Medical Student

Cholecystitis : Overview

noreply@blogger.com (Han Idris) — Wed, 25 Apr 2012 00:43:00 +0000

Author

Alan A Bloom, MD Associate Clinical Professor of Medicine, Albert Einstein College of Medicine; Attending Physician, Department of Gastroenterology, Veterans Affairs Hospital, Bronx

Alan A Bloom, MD is a member of the following medical societies: American College of Physicians, American Gastroenterological Association, American Medical Association, American Society for Gastrointestinal Endoscopy, New York Academy of Medicine, and New York Academy of Sciences

Coauthor(s)

Zahir Amin, MD, MBBS, MRCP, FRCR Consulting Staff, Department of Imaging, University College Hospital, UK

Zahir Amin, MD, MBBS, MRCP, FRCR is a member of the following medical societies: British Institute of Radiology, British Medical Association, and Royal College of Radiologists

BS Anand, MD Professor, Department of Internal Medicine, Division of Gastroenterology, Baylor College of Medicine

BS Anand, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association, and American Society for Gastrointestinal Endoscopy

Cholecystitis is defined as inflammation of the gallbladder that occurs most commonly because of an obstruction of the cystic duct from cholelithiasis. Ninety percent of cases involve stones in the cystic duct (ie, calculous cholecystitis), with the other 10% of cases representing acalculous cholecystitis.[1]

Risk factors for cholecystitis mirror those for cholelithiasis and include increasing age, female sex, certain ethnic groups, obesity or rapid weight loss, drugs, and pregnancy. Although bile cultures are positive for bacteria in 50-75% of cases, bacterial proliferation may be a result of cholecystitis and not the precipitating factor.

Acalculous cholecystitis is related to conditions associated with biliary stasis, including debilitation, major surgery, severe trauma, sepsis, long-term total parenteral nutrition (TPN), and prolonged fasting. Other causes of acalculous cholecystitis include cardiac events; sickle cell disease; Salmonella infections; diabetes mellitus; and cytomegalovirus, cryptosporidiosis, or microsporidiosis infections in patients with AIDS. For more information, see the Medscape Reference article Acalculous Cholecystopathy.

Uncomplicated cholecystitis has an excellent prognosis, with a very low mortality rate. Once complications such as perforation/gangrene develop, the prognosis becomes less favorable. Some 25-30% of patients either require surgery or develop some complication.

The most common presenting symptom of acute cholecystitis is upper abdominal pain. The physical examination may reveal fever, tachycardia, and tenderness in the RUQ or epigastric region, often with guarding or rebound. However, the absence of physical findings does not rule out the diagnosis of cholecystitis.

Delays in making the diagnosis of acute cholecystitis result in a higher incidence of morbidity and mortality. This is especially true for ICU patients who develop acalculous cholecystitis. The diagnosis should be considered and investigated promptly in order to prevent poor outcomes.

Initial treatment of acute cholecystitis includes bowel rest, intravenous hydration, correction of electrolyte abnormalities, analgesia, and intravenous antibiotics. For mild cases of acute cholecystitis, antibiotic therapy with a single broad-spectrum antibiotic is adequate. Outpatient treatment may be appropriate for cases of uncomplicated cholecystitis. If surgical treatment is indicated, laparoscopic cholecystectomy represents the standard of care.

Patients diagnosed with cholecystitis must be educated regarding causes of their disease, complications if left untreated, and medical/surgical options to treat cholecystitis. For patient education information, see the Liver, Gallbladder, and Pancreas Center, as well as Gallstones and Pancreatitis.

Ninety percent of cases of cholecystitis involve stones in the cystic duct (ie, calculous cholecystitis), with the other 10% of cases representing acalculous cholecystitis.[1]

Acute calculous cholecystitis is caused by obstruction of the cystic duct, leading to distention of the gallbladder. As the gallbladder becomes distended, blood flow and lymphatic drainage are compromised, leading to mucosal ischemia and necrosis.

Although the exact mechanism of acalculous cholecystitis is unclear, several theories exist. Injury may be the result of retained concentrated bile, an extremely noxious substance. In the presence of prolonged fasting, the gallbladder never receives a cholecystokinin (CCK) stimulus to empty; thus, the concentrated bile remains stagnant in the lumen.[2, 3]

A study by Cullen et al demonstrated the ability of endotoxin to cause necrosis, hemorrhage, areas of fibrin deposition, and extensive mucosal loss, consistent with an acute ischemic insult.[4] Endotoxin also abolished the contractile response to CCK, leading to gallbladder stasis.

Etiology

Risk factors for calculous cholecystitis mirror those for cholelithiasis and include the following :

Female sex
Certain ethnic groups
Obesity or rapid weight loss
Drugs (especially hormonal therapy in women)
Pregnancy
Increasing age

Acalculous Cholecystitis is related to conditions associated with biliary stasis, to include the following :

Critical illness
Major surgery or severe trauma/burns
Sepsis
Long-term total parenteral nutrition (TPN)
Prolonged fasting

Other causes of acalculous cholecystitis include the following :

Cardiac events, including myocardial infarction
Sickle cell disease
Salmonella infections
Diabetes mellitus[5]
Patients with AIDS who have cytomegalovirus, cryptosporidiosis, or microsporidiosis
Patients who are immunocompromised are at increased risk of developing cholecystitis from a number of different infectious sources. Idiopathic cases exist.

Epidemiology

An estimated 10-20% of Americans have gallstones, and as many as one third of these people develop acute cholecystitis. Cholecystectomy for either recurrent biliary colic or acute cholecystitis is the most common major surgical procedure performed by general surgeons, resulting in approximately 500,000 operations annually.

Age distribution for cholecystitis

The incidence of cholecystitis increases with age. The physiologic explanation for the increasing incidence of gallstone disease in the elderly population is unclear. The increased incidence in elderly men has been linked to changing androgen-to-estrogen ratios.

Sex distribution for cholecystitis

Gallstones are 2-3 times more frequent in females than in males, resulting in a higher incidence of calculous cholecystitis in females. Elevated progesterone levels during pregnancy may cause biliary stasis, resulting in higher rates of gallbladder disease in pregnant females. Acalculous cholecystitis is observed more often in elderly men.

Prevalence of cholecystitis by race and ethnicity

Cholelithiasis, the major risk factor for cholecystitis, has an increased prevalence among people of Scandinavian descent, Pima Indians, and Hispanic populations, whereas cholelithiasis is less common among individuals from sub-Saharan Africa and Asia.[6, 7] In the United States, white people have a higher prevalence than black people.

Prognosis

Uncomplicated cholecystitis has an excellent prognosis, with very low mortality. Most patients with acute cholecystitis have a complete remission within 1-4 days. However, 25-30% of patients either require surgery or develop some complication.

Once complications such as perforation/gangrene develop, the prognosis becomes less favorable. Perforation occurs in 10-15% of cases. Patients with acalculous cholecystitis have a mortality ranging from 10-50%, which far exceeds the expected 4% mortality observed in patients with calculous cholecystitis. In patients who are critically ill with acalculous cholecystitis and perforation or gangrene, mortality can be as high as 50-60%.

Refferences :

1. Huffman JL, Schenker S. Acute acalculous cholecystitis - a review. Clin Gastroenterol Hepatol. Sep 9 2009;[Medline].

2. Donovan JM. Physical and metabolic factors in gallstone pathogenesis. Gastroenterol Clin North Am. Mar 1999;28(1):75-97. [Medline].

3. Sitzmann JV, Pitt HA, Steinborn PA, et al. Cholecystokinin prevents parenteral nutrition induced biliary sludge in humans. Surg Gynecol Obstet. Jan 1990;170(1):25-31. [Medline].

4. Cullen JJ, Maes EB, Aggrawal S, et al. Effect of endotoxin on opossum gallbladder motility: a model of acalculous cholecystitis. Ann Surg. Aug 2000;232(2):202-7. [Medline]

5. Forbes LE, Bajaj M, McGinn T, et al. Perihepatic abscess formation in diabetes: a complication of silent gallstones. Am J Gastroenterol. Apr 1996;91(4):786-8. [Medline].

6. Huang J, Chang CH, Wang JL, Kuo HK, Lin JW, Shau WY, et al. Nationwide epidemiological study of severe gallstone disease in Taiwan. BMC Gastroenterol. Aug 22 2009;9:63. [Medline].

7. Lee SW, Yang SS, Chang CS, Yeh HJ. Impact of the Tokyo guidelines on the management of patients with acute calculous cholecystitis. J Gastroenterol Hepatol. Aug 3 2009; [Medline]

Source : http://emedicine.medscape.com

An Update on Emerging Therapies for the Practical Management of Diabetes

noreply@blogger.com (Han Idris) — Wed, 14 Mar 2012 02:40:00 +0000

Eleuterio Ferrannini, MD; Dr. Diamant; Dr. Barnett; Dr. Davies, PhD; Dr. Hanefeld, PhD

CME Released: 10/24/2011; Valid for credit through 10/24/2012

Despite the availability of multiple pharmacologic agents, the treatment of patients with type 2 diabetes mellitus remains suboptimal. Given the disease's high and increasing prevalence, the morbidity, mortality, and economic consequences of type 2 diabetes are a great burden to patients, healthcare systems, and society.

Newer incretin-based agents for the treatment of type 2 diabetes include the glucagon-like peptide-1 (GLP-1) agonists, such as exenatide (now also available as a once-weekly injection) and liraglutide, as well as the dipeptidyl peptidase-4 (DPP-4) inhibitors, such as sitagliptin, saxagliptin, and the recently approved linagliptin, which can be used as a single dose even in patients with moderate to severe renal impairment.

Both classes have important clinical advantages in terms of weight control, reduced risk for hypoglycemias, and their effects on the insulin-secreting beta cells.

The latest emerging class is the SGLT2 inhibitors, which suppress glucose reabsorption in the kidney, thereby leading to the excretion of glucose in the urine. Once approved, they will be the only orally available antidiabetic drugs to trigger body weight reduction. They are also unique in that their glucose-lowering mechanism is completely insulin independent.

Together, these new classes have greatly expanded the choices for clinicians to help patients with type 2 diabetes achieve tighter glycemic control and better outcomes today and in the future.

Source : http://www.medscape.org/viewarticle/751705

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New Frontiers in Diabetes Management: The Next Generation of Insulins

noreply@blogger.com (Han Idris) — Tue, 13 Mar 2012 04:19:00 +0000

Bernard Zinman, MD; Stephen Colagiuri, MD; Stephen Gough, MD, FRCP; Chantal Mathieu, MD, PhD

CME Released: 12/22/2011; Valid for credit through 12/22/2012

A wealth of clinical evidence indicates that tight glycemic control can prevent or delay complications in both type 1 and type 2 diabetes, but achieving this goal is a continuing challenge.

Clinicians often do not initiate or intensify therapy appropriately in their patients with diabetes. More aggressive treatment is necessary and should include earlier introduction and appropriate intensification of insulin therapy in patients with type 2 diabetes. Unfortunately, earlier initiation of insulin is hindered by fear of hypoglycemia, weight gain, and injections. Fear of hypoglycemia remains a major challenge for both physicians and patients and is a significant barrier to achieving optimal glycemic control.

Physicians treating patients with diabetes need to be comfortable with the use of insulin, as well as confident about integrating new formulations of insulin into their diabetes treatment plans.

Neutral protein Hagedorn (NPH) insulin is associated with a distinct peak at 6 hours, which may cause hypoglycemia, does not provide 24-hour control, and is associated with high inter- and intra-individual variability.

The advent of the long-acting insulin analogues in the past decade has revolutionized insulin therapy by offering flexibility in dosing and more options for tailoring therapy.

Next-generation basal insulin analogues are being studied, addressing the major challenges in diabetes care. The furthest along in development is degludec, with an elimination half-life longer than 24 hours. It is associated with significantly less pharmacodynamic variability which may be directly related to the drug's lower rate of hypoglycemic episodes.

Another basal insulin analogue designed to deliver improved clinical features is LY2605541, which has just moved into phase 3 clinical development.

Source : http://www.medscape.org/viewarticle/755996

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Brain Food: Fending Off Mental and Neurologic Illness With Diet

noreply@blogger.com (Han Idris) — Tue, 28 Feb 2012 22:44:00 +0000

Author

Bret S. Stetka, MD, Editorial Director, Medscape From WebMD

Reviewers

Michael T. Compton, MD, MPH, Professor of Psychiatry and Behavioral Sciences, The George Washington University School of Medicine and Health Sciences, Washington, DC

Disclosure: Michael T. Compton, MD, MPH, has disclosed no relevant financial relationships.

Felice N. Jacka, PhD, Associate Professor, Barwon Psychiatric Research Unit, Deakin University, Geelong, Australia

Felice N. Jacka, PhD, has disclosed no relevant financial relationships.

Which Foods Are Best for the Brain ?

Diet is inextricably linked to conditions such as heart disease, obesity, and diabetes. However, what we consume also seems to have significant implications for the brain: Unhealthy diets may increase risk for psychiatric and neurologic conditions, such as depression and dementia, whereas healthy diets may be protective. Based primarily on recent Medscape News coverage, the following slideshow collects some of the more prominent investigations on nutrition and the brain into a single resource to aid in counseling your patients.

Make for Malta in Depression, Stroke, and Dementia

A 2009 study published in Archives of General Psychiatry found that people who follow Mediterranean dietary patterns -- that is, a diet high in fruits, vegetables, nuts, whole grains, fish, and unsaturated fat (common in olive and other plant oils) -- are up to 30% less likely to develop depression than those who typically consume meatier, dairy-heavy fare.[1] The olive oil-inclined also show a lower risk for ischemic stroke[2,3] and are less likely to develop mild cognitive impairment and Alzheimer disease, particularly when they engage in higher levels of physical activity.[4,5]

Fat: The Good and the Bad

A study conducted in Spain[6,7] reported that consumption of both polyunsaturated fatty acids (found in nuts, seeds, fish, and leafy green vegetables) and monounsaturated fatty acids (found in olive oil, avocados, and nuts) decreases the risk for depression over time. However, there were clear dose-response relationships between dietary intake of trans fats and depression risk, whereas other data support an association between trans fats and ischemic stroke risk.[8] Trans fats are found extensively in processed foods, including many commercial chocolates (hence, check that label when considering the chocolate slide below). A deficiency in polyunsaturated fatty acids has been linked to attention deficit/hyperactivity disorder in children.[9]

Fish Oil to Fend Off Psychosis ?

Thanks to their high levels of polyunsaturated fatty acids, namely omega-3 fatty acids, fish can help fend off numerous diseases of the brain. A 2010 study correlated fish consumption with a lower risk for psychotic symptoms,[10] and concurrent work suggested that fish oil may help prevent psychosis in high-risk individuals.[11] Although data are conflicting, new research shows that the omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid are beneficial in depression and postpartum depression, respectively, and other research suggests that omega-3 deficiency may be a risk factor for suicide.[12-16] Oily, cold-water fish, such as salmon, herring, and mackerel, have the highest omega-3 levels.

Berries for Oxidative Stress

Polyphenols, namely anthocyanins, found in berries and other darkly pigmented fruits and vegetables may slow cognitive decline through antioxidant and anti-inflammatory properties. A study in rats from 2010 showed that a diet high in strawberry, blueberry, or blackberry extract leads to a "reversal of age-related deficits in nerve function and behavior involving learning and memory."[17] In vitro work by the same group found that strawberry, blueberry, and acai berry extracts -- albeit in very high concentrations -- can induce autophagy, a means by which cells clear debris, such as proteins linked to mental decline and memory loss.[18] Berry anthocyanins may also reduce cardiovascular disease risk by reducing oxidative stress and attenuating inflammatory gene expression.[19]

A "Whole" Diet: Make Room for Red Meat ?

A so-called "whole" diet high in fruits, vegetables, whole grains, and high-quality meats and fish results in a 30% risk reduction for depression and anxiety disorders, compared with consumption of a "Western diet" high in processed foods and saturated fats, according to a 2010 study.[20] Even unprocessed red meat seems to be protective against depressive and anxiety disorders,[21] in contrast to many studies in which red meat often falls into the category of "unhealthy" food. In speaking with Medscape News, principal investigator Dr. Felice Jacka specifically addressed the importance of farming practices: Despite the growing locavore movement, much of the livestock in the United States is still raised on industrial feedlots, which "...increases saturated fat and decreases very important good fatty acids...pasture-raised animals have a much healthier fatty acid profile." A "whole" dietary pattern may also reduce depression risk, as assessed at 5-year follow-up.[22]

Alcohol: Always in Moderation

The Greeks touted "nothing in excess," a refrain that still rings true: Low to moderate* alcohol consumption has been associated with numerous potential physiologic benefits, including improved cholesterol profiles, beneficial effects on platelet and clotting function, and improved insulin sensitivity.[23] According to a recent meta-analysis, limited alcohol use is associated with a lower risk for overall and Alzheimer dementia,[24] a finding supported by a 2011 study of German primary care patients.[23] Moderate alcohol intake may also protect against cerebrovascular disease, with wine potentially having added benefit because of its polyphenolic antioxidant components (ie, resveratrol).[25-27] However, the health costs of alcohol consumption beyond low to moderate intake can quickly outweigh benefits to the brain, as heavy and long-term alcohol use can lead to alcohol abuse and dependence, impair memory function, contribute to neurodegenerative disease, and hinder psychosocial functioning.

*The US Food and Drug Administration defines "moderate alcohol consumption" as up to 1 drink per day for women and up to 2 drinks per day for men. One drink is equivalent to 12 fluid ounces of regular beer, 5 fluid ounces of 12% alcohol wine, or 1.5 fluid ounces of distilled spirits.

Brewed Awakening: Coffee for Depression and Stroke

The world's most widely used stimulant might do more than just wake us up: A 2011 meta-analysis[28] found that consumption of 1-6 cups of coffee a day cut stroke risk by 17%. Although it may increase blood pressure, coffee beans contain antioxidant compounds that may reduce oxidation of low-density lipoprotein cholesterol, and coffee consumption has also been associated with increased insulin sensitivity and reduced concentrations of inflammatory markers.[29] Another 2011 study[30] reported that women who drink 2-3 cups of coffee per day have a 15% decreased risk for depression, compared with those who drink less than 1 cup per week. A 20% decreased risk was seen in those who drank 4 cups or more. The short-term effect of coffee on mood may be due to altered serotonin and dopamine activity, whereas the mechanisms behind its potential long-term effects on mood may relate to its antioxidant and anti-inflammatory properties, both factors that are thought to play a role in depressive illnesses.[29-32]

Chocolate -- and Still More Antioxidants

Chocolate -- the darker the better -- seems to help scavenge free radicals and improve endothelial and platelet function, likely via flavanols (such as catechin), a group of plant-derived polyphenols.[33] A 2010 cohort study published in European Heart Journal found that consumption of 6 g of chocolate daily -- a standard Hershey bar weighs 43 g -- was associated with a 39% lower combined risk for myocardial infarction and stroke in adults,[34] whereas data collected from the Swedish Mammography Cohort demonstrated a 20% decreased risk for stroke in women who regularly consume chocolate.[35] Although chocolate has been associated with a positive influence on mood, possibly mediated by the dopamine and opioid systems, an extensive review by Parker and colleagues[36] suggests that the benefits are not sustained, with emotional "comfort" eating actually contributing to depressed mood.

What Not to Eat ?

Saturated fats and refined carbohydrates have highly detrimental effects on the immune system, oxidative stress, and neurotrophins, all factors that are known to play a role in depression. The study by Akbaraly and colleagues cited previously[22] showed that a diet rich in high-fat dairy foods and fried, refined, and sugary foods significantly increases risk for depression. Similar findings were seen in another study from Spain,[7] showing that intake of such foods as pizza and hamburgers increased the risk for depression over time, and in another study, women with a diet higher in processed foods were more likely to have clinical major depression or dysthymia.[17] Research published last year[37] also showed for the first time that quality of adolescents' diets was linked to mental health: Healthier diets were associated with reduced mental health symptoms and unhealthy diets with increased mental health symptoms over time. Excess salt intake has been long known to increase blood pressure and stroke risk[38,39]; however, recent data also correlate high salt intake, as well as diets high in trans or saturated fats, with impaired cognition.[40,41]

References :

1. Sánchez-Villegas A, Delgado-Rodríguez M, Alonso A, et al. Association of the Mediterranean dietary pattern with the incidence of depression: the Seguimiento Universidad de Navarra/University of Navarra follow-up (SUN) cohort. Arch Gen Psychiatry. 2009;66:1090-1098.

2. Fung TT, Rexrode KM, Mantzoros CS, Manson JE, Willett WC, Hu FB. Mediterranean diet and incidence of and mortality from coronary heart disease and stroke in women. Circulation. 2009;119:1093-1100.

3. Kastorini CM, Milionis HJ, Ioannidi A, et al. Adherence to the Mediterranean diet in relation to acute coronary syndrome or stroke nonfatal events: a comparative analysis of a case/case-control study. Am Heart J. 2011;162:717-724.

4. Scarmeas N, Stern Y, Mayeux R, Manly JJ, Schupf N, Luchsinger JA. Mediterranean diet and mild cognitive impairment. Arch Neurol. 2009;66:216-225.

5. Scarmeas N, Luchsinger JA, Schupf N, et al. Physical activity, diet, and risk of Alzheimer disease. JAMA. 2009;302:627-637.

6. Sánchez-Villegas A, Verberne L, De Irala J, et al. Dietary fat intake and the risk of depression: the SUN project. PLoS One. 2011;6:e16268.

7. Sánchez-Villegas A, Toledo E, de Irala J, Ruiz-Canela M, Pla-Vidal J, Martínez-González MA. Fast-food and commercial baked goods consumption and the risk of depression. Public Health Nutr. 2012;15:424-432.

8. Yaemsiri S, Sen S, Tinker L, et al. Dietary fat intake and incidence of ischemic stroke in postmenopausal US women: the Womens Health Initiative. Stroke. 2010;41:e200-e253.

9. Millichap JG, Yee MM. The diet factor in attention-deficit/hyperactivity disorder. Pediatrics. 2012;129:330-337.

10. Hedelin M, Löf M, Olsson M, et al. Dietary intake of fish, omega-3, omega-6 polyunsaturated fatty acids and vitamin D and the prevalence of psychotic-like symptoms in a cohort of 33000 women from the general population. BMC Psychiatry. 2010;10:38.

11. Amminger GP, Schäfer MR, Papageorgiou K, et al. Long-chain omega-3 fatty acids for indicated prevention of psychotic disorders: a randomized, placebo-controlled trial. Arch Gen Psychiatry. 2010;67:146-154.

12. Judge MP, Beck CT, Durham H, et al. Maternal docosahexaenoic acid (DHA, 22:6n-3) consumption during pregnancy decreases postpartum depression (PPD) symptomatology. FASEB J. 2011;25:349.7.

13. Lucas M, Mirzaei F, O'Reilly EJ, et al. Dietary intake of n-3 and n-6 fatty acids and the risk of clinical depression in women: a 10-y prospective follow-up study. Am J Clin Nutr. 2011;93:1337-1343.

14. Makrides M, Gibson RA, McPhee J, et al. Effect of DHA supplementation during pregnancy on maternal depression and neurodevelopment of young children: a randomized controlled trial. JAMA. 2010;304:1675-1683.

15. Sublette ME, Ellis S, Geant AL, Mann JJ. Meta-analysis of the effects of eicosapentaenoic acid (EPA) in clinical trials in depression. J Clin Psychiatry. 2011;72:1577-1584.

16. Lewis MD, Hibbeln JR, Johnson JE, Lin YH, Hyun DY, Loewke JD. Suicide deaths of active-duty US military and omega-3 fatty-acid status: a case-control comparison. J Clin Psychiatry. 2011;72:1585-1590.

17. Medscape.com. New mechanism for berries' potential brain benefits uncovered. http://www.medscape.com/viewarticle/727764 Accessed January 10, 2012.

18. Berry extracts and brain aging: clearance of toxic protein accumulation in brain via induction of autophagy. Program and abstracts of the 240th National Meeting of the American Chemical Society; August 22-26, 2012; Boston, Massachusetts.

19. Basu A, Rhone M, Lyons TJ. Berries: emerging impact on cardiovascular health. Nutr Rev. 2010;68:168-177.

20. Jacka F, Pasco JA, Mykletun A, et al. Association of Western and traditional diets with depression and anxiety in women. Am J Psychiatry. 2010;167:305-311.

21. Jacka FN, Pasco JA, Williams LJ, et al. Red meat consumption and mood and anxiety disorders. Psychother Psychosom. . [In press].

22. Akbaraly TN, Brunner EJ, Ferrie JE, Marmot MG, Kivimaki M, Singh-Manoux A. Dietary pattern and depressive symptoms in middle age. Br J Psychiatry. 2009;195:408-413.

23. Wayerer S, Schäufele M, Wiese B, et al; German AgeCoDe Study group (German Study on Ageing, Cognition and Dementia in Primary Care Patients). Current alcohol consumption and its relationship to incident dementia: results from a 3-year follow-up study among primary care attenders aged 75 years and older. Age Ageing. 2011;40:456-463.

24. Peters R, Peters J, Warner J, Beckett N, Bulpitt C. Alcohol, dementia and cognitive decline in the elderly: a systematic review. Age Ageing. 2008;37:505-512.

25. de Gaetano G, Di Castelnuovo A, Rotondo S, Iacoviello L, Donati MB. A meta-analysis of studies on wine and beer and cardiovascular disease. Pathophysiol Haemost Thromb. 2002;32:353-355.

26. Matos RS, Baroncini LA, Précoma LB, et al. Resveratrol causes antiatherogenic effects in an animal model of atherosclerosis. Arq Bras Cardiol. 2012 Jan 9. [Epub ahead of print]

27. Bertelli AA, Das DK. Grapes, wines, resveratrol, and hearth health. J Cardiovasc Pharmacol. 2009;54:468-476.

28. Larsson SC, Orsini N. Coffee consumption and risk of stroke: a dose-response meta-analysis of prospective studies. Am J Epidemiol. 2011;174:993-1001.

29. Pasco JA, Nicholson GC, Williams LJ, et al. Association of high-sensitivity C-reactive protein with de novo major depression. Br J Psychiatry. 2010;197:372-377.

30. Lucas M, Mirzaei F, Pan A, et al. Coffee, caffeine, and risk of depression among women. Arch Intern Med. 2011;171:1571-1578.

31. Ng F, Berk M, Dean O, Bush AI. Oxidative stress in psychiatric

disorders: evidence base and therapeutic implications. Int J Neuropsychopharmacol. 2008;11:851-876.

32. O'Connor A. Coffee drinking linked to less depression in women. New York Times. February 13, 2012. http://well.blogs.nytimes.com/2011/09/26/coffee-drinking-linked-to-less-depression-in-women/ Accessed January 11, 2012.

33. Corti R, Flammer AJ, Hollenberg NK, Lüscher TF. Cocoa and cardiovascular health. Circulation. 2009;119:1433-1441.

34. Buijsse B, Weikert C, Drogan, Bergmann M, Boeing H. Chocolate consumption in relation to blood pressure and risk of cardiovascular disease in German adults. Eur Heart J. 2010;31:1616-1623.

35. Larsson SC, Virtamo J, Wolk A. Chocolate consumption and risk of stroke in women. J Am Coll Cardiol. 2011;58:1828-1829.

36. Parker G, Parker I, Brotchie H. Mood state effects of chocolate. J Affect Disord. 2006;92:149-159.

37. Jacka FN, Kremer P, Berk M, et al. A prospective study of diet quality and mental health in adolescents. PLoS One. 2011;6:e24805.

38. Frieden TR, Briss PA. We can reduce dietary sodium, save money, and save lives. Ann Intern Med. 2010:152:526-527, W182.

39. Dickinson BD, Havas S; Council on Science and Public Health, American Medical Association. Reducing the population burden of cardiovascular disease by reducing sodium intake: a report of the Council on Science and Public Health. Arch Intern Med. 2007;167:1460-1468.

40. Fiocco AJ, Shatenstein B, Ferland G, et al. Sodium intake and physical activity impact cognitive maintenance in older adults: the NuAge Study. Neurobiol Aging. 2011 Aug 18. [Epub ahead of print]

41. Parrott MD, Greenwood CE. Dietary influences on cognitive function with aging: from high-fat diets to healthful eating. Ann N Y Acad Sci. 2007;1114:389-397.

Source : http://www.medscape.com/features/slideshow/brain-food

Acute Pancreatitis : Clinical Manifestation

noreply@blogger.com (Han Idris) — Sat, 03 Dec 2011 00:30:00 +0000

Author Timothy B Gardner, MD Assistant Professor, Department of Medicine, Dartmouth Medical School; Director of Pancreatic Disorders, Section of Gastroenterology, Dartmouth-Hitchcock Medical Center Timothy B Gardner, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians-American Society of Internal Medicine, American Gastroenterological Association, American Medical Association, American Pancreatic Association, and American Society for Gastrointestinal Endoscopy Disclosure: Nothing to disclose. Coauthor(s) Brian S Berk, MD Assistant Professor, Department of Medicine, Dartmouth Medical School; Director of End Stage Liver Disease, Section of Gastroenterology, Dartmouth Hitchcock Medical Center Brian S Berk, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, and American Gastroenterological Association Disclosure: Nothing to disclose. Chief Editor Julian Katz, MD Clinical Professor of Medicine, Drexel University College of Medicine Julian Katz, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Geriatrics Society, American Medical Association, American Society for Gastrointestinal Endoscopy, American Society of Law, Medicine & Ethics, American Trauma Society, Association of American Medical Colleges, and Physicians for Social Responsibility Disclosure: Nothing to disclose. Additional Contributors Tushar Patel, MB, ChB Professor of Medicine, Ohio State University Medical Center Tushar Patel, MB, ChB is a member of the following medical societies: American Association for the Study of Liver Diseases and American Gastroenterological Association Disclosure: Nothing to disclose. Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference Disclosure: Medscape Salary Employment Noel Williams, MD Professor Emeritus, Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada; Professor, Department of Internal Medicine, Division of Gastroenterology, University of Alberta, Edmonton, Alberta, Canada Noel Williams, MD is a member of the following medical societies: Royal College of Physicians and Surgeons of Canada Disclosure: Nothing to disclose. Paul Yakshe, MD Assistant Professor of Medicine, University of Minnesota, Medical Director of Pancreas and Biliary Clinic, Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, Fairview University Medical Center Paul Yakshe, MD is a member of the following medical societies: American College of Gastroenterology, American Pancreatic Association, and American Society for Gastrointestinal Endoscopy Disclosure: Nothing to disclose.

Clinical Presentation

History

The cardinal symptom of acute pancreatitis is abdominal pain, which is characteristically dull, boring, and steady. Usually, the pain is sudden in onset and gradually intensifies in severity until reaching a constant ache. Most often, it is located in the upper abdomen, usually in the epigastric region, but it may be perceived more on the left or right side, depending on which portion of the pancreas is involved. The pain radiates directly through the abdomen to the back in approximately one half of cases.

Nausea and vomiting are often present along with accompanying anorexia. Diarrhea can also occur. Positioning can be important, because the discomfort frequently improves with the patient in the supine position. The duration of pain varies but typically lasts more than a day. It is the intensity and persistence of the pain that usually causes patients to seek medical attention.

Ask the patient about recent operative or other invasive procedures (eg, endoscopic retrograde cholangiopancreatography [ERCP]) or family history of hypertriglyceridemia. Patients frequently have a history of previous biliary colic and binge alcohol consumption, the major causes of acute pancreatitis.

Atypical acute pancreatitis may be misdiagnosed. In a study of patients with pancreatitis discovered at autopsy, 13% presented with abdominal pain, 19% had disease that occurred in the postoperative setting, and 68% presented with various cardiac, pulmonary, hepatic, renal, abdominal, and metabolic disturbances.

Physical Examination

The following physical examination findings may be noted, varying with the severity of the disease:

Fever (76%) and tachycardia (65%) are common abnormal vital signs; hypotension may be noted
Abdominal tenderness, muscular guarding (68%), and distention (65%) are observed in most patients; bowel sounds are often diminished or absent because of gastric and transverse colonic ileus; guarding tends to be more pronounced in the upper abdomen
A minority of patients exhibit jaundice (28%)
Some patients experience dyspnea (10%), which may be caused by irritation of the diaphragm (resulting from inflammation), pleural effusion, or a more serious condition, such as acute respiratory distress syndrome (ARDS); tachypnea may occur; lung auscultation may reveal basilar rales, especially in the left lung
In severe cases, hemodynamic instability is evident (10%) and hematemesis or melena sometimes develops (5%); in addition, patients with severe acute pancreatitis are often pale, diaphoretic, and listless
Occasionally, in the extremities, muscular spasm may be noted secondary to hypocalcemia

A few uncommon physical findings are associated with severe necrotizing pancreatitis:

The Cullen sign is a bluish discoloration around the umbilicus resulting from hemoperitoneum
The Grey-Turner sign is a reddish-brown discoloration along the flanks resulting from retroperitoneal blood dissecting along tissue planes; more commonly, patients may have a ruddy erythema in the flanks secondary to extravasated pancreatic exudate
Erythematous skin nodules may result from focal subcutaneous fat necrosis; these are usually not more than 1 cm in size and are typically located on extensor skin surfaces; in addition, polyarthritis is occasionally seen

Rarely, abnormalities on funduscopic examination may be seen in severe pancreatitis. Termed Purtscher retinopathy, this ischemic injury to the retina appears to be caused by activation of complement and agglutination of blood cells within retinal vessels. It may cause temporary or permanent blindness.

Complications

Acute fluid collections may occur, typically early in the course of acute pancreatitis. They are primarily detected by imaging studies rather than by physical examination. Because they lack a defined wall and usually regress spontaneously, most acute fluid collections require no specific therapy.

An acute pseudocyst is a collection of pancreatic fluid that is walled off by granulation tissue after an episode of acute pancreatitis; it requires 4 or more weeks to develop. Although pseudocysts are sometimes palpable on physical examination, they are usually detected with abdominal ultrasonography or computed tomography (CT).

Intra-abdominal infection is common. Within the first 1-3 weeks, fluid collections or pancreatic necrosis can become infected and jeopardize clinical outcome. From 3 to 6 weeks, pseudocysts may become infected or a pancreatic abscess may develop. A pancreatic abscess is a circumscribed intra-abdominal collection of pus, within or in proximity to the pancreas. It is believed to arise from localized necrosis, with subsequent liquefaction that becomes infected.

The intestinal flora is the predominant source of bacteria causing the infection. The usual suspects are Escherichia coli (26%), Pseudomonas species (16%), Staphylococcus species (15%), Klebsiella species (10%), Proteus species (10%), Streptococcus species (4%), Enterobacter species (3%), and anaerobic organisms (16%). Fungal superinfections may occur weeks or months into the course of severe necrotizing pancreatitis.

Pancreatic necrosis is a nonviable area of pancreatic parenchyma that is often associated with peripancreatic fat necrosis and is principally diagnosed with the aid of dynamic spiral CT scans. Distinguishing between infected and sterile pancreatic necrosis is an ongoing clinical challenge. Sterile pancreatic necrosis is usually treated with aggressive medical management, whereas almost all patients with infected pancreatic necrosis require surgical debridement or percutaneous drainage if they are to survive.

Hemorrhage into the gastrointestinal (GI) tract retroperitoneum or the peritoneal cavity is possible because of erosion of large vessels. Intestinal obstruction or necrosis may occur. Common bile duct obstruction may be caused by a pancreatic abscess, pseudocyst, or biliary stone that caused the pancreatitis. An internal pancreatic fistula from pancreatic duct disruption or a leaking pancreatic pseudocyst may occur.

In the weeks (to months) following presentation, the physician’s attention shifts to developing signs of intra-abdominal infection, pancreatic pseudocyst, intra-abdominal hemorrhage, colon perforation, obstruction or fistulization, and multiorgan system failure.

Source :

http://emedicine.medscape.com
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Acute Pancreatitis : Overview

noreply@blogger.com (Han Idris) — Fri, 02 Dec 2011 23:35:00 +0000

Author

Timothy B Gardner, MD Assistant Professor, Department of Medicine, Dartmouth Medical School; Director of Pancreatic Disorders, Section of Gastroenterology, Dartmouth-Hitchcock Medical Center

Timothy B Gardner, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians-American Society of Internal Medicine, American Gastroenterological Association, American Medical Association, American Pancreatic Association, and American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.
Coauthor(s)

Brian S Berk, MD Assistant Professor, Department of Medicine, Dartmouth Medical School; Director of End Stage Liver Disease, Section of Gastroenterology, Dartmouth Hitchcock Medical Center

Brian S Berk, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, and American Gastroenterological Association

Disclosure: Nothing to disclose.
Chief Editor

Julian Katz, MD Clinical Professor of Medicine, Drexel University College of Medicine

Julian Katz, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Geriatrics Society, American Medical Association, American Society for Gastrointestinal Endoscopy, American Society of Law, Medicine & Ethics, American Trauma Society, Association of American Medical Colleges, and Physicians for Social Responsibility

Disclosure: Nothing to disclose.
Additional Contributors

Tushar Patel, MB, ChB Professor of Medicine, Ohio State University Medical Center

Tushar Patel, MB, ChB is a member of the following medical societies: American Association for the Study of Liver Diseases and American Gastroenterological Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Noel Williams, MD Professor Emeritus, Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada; Professor, Department of Internal Medicine, Division of Gastroenterology, University of Alberta, Edmonton, Alberta, Canada

Noel Williams, MD is a member of the following medical societies: Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Paul Yakshe, MD Assistant Professor of Medicine, University of Minnesota, Medical Director of Pancreas and Biliary Clinic, Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, Fairview University Medical Center

Paul Yakshe, MD is a member of the following medical societies: American College of Gastroenterology, American Pancreatic Association, and American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Background

This article focuses on recognition and management of acute pancreatitis. Pancreatitis is an inflammatory process in which pancreatic enzymes autodigest the gland. The gland sometimes heals without any impairment of function or any morphologic changes; this process is known as acute pancreatitis. Pancreatitis can also recur intermittently, contributing to the functional and morphologic loss of the gland; recurrent attacks are referred to as chronic pancreatitis.

Both forms of pancreatitis present in the emergency department (ED) with acute clinical findings. Recognizing patients with severe acute pancreatitis as soon as possible is critical for achieving optimal outcomes (see Presentation).

Once a working diagnosis of acute pancreatitis is reached, laboratory tests are obtained to support the clinical impression, to help define the etiology, and to look for complications. Diagnostic imaging is unnecessary in most cases but may be obtained when the diagnosis is in doubt, when severe pancreatitis is present, or when a given imaging study might provide specific information needed to answer a clinical question. Image-guided aspiration may be useful. Genetic testing may be considered (see Workup).

Management depends largely on severity. Medical treatment of mild acute pancreatitis is relatively straightforward. Treatment of severe acute pancreatitis involves intensive care; the goals of medical management are to provide aggressive supportive care, to decrease inflammation, to limit infection or superinfection, and to identify and treat complications as appropriate. Surgical intervention (open or minimally invasive) is indicated in selected cases (see Treatment).

Pathophysiology

Normal pancreatic function

The pancreas is a gland located in the upper posterior abdomen. It is responsible for insulin production (endocrine pancreas) and the manufacture and secretion of digestive enzymes (exocrine pancreas) leading to carbohydrate, fat, and protein metabolism. Approximately 80% of the gross weight of the pancreas supports exocrine function, and the remaining 20% is involved with endocrine function. The focus of this article is on the exocrine function of the pancreas.

The pancreas accounts for only 0.1% of total body weight but has 13 times the protein-producing capacity of the liver and the reticuloendothelial system combined, which together make up 4% of total body weight. Digestive enzymes are produced within the pancreatic acinar cells, packaged into storage vesicles called zymogens, and then released via the pancreatic ductal cells into the pancreatic duct, where they are secreted into the small intestine to begin the metabolic process.

In normal pancreatic function, up to 15 different types of digestive enzymes are manufactured in the rough endoplasmic reticulum, targeted in the Golgi apparatus and packaged into zymogens as proenzymes. When a meal is ingested, the vagal nerves, vasoactive intestinal polypeptide (VIP), gastrin-releasing peptide (GRP), secretin, cholecystokinin (CCK), and encephalins stimulate release of these proenzymes into the pancreatic duct.

The proenzymes travel to the brush border of the duodenum, where trypsinogen, the proenzyme for trypsin, is activated via hydrolysis of an N-terminal hexapeptide fragment by the brush border enzyme enterokinase. Trypsin then facilitates the conversion of the other proenzymes to their active forms.

A feedback mechanism exists to limit pancreatic enzyme activation after appropriate metabolism has occurred. It is hypothesized that elevated levels of trypsin, having become unbound from digesting food, lead to decreased CCK and secretin levels, thus limiting further pancreatic secretion.

Because premature activation of pancreatic enzymes within the pancreas leads to organ injury and pancreatitis, several mechanisms exist to limit this occurrence. First, proteins are translated into the inactive proenzymes. Later, posttranslational modification of the Golgi cells allows their segregation into the unique subcellular zymogen compartments. The proenzymes are packaged in a paracrystalline arrangement with protease inhibitors.

Zymogen granules have an acidic pH and a low calcium concentration, which are factors that guard against premature activation until after secretion has occurred and extracellular factors have triggered the activation cascade. Under various conditions, disruption of these protective mechanisms may occur, resulting in intracellular enzyme activation and pancreatic autodigestion leading to acute pancreatitis.
Pathogenesis of acute pancreatitis

Acute pancreatitis may occur when factors involved in maintaining cellular homeostasis are out of balance. The initiating event may be anything that injures the acinar cell and impairs the secretion of zymogen granules; examples include alcohol use, gallstones, and certain drugs.

At present, it is unclear exactly what pathophysiologic event triggers the onset of acute pancreatitis. It is believed, however, that both extracellular factors (eg, neural and vascular response) and intracellular factors (eg, intracellular digestive enzyme activation, increased calcium signaling, and heat shock protein activation) play a role. In addition, acute pancreatitis can develop when ductal cell injury leads to delayed or absent enzymatic secretion, as with the CFTR gene mutation.

Once a cellular injury pattern has been initiated, cellular membrane trafficking becomes chaotic, with the following deleterious effects:

Lysosomal and zymogen granule compartments fuse, enabling activation of trypsinogen to trypsin.
Intracellular trypsin triggers the entire zymogen activation cascade.
Secretory vesicles are extruded across the basolateral membrane into the interstitium, where molecular fragments act as chemoattractants for inflammatory cells

Activated neutrophils then exacerbate the problem by releasing superoxide (the respiratory burst) or proteolytic enzymes (cathepsins B, D, and G; collagenase; and elastase). Finally, macrophages release cytokines that further mediate local (and, in severe cases, systemic) inflammatory responses. The early mediators defined to date are tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and IL-8.

These mediators of inflammation cause an increased pancreatic vascular permeability, leading to hemorrhage, edema, and eventually pancreatic necrosis. As the mediators are excreted into the circulation, systemic complications can arise, such as bacteremia due to gut flora translocation, acute respiratory distress syndrome (ARDS), pleural effusions, gastrointestinal (GI) hemorrhage, and renal failure.

The systemic inflammatory response syndrome (SIRS) can also develop, leading to the development of systemic shock. Eventually, the mediators of inflammation can become so overwhelming to the body that hemodynamic instability and death ensue.

In acute pancreatitis, parenchymal edema and peripancreatic fat necrosis occur first; this is known as acute edematous pancreatitis. When necrosis involves the parenchyma, accompanied by hemorrhage and dysfunction of the gland, the inflammation evolves into hemorrhagic or necrotizing pancreatitis. Pseudocysts and pancreatic abscesses can result from necrotizing pancreatitis because enzymes can be walled off by granulation tissue (pseudocyst formation) or via bacterial seeding of pancreatic or peripancreatic tissue (pancreatic abscess formation).

Li et al compared 2 set of patients with severe acute pancreatitis—one with acute renal failure and the other without it—and determined that a history of renal disease, hypoxemia, and abdominal compartment syndrome are significant risk factors for acute renal failure in patients with severe acute pancreatitis.[1] In addition, patients with acute renal failure were found to have a significantly greater average length of stay in the hospital and in the intensive care unit (ICU), as well as higher rates of pancreatic infection and mortality.

Etiology

Long-standing alcohol consumption and biliary stone disease cause most cases of acute pancreatitis, but numerous other etiologies are known. In 10-30% of cases, the cause is unknown, though studies have suggested that as many as 70% of cases of idiopathic pancreatitis are secondary to biliary microlithiasis.
Biliary tract disease

One of the most common causes of acute pancreatitis in most developed countries (accounting for approximately 40% of cases) is gallstones passing into the bile duct and temporarily lodging at the sphincter of Oddi. The risk of a stone causing pancreatitis is inversely proportional to its size.

It is thought that acinar cell injury occurs secondary to increasing pancreatic duct pressures caused by obstructive biliary stones at the ampulla of Vater, although this has not been definitively proven in humans. Occult microlithiasis is probably responsible for most cases of idiopathic acute pancreatitis.
Alcohol

Alcohol use is a major cause of acute pancreatitis (accounting for at least 35% of cases[2] ). On the cellular level, ethanol leads to intracellular accumulation of digestive enzymes and their premature activation and release. On the ductal level, it increases the permeability of ductules, allowing enzymes to reach the parenchyma and cause pancreatic damage. Ethanol increases the protein content of pancreatic juice and decreases bicarbonate levels and trypsin inhibitor concentrations. This leads to the formation of protein plugs that block pancreatic outflow.

Most commonly, the disease develops in patients whose alcohol ingestion is habitual over 5-15 years. Alcoholics are usually admitted with an acute exacerbation of chronic pancreatitis. Occasionally, however, pancreatitis can develop in a patient with a weekend binging habit, and several case reports have described a sole large alcohol load precipitating a first attack. Nevertheless, the alcoholic who imbibes routinely remains the rule rather than the exception.

Currently, there is no universally accepted explanation for why certain alcoholics are more predisposed to developing acute pancreatitis than other alcoholics who ingest similar quantities are.

Endoscopic Retrograde Cholangiopancreatography
Pancreatitis occurring after endoscopic retrograde cholangiopancreatography (ERCP) is probably the third most common type (accounting for approximately 4% of cases). Whereas retrospective surveys indicate that the risk is only 1%, prospective studies have shown the risk to be at least 5%.

The risk of post-ERCP acute pancreatitis is increased if the endoscopist is inexperienced, if the patient is thought to have sphincter of Oddi dysfunction, or if manometry is performed on the sphincter of Oddi. No medical measures, with the exception of aggressive preintervention intravenous (IV) hydration, have been durably shown to prevent post-ERCP pancreatitis in randomized studies.

Trauma

Abdominal trauma (approximately 1.5%) causes an elevation of amylase and lipase levels in 17% of cases and clinical pancreatitis in 5% of cases. Pancreatic injury (see the image below) occurs more often in penetrating injuries (eg, from knives, bullets) than in blunt abdominal trauma (eg, from steering wheels, horses, bicycles). Blunt injury to the abdomen or back may crush the gland across the spine, leading to a ductal injury.

CT scan of abdomen in child with traumatic pancreaCT scan of abdomen in child with traumatic pancreatitis. Fluid collection adjacent to pancreas will become pseudocyst. Note that pancreas is lacerated, nearly cut in half, by force of abdominal trauma. Also, note typical location of this injury in relation to vertebral column.

Drugs

Considering the small number of patients who develop pancreatitis compared to the relatively large number who receive potentially toxic drugs, drug-induced pancreatitis is a relatively rare occurrence (accounting for approximately 2% of cases) that is probably related to an unknown predisposition. Fortunately, drug-induced pancreatitis is usually mild.

Drugs definitely associated with acute pancreatitis include the following:
Azathioprine Sulfonamides Sulindac Tetracycline Valproic acid, Didanosine Methyldopa Estrogens Furosemide 6-Mercaptopurine Pentamidine 5-aminosalicylic acid compounds Corticosteroids Octreotide

Drugs probably associated with acute pancreatitis include the following:

Chlorothiazide and hydrochlorothiazide Methandrostenolone (methandienone) Metronidazole Nitrofurantoin Phenformin Piroxicam Procainamide Colaspase Chlorthalidone Combination cancer chemotherapy drugs (especially asparaginase) Cimetidine Cisplatin Cytosine arabinoside Diphenoxylate Ethacrynic acid
In addition, there are many drugs that have been reported to cause acute pancreatitis in isolated or sporadic cases.

Less common causes

The following causes each account for less than 1% of cases of pancreatitis.

Infection

Several infectious diseases may cause pancreatitis, especially in children. These cases of acute pancreatitis tend to be milder than cases of acute biliary or alcohol-induced pancreatitis.

Viral causes include mumps virus, coxsackievirus, cytomegalovirus (CMV), hepatitis virus, Epstein-Barr virus (EBV), echovirus, varicella-zoster virus (VZV), measles virus, and rubella virus. Bacterial causes include Mycoplasma pneumoniae, Salmonella, Campylobacter, and Mycobacterium tuberculosis. Worldwide, Ascaris is a recognized cause of pancreatitis resulting from the migration of worms in and out of the duodenal papillae.

Pancreatitis has been associated with AIDS; however, this may be the result of opportunistic infections, neoplasms, lipodystrophy, or drug therapies.

Hereditary pancreatitis

Hereditary pancreatitis is an autosomal dominant gain-of-function disorder related to mutations of the cationic trypsinogen gene (PRSS1), which has an 80% penetrance. Mutations in this gene cause premature activation of trypsinogen to trypsin.

In addition, the CFTR mutation plays a role in predisposing patients to acute pancreatitis by causing abnormalities of ductal secretion. At present, however, the phenotypic variability of patients with the CFTR mutation is not well understood. Certainly, patients homozygous for the CFTR mutation are at risk for pancreatic disease, but it is not yet clear which of the more than 800 mutations carries the most significant risk. In addition, the role of CFTR heterozygotes in pancreatic disease is unknown.

Mutations in the SPINK1 protein, which blocks the active binding site of trypsin, rendering it inactive, also probably play a role in causing a predisposition toward acute pancreatitis.

This probably explains the predisposition, rather than the cause, of acute pancreatitis in these patients. If enough mutant enzymes become activated intracellularly, they can overwhelm the first line of defense (ie, pancreatic secretory trypsin inhibitor) and resist backup defenses (ie, proteolytic degradation by mesotrypsin, enzyme Y, and trypsin itself). Activated mutant cationic trypsin can then trigger the entire zymogen activation cascade.

Hypercalcemia

Hypercalcemia from any cause can lead to acute pancreatitis. Causes include hyperparathyroidism, excessive doses of vitamin D, familial hypocalciuric hypercalcemia, and total parenteral nutrition (TPN). Routine use of automated serum chemistries has allowed earlier detection and reduced the frequency of hypercalcemia manifesting as pancreatitis.

Developmental abnormalities of pancreas
The pancreas develops from 2 buds stemming from the alimentary tract of the developing embryo. There are 2 developmental abnormalities commonly associated with pancreatitis: pancreas divisum and annular pancreas.

Pancreas divisum is a failure of the dorsal and ventral pancreatic ducts to fuse during embryogenesis. Probably a variant of normal anatomy, it occurs in approximately 5% of the population (see the images below); in most cases, it may actually protect against gallstone pancreatitis. It appears that the presence of stenotic minor papillae and an atretic duct of Santorini are additional risk factors that together contribute to the development of acute pancreatitis through an obstructive mechanism (although this is controversial).

Pancreas divisum associated with minor papilla stePancreas divisum associated with minor papilla stenosis causing recurrent pancreatitis. Because pancreas divisum is relatively common in general population, it is best regarded as variant of normal anatomy and not necessarily as cause of pancreatitis. In this case, note bulbous contour of duct adjacent to cannula. This appearance has been termed Santorinicele. Dorsal duct outflow obstruction is probable cause of pancreatitis when Santorinicele is present and associated with minor papilla that accommodates only guide wire.

Recurrent pancreatitis associated with pancreas diRecurrent pancreatitis associated with pancreas divisum in elderly man. Pancreatogram of dorsal duct shows distal stenosis with upstream chronic pancreatitis. After stenosis was dilated and stented, pain resolved and patient improved clinically during 1 year of quarterly stent exchanges. Follow-up CT scans showed resolution of inflammatory mass. Although ductal biopsies and cytology were repeatedly negative, pain and pancreatitis returned when stents were removed. Patient d eveloped duodenal outflow obstruction and was sent to surgery; Whipple procedure revealed periampullary adenocarcinoma (of minor papilla).

Annular pancreas is an uncommon congenital anomaly in which a band of pancreatic tissue surrounds the second part of the duodenum. Usually, it does not cause symptoms until later in life. This condition is a rare cause of acute pancreatitis, probably through an obstructive mechanism.

Sphincter of Oddi dysfunction can lead to acute pancreatitis by causing increased pancreatic ductal pressures. However, the role of pancreatitis induced by such dysfunction in patients without elevated sphincter pressures on manometry remains controversial.

Hypertriglyceridemia

Clinically significant pancreatitis usually does not occur until a person’s serum triglyceride level reaches 1000 mg/dL. It is associated with type I and type V hyperlipidemia. Although this view is somewhat controversial, most authorities believe that the association is caused by the underlying derangement in lipid metabolism rather than by pancreatitis causing hyperlipidemia. This type of pancreatitis tends to be more severe than alcohol- or gallstone-induced disease.

Tumors

Obstruction of the pancreatic ductal system by a pancreatic ductal carcinoma, ampullary carcinoma, islet cell tumor, solid pseudotumor of the pancreas, sarcoma, lymphoma, cholangiocarcinoma, or metastatic tumor can cause acute pancreatitis. The chance of pancreatitis occurring when a tumor is present is approximately 14%. Pancreatic cystic neoplasm, such as intraductal papillary-mucinous neoplasm (IPMN), mucinous cystadenoma, or serous cystadenoma, can also cause pancreatitis.

Toxins

Exposure to organophosphate insecticide can cause acute pancreatitis. Scorpion and snake bites may also be causative; in Trinidad, the sting of the scorpion Tityus trinitatis is the most common cause of acute pancreatitis. Hyperstimulation of pancreas exocrine secretion appears to be the mechanism of action in both instances.

Surgical procedures

Acute pancreatitis may occur in the postoperative period of various surgical procedures (eg, abdominal or cardiopulmonary bypass surgery, which may insult the gland by causing ischemia). Postoperative acute pancreatitis is often a difficult diagnosis to confirm, and it has a higher complication rate than pancreatitis associated with other etiologies. The mechanism is unclear.

Vascular abnormalities

Vascular factors, such as ischemia or vasculitis, can play a role in causing acute pancreatitis. Vasculitis can predispose patients to pancreatic ischemia, especially in those with polyarteritis nodosa and systemic lupus erythematosus.

Autoimmune pancreatitis

Autoimmune pancreatitis, a relatively newly described entity, is an extremely rare cause of acute pancreatitis (prevalence, 0.82 per 100,000 individuals). When it does cause acute pancreatitis, it is usually in young people (approximately 40 years) who also suffer from inflammatory bowel disease. The pathogenesis is unclear.

Epidemiology

United States statistics

Acute pancreatitis has an incidence of approximately 40 cases per year per 100,000 adults.[3] In 2007, nearly 220,000 patients with acute pancreatitis are expected to be admitted to non–federally funded hospitals. In 1998, 183,000 patients with acute pancreatitis were admitted. This trend in rising incidence has been recognized over the past several decades.[4]
International statistics

Worldwide, the incidence of acute pancreatitis ranges between 5 and 80 per 100,000 population, with the highest incidence recorded in the United States and Finland.[5] In Luneburg, Germany, the incidence is 17.5 cases per 100,000 people. In Finland, the incidence is 73.4 cases per 100,000 people. Similar incidence rates have been reported in Australia. The incidence of disease outside North America, Europe, and Australia is less well known.

In Europe and other developed nations, such as Hong Kong, more patients tend to have gallstone pancreatitis, whereas in the United States, alcoholic pancreatitis is most common.
Age-related demographics

The median age at onset depends on the etiology.[6] The following are median ages of onset for various etiologies:

Alcohol-related - 39 years
Biliary tract–related - 69 years
Trauma-related - 66 years
Drug-induced etiology - 42 years
ERCP-related - 58 years
AIDS-related - 31 years
Vasculitis-related - 36 years

Hospitalization rates increase with age. For people aged 35-75 years, the rate doubles for males and quadruples for females.

Sex-related demographics

Generally, acute pancreatitis affects males more often than females. In males, the etiology is more often related to alcohol; in females, it is more often related to biliary tract disease. Idiopathic pancreatitis has no clear predilection for either sex.
Race-related demographics

The hospitalization rates of patients with acute pancreatitis per 100,000 population are 3 times higher for blacks than whites. These racial differences are more pronounced for males than females. The risk for African Americans aged 35-64 years is 10 times higher than for any other group. African Americans are at higher risk than whites in that same age group.

The annual incidence of acute pancreatitis in Native Americans is 4 per 100,000 population; in whites, 5.7 per 100,000 population; and in blacks, 20.7 per 100,000 population.[7]

Prognosis

Overall mortality in patients with acute pancreatitis is 10-15%. Patients with biliary pancreatitis tend to have a higher mortality than patients with alcoholic pancreatitis. This rate has been falling over the last 2 decades as improvements in supportive care have been initiated. In patients with severe disease (organ failure), who account for about 20% of presentations, mortality is approximately 30%.[8] This figure has not decreased in the past 10 years. In patients with necrosis without organ failure, mortality approaches zero.

In the first week of illness, most deaths result from multiorgan system failure. In subsequent weeks, infection plays a more significant role, but organ failure still constitutes a major cause of mortality. Acute respiratory distress syndrome (ARDS), acute renal failure, cardiac depression, hemorrhage, and hypotensive shock all may be systemic manifestations of acute pancreatitis in its most severe form.

Identifying patients in greatest need of aggressive medical treatment by differentiating their disease severity as mild or severe is recommended. In mild disease, the pancreas exhibits interstitial edema, an inflammatory infiltrate without hemorrhage or necrosis, and, usually, minimal or no organ dysfunction. In severe disease, the inflammatory infiltrate is severe, associated with necrosis of the parenchyma, often accompanied by evidence of severe gland dysfunction, and it may be associated with multiorgan system failure.

Different strategies have been used to assess the severity of acute pancreatitis and predict outcome (see Workup and Staging). Several clinical scoring systems (eg, Ranson criteria, Glasgow, Imrie) are available. The APACHE II scoring system, though cumbersome, appears to be the best validated. Biological markers have also been used for this purpose. Genetic markers are being studied and have not yet come into clinical use.

Peritoneal lavage has a high specificity (93%); however, it has a low sensitivity (54%). Dynamic CT scanning of the abdomen is widely available and useful in predicting the outcome of acute pancreatitis. When the Balthazar criteria (see Workup and Computed Tomography) are used, sensitivity is 87% and specificity is 88%.

Patient Education

Educate patients about the disease, and advise them to avoid alcohol in binge amounts and to discontinue any risk factor, such as fatty meals and abdominal trauma.

Refference :

Li H, Qian Z, Liu Z, Liu X, Han X, Kang H. Risk factors and outcome of acute renal failure in patients with severe acute pancreatitis. J Crit Care. Jun 2010;25(2):225-9.[Medline]
Whitcomb DC, Yadav D, Adam S, et al. Multicenter approach to recurrent acute and chronic pancreatitis in the United States: the North American Pancreatitis Study 2 (NAPS2). Pancreatology. 2008;8(4-5):520-31. [Medline]. [Full Text].
Granger J, Remick D. Acute pancreatitis: models, markers, and mediators. Shock. Dec 2005;24 Suppl 1:45-51. [Medline].
Singla A, Csikesz NG, Simons JP, Li YF, Ng SC, Tseng JF, et al. National hospital volume in acute pancreatitis: analysis of the Nationwide Inpatient Sample 1998-2006. HPB (Oxford). Aug 2009;11(5):391-7. [Medline]. [Full Text].
Banks PA. Epidemiology, natural history, and predictors of disease outcome in acute and chronic pancreatitis. Gastrointest Endosc. Dec 2002;56(6 Suppl):S226-30. [Medline].
Morinville VD, Barmada MM, Lowe ME. Increasing incidence of acute pancreatitis at an American pediatric tertiary care center: is greater awareness among physicians responsible?. Pancreas. Jan 2010;39(1):5-8. [Medline].
Akhtar AJ, Shaheen M. Extrapancreatic manifestations of acute pancreatitis in African-American and Hispanic patients. Pancreas. Nov 2004;29(4):291-7. [Medline].
Whitcomb DC. Clinical practice. Acute pancreatitis. N Engl J Med. May 18 2006;354(20):2142-50. [Medline].

Source :

http://emedicine.medscape.com
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Methamphetamine Use May Boost Schizophrenia Risk

noreply@blogger.com (Han Idris) — Thu, 01 Dec 2011 04:54:00 +0000

News Author: D. Brauser

CME Author: Laurie Barclay, MD

Authors and Disclosures

CME Released: 11/23/2011; Valid for credit through 11/23/2012

Clinical Context

Findings of epidemiologic studies have suggested that cannabis use may increase the risk for the development of schizophrenia. In Japan, there is a long history of clinical studies suggesting that methamphetamine exposure may cause a persistent schizophrenia-like psychosis. However, the Western literature does not support this possibility.

According to the stress-vulnerability theory of schizophrenia, heavy exposure to any drug of abuse, particularly one that can cause acute psychosis, could interact with risk factors to increase vulnerability to the development of persistent psychosis.

The objective of this large-scale study by Callaghan and colleagues was to evaluate the association between drug use and later development of schizophrenia among a cohort of drug users initially free of persistent psychosis. In addition to methamphetamine users, the study cohort also included a second stimulant group (cocaine) and 3 nonstimulant drug use groups (cannabis, alcohol, and opioids). In addition, records from a group of non–drug-using patients with appendicitis were included as a population proxy, "healthy control" comparison group.

Study Synopsis and Perspective

Heavy methamphetamine use may be associated with an increased risk for schizophrenia, new research suggests.

A large cohort study of California inpatients without a history of psychiatric disorders found that those with methamphetamine-related conditions were 9 times more likely to have a subsequent schizophrenia diagnosis than non–drug users, and an almost 1.5- to 3-fold diagnosis risk compared with heavy users of cocaine and opioids, but not cannabis.

"This provides the first world-wide evidence for a long-standing debate that suggests that methamphetamines may facilitate the development of schizophrenia in a small subset of users," lead author Russell C. Callaghan, PhD, research scientist at the Center for Addiction and Mental Health (CAMH) in Toronto, Canada, told Medscape Medical News.

"Methamphetamine users often present to clinical and emergency department settings with psychosis. And our findings suggest that these people need to be monitored closely for an attenuation of their psychotic symptoms. Also, given the side effects with antipsychotic medications, I think we really need to prescribe those treatments judiciously," said Dr. Callaghan.

He added that the study findings do not apply to patients who take lower and controlled doses of amphetamines for medical purposes, such as for attention-deficit/hyperactivity disorder.

Nora Volkow, MD, director of the National Institute on Drug Abuse, told Medscape Medical News that although the results need to be replicated, they are important clinically.

"As with anything else in science, one study can wake you up and tell you that you need to be alert. Many times things are right in front of your eyes, but if you're not looking for them you don't see them," she said.

"I would hope that this paper would make clinicians much more aware of the possibilities that methamphetamines could increase the vulnerability for schizophrenia."

The study was published online November 8 in the American Journal of Psychiatry.

Link to Parkinson's Disease

As previously reported by Medscape Medical News, the same research team found evidence for a possible association between heavy methamphetamine use and Parkinson's disease.

Although previous studies from Japanese researchers have also suggested a connection between methamphetamine use and "a persistent schizophrenia-like psychosis," most have lacked long-term follow-up.

According to Dr. Callaghan, many North American researchers have discounted this link because they believe the psychosis was already present and undiagnosed in the methamphetamine users.

"So we wanted to examine this issue and compare it between several large groups initially free of persistent psychosis, including those using drugs other than methamphetamines," he said.

The investigators evaluated California hospital records for adult patients admitted between 1990 and 2000 for dependence or abuse of methamphetamines (n = 42,412), cannabis (n = 23,335), alcohol (n = 408,604), cocaine (n = 39,390), or opioids (n = 56,844).

In addition, records from a group of non–drug-using patients with appendicitis were included as a population proxy, "healthy control" comparison group (n = 188,732).

Similar Risk for Cannabis Use

Appendicitis was chosen because "it is a relatively common reason for hospital admissions, is not associated with socioeconomic status, does not appear on theoretical grounds to be related to schizophrenia or substance use disorders, [and] has a well-defined clinical course," explain the researchers.

Readmission records for up to 10 years later for all study participants were then examined for a schizophrenia diagnosis (disorganized, catatonic, paranoid, or residual type), as specified in the International Classification of Diseases, Ninth Revision.

Results showed that the group of heavy methamphetamine users had a significantly higher risk for a schizophrenia diagnosis than did the healthy comparison group (hazard ratio [HR], 9.37; P < .001). In fact, the risk for schizophrenia was significantly higher for all drug cohorts than for the appendicitis group (P < .001 for all). The risk was also significantly higher for the methamphetamine group compared with those using opioids (HR, 2.81; P < .001), alcohol (HR, 1.68; P < .001), and cocaine (HR, 1.46; P = .002). However, there was no significant risk difference between users of methamphetamines and cannabis. "Our findings add to the growing literature on cannabis as a risk factor for schizophrenia and, in addition, suggest that methamphetamine use sufficient to warrant a hospital diagnosis may also be a risk factor," write the investigators. They add, however, that they have "some skepticism about the suggestion" that this risk is increased in all major drug use groups and that it will need replication.

Mechanism Unclear

"We really do not understand how these drugs might increase schizophrenia risk," co-investigator Stephen Kish, MD, senior scientist and head of the Human Brain Laboratory at CAMH, said in a release.

"Perhaps repeated use of methamphetamine and cannabis in some susceptible individuals can trigger latent schizophrenia by sensitizing the brain to dopamine, a brain chemical thought to be associated with psychosis."

The investigators note that further research is needed, including long-term follow-up studies. Dr. Callaghan reported that his team is now working on extending the current study to Sweden and other states in the United States, and eventually to western Australia, "to see if these patterns can replicate."

"We hope that understanding the mechanism of the drug addiction-schizophrenia relationship will help in the future development of better therapies for both conditions," he said.

The overall finding was surprising because the field has not really paid attention to these potential issues, although there has been a lot of interest in marijuana use," said Dr. Volkow.

"We've known that methamphetamine use produces psychosis, but it tends to be of short duration and then disappear. This data is showing that that's not necessarily the case and there are some subjects that may go on to have a full-blown diagnosis of schizophrenia.

" Dr. Volkow added that this study confirms findings from previous imaging studies, using both animal and human populations, showing that repeated exposure to drugs affects the biochemistry, function, and even structure of the brain. She also noted that the finding that alcohol use increased the risk for schizophrenia was unusual and unexpected.

"The investigators discuss that they aren't clear why this happened. So it will be interesting to see if it replicates.

" Study limitations voiced by the investigators and Dr. Volkow included concerns about the retrospective design and the accuracy of the schizophrenia diagnoses.

"Also, how do you ensure that individuals who started to have a psychotic break, and therefore started using methamphetamines as a way to try and compensate, weren't confounders?"

"It is replication that will really determine whether in fact this is a concern or not. But until then, I think we need to keep our eyes open," concluded Dr. Volkow. The study was supported indirectly by an institutional grant from the Ontario Ministry of Health and Long-Term Care. Dr. Volkow and 6 of the 8 study authors, including Dr. Callaghan, have disclosed no relevant financial relationships. Dr. Kish reports having received research funding from the National Institute on Drug Abuse and remuneration as an expert witness on amphetamine toxicity. Co-investigator Gary Remington, MD, PhD, reports having received research support from Medicure, Neurocrine Biosciences, and Novartis and serving as an advisor to Roche.

Am J Psychiatry. Published online November 8, 2011.

Study Highlights

* This population-based cohort study used data from California inpatient hospital discharge records from 1990 through 2000.

* Using propensity scores, the investigators matched 42,412 patients with methamphetamine-related conditions and those with other drug use disorders to individuals with primary appendicitis, who served as a population proxy comparison group.

* The methamphetamine cohort was also matched to the other drug cohorts (cannabis, cocaine, alcohol, and opioids).

* Matching was 1:1 based on age, race, sex, time from the index admission until the last date in the study file, California region of residence, Charlson comorbidity index score at index admission, and the number of hospital admissions after the index admission until readmission with schizophrenia (the outcome measure) or study end.

* Between-group differences in the rates of subsequent admission with schizophrenia diagnoses were estimated with use of Cox modeling.

* The risk for schizophrenia was significantly higher in the methamphetamine cohort vs the appendicitis group (HR, 9.37) and the cocaine, opioid, and alcohol groups (HRs ranging from 1.46 - 2.81), but this risk was not significantly different from that of the cannabis group.

* Compared with the appendicitis group, all drug cohorts had a higher risk for schizophrenia. The HRs were 8.16 for cannabis, 5.84 for cocaine, 5.56 for alcohol, and 3.60 for opioids.

* Limitations of this study include difficulty in confirming schizophrenia diagnoses independent of drug intoxication and the possibility that undetected schizophrenia predated drug exposure.

* In addition, study participants were limited to substance users with severity sufficient enough to receive a hospital diagnosis, precluding determination of a dose-response relationship.

* On the basis of these findings, the investigators concluded that methamphetamine-related disorders are associated with a higher risk for schizophrenia than are other drug use disorders, except for cannabis use disorders.

* They suggest that the increased risk for schizophrenia in methamphetamine users may be explained by shared etiologic mechanisms involved in the development of schizophrenia.

* Other explanations might include shared genetic and environmental vulnerability factors (such as low socioeconomic status) or a premorbid state (such as depression, anxiety, and poor cognitive functioning) leading to substance use as an attempt at self-medication.

* Finally, the mechanism could be pathologic drug-induced sensitization, in which repeated exposure to a dopaminergic stimulant induces a hyperdopaminergic state sufficient to induce psychosis in vulnerable individuals.

Clinical Implications

* In this population-based cohort of drug users initially free of persistent psychosis, methamphetamine use was associated with a higher risk for schizophrenia vs use of other drugs, except for cannabis. The risk for schizophrenia was 9-fold higher in the methamphetamine cohort vs the control group admitted to the hospital with appendicitis.

* Compared with the appendicitis group, all drug cohorts in this population-based cohort of drug users initially free of persistent psychosis had a higher risk for schizophrenia. This risk was highest for methamphetamines or cannabis, followed by cocaine, alcohol, and opioids.

http://www.medscape.org

Coffee Associated With Lower Risk for Endometrial Cancer

noreply@blogger.com (Han Idris) — Thu, 01 Dec 2011 03:56:00 +0000

News Author: Emma Hitt, PhD
CME Author: Hien T. Nghiem, MD

Authors and Disclosures

CME Released: 11/28/2011; Valid for credit through 11/28/2012

Clinical Context

In the United States, endometrial cancer is the most common gynecologic cancer. One of the most important mechanisms in endometrial carcinogenesis is the prolonged exposure to excessive unopposed estrogens, resulting in stimulation of the endometrium. Recent studies have demonstrated that at baseline, high circulating levels of estrogens, C-peptide, and fasting insulin were associated with an increased risk for endometrial cancer. Coffee has been reported to lower levels of estrogen and insulin, but prospective data on the relationship between coffee consumption and the risk for endometrial cancer are limited.

The aim of this study by Giovannucci and colleagues was to examine the association between coffee consumption and endometrial cancer risk.

Study Synopsis and Perspective

Drinking at least 4 cups of coffee per day is associated with a lower risk for endometrial cancer, according to new data from the Nurses' Health Study.

Youjin Je, a doctoral candidate in the lab of Edward Giovannucci, MD, ScD, from the Department of Nutrition and Epidemiology at the Harvard School of Public Health in Boston, Massachusetts, and colleagues published their findings online November 22 in Cancer Epidemiology, Biomarkers & Prevention.

"Coffee consumption may be related to endometrial cancer development due to the potential role of caffeine," Dr. Giovannucci and colleagues write. "Several epidemiologic studies have reported an inverse association between coffee intake and endometrial cancer risk, but data from prospective studies are limited."

Therefore, the researchers prospectively examined the link between drinking coffee and endometrial cancer risk, using prospective data from the Nurses' Health Study.

The analysis included data from 67,470 women aged 34 to 59 years in 1980. Cumulative average coffee intake was determined by questionnaire. During 26 years of follow-up, researchers documented 672 cases of endometrial cancer.

Drinking fewer than 4 cups of coffee per day was not associated with a change in endometrial cancer risk compared with drinking 1 or less cups per day. The researchers accounted for numerous factors in their multivariable analysis, including body mass index, age at menopause, age at menarche, parity and age at last birth, oral contraceptive use, postmenopausal hormone use, and smoking and alcohol consumption.

However, drinking 4 or more cups of coffee per day was associated with a 25% relative risk reduction compared with consuming less than 1 cup daily (multivariable rate ratio [RR], 0.75; 95% confidence interval [CI], 0.57 - 0.97; P trend = .02). Drinking between 2 and 3 cups of coffee per day was linked with a 7% reduced risk, but the difference did not reach statistical significance (RR, 0.93; 95% CI, 0.76 - 1.14; P trend = .02).

In terms of absolute risk reduction, women who drank 4 or more cups of coffee reduced their risk for endometrial cancer from 56 cases per 100,000 women to 35 cases per 100,000 women. The investigators saw a similar association when they restricted their analysis to caffeinated coffee consumption. In that case, there was a 30% relative risk reduction in endometrial cancer risk associated with consumption of 4 or more cups compared with less than 1 cup a day.

For decaffeinated coffee consumption, drinking 2 or more cups per day was linked with a 22% relative reduction in risk for endometrial cancer vs drinking less than 1 cup per month, but the difference did not reach statistical significance, perhaps because of the smaller cohort size (RR, 0.78; 95% CI, 0.57 - 1.08; P trend = .58). The researchers saw no association between tea drinking and endometrial cancer risk.

In subgroup analyses, there was a stronger inverse association with high coffee intake among obese women. "Because obese women tend to have insulin resistance, oxidative stress, and relatively low levels of [sex hormone binding globulin], the potential abilities of coffee to improve those conditions may have contributed to a decreased risk of endometrial cancer among obese women," the authors write.

"Coffee has already been shown to be protective against diabetes due to its effect on insulin," noted Dr. Giovannucci in a written release. "So we hypothesized that we'd see a reduction in some cancers as well." According to Dr. Giovannucci, laboratory testing has found that coffee has many more antioxidants than most vegetables and fruits.

The authors have disclosed no relevant financial relationships.

Cancer Epidemiol Biomarkers Prev. Published online November 22, 2011.

Study Highlights

* This study prospectively assessed coffee consumption in relationship to endometrial cancer risk in the Nurses' Health Study with 67,470 female participants 34 to 59 years old in 1980.

* Cases included in this study were endometrial adenocarcinoma.

* A previous validated semiquantitative food frequency questionnaire was used to assess dietary intake, including coffee and tea.

* Cumulative average coffee intake was calculated with all available questionnaires to assess long-term effects.

* Cox regression models were used to calculate incidence RRs, controlling for other risk factors.

* During the 26 years of follow-up, a total of 672 cases of endometrial cancer were documented.

* Results demonstrated that fewer than 4 cups of coffee per day were not associated with a lowered risk for endometrial cancer.

* However, women who consumed 4 or more cups of coffee had a 25% lower risk for endometrial cancer than those who consumed less than 1 cup per day (multivariable RR, 0.75; 95% CI, 0.57- 0.97; P trend = .02).

* A similar association was found with caffeinated coffee consumption (RR for ≥ 4 cups/day vs < 1 cup/day, 0.70; 95% CI, 0.51 - 0.95), yielding a 30% lower risk for endometrial cancer.

* For decaffeinated coffee consumption, a suggestive inverse association was found among women who consumed 2 or more cups per day vs less than 1 cup per month in which there was a 22% relative reduction in endometrial cancer risk. However, the difference did not reach statistical significance, perhaps because of the smaller cohort size (RR, 0.78; 95% CI, 0.57 - 1.08; P trend = .58).

* Tea consumption was not associated with endometrial cancer risk.

* The inverse association of endometrial cancer risk with 4 or more cups of coffee per day seemed stronger among obese women, past or current smokers, postmenopausal women, and those without current postmenopausal hormone use. However, there were no significant interactions were observed between these variables and coffee intake.

Clinical Implications

* An important mechanism in endometrial carcinogenesis is prolonged exposure to excessive unopposed estrogens. Recent studies have demonstrated that high circulating levels of estrogens, C-peptide, and fasting insulin were associated with an increased risk for endometrial cancer.

* Prospective data suggest that 4 or more cups of coffee per day are associated with a lower risk for endometrial cancer.

Source : http://www.medscape.org

Acupuncture in Children Safe With Mild Adverse Events

noreply@blogger.com (Han Idris) — Tue, 29 Nov 2011 05:38:00 +0000

News Author: Rod Franklin
CME Author: Charles P. Vega, MD

Authors and Disclosures

CME/CE Released: 11/23/2011; Valid for credit through 11/23/2012

Clinical Context

Acupuncture is a popular treatment technique used for a wide variety of conditions, but a systematic "review of reviews" examining a collection of analyses of clinical data found that the benefits of acupuncture may not outweigh its risks. This study by Ernst and colleagues, which was published in the April 2011 issue of Pain, found that acupuncture was effective in the treatment of neck pain, but not for other indications. Moreover, researchers found 95 cases of severe adverse events (AEs) related to acupuncture, of which pneumothorax and infection were the most common.

Fewer children than adults receive acupuncture, but the safety of this procedure might be even more important for children. The current study by Adams and colleagues examines the rate and character of AEs associated with the use of acupuncture among children.

Study Synopsis and Perspective

A systematic review analyzing decades of needle acupuncture therapy in children aged 0 to 17 years reveals an 11.8% incidence of mild AEs and few severe AEs, prompting investigators to characterize the treatment as safe for younger patients, according to research published online November 21 in Pediatrics.

Led by Denise Adams, PhD, from the CARE program at the Department of Pediatrics, University of Alberta, Edmonton, Canada, investigators documented 279 AEs in patients aged 0 to 17 years. These included AEs cited in reports other than cohort studies and clinical trials. Drawing on guidance from the Common Terminology Criteria for Adverse Events scale, 253 AEs were adjudicated as mild, 1 was categorized as moderate, and 25 were classified as serious.

By restricting their analysis to the randomized controlled trials and cohort studies, Dr. Adams and colleagues were able to calculate the AE incidence.

"What we did was look at all the AEs reported in studies that involved needle acupuncture and found that 170 of 1487 patients equaled 11.4%," Dr. Adams told Medscape Medical News. "These values included patients treated who did not receive needle acupuncture. In order to examine patients treated with only needle acupuncture, we removed numerator (n = 2) and denominator (n = 65) values for the patients in the acupressure and conventional treatment groups, and so the values become 168 AEs for 1422 patients, or 11.8% (95% confidence interval, 10.1 - 13.5)."

The analysis was based on a search of 18 databases and a review of reference lists that identified 37 acupuncture reports meeting prespecified inclusion criteria. Nine of the reports described random controlled trials, 6 described cohort studies, and 22 described case reports or series of cases. Of those, 33 reports focused entirely on pediatric acupuncture patients.

Mild AEs were deemed to be those that generally required no specific medical intervention. These included cases in which the child experienced pain or bruising; transient hemorrhage at the puncture site; numbness; aggravation of an existing condition; or vasovagal reactions such as dizziness, nausea, or vomiting.

In 158 instances, mild AEs occurred while the child was being treated by a certified acupuncturist. In 83 cases the event occurred under the care of a physician trained in the procedure, and in 11 cases, a mild AE was recorded when an unspecified practitioner was involved. Provider credentials were not reported in 1 instance.

Serious AEs included 12 cases of thumb deformity, all occurring in 1 Chinese clinic between 1983 and 1989, and 5 cases of infection. There was also 1 case each of fatal cardiac rupture, pneumothorax, nerve impairment, subarachnoid hemorrhage, intestinal obstruction, hemoptysis, reversible coma, and overnight hospitalization.

Five serious AEs were suspected to have been caused by technical errors, rather than the procedure itself. These may have included improper sterilization or technique, or poor knowledge of anatomy. Numerous errors, including the insertion of needles through clothing and needle punctures in the diaphragm, pericardium, and right ventricular wall, were detected in the cardiac rupture case, which resulted in the death of a 9-year-old boy who suffered from malnutrition, pulmonary tuberculosis, and a severely enlarged heart.

Eighteen of the serious AEs were associated with care provided by an unspecified practitioner, 6 occurred under the care of a certified acupuncturist, and 1 occurred under the care of a physician certified in acupuncture.

Investigators acknowledged that more expansive and uniform research efforts would probably improve the conclusiveness of AE incidence estimates, especially in light of larger-scale surveys that previously have reported similar AEs in adults with incidences as high as 29.5%.

The higher rate of AEs detected in reviews of adult patients may be in part because of the much larger number of patients studied, as well as the prospective design of many of these trials. "In an editorial published a decade ago, MacPherson strongly encouraged the conduct of prospective practice surveys as a way of gathering the strongest safety evidence and overcoming limitations of both retrospective surveys and literature reviews," the authors write.

"The current pediatric acupuncture safety literature is limited to case reports and small studies or the inclusion of small numbers of children in predominantly adult studies. To produce convincing risk estimates for pediatric acupuncture, prospective large-scale pediatric studies and standardized reporting criteria are needed," they conclude.

The work was supported by Alberta Innovates-Health Solutions, which provides salary support to one of the investigators for health scholar activities. The other authors have disclosed no relevant financial relationships.

Pediatrics. Published online November 21, 2011.
Resources

The Cleveland Clinic's Web site provides patient education information on acupuncture. Additionally, the National Center for Complementary and Alternative Medicine provides extensive evidence based information on a wide range of therapies.
Study Highlights

* Researchers examined 18 health databases for research regarding acupuncture among children from birth to age 17 years. All studies included data on needle acupuncture as well as assessments of AEs.

* AEs were classified as mild (not requiring a specific medical intervention), moderate (minimal or noninvasive intervention), or serious (requiring hospitalization or invasive procedures, or were life-threatening).

* The original search yielded a total of 5288 nonduplicated references, but only 37 studies met full inclusion criteria. 30 of these included studies were published in English, and 22 were case reports or case series. 9 studies were randomized controlled trials.

* A total of 279 AEs were identified in the collective research, and 146 of these events occurred during randomized trials.

* 253 AEs were classified as mild, 1 AE was moderate, and 25 AEs were serious.

* Regarding causality, the numbers of AEs considered certainly, probably/likely, and possibly related to acupuncture were 57, 53, and 167, respectively.

* The most common serious AEs associated with acupuncture were thumb deformity (12 cases) and infection (5 cases). Most cases were related to treatment with unspecified practitioners as opposed to certified acupuncturists.

* All of the cases of thumb deformity were reported from a clinic in China.

* Infections associated with acupuncture included HIV, septic sacroiliitis, septic arthritis of the lumbar spine, pyogenic spondylitis, and osteomyelitis of the frontal bone.

* Mild AEs included crying, pain, bruising, transient hemorrhage of the puncture site, aggravation of preexisting symptoms or conditions, and vasovagal reactions.

* When data from randomized trials and cohort studies were combined, the rate of AEs for all children receiving acupuncture was 11.4%. Restricting the data to children who received needle acupuncture alone slightly increased the rate of AEs to 11.8% (95% confidence interval, 10.1 - 13.5).

Clinical Implications

* A previous review of clinical data by Ernst and colleagues found that acupuncture was effective in the treatment of neck pain, but not for other indications.

* In the current study by Adams and colleagues, the overall rate of AEs associated with the use of needle acupuncture among children was 11.8%. The vast majority of events was mild, and a disproportionate number of these AEs came from randomized trials.

http://www.medscape.org

Aggressive Children Linked With Having Future Health Problems CME

noreply@blogger.com (Han Idris) — Tue, 29 Nov 2011 05:26:00 +0000

News Author: Yael Waknine
CME Author: Hien T. Nghiem, MD

Authors and Disclosures

CME Released: 11/23/2011; Valid for credit through 11/23/2012

Study Synopsis and Perspective
Aggressive behavior in children may be linked to an increased risk for health problems 30 years later, a new study suggests.

Investigators from the Université de Sherbrooke, Québec; Concordia University, Montreal; the University of Ottawa, Canada; and the University of California, Davis, found that adults who scored higher on measures of aggression when they were children had an 8.1% increased risk for medical visits that did not include obstetrics or gynecology.

With increasing healthcare costs and an aging population, it is important to identify reliable predictors of poor health in adults, noted first author Caroline Temcheff, PhD, from the Université de Sherbrooke, in a news release.

The study was published online November 14 in the CMAJ.

Public Health Risk

The investigators analyzed data collected from the Concordia Longitudinal Risk Project for 3913 children originally recruited in grades 1, 4, and 7 who lived in low-income Montreal neighborhoods.

Children were asked to nominate up to 4 boys and girls in their class who best matched items on a Pupil Evaluation Inventory that covered behaviors such as aggression, withdrawal, and likability.

Factors included children who were "mean and cruel" toward others, those who were "too shy to make friends easily," and youngsters who were "especially nice." Scores were summed for each child to create a profile of aggressiveness vs likability.

Researchers then examined the number of medical services each child received between 1992 and 2006, at which time the mean age of the study participants was 39 years.

In addition to increased medical visits, the researchers found that adults who were aggressive as children had a 10.7% increased risk for injury. Risk for lifestyle-related illnesses such as obesity, type 2 diabetes, ulcers, alcohol dependence, and drug use also was raised, by a whopping 44.2%.

Other sequelae included a 6.2% increase in visits to specialists, a 12.4% increase in need for emergency department services, a 23.5% increase in dental visits, and a 10.9% increase in hospital admissions.

"Childhood aggression should be considered a health risk when designing interventions to improve public health, particularly those targeting children and families," the researchers write.

They note that possible explanations for these poor outcomes include leaving school prematurely with less education about health, lack of high school education and the resulting increased likelihood of high-injury manual jobs, and the stress factors associated with experiencing lower education combined with low income. Deficits in executive functioning and impulse control may be an underlying factor, they add.

Stress Response

Accordingly, the authors recommend a developmental approach to preventing and treating childhood aggression, an approach that Sarah Stewart-Brown, PhD, from the Department of Public Health at the University of Warwick, United Kingdom, supports.

In an accompanying commentary, she explains that childhood aggression is likely a response to a stressful environment and may interfere with normal physiologic response, predisposing people to lifestyles in which they misuse drugs and alcohol to provide short-term relief.

"There is good evidence that school-based programs can improve children's' behaviour," she writes, adding that interventions to help parents with parenting may be even more vital.

"A life-long approach to teaching children, teenagers, and young adults appropriate self-care and age-appropriate ways of managing their stress and impulses may effectively prevent poor health outcomes later in life," the researchers concur.

The authors and Dr. Stewart-Brown have disclosed no relevant financial relationships.

CMAJ. Published online November 14, 2011. Abstract, Commentary

Clinical Context

The literature suggests that early patterns of aggressive behavior in both girls and boys are predictive of a variety of health risks in adulthood. Currently, childhood aggression has been shown to predict such health risks as not completing high school, teen pregnancy and single motherhood, poverty, engaging in high-risk and/or unprotected sex, and dangerous driving. However, a longitudinal examination of the predictive links between childhood aggression, negative physical health outcomes in adulthood, and overall use of healthcare services has not been done.

The aim of this study by Temcheff and colleagues was to evaluate the use of healthcare services and a variety of physical health outcomes in adulthood to extend the current body of knowledge regarding the long-term negative sequelae of childhood aggression.

Study Highlights

* Participants of the Concordia Longitudinal Risk Project were eligible for the current study if they had received medical care in the province of Quebec between 1992 and 2006, and if they were able to retrieve their medical and education records.

* The Concordia Longitudinal Risk Project was conducted from 1976 to 1978, in which 4109 children in grades 1, 4, and 7 were evaluated for long-term sequelae of maladaptive behavior in childhood.

* 3913 of 4109 participants in the Concordia project participated in the study.

* The primary outcome was use of the healthcare system, as determined by records from the Régie de l'assurance maladie du Québec and the Ministère de la santé et des services sociaux.

* There were 9 outcome variables: (1) total number of medical visits (not including obstetric and gynecologic visits); (2) medical visits for injuries; (3) medical visits for lifestyle-related illness (ie, obesity, type 2 diabetes, ulcers, alcohol dependence, drug use); (4) visits to medical specialists; (5) visits to emergency departments; (6) visits to dentists; (7) hospital admissions; (8) medical visits for infections; and (9) gynecologic and obstetric visits (women only).

* The controlled variables were socioeconomic status of the neighborhood in which participants lived in 1986 and level of education.

* Hierarchical multiple regression was used to explore the association between childhood behavior and physical health in adulthood.

* During the 15-year period studied, childhood aggression corresponded to increased medical visits (8.1% per 1 SD increase in aggression), injuries (10.7%) or lifestyle-related illnesses (44.2%), visits to specialists (6.2%), and visits to emergency departments (12.4%). Other sequelae included a 23.5% increase in dental visits and a 10.9% increase in hospital admissions.

* There was a positive relationship between social withdrawal during childhood and government-funded visits to dentists (a 14.6% increase).

* Peer-rated likeability during childhood showed negative relationships with use of healthcare services (3.6% decrease), medical visits because of injuries (9.0% decrease), and government-funded visits to dentists (11.2% decrease).

* A main effect of sex was seen for overall use of medical services; number of medical visits to specialists, emergency departments, and dentists; total number of admissions to the hospital; and medical visits because of infections. Women were more likely than men to seek medical attention; however, this effect was reversed for medical visits because of injuries.

* There was no overall effect on use of gynecologic services when the period from 1992 to 2006 was considered.

* There was a consistently negative relationship in the level of education among overall use of medical services, number of medical visits because of infections, visits to emergency departments, number of dental visits, and total number of admissions to the hospital.

* Level of education showed significant effects during both early and later adulthood among women. Among younger women, level of education showed a robust negative predictive effect; however, among older women, this relationship was reversed.

* Living in a poorer neighborhood during early adulthood decreased overall use of medical services by 3.4% but increased the number of visits to specialists, emergency departments and dentists, and total number of admissions to the hospital.

Clinical Implications

* Childhood aggression is related to future health risks such as not completing high school, teen pregnancy and single motherhood, poverty, engaging in high-risk and/or unprotected sex, and dangerous driving.

* Childhood aggression directly and positively predicted overall use of healthcare services in adulthood for participants, even after controlling for sex, education, and neighborhood poverty.

http://www.medscape.org

Change in C diff Antibiotics Yields More Postsurgical Infections

noreply@blogger.com (Han Idris) — Tue, 29 Nov 2011 03:47:00 +0000

News Author: Larry Hand
CME Author: Charles P. Vega, MD

Authors and Disclosures

CME Released: 11/28/2011; Valid for credit through 11/28/2012

Clinical Context

Infection can be common after transrectal ultrasonography-guided prostate (TRUSP) biopsy, and the authors of the current study provide a review of the practice of antibiotic prophylaxis before this procedure. Although the most effective antibiotic regimen is not firmly established, it appears clear that prophylaxis helps to reduce the rate of symptomatic complications after TRUSP biopsy. Ciprofloxacin is the most commonly prescribed antibiotic for this purpose, and one study found no significant difference in efficacy in comparing 1-day and 3-day regimens of ciprofloxacin. Meanwhile, 2 studies have suggested that amoxicillin-clavulanate ("co-amoxiclav") performs less effectively as antibiotic prophylaxis for TRUSP biopsy.

Nonetheless, there is concern regarding the risk for Clostridium difficile (C diff) infection after treatment with broad-spectrum antibiotics such as ciprofloxacin. The current study by Neal and colleagues examines rates of postbiopsy infection during periods when gentamicin plus amoxicillin-clavulanate was used in place of ciprofloxacin as prophylaxis.

Study Synopsis and Perspective

A change in antibiotic regimens in an effort to reduce C diff infections at a UK hospital paradoxically led to higher overall infection rates after prostate biopsy. The hospital has now reverted to the previous standard antibiotic for this common surgical procedure, and this has led to a reduction in postsurgery infections, according to a study published in the November issue of the British Journal of Urology International.

After an audit of 709 records of patients who underwent biopsies to diagnose prostate cancer, the researchers found that 255 patients administered the new antibiotic regimen (co-amoxiclav [amoxicillin-clavulanate] and gentamicin) developed more than 5 times as many postsurgery infections compared with 454 patients administered the previous regimen (ciprofloxacin). The researchers write that the result was significant (P < .001). Almost 13% of the patients receiving co-amoxiclav and gentamicin developed infections compared with just 2.4% of patients receiving ciprofloxacin. Twelve patients were readmitted with sepsis, and 1 patient was readmitted with septic shock. "This is the first study to compare the use of co-amoxiclav and gentamicin with the use of ciprofloxacin for [ultrasonography-guided prostate biopsy]," senior author David Neal, FMedSci, FRCS, professor of surgical oncology at Addenbrooke Hospital in Cambridge, United Kingdom, said in a statement. "This audit study supports the use of locally determined prophylactic regimes for this procedure." The change in antibiotics had been spurred by rising C diff rates in the United Kingdom, which may have been the result of widespread use of broad-spectrum antibiotics such as ciprofloxacin. "The new regime was introduced on the proviso that both the hospital-acquired infection rates and postoperative infection rates would be closely monitored," Dr. Neal said. "Given that there were no cases of C. difficile recorded in our study, but postoperative infection rates increased significantly, the decision was taken to revert back to the original regime." Once that was done the overall rate of infection went back down to 3.8%. The researchers write that although ultrasonography-guided prostate biopsy is a common procedure across the United Kingdom, no national guidelines on the use of antibiotics exist, and local protocols vary widely. In this case, that proved significant. They recommended that any alteration in antibiotic use should be based on local C diff rates and on strong clinical evidence to avoid increases in the risk of ill health, "as well as the financial burden of treating new complications," Dr. Neal said.

The authors have disclosed no relevant financial relationships.
BJU Int. 2011;108:1597-1602.

Study Highlights

* Researchers examined rates of infection at a single hospital in the United Kingdom after TRUSP biopsies were performed in 2008 and 2009.

* Because of concern regarding C diff infection, the hospital changed its antibiotic prophylaxis regimen for TRUSP biopsy. In the first period, clinicians prescribed ciprofloxacin 500 mg orally before the procedure followed by ciprofloxacin 500 mg twice daily for 3 to 5 days. During the second period of treatment, patients received gentamicin 120 mg intravenously before the procedure plus amoxicillin-clavulanate 375 to 625 mg daily for 3 days. In the third period of treatment, the hospital returned to a 3-day course of ciprofloxacin as prophylaxis.

* Researchers examined electronic databases for reports of hospital admission and microbiology studies to identify infectious complications within 4 weeks of TRUSP biopsy. Infections were defined by use of standard criteria.

* 709 patients provided study data. The mean patient age was 68 years, and the average number of prostate biopsies taken was 11.

* The overall rates of infectious complications associated with the 5-day and 3-day treatment regimens with ciprofloxacin during period 1 were 0.8% and 2%, respectively.

* The rate of infectious complications increased to 14.4% with gentamicin and amoxicillin-clavulanate 375 mg and was only marginally decreased (11.4%) with amoxicillin-clavulanate 625 mg.

* After ciprofloxacin as prophylaxis was reintroduced in period 3, the rate of complications decreased to 3.8%.

* Higher rates of admission for sepsis accounted for a large part of the difference between prophylaxis with amoxicillin-clavulanate and prophylaxis with ciprofloxacin. The rates of hospital admissions for infectious complications among patients receiving amoxicillin-clavulanate and patients receiving ciprofloxacin were 4.7% and 0.9%, respectively.

* There was no difference in the rate of infectious complications based on 3 days vs 5 days of treatment with ciprofloxacin or high-dose vs low-dose amoxicillin-clavulanate.

* A minority of patients with infectious complications had a positive result on bacterial culture of the blood or urine. Positive culture results from all patients who received amoxicillin-clavulanate grew Escherichia coli, which was sensitive to amoxicillin-clavulanate.

* There were no cases of C diff complications after TRUSP biopsy.

Clinical Implications

* Antibiotic prophylaxis helps to reduce the rate of symptomatic complications after TRUSP biopsy. Ciprofloxacin is the most commonly prescribed antibiotic for this purpose, and one study found no significant difference in efficacy in comparing 1-day vs 3-day regimens of ciprofloxacin. Meanwhile, 2 studies have suggested that amoxicillin-clavulanate performs less effectively as antibiotic prophylaxis for TRUSP biopsy.

* In the current study by Neal and colleagues, antibiotic prophylaxis with ciprofloxacin was associated with a lower rate of infectious complications after TRUSP biopsy vs a regimen of gentamicin plus amoxicillin-clavulanate. No case was complicated by C diff infection.

http://www.medscape.org

Several Medications Associated With Erectile Dysfunction

noreply@blogger.com (Han Idris) — Tue, 29 Nov 2011 01:33:00 +0000

Several Medications Associated With Erectile Dysfunction CME

News Author: Emma Hitt, PhD
CME Author: Charles P. Vega, MD

Authors and Disclosures

CME Released: 11/28/2011; Valid for credit through 11/28/2012

Clinical Context

More than one third of men older than 60 years can have erectile dysfunction (ED), and multiple chronic medical conditions as well as habits such as smoking can increase the risk for incident ED. Medications also play a role in promoting ED, and the authors of the current study describe drugs most commonly linked with a higher risk for ED. These include beta-blockers, thiazide diuretics, clonidine, selective serotonin reuptake inhibitors, tricyclic antidepressants, spironolactone, and cimetidine.

Although many drugs can individually promote ED, there is less research regarding how the number of medications used affects the risk for ED. The current study by Londoño and colleagues addresses this issue.

Study Synopsis and Perspective

ED rises in likelihood and severity as the number of medications a man takes increases, according to new research. This is true even after accounting for the underlying medical conditions for which these medications are used.

Diana C. Londoño, MD, from the Department of Urology at the Kaiser Permanente Los Angeles Medical Center, California, and colleagues from Kaiser Permanente published their findings online November 15 in the British Journal of Urology International.

According to the researchers, several medications have been linked to ED, including antihypertensives and psychogenic medications, but few studies have examined the role of polypharmacy as an "aggravating component for worsening degrees of ED," they write. The current study, therefore, sought to evaluate whether polypharmacy use increases the severity of ED and whether these effects can be explained by the medical conditions themselves.

Results from a cross-sectional study of questionnaire responses from 37,712 men in the California Men’s Health Study (CMHS), ranging in age from 45 to 69 years, were evaluated. The number of drugs taken was determined from the year before enrollment through electronic pharmacy records and questionnaire responses.

Of the respondents, 10,717 (29%) reported having moderate or severe ED. Among the 37,712 respondents identified, 21,586 (57%) took more than 3 medications in the year before completing the baseline survey.

Regardless of age, an increasing number of medications was linked to an increasing prevalence of ED; in men taking 0 to 2, 3 to 5, 6 to 9, and 10 or more medications, the percentages of men reporting moderate ED were 15.9%, 19.7%, 25.5%, and 30.9%, respectively (P < .001). With adjustment for age, race, smoking, diabetes, hypertension, hyperlipidemia, peripheral vascular disease, coronary artery disease, and body mass index, men taking more than 10 medications were more likely to have ED (odds ratio, 1.65; 95% confidence interval, 1.52 - 1.80) than those taking fewer than 3 medications. There was also evidence of a dose-response relationship "that persisted even in subsets of men with specific underlying conditions," the authors note. The study has several potential limitations, including reliance on self-reported information and the cross-sectional design, which precludes conclusions about causality. "Despite these potential limitations," write the authors, "these data help emphasize the importance of assessing medication use as part of the evaluation of ED. The presence of ED may signal the use of duplicate or non-essential medications. It may also trigger an assessment of current medications and their potential side effects, and a tailoring of regimens to maximize the treatment effects, while diminishing potential unwanted side effects. Decreases or changes in the amount of or type of medication may significantly improve a man's health-related quality of life because his ED may improve from moderate to mild." "The present research shows a new association between polypharmacy and worsening degrees of erectile function, even when individual medical conditions and other risk factors have been accounted for," Dr. Londoño and colleagues conclude. "[P]olypharmacy itself should be part of the differential diagnosis in the evaluation of ED when other causes have been accounted for and investigated by the treating physician," they suggest. "This study highlights that while physicians still need to treat patients with medications when indicated, they should be aware that erectile dysfunction may occur," noted Michael Kanter, MD, regional medical director of Quality & Clinical Analysis for the Southern California Permanente Medical Group in a written release. "These men would benefit from lifestyle changes such as changes in their diet, regular exercise, and not smoking, which would help control their hypertension, diabetes, and stress and reduce erectile dysfunction risk," Dr. Kanter said. "Physicians can use this as an opportunity to talk with their patients about risks of erectile dysfunction and the underlying health conditions causing their need for multiple medications." The authors have disclosed no relevant financial relationships. BJU Int. Published online November 15, 2011.

Study Highlights

* Study data were drawn from the CMHS, which enrolled male members of Kaiser Permanente health plans if they were between 45 and 69 years old. Men with a personal history of prostate cancer were excluded from the current analysis.

* All participants completed questionnaires regarding demographic data, body weight and height, smoking status, past medical data, and ED symptoms.

* Researchers used pharmacy database records to track medication use. Drugs were counted as having long-term use if men had received at least 100 days' supply during the past year.

* The main study outcome was the relationship between ED and the use of multiple medications. Phosphodiesterase inhibitors were not included as long-term medications in this analysis.

* Researchers performed a multivariate analysis for their main outcome, which included chronic illnesses, smoking history, and body mass index as potential confounders.

* 37,712 men provided data for study analysis. 62% of men were white, and many had disease risk factors for ED.

* Use of more than 3 medications was more common among older men, African Americans, and men with a higher body mass index.

* 29% of men reported moderate or severe ED. Among men taking 0 to 2, 3 to 5, 6 to 9, and 10 or more medications, the prevalence rates of ED were 15.9%, 19.7%, 25.5%, and 30.9%, respectively.

* After full adjustment, the use of 6 or more medications was independently associated with a higher risk for ED.

* The main study outcomes were not significantly altered in subgroup analysis based on the presence of diabetes, hypertension, hyperlipidemia, or depression.

Clinical Implications

* Medications that are likely to promote a higher risk for ED include beta-blockers, thiazide diuretics, clonidine, selective serotonin reuptake inhibitors, tricyclic antidepressants, spironolactone, and cimetidine.

* In the current study by Londoño and colleagues, a higher number of medications used by middle-aged and older men corresponded with an increasing risk for ED, independent of the presence of chronic diseases.

Source : http://www.medscape.org

What Is Vinnegar ?

noreply@blogger.com (Han Idris) — Tue, 22 Nov 2011 03:02:00 +0000

Vinegar is a liquid substance consisting mainly of acetic acid and water, the acetic acid being produced through the fermentation of ethanol by acetic acid bacteria. Commercial vinegar is produced either by fast or slow fermentation processes. Slow methods generally are used with traditional vinegars, and fermentation proceeds slowly over the course of weeks or months. The longer fermentation period allows for the accumulation of a nontoxic slime composed of acetic acid bacteria. Fast methods add mother of vinegar (i.e., bacterial culture) to the source liquid before adding air using a venturi pump system or a turbine to promote oxygenation to obtain the fastest fermentation. In fast production processes, vinegar may be produced in a period ranging from 20 hours to three days.

Varieties

Malt

Malt vinegar is made by malting barley, causing the starch in the grain to turn to maltose. Then an ale is brewed from the maltose and allowed to turn into vinegar, which is then aged. It is typically light brown in color.

In the United Kingdom, salt and malt vinegar is a traditional seasoning for chips and crisps.

Wine

Wine vinegar is made from red or white wine, and is the most commonly used vinegar in Mediterranean countries and Central Europe. As with wine, there is a considerable range in quality. Better quality wine vinegars are matured in wood for up to two years, and exhibit a complex, mellow flavor. Wine vinegar tends to have a lower acidity than that of white or cider vinegars. More expensive wine vinegars are made from individual varieties of wine, such as Champagne, sherry, or pinot grigio.

Sherry vinegar

Production of sherry vinegar is linked to the production of wines of Jerez. The vinegar is made exclusively from the acetic fermentation of Sherry wines; the taste of this vinegar is stronger than wine. The resulting color of this vinegar is dark mahogany, it's concentrated and has generous aromas; the nose will notice the hue of wood. Sherry vinegar is ideal for vinaigrettes and salad dressings and for flavoring various foods.

There is evidence of its existence back in the first century after Christ, in the writings of Cadiz wiseman Columella. It is currently presented with quality products certified by the government of Andalusia and its production is regulated by the Consejo Regular del Vino y Brandy de Jerez (Council regulating the production of Jerez wine and brandy). Two types are found: "Vinagre de Jerez", which is aged for six months or "Vinagre de Jerez Reserva", which is aged for a minimum of two years (although the Council allows to specify the age if this is greater, and vinegar 20 or 30 years can old be found).

Apple cider

Apple cider vinegar, otherwise known simply as cider vinegar or ACV, is made from cider or apple must, and has a brownish-yellow color. It often is sold unfiltered and unpasteurized with the mother of vinegar present, as a natural product. Because of its acidity, apple cider vinegar may be very harsh, even burning, to the throat. If taken straight, (as opposed to used in cooking), it can be diluted (e.g., with fruit juice or water) before drinking. It is also sometimes sweetened with sugar or honey. There have been reports of acid chemical burns of the throat from apple cider vinegar tablets, but doubt remains as to whether apple cider vinegar was in fact an ingredient in the evaluated products. The pH of apple cider vinegar is typically between pH 4.25 - 5.00 if undiluted.

Fruit

Fruit vinegars are made from fruit wines, usually without any additional flavoring. Common flavors of fruit vinegar include apple, blackcurrant, raspberry, quince, and tomato. Typically, the flavors of the original fruits remain in the final product.

Most fruit vinegars are produced in Europe, where there is a growing market for high-priced vinegars made solely from specific fruits (as opposed to nonfruit vinegars which are infused with fruits or fruit flavors). Several varieties, however, also are produced in Asia. Persimmon vinegar, called gam sikcho (감식초), is popular in South Korea. Jujube vinegar photo, called zaocu or hongzaocu (simplified Chinese: 枣醋 / 红枣醋; traditional Chinese: 醋紅 / 紅棗醋), and wolfberry vinegar photo, called gouqicu (Chinese: 枸杞醋), are produced in China.

Jamun sirka (Hindi: जामुन सिरका), a vinegar produced from the jamun (or rose apple) fruit in India, is considered to be medicinally valuable for stomach, spleen and diabetic ailments.

Balsamic

Balsamic vinegar is an aromatic, aged type of vinegar traditionally crafted in the Modena and Reggio Emilia provinces of Italy from the concentrated juice, or must, of white grapes (typically of the Trebbiano variety). It is very dark brown in color, and its flavor is rich, sweet, and complex, with the finest grades being the product of years of aging in a successive number of casks made of various types of wood (including oak, mulberry, chestnut, cherry, juniper, ash, and acacia). Originally a product available to only the Italian upper classes, a cheaper form of balsamic vinegar became widely known and available around the world in the late 20th century. True balsamic vinegar (which has Protected Designation of Origin status) is aged for 12 to 25 years. Balsamic vinegars that have been aged for up to 100 years are available, though they are usually very expensive. The commercial balsamic sold in supermarkets is typically made with concentrated grape juice mixed with a strong vinegar, which is laced with caramel and sugar. Regardless of how it is produced, balsamic vinegar must be made from a grape product.

Balsamic vinegar has a high acidity level, but the tart flavor is usually hidden by the sweetness of the other ingredients, making it very mellow.

Rice

Rice vinegar is most popular in the cuisines of East and Southeast Asia. It is available in "white" (light yellow), red, and black varieties. The Japanese prefer a light rice vinegar for the preparation of sushi rice and salad dressings. Red rice vinegar traditionally is colored with red yeast rice. Black rice vinegar (made with black glutinous rice) is most popular in China, and it is also widely used in other East Asian countries.

White rice vinegar has a mild acidity and a somewhat "flat", uncomplex flavor. Some varieties of rice vinegar are sweetened or otherwise seasoned with spices or other added flavorings.

Coconut

Coconut vinegar, made from fermented coconut water, is used extensively in Southeast Asian cuisine (particularly in the Philippines and Sri Lanka, major producers, where it is called suka ng niyog or vinakiri), as well as in some cuisines of India. A cloudy white liquid, it has a particularly sharp, acidic taste with a slightly yeasty note.

Palm

Palm vinegar (sukang paombong)

Palm vinegar, made from the fermented sap from flower clusters of the nipa palm (also called attap palm), is used most often in the Philippines, where it is produced, and where it is called sukang paombong. Its pH is between five and six.

Cane

Cane vinegar, made from sugar cane juice, is most popular in the Philippines, in particular, the Ilocos Region of the northern Philippines (where it is called sukang iloko), although it also is produced in France and the United States. It ranges from dark yellow to golden brown in color, and has a mellow flavor, similar in some respects, to rice vinegar, though with a somewhat "fresher" taste. Contrary to expectation, containing no residual sugar, it is not sweeter than other vinegars. In the Philippines, it often is labeled as sukang maasim, although this is simply a generic term meaning "sour vinegar".

Cane vinegars from Ilocos also varies in two different types: basi (sweet) and suka (sour). The sweet vinegar is used as a wine in Ilokanos, while the other type of vinegar is used as a seasoning and preservative.

A white variation has become quite popular in Brazil in recent years, where it is the cheapest type of vinegar sold. It is now common for other types of vinegar (made from wine, rice and apple cider) to be sold mixed with cane vinegar to lower the costs.

Raisin

Raisin vinegar produced in Turkey

Vinegar made from raisins, called khall ʻinab (Arabic: خل عنب‎ "grape vinegar") is used in cuisines of the Middle East, and is produced there. It is cloudy and medium brown in color, with a mild flavor.

Date

Vinegar made from dates is a traditional product of the Middle East.

Beer

Vinegar made from beer is produced in the United Kingdom, Germany, Austria, and the Netherlands. Although its flavor depends on the particular type of beer from which it is made, it is often described as having a malty taste. That produced in Bavaria is a light golden color with a very sharp and not-overly-complex flavor.

Honey

Vinegar made from honey is rare, although commercially available honey vinegars are produced in Italy, France, Romania and Spain.

East Asian black

Chinese black vinegar is an aged product made from rice, wheat, millet, sorghum, or a combination thereof. It has an inky black color and a complex, malty flavor. There is no fixed recipe, so some Chinese black vinegars may contain added sugar, spices, or caramel color. The most popular variety, Zhenjiang vinegar (鎮江香醋), originated in the city of Zhenjiang, in the eastern coastal province of Jiangsu, China[9] and also is produced in Tianjin and Hong Kong.

A somewhat lighter form of black vinegar, made from rice, also is produced in Japan, where it is called kurozu. Since 2004, it has been marketed as a healthful drink; its manufacturers claim it contains high concentrations of amino acids. Recent research on kurozu has revealed its anticancer properties in vivo on rats[10][11] and in vitro on human cancer cells.

Flavored vinegars

Popular fruit-flavored vinegars include those infused with whole raspberries, blueberries, or figs (or else from flavorings derived from these fruits). Some of the more exotic fruit-flavored vinegars include blood orange and pear.

Herb vinegars are flavored with herbs, most commonly Mediterranean herbs, such as thyme, tarragon or oregano. Such vinegars can be prepared at home by adding sprigs of fresh or dried herbs to vinegar purchased at a grocery store; generally a light-colored, mild tasting vinegar, such as that made from white wine, is used for this purpose.

Sweetened vinegar is of Cantonese origin, and is made from rice wine, sugar and herbs, including ginger, cloves, and other spices.

Job's tears

In Japan, an aged vinegar also is made from Job's tears, a tall, grain-bearing, tropical plant. The vinegar is similar in flavor to rice vinegar.

Kombucha

Kombucha vinegar is made from kombucha, a symbiotic culture of yeast and bacteria. The bacteria produce a complex array of nutrients and populate the vinegar with bacteria which some claim promotes a healthy digestive tract, although no scientific studies have confirmed this. Kombucha vinegar primarily is used to make a vinaigrette, and is flavored by adding strawberries, blackberries, mint, or blueberries at the beginning of fermentation.

Kiwifruit

A byproduct of commercial kiwifruit growing is a large amount of waste in the form of firstly misshapen or otherwise rejected fruit that may constitute up to 30 per cent of the crop and secondly kiwifruit pomace which is the presscake residue left after kiwifruit juice manufacture. One of the uses for this waste is the production of kiwifruit vinegar, produced commercially in New Zealand[13] since, at least, the early 1990s, and in China in 2008. Sinamak

A variation of cane vinegar from the Philippines (sukang maasim) is called sinamak which is simply a spiced version that mixes the cane vinegar with siling labuyo, onions and garlic.

Distilled vinegar

Any type of vinegar may be distilled to produce a colorless solution of about 5% to 8% acetic acid in water. This is variously known as distilled spirit or "virgin" vinegar, or white vinegar, and is used for medicinal, laboratory and cleaning purposes, as well as in cooking, baking, meat preservation, and pickling. The most common starting material, because of its low cost, is malt vinegar.
Spirit vinegar

The term 'spirit vinegar' is sometimes reserved for the stronger variety (5% to 20% acetic acid) made from sugar cane or from chemically produced acetic acid.

Potential hazards

Esophageal injury by apple cider vinegar tablets has been reported, and because vinegar products sold for medicinal purposes are neither regulated nor standardized, they vary widely in content, pH, and other respects.[4] Long-term heavy vinegar ingestion may also cause hypokalemia, hyperreninemia, and osteoporosis.

Vinegar has an incredibly long and fascinating history with many very different uses developed over the years. It probably developed when someone left fruit to go bad or wine to turn sour until ultimately the fruit and wine turned into vinegar. As to uses, well they are as many and varied as the many very different types and flavours of vinegar and they include:

* Start your day with a glass of honey and warm water to which a tablespoon of apple cider vinegar has been added. This helps keep the body free of toxins and helps the skin stay spot and pimple free.

* If you don't fancy using vinegar with honey, try it with orange juice instead. Drink it every morning to help wake up your system.

* Use vinegar mixed with olive oil and a pinch of salt as a dressing for lettuce or sliced tomatoes.

* Use a sprinkling of vinegar over fatty foods like fish and chips to reduce fat and help you stay slim and healthy.

* Add white vinegar to water used to boil vegetables to keep them firm and flavoursome.

* Use vinegar in water used to boil pasta or rice and to help reduce starch levels and lower your calorie intake.

* A few teaspoonfuls of vinegar in a cup of hot water left to cool is a good remedy for a sore throat.

* Make your own cottage cheese by simmering a pint of fresh milk and at boiling point remove the pan from the heat for a few minutes to allow it to cool before adding a tablespoon of white vinegar. The end result will be curds and whey such as typify cottage cheese.

* Use vinegar, a cupful is sufficient, added to a tablespoon each of sugar and honey and boil until it reduces by fifty per cent. Add a little olive oil and some crushed garlic and a sprinkling of black pepper. Use the vinegar based end product to coat meat or vegetables before baking in the oven.

* Make cheap meat tender by soaking it in red or white vinegar and leaving it to stand overnight.

All of those tips, and countless more, not only make food more flavoursome but they can also help delay the onset of ailments associated with the aging process, such as memory loss and poor digestion.

Article Source: http://en.wikipedia.org/wiki/Vinegar and Others

How to be Healthy As You Age

noreply@blogger.com (Han Idris) — Tue, 22 Nov 2011 02:57:00 +0000

If you're curious about how to stay fit as you head into your golden years, then you're not alone. Staying healthy into old age often requires lifestyle changes. Here are some of the most widely recognized expert-recommended ways to stay healthy into old age.

1. Eat Healthy - Eating a healthy diet means staying away from fast food, avoiding trans fats, refined sugars, and other harmful food additives and eating plenty of raw fruits and vegetables. Balance is the key when it comes to dieting. Restrictive diets aren't necessarily the best approach to eating healthy. If you're trying to keep your body in good health, choose a diversity of foods to eat, but stay away from highly processed foods.

2. Drink Water - Instead of drinking soda or juice, choose water. Water has a detoxifying effect on the body and if you don't drink enough water, toxins and metabolic byproducts build up in your body. Choosing water over juice can also help you lose a few extra pounds too by reducing your caloric intake each day. The body needs water for every chemical reaction that takes place internally. Without water, your body simply doesn't function properly.

3. Lose Weight - If you follow the advice above, then losing weight will probably happen naturally. If you're carrying around extra pounds, your body suffers for it. Each pound of fat requires a blood supply and that means the heart has to work harder to keep the body's fat stores supplied. When you lose weight, you take a load off your heart, which is a step in the right direction toward good health.

4. Exercise - Moderate exercise performed regularly is an important part of staying healthy as you age. Don't turn into a couch potato! Get up and move! Exercise keeps the blood pumping through the body to nourish cells and tissues. Exercise also promotes weight loss by burning extra calories and causing you to crave foods that are healthier for you. Be sure you drink plenty of water when you're exercising!

5. Reduce Stress - Stress can cause all kinds of problems for your body. Stress can cause your blood pressure to go up, your blood sugars to go askew, and your hormones to get out of whack. Some people have to get natural hormone replacement therapy just to rebalance things if they've had an overabundance of stress in their lives for many years. By keeping your stress levels under control, you can avoid circulatory and hormonal problems as long as possible.

Everyone wants to age gracefully and if you're at the time in your life when you're thinking about these things, it's time to do something. Take up a healthy lifestyle that will help your body function at it's best for as long as possible!

Article Source: http://EzineArticles.com and others

Brain Power And Brain Games

noreply@blogger.com (Han Idris) — Tue, 22 Nov 2011 01:33:00 +0000

Unlock Your Hidden Brain Power, Discover How To Harness The Secret Law Of Attraction & Go Way Beyond The Teachings Of The Secret...

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Visit Game Brains here

Diet Plans For Fat Lose

noreply@blogger.com (Han Idris) — Tue, 22 Nov 2011 01:15:00 +0000

Diet Plans For Men & Women, Training Programs For 3 Levels Of Fitness, Motivation Strategies & More

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How to Lost Weight ???

noreply@blogger.com (Han Idris) — Tue, 22 Nov 2011 00:43:00 +0000

Lose Weight, Look Younger, Get Energized And Gain Confidence With The Same Easy 7 Week Program Philip Mccluskey Used To Lose Over 200lbs And Keep It Of Permanently. Experience The World's Sexiest Diet Now.

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Fight Against Cancer

noreply@blogger.com (Han Idris) — Thu, 17 Nov 2011 11:07:00 +0000

Some people in this world have unbelievably robust wills and can persevere with their chin held high in the face of the worst possibilities. Other folks cannot handle bad situations or tell the truth at all and look puzzled and misplaced. You might be tough on the outside, but cancer could bust your will. Learn how to fight to reverse cancer using these ideas.

A coffee enema is the little known secret of cancer survivors. Take advantage of the support and encouragement that you'll get when you get the opportunity to hear the true life stories of these cancer survivors. Many individual sufferings with cancer has gone through the traumatic path of near-death experiences before discovering the coffee enema. It is this therapy that really helped their body to heal itself naturally.

Don't be fooled into believing that alcohol in any way helps to prevent cancer. It does not. Wine may slow down cancer only because of the grapes. Ingesting large quantities of alcohol can actually put you at a greater risk of hastening cancer. The occasional drink is not going to hurt, but keep your consumption to a minimum.

You can cut your danger of developing skin cancer significantly by staying out of the sun between the hours of 10:00 am and 2:00 pm. Through that time of the day, the suns rays are the strongest and as a result does the most harm. Regardless of what time you go outdoors, remember to always wear sunblock.

Once you are diagnosed with cancer, it can be vital for you to do research concerning the illness. You'll want to understand everything that you can so that you're taking the appropriate methods for treatment instead of blindly putting your health into the hands of others.

Limit the quantity of red meats, and in particular processed meats, in your diet plan. A wholesome diet regime is linked to reduced risks of cancer. Consuming a huge quantity of red, processed meats will increase the fat content material of your diet. The processing in certain meat exposes you to some potentially harmful chemicals and preservatives. All of these items can be of high threat factors for cancer.

Whilst cancer has quite a few faces, it is not generally a walking death sentence. Lots of people will beat the illness with support from physicians, counselors, loved ones, and buddies. Each and every step can be challenging, but is well worth the endurance to a wholesome life after filled with promise and love. Cancer is horrible illness which will be treated.

If you are interested in getting rid of cancer, you could really use some help on how to do coffee enema that has the reputation to help patients combat cancer !

Article Source: http://EzineArticles.com/?expert=David_X_Chong

Viral Therapy

noreply@blogger.com (Han Idris) — Thu, 17 Nov 2011 11:05:00 +0000

Productive viral infection mimics oncogenic transformation in several respects, and some of the same molecular mechanisms are employed by viruses and cancer cells to disrupt key homeostatic mechanisms. These similarities serve as the foundation for the development of ''oncolytic'' viruses that are designed to specifically target and kill cancer cells. Although some targeting strategies involve engineering viruses so that they bind specifically to cancers, an even more attractive approach involves developing viruses that can only replicate in cancer cells that contain specific defects in homeostatic control. For example one of the products of the adenovirus E1B locus is a protein that specifically disrupts p53 function, thereby undermining the host p53-dependent antiviral response that would otherwise result in inhibition of DNA synthesis and/or apoptosis. Mutant forms of adenovirus that lack E1B 55K should only replicate in cells with defective p53 function, i.e., cancers. Several groups have developed E1B mutant adenoviruses for cancer therapy, and promising results have been obtained with several of them, including Onyx Pharmaceuticals'. Another promising approach exploits the presence of mutant active Ras.

Rhabdoviruses are RNA viruses that are also being developed as oncolytic agents. Their tumor selectivity is related largely to the fact that tumor cells are often resistant to the antiviral effects of type I interferons (IFNs), which can completely suppress viral replication in normal cells. Eliminating viral mechanisms that suppress autocrine IFN production enhances oncolytic activity while further reducing toxicity to normal host tissues. The investigators designed a synthetic lethal RNAi screen to identify cytoprotective pathways that limit tumor cell killing induced by the Maraba rhabdovirus in three different human cancer cell lines. Their ''hits'' were enriched for genes that function within two of the three major pathways that respond to endoplasmic reticular (ER) stress, commonly referred to as the unfolded protein response (UPR). More specifically, the screen implicated the ATF6 and IRE1/XBP1 pathways, as well as downstream genes involved in the transport of protein aggregates out of the ER to the proteasome, in cytoprotection. Importantly, the group also identified a novel small molecule inhibitor of IRE1 that also sensitized tumor but not normal cells to the oncolytic effects of the virus in vitro and in xenografts.

Therefore, if the inhibitor can be further optimized to increase its potency, there is a good chance that these preclinical observations can be translated in patients with cancer. At first glance it might seem surprising that hits within the PERK/eIF2a arm of the UPR were not identified, but in fact this makes sense. Phosphorylation of eIF2a results in global downregulation of cap-dependent host translation, so viruses have evolved many different mechanisms to prevent eIF2a phosphorylation or its downstream consequences in normal cells. Furthermore, we have observed that many tumor cells fail to display increased eIF2a phosphorylation or translational arrest in response to proteotoxic and ER stress, so this arm of the UPR may be disabled in a large subset of cancers anyway. In these cancers the coupling between the proteasome and autophagy is disrupted, which may also be advantageous for productive viral infection if autophagy plays somerole in limiting it. One might also predict that knockdown of UPR or ER-associated decay (ERAD) components would cause a buildup of protein aggregates within the ER and that subsequent viral infection dramatically exacerbates the situation by overwhelming an already stressed ER-Golgi network with increased protein synthetic load.

Indeed, UPR inhibition did cause features of ER stress in infected cells, but they resolved quickly and did not lead to an obvious increase in the accumulation of protein aggregates, strongly suggesting that the sensitization caused by pretreatment with UPR inhibitors was not caused by this mechanism. Rather, UPR inhibition appeared to ''precondition'' the cells to subsequent virus-induced cell death by upregulating expression of the caspase adaptor protein, RAIDD, and promoting activation of caspase-2, and knockdown of caspase-2 almost completely rescued the synthetic lethal interaction between UPR inhibition and viral infection. Recent work from Doug Green's group demonstrated that RAIDD-mediated caspase-2 activation is controlled by the stress-responsive transcription factor, HSF-1, suggesting that heatshocked proteins and/or other (perhaps ER-based?) molecular chaperones may play central roles in controlling stressinduced caspase-2 activation.

Left unresolved are the molecular mechanisms that link UPR inhibition to RAIDD upregulation and viral infection to caspase-2 activation. It does seem likely that some (possibly subtle) perturbation of protein aggregate clearance plays a role, but how, and especially why, this low-level stress, that appears to be completely resolved prior to viral infection, sets the stage for subsequent apoptosis awaits further investigation.

Article Source: http://EzineArticles.com/6688214

The Myelodysplastic Syndromes (MDSs)

noreply@blogger.com (Han Idris) — Thu, 17 Nov 2011 10:04:00 +0000

The myelodysplastic syndromes (MDSs) are a heterogeneous group of myeloid malignancies characterized by clonal hematopoiesis, impaired differentiation, peripheral blood cytopenias, and increased risk of progression to acute myeloid leukemia. Although recent studies have identified recurrent somatic mutations in most patients with MDS, approximately 20% of patients with MDS had no known somatic genetic or cytogenetic abnormalities in the largest studies to date. Two recent studies report the results of whole-exome sequencing in patients with MDS. Notably, themost frequent novel recurrent mutations found occurred in genes encoding members of the RNA-splicing machinery. The paradigm that alterations in splicing contribute to the pathogenesis of human disease and promote tumorigenesis is well described. However, the majority of disease-associated splicing abnormalities discovered previously were in cis-acting elements that disrupt splice site selection at specific loci.

By contrast identified mutations in the trans-acting members of the spliceosome necessary for processing pre-mRNA to mature mRNA. The genetic data supporting these mutations as disease alleles are compelling; the majority of the mutations in SF3B1 and all of the mutations in U2AF35 and SRSF2 are recurrent, heterozygous point mutations, suggesting a gain of function conferred by these recurrent mutations. In contrast rarer mutations in ZRSR2 and PRPF40B occurred as missense or nonsense mutations, suggesting that these mutations might result in loss of function. In addition, it was found that spliceosomal gene mutations are largely mutually exclusive of one another, consistent with a general role of spliceo some mutations in MDS pathogenesis.In order to understand the spectrum of spliceosomal gene mutations, both groups also sequenced a spectrum of myeloid malignancies in addition to MDS. These data led both groups to note a striking association between SF3B1 mutations and MDS characterized by the presence of ring sideroblasts (RS). Although rare SF3B1 mutations have been reported previously in epithelial cancers derived from pancreas, breast, and ovary, SF3B1 mutations occur in the majority of patients with MDS with RS and much less commonly in other hematologic malignancies.

Although mutations in the other spliceosomal components were more common in other subtypes of MDS, the mutations appear to be most enriched in myeloid malignancies with some component of dysplasia, including MDS of all subtypes and chronic myelomonocytic leukemia. It was noted that mutations in SF3B1 in MDS are associated with longer overall and leukemia-free patient survival. Given the already-known favorable prognosis of MDS with RS, studies to identify whether the prognostic effect of these mutations is independent of MDS histopathologic findings are needed. Moreover, previous reports noting splicing alterations in hematologic malignancies, such as the report of frequent missplicing of GSK3b in CML, will need reevaluation to determine if these cancer-specific splicing alterations result from somatic mutations in the spliceosome. To understand the biological consequences of spliceosomal mutations in hematopoiesis, the authors overexpressed wild-type and mutant forms of U2AF35 hematopoietic cells from wild-type mice. Competitive transplantation with similarly transduced control cells revealed a competitive disadvantage with U2AF35 mutant overexpression.

Further work to characterize the effects of these mutations on other aspects of hematopoietic stem cell function including self-renewal, differentiation, and leukemogenesis are needed. Moreover, comparison of the biological effects of expression of recurrent point mutations with downregulation of expression may be very helpful in understanding the biological consequences of spliceosomal component alterations in neoplastic transformation. The mutations in the spliceosomal complex in different myeloid malignancies suggest that these proteins may have distinct functions at different stages of hematopoietic differentiation. Very little is known about the expression of the various Serine/Arginine-rich (SR) proteins in normal and malignant hematopoiesis or about the function of the spliceosome in normal hematopoietic development. Numerous splicing factors have been targeted for constitutional knockout in mice, but these resulted in largely embryonic or perinatal lethality. Conditional gene targeting in a tissue-specific manner has only been carried out for Srsf1 and Srsf2 so far. Mice with cardiac-specific deletion of Srsf1 develop severe dilated cardiomyopathy, leading to death by 6-8 weeks of life, whereas cardiac-specific Srsf2 knockout mice develop a milder cardiomyopathy and have a relatively normal life span.

These results suggest that the SR proteins fulfill specialized, nonredundant functions. Data arguing for a role of spliceosomal components outside of pre-mRNA processing have also come from in vivo modeling. For instance, in vivo analysis of Sf3b1 knockout mice identified genetic intersection with Polycomb Group protein loss, leading to the identification of multiple physical interactions between SF3B1 and members of the PRC1 complex and the BCL6 corepressive complex. Further work to analyze the role of disordered PRC1 activity and BCL6 activity in MDS-RS pathogenesis is now warranted. Studies shows that the effects of expressing U2AF35 in wildtype and mutant forms on gene expression and showed that overexpression of U2AF35 mutants led to a greater frequency of transcripts with unspliced introns and increased expression of members of the nonsense-mediated decay pathway. They concluded that U2AF35 mutations, and possibly other spliceosomal pathway mutations, function in a dominant-negative manner to inhibit normal splicing, a hypothesis requiring further evaluation. Previous studies have noted overexpression of SR family proteins in epithelial cancers, and overexpression of SR proteins (including SRSF1 and SRSF2) leads to cellular transformation ability in other cellular contexts; as such, future studies will need to dissect differences between the role of mutant and wild-type spliceosome proteins in oncogenic transformation.

Identification of splicing factor mutations in MDS may also provide a possibility for therapeutic intervention. An excellent example comes from investigational therapies for the hereditary disorder Duchenne muscular dystrophy (DMD). DMD most commonly results from mutations in a repetitive domain of Dystrophin. Mutations in this domain can be overcome by ''skipping'' the mutated exon to generate truncated functional dystrophin protein. Amazingly, a strategy of delivering an antisense oligonucleotide to block an enhancer of exon splicing of the mutated exon and result in a stable mRNA transcript and dystrophin gene product has been utilized successfully in early clinical trials. In addition, compounds that specifically target the SF3A/B subunits of U2 snRNP to result in nuclear export of intron-bearing precursors exist and should be studied further to determine if they interfere with the aberrant splicing due to recurrent mutations in these subunits. These that these two studies have uncovered a novel pathway of importance to myeloid malignancies that may lead to novel therapeutic approaches for patients with MDS.

Article Source: http://EzineArticles.com/6688227

Neoplastic Cells

noreply@blogger.com (Han Idris) — Thu, 17 Nov 2011 05:54:00 +0000

Neoplastic cells may express membrane-bound molecules, which they did not express before or only in low quantities, or mutated membrane molecules. As a selective response to immune destruction, tumor cells may use several escape strategies, many of which involve down-regulation of Major histocompatibility complex molecules or other molecules implicated in the antigen-presentation pathway. Such tumor cells do not express tumor-specific peptides on the outer membrane, and consequently they cannot be recognized by Cyto toxic lymphocytes(CTL). Tumor cells may also directly inhibit the recognition or the function of immune cells by releasing immune inhibitory molecules.

However, cells other than CTL attack tumor cells: NK cells, polymorphonuclear leukocytes (PMN), and macrophages/DC do not recognize tumor cells via peptides. These cells seem to be involved in the recently described, natural immunity against tumor cells. Moreover, mice deficient in the innate immune system show higher incidence of tumor cell induction and outgrowth compared to wild-type mice. Thus, cells from the innate immune system may play a role both in the destruction of the tumor cells and in the regulation of Major histocompatibility complex expression on cells with which they interact. However, an important question in the discussion is whether the so-called selective response of tumor cells to immune destruction is

(1) a global inductible response of all tumor cells, i.e., the immune system induces the tumor cells to change character in such a way that the cancer cells become less sensitive to the immune effectors, or

(2) a selective response of surviving tumor cells, i.e., the immune effectors kill sensitive tumor cells but not mutated tumorigenic cells or the ones that have changed (down-regulated) certain characters, which render them invulnerable to the immune attack.

To activate the immune system, neoplastic cells must, in addition to the expression of tumor-associated antigens (TAA), induce cellular stress signals, danger signals, or damage-associated signals that alert the innate immune system. Cell death, damage-associated molecular-pattern molecules, and endogenous danger signals are all associated with expression of heat-shock proteins, chromatin-associated protein high-mobility group box 1, and others. This is followed by the expression of "eat me" signals and suppression of "don't eat me" signals on the "troubled" cells, which are then taken-up by immature Dendritic cells.

The consequence of the dendrocyte "troubled" cells interaction will greatly differ, depending on the necrotic versus apoptotic status of the "troubled" cells. If the "troubled" cells are necrotic, then they release inflammatory molecules that induce the immature dendrocytes to mature and elicit cross-priming of the immune system. Necrotic cell death releases HMGB1 and proteins derived from the tissue injury, such as hyaluronan fragments and nonprotein purinergic molecules such as ATP and uric acid, and induces inflammation due to IL-1b, IFNg, and Tumor necrosis factor. Cell death, damage-associated molecular-pattern molecules activate cells of the innate immune system by triggering TLR or other alarm-signal receptors. In contrast, if the immature Dendritic Cells take up "troubled" cells undergoing apoptotic cell death, they turn into tolerogenic dendrocytes due in part to the activity of caspases that render HMGB1 inactive.

This causes absence of induction of inflammation and no differentiation of immature Dendritic Cells to mature ones. In addition to Cell death, damage-associated molecular-pattern molecules and endogenous danger signals, tumor cells may release effector molecules that stimulate the immune cells to collaborate in tumor growth in the sub-threshold neoplastic states. The complement system, in particular properdin, seems to play an important role in this process by amplifying the production of reactive oxygen and nitrogen species by myeloid-derived suppressor cells. In fact, growing neoplastic cells may be considered by the tissue as a physical wound, and the tissue response to such "intrusion" is wound healing. This means attraction of stromal, endothelial, and epithelial cells, release of chemokines and cytokines as well as molecules of the blood-clotting system. Thus, both normal repair systems, different danger signals, and the immune system may take part in the initiation process from a transformed neoplastic cell to an established, solid tumor.

By Javed Shaik. He is a Graduate in Biotechnology, and is a enthusiast in Cancer Education and Research.

Article Source: http://EzineArticles.com/6688483

Healing Your Disease

noreply@blogger.com (Han Idris) — Thu, 17 Nov 2011 05:50:00 +0000

Healing takes place when the conditions are right, doesn't this hold true for most if not all things? Let's look at the conditions that enable healing to take place; Answer the following questions after deep contemplation, listening to inner feelings, you are after the unconscious answers. It is the unconscious that enables healing.

1. Desire - You must desire what you want. Write out what you want

2. What then? - If you had this goal fully and completely, what then?.

What then? What then?

3. Specific - Know exactly what you want. Look at what you wrote above. Imagine your goal with all your senses. See how you live with your goal. Notice the changes in your life as a result of achieving this goal. Do you still want it? If you had achieved your goal right now, would you keep it? would you continue to keep the goal for many years to come?.

4. Did any doubts or objections arise? If so write them down.

5. Importance - Rate how important your goal is to YOU, how badly do you want it? Give your goal an importance rating out of 100. First look at other goals you have achieved and not achieved in the past and rate them first. This way you your rating will be more accurate. Also when rating your goal, sit with eyes closed and imagine a gauge with the numbers from 0 to 100 and a red needle to indicate the importance. Now let the needle under the control of your unconscious mind tell you how important your goal is.

6. Urgency - Urgency magnifies importance. When do want the healing to begin? When do you want the healing to be completed by?

7. Realistic - Is your goal realistic and reasonable? Do you believe it to be attainable?

8. Motivation - Does your goal excite you? Does the thought of attaining your goal uplift you and fill you with passion?

9. Flexibility - Are you willing to modify your behavior to do more of what works and less of what doesn't work? Are you aware of where you are rigid in your behaviors and beliefs?

10. Permission - Are you allowed to have your goal?

11. Willingness - Are you willing to do what is necessary?

12. Beliefs - What beliefs are necessary to be a part of your new pathway (attaining and maintaining your goal?)

13. Limiting beliefs - What beliefs that you hold, will prevent you from attaining your goal?

14. Experiences - What experiences will maintain your goal attaining beliefs?

What experiences will maintain your present state/illness, limiting beliefs?

15. Action - All results are a result of actions. You have to work at it. Every day do actions that you know are beneficial to achieving your goal. List the actions you take. Congratulate yourself at the end of each day for the actions you took that day.

What do you need to do to have your goal?

16. Persistence - Constantly take the actions and effort to do what is necessary.

17. Space - Healing takes place in the empty space. Health fills the vacuum. Love the void and love will fill the void. Where can you create an internal space?

18. Meditation/self hypnosis - Communicate with your unconscious mind. Your unconscious mind is in control of the healing/illness system. The more you are in touch with the unconscious mind the better.

19. Fear - Eliminate (release) fear (not scaredness), have the courage to investigate your fears, and get help if necessary to release them. Do you fear yourself?

If you do, why?

20. Love - Love really does heal all. This maybe an overdone cliché, but nevertheless, it is absolutely true! Discover what love is. How was love demonstrated in your family as a child? What did you learn about love? Do you love yourself? What do you have to do to earn love, acceptance?

21. Release - Release, work through feelings of resentment, helplessness, hatred, anger etc, these are all valid emotions, but they create chemical toxins when they are repressed, as do all repressed feelings.

22. Commitment - 100% commitment means success. How can you raise your commitment to 100%?

What is preventing you from being 100% committed?

Healing a terminal or chronic illness is a matter of creating the correct conditions. The list above is helpful in aiding you to discover information about the correct conditions for you. Get uncomfortable, pry, ask, demand, seek, do!!! or be comfortable and not do. The choice is yours - be aware of the consequences.

By Philip Martin

Philip Martin is a Naturopath, Hypnotherapist and Author of "Life Patterns, the Secret to Emotional Freedom" and "The 5 Step Cancer Healing Process, a clear and defined pathway". He is a gifted therapist based on the Sunshine Coast Qld. Australia.

Article Source: http://EzineArticles.com/6687776

Thyroid Cysts VS Thyroid Cancer

noreply@blogger.com (Han Idris) — Thu, 17 Nov 2011 01:41:00 +0000

There are many different things that can go wrong with the brownish-red gland called the thyroid. The problem I am going to focus on are thyroid cysts.

A butterfly shaped gland, part of the endocrine system, the thyroid gland is known as the "master gland of the body. It is located at the base of the throat below the area of the Adam's apple. This gland,weighing less than an ounce, produces the hormones that are responsible for many functions such as the metabolic rate of the body, weight control and growth.

What is a thyroid cyst? It is a fluid filled sac that has grown on the gland. Resembling a filled water balloon, the cyst is usually small and does not cause any problems. Normally the cyst does not interfere with the hormone producing function of the thyroid. The cyst may grow very slowly or develop very quickly.

The two types of thyroid cysts are cystic. entirely filled with fluid, and complex, composed of both fluids and solids. Usually harmless, the cysts may persist for years and never cause any health problems. They can shrink away on their own. There are occasions though when problems do arise such as bleeding into the cyst causing it to enlarge. If this happens there may be pain, difficulty breathing and even an increase in your heart beats.

The majority of people that have thyroid cysts do not know until the lump is discovered by a physician during an examination of the neck. This is so because having a cyst on the thyroid does not present symptoms if they are that small. Cysts that larger may not present any health issues but will be more noticeable and can be more easily felt. They can become large enough to press against the windpipe or the vocal chords. On occasion a large cyst may interfere with thyroid hormone production causing the body to become either hyperthyroidism, overproduction, or hypothyroidism, under production of the hormones.

Thyroid cysts are rarely malignant. Their content is usually normal body fluids. The major symptom of a cancerous cyst is that it feels hard and tends to grow large quickly. When such a case arises, the physician may want to do a biopsy procedure called a fine needle aspiration. The procedure for a FNA is the insertion of a very fine needle into the cyst to extract a sample of the contents. Other procedures that may be used to check out the cyst are ultrasound, CT scan or radioactive iodine scan. These tests will give different results to help the physician make the diagnosis and treatment plan.

Most of the time there is no treatment plan need for thyroid cysts especially if they are small. Your physician will want to do follow-ups on a regular basis by taking blood tests to make sure that it is not causing any function problems for the thyroid gland. The size of the growth will also be monitored.

The cyst may be aspirated to drain it and that may be the end of it. If it continues to fill and is "suspicious", surgery may be the next step.

Having a cyst develop on your thyroid gland does not mean that you have thyroid cancer but it is well worth the time to have it checked out. Having my cyst removed after being aspirated three times lead to the discovery of papillary thyroid cancer in my thyroid gland and several lymph nodes.

Article Source: http://EzineArticles.com/6692661

Peptic Ulcer Disease : Differential Diagnosis & Workup

noreply@blogger.com (Han Idris) — Thu, 21 Oct 2010 10:06:00 +0000

Differential Diagnoses

Biliary Colic
Mesenteric Artery Ischemia
Cholecystitis
Pancreatic Cancer
Cholelithiasis
Pancreatitis, Acute
Gastritis, Acute
Pancreatitis, Chronic
Gastritis, Chronic
Gastroesophageal Reflux Disease

Peptic Ulcer Disease : Overview

noreply@blogger.com (Han Idris) — Thu, 21 Oct 2010 09:48:00 +0000

Author: Tri H Le, MD, Assistant Professor of Medicine, Division of Gastroenterology and Hepatology, Penn State Milton S Hershey Medical Center Coauthor(s): George T Fantry, MD, Director of Clinical Gastroenterology, Department of Internal Medicine, Division of Gastroenterology, Associate Professor, University of Maryland School of Medicine.

Peptic ulcer disease (PUD) is a common disorder that affects millions of individuals in the United States each year. PUD has a major impact on our health care system by accounting for roughly 10% of medical costs for digestive diseases. In the last two decades, major advances have been made in the understanding of the pathophysiology of PUD, particularly regarding the role of Helicobacter pylori infection and nonsteroidal anti-inflammatory drugs (NSAIDs). This has led to important changes in diagnostic and treatment strategies, with the potential for improving the clinical outcome and for decreasing health care costs.

Pathophysiology
Peptic ulcers are defects in the gastric or duodenal mucosa that extend through the muscularis mucosa. H pylori infection and NSAID use are the most common etiologic factors. Other, less common causes are hypersecretory states, such as Zollinger-Ellison syndrome, G-cell hyperplasia, mastocytosis, and basophilic leukemias.

Under normal conditions, a physiologic balance exists between peptic acid secretion and gastroduodenal mucosal defense. Mucosal injury and, thus, peptic ulcer occur when the balance between the aggressive factors and the defensive mechanisms is disrupted. Aggressive factors, such as NSAIDs, H pylori, alcohol, bile salts, acid, and pepsin, can alter the mucosal defense by allowing back diffusion of hydrogen ions and subsequent epithelial cell injury. The defensive mechanisms include tight intercellular junctions, mucus, mucosal blood flow, cellular restitution, and epithelial renewal.

Frequency

United States

* One-year point prevalence is 1.8%. Lifetime prevalence is approximately 10%. PUD affects approximately 4.5 million people annually.

International
The frequency of PUD in other countries is variable and determined primarily by association with the major causes of PUD: H pylori and NSAIDs.1
Mortality/Morbidity

Medical office visits and hospitalizations for PUD have decreased in the last few decades. The mortality rate, which has decreased modestly in the last few decades as well, is approximately 1 death per 100,000 cases. The hospitalization rate is approximately 30 patients per 100,000 cases.

Sung et al examined the rate of bleeding-related versus non-bleeding–related causes of mortality in 577 patients with peptic ulcer bleeding.2 The causes of death were classified as follows:

* Bleeding-related mortality
o Death from uncontrolled bleeding
o Death during surgery for uncontrolled bleeding
o Death within 48 hours after endoscopy
o Death from surgical complications or within 1 month following surgery
o Endoscopic-related mortality
* Non-bleeding–related mortality
o Death from cardiac causes
o Death from pulmonary causes
o Death from cerebrovascular disease
o Death from multiorgan failure
o Death from terminal malignancy

The investigators determined that among patients suffering from peptic ulcer bleeding, deaths from non-bleeding–related causes (79.7%) were significantly higher than those from bleeding-related causes (18.4%). Terminal malignancy (33.7%), multiorgan failure (23.9%), and pulmonary conditions (23.5%) were the most frequent non-bleeding–related causes of mortality.

Most bleeding-related deaths in the study resulted when attempts at immediate bleeding control failed (29.2%) or occurred in patients who died within 48 hours after endoscopic therapy (25.5%). The mean age of patients who suffered bleeding-related mortality (75.4 years) was found to be greater than that of patients who died from the other listed causes (71.7 years; P = 0.010).

According to the study's authors, clinicians can attempt to optimize the management of patients with peptic ulcer bleeding by concentrating not only on achieving hemostasis, but also on reducing the patients' risks for multiorgan failure and cardiopulmonary death.

Sex

* Prevalence has shifted from predominance in males to similar occurrences for both sexes.
* Lifetime prevalence is approximately 11-14% for men and 8-11% for women.

Age

* Age trends for ulcer occurrence reveal declining rates in younger men, particularly for duodenal ulcer, and increasing rates in older women.
* Trends reflect complex changes in risk factors for PUD, including age-cohort phenomena with the prevalence of H pylori infection and the use of NSAIDs in older populations.

Clinical History * Epigastric pain (the most common symptom)
o Gnawing or burning sensation
o Occurs 2-3 hours after meals
o Relieved by food or antacids
o Patient awakens with pain at night.
o May radiate to the back (consider penetration)
* Nausea
* Vomiting, which might be related to partial or complete gastric outlet obstruction
* Dyspepsia, including belching, bloating, distention, and fatty food intolerance
* Heartburn
* Chest discomfort
* Anorexia, weight loss
* Hematemesis or melena resulting from gastrointestinal bleeding
* Dyspeptic symptoms that might suggest PUD are not specific because only 20-25% of patients with symptoms suggestive of peptic ulceration are found on investigation to have a peptic ulcer.

Physical

* In uncomplicated PUD, clinical findings are few and nonspecific.
o Epigastric tenderness
o Guaiac-positive stool resulting from occult blood loss
o Melena resulting from acute or subacute gastrointestinal bleeding
o Succussion splash resulting from partial or complete gastric outlet obstruction

Causes
* H pylori infection
o H pylori infection and NSAID use account for most cases of PUD.
o The rate of H pylori infection for duodenal ulcers in the United States is less than 75% for patients who do not use NSAIDs. Excluding patients who use NSAIDs, 61% of duodenal ulcers and 63% of gastric ulcers are positive for H pylori in one study. This rate also depends on the demographic, which appears to be less frequent in whites as compared to nonwhites.
o Prevalence in complicated ulcers (ie, bleeding, perforation) is significantly lower than that found in uncomplicated ulcer disease.
* Nonsteroidal anti-inflammatory drugs
o Similar to H pylori infection, NSAID use is a common cause for PUD.
o Corticosteroids alone do not increase the risk for PUD; however, they can potentiate the ulcer risk in patients who use NSAIDs concurrently.
* Severe physiologic stress
o Burns
o CNS trauma
o Surgery
o Severe medical illness
* Hypersecretory states (uncommon)
o Gastrinoma (Zollinger-Ellison syndrome) or multiple endocrine neoplasia (MEN-I)
o Antral G cell hyperplasia
o Systemic mastocytosis
o Basophilic leukemias
* Diseases associated with an increased risk of PUD include cirrhosis, chronic obstructive pulmonary disease, renal failure, and organ transplantation.
* Additional rare, miscellaneous causes include radiation-induced or chemotherapy-induced ulcers, vascular insufficiency (crack cocaine), and duodenal obstruction.