous epithelial cells of the esophagus

  • Gastric epithelial cells are “used to” acid


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What do we know about Barrett’s esophagus? 5 years?

  • Patients with at least weekly symptoms of GERD—3-15% are found to have Barrett’s

  • May be a gross underestimate—autopsy findings were 20-fold higher than clinical studies

  • Caucasian males greater than 55; 2:1 ratio; big bellies contribute…Body fat increases intraabdominal pressure; fatty foods decrease LES pressure; high dietary intake of nitrates

  • Increased insulin resistance results in high serum levels of insulin-like growth factor-1

  • Adenocarcinoma of the esophagus (10% in 1960; 50% in 2005);

  • One of fastest rising cancers in U.S.


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What do we know about Barrett’s esophagus? 5 years?

  • Progression to dysplasia is an ominous histologic finding—precursor to invasive adenocarcinoma

  • Annual risk is 0.5% per year

  • 30x to 40 x greater risk of adenocarcinoma w/ Barrett’s if greater than 2 cm of Barrett mucosa on endoscopy

  • Does ultra-aggressive anti-secretory therapy have anti-proliferative effects on intestinal metaplasia? Recent studies say yes…higher than conventional PPI doses

  • BID dosing if QD doesn’t relieve symptoms of GERD (35% of patients are on BID dosing)

  • Add H2 blocker at HS—double the OTC dose (Zantac 300 po hs)

  • Nocturnal symptoms are more often associated with severe disease—esophageal cancer, otolaryngologic and pulmonary disorders


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Esophageal candidiasis/rupture 5 years?

  • HIV patients—dysphagia in AIDS patients—also consider Herpes simplex and CMV esophagitis

  • Irritation and possible rupture in postmenopausal females taking bisphosphonates (Fosamax and friends)

  • Other pills “stick”

  • Lye, acids, and detergents


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Esophageal dysmotility syndromes 5 years?

  • Achalasia--LES is too tight, lack of peristalsis in lower third of esophagus; LES needs to be dilated frequently

  • Viagra has been used to open the LES (nitric oxide relaxes the sphincter)

  • Esophageal spasms (women and other spastic disorders)


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Esophageal varices 5 years?

  • How do you develop esophageal varices?

  • Due to increased pressure in the portal system of the liver

  • Primarily due to cirrhosis of the liver; 90% of patients with cirrhosis will develop varices

  • Worldwide, hepatic schistosomiasis is the second most common cause of variceal bleeding

  • Beta blockers to reduce portal pressure

  • 40% die with first episode, rebleeding occurs in more than half within one year


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Major causes of cirrhosis of the liver today are… 5 years?

  • Hepatitis C (15% clear on own; 85% develop chronic hepatitis; chronic hepatitis can lead to cirrhosis and hepatocellular carcinoma)

  • Hepatitis B (10% develop chronic hepatitis, 90% clear on own as adults; opposite percentages with infants and vertical transmission)

  • Alcohol (fatty liver)

  • Diabetes (fatty liver)

  • Obesity (fatty liver)

  • NASH (Non-alcoholic steato-hepatitis, also known as non-alcoholic fatty liver disease--NAFLD)


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Hepatitis C virus--1989 5 years?

  • Cirrhosis with progression to hepatocellular cirrhosis


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Hepatitis C virus—identified in 1989 5 years?

HIGH RISK GROUPS—primary factors

  • IV drug user (even 1 time experimental drug use)

  • Blood transfusions prior to July1992 —or organ transplant recipients

  • Persons who have ever received hemodialysis

  • Hemophiliacs who received clotting factor concentrates prior to 1987

  • Children born to HCV-infected moms (screen at age 1 or older)


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Hepatitis C high risk factors 5 years?

  • HCW after a needle stick injury or mucosal exposure to HCV-positive blood

  • Current sexual partners of monogamous HCV-infected persons (prevalence is low, but a negative test provides reassurance)

  • How about MULTIPLE partners—how many?

  • Intranasal cocaine use

  • Tattoos (prison applied?)

  • Body piercings

  • Receipt of injection in a developing world


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Treatment of Hepatitis C wait between getting a tattoo and donating blood

  • 24 weeks vs 48 weeks depending on genotype

  • Pegylated interferon + ribivirin


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The stomach wait between getting a tattoo and donating blood

  • “Whoever said the way to a man’s heart is through his stomach flunked geography…”

    --anonymous

  • The stomach is a saccular organ with a volume of 1200 to 1500 ml but a capacity of greater than 3000 ml


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Gastric acid wait between getting a tattoo and donating blood

  • At maximal secretory rates, the stomach intraluminal concentration of hydrogen ion is 3 million times greater than that of the blood and tissues

  • The mucosal barrier protects the gastric mucosa from autodigestion and is created by:

  • mucus secretion;

  • bicarbonate secretion

  • epithelial barrier and,

  • mucosal blood flow

  • Truly a physiological marvel, or gastric walls would suffer the same fate as a T-bone


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Peptic ulcer disease wait between getting a tattoo and donating blood

  • Usually solitary lesions less than 4 cm in diameter

  • Duodenum, first portion

  • Stomach, antrum

  • GE junction, in the setting of GERD

  • 4 million people have peptic ulcers; 350,000 new cases per year, 100,000 hospitalized, 3000 die

  • Male/female for duodenal = 3:1; male/female for gastric = 1.5 to 2:1

  • Imbalance between the gastroduodenal mucosal defense mechanisms and the damaging forces—gastric acid and pepsin

  • Hyperacidity is NOT a prerequisite

  • H. pylori is present in 100% of duodenal ulcers and about 70% of patients with gastric ulcers


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Gastric ulcers (peptic ulcer disease) wait between getting a tattoo and donating blood

  • Helicobacter pylori—the most common infection worldwide

  • Elaborates urease and produces ammonia which buffers gastric acid in the immediate vicinity

  • Gastric ulcers

  • Chronic inflammation (gastritis) and regeneration of the antrum

  • The only bacteria known to be “oncogenic”

  • Is it normal flora?

  • How do you “catch” it?

  • How do you treat it?

  • Is H. pylori a good thing?


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Gastric ulcer caused by NSAIDS wait between getting a tattoo and donating blood

  • 2.74 RR of any GI complication

  • If over 50, RR is 5.57

  • RR 12.7 with NSAIDS and warfarin; 4.76 with NSAIDS and steroids

  • PPIs decrease ulcer/ bleed by 4-fold


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Gastric cancer wait between getting a tattoo and donating blood

  • In 1930, gastric cancer was the most common cause of cancer death in the U.S.

  • Annual mortality rate in the US has dropped from 38 to 7 per 100,000 in men and from 28 to 4 per 100,000 in women.

  • Causes 2.5% of all cancer deaths in U.S. and is the leading cause of deaths from cancer worldwide

  • H. pylori and diet play a major role

  • N-nitroso compounds and nitrates, benzopyrene

  • Consumption of preserved, smoked, and cured and salted foods

  • Water contamination with nitrates


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Bariatric surgery—BMI ≥ 30 wait between getting a tattoo and donating blood

  • Swedish study—2010 patients; 74% followed for 10 years; 0 relapsed into obesity; found that the most effective therapy was the gastric bypass—removing most of the lower part of the stomach and attaching to a loop of small bowel

  • Stapling only half as effective

  • Lap-banding

  • Risk? Only about ¼ of 1 percent mortality rate

  • Long-term effects? malabsorption

  • Cure for type 2 diabetes? Duodenal exclusion surgery


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The small intestine—duodenum, ileum, jejunum wait between getting a tattoo and donating blood

  • Small intestine is ~6-7 meters (18 to 22 feet) in length; large intestine is ~1.5 meters in length

  • First 25 cm (12 inches) is duodenum

  • Normal renewal of the epithelial lining of the small intestine every 4 to 6 days; colonic turnover every 3 to 8 days

  • Remarkable capacity for repair, but it also renders the intestine particularly vulnerable to agents that interfere with cell replication, such as radiation and chemotherapy


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The small intestine and grapefruit juice wait between getting a tattoo and donating blood

  • Metabolizing enzymes to break drugs are located in the small intestine

  • CYP3A4 metabolized 40-60% of all drugs (11000)

  • Grapefruit juice/grapefruit inhibits this enzyme; drugs metabolized by this enzyme enter the system in a higher bioavailability—hence, drug toxicity


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Grapefruit juice interactions increase bioavailability and increase the risk for toxicity

  • Amiodarone HCl—increased absorption with GFJ increasing risk of adverse effects and toxicities:

    pulmonary toxicity, hypotension, and cardiac arrhythmias, (TSH). Avoid using Amiodarone in patients who may not understand the toxic potential of this interaction.

  • Felodipine (Plendil), nisoldipine (Sular), nicardipine HCl (Cardene), nifedipine (Procardia), isradipine (Dynacirc)—increased toxicity with headaches and peripheral edema

  • Simvastatin (Zocor)—300% increase in bioavailability with grapefruit vs. atorvastatin (Lipitor) 25% increase; rosuvastatin (Crestor)—no interaction


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Grapefruit juice/grapefruit increase the risk for toxicity

  • Avoid grapefruit juice and grapefruit with antibiotics

  • One interaction is especially dangerous

  • Interaction between grapefruit juice and erythromycin

  • Accumulates and may cause tachycardia

  • Prolongs QT interval and may cause death from “torsades de points”


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Fluids and the small intestine increase the risk for toxicity

  • A typical adult imbibes 2 liters of fluid per day, to which is added 1-1.5 liters of saliva; 2 liters of gastric juice; 1 liter of bile; 2 liters of pancreatic juice, and 1 liter of intestinal secretions

  • Of these 9 liters presented to the intestine, less than 200 gm of stool are excreted per day, of which 65 to 85% is water.

  • Jejunal absorption is 3 to 5 liters/day; ileal absorption is 2 to 4 liters per day; colon absorbs 1 to 2 liters per day but is capable of absorbing almost 6 liters per day.


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The duodenum (12 fingerbreadths), —the organ of nausea increase the risk for toxicity

  • 5-HT3 (serotonin) receptors)

  • Serotonin release causes nausea--Makes ya’ sick to your duodenum

  • 5-HT3 blockers--The “setrons”—ondansetron (Zofran), granisetron (Kytril), doasetron (Anzemet), palonosetron

  • Adding ondansetron to oral rehydration in kids reduces nausea and vomiting and decreases the need for IV fluids by greater than 50%


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Celiac disease and the duodenum increase the risk for toxicity

  • 1 in 250 in U.S.; greater prevalence in 1st and 2nd degree relatives; ?duration of breast feeding; age at which a person ingests gluten; cigarette smoking

  • Autoimmune disease—HLA-DQ2; HLA-DQ8

  • Ingested gluten crosslinks with tissue transglutaminase released in the lamina propria and epithelium of the small intestine

  • Ingested gluten crosslinks with tissue transglutaminase released in the lamina propria and epithelium of the intestine

  • Leads to the deamidation of the gluten peptides

  • CD4 cells become stimulated; cytokines IF-γ and IL-4 which damage villi; flattened villi and malabsorption

  • Anti-transglutaminase antibodies


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Celiac disease increase the risk for toxicity

  • Classic symptomatic presentation characterized by diarrhea, abdominal pain, weight loss, flatulence, and nutritional deficiencies

  • Atypical presentation characterized by gait ataxia, seizures, peripheral neuropathy, aphthous stomatitis, arthritis, migraine headaches

  • Associated with other autoimmune diseases—Type 1 diabetes, autoimmune myocarditis, primary biliary cirrhosis

  • Gluten-free diets and the improvement of symptoms


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Celiac disease increase the risk for toxicity

  • Absorption problems result in anemias—iron deficiency (growth problems in kids); folate deficiency; calcium absorption problems (osteopenia)

  • Always check for osteopenia and osteoporosis in your long-term patients with celiac disease!

  • aphthous ulcers are both strongly associated w/ celiac disease (This Week in Medicine, MDConsult, 1/31/07)


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Gastroenteritis… increase the risk for toxicity

  • Umbilicus (belly button)—embryologic origins with colon (Homer and Dr. Colón)

    Word o’ the day…

    Omphaloskepsis (om-fuh-lo-SKEP-sis); noun

  • Definition: Contemplation of one’s navel. (From Geek omphalos (navel) + skepsis (act of looking, examination)

  • Peri-umbilical pain

  • Causes of gastroenteritis—food poisoning, viral infections, bacterial infections


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Gastroenteritis increase the risk for toxicity

  • Infectious gastroenteritis—causes more than 12,000 deaths per day from dehydration among children in developing countries and constituting one half of all deaths worldwide before age 5

  • Attack rates of one to two illnesses per person per year in U.S.—results in an estimated 99 million acute cases of either vomiting or diarrhea per year—approximately 40% of the population


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Viral gastroenteritis increase the risk for toxicity

  • Rotavirus—140 million cases and 1 million deaths worldwide per year; 6 to 24 months of age; shed 1,000,000,000,000 (10¹² particles)/ml of stool (the minimum infective inoculum is only 10 particles, hence the rampant outbreaks in daycare and pediatric populations in hospitals)

  • Norwalk virus (norovirus)—rare in young kids; incubation period of 1 to 2 days followed by 12 to 60 hours of “shuking”


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Noroviruses increase the risk for toxicity

  • Responsible for majority of nonbacterial food-borne epidemic gastroenteritis in older children and adults;

  • Salad bars (cold foods, raw shellfish), person-to-person,water on cruise ships

  • Has also been found in the community and in nursing homes

  • Vicious cycle of vomiting and diarrhea for an average of 23 hours—known as “shuking”

  • start shedding virus before symptoms occur and shed virus for 4 days after symptoms subside (hence, the rapid spread of infection); can shed virus up to 4 to 8 weeks after illness


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Bacterial entercolitis increase the risk for toxicity

  • Ingestion of preformed toxin in food—Staphylococcus aureus, Vibrio species, Clostridium perfringens

  • Infection by toxigenic organisms, which proliferate in the gut lumen and elaborate an enterotoxin (Cholera toxin is the prototype secretagogue)

  • Infection by enteroinvasive organisms, which proliferate, invade, and destroy mucosal epithelial cells (Salmonella, Yersinia enterocolitica)


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Acute appendicitis increase the risk for toxicity

  • Acute appendicitis presents initially with peri-umbilical pain and subsequently localizes to the right lower quadrant (RLQ)

  • High risk occupation for acute appendicitis?

  • Pig farmers


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Salmonella in raw or undercooked eggs and chicken increase the risk for toxicity

  • Pasteurized eggs for “seizure” salad (Caesar salad), eggnog, and guacamole

  • Salmonella in chicken

  • No more sunny-side up, especially for high-risk patients (unless the eggs are pasteurized)


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Campylobacter increase the risk for toxicityjejuni

  • Undercooked chicken

  • 180º whole chicken

  • 170º white meat

  • 180º dark meat


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E. Coli 0157:H7— increase the risk for toxicitythe “burger” bug

  • 3rd most deadly toxin in the world

  • 10-100 pathogens to make you ill or kill you

  • Very young, very old, very immunocompromised

  • Acute Renal Failure in Kids—hemolytic uremic syndrome

  • Swimming pools, petting zoos

  • Mickey D’s—30 outbreaks per year

  • Supportive Treatment

  • Prevent—cook burgers to 160º F

  • Produce is the biggest offender for E.Coli O157:H7


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Crohn’s disease—inflammatory bowel disease increase the risk for toxicity

  • Primarily small bowel, but can include anywhere from the esophagus to the rectum

  • Skip lesions; fistulas; strictures

  • Cause? Bacteria? Mycobacterium paratuberculosis?

  • Autoimmune response


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Signs and symptoms increase the risk for toxicity

  • Usually begins with intermittent attacks of relatively mild diarrhea, fever, and abdominal pain, spaced by asymptomatic periods lasting for weeks to many months

  • 1/5th of patients with abrupt onset, with acute RLQ pain, fever, and diarrhea

  • Diff dx suggesting acute appendicitis or acute bowel perforation

  • Chronic disease with fibrosing strictures, marked loss of albumin, generalized malabsorption, B12 malabsorption, or malabsorption of bile salts leading to steatorrhea


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Treatment increase the risk for toxicity

  • Methotrexate to reduce the immune response

  • Inflammation via TNF-alpha

  • Drugs that block TNF-alpha include infliximab (Remicade), adalimumab (Humira), etanercept (Enbrel)

  • Certolizumab pegol (Cemzia)


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Antibiotic-associated diarrhea increase the risk for toxicity

  • “the usual, run-of-the-mill diarrhea” vs.

  • Clostridium difficile diarrhea (new strain)—the “floxacins” and Clindamycin are the biggest offenders for C. difficile


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Clostridium difficile increase the risk for toxicity

  • Clostridium difficile (difficult to culture, hence, difficile) and soap and water kill spores better than alcohol-based gels

  • New strain (2003) produces more toxin and causes more severe outbreaks—produces 16x more toxin A and 23 times more toxin B; characterized by the deletion of a gene that downregulates the production of both toxins

  • Major risk factor? Use of the fluoroquinolones; Other antibiotics? Amox/Ampicillin, 2nd/3rd generation cephalosporins


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A few more notes on increase the risk for toxicityC. diff

  • Has your patient had dental work with prescribed antibiotics?

  • Treatment—vancomycin, metronidazole

  • Stool transplants in chronic C. diff

  • High risk of recurrence in patients over 65, patients with severe underlying disease, and additional antibiotic use after discontinuing therapy for C. diff.

  • Surawicz CM. Reining in recurrent Clostridium difficile infection—Who’s at risk? Gastroenterology 2009 Apr;136:1152.


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Necrotizing entercolitis (NEC) of the newborn increase the risk for toxicity

  • Acute, necrotizing inflammation of the small and large intestine and is the most common acquired gastrointestinal emergency of neonates, particularly those who are premature or of low birth weight

  • Any time in the first 3 months, peak around time infants are started on oral foods (2 to 4 days old)

  • Another cause: Maternal cocaine use can compromise intestinal blood flow, too


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The sheep increase the risk for toxicity

  • You wanna do WHAT with my intestines?

  • Clinical uses of a sheep’s cecum


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Movin’ right along …to the large bowel increase the risk for toxicity

  • What are the functions of the large bowel?


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Functions of the large bowel increase the risk for toxicity

  • Defense against bacteria--normal flora

  • Production of Vitamin K

  • Peristalsis and movement of feces

  • Acetylcholine triggers peristalsis (anticholinergic drugs)

  • Nicotine

  • Serotonin also triggers peristalsis

  • SSRIs and diarrhea


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Functions of the large bowel increase the risk for toxicity

  • Net absorption of water and salts/net secretion of K+--diarrhea and potassium depletion


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Constipation increase the risk for toxicity

  • “If you need time to think, ask older patients to describe their bowel habits”.

    --Clifton Meador, M.D

  • The scope of the problem? 15% of the population suffers from chronic constipation, and over $1 billion is spent on laxatives annually

  • Normal number of bowel movements?

  • 3 per day to 3 per week or fewer than seven bowel movements over a 2-week period with no medication usage as a precipitating cause


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Constipation increase the risk for toxicity

  • + Rome III criteria w/ 5 other signs other than stool frequency: straining, lumpy or hard stools, incomplete evacuation, sensation of obstruction, need for manual maneuvers to facilitate evacuation

  • If 2 or more of these 6 criteria are present for at least 12 weeks during the previous 12 months, a diagnosis of functional constipation can be made


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Constipation—causes? increase the risk for toxicity

  • Drugs—anticholinergic, opiods (codeine, oxycodone)

  • reduced fluid and fiber intake

  • laxative abuse— “prune abuse”

  • dementia—the “neglect of the call to stool”

  • cancer of the colon

  • decreased activity

  • The infamous “other” category


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New drug for opiate-induced constipation increase the risk for toxicity

  • Relistor (REL-i-store). It’s almost impossible to not get constipated from opiods because of their effects on motility. Relistor (methlynaltrexone) is an opiod antagonist. Hmmmm…if it antagonizes opiods then how do the opiods manage the pain. Here’s the beauty of Relistor. Once the “methyl group” is added to naltrexone, it prevents the antagonist from entering the brain and reducing the opiods effects in the brain. Relistor just blocks the opiod effect in the bowels. Almost 50% of the patients will find relief within just 4 hours of taking Relistor—hallelujah! It’s an injection by the way—subQ and it’s primarily approved for palliative care patients that are not getting relief from any other regimen.


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Treatment for diarrhea increase the risk for toxicity

  • Lomotil for diarrhea (atropine sulfate + diphenoxylate HCl)

  • Loperamide (Imodium)

  • Undiarrhea (Taiwan)

  • Stopit (Israel)

  • “Lomotil is so good, it will…”


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Colon cancer—98% adenocarcinomas (large intestine) increase the risk for toxicity

  • The numbers…

  • Peak incidence for colorectal carcinoma is 60 to 79 years; fewer than 20% of cases occur before the age of 50

  • Cecum and ascending colon, 38%; transverse colon, 18%; descending colon, 8%; sigmoid, 35%; multiple sites at presentation, 1%

  • Risk factors?


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Genetics increase the risk for toxicity

  • Who’s yo’ daddy?

  • When should you start screening family members with a history of early-onset cancer?

  • Dad with colon cancer at diagnosed at 42?


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And yo’ momma? increase the risk for toxicity

  • Patients with a family history of 2 second-degree relatives w/ colorectal cancer should also start screening at age 40


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Risk factors--polyps increase the risk for toxicity

  • Three types

  • Tubular adenomas—cancer is rare in tubular adenomas smaller than 1 cm in diameter

  • Villous adenomas—tend to be large and sessile; risk of cancer is high (approaching 40%) in sessile villous adenomas greater than 4 cm in diameter

  • Tubulovillous adenoma—mixture of the two


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Aspirin and polyps- increase the risk for toxicity-38% of those taking an 81.5 mg (low-dose aspirin) had a new polyp compared to 47% in the placebo group. This is a risk reduction of 9%. Now, this isn’t a jaw-dropping difference however, IF colon cancer is a high risk in your family or in a specific patient population, a low-dose aspirin might give you an edge against the disease. (April 2001, American Association of Cancer Research meeting, San Francisco)


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Risk factors increase the risk for toxicity

  • Constipation

  • “Gosh, I remember when happy hour was something other than a good bowel movement!”


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Hereditary colon cancers increase the risk for toxicity

  • What about the use of COX-2 inhibitors for the prevention of colon cancer in patients with familial adenomatous polyposis (FAP)—absolutely

  • Screening should start as young as 20 in FAP patients


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Ulcerative colitis—inflammatory bowel disease increase the risk for toxicity

  • Limited to the colon and affects only the mucosa and submucosa; extends in a continuous fashion proximally from the rectum

  • Peak onset between 20 and 25 years of age

  • Risk for colon cancer—risk is highest in patients with pancolitis of 10 or more years duration; 30% @ 35 years after dx

  • Dysplasia (distortion of the normal orientation and architecture of cells)—low-grade dysplasia vs. high-grade dysplasia and ulcerative colitis


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Colon Cancer increase the risk for toxicity

  • Get it in and get it out!

  • GI transit time…less than 72 hours

  • How can you tell? Eat corn tonight…

  • Floaters vs. sinkers

  • Other dietary risks—obesity; high content of refined carbohydrates; intake of red meat; decreased fiber


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Don’t forget your colonoscopies! Every 10 years after 50 increase the risk for toxicity

  • Or sigmoidoscopy every 5 years

  • Don’t forget to ask about a change in bowel habits.

  • Exit time for colonoscopies should be at least 8 minutes to increase the detection of polyps


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Dietary prevention of colon cancer? increase the risk for toxicity

  • Fiber decreases proliferation

  • Decreases insulin release from pancreas (growth hormone)

  • Decreases ILGF-1

  • Calcium and vitamin D?

  • Decreased red meat?


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Speaking of gas… increase the risk for toxicity

  • What is the BFR (basal flatal rate)?

  • How often do we pass gas per day?

  • The PPFR (post-prandial flatal rate)?The PPFR after a meal comprised of 51% baked beans?

  • Gender differences?


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Diverticular disease increase the risk for toxicity

  • A diverticulum is a blind pouch communicating with the lumen of the gut

  • Rare under 30; over age 60 the incidence approaches 50%

  • Usually multiple diverticula = diverticulosis

  • 2 factors are important in their genesis

    a) focal weakness in the colonic wall

    b) increased intraluminal pressure

  • 20% w/ diverticula exhibit symptoms; lower abdominal discomfort, constipation, distention, sensation of never being able to empty the rectum completely


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The rectum—a portal of entry… increase the risk for toxicity

  • Comments from patients during rectal exams: (Dr. James Ralph)

  • “Find Amelia Earhart yet?”

  • “Can you hear me NOW?”

  • “Hey, now I know how a muppet feels…”

  • “How long have you been in politics?”

  • “Remind me never to become an altar boy.”

  • “Could you write me a note for my wife, saying that my head is not, in fact, up there?”


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The rectum increase the risk for toxicity

  • Rectal foreign objects

  • HPV and rectal warts

  • Herpes

  • Other STIs

  • Rectal cancer—squamous carcinoma of the rectum (HPV)


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The end. increase the risk for toxicity

  • Barb Bancroft, RN, MSN, PNP

  • CPP Associates, Inc.

  • www.barbbancroft.com

  • [email protected]


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Bibliography increase the risk for toxicity

  • Bariatric Surgery—Journal of the American Medical Association (292:1724, 2004); Emergency Medicine (37#7;31, 2005); British Medical Journal (331:128, 2005)

  • Celiac disease—Patient Care (March 2005; 16-20); Nutrition in Clinical Care (8#2; 55, 2005)

  • Ondansetron and oral rehydration—N Engl J Med (354;1698, 2006 April)

  • Proton pump inhibitors and C. difficile colitis– JAMA 2005; 294:2989-2995.

  • Probiotics. Canani RB et al. Probiotics for treatment of acute diarrheal illness in children: Randomised clinical trial of five different preparations. BJM 2007 Aug 18:335-340.


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