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Although the only contraindications to vaginal delivery in Crohn disease is active perianal disease generic 5 mg norvasc fast delivery blood pressure medication nightmares, the likelihood of having a Caesarean section is increased 1 generic norvasc 2.5 mg amex prehypertension 37 weeks pregnant. Having an extensive episotomy at delivery may contribute to the 18% risk of a woman developing perianal diseas after childbirth (Iinyckyj 1999) order norvasc 5 mg without a prescription lipo 6 arrhythmia. Breastfeeding may or may not be a risk factor for the development of Crohn disease in the infant (Klememt 2004 discount norvasc 10mg mastercard pulse pressure with exercise; Jantchou P, 2005). Flexible sigmoidoscopy during pregnancy does not increase the risk of premature labout (Cappell 1996). Shaffer 297 Scheme Classification Output volume Pancreatic Low (<200 ml/day) High (>200 ml/day) Intestinal Low (<500 ml/day) High (>500 ml/day) Etiological Underlying disease Printed with permission: Messmann H, et al. Antibiotics may be a useful bridge to the use of immunomodulators (Dejaco 2003). This reflects the fact that fistulas may remain active long after they stop draining (Schwartz 2005). A side-to- side rather than an end-to-end anastomesis results in fever complications but no difference in recurrence rates (Smillis 2007). In the first year after surgery, symptoms will develop in 20-30%, and for every year thereafter 10% will develop symptoms. The symptomatic recurrence is 13-100% after an initially successful balloon dilation. Repeat dilation is appropriate, but the length of the symptom-free internal will be the main parameter used to decide between surgery and re-do endoscopic balloon dilation (Van Assche et al. Endoscopic stenting may reduce the recurrence rates after endoscopic balloon dilation (Matsuhashi 2000), but the injection of steroids into the affected area may actually accelerate relapse (East 2007). During the active phase, patients develop a mixed picture of an inflammatory reaction and malnutrition, with slight increases in energy expenditure and a relative increase in fat and decrease in carbohydrate oxidation. These changes are non-specific and are quickly reversible when patients are given nutritional support. The fat composition of the enteral diet seems to be important in terms of its therapeutic effect (Gonzalez- Huix et al. Prebiotics arenon-digestible food ingredients that beneficially affect the host by selectively stimulating the growth and/or activity of one, or a limited number of bacteria in the colon, thus improving host health (Bengmark 2005, Lim 2005). The rationale behind prebiotic use is to increase the endogenous numbers of beneficial bacterial strains including lactobacillus and bifidobacterium. Another viable option is to use both prebiotic and probiotic administration in conjunction, referred to as synbiotics (Bengmark 2005, Bengmark 2005). The rationale behind synbiotic treatment is that the combined probiotic and prebiotic would exert a beneficial effect greater than would be observed when administered individually. Probiotics may function via the modulation of cell proliferation and apoptosis (Ichikawa 1999). Identification of these probiotic responsiveness genes may lead to screening to determine i) whether a patient will be responsive to probiotic therapy, and ii) to which probiotics they would respond more efficiently (Geier 2007). There have been a large number of probiotic species identified, most of which have differing mechanisms of action. Further complexity stems from the finding that the mode of First Principles of Gastroenterology and Hepatology A. Shaffer 303 action of a given probiotic can differ based on the presence of other probiotics or enteric bacteria in the surrounding environment, and also the disease setting in which the probiotic is used (Shanahan 2004). If there is only proctitis, then no special screening is necessary beyond the guidelines for the average risk individual. In the hands of expert pathologist, the risk of false-positive and false-negative diagnosis of dysplasia is 5% and 48%, respectively (Provenzale 2001). A number of methods have been introduced to improve the diagnostic sensitivity and specificity of detecting dysplasia or colorectal cancer, including improved training of endoscopist and improved equipment, and as well as new laboratory procedures (Table 38). Shaffer 305 Chromoendoscopy (intravital staining, contrast endoscopy) permits assessment of the pit patterns (Jung 1999). The diagnostic sensitivity and specificity to detect transmural inflammation is 70% and 83%, respectively (Shen 2004). High contrast images are obtained from the confocal endomicroscope, as well as simultaneously obtaining standard endoscopic standard images. The approach of polypectomy and colonscopic follow- up is the standard of care, as long as the adenoma has been completely removed, the margins are free of dysplasia, and there is no flat dysplasia anywhere in the colon either close to or away from the polyp. Shaffer 312 Is it important to distinguish between Crohns and Ulcerative Colitis? Introduction This chapter presents an overview of colonic physiology and the diseases that affect the colon. It discusses lower gastrointestinal bleeding, infectious diseases affecting the colon and diseases specifically involving the anus. Function The colon contributes to three important functions in the body: (1) concentration of fecal effluent through water and electrolyte absorption, (2) storage and controlled evacuation of fecal material and (3) digestion and absorption of undigested food. Although the colon is not essential for survival, its functions contribute significantly to the overall well-being of humans. The colon can be functionally divided through the transverse colon into two parts, the right and left colon. The right colon (cecum and ascending colon) plays a major role in water and electrolyte absorption and fermentation of undigested sugars, and the left colon (descending colon, sigmoid colon and rectum) is predominantly involved in storage and evacuation of stool. Functional Anatomy The human colon is a muscular organ measuring approximately 125 cm in length in vivo. The mucosa lacks the villous projections found in the small intestine and presents a relatively smooth surface, but numerous crypts extend from its surface. Cell types lining the surface and the crypts resemble those in the small intestine but are composed of significantly greater numbers of goblet cells. These cells secrete mucus into the lumen, and mucus strands can often be identified in association with stool. This observation is misconstrued by some patients as a response to underlying colonic pathology. The haustral folds, which help define the colon on barium x-ray, are not a static anatomical feature of the colon but rather result from circular muscle contractions that remain constant for several hours at a time. The outer or longitudinal muscle is organized in three bands, called taeniae coli, which run from the cecum to the rectum where they fuse together to form a uniform outer muscular layer. These muscular bands and elongated serosal fat saccules, called appendices epiploicae, aid in the identification of the colon in the peritoneal cavity. The colon is innervated by the complex interaction of intrinsic (enteric nervous system) and extrinsic (autonomic nervous system) nerves. The cell bodies of neurons in the enteric nervous system are organized into ganglia with interconnecting fiber tracts, which form the submucosal and myenteric plexi. These nerves are organized into local neural reflex circuits, which modulate motility (myenteric), secretion, blood flow and probably immune function (submucosal). Their receptor subtypes provide pharmacological targets for the development of drugs designed to alter colonic functions such as motility. The importance of the enteric nervous system is exemplified by Hirschsprungs disease, where there is a congenital absence of nitric oxide containing inhibitory neurons over variable lengths of the rectum and colon. Shaffer 315 Infants typically present with bowel obstruction or severe constipation. Barium x-rays identify the affected region as a constricted segment because the excitatory effects of the neurotransmitter acetylcholine are unopposed as a result of the absence of inhibitory neurotransmitter. The autonomic nervous system comprises sensory nerves, whose cell bodies are found in the dorsal root ganglia, and motor nerves, the sympathetic and parasympathetic nerves. Parasympathetic nerves innervating the right colon travel in the vagus nerve, and those innervating the left colon originate from the pelvic sacral nerves. Parasympathetic nerves are predominantly excitatory, and sympathetic nerves are inhibitory. Autonomic nerves modulate the enteric neural circuits within the colon and participate in neural reflexes at the level of the autonomic ganglia, spinal cord and brain.

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Central nervous system | The brain and Arachidonic acid | A molecule that synthesizes spinal cord purchase norvasc 10 mg line peak pulse pressure qrs complex. Bacterium | One-celled organism without Chemical genetics | A research approach a nucleus that reproduces by cell division order norvasc 5mg amex blood pressure low symptoms; can resembling genetics in which scientists custom- infect humans generic 10mg norvasc with mastercard blood pressure 50, plants order 2.5 mg norvasc blood pressure categories, or animals. Medicines By Design I Glossary 51 Cholesterol | A lipid unique to animal cells that Dose-response curve | A graph drawn to is used in the construction of cell membranes and show the relationship between the dose of a drug as a building block for some hormones. G protein | One of a group of switch proteins Combinatorial genetics | A research process involved in a signaling system that passes incoming in which scientists remove the genetic instructions messages across cell membranes and within cells. Genomics | The study of all of an organisms Cytochrome P450 | A family of enzymes genetic material. Neurotransmitter | A chemical messenger that allows neurons (nerve cells) to communicate with Lipid | A fatty, waxy, or oily molecule that each other and with other cells. Nucleus | The membrane-bound structure within a cell that contains most of the cells Liposome | Oily, microscopic capsules designed genetic material. Organelle | A specialized, membrane-bound structure that has a dened cellular function; Membrane | A thin covering surrounding a cell for example, the nucleus. Pharmacodynamics | The study of how drugs Metabolism | All enzyme-catalyzed reactions act at target sites of action in the body. Steroid | A type of molecule that has a multiple ring structure, with the rings sharing molecules Receptor | A specialized molecule that receives of carbon. Toxicology | The study of how poisonous substances interact with living organisms. X-ray crystallography | A technique used to determine the detailed, three-dimensional structure of molecules based on the scattering of X rays through a crystal of the molecule. A cell, which is the basic building block of tissue, contains on the aver- age 1014 atoms. These phenomena are so dier- ent from the predictable properties of inanimate matter that many scientists in the early 19th century believed that dierent laws governed the structure and organization molecules in living matter. These molecules tend to be larger and more com- plex than molecules obtained from inorganic sources. It was thought that the large molecules found in living matter could be produced only by living organ- isms through a vital force that could not be explained by the existing laws of physics. This concept was disproved in 1828 when Friedrich Wohler synthe- sized an organic substance, urea, from inorganic chemicals. Soon thereafter many other organic molecules were synthesized without the intervention of biological organisms. Today most scientists believe that there is no special vital force residing in organic substances. The atomic structure of many complex biological molecules has now been determined, and the role of these molecules within living systems has been described. It is now possible to explain the functioning of cells and many of their interactions with each other. Even when the structure of a complex molecule is known, it is not possible at present to predict its function from its atomic structure. The mechanisms of cell nourishment, growth, reproduction, and communication are still understood only qualitatively. However, biological research has so far not revealed any areas where physical laws do not apply. The amazing properties of life seem to be achieved by the enormously complex organization in living systems. The aim of this book is to relate some of the concepts in physics to living systems. Each chapter contains a brief review of the background physics, but most of the text is devoted to the applications of physics to biology and medicine. The biological systems to be discussed are described in as much detail as is necessary for the physical analysis. Whenever possible, the analysis is quantitative, requiring only basic algebra and trigonometry. We calculate the height to which a person can jump, and we discuss the eect of an animals size on the speed at which it can run. In our study of uids we examine quantitatively the circulation of blood in the body. The theory of uids allows us also to calculate the role of diusion in the functioning of cells and the eect of surface tension on the growth of plants in soil. Using the principles of electricity, we analyze quantitatively the conduction of impulses along the nervous system. There are, of course, severe limits on the quantitative application of physics to biological systems. Many of the advances in the life sciences have been greatly aided by the application of the techniques of physics and engineering to the study of living systems. Both in common use and in the sci- entic literature one often nds pressure also expressed in units of dynes/cm2, Torr (mm Hg), psi, and atm. In those cases conversion factors have been provided either within the text or in a compilation at the end of Appendix A. Hobbie and David Cinabro for their careful reading of the manuscript and helpful suggestions. In this third edition I want to express my appreciation for the encouragement and compe- tent direction of Tom Singer and Jason Malley editors at Elsevier/Academic Press and for the help of Sarah Hajduk and Ramesh Gurusubramanian in the production of this edition. It was the rst branch of physics that was applied success- fully to living systems, primarily to understanding the principles governing the movement of animals. Our present concepts of mechanics were formulated by Isaac Newton, whose major work on mechanics, Principia Mathematica, was published in 1687. The early Greeks, who were interested in both science and athletics, were also the rst to apply physical principles to animal movements. Aristotle wrote, The animal that moves makes its change of position by pressing against that which is beneath it. Runners run faster if they swing their arms for in extension of the arms there is a kind of leaning upon the hands and the wrist. After the decline of ancient Greece, the pursuit of all scientic work entered a period of lull that lasted until the Renaissance brought about a resurgence in many activities including science. During this period of revival, Leonardo da Vinci (14521519) made detailed observations of ani- mal motions and muscle functions. Since da Vinci, hundreds of people have contributed to our understanding of animal motion in terms of mechanical principles. Their studies have been aided by improved analytic techniques and the development of instruments such as the photographic camera and electronic timers. The development of prosthetic devices such as articial limbs and mechanical hearts is an active area of biomechanical research. Mechanics, like every other subject in science, starts with a certain number of basic concepts and then supplies the rules by which they are interrelated. Appendix A summarizes the basic concepts in mechanics, providing a review rather than a thorough treatment of the subject. We will now begin our dis- cussion of mechanics by examining static forces that act on the human body. We will rst discuss stability and equilibrium of the human body, and then we will calculate the forces exerted by the skeletal muscles on various parts of the body. This weight can be considered a force acting through a single point called the center of mass or center of gravity.

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Severe hypoglycemia is dened as hypoglycemia because of their reduced personnel cheap norvasc 5mg on line pulse pressure 22, or family members of severe cognitive impairment requiring as- ability to recognize hypoglycemic symp- these individuals should know sistance from another person for recov- toms and effectively communicate their where it is and when and how to ery (76) buy norvasc 10mg line heart attack x factor. Glucagon administra- Symptoms of hypoglycemia include cheap norvasc 5mg arteria umbilical, tient education purchase 2.5mg norvasc free shipping blood pressure medication helps ed,dietaryintervention (e. The with type 1 diabetes with severe hypogly- does not need to be a health care pro- patient treated with noninsulin therapies or cemia and hypoglycemia unawareness fessional to safely administer glucagon. Adequate uid and human islet transplantation may be an op- cagon kits are not expired. Infection or tion, but the approach remains experimen- dehydration is more likely to necessitate Hypoglycemia Prevention tal (83,84). Teach- ing glucose-lowering drugs such as insulin ing people with diabetes to balance insulin References to glycemic targets. Diabetes Care 2017;40:538545 acting carbohydrates at the hypoglycemia unawareness (or hypoglycemia-associated 2. Hypoglycemia treatment requires of diabetes on thedevelopment and progression of ingestion of glucose- or carbohydrate- promise stringent diabetes control and quality long-term complications in insulin-dependent dia- containing foods. N Engl J Med 1993;329:977986 sponse correlates better with the glucose cient counterregulatory hormone release, 3. Evidence of a strong content of food than with the carbohy- autonomic response, which both are risk fac- associationbetweenfrequencyofself-monitoring drate content of food. Pure glucose is ofbloodglucoseandhemoglobinA1clevelsinT1D the preferred treatment, but any form tors for, and caused by, hypoglycemia. Diabetes of carbohydrate that contains glucose ollary to this vicious cycle is that several Care 2013;36:20092014 weeks of avoidance of hypoglycemia has 4. Added fat may been demonstrated to improve counterregu- Structuredself-monitoringofbloodglucosesignif- retard and then prolong the acute glyce- icantly reduces A1C levels in poorly controlled, lation and hypoglycemia awareness in many mic response. In type 2 diabetes, ingested noninsulin-treated type 2 diabetes: results from protein may increase insulin response patients (86). Diabetes without increasing plasma glucose con- more episodes of clinically signicant hy- Care 2011;34:262267 poglycemia may benetfromatleast 5. Dual use of Department of Veterans sources high in protein should not be Affairs and Medicare benets and use of test used to treat or prevent hypoglycemia. Patients of patients with hyperglycemia in the hos- who self-monitor blood glucose and their unused mia unless further food is ingested after pital, please refer to Section 14 Diabetes testing results. Accessed 18 Au- precipitate diabetic ketoacidosis or nonke- gust 2015 Glucagon totic hyperosmolar state, life-threatening 8. Fre- treatment of hypoglycemia in people un- care to prevent complications and death. Empirically es- insulin glargine when administered as add-on to 379387 tablishing blood glucose targets to achieve HbA1c glucose-lowering drugs in insulin-naive people 23. A clin- 416 mic control in adults with type 1 diabetes using ical trial of continuous subcutaneous insulin infusion 10. Frequencyofself-monitoringblood tients with type 1 diabetes using real-time of Diabetes Interventions and Complications glucose and attainment of HbA1c target values. Effect of prior intensive insulin Acta Diabetol 2016;53:5762 2006;29:27302732 treatment during the Diabetes Control and Com- 12. Farmer A; Diabetes Glycaemic Education and cose monitoring on quality of life, treatment sat- Diabetes Care 2011;34:5354 Monitoring Trial Group. Translating the A1C assay into insulin-treated patients with type 2 diabetes in 29. Diabetes of blood glucose in patients with type 2 diabetes 1383 Care 2016;39:14621467 mellitus who are not using insulin. Sustained benetof differences in the relationship of glucose concen- self-monitoring in non-insulin-treated type 2 di- continuous glucose monitoring on A1C, glucose trations and hemoglobin A1c levels. Com- sociationofsicklecelltraitwithhemoglobinA1cin proves rst continuous glucose monitoring system parative effectiveness and safety of methods African Americans. Novel glucose-sensing Real-time continuous glucose monitoring signi- tions: a transethnic genome-wide meta-analysis. Lancet 2016;388:22542263 Care 2013;36:41604162 Children Network (DirecNet) Study Group. Racial dis- glucose monitoring and intensive treatment of Safety of a hybrid closed-loop insulin delivery sys- parity in A1C independent of mean blood glucose type 1 diabetes. Effect treated with multiple daily insulin injections: the 375:644654 of intensive diabetes therapy on the progression S64 Glycemic Targets Diabetes Care Volume 41, Supplement 1, January 2018 of diabetic retinopathy in patients with type 1 di- 63. Trial/Epidemiology of Diabetes Interventions and 30yearsduration:theDiabetesControlandCom- Glucose concentrations of less than 3. Retinopathy and plications Trial/Epidemiology of Diabetes Interven- (54 mg/dL) should be reported in clinical trials: nephropathy in patientswithtype 1 diabetesfour tions and Complications and Pittsburgh Epidemiology a joint position statement of the American Diabe- years after a trial of intensive therapy. Hypo- diabetic microvascular complications in Japanese Association between 7 years of intensive treat- glycemia anddiabetes:a report of aworkgroupof patients with non-insulin-dependent diabetes ment of type 1 diabetes and long-term mortality. Effect of intensive blood-glucose control of Cardiology Foundation; American Heart Asso- dementia in older patients with type 2 diabetes with metformin on complications in overweight ciation. Dia- tional treatment and risk of complications in the American Heart Association. Severe hypoglycemia and cular and microvascular complications of type 2 Engl J Med 2015;372:21972206 risks of vascular events and death. Glucose control and vascular correction appears in Diabetologia 2009;52: talityofpatientswithdiabetesreportingsevere complications in veterans with type 2 diabetes. Potential overtreatment of diabe- of transplantation of human islets in type 1 dia- of hyperglycaemia on microvascular outcomes in tes mellitus in older adults with tight glycemic betes complicated by severe hypoglycemia. Diverse causes of hypoglycemia- EpidemiologyofDiabetesInterventionsandCom- position statement of the American Diabetes Asso- associated autonomic failure in diabetes. In- ciation and the European Association for the Study J Med 2004;350:22722279 tensive diabetes treatment and cardiovascular of Diabetes. Diabetes Care 2009;32:13351343 Diabetes Care Volume 41, Supplement 1, January 2018 S65 American Diabetes Association 7. There is strong and consistent evidence that obesity management can delay the progression from prediabetes to type 2 diabetes (1,2) and may be benecialin the treatment oftype2 diabetes (38). In overweight and obese patients with type 2 diabetes, modest and sustained weight loss has been shown to improve glycemic control and to reduce the need for glucose-lowering medications (35). Small studies have demonstrated that in obese patients with type 2 diabetes more extreme dietary energy restriction with very- low-calorie diets can reduce A1C to,6. Weight lossinduced improvements in glycemia are most likely to occur early in the natural history of type 2 diabetes when obesity-associated insulin resistance has caused reversible b-cell dysfunction but insulin secretory capacity re- mains relatively preserved (5,8,10,11). The goal of this section is to provide evidence- based recommendations for dietary, pharmacologic, and surgical interventions for obesity management as treatments for hyperglycemia in type 2 diabetes. S66 Obesity Management for the Treatment of Type 2 Diabetes Diabetes Care Volume 41, Supplement 1, January 2018 Table 7. The latter two well-controlled diabetes (A1C less than strategies may be prescribed for carefully 6. Greater c Diet,physical activity, and behavior- energy decit or provide approximately weight loss produces even greater bene- altherapydesigned toachieve. A maintaining long-term weight loss in pa- lifestyle intervention group of the Look c For patients who achieve short- tients with type 2 diabetes. Such programs should sive lifestyle intervention participants patients health status and preferences. In- ticipation in high levels of physical blood pressure, and lipid-lowering med- terventionsshould beprovided bytrained activity (200300 min/week).

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This triad was also the most commonly reported resistance pattern among O157 strains isolated from cattle and ground beef collected between 1988 and 1993 (Johnson et al norvasc 2.5mg arteria humeral. Resistance to streptomycin generic norvasc 10mg on line pulse pressure method, sulfamethoxazole and tetracycline was similar to past surveys buy norvasc 5 mg fast delivery blood pressure understanding. This triad of drugs are rarely used to treat diarrhoea in humans 10 mg norvasc free shipping blood pressure ranges for athletes, but sulfa-containing drugs and tetracycline are used in animals. Continued surveillance for antimicrobial resistance in O157strains from human and various animal sources may be useful in identifying reservoirs for this pathogen and practices that encourage development of resistance (Johnson et al. Subtherapeutical doses of tylosin have been commonly used in livestock in Denmark, since, there, 90 percent of Enterococci isolated in pigs are resistant to tylosin. In contrast, in Finland, where tylosin has rarely been used subtherapeutically, only 15 percent of the Enterococci are tylosin resistant. In the Netherlands, avoparcin was used subtherapeutically in pigs and 39 percent of the Enterococci isolated from pigs are avoparcin resistant, as they are to the similar one used in human medicine, vancomycin. In countries that have banned certain subtherapeutic uses of antibiotics, decreases in resistance to those antibiotics have been reported, restoring the effectiveness of those antibiotics for treating disease. For example, in Denmark, after a 1995 ban on the use of avoparcin as a growth promoter, glycopeptide-resistant Enterococci in Danish broiler flocks declined from 82 to 12 percent. Giving antimicrobial agents to chickens and other food animals selects for antimicrobial resistance among bacteria (e. Gentamicin and vancomycin are important antimicrobial agents for the treatment of human enterococcal infections. This highlights concern that the food supply can provide the seeds of antimicrobial- resistant Enterococci, which may be carried in the intestinal flora of the general population. Once introduced into a medical facility, they may blossom to clinical importance under the increased selective pressures of antimicrobial use in humans. Gentamicin resistance among Enterococci isolated from meat purchased from grocery stores and from outpatient human stools were studied in the United States of America during the period 19982001 (Kretsinger et al. Bacitracin is widely used as a topical or ophthalmic antibiotic ointment for wounds. It is used in some hospitals as the primary antibiotic barrier for patients with severe burns. It is also widely used in the United States of America to promote the growth of chickens and other livestock. This bifunctional gene confers resistance to essentially all clinically available aminoglycosides except streptomycin, thereby eliminating synergism between aminoglycosides and a cell-wall-active agent such as ampicillin or vancomycin. This gene has been detected in various species of Enterococci significant to human infection and among Enterococci isolated from food-producing animals. Three recently identified gentamicin-modifying genes are also associated with gentamicin resistance in Enterococci and the elimination of synergy between aminoglycosides and cell-wall-active agents. The aph(2)-Ib gene is associated with gentamicin and other types of aminoglycoside resistance in E. The aph(2)-Ic gene is associated with gentamicin and the elimination of ampicillin/gentamicin synergism, and was first described in 1997 in a veterinary isolate of Enterococcus gallinarum, and has also been identified in human E. The aph(2)-Id gene, first described in 1998 in a human Enterococcus casseliflavus isolate, confers high-level resistance to gentamicin but not to amikacin (Tsai et al. To further understand the potential spread of gentamicin resistance genes among Enterococci, Donabedian et al. They confirmed gentamicin resistance from human stool specimens and from chicken and pork purchased in grocery stores, finding evidence of dissemination across a broad geographical area of the country. The aac(6)-Ieaph(2)-Ia gene was the most common gene among the gentamicin-resistant isolates evaluated in this study, and was detected in various enterococcal species, including the E. Their observations provide evidence of a large reservoir for this resistance gene in humans, food and food-producing animals, indicating widespread dissemination of this resistance determinant. Because they have shown that Enterococci isolated from animals and humans possess the same aminoglycoside resistance gene content, it will be important to determine the transferability of these resistance genes, since the dissemination of genes can occur by horizontal transfer. Their additional findings of a high prevalence of gentamicin-resistant Enterococci in the faeces of food-producing animals on farms also suggest that the occurrence of gentamicin-resistant Enterococci in food can be attributed to the presence of the organism in food-producing animals. Furthermore, it is likely that the occurrence of gentamicin-resistant Enterococci in food-producing animals is a consequence of gentamicin use in these animals. In Sweden, all antibiotics have been banned as growth promoters since 1986, including avoparcin. In other northern European countries, where avoparcin has been used as a growth promoter, Enterococci resistant to this antibiotic and also to vancomycin are common in healthy people. Tetracyclines have been widely used as growth promoters and as therapeutic agents in animal husbandry. Despite several warnings about the increased resistance of micro- organisms to tetracyclines and their banning as growth promoters, actually more of the 65 percent of the antibiotics prescribed in the European Community for veterinary therapeutic use are tetracyclines (Kuhne et al. These authors demonstrated the presence of tetracycline residues in bones of slaughtered animals and assessed the potential risk from mechanical deboning of meat, and the use of meat and bone meal in animal feeding, pointing out that the thermal treatment required by the European Community for hazardous micro-organisms and agents is a minimum of 133C, but bones must be heated to at least 140C to obtain a significant decrease in tetracycline residues. Another potential risk that has to be considered is the use of chitin-derivate products for animal feeding or as source of peptone to prepare culture media. Another aspect of the resistance problem that has also to be considered is that recently some similarities between bacterial resistance patterns to antibiotics and to Risk assessment 21 biocides (antiseptics, disinfectants, preservatives) have been reported. Gram-negative bacteria that have developed resistance to cationic biocides (chlorhexidine salts and quaternary ammonium compounds) may also be resistant to some antibiotics (Russell, 2000). There is clear evidence that, with an increase in the consumption of antimicrobial agents by humans or animals, there is a resultant increase in antimicrobial resistance (Donabedian et al. Farming implies some sort of intervention in the rearing process to enhance production, such as regular stocking, feeding and protection from predators. Aquaculture is becoming a more concentrated industry of fewer but much larger farms. Infective diseases are always a hazard, and may cause major stock losses and problems of animal welfare. To control infectious diseases in aquaculture, the same strategies used in other areas of animal production are employed. Whenever antibiotics are used, they should be strictly controlled under the same code applying to other veterinary medicines. As there are no antibiotics specifically designed for aquaculture, authorized products developed for other areas of veterinary medicine are used. In the United States of America, the majority of fish farming enterprises where antibiotics might be used have pond-like or tank structures, rather than open-water habitats, like oceans or lakes. It is estimated that nearly 150 pounds of antibiotics are applied per acre (170 kg/ ha) of salmon harvested in the United States of America, and since pens are placed in natural seawaters, antibiotics and the resultant resistant bacteria are in contact with the environment. Aquaculture promotes the production of various sizes and types of aquatic organisms, and the use of antibiotics and drugs in the fish industry is complicated because of the need to administer the compounds usually direct into the water where the organisms live. Several factors have to be considered: the safety of aquatic fish products, the integrity of the environment, the safety of target animals, and the safety of the persons administering the compounds. The most frequent fish infections treated with antibiotics are skin ulcers, diarrhoea and blood sepsis. The micro-organisms responsible for these infections belong to bacterial families that also produce infections in humans. Even when treatment is suspended before the fish is sold for consumption, the resistance can still be transmitted. For this reason, the environmental and health impact of the use of antibiotics in aquaculture is recognized; in many countries the use of antibiotics in aquaculture is under veterinary medicine control. In extensive and semi-extensive coastal shrimp farms, antibiotic use was also very low. In some countries, there was a higher use of antibiotics for intensive shrimp farming, with oxytetracycline and oxolinic acid being the antibiotics mainly used.

B. Zuben. New York Institute of Technology.

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