Inflammatory Bowel Disease - A Holistic Perspective

The IBS Miracle

Today to Discover: My unique holistic system to immediately get symptomatic relief and completely cure your condition within 3 to 8 weeks using my powerful 100% natural system. The horrible truth about conventional Ibs treatments. A list of the original hidden research papers (together with all the details you need to locate them yourself) published by scientists and MDs reporting how they cured Ibs using natural methods so you'll see that my system is backed by scientific evidence! 78 different scientific sources to be exact! How simple over the counter products will immediately reduce cramps and abdominal pain. The dietary changes you should make to live an Ibs-free life. How to make your body combat Ibs and re-balance itself. The link between lifestyle and Ibs. The specific foods that trigger Ibs symptoms. Foods that are marketed as being ery healthy that will actually cause your Ibs to get worse. Herbs that are extremely potent in stopping diarrhea, constipation and gas. Simple alternative treatments that will cure your Ibs faster than you ever thought possible. I will show you step by step how to do this. The food items you have to include in your diet if you want to get rid of your Ibs fast. The food items you should limit if you want to get rid of Ibs. Convenient printable charts that will tell you exactly the foods to avoid and the foods to include. The secret 100% natural remedies that you should use, and are guaranteed to make a dramatic impact on your Ibs condition in just a few days! Read more here...

The IBS Miracle Summary

Rating:

4.6 stars out of 11 votes

Contents: 60 Page EBook
Author: James Walden
Official Website: theibsmiracle.com
Price: $37.00

Access Now

My The IBS Miracle Review

Highly Recommended

The author has done a thorough research even about the obscure and minor details related to the subject area. And also facts weren’t just dumped, but presented in an interesting manner.

All the testing and user reviews show that The IBS Miracle is definitely legit and highly recommended.

Factors Influencing Nutritional Decline in Diarrhea

Factors that influence a nutritional decline during a period of diarrhea include reduced food intake, diminished nutrient absorption due to malabsorption of macro- and micronutrients and shorter intestinal transit time, direct loss of protein and other nutrients, and an increase in the body's demand for nutrients. In addition, diarrhea of infectious origins causes cytokine-induced malnutrition, which results from the action of proinflammatory

Management of Diarrhea

An invariable accompaniment of diarrhea, particularly persistent diarrhea, is protein-energy malnutrition. However, dehydration is the most immediate complication of diarrhea. Clinical management of acute diarrhea includes four major components (i) replacement of fluid and electrolyte losses, (ii) zinc therapy, (iii) antimicrobial therapy when indicated, and (iv) continued feeding to supply a sufficient quantity of nutrients to meet both the patient's usual maintenance requirement and the increased needs imposed by infection and malabsoption.

Dietary Management of Diarrhea Including Persistent Diarrhea

Data suggest that continued feeding during diarrhea is generally well tolerated and it minimizes the nutritional cost associated with diarrhea. A child should receive the same type of food during an episode of diarrhea as when the child is healthy. Feeding is usually tolerated, with the occasional exception of lactose intolerance. A small subgroup of children exclusively receiving nonhuman milk may have a higher rate of complications. These children should be closely supervised and provided with alternatives if needed. Full feedings will help to minimize growth faltering and a decline in nutritional status. Growth faltering may still occur, especially in severely undernourished children, due to poor nutrient absorption.

Diarrhea and Dehydration

Diarrhea refers to stools that are abnormally frequent and liquid. The modifier abnormal is critical because stools can normally be frequent and liquid in young children. Acute diarrheal illnesses account for more than 3 million ambulatory pediatric visits, 10 million sick days, and 100,000 hospital admissions per year in the United States. In the United States, rotavirus predominantly affects infants between 3 to 15 months. The peak incidence is in the winter months, and rotavirus accounts for as many as 50 percent of the cases of acute diarrhea in winter. Enteric adenoviruses (serotypes 40 and 41) are the second most common viral pathogen in infants. In summer most of the cases of diarrhea are caused by bacteria (including Escherichia coli, Salmonella, and Shigella). Parasitic causes of diarrhea are rare in neonates. A history of bloody diarrhea strongly suggests a bacterial pathogen, particularly in an older infant or a child. It is important to know that, in infants less than 6...

Inflammatory Bowel Disease Animal Models

Environmental, immune and genetic susceptibilities have all been implicated in the pathogenesis of inflammatory bowel disease (IBD). The development of various experimental models (Table 1) has enabled researchers to study the development of inflammation in the intestine, under conditions where the underlying lesion is better understood.

Inflammatory Bowel Disease

Pregnant patients with inflammatory bowel disease are at increased risk for nutritional and metabolic abnormalities that may put the fetus at increased risk for intrauterine growth restriction. Pregnancy itself, however, seems to have little effect on inflammatory bowel disease. When an exacerbation does occur during pregnancy it most frequently happens in either the first trimester or the postpartum period. It is hypothesized that this is due to a correlation with levels of circulating corticosteroids during pregnancy. In general, the treatment of the pregnant patient with inflammatory bowel disease is the same as that of the nonpregnant patient. Antidiarrheal drugs including codeine, opium, paregoric, and Lomotil may also be used safely in pregnancy. While sulfasalazine and corticosteroids may be safely used in pregnancy, the possibility of the development of gestational diabetes must be considered in all patients on steroid therapy. Sulfa drugs are theoretically contraindicated in...

Virotypes diarrheaproducing E coli

Recently, E. coli strains have been categorized on the basis of certain virulence factors (i.e. virotyping). This classification scheme is based on the production of certain E. coli toxins, patterns of E. coli adherence to particular host cells, the abilities of E. coli strains to invade the intestinal epithelium, and the patterns of intestinal mucosal pathology produced by E. coli. Virotyping therefore more directly relates various E. coli strains to the actual disease process than does serotyping. Currently, diarrhea-causing E. coli are divided into five virotypes enterotoxigenic E. coli (ETEC), enteropathogenic E. coli (EPEC), entero-hemorrhagic E. coli (EHEC), enteroinvasive E. coli (EIEC) and enteroaggregative E. coli (EAEC). The various properties of these E. coli virotypes are presented in Table 1. Enterotoxigenic E. coli (ETEC) produce a diarrheal disease similar to that caused by Vibrio cho-lerae, although less severe. Nonetheless, ETEC diarrhea when combined with...

Specific Therapy of Acute Diarrhea

-Erythromycin 250 mg PO qid for 5-10 days OR -Azithromycin (Zithromax) 500 mg PO x 1, then 250 mg PO qd x 4 OR -Ciprofloxacin (Cipro) 500 mg PO bid for 5 days. Enterotoxic Enteroinvasive E coli (Travelers Diarrhea) -Ciprofloxacin (Cipro) 500 mg PO bid for 5-7 days OR -Trimethoprim SMX (Bactrim), one DS tab PO bid for 5-7 days. Antibiotic-Associated and Pseudomembranous Colitis (Clostridium difficile)

The Pervasiveness of Diarrhea Implications for Epidemiology

The body has a relatively limited range of responses to a much broader range of diseases fever, pain, vomiting, rash, seizures, difficulty breathing, and so forth. The term diarrheal disease describes one symptom that can be produced by a number of causes ranging from viruses to bacteria, parasites, malabsorption of lactose, or immune deficiencies. And diarrhea is no simple label. An extensive anthropological literature (e.g., Kendall 1990, Nichter 1993, Scrimshaw and Hurtado 1988, Weiss 1988) documents the broad variety of terms used to describe and categorize diarrheal diseases around the world and efforts to use these terms in prevention programs. Depending on the locale, caretakers pay attention to and categorize diarrhea using color and form of stools, age of the child, presence of a variety of supernatural causes, and other clues. More than two and a half million children under the age of five succumb to diarrhea and dehydration each year (Kosek et al. 2003). Most cases of...

Clinical Types and Etiology of Diarrhea

Since nutritional costs of diarrhea vary by etiology and clinical type, a discussion of different types of diarrhea is pertinent. Diarrheal episodes can be classified based on clinical presentation as inflammatory (dysentery) and noninflammatory (nondysentery) diarrhea. Therefore, the clinical presentation of diar-rheal illnesses may suggest a causative diagnosis. Diar-rheal episodes can also be classified based on duration as acute (14 days) diarrhea. The diarrhea is generally due to either infectious or noninfectious causes. This article focuses on infectious diarrhea. Pathogens that cause infectious diarrhea include bacteria, viruses, and parasites (Table 1). Most diarrheal episodes are acute. Occasionally, they become prolonged, leading to a vicious cycle of malabsorption, malnutrition, and failure to thrive. Noninfectious diarrhea tends to be persistent because it is often due to a chronic health problem. However, most persistent diarrhea is due to infection or is a sequeale of...

Diarrhea Malnutrition Interaction

Diarrheal illnesses are more common, last longer, are clinically more severe, and are more likely to have a fatal outcome for impoverished children in less developed countries because of a complex interaction between infection, protein-energy malnutrition, and micronutrient deficiencies. Diarrhea and malnutrition have a bidirectional relationship in which malnutrition increases the incidence and duration of diarrhea and, conversely, diarrhea exerts a negative effect on nutritional status. Malnourished children have defects in cell-mediated immune functions and a decrease in IgA-containing cells in the jejunal mucosa. Malnutrition produces morphological and functional changes in virtually all organs. Changes in the intestine include thinning of the gut epithelium, marked flattening and broadening of villi, extensive infiltration of the lamina propria, and diminished secretion of gastric acid. These changes lead to an increased risk of diarrhea. The risk of developing diarrhea may be...

TABLE 771 Extraintestinal Manifestations of Inflammatory Bowel Disease

Hepatobiliary disease is common in patients with inflammatory bowel disease and includes pericholangitis, chronic active hepatitis, primary sclerosing cholangitis, and cholangiocarcinoma. Gallstones are detected in up to 33 percent of patients with Crohn's disease. Ihe incidence of acute and chronic pancreatitis is increased in patients with Crohn's disease and ulcerative colitis.

Irritable bowel syndrome

Irritable bowel syndrome (IBS) is a widespread functional gastrointestinal disorder that affects 10-20 of the Western population (Drossman et al., 2002). The main clinical features of IBS include abdominal pain, bloating, flatulence and variable bowel habit. Current treatments for IBS are regarded as relatively ineffective. The pathophysiology of IBS remains unknown, but there is evidence that at least in part of the patients an imbalanced intestinal microbiota is associated with the onset of disease. electrophoresis (PCR-DGGE), has shown more temporal instability in the predominant bacterial populations of IBS patients compared to healthy controls (Matto et al., 2005). The same kind of general instability of the predominant microbiota combined with changes in the clostridial population was found to be typical for IBS in a study by Maukonen et al. (2006). An increased formation of colonic hydrogen (King et al., 1998) and an abnormal pattern of short-chain fatty acids (Treem et al.,...

Food Intake during Diarrhea

Food intake during diarrhea is often reduced due to poor appetite (anorexia), vomiting, deliberate withholding of food, and inappropriate dietary supplementation with diluted food items. Diarrhea can also be associated with fever. Both fever and anorexia have clear effects on the nutritional status of the host. An increase in body temperature of 1 C causes an increase in the basal metabolic rate of 12-23 . Although the reason for anorexia is not clear, its effect can be important. In a controlled study in Bangladesh, 41 hospitalized children with acute diarrhea consumed only about half of the total calories consumed by healthy children despite an educational intervention.

TABLE 1234 Causes of Diarrhea

Treatment of diarrhea will vary depending on cause. A suspicion of Hirschsprung or Crohn's disease warrants surgical consultation. Malabsorption, hemolytic-uremic syndrome, cystic fibrosis, or persistent diarrhea with weight loss and failure to thrive warrants pediatric consultation. Other causes may only require 24 h of rehydration solution and avoiding fatty or high-carbohydrate-containing foods for 2 or 3 days. Stool cultures are warranted in children with bloody diarrhea, diarrhea for more than 5 days, or toxic appearance or to track an epidemic form of illness.

Global Burden of Diarrhea and Epidemiological Trends

Diarrheal illnesses in young children are among the leading causes of morbidity and mortality in developing countries. Diarrhea is an important cause of morbidity in developed countries as well. In developing countries, children younger than 5 years old suffer 3-10 episodes of diarrhea per year, whereas in developed countries young children have on average 1 or 2 diarrheal episodes per year. The advent of oral rehydration therapy (ORT) and its use in the past three decades have dramatically reduced the case fatality rate for diarrhea. However, globally the estimated 3 billion annual episodes of diarrhea account for approximately 2 million deaths in children younger than 5 years old. The majority of diarrhea-related mortality occurs in developing countries and the highest rates of diarrhea occur among infants with malnutrition. The case fatality rate is highest among children 6 months to 1 year old. The primary reason is that for most children Although dehydration is the most direct...

Irritable Bowel Syndrome IBS

IBS is manifested in about 8 to 19 of the population and is associated with symptoms of abdominal pain, constipation and or diarrhea, and gas. About 85 of those with IBS have an increase in symptoms when experiencing stress. Therefore, the treatment of choice is relaxation therapy and research has shown that relaxation therapy combined with finger temperature biofeedback is the most effective. Although more direct forms of feedback have been tried, such as colonic motil-ity sounds, rectal feedback using rectal balloons, and feedback of the electrical activity of the lower gut, these techniques have not proven effective and at this time are not used in general practice. The biofeedback is usually combined with client education about the relationship between stress and symptoms.

Gastrointestinal Disorders

Mentally retarded individuals frequently present to the ED with gastrointestinal bleeding and it is the most common reason for hospital admission. In 70 percent of cases studied, erosive esophagitis was the diagnosis.20 A large number of developmentally disabled individuals also have ulcers, usually duodenal. Such conditions respond well to aggressive treatment with proton pump inhibitors and H 2 blockers. In addition, perhaps as many as 40 percent of mentally retarded individuals have a neurogenic bowel with resulting constipation, overflow diarrhea, and infrequent rectal tears. It is important to carefully evaluate for constipation. Treatment must include both acute and long-term measures, including establishment of a regular stool pattern and provision of adequate fluid and fiber intake. It is also important to determine whether the patient has pica and may have developed bezoars. About 10 percent of individuals with pica will develop intestinal obstruction. 21 While surgery is...

Vomiting Diarrhea And Constipation

Diarrhea Vomiting, diarrhea, and constipation are among the most common complaints of patients presenting to emergency departments. Gastrointestinal dysfunction is the final common pathway for a variety of diseases. Therefore, many patients complaining of vomiting, diarrhea, or constipation have a cause for their symptoms remote from the gastrointestinal system. Emergency physicians must consider not only the gastrointestinal emergencies manifested as vomiting, diarrhea, or constipation but also the nongastrointestinal emergencies manifested as gastrointestinal dysfunction. An important and often difficult step in the evaluation of patients with vomiting, diarrhea, or constipation is having the patient define the illness. The layperson's definitions of vomiting, diarrhea, and constipation often differ tremendously from the medical definitions. For example, patients often say vomiting when they really mean coughing up sputum. Some patients complain of constipation and mean that they...

Toddler Diarrhea

One troublesome diet-related problem occurring in preschool children is 'toddler diarrhea.' Young children are susceptible to gastrointestinal infections because of immature, inexperienced immune systems and poor hygiene from their habit of 'mouthing' almost everything they handle. Children are also prone to develop loose stools in response to minor nongastrointestinal infections. However, some children suffer frequent episodes of loose watery stools with or without increased stool frequency and without evidence of infection. These episodes of diarrhea may last weeks or months. Since it may be difficult to distinguish this diarrhea from other significant gastrointestinal pathology, affected children may be subjected to a lot of unrewarding clinical investigation. Children with toddler diarrhea usually grow normally, unlike most children with significant gastrointestinal pathology. Typically, they are untroubled by their diarrhea although their parents are understandably very concerned...

Diarrhea

Diarrhea is defined as a decrease in stool consistency and or an increase in stool frequency and volume. It results from a complex interplay between colonic epithelial cell function, luminal factors, intestinal motility, and other factors. Mechanisms of diarrhea can also be viewed from the perspective of absorptive capacity of the small intestine and colon. Of the 8-101 of fluid processed by the small and large intestines daily (composed of intake as well as gastrointestinal secretions), the smaller intestine absorbs 80-90 of the net load. The normal adult colon absorbs approximately 1 l of fluid per day but has a capacity to absorb 3 or 41 per day diarrhea results when this threshold is exceeded. From a pathophysiological perspective, four mechanisms of diarrhea are traditionally described osmotic, secretory, motility, and inflammatory. A degree of overlap occurs between these different types of diarrhea. Osmotic diarrhea occurs when the failure to absorb a solute (usually a...

Antidiarrheals

A number of antidiarrheal compounds, drugs that generally act by prolonging intestinal transit time through an effect on bowel motility, have been evaluated in clinical trials. These agents include difenoxin, diphenoxylate-atropine,51 lidamidine,52,53 loperamide,53-57 and loperamide-oxide.55-59 These trials of patients with acute diarrhea have generally been conducted among general practice networks. Trials evaluating loperamide or loperamide oxide have generally used time to first relief and time to complete relief as endpoints, the latter indicating the time between taking the loading dose and the start of the 24-hour period in which no watery or loose stools were passed. The majority of these reports have indicated a benefit of antidiarrheals on symptoms. Some have reported the benefit being experienced in the early phase of the illness, with no impact on total duration of symptoms. The most common adverse effect of these medications was constipation. Two RCTs found that...

Other Nutritional Diseases

In many countries of the world, HIV infection and acquired immunodeficiency syndrome (AIDS) has become one of the leading causes of undernutrition and cachexia, especially in younger patients. Indeed, many of the syndromes and consequences of protein-energy malnutrition are also seen in AIDS cachexia, such as frequent respiratory and other infections, diarrhea, malabsorption, and rashes. Weight loss is an AIDS-defining symptom, and weight loss of a third of usual weight usually signifies terminal illness. Fortunately, new generations of protease inhibitors and other medications have dramatically slowed the progression of HIV infection in many patients, as well as reducing the vertical transmission rate. Indeed, some studies have suggested that multivitamin supplementation of pregnant mothers may itself reduce vertical transmission rates in developing countries where antivirals are difficult to obtain. Proper attention to nutrition, with early enteral energy and micronutrient...

Characteristics of the organism and its antigens

E. histolytica is a protozoan parasite that lives in the large bowel (probably mostly adhering to the mucosa) as an ameboid and phagocytic trophozoite dividing by binary fission. Responding to unknown stimuli, trophozoites may develop into resistant cysts which are shed in the feces and, by being ingested orally, are responsible for parasite transmission. Pathology occurs when trophozoites penetrate the mucosa causing ulceration and bloody diarrhea (amebic dysentery, AD) less frequently dissemination to the liver takes place with, ultimately, extensive tissue destruction (hepatic amebiasis or amebic liver abscess, ALA). ALA is about seven times less

Modulation Of 5fu Activation Pathways

Intravenous infusions of uridine must be performed via a central venous catheter in order to avoid phlebitis at the site of administration. Therefore more convenient ways of administering the drug have been explored. Preclinical data showed that with oral administration of uridine to mice it was possible to obtain plasma concentrations of approx 100 M (188) that are sufficient to reduce 5-FU toxicity (189). Similar pharmacokinetic data have been obtained in humans (190) when uridine was administered repeatedly, the dose had to be lowered to 5 g m2 every 6 h due to the occurrence of diarrhea. Using this schedule the myelosup-pression of 5-FU was reduced (191). Initial studies have been performed with UDPG administration to patients plasma uridine peak values were 40-60 M, and a concentration of 20-25 M was still present 8 h after the second dose (unpublished results). The studies could however not be continued. Another prodrug, PN401 (an acytelated prodrug of uridine), has also been...

Oversimplification and Other Dangers

On the other hand, not all systems will be easily classifiable because some systems explicitly accept both aspects of a contrast and focus on either one depending on the illness or condition in question. Take, for example, the old intrusion versus extrusion contrast (Clements, 1932). This model contrasts the bodily intrusion of substances or essences to the extrusion of such as the cause of illness. Extrusion would include, for example, soul loss, or the loss of blood, or even the non-absorption or leaching of nutrients, as with diarrhea. In intrusion-caused illnesses, on the other hand, noxious substances (e.g., poisons, germs, evil spirits) pierce or infiltrate the body's barriers. Illness due to bleeding and illness due to soul loss are classified together in this model as extrusion-caused germs and evil spirits are both categorized as intrusive. However, treatments for germ-caused or spirit-caused illness can differ. In any case, one medical system can allow for both intrusion and...

Pathogenesis And Immunity

HuAst have been detected in all countries where they have been sought and thus have a worldwide distribution. In temperate countries, HuAst infection peaks in winter usually 4-6 weeks prior to the rotavirus peaks. 23 In general, HuAst diarrhea is predominantly a disease of infants with an age-specific incidence of 0.38 for those under 6 months and 0.40 for those aged 6-12 months. 24 However, further episodes of infection with different astrovirus serotypes do occur subsequently. These are usually milder than the first infection. Astrovirus is the second or third most important cause of diarrheal disease in children being responsible for 5-10 of cases in hospital-based studies and for 10-25 of cases in community-based studies. 25 Globally, serotype 1 is most frequently detected. 22,26-28 Recently, HuAst serotype 3 has been associated with higher stool viral levels and increased incidence of persistent diarrhea. 16 Outbreaks of astrovirus infection have been described involving the...

Bacteriophage Therapy

Infectious disease offers another attractive alternative to antimicrobials, because they are highly specific to a bacterial species, are nontoxic to the animal host, and can increase in titre as they infect and kill their target bacteria. 14 In experimentally infected animals, bacte-riophages have been shown to prevent and treat E. coli induced diarrhea in calves, piglets, and lambs, and to prevent E. coli respiratory infections in broiler chick-ens. 15,16

Introduction And Definition Of Issues

Van Schothorst (1998) suggested that hazard characterization might be better termed impact characterization. The impact can vary from mild (simple acute diarrhea) to severe (chronic illness or death), depending largely on the susceptibility of the person exposed. To accommodate the many assumptions associated with impact characterizations, a worst-case scenario often is used to estimate the risk presented by a particular pathogen in a specific food. Van Schothorst points out that assumptions and uncertainties of hazard characterization ultimately can lead to an unreliable risk assessment, as well as credibility and liability problems.

Racialethnic or socioeconomic status and foodborne illnesses

Because data on foodborne incidence in racial ethnic groups are sparse and in socioeconomic groups are unavailable, incidence of diarrhea is useful as a surrogate for cases of foodborne illnesses. Health insurance coverage can indicate which demographic groups are likely to seek medical care for gastroenteritis. The percentage of persons in the United States without health care insurance in 2002 was 16.1 and 15.4 had public health plan coverage most of those without health care insurance were categorized in the poor or near poor socioeconomic strata (Cohen et al., 2005). Herikstad et al. (2002) reported incidence of diarrhea by demographic descriptors and included data on medical care, which provides some insight into which members of various racial ethnic groups and socioeconomic strata are seeking medical care for foodborne illnesses.

Differences in foodborne illness by demographic group

Hispanics reported more cases of diarrhea, but Asians were significantly more likely to seek medical advice for their illness (Herikstad et al., 2002). African Americans were hospitalized for diarrhea more often than other racial ethnic groups. Females have been reported to have more cases of diarrhea and were significantly more likely to be hospitalized for their illness. Foodborne illnesses reported by FoodNet in 2003 were generally more common in Caucasians notable differences from this generalization were the incidences for Shigella and Yersinia, where high incidence was reported for both groups for Shigella and for Yersinia and African Americans (FoodNet, 2005).

TABLE 564 Standardized Cardiac Biopsy Grading System

Untreated acute cardiac rejection results in progressive myocardial dysfunction. Diastolic dysfunction occurs first, followed by systolic dysfunction as the degree of myocardial damage increases. Diastolic dysfunction causes symptoms of congestive heart failure with shortness of breath, fatigue, and malaise. Progressive myocardial dysfunction results in low-output syndrome, with symptoms including nausea, vomiting, and or diarrhea. Severe rejection leads to hypotension and circulatory collapse. Symptoms of rejection may be mistakenly attributed to a viral syndrome or gastroenteritis. Physical examination reveals signs of heart failure, including distended neck veins, an S 3 gallop on cardiac auscultation, rales on pulmonary auscultation, and occasionally the presence of ascites or peripheral edema. Chest x-rays show enlargement of the cardiac silhouette and pulmonary vascular congestion. ECGs may demonstrate in addition to dysrhythmias a decrease in amplitude and widening of the QRS...

Discovery And Impact Of C Difficile

C. difficile is an anaerobic, spore-forming, gram-positive rod. This bacterial species owes its name to the difficult circumstances of its first isolation in 1935 from the intestinal flora of healthy neonates. 1 In the laboratory conditions of those days, its slow growth and requirement for culture under anaerobic atmosphere posed some difficulties now essentially resolved by modern techniques developed for the cultivation of anaerobes. Colonization most likely occurs by fecal-oral transmission, and ingested spores of C. difficile can survive the passage through gastric acid and germinate into the colon. In the preantibiotic era, pseudomembranous colitis was a rare complication of intraabdominal surgery. 2 However, this life-threatening condition became more frequent with the increased use of antibiotics and, in 1978, C. difficile was identified as the etiologic agent of pseudomembranous colitis. 3 This bacterium is now recognized as the cause of approximately 20 of all cases of...

Pathophysiology And Genomics Of Virulence Determinants

C. difficile's main virulence determinants are two exotoxins toxins A and B. In animal models, toxin A was shown to be an enterotoxin inducing both diarrhea and inflammation. By contrast, in tissue culture, toxin B was much more cytotoxic than toxin A and was designated as cytotoxin. The genes for toxin A (tcdA) and toxin B (tcdB) are highly homologous, and the carboxy-terminal regions of both toxins encode a glucosyltransferase specific for the host small GTP-binding proteins of the Rho family. Glucosylation of these small GTP-binding proteins leads to a disorganization of the cytoskeleton and provokes cell death. The toxins also trigger inflammatory response and fluid secretion. Epithelial damages such as necrosis and ulceration can eventually lead to the formation of the characteristic pseudomembranes observed in pseudomem-branous colitis. 5 The level of humoral response against C. difficile toxins appears to confer a certain amount of protection to the host, which may explain why...

Clinical Features And Treatment

C. difficile infection has been shown to cause a wide spectrum of intestinal symptoms including mild to severe diarrhea, chronic diarrhea, colitis, pseudomembranous colitis, and toxic megacolon. 2 Although C. difficile is occasionally isolated in extraintestinal pathologies, these cases are infrequent and usually involve a polymicrobial infection. Typically, C. difficile-associated diarrhea appears within 1-2 weeks following the administration of an antibiotic. Watery stools may contain mucus and sometimes blood. Patients may present fever, abdominal cramps, and leukocytosis. However, even severe cases may present no diarrhea or just loose stools. Radiographic evidence of distended colon can indicate toxic megacolon. Prolonged or severe disease can be complicated by dehydration problems, bowel perforation, and death. Diagnosis is based on history of recent or ongoing antibiotherapy, appearance of diarrhea or other symptom of colitis, and demonstration of infection by toxigenic C....

Laboratory Diagnostic Approaches

Because many hospitalized patients are asymptomatic carriers, testing patients for C. difficle infection is only recommended if diarrheal stools are present. 12 Laboratory diagnosis is performed by detection of toxigenic C. difficile by culture, immunodetection of toxin, or cytotoxicity assay. 18 Enzyme immunoassays (EIAs) for toxin detection are now widely available from several manufacturers. These tests are rapid and simple to perform directly from stool samples. Most assays use monoclonal antibodies against toxin A. However, because some clinical isolates have been shown to produce only toxin B and still cause the disease, more recent EIAs combine the detection of both toxins A and B. However, none of the EIAs is as sensitive as the cytotoxicity assay. 19 This is why in the event that EIA testing is negative and diarrhea persists, it is recommended to repeat EIA testing on a second sample and even a third sample from patients suspected of infection by toxigenic C. difficile. 5

Cpe And Gi Disease Disease Summary

CPE-positive strains cause C. perfringens type A food poisoning, which currently ranks as the third most common cause of food poisoning in the United States. 12 In addition, enterotoxin-producing C. perfringens is an important etiological agent of non-food-borne human GI illnesses such as antibiotic-associated diarrhea (AAD) and sporadic diarrhea (SD). 13 The symptoms of CPE-related illnesses range from acute diarrhea and abdominal cramping (C. perfringens type A food poisoning) to more severe and chronic diarrhea (AAD and SD). C. perfringens type A food poisoning is typically self-limiting (the diarrhea removes the enterotoxin from the GI tract), so only the replenishment of fluids and electrolytes is required for treatment. Patients suffering from AAD or

Multidrug Resistant Tuberculosis

The vast majority of MDR TB outbreaks have been in the HIV population. Clinically, the most common pattern is resistance to isoniazid and rifampin. 4 Available data suggest no difference in isoniazid resistance among those patients with or without HIV. Rifampin monoresistant tuberculosis has become a problem, especially in those with AIDS.10 Cases with rifampin monoresistance were more commonly seen in patients who had previously had tuberculosis, a history of diarrhea, rifabutin use, or antifungal therapy.10

Nonresponsive Celiac Disease

In patients whose serologic tests have returned to normal and where a careful dietary review, including a detailed food record, does not reveal any potential source of gluten contamination, the occurrence of a second associated disease or a complication of celiac disease must be considered. A common associated disorder would be microscopic colitis, either lymphocytic or collagenous. Typically, these patients will have watery diarrhea whereas symptoms related to malabsorption such as weight loss, bloating, and steatorrhea will have resolved. The patient will continue to have watery diarrhea or may, indeed, develop watery diarrhea while on a gluten-free diet. The taking of biopsies from the colon can readily identify this condition. Whilst in some patients adhering to a strict gluten-free diet may improve the colitis, in many circumstances, it does not or it has not sufficed. The use of empiric therapy such as Pepto-Bismol , loperamide, or, in some circumstances, delayed release...

Causes of Lower Gastrointestinal Bleeding

OTHER ETIOLOGIES Numerous other lesions may result in lower GI hemorrhage. Although carcinoma and hemorrhoids are relatively common causes of bleeding, massive hemorrhage is unusual. Similarly, inflammatory bowel disease, polyps, and infectious gastroenteritis rarely cause severe bleeding. Finally, Meckel diverticulum is an unusual but important etiology to keep in mind.

Infections and Enteric Parasites

These infections can results in vomiting, diarrhea, and abdominal pain, in addition to systemic effects such as fever. Clinical symptoms vary according to pathogen. Bacteria can be classified based on their pathological mechanism (Table 1) as well as by their site of activity and the nature of clinical signs and symptoms manifest. Signs and symptoms vary significantly by pathogen and age at presentation, with some forms presenting as crampy abdominal pain with watery diarrhea of relatively short duration, bloody diarrhea, systemic signs and symptoms of inflammation with frank sepsis, and shock. Common bacterial, viral, and parasitic infections involving the colon are outlined in Tables 2 and 3.

Entamoeba histolytica

The World Health Organization estimates 50 million infections and 100,000 deaths per year (Anonymous, 1997). The clinical presentation of E. histolytica can be asymptomatic, symptomatic without tissue invasion, and symptomatic with tissue invasion. Asymptomatic infection may be related to two genetically distinct invasive and noninvasive strains of E. histolytica (Zaki and Clark, 2001). Approximately 10 of infected individuals will have clinical symptoms such as dysentery, colitis, or in few instances, amebomas. Amebomas are localized granulomatous tissues with tumor-like lesions resulting from chronic ulceration. They may be mistaken for malignancy. Amoebic dysentery is characterized by diarrhea with cramping, lower abdominal pain, low fever, and the presence of blood and mucus in feces. Ulcers start at the surface of the epithelium that deepens into a classic flask-shaped ulcer.

Identifying Types of Dehydration

It should be noted that hypotonic dehydration is the result of treating isotonic dehydration with nonelectrolyte-containing fluids and can lead to a potentially dangerous condition know as hyponatremia (low blood sodium). This may be a particular problem in the case of 'overzealous hydrators' such as athletes who overcompensate for sweat losses. Hypotonic dehydration is also seen in infants and children who may be afflicted with gastrointestinal disturbances such as diarrhea, stomach flu, or acute gastroenteritis if water alone is used to hydrate. The American Academy of Pediatrics has published guidelines for oral rehy-dration therapy of infants and children younger than 5 years old with acute gastroenteritis. Table 3 gives the Academy's guidelines for the other than sweating Gastrointestinal fluid loss vomiting, diarrhea Blood electrolytes normal Can develop when isotonic dehydration is treated with only water Hypotonic dehydration can occur anytime the body sodium loss exceeds...

Adverse Effects of Non Oral Enteral Feeding

Regardless of delivery route, diarrhea and aspiration are the two most common problems that can occur when tube feeding is begun. In hospital patients, diarrhea and often incontinence occur in 25 percent of patients on general units and as many as 65 percent of patients in critical care units. The feeding solutions themselves are responsible for many of these cases. The problem is likely less in nursing homes and patients cared for at home. In most cases, instilling feeding solutions into the stomach, duodenum, or jejunum probably has little impact on the likelihood of aspiration, although reports are conflicting. Upper airway secretions are a more important variable in the risk for aspiration.

Treating Different Types of Dehydration

In the majority of simple, nonsevere dehydration cases, plain water is an adequate rehydration solution. However, there are instances (e.g., children younger than 5 years of age dehydrated by vomiting and diarrhea) when water containing sodium and potassium is the proper hydrating agent. The most effective way of preventing and treating mild to moderate dehydration in infants and children with acute diarrhea is the oral administration of oral rehydration solutions (ORSs). There are a number of commercially available ORSs. These solutions are designed to replace fluid and electrolytes when both water and food intake have been restricted or compromised by diarrheal disease. The World Health Organization recommends the ORS shown in Table 4 for individuals afflicted with diarrheal disease and vomiting. Oral modes of fluid and electrolyte administration are always preferred in mild (3-5 ) to moderate (6-9 ) dehydration however, intravenous fluids may be required in cases of severe...

Characteristics of the organisms and their antigens

Ties and immunological characteristics, classification of these toxins based on their pharmacologic properties and cellular targets is far from complete. For the purpose of this review Clostridia toxins will be categorized according to the diseases they produce into four groups 1) neurotoxins, represented primarily by C. tetani and C. botulinum which are associated with tetanus and botulism in humans 2) entero-toxins, represented by C. perfringens enterotoxin produced by some strains of C. perfringens type A which mediate acute food poisoning, C. perfringens e and i toxins causing entertoxemia in sheep, calves, lambs and guinea pigs, and C. sordellii hemorrhagic toxin which is associated with diarrhea in cattle and sheep 3) histotoxins or cytolytic toxins, represented by some of the C. perfringens toxins that are associated with gas gangrene and anaerobic cellulitis, and C. sordellii lethal toxin (LT), one of the causes of gas gangrene and 4) cytoskeleton-altering toxins, represented...

Evasive strategies by the organism

Clostridia have devised many ways to enter the host and cause disease. In the case of gas gangrene and wound infections C. perfringens enters the host through traumatic or surgical wound often taking advantage of poor blood supply in the wound area. Once Clostridia grow they release their toxins and cause disease. In C. difficile-associated colitis the bacteria multiply when the normal bowel flora is disrupted by antibiotics. C. difficile then releases its toxins which target intestinal epithelial cells and cause diarrhea and colonic inflammation. In the case of botulism, however, the organism does not grow in the host but the disease is caused by ingestion of C. botulinum toxins present in contaminated food.

Immune responses of the host and vaccines

Amount of toxins required to produce disease, which may be inadequate to produce an immunogenic response. Despite the absence of systemic immunity following disease, toxoid immunization against tetanus provides immunity for up to 5 years. Passive immunization with tetanus immunoglobulin is also of great value in suspected cases. An antibotulinum toxin antibody has also been available for laboratory workers, and intravenous treatment with gamma globulin preparations containing a high-titer antibody to C. difficile toxin was effective in treating patients with relapsing C. difficile diarrhea.

Clinical Features

Pseudomembranous colitis results in a spectrum of clinical manifestations that vary from frequent, mucoid, watery stools to a toxic picture that includes profuse diarrhea (20 to 30 stools per day), crampy abdominal pain, fever, leukocytosis, dehydration, and hypovolemia. Examination of the stool may reveal the presence of fecal leukocytes. These are not generally found in more benign forms of antibiotic-induced diarrhea. Complications of the disease include severe electrolyte imbalance, hypotension, and anasarca from decreased serum albumin. Rarely, toxic megacolon or colonic perforation may occur in patients with pseudomembranous colitis. The disease typically begins 7 to 10 days after the institution of antibiotic therapy, although in some cases symptoms may be noted within a few days or up to 8 weeks after the antibiotic is discontinued. C. difficile colitis has now been established as a nosocomial infection in hospitals.

Chapter References

Russel M, Stockbrugger RW Epidemiology of inflammatory bowel disease An update. Scand J Gastroenterol 31 417, 1996. 2. Walker-Smith JA, Savage MO Effects of inflammatory bowel disease on growth Growth matters. Kabi Pharmacia 12 10, 1993. 3. Hebbar M, Wattel E, Mastrini S, et al Association between myelodysplastic syndromes and inflammatory bowel diseases Report of seven new cases and review of the literature. Leukemia 11 2188, 1997. 4. Freeman HJ Osteomyelitis and osteonecrosis in inflammatory bowel disease. Can J Gastroenterol 11 601, 1997. 8. Farraye FA, Peppercorn MA Inflammatory bowel disease Advances in the management of ulcerative colitis and Crohn's disease. Consultant 28 39, 46-7, 1988. 17. Demaio J, Bartlett JG Update on diagnosis of Clostridium difficile associated diarrhea. Curr Clin Top Infect Dis 15 97, 1995. 18. Gerding DN, Johnson S, Peterson LR, et al Clostridium difficile associated diarrhea and colitis. Infect Control Hosp Epidemiol 16 459, 1995. 19. Teasley DG,...

Travel as a risk factor for foodborne illness

Gastroenteritis is a worldwide phenomenon shared by developing and developed countries. Estimating the contribution of foodborne illnesses to the total diarrheal burden is greatly complicated by the lack of medical or surveillance systems to track illnesses (Flint et al., 2005). Incidence rates by specific pathogens vary by country and could be influenced by diet and the possibility of immunity among indigenous populations. A comparison of incidence of foodborne illness in England and the United States shows higher population rates in the United States for illnesses in general (Adak et al., 2002). However, both countries have high incidence of Escherichia coli, Salmonella, Yersinia, and Norovirus infections, and England and Wales reported higher incidence of Aeromonas and Rotavirus infections. Denmark reports increased mortality from Salmonella, Campylobacter, Yersinia, and Shigella (Helms et al., 2003). There are also literature reports on incidence of infection from Salmonella in...

TABLE 792 World Health Organization Recipe for Oral Rehydration Therapy

Dietary Restrictions Patients should be counseled to avoid caffeine, sorbitol-containing chewing gum, lactose, and raw fruits until after the diarrhea subsides. Disposition Patients with the noninfectious emergencies outlined above warrant hospitalization. Most other patients can be discharged home safely. When deciding whether to admit a patient with diarrhea, conservatism should be the rule with the young and the elderly. They do have higher morbidity and mortality rates and should be evaluated with a careful eye. Regardless of age, any toxic patient should be admitted, as should any patient who cannot convincingly comply with oral rehydration guidelines. Upon discharge, patients with infectious diarrhea should be counseled on limiting the spread of disease through the use of judicious hand washing. Work excuses should be given liberally to patients employed in the food, day care, and health care industries.

Hivaids threatening health and the economy and viability of nations

In CD4+T helper cell counts, from normal levels between 500 and 1600, to 350 when anti-retrovirals are recommended (www.thebody.com nmai tcell.htm). Diarrhea ( 200 g day of adult stool and frequent liquid stools) is However, in secretory or osmotic diarrhea, there is a rapid loss of sodium, fluid and damage to the microvilli. Unless the patient is rehydrated, he she will die. In AIDS patients with a depleted immune response, the range of microbes that cause diarrhea is larger and the inoculum needed to induce the event is lower than in healthy subjects. Microbial overgrowth can occur in the intestine, leading to shock and other adverse outcomes. Chronic diarrhea causes severe wasting as appetite is lost and essential nutrients are not adsorbed. Death from AIDS often occurs with gastrointestinal infections and diarrhea, and indeed, many non-AIDS deaths are due to these infections. It has been estimated that a child dies every 15 seconds from diarrheal diseases (Fig. 6.1). Without...

Malabsorption of Nutrients

Malabsorption in diarrheal illness may result from the epithelial destruction by the pathogen. Diminished nutrient absorption often begins during acute diarrhea. At this time, the body is less able to absorb needed macronutrients, including fats and proteins, as well as some carbohydrates. This is most severe in undernourished children who suffer from persistent diarrhea due to damage to the gut epithelium. When the gut is damaged, food is not properly digested or absorbed. The causes of insufficient nutrient absorption include diminished concentration of bile acids, which are used for fat absorption damaged epithelial cells, which provide the absorptive surface on the bowel and a deficiency of disaccharides due to damaged microvilli, which normally produce the needed enzymes. In symptomatic rotavirus infection, the most common cause of acute severe diarheal illness worldwide, there is a 42 decrease in the absorption of nitrogen and fat, a 48 decrease in absorption of carbohydrates,...

Feeding during the Convalescent Period

The convalescent period is the recovery period for the body during which the child's diarrhea has stopped but the body has not yet fully recovered to its initial condition. During the first few weeks, the child's appetite will be returning and the child may consume up to twice as much as usual. This is a necessary part of the process because even if the child was fully fed during diarrhea, he or she most likely did not absorb sufficient nutrients. During this time, the child's nutritional state should return to at least the level before the child became ill. The desired energy intake ranges from 100 to 160J kg per day, which is achieved with a high-energy, low-bulk, and low-viscosity diet. This is needed for a catch-up growth period and rapid nutritional recovery.

Supplementation with Micronutrients

ORT reduces mortality from dehydrating diarrhea, but it does not decrease the duration of episodes or their consequences, such as malnutrition. In addition, adherence to recommendations regarding ORT in children is poor because caregivers want to reduce the duration of illness. This often leads to use of antibiotics and other treatment of no proven value. In addition, there are indications that knowledge and use of appropriate home therapies, including ORT, to manage diarrhea successfully may be declining in some countries. The limitations of ORT and continued high diarrhoeal morbidity, mortality, and associated malnutrition led to a search for adjunct therapies. Zinc and vitamin A are essential to repair the intestinal mucosa and boost immunological responses. These supplements should be given during periods of diarrhea.

Future consumer trends

Consumers must rely on the training and diligence of commercial food workers who have assumed the role of assuring the safety of foods during preparation. Safe storage of foods prepared away from home then transported to the point of consumption raises concerns that temperature abuse could lead to re-emergence of some types of low-incidence foodborne illnesses, such as Staphylococcus aureus or Bacillus cereus (Little et al., 2002). These researchers concluded that establishments where the manager had participated in food safety training have less food contamination than those without trained managers. Cohen et al. (2001) evaluated the efficacy of an in-house food safety training program and learned that success was dependent on the motivation of the workers to practice safe food handling behaviors. Workers in food establishments in England, most of whom (95 ) had received some type of food safety training, were surveyed regarding their food handling practices (Clayton et al., 2002)....

Mineral Needs Of Broilers

Supplemental sources of calcium include ground limestone and crushed marine shells. The limestone should be low in magnesium, as dolomitic limestones may cause diarrhea, although a certain amount can be tolerated. Oyster shell is similar in calcium content to ground limestone. Most phosphorus supplements also contain high levels of calcium that are highly digestible by chickens.

The challenge of delivering probiotics in dairy formulations

Probiotics are most often incorporated in yogurt and fermented milk, but other food lines are being developed and numerous products are sold in tablet, capsule, and powder forms. In the parts of the world where HIV AIDS is most prevalent, namely Africa and Asia, probiotic products are not widely available. However, many communities use fermentation as a means of food preparation, for example in Africa, where raw milk, koko, bushera, cassava, and togwa are fermented some of these have been reported to improve the nutritional quality, protein digestibility, and availability of amino acids 57 . Starter cultures differ amongst the regions. In India, lactococci and yeast are used to make yogurt 58 , while in other countries, it is L. delbrueckii subsp bulgaricus and Streptococcus thermophilus. None of these strains are true probiotics in the sense that they are designed to ferment the milk, not confer specific health benefits on the host. One study using Indian Dahi has shown a reduction...

E coli indigenous to the gastrointestinal tract

E. coli is a member of the indigenous (i.e. normal) microflora (400-500 species) present in the gastrointestinal tract of humans and animals. Indigenous E. coli differ from the pathogenic ETEC, EPEC, EHEC, EIEC and EAEC virotypes discussed above. The indigenous E. coli are not usually responsible for intestinal infection or diarrhea, but may translocate across the intestinal barrier to cause extraintestinal infections in other tissues and even bacteremia -septicemia. Consequently, indigenous E. coli are 'opportunistic' pathogens and can cause disease depending upon increased populations of E. coli in the intestines ('intestinal overgrowth') and predisposing host factors, such as compromised immune defenses and increased intestinal permeability. Thus, E. coli septicemia in debilitated patients probably originates from the patient's own gastrointestinal tract rather than from E. coli contamination from the environment, even if entering via wound sires.

Physical Examination

Clinical assessment of the severity of illness of young, febrile infants is, however, problematic. Young infants lack social skills, such as the social smile, and their ability to interact with examiners is limited. There is a report in the literature of an infant with group B streptococcal bacteremia who was judged by house staff and faculty to be clinically well.12 The absence of any diagnostic abnormalities in the medical history or on physical examination suggests the need for extensive laboratory tests to detect occult infection. These tests would include a complete blood count (CBC) and differential, erythrocyte sedimentation rate (ESR), blood culture, lumbar puncture, chest x-ray, urinalysis and culture, and a stool culture if there is a history of diarrhea, particularly if leukocytes are noted on a stool smear. Some authors also recommend a quantitative C-reactive protein as an index of serious bacterial infection. 1 d8 Urinary tract infections may not produce symptoms other...

TABLE 1123 Clinical Assessment of Severity of Dehydration

Contraindications to oral rehydration are severe vomiting or a required regimen of oral feedings. For the child with less than 5 percent dehydration, oral rehydration should be attempted. If the infant has been breast-fed, feeding should be continued and oral electrolyte-glucose solution given in addition until diarrhea subsides. If the infant has been fed a cow's-milk-based diet, feedings should be resumed slowly after initial feedings with oral rehydration solutions as tolerated, preferably with a lactose-free formula. Increased stool output may occur as feedings are increased, but a gradual increase of caloric intake over 4 or 5 days should avoid exacerbation of diarrhea. The total fluid intake of oral electrolyte solution and regular diet should be approximately 150 mL kg day. 2 2,22,23,24 and25

Hemodynamically Unstable Patients

Shunt-dependent lesions mandate immediate surgical referral for repair or palliation of the anatomic condition. It may be necessary to stabilize and restore some function to the shunt-dependent lesion while awaiting transport to a tertiary care facility. One method of providing this care is with the use of prostaglandin infusion to reopen the shunt pharmacologically. Prostaglandin E infusions are successful in reopening the ductus arteriosus in nearly 95 percent of such patients and may allow for less emergent repair of the underlying defect. It is infused at a rate of 0.05 to 0.1 pg kg min initially. If there is no improvement within several minutes, it is increased progressively in 0.2 pg kg min increments. The minimal effective dosage should be used, because of adverse effects that include fever, skin flushing, diarrhea, and periodic apnea. Intubation and ventilatory support are often necessary as well.

Clinical Significance

Migraine Cycle

Frequently, Balantidium infections can be asymptomatic however, severe dysentery similar to those with amoebiasis may be present. Symptoms include diarrhea or dysentery, tenesmus, nausea, vomiting, anorexia, and headache. Insomnia, muscular weakness, and weight loss have also been reported. Diarrhea may persist for weeks or months prior to development of dysentery. Fluid loss is similar to that observed in cholera or cryptosporidiosis. Symptomatic infections can occur, resulting in bouts of dysentery similar to amebiasis. Colitis caused by Balantidium is often indistinguishable from E. histolytica (Castro et al, 1983). Diarrhea, nausea, vomiting, headache, and anorexia are characteristic of balantidiasis. inflammatory vaginitis has been reported. Balantidium has been described in the urinary bladder of an infected individual (Knight, 1978a Ladas et al., 1989 Maleky, 1998). Pulmonary lesions can occur in immunocompromised patients without obvious contact with pigs, nor history of...

Graftversushost disease

Clinically, graft-versus-host disease can appear as one of two distinct forms. Acute graft-versus-host disease has its onset early following the infusion of donor immunocompetent cells and is characterized by the cytolytic destruction of the recipient epidermal cells, hepatocytes and gastrointestinal cells, producing a characteristic cutaneous erythroderma, elevation in hepatocellular enzymes and diarrhea. A high rate of fatality is found in both animals and humans with severe acute graft-versus-host disease due to the denudation of the gastrointestinal tract, epidermal sloughing, sepsis and bleeding. Individuals, who do not die from acute graft-versus-host disease, are at risk of developing chronic graft-versus-host disease, which has many similarities to autoimmune diseases, including sclerodermatous skin changes, the production of autoantibodies, etc. In model animal systems, graft-versus-host disease is usually produced by the infusion of homozygous donor immunocompetent cells...

Human graftversushost disease

Graft-versus-host disease has its major clinical significance in human bone marrow transplantation. Graft-versus-host disease is also seen following the infusion of nonirradiated allogeneic blood products into immunosuppressed recipients, including patients with primary cellular immunodeficiencies and cancer. Graft-versus-host disease due to infusion of histoincompatible immunocompetent cells usually results in the death of the recipient. Graft-versus-host disease that is usually seen following histocompatible bone marrow transplantation is much milder and usually does not result in the death of the patient if prophylactic anti-graft-versus-host disease drugs are given. When human bone marrow is transplanted, it usually contains 20-40 peripheral blood mononuclear cells, meaning that as many as 5-10 of the total transplanted cells are mature peripheral blood T lymphocytes. Following the transplantation of histocompatible human bone marrow, acute graft-versus-host disease is a frequent...

Molecular Characterization Of Giardia From Children And Animals

To characterize Giardia from humans and animals, fecal samples were obtained from six children with chronic recurrent diarrhea and abdominal pain, seven asymptomatic children, and three dogs. Controls were as follows G. intestinalis group A Portland M54878 group B Belgian U09491 Bris 91 Hepu 1279 L29192 and dog 6 AF199449. DNA isolation was performed according to the phenol-chloroform-isoamilic alcohol method. 20 The gene 16S ribosomal RNA (ssRNA) fragment of 290pb was amplified by PCR using forward primer 5'-CATCCGGTCGATCCTGCC-3' and the reverse primer 5'-AGTCGAACCCTEATTCTCCGCCAGG-3', under conditions previously described. 21 The amplification products were purified using Qinquick kit (Qiagen). Double-stranded DNA sequencing was performed using the ABl Prism Big Dye Terminator Cycle Sequencing Kit (Applied Biosystems) and a set of internal primers. Sequencing alignments of 16S rDNA was performed using clustal W, and a phylogenetic tree was designed using the neighbor-joining method...

TABLE 1222 Assessment of Dehydration

Bacteria that invade the mucosa of the terminal ileum and colon can cause dysentery, which is characterized by frequent bowel movements that contain blood, mucus, or pus. The diarrhea is often accompanied by fever, tenesmus, and painful defecation. Infants and children who have bloody or mucousy diarrhea after having received antibiotics may have antibiotic-associated pseudomembranous colitis due to infection with cytotoxigenic C. difficile. Infestations with Entamoeba histolytica may also cause dysentery. Table 122-3 lists the enteric infections that cause children to have bloody diarrhea.

Discharge Instructions

Infants and children who are not dehydrated or who have responded well to oral or IV hydration may be discharged with instructions to take ORS solutions and age-appropriate feedings. The family should be instructed to return to the emergency department or to their own physician if the child becomes unable or unwilling to drink the ORS solution, begins to vomit, has increased emesis, develops bilious emesis, or shows signs of dehydration, such as decreasing urine output or decreased tearing, or if there is a decrease in the child's level of activity or state of alertness. Infants and small children should be reevaluated within 24 h especially if they continue to have diarrhea. The family should be instructed to telephone their primary care provider and he or she should decide if a visit is necessary. If the family does not have a primary care physician, then the family should contact the emergency department.

Fluid Resuscitation

Appropriate fluid replacement should be instituted promptly. Water and electrolyte losses occur secondary to polyuria caused by the osmotic diuresis produced by glycosuria, hyperventilation, vomiting, and diarrhea. Dry mucous membranes, poor skin turgor, and orthostatic hypotension in the older child are the most accurate clinical indications of dehydration. Virtually all patients with DKA are at least 5 to 10 percent dehydrated and require both maintenance and replacement fluid therapy. However, fluid resuscitation that is too aggressive can result in cerebral edema, the most lethal complication of DKA. For initial rehydration, 10 to 20 mL kg h of 0.9 NS solution should be given for the first 1 to 2 h of resuscitation to establish adequate vascular volume and improve tissue perfusion. If signs of shock are present, a 20 mL kg bolus of 0.9 normal saline solution should be given and may need to be repeated if dehydration and shock are severe. However, for the majority of patients, the...

Table 106 Complications of Diverticular Disease

Some sort of change in bowel habits is almost always present, usually diarrhea. On physical examination, left lower quadrant tenderness is expected often with associated mass effect or focal peritoneal signs. The presence of diffuse peritoneal signs or free air on plain films indicates free perforation, and no further diagnostic workup is necessary. Otherwise, contrast CT is the study of choice to help triage patients toward medical or surgical management.

Other Organisms Shigella

Shigella requires a very low dose to cause infection and does not grow very well in food. Thus, it is more commonly spread case to case, especially among kindergarten and primary school children. Affected patients may excrete the organisms for weeks. Nevertheless, some large and important outbreaks have been caused by food contaminated by sewage-polluted water or food handlers. In 1995, an extensive S. sonnei outbreak caused by lettuce imported from Spain affected people in many countries in northern Europe. In another outbreak caused by shrimp, infection was transmitted by a food handler who mixed the shrimp by hand with mayonnaise and tomato sauce. The incubation period is 24-48 h, and although bloody or mucoid diarrhea

Vibrio parahaemolyticus

Like V. cho erae (and several other aquatic organisms described later), V. parahaemo yticus is an aquatic organism that thrives in shallow coastal waters. Deep-sea fish do not tend to harbor the organism and usually become contaminated in fish markets. Precooked frozen shrimp may be contaminated and cause FP if served without further cooking, as in a seafood cocktail. Vibrio parahaemo yticus FP is associated with raw, undercooked, or contaminated seafood and is especially common in Japan and probably other countries in which seafood is a staple of the diet. Contamination from raw to cooked seafood is a common cause. The incidence of V. parahaemo yticus FP has increased in many Asian countries and the United States since 1996, and this is thought to be caused by a pandemic clone. Diarrhea, abdominal pain, and nausea are the predominant symptoms. The diarrhea can be severe, with blood or mucus in the stool. Vomiting is a less common feature, but fever can occur. The incubation period...

Aeromonas and Plesiomonas shigelloides

Aeromonas is another aquatic organism that prefers brackish and fresh water. It is generally accepted as a cause of FP, after initial doubts, in both adults and children. A profuse watery diarrhea is typical, although a dysentery-like syndrome is sometimes associated with it. The incubation period is 18-24 h. Sporadic infections are more common than full-blown outbreaks. Consumption of raw shellfish should be avoided (not only for aeromonas). P esiomonas shige oides is also an aquatic organism, and FP from it is rare. Its role in FP has not been fully elucidated. Diarrhea is the usual symptom, and the incubation period is approximately 24 h.

Bacillus subtilis and Bacillus licheniformis

Bacillus subtilis is a member of the Bacillus genus and is similar to B. cereus, except that its natural habitat is slightly different, and so the foods causing illness also differ. It has been recognized increasingly as a cause of GE, characterized mainly by vomiting. The incubation period is short, 2 or 3h, although many cases occur within 1 h. Foods implicated include meat and vegetable products such as meat pies, sausage rolls, curries with accompanying rice dishes, and even bread, crumpets, and pizza. The organism is present at high levels in implicated food (105-109cfu g) and can be isolated easily from both food and feces. Another member of this genus, Bacillus licheniformis, tends to cause diarrhea. Cooked meats and vegetables have been implicated. The median incubation period is approximately 8 h. Other members of this genus can also cause FP.

Management of lower GI bleeding

Resuscitation of the patient is the priority, with airway control and provision of oxygen plus large bore intravenous access. Blood should be taken for estimation of haemoglobin, urea, electrolytes, liver function and coagulation profile. Blood should be cross-matched and blood, and products given as required. Urinary and nasogastric catheters are helpful and arterial blood gas analysis will also help to guide the resuscitative effort. The history is important and evidence should be sought of previous GI bleeding, peptic ulcer or inflammatory bowel disease, liver disease, non-steroidal or warfarin usage. The abdomen and anorectum must be carefully examined and bedside examination of the anal canal and rectum are mandatory. If there is any suspicion of an upper GI source, this should be ruled out by upper GI endoscopy.

Foodborne And Waterborne Diseases

Foodborne and waterborne disease is the most widespread public health challenge facing contemporary medicine. The spectrum of illness is changing with the emergence of new pathogens and reemergence of old ones. Individual outbreaks of foodborne or waterborne illnesses have caused sickness in hundreds of thousands of people. The number of identified outbreaks has increased over the past 20 years.1 The globalization of the food economy and explosion in international travel have facilitated the transmission of disease between continents.1 Patients can present with uncommon pathogens and develop life-threatening complications or chronic illnesses. Emergency physicians need to understand the scope and magnitude of foodborne and waterborne illnesses. They should be able to recognize risk factors in the vast population of patients who present with diarrheal illness that compels a more aggressive investigation. Physicians should be cognizant of which pathogens can and cannot be tested for in...

Operations and Endovascular Procedures

After aneurysm operations the patients are often treated in the intensive care unit (ICU) for at least 24 h, and all organ functions are meticulously monitored. After emergency aortic surgery the risk for complications is greater and patients remain in the ICU for several days. Impaired organ perfusion and embolization are common in this group and the nursing staff frequently suspect complications and will alert the doctor on call despite the patient's being under sedation. The primary aim when examining the patient is to diagnose complications requiring immediate surgical treatment, such as intestinal ischemia and large major embolization to the kidneys and legs. Abdominal pain and diarrhea during the first postoperative day, especially if there is blood in the stools, strongly indicates intestinal ischemia. Seventy-five percent of patients with ischemic colitis have diarrhea the first days after surgery. Physical examination findings are a distended abdomen with signs of intestinal...

Table 113 Diagnostic criteria for toxic shock syndrome

Gastrointestinal vomiting, profuse diarrhea Muscular myalgia, or 5-fold increase in CPK Mucous membrane hyperemia vagina, conjunctiva, or pharynx Renal insufficiency at lease twice normal BUN or creatinine Hepatic at least twice normal bilirubin, transaminases Blood thrombocytopenia (

ORigin Botanical facts

Introduced ginger to the Mediterranean area, and in the 16 th century, Francisco de Mendoza of Spain brought it to the West Indies. In England and Colonial America, ginger was made into ginger beer, a popular home remedy for diarrhea, nausea, and vomiting and a precursor to today's ginger ale.

Acute Overdose Toxicity

Despite the tremendous popularity of SSRIs, there is limited information on their toxicity in overdose. The greatest amount of human overdose experience has been with fluoxetine.11 The information from case series involving the other SSRIs is consistent with the information accumulated on fluoxetine. 12,13,14 and 15 However, important differences may exist between the different SSRIs that will become evident only with greater exposure of patients to individual SSRIs. Fortunately, all of the SSRIs are characterized by a high toxic to therapeutic ratio, and fatalities are uncommon with pure SSRI overdoses. Approximately one-half of all adult patients and 75 percent of pediatric patients remain asymptomatic following SSRI overdose. The most common symptoms seen in SSRI overdose include nausea, vomiting, sedation, tremor, and sinus tachycardia. These symptoms are almost identical to the adverse effect profile of SSRIs except for sinus tachycardia, which is more common in overdose and...

Models of spontaneous colitis

A spontaneous colitis occurs in a selective strain of C3H HeJ mice noted at the Jackson laboratories to have diarrhea and rectal ulceration. The disease coincides with the onset of bacterial colonization and is focal in distribution. It spontaneously resolves as the mice age. The severity of the disease is variable and depends on the animal facility in whcih the mice are housed.

Interactions between Nutrition and Immunity

Infection, in turn, is associated with profound effects on nutritional status resulting from decreased nutrient intake due to loss of appetite, decreased nutrient absorption as a result of intestinal damage and malabsorption, and nutrient losses arising from diarrhea and increased urinary excretion. Moreover, the inflammatory processes following infection can cause oxidative damage to host cells, and the prevention of such damage increases the demand for antioxidant defenses, including the vitamins C and E and a variety of enzymes that depend on trace metals for their function. In addition to its effects on nutritional status, the acute phase response is accompanied by marked changes in a variety of

Paulo M Hoff MD and Everardo D Saad MD

After the demonstration of the unacceptably high toxicity of intravenous tegafur in the early U.S. studies (1), further clinical development of orally administered tegafur and later UFT took place mainly in Japan (reviewed in ref. 2). The addition of leucovorin enhanced the antitumor activity of UFT in animal models (3) and augmented the inhibition of thymidylate synthase in gastric tumors in humans (4). Following these studies, clinical development of the UFT leucovorin combination was pursued in the West. Six phase I studies of the combination were reported from Spain and the United States (Table 1). Daily doses of UFT ranging from 200 to 600 mg m2, administered once, twice, or three times daily, were given either continuously (5) for 14 d every 4 wk (7,9) or for 28 d every 5 (8,10) or 6 wk (6). Leucovorin doses used in the studies ranged from 30 to 150 mg d. Dose-limiting toxic effects were diarrhea, mucositis, vomiting, fatigue, leukopenia, abdominal pain, and abnormal liver...

Appendix Information on Recommended Measures Child Health Questionnaire

The GIQLI is a self-reported, system-specific measure designed for use with people who have different gastrointestinal disorders 35, 37, 38 . The 36 items, reflecting physical, emotional, and social function as well as typical gastrointestinal symptoms, are each scored on a 5-point scale. Items are summed to produce a total score ranging from 0 to 176, with higher scores denoting better QoL. The measure was developed in German and English. French and Spanish GIQLI versions have been validated 100, 117 . The GSRS is a clinical symptom rating scale originally designed for patients with irritable bowel syndrome and peptic ulcer disease 122 . It has subsequently been evaluated in patients with GERD 105, 123 . GSRS for use with GERD patients contains 15 items, each assessed on a 1-point to 7-point scale, with 7 representing extreme discomfort. The items combine into five syndromes labeled reflux, abdominal pain, indigestion, diarrhea, and constipation. Mean scores are calculated from the...

Cardiovascular Complications

Management of pulmonary edema in ESRD patients is usually similar to treatment in non-ESRD patients. Cornerstones of therapy in both types of patients include oxygen, nitrates, ACE inhibitors, and morphine. Diuretics, such as furosemide, are still effective in treating CHF in ESRD patients even with minimal urine output. 7 In pulmonary edema, intravenous furosemide in doses of 60 to 100 mg provides pulmonary vasodilatation, improving oxygenation. Preload reduction in ESRD patients can also be accomplished by inducing diarrhea with sorbitol and by phlebotomy. Phlebotomy of as little as 150 mL of blood is safe and effective in treating pulmonary edema.8 For example, phlebotomy of 150 mL in a patient with a hematocrit of 20 percent results in the loss of 120 mL of plasma and 30 mL of packed red blood cells (10 g of hemoglobin). The improved oxygenation by phlebotomy will more than offset the decrease in oxygen-carrying capacity due to the decrease on hemoglobin. Phlebotomized blood...

Key Nutrients Involved in Host Resistance to Infection

Retinol (vitamin A) Vitamin A is essential for the maintenance of mucosal surfaces and plays a role in cytokine regulation. Vitamin A supplementation has been reported to reduce child mortality from diarrheal diseases and HIV AIDS, and to decrease the prevalence, severity, and duration of diarrheal episodes (particularly in nonbreastfed infants). Vitamin A is also involved in increasing levels of long-term measles-specific antibodies in response to measles vaccination and in reducing measles-related morbidity. Zinc supplementation has been found to improve infectious morbidity in individuals with sickle cell disease. In malnourished children, zinc supplementation improves epithelial integrity, decreases the duration of diarrheal episodes and mortality from diarrhea, decreases the incidence of respiratory tract infection respiratory morbidity, and improves T-cell-mediated immunity. Maternal zinc deprivation results in small thymus and spleen size in the neonate.

Urine Urea Nitrogen Loss as a Marker of Catabolism

As part of the host response to injury, infection, or tumor, patients frequently lose protein in the urine in the form of nitrogen. For example, 16 g of urea nitrogen in the urine per day represents a 1-lb loss of lean body mass, such as muscle tissue. In some aggressive cancers, urea nitrogen loss can be as high as 24 g per day. The loss of 1g of urinary urea nitrogen is equal to 6.25 g of dry protein. A total of 6.25 g of dry protein is equal to approximately 1 oz. of lean body mass. A loss of 16 g of urinary urea is equal to the loss of 1 lb of skeletal muscle or lean body mass per day. Specific areas of lean body mass loss that may result in a functional impairment of the respiratory muscles include the diaphragm, heart muscle, and GI mucosa. The loss of lean body mass in these areas can contribute to the development of respiratory failure, heart failure, and diarrhea, respectively. The rapid development of malnutrition can occur in patients with infection due to large losses of...

Genetic disruption of IL2R subunits

As IL-2 is required to maintain the growth and viability of T cells in vitro, one might expect disruption of the genes encoding IL-2 or any of the IL-2R subunits to significantly impair T cell development or expansion. However, mice lacking the IL-2, IL-2Ra or IL-2R(3 genes demonstrate apparently normal development of T, B and NK cells and, rather than showing reduced lymphocyte expansion, frequently demonstrate hyperproliferation of lymphocytes and development of T cell-dependent autoimmune disorders such as hemolytic anemia and inflammatory bowel disease. In contrast, yc- mice show severely impaired lymphocyte development, consistent with the involvement of yc in other cytokine receptor complexes. Indeed, the IL-7 receptor utilizes yc and has been shown to be essential for B cell and thymocyte development. Collectively, these results suggest that in the absence of IL-2 or a functional IL-2R, other yc-dependent cytokine receptors can mediate lymphocyte development and expansion in...

Structural Considerations

The entire epithelium of the small intestine is replaced every 3-6 days, making it one of the fastest growing tissues of the body. The rates of cell division and turnover are influenced by luminal contents, including nutrients and growth factors, and by gastrointestinal hormones. In general, increased cell loss results in higher rates of cell proliferation. The mechanisms balancing cell loss and renewal are poorly understood, but result in rapid repair of damaged mucosa. The high mitotic rate of the gastrointestinal mucosa makes it susceptible to x-radiation and cancer chemotherapy with resulting diarrhea and other problems.

Gastrointestinal Decontamination

The use of cathartics to hasten GI transit and facilitate decontamination has no proven efficacy in hydrocarbon ingestions. Many patients will already have diarrhea from the hydrocarbon, and further catharsis is not required. Oil-based cathartics, which had been used in the past to thicken the ingested hydrocarbon to increase its viscosity and decrease the subsequent risk of aspiration, are contraindicated. They may actually increase GI absorption and are associated with an increased risk of lipoid pneumonia when aspirated.

Secondary Lactase Deficiency

Secondary lactase deficiency is distinct from genetically determined loss of lactase with age. Secondary lactase deficiency is frequently associated with diseases of the small intestine. Enteric viruses, such as rotavirus and Norwalk agent, can induce lactase deficiency by penetration of the enterocyte in the small intestine Rotaviruses are a principal cause of diarrhea and lactose intolerance in infancy. Denudation of the brush border of the jejunal mucosa associated with diarrhea can lead to the loss of the other two disaccharides, maltase and sucrose. Continued diarrhea may also lead to severe complications such as monosaccharide intolerance. Giardiasis have also

Invasion by Lymphatic Permeation

Have Another Test Barium Enema

The deranged lymph flow in the initial stages may be radiologically demonstrated as edema in the wall of the bowel with mucosal thickening and luminal narrowing (Figs. 4-83 and 4-84). As the metastatic lymphatic edema increases, nodular tumor deposits occur that may be evident as thumbprinting in the colon and cob-blestoning of the small intestine (Fig. 4-85), changes mimicking inflammatory bowel disease.78 79 Radiologic demonstration of these findings indicates that extensive lymphatic permeation has occurred and that resection will not be curative.77 The process can also result in diversion of lymph flow into veins through direct lym-phaticovenous communications81 or through shared channels intrinsic to lymph nodes.82

Future Development Of Uft Plus Lv Therapy

In another study of patients with advanced CRC, a combination of UFT (300 mg m2 d) plus LV (15 mg d) for 14 d was given together with oxaliplatin (85 mg m2) on d 1 and 14, in 28-d cycles (29). Eighteen percent of the patients developed diarrhea and 9 had nausea vomiting. There was no severe hematological toxicity. In one study, 18 patients with advanced rectal cancer received the combination treatment of UFT LV plus radiotherapy (30). Eleven patients had an operation after a median of 40 d. Two patients had a complete pathological response and 16 patients were alive after a median of 45 wk (range 17-84 wk). After a median follow up of 12 mo, 9 11 patients are still alive. The tox-icity of the treatment was low, with no hematological adverse reactions and mainly grade I or II nonhematological toxicity. Only one patient had grade III diarrhea. It seems that high dose radiotherapy combined with UFT LV downstages more than 50 of patients with inoperable rectal cancer and can produce...

Hemorrhagic Shock and Encephalopathy Syndrome

Hemorrhagic shock and encephalopathy syndrome (HSES) was first reported by Levin et al.65 in 1983. This acute, frequently lethal syndrome usually occurs at about 3 to 4 months of age.66 The cause remains unknown.67 There is a prodromal period lasting on average 2 to 3 days during which the child exhibits fever, irritability, diarrhea, or signs of an upper respiratory tract infection. It then deteriorates into profound shock, seizures, coma, DIC, and oliguria. Cerebral edema, hypoxia, and boundary zone infarction may be seen. Rarely, SDH and retinal hemorrhages are seen in these cases and are attributed to the coagulation disorders present. The

Withholding Food and Water The Patient Experience

Robert McCann reported an experience with thirty-two dying cancer patients in a hospice-like setting. These patients were sufficiently aware to judge hunger and thirst, and were offered food and water as desired. Nearly two-thirds experienced neither hunger nor thirst one-third had hunger only initially. Oral feeding as desired and or mouth lubrication effectively met needs when they occurred and caregivers could focus on patient comfort.

Pyrogen Test Development

In the mid-1920s, Seibert (1) completed a series of classic studies, which proved conclusively that injection fevers associated with intravenous therapy resulted from heat-stable, filterable bacterial products that are commonly referred to as pyrogens. To ascertain the presence or absence of febrile responses caused by her test solutions, Seibert selected the rabbit as her animal test model, a choice that was later proven to be fortuitous (2). Since that time, many other species have been shown to have fever reactions when injected with bacterial pyrogens. Monkeys, horses, dogs, and cats, like the rabbit, have reproducible fever responses that are similar in nature to those of humans. On the other hand, the temperature response to pyrogens in rats, guinea pigs, mice, hamsters, and chicks is irregular and unpredictable, thus rendering them unsuitable for investigations of fever (3). For reasons of convenience and economics, the final selection of an animal test model for pyrogen...

Fissure In Ano Anal Fissure

Most often, the traditional midline anal fissure is caused by the trauma produced by the passage of a particularly hard and large fecal mass, but it is also seen after acute episodes of diarrhea. Fissures persist because of the severe, chronic internal sphincter spasm that occurs along with the secondary infection of its base.

Blister Beetles Coleoptera

Although there are more members of the Coleoptera or beetle family than any other arthropod, the only ones with clinical significance for envenomation in humans are blister beetles. Blister beetles (families Staphylindae and Meloidae) are found throughout the United States, and include beetles known as Spanish fly ( Lytta vesicatoria).1 When disturbed or crushed on the skin, they exude a vesicating agent called cantharidin from the joints of their legs or from their bodies that can penetrate the epidermis to produce irritation and blistering within a few hours of contact. If ingested, cantharidin can produce intense gastrointestinal disturbances with symptoms of nausea, vomiting, diarrhea, and abdominal cramps.20 Initial contact with the beetle produces a burning, tingling sensation and a mild rash. Within a few hours, flaccid, elongated vesicles and bullae develop from a few millimeters to several centimeters in diameter. Blebs erupt 2 to 5 h after contact and can be hemorrhagic and...

Fluids and Electrolytes

Diarrhea is usually the most distressing problem for patients with malabsorption and may cause dehydration. Care should be taken to correct fluid losses with appropriately designed oral rehydration solutions. Even in the setting of massive secretory diarrhea, such as seen with cholera infections, oral rehydration solutions are effective at treating dehydration. Data support the safety and efficacy of oral rehydration solutions of reduced osmolarity in children with dehydration from acute diarrhea. An oral rehydration solution composed of glucose 75 mmol L, sodium 75mmol L, potassium 20mmol L, base 30mEq L, and osmolality 245mOsm L is well suited for the rehydration and maintenance therapy during dehydration due to diarrhea. In some cases of severe diarrhea, parenteral hydration is the mainstay of therapy. Examples include glucose-galactose malabsorption, congenital chloride diarrhea, microvillous inclusion disease, and tufting enteropathy. These cases, as well as other severe causes...

How To Manage Irritable Bowel Syndrome

How To Manage Irritable Bowel Syndrome

Having issues with irritable bowel syndrome and want to know the correct way to manage the problem? Finally, This Books Explains Everything You'll Never Wonder If The Misery Will End... This Book Will Ease Your Pain And Enable Your Old Day-To-Day Life Stop Fighting Irritable Bowel Syndromes With Products And Home Remedies That Always Seem To Make Things Worse Than They Ever Were. Stop the suffering once and for all, YOU don't have to live with IBS anymorebr There's finallya new, breakthroughbookcreated just for people like you

Get My Free Ebook