A specially designed instrument is needed in neurogastroenterology research since the gut wall has an outstanding capacity to expand and  contract  spontaneously and by  reflex . When this occurs, a balloon placed anywhere in the gut has to be inflated or deflated very rapidly in order to maintain a constant pressure in this balloon.


Barostat-balloon systems have been used anywhere in the gut, including the  esophagus , [ 4 ]   stomach , [ 5 ]   small bowel , [ 6 ]   colon , and the  rectum ampulla . [ 7 ]


Computer -driven barostats have widely been used to assess sensation and pain thresholds in the gut. Assessment of pain thresholds in the ampulla recti has been proposed as  diagnostic  measure in  irritable bowel syndrome . [ 8 ] [ 9 ]


Bowel management  is the process which a person with a bowel disability uses to manage  fecal incontinence  or  constipation . [ 1 ]  People who have a medical condition which impairs control of their  defecation  use bowel management techniques to choose a predictable time and place to evacuate. [ 1 ]  A simple bowel management technique might include diet control and establishing a toilet routine. [ 1 ]  As a more involved practice a person might use an  enema  to relieve themselves. [ 1 ]  Without bowel management, the person might either suffer from the feeling of not getting relief, or they might soil themselves. [ 1 ]


Bowel control is often a challenge for children who are born with anomalies in their  anus  or  rectum ,  Hirschsprung's disease , and/or  spina bifida . Medical providers can help anyone with long term bowel problems to develop a routine in such cases to assist children in managing their bowels so that they can otherwise live normally. [ 1 ]


Bowel management is achieved mainly through a daily  enema  which empties the  colon  to prevent unwanted and uncontrolled bowel movements that day. [ 2 ]  Some patients also use  laxatives  and a  controlled diet  as part of their bowel management regimen. Another alternative is  transanal irrigation .


Transanal irrigation of the rectum and colon is designed to assist the evacuation of faeces from the bowel by introducing water into rectum via the anus. [ 3 ]  By regularly emptying the bowel using transanal irrigation, controlled bowel function is often re-established to a high degree in patients with bowel incontinence and/or constipation. This enables the users to develop a consistent bowel routine by choosing the time and place of evacuation. [ 3 ]   An international consensus on when and how to use transanal irrigation for people with bowel problems was published 2013. The article offers practitioners a clear, comprehensive and simple guide to practice for the emerging therapeutic area of transanal irrigation. [ 3 ]


Determining the appropriate regimen to achieve successful bowel management is done under medical supervision. Care is tailored to suit each child and often requires a trial and error approach over the course of a week. The patient has an  X-ray  taken which is reviewed by their doctor. The doctor then recommends a course of action (e.g. enemas,  laxative , and/or controlled diet). The next day, the process is repeated with modifications to help the child achieve a completely empty colon. After the course of this week the doctor can determine the precise amount and combination of what the child needs to achieve bowel management. From then on the patient can continue the regimen on their own. [ 2 ]


Bowel management does not cure  fecal incontinence , but can greatly increase quality of life. With successful bowel management, a child may be more apt to establish independence in normal daily life. Children with severe incontinence may also be able to attend school and participate in activities they otherwise would never be able to. [ 2 ]


Depending on the prognosis, some patients will continue using these techniques for life while others may gain some degree of bowel control and become "potty trained". Children who practice bowel management often become unhappy as they age, especially at  puberty , due to feeling that the administration of enemas is an intrusion on their privacy, especially as it is difficult for them to administer the enema themselves. An operation called a continent appendicostomy or  Malone procedure  is available. This allows a person to give themselves an enema by inserting a  catheter  into a small orifice at the  navel . [ 4 ] [ 5 ]


The medical definition of  fecal incontinence  is the incapacity to voluntarily hold  feces  in the rectum. There are two subgroups to those with fecal incontinence: real fecal incontinence and pseudoincontinence. [ 6 ]


For a child with real fecal incontinence, the normal mechanism of bowel control is not working. An alteration of the muscles that surround the  anorectal canal  along with poor  sphincters  (the muscles that control the anus) are responsible for fecal incontinence in children operated on for  anorectal malformations  with a bad prognosis. Some patients operated on for Hirschsprung's disease have this anatomic problem as do those with spinal problems. The supply of  nerve  connections of these muscles is important for their correct function. A deficit of nerve connections occurs in anorectal anomalies as well as in other conditions. In cases of  spina bifida , or following  spinal cord  injury, the contraction and relaxation of the muscles, as well as sensation, are deficient. The presence and the passage of feces and the perception of the difference between solid and liquid feces and gas are limited.


In cases of pseudoincontinence, a child is believed to have fecal incontinence. However, investigation shows that they have severe constipation and fecal impaction. When the  impaction  is treated and the patient receives enough laxatives to pass stool, they become continent.


Children who have fecal incontinence after the repair of an  imperforate anus  are usually those born with a bad prognosis type of defect and severe associated defects (defect of the sacrum, poor muscle complex). However, such children can still achieve a good quality of life when treated with the bowel management program. Children operated on for imperforate anus and who have fecal incontinence can be divided into two groups that require individualized treatment plans:


Children with constipation (colonic hypomotility) : No special diet or medications are necessary for children with  colonic hypomotility , a type of  constipation . Their tendency towards constipation helps them to remain clean between enemas. The real challenge is to find an enema capable of cleaning the colon completely. Soiling episodes or "accidents" occur when there is an incomplete cleaning of the bowel.


Children with loose stools and diarrhea (colonic hypermotility) : This group of children has an overactive colon. Rapid transit of stool results in frequent episodes of  diarrhea . This means that even when an enema cleans the colon rather easily, stool keeps on passing fairly quickly from the cecum to the  descending colon and the anus. To prevent this, a constipating diet and/or medications to slow down the colon are necessary. Eliminating foods that further loosen bowel movements will help the colon to slow down. Those who experience hypermotility may have to follow a constipating diet and avoid laxative foods. The diet is rigid and includes food such as banana, apple, baked bread, white pasta with no sauce, boiled meat, and others, while fried foods and  dairy products  are avoided. [ 5 ]


Buried bumper syndrome  ( BBS ) is a condition that affects feeding tubes placed into the stomach ( gastrostomy tubes ) through the abdominal wall.  Gastrostomy tubes include an internal bumper, which secures the inner portion of the tube inside the stomach, and external bumper, which secures the outer portion of the tube and opposes the abdomen. Buried bumper syndrome occurs when the internal bumper of a gastrostomy tube erodes into the wall of the stomach. The internal bumper may become entirely buried within the fistulous tract. The main causative factor is excessive tightening of the external bumper, leading to increased pressure of the internal bumper on the wall of the stomach.  Additional risk factors include:  obesity , weight gain,  malnutrition ,  corticosteroid  therapy, and poor wound healing.


Buried bumper syndrome may be entirely asymptomatic, though tube dysfunction is common.  The gastrostomy tube may leak around the entry site, or it may become difficult to infuse feeds, fluids or medications. Less often, bleeding, infection, abscess or peritonitis may occur. Diagnosis is achieved most often with  upper endoscopy .   Computed tomography  imaging may also confirm the diagnosis. Treatment consists of removal of the gastrostomy tube, either via simple external traction or endoscopic removal.  Surgery is rarely necessary.


Buried bumper syndrome may be asymptomatic, especially early in the course.  Dysfunction of the tube occurs commonly, including leakage around the insertion site, inability to administer feedings or fluids, or need for more pressure when giving feeds. [ 1 ]   Buried bumper syndrome may cause abdominal pain or swelling ( erythema ) at the site of insertion of the PEG tube. Less commonly, buried bumper syndrome may also be complicated by acute infectious illness (sepsis), abscess formation, gastrointestinal bleeding or peritonitis. [ 2 ] [ 3 ]  In some cases, the internal bumper may be felt by palpating the abdomen. [ 2 ]  Inspection of the tube typically reveals an inability to easily rotate the tube. [ 2 ]


Buried bumper syndrome occurs when this internal bumper erodes into the wall of the stomach, sometimes becoming entirely buried within the wall of the stomach. Buried bumper syndrome tends to be a late complication of gastrostomy tube placement, but can rarely occur as early as 1 to 3 weeks after tube placement. [ 4 ] [ 5 ]   Most cases occur more than 1 year after initial placement of the PEG tube. [ 2 ]


Excessive tightening of the external bumper is the primary risk factor for buried bumper syndrome.  Maintaining the external bumper in a loose position may help prevent buried bumper syndrome. [ 6 ]  Additional risk factors include obesity, medications, poor wound healing, malnutrition, etc. Feeding tubes with soft balloon internal bumpers are less likely to cause buried bumper syndrome, compared with more firm or stiff polyurethane internal bumpers. [ 7 ]


Buried bumper syndrome may be suspected based on features consistent with this disorder.  The diagnosis is confirmed either endoscopically (via  upper endoscopy ) or with computed tomography. [ 8 ]  Upper endoscopy may reveal overgrowth of stomach tissue over the internal bumper (incomplete buried bumper syndrome). [ 1 ]  If the bumper has eroded deep into the gastric mucosa, it may not be visualized during endoscopic evaluation (complete buried bumper syndrome). [ 1 ]


Prevention consists of maintaining a space of 1–2 cm between the external bumper of the gastrostomy tube and the abdominal wall, which avoids excess pressure of the internal bumper onto the stomach wall. Mobilizing and rotating the tube may prevent mucosal overgrowth and aid in avoiding buried bumper syndrome. [ 7 ]


Treatment of buried bumper syndrome consists of removal of the gastrostomy tube.  For mild cases with externally removable tubes, simple external traction may be used to remove the tube.  Several different approaches may be utilized, including endoscopy. [ 9 ] [ 10 ]  If endoscopic removal is pursued, a new feeding tube may be placed during the same procedure. [ 11 ]  Where endoscopic removal is not possible, surgery may be necessary (laparoscopic or laparotomy).


Buried bumper syndrome occurs in 0.3–2.4% of patients. Malnutrition, malignancy, chemoradiation, and corticosteroid therapy are additional risk factors. [ 7 ]


In 1980, the first percutaneous endoscopic gastrostomy (PEG) tube was reported, as an alternative to an open surgical placement of feeding tubes.  The first cases of buried bumper syndrome were reported in 1988 and 1989. [ 7 ]  The term "buried bumper syndrome" was first used in 1990. [ 9 ]


Burning mouth syndrome  ( BMS ) is a burning, tingling or scalding sensation in the mouth, lasting for at least four to six months, with no underlying known dental or medical cause. [ 3 ] [ 7 ]  No related  signs of disease  are found in the mouth. [ 3 ]   People with burning mouth syndrome may also have a subjective  xerostomia  (dry mouth sensation where no cause can be found such as reduced salivary flow),  paraesthesia  (altered sensation such as tingling in the mouth), or an altered sense of taste or smell. [ 3 ]


A burning sensation in the mouth can be a  symptom  of another disease when local or systemic factors are found to be implicated; this is not considered to be burning mouth syndrome, [ 3 ]   which is a syndrome of  medically unexplained symptoms. [ 3 ]   The  International Association for the Study of Pain  defines burning mouth syndrome as "a distinctive  nosological  entity characterized by unremitting oral burning or similar pain in the absence of detectable  mucosal  changes" [ 1 ]  and "burning pain in the tongue or other oral mucous membranes", [ 8 ]  and the  International Headache Society  defines it as "an intra-oral burning sensation for which no medical or dental cause can be found". [ 6 ]  To ensure the correct diagnosis of burning mouth syndrome, Research Diagnostic Criteria (RDC/BMS) have been developed. [ 9 ]


Insufficient evidence leaves it unclear if effective treatments exist. [ 3 ]


By definition, BMS has no signs. Sometimes affected persons will attribute the symptoms to sores in the mouth, but these are in fact normal anatomic structures (e.g.  lingual papillae ,  varices ). [ 10 ]  Symptoms of BMS are variable, but the typical clinical picture is given below, considered according to the  Socrates pain assessment method  (see table). If clinical signs are visible, then another explanation for the burning sensation may be present.  Erythema  (redness) and  edema  (swelling) of papillae on the tip of the tongue may be a sign that the tongue is being habitually pressed against the teeth. The number and size of  filiform papillae  may be reduced. If the tongue is very red and smooth, then there is likely a local or systemic cause (e.g. erythematous candidiasis,  anemia ). [ 5 ]


In about 50% of cases of burning mouth sensation  no identifiable cause is apparent; [ 1 ]  these cases are termed (primary) BMS. [ 11 ]  Several theories of what causes BMS have been proposed, and these are supported by varying degrees of evidence, but none is proven. [ 5 ] [ 11 ]
As most people with BMS are postmenopausal women, one theory of the cause of BMS is of  estrogen  or  progesterone  deficit, but a strong statistical correlation has not been demonstrated. [ 5 ]  Another theory is that BMS is related to  autoimmunity , as abnormal antinuclear antibody and rheumatoid factor can be found in the serum of more than 50% of persons with BMS, but these levels may also be seen in elderly people who do not have any of the symptoms of this condition. [ 5 ]  Whilst salivary flow rates are normal and there are no clinical signs of a dry mouth to explain a complaint of dry mouth, levels of salivary proteins and phosphate may be elevated and salivary pH or buffering capacity may be reduced. [ 5 ]


Depression and  anxiety  are strongly associated with BMS. [ 5 ] [ 13 ] [ 14 ]  It is not known if depression is a cause or result of BMS, as depression may develop in any setting of constant unrelieved irritation, pain, and sleep disturbance. [ 5 ] [ 12 ] [ 15 ]  It is estimated that about 20% of BMS cases involve  psychogenic factors , [ 14 ]  and some consider BMS a  psychosomatic illness , [ 5 ] [ 13 ]  caused by  cancerophobia , [ 13 ] [ 14 ]  concern about  sexually transmitted infections , [ 14 ]  or  hypochondriasis . [ 13 ]


Chronic low-grade trauma due to  parafunctional habits  (e.g. rubbing the tongue against the teeth or pressing it against the palate), may be involved. [ 12 ]  BMS is more common in persons with  Parkinson's disease , so it has been suggested that it is a disorder of reduced pain threshold and increased sensitivity. Often people with BMS have unusually raised taste sensitivity, termed  hypergeusia  ("super tasters"). [ 1 ]   Dysgeusia  (usually a bitter or metallic taste) is present in about 60% of people with BMS, a factor which led to the concept of a defect in sensory peripheral neural mechanisms. [ 12 ]  Changes in the oral environment, such as changes in the composition of saliva, may induce neuropathy or interruption of nerve transduction. [ 1 ] [ 11 ]  The onset of BMS is often spontaneous, although it may be gradual. There is sometimes a correlation with a major life event or stressful period in life. [ 10 ]  In women, the onset of BMS is most likely three to twelve years following menopause. [ 5 ]


Metals


Plastics


Several local and systemic factors can give a burning sensation in the mouth without any clinical signs, and therefore may be  misdiagnosed  as BMS. Some sources state that where there is an identifiable cause for a burning sensation, this can be termed "secondary BMS" to distinguish it from primary BMS. [ 16 ] [ 17 ]  However, the accepted definitions of BMS hold that there are no identifiable causes for BMS, [ 1 ] [ 3 ] [ 6 ]  and where there are identifiable causes, the term BMS should not be used. [ 3 ]


Some causes of a burning mouth sensation may be accompanied by clinical signs in the mouth or elsewhere on the body. For example, burning mouth pain may be a symptom of  allergic contact stomatitis . This is a contact sensitivity ( type IV hypersensitivity  reaction) in the oral tissues to common substances such as  sodium lauryl sulfate ,  cinnamaldehyde  or dental materials. [ 4 ]  However, allergic contact stomatitis is accompanied by visible lesions and gives positive response with patch testing. Acute (short term) exposure to the  allergen  (the substance triggering the allergic response) causes non-specific inflammation and possibly  mucosal ulceration . Chronic (long term) exposure to the allergen may appear as chronic inflammatory, lichenoid (lesions resembling oral  lichen planus ), or  plasma cell gingivitis , which may be accompanied by glossitis and  cheilitis . [ 12 ]  Apart from BMS itself, a full list of causes of an oral burning sensation is given below:


BMS is a  diagnosis of exclusion , i.e. all other explanations for the symptoms are ruled out before the diagnosis is made. [ 1 ] [ 16 ]  There are no clinically useful investigations that would help to support a diagnosis of BMS [ 3 ]  (by definition all tests would have normal results), [ 1 ]  but  blood tests  and / or  urinalysis  may be useful to rule out anemia, deficiency states, hypothyroidism and diabetes. Investigation of a dry mouth symptom may involve  sialometry , which objectively determines if there is any reduction of the salivary flow rate (hyposalivation). Oral candidiasis can be tested for with use of a swabs, smears, an oral rinse or saliva samples. [ 11 ]   It has been suggested that allergy testing ( e.g. ,  patch test ) is inappropriate in the absence of a clear history and clinical signs in people with a burning sensation in the mouth. [ 11 ]  The diagnosis of a people with a burning symptom may also involve psychologic screening e.g. depression questionnaires. [ 1 ]


The second edition of the  International Classification of Headache Disorders  lists diagnostic criteria for "Glossodynia and Sore Mouth":


A burning sensation in the mouth may be primary (i.e. burning mouth syndrome) or secondary to systemic or local factors. [ 1 ]  Other sources refer to a "secondary BMS" with a similar definition, i.e. a burning sensation which is caused by local or systemic factors, [ 16 ]  or "where oral burning is explained by a clinical abnormality". [ 17 ]  However this contradicts the accepted definition of BMS which specifies that no cause can be identified. "Secondary BMS" could therefore be considered a misnomer. BMS is an example of  dysesthesia , or a distortion of sensation. [ 5 ]


Some consider BMS to be a variant of  atypical facial pain . [ 22 ]  More recently, BMS has been described as one of the 4 recognizable symptom complexes of chronic  facial pain , along with atypical facial pain,  temporomandibular joint dysfunction  and  atypical odontalgia . [ 23 ]  BMS has been subdivided into three general types, with type two being the most common and type three being the least common. [ 1 ]  Types one and two have unremitting symptoms, whereas type three may show remitting symptoms. [ 1 ]


Sometimes those terms specific to the tongue (e.g.  glossodynia ) are reserved for when the burning sensation is located only on the tongue. [ 21 ]


If a cause can be identified for a burning sensation in the mouth, then treatment of this underlying factor is recommended. If symptom persist despite treatment a diagnosis of BMS is confirmed. [ 11 ]  BMS has been traditionally treated by reassurance and with  antidepressants ,  anxiolytics  or  anticonvulsants . A 2016  Cochrane review  of treatment for burning mouth syndrome concluded that strong evidence of an effective treatment was not available, [ 3 ]  however,  a systematic review in 2018 found that the use of antidepressants and alpha-lipoic acids gave promising results. [ 24 ] [ 25 ]


Other treatments which have been used include  atypical antipsychotics ,  histamine receptor antagonists , and  dopamine agonists . [ 26 ]  Supplementation with vitamin complexes and  cognitive behavioral therapy  may be helpful in the management of burning mouth syndrome. [ 27 ]


BMS is benign (importantly, it is not a symptom of  oral cancer ), but as a cause of chronic pain which is poorly controlled, it can detriment  quality of life , and may become a fixation which cannot be ignored, thus interfering with work and other daily activities. [ 10 ] [ 28 ]  Two thirds of people with BMS have a spontaneous partial recovery six to seven years after the initial onset, but in others the condition is permanent. [ 5 ] [ 15 ]  Recovery is often preceded by a change in the character of the symptom from constant to intermittent. [ 15 ]  No clinical factors predicting recovery have been noted. [ 15 ]


If there is an identifiable cause for the burning sensation, then psychologic dysfunctions such as anxiety and depression often disappear if the symptom is successfully treated. [ 5 ]


BMS is fairly uncommon worldwide, affecting up to five individuals per 100,000 general population. [ 3 ]  People with BMS are more likely to be middle aged or elderly, and females are three to seven times more likely to have BMS than males. [ 1 ] [ 29 ]  Some report a female to male ratio of as much as 33 to 1. [ 6 ]  BMS is reported in about 10–40% of women seeking medical treatment for  menopausal  symptoms, and BMS occurs in about 14% of postmenopausal women. [ 5 ] [ 15 ] [ contradictory ]  Males and younger individuals of both sexes are sometimes affected. [ 10 ]


Asian and Native American people have considerably higher risk of BMS. [ 5 ]


Sheila Chandra , a British singer of  Indian  heritage, retired due to this condition. [ 30 ]


Caustic ingestion  occurs when someone accidentally or deliberately ingests a  caustic or corrosive substance . Depending on the nature of the substance, the duration of exposure and other factors it can lead to varying degrees of damage to the  oral mucosa , the  esophagus , and the  lining of the stomach . [ 4 ]


The severity of the injury can be determined by  endoscopy  of the upper digestive tract, although  CT scanning  may be more useful to determine whether surgery may be required. [ 4 ]


During the healing process,  strictures  of the oesophagus may form, which may require  therapeutic dilatation  and insertion of a  stent . [ 4 ]


Immediate manifestations of caustic substance ingestions include erosions of mucosal surfaces of the gastrointestinal tract or airway (which can cause bleeding if the erosions extend to a blood vessel), mouth and tongue swelling, drooling or hypersalivation, nausea, vomiting,  dyspnea ,  dysphonia / aphonia , irritation of the eyes and skin. [ 1 ] [ 2 ]  Perforation of the esophagus can lead to  mediastinitis  or perforation of the stomach or bowel can lead to  peritonitis [ 1 ]  Swelling of the airway or  laryngospasm  can occur leading to compromised breathing. Injuries affecting the respiratory system include aspiration pneumonia and laryngeal sores. [ 3 ]  Signs of respiratory compromise include  stridor  and a change in a person's voice.


Later manifestations of caustic substance ingestions include  esophageal strictures  or stenosis; which can result in chronic pain and malnutrition. [ 1 ]  Esophageal strictures more commonly occur after more severe mucosal injury, occurring in to 71% and 100% of grade 2b and 3 mucosal lesions respectively. [ 2 ]  Remote manifestations of caustic ingestions include esophageal cancer. People who have a history of caustic substance ingestion are 1000-3000 times more likely to develop esophageal cancer with most cases occurring 10–30 years after the ingestion. [ 2 ]


Acids  with a  pH  of less than 2 or  alkalis  with a pH above 12 are capable of causing the most extensive injuries in ingestions. [ 1 ]  Alkalis damage tissue by saponifying fats, leading to liquefaction necrosis which allows the alkalis to reach deeper tissues. Acids denature proteins via coagulation necrosis, this type of necrosis is thought to prevent the acid from reaching deeper tissues. [ 1 ] [ 2 ]  Clinically, the pH, concentration, volume of ingested substance in addition to the duration of time in contact with tissue as well as percentage of body surface area involved determine the severity of the injury. [ 1 ]


The severity of injuries to the mucosa of the gastrointestinal tract is commonly rated using the Zargar criteria. [ 5 ]


Common treatments used for toxic substance ingestions are ineffective, or are even harmful, when implemented in ingestions of caustic substances. Clinical attempts to empty the stomach can cause further injuries. [ 1 ]   Activated charcoal  does not neutralize caustics and can also obscure endoscopic visualization. [ 1 ]  There is no known clinical benefit of neutralization of the caustic substances; neutralization releases heat as well as causing gaseous distention and vomiting, all of which can worsen injuries. [ 1 ]


Signs of airway compromise including decreased level of consciousness, stridor, change in voice, inability to control oral secretions necessitate intubation and mechanical ventillation. [ 1 ]  IV fluids are often needed to maintain hydration and replace insensible water losses.


Endoscopy should be done within the first 24–48 hours of ingestion as subsequent wound softening increases the risk of perforation. [ 1 ]  Endoscopically inserted nasogastric tubes can serve as a stent to prevent esophageal strictures as well as allow tube feedings. [ 1 ]  A CT scan, often enhanced with contrast, can also be used to evaluate injuries. [ 1 ]


The most common surgical methods of treatment in children include esophageal dilation and esophageal replacement as less commonly implantation of an esophageal stent. [ 3 ]


In general, most ingestions in children involve exploratory ingestions of small amounts of caustic substances, with the rare exception being cases of child abuse where larger amounts are often ingested. Caustic ingestions in adults usually involve larger amounts of ingested material during attempts of self harm. [ 1 ]  Due to the greater amount of material usually ingested; injuries are often more severe in the intentional ingestions of adolescents and adults as compared to those of children. [ 1 ]  Commonly ingested substances include  ammonium hydroxide  (found in general cleaner and grease remover),  sodium hydroxide  or  potassium hydroxide  (found in drain opener or oven cleaner),  sodium hypochlorite  (bleach),  oxalic acid  (metal polish) and  hydrochloric acid  (toilet bowl cleaner). [ 1 ]  Storage of caustic substances in water or drink containers is a risk factor for accidental ingestion of these materials, particularly in children. [ 2 ]  Boys of preschool age are at the greatest risk of accidental caustic ingestion. [ 3 ]


Preventative measures have been recommended that are intended to decrease the risk of accidental ingestion of caustic substances including: [ 3 ]


Cecal bascule  is a cause of  large bowel obstruction  where there is folding of the  cecum  anteriorly over the  ascending colon . It is one of two types of cecal  volvulus , the other being axial ileocolic.  It is caused by rotational torsion of the cecum or ascending colon along its own axis. In cecal bascule, the base of the cecum folds anteriorly over the ascending colon, creating a flap-valve, obstructing emptying of the cecum. [ 1 ]  The condition can be complicated by  necrosis  or  organ perforation  before the diagnosis is made, particularly if the  ileocecal valve  is competent, preventing retrograde decompression of the cecum into the  ileum . [ 2 ]


Checkpoint inhibitor induced colitis  is an inflammatory condition affecting the colon ( colitis ), which is caused by cancer  immunotherapy  ( checkpoint inhibitor therapy ). Symptoms typically consist of  diarrhea ,  abdominal pain  and  rectal bleeding . Less commonly,  nausea  and  vomiting  may occur, which may suggest the present of  gastroenteritis . The severity of diarrhea and colitis are graded based on the frequency of bowel movements and symptoms of colitis, respectively.


The gold standard for the diagnosis of checkpoint inhibitor induced colitis is  colonoscopy  with evaluation of the  terminal ileum . However, in most cases, a  flexible sigmoidoscopy  is sufficient. Infection should be ruled out with stool studies, including  Clostridioides difficile , bacterial culture, ova and parasites. Symptoms of upper abdominal pain, nausea or vomiting warrant evaluation with  upper endoscopy .


Treatment of immune checkpoint inhibitor colitis is based on severity, as defined by the grade of diarrhea and colitis. Mild cases by managed with temporary interruption of immune checkpoint inhibitor therapy, dietary modification (low residue), and/or  loperamide . More severe cases require immune suppression with  corticosteroid therapy . If steroids are ineffective,  infliximab  may be considered. If colitis fails to improve with infliximab, then  vedolizumab  may be effective.


The most common symptom is diarrhea, which occurs in 92 percent of cases, followed by abdominal pain (82%) and rectal bleeding (64%). [ 2 ]  About 46% of cases include fever and 36% involve nausea and vomiting. [ 2 ]  Less often, nausea and vomiting may be present. Weight loss has been reported. [ 1 ]  Onset of diarrhea generally occurs about 6–7 weeks after starting immune checkpoint inhibitor therapy. [ 1 ]


The extent of diarrhea is graded based on severity, from 1 to 5.  Grade 1 diarrhea is defined by an increase in the number of stools below four per day (compared with baseline). Grade 2 diarrhea is defined by an increase of 4–6 bowel movements per day.  Grade 3 diarrhea is defined by an increase by 7 or more bowel movements per day.  Grade 4 diarrhea involves life-threatening consequences, such as shock, whereas grade 5 results in death.


The extent of colitis is also graded based on severity, from 1 to 5. Grade 1 colitis does not result in any symptoms, while grade 2 colitis leads to abdominal pain, mucous and blood in the stools.  Grade 3 colitis is defined by severe pain,  peritoneal signs  and  ileus .  Grade 4 colitis is defined by life-threatening consequences, including perforation, ischemia, necrosis, bleeding, or toxic megacolon.  Grade 5 colitis results in death.


High grade colitis may lead to severe complications, including perforation, toxic megacolon and death. Bleeding may occur due to colitis. Treatment with corticosteroids may lead to infectious complications, including:  urinary tract infections ,  C. difficile infection , and  pneumonia . [ 3 ]


Immune checkpoints are important for the normal development of  T regulatory cells  (Tregs) in the intestine. Mice with the CTLA-4 gene removed (e.g. CTLA-4 knockout) develop severe autoimmune disease, with diffuse infiltration of T cells in multiple organs and fatal enterocolitis. [ 2 ]


Immune checkpoint inhibitor colitis is typically characterized by either diffuse mucosal inflammation or focal active colitis with patchy crypt abscesses. [ 4 ]  Common findings of acute colitis include: intraepithelial neutrophilic infiltrates, crypt abscesses, and increased apoptotic cells within crypts. However, the histologic appearance varies, and evidence of chronic inflammation is seen in some cases, including intraepithelial lymphocytes or basal lymphocytes and crypt architecture distortion. [ 4 ]  Histologic inflammation may occur as early as 1–2 weeks after immune checkpoint inhibitor therapy, well before the onset of symptoms. [ 4 ]


Anti-PD-1 induced colitis may lead to more CD8+ T cell inflammation, whereas Anti-CTLA4 induced colitis may involve more CD4+ T cell infiltration and higher mucosal levels of the inflammatory molecule  TNF alpha .


Amongst people treated with immune checkpoint inhibitors, those with  Faecalibacterium  genus and other  Bacillota  present in the colonic flora have longer progression-free survival and overall survival.  In addition, a higher rate of checkpoint inhibitor induced colitis is associated with the presence of Faecalibacterium in the fecal microbiota. [ 5 ]


Colonoscopy  with evaluation of the  terminal ileum  is the gold standard in the diagnosis of checkpoint inhibitor induced colitis. [ 4 ] [ 2 ]  However, in most cases, a limited evaluation of the distal colon with  flexible sigmoidoscopy  is sufficient. [ 4 ] [ 2 ] [ 6 ]  Endoscopic findings may include loss of vascular pattern, erythema, edema, erosions, ulcers, exudates, granularity, and bleeding. [ 1 ] [ 7 ]  Biopsies should be taken even in endoscopic findings are normal, as inflammation may not be immediately apparent and may only be seen on histology ( microscopic colitis ). [ 4 ]


Symptoms of nausea, vomiting and epigastric pain may suggest involvement of the upper gastrointestinal tract. If present, evaluation with  upper endoscopy  is warranted. [ 4 ]


There are no stool tests or blood tests specific for checkpoint inhibitor induced colitis. [ 1 ]  However, diagnostic evaluation should include ruling out infectious causes for diarrhea and colitis. [ 4 ]  Stool studies should include:  Clostridioides difficile toxin , bacterial culture, ova and parasites. Testing for  CMV infection  should be considered. [ 4 ]   Fecal calprotectin  may be helpful, and is very sensitive and specific for inflammation in the intestines. [ 4 ]  Elevations in fecal calprotectin correlate with the extent of intestinal inflammation. [ 2 ]


Computed tomography  (CT) imaging may show evidence of colitis, though the sensitivity is relatively low (50%). [ 1 ]  Free air in the peritoneum indicates bowel perforation. [ 1 ]  Abdominal imaging may be necessary to rule out toxic megacolon or perforation. [ 1 ]


Though rare, gastrointestinal metastases (rare) should be considered as a cause of symptoms. [ 4 ]


Treatment varies depending on the severity of disease.  For mild disease, supportive care may be sufficient, including  loperamide  and a low residue or bland diet.  For more severe disease, the immune checkpoint inhibitor should be discontinued.   Corticosteroid  therapy is used to decrease inflammation, at a dose of roughly  prednisone  1–2 mg per kg of body weight per day. In cases that do not respond to corticosteroid therapy,  infliximab  may be used.  For cases that fail to respond to infliximab, or where infliximab is contraindicated,  vedolizumab  may be used. [ 8 ]  Overall, response rates from treatment are 59% for corticosteroids, 81% for infliximab, and 85% for vedolizumab. [ 9 ]


Surgery with resection of the colon ( colectomy ) is necessary in some instances, [ 10 ]  particularly if severe complications occur, such as perforation [ 1 ]  or toxic megacolon.


Fecal calprotectin, a stool test and marker of inflammation, may be used to follow improvement in colitis. [ 8 ]


The prevalence of checkpoint inhibitor induced colitis varies depending on the regimen of immunotherapy. The incidence is 0.7 – 1.6% for anti- programmed cell death protein 1  (PD1) agents, 5.7 – 9.1% for anti- cytotoxic T-lymphocyte associated protein 4  (CTLA-4), and about 13.6% for combination therapy. [ 2 ]  The risk associated with  ipilimumab  is  dose dependent , such that higher doses are associated with higher rates of colitis. [ 11 ]  However, other agents ( nivolumab  and  pembrolizumab ) are not associated with a dose dependent effect on the risk of immune mediated colitis. [ 11 ]


Risk factors for immune mediated colitis include  Caucasian race , treatment with an anti-CTLA4 based regimen, melanoma as cancer type, [ 3 ]   nonsteroidal anti-inflammatory drug  (NSAID) use, [ 8 ]  and a prior history of checkpoint inhibitor induced colitis.


Chromoendoscopy  is a medical procedure wherein  dyes  (often the same  stains  used in  histology ) are instilled into the  gastrointestinal tract  at the time of visualization with fibre-optic  endoscopy . The purpose of chromoendoscopy is chiefly to enhance the characterization of  tissues , although dyes may be used for other functional purposes. The detail achieved with chromoendoscopy can often allow for identification of the tissue type or pathology based upon the pattern uncovered. [ 1 ]


Stains used in chromoendoscopy have three major mechanisms. Absorptive stains have an affinity for particular mucosal elements, and include  Lugol's iodine ,  methylene blue ,  toluidine blue  and  crystal violet  (gentian violet) . Lugol's iodine specifically stains non- keratinized   squamous   epithelium , and consequently is useful for identifying squamous tissue, squamous  dysplasia  and  squamous cell carcinomas . Methylene blue stains absorptive  epithelium  and is useful for identifying abnormality in the  small intestine  and  colon .  Barrett's esophagus  involves change in the mucosa of the  esophagus  into a tissue that includes glands ( intestinal metaplasia ), and as a result, can be identified with  methylene blue  staining. [ 2 ]  Also, methylene blue has been used to identify  dysplasia  in patients with  ulcerative colitis . [ 1 ]  Toluidine blue stains nuclei of malignant cells blue, and is used in oral and esophageal squamous cell carcinoma. Crystal violet is absorbed into intestinal and neoplastic cells and is used to identify Barrett's esophagus and colonic neoplasms. [ citation needed ]


Contrast stains are not absorbed but rather provide contrast by permeating between irregularities in the  mucosa  to highlight irregularities. The primary contrast stain is  indigo carmine , administered at varying concentrations between 0.1% and 0.8%. The chief utility of indigo carmine is in the identification of  dysplastic cells  in individuals with chronic  ulcerative colitis . [ citation needed ]


Reactive stains undergo an observable change due to a chemical process related to the function of the gastrointestinal tract.  Congo red  is used as a test for  achlorhydria  in the stomach, to test adequacy of vagotomy ( post adequate vagotomy, gastric acid secretion is abolished) and to detect presence of ectopic gastric tissue, as it changes colour from red to black at a pH less than 3. Should acid not be present in the stomach, it would remain red. [ 3 ]


The most common applications for chromoendoscopy are the following: identification of  squamous cell carcinomas  or  dysplasia  of the  esophagus , identification of  Barrett's esophagus  and dysplasia, identification of early  gastric cancer , characterization of  colonic polyps  and  colorectal cancer , and in screening for  dysplasia  in individuals with  ulcerative colitis . [ 1 ]  A Cochrane review updated in 2016 found strong evidence that chromoscopy enhances the detection of cancerous tumours in the colon and rectum when compared to plain colonoscopy. [ 4 ]


The dyes used for chromoendoscopy are typically considered to be safe. Some dyes such as  indigo carmine  may discolour the feces temporarily. Lugol's iodine when applied to the esophagus can lead to discomfort, inflammation (of the esophagus or stomach) or rarely allergy.  Sodium thiosulfate  has been used to avert this. [ 1 ]


The stains are typically applied to the  mucosal  lining of the gastrointestinal tract using a device known as a spray catheter that is inserted into the endoscope. Before staining, the mucosa may need to be treated with an agent to remove excess mucus to enhance staining.  N-acetylcysteine  and  acetic acid  are typically used for this purpose. One or two minutes after staining with the dye, the mucosa typically is washed with water to remove excess amounts of the dye, which can obscure visualization. Depending on the reason for which chromoendoscopy is being performed, the dye can be sprayed directly on a suspected abnormality (such as for identification of  squamous cell carcinoma ) or diffusely to the mucosa (such as for screening for  dysplasia  in  ulcerative colitis [ 1 ]


When the stain is applied diffusely in the colon, a complete  colonoscopy  is performed with the instrument lying in the  cecum . The mucosa is washed and the dye is applied to tissue while the  endoscope  is retracted by 20 to 30 centimetres. That area of mucosa is characterized, and then the procedure is repeated in the next area of the colon that is more distal, until the procedure is completed. [ 1 ]


Stains can be used in conjunction with other techniques that allow for better identification of mucosa, such as  magnification   endoscopy . [ 1 ]  Various classification of "pit patterns" in the mucosa have been used to attempt to correlate to tissue type. The most commonly used rubric is the Kudo classification. [ 5 ]


Various other techniques have been used to delineate the mucosa of the gastrointestinal tract without the use of dyes.  Narrow-band imaging  is a technique where ambient light of a blue and green wavelengths are used to highlight detail, particularly of vascular structures. It has the advantage requiring only a change in light source, and is less cumbersome than instillation of dye. [ 1 ]  A similar technique to narrow-band imaging using blue and green filters has been used in endoscopes manufactured by  Fujinon , termed Fuji Intelligent Chromoendoscopy (FICE), and has been referred to as virtual chromoendoscopy. [ 6 ]  Other techniques that can enhance detail of mucosa include  confocal microscopy ,  magnification   endoscopy  and  optical coherence tomography . [ citation needed ]


The  CIOMS/RUCAM scale  is a tool to predict whether  liver  damage can be attributed to a particular  medication .


Determining  hepatotoxicity  (toxic effects of a substance on the liver) remains a major challenge in clinical practice due to lack of reliable markers. [ 1 ]  Many other conditions lead to similar clinical as well as pathological picture. To diagnose hepatotoxicity, a causal relationship between the use of the toxin or drug and subsequent liver damage has to be established, but might be difficult, especially when idiosyncratic reaction is suspected. [ 2 ]


The  CIOMS /RUCAM scale has been proposed to establish causal relationship between offending drug and liver damage. The CIOMS/RUCAM scale involves a scoring system which categorizes the suspicion into "definite or highly probable" (score > 8), "probable" (score 6-8), "possible" (score 3-5), "unlikely" (score 1-2) and "excluded" (score ≤ 0). In clinical practice physicians put more emphasis on the presence or absence of similarity between the biochemical profile of the patient and known biochemical profile of the suspected toxicity ( e.g. cholestatic damage in  amoxycillin-clauvonic acid  ). [ 1 ]


The  Clichy criteria  are a group of criteria proposed in determining the survival of individuals with  acute liver failure . It was based on a study of patients presenting with viral hepatitis, of which individuals with the lowest survival were identified.


Two criteria predicted the prognosis of patients with poor survival:


The positive predictive value of mortality was 82% and the negative predictive value of mortality was 98% in individuals meeting these criteria.


The  kidney bean sign  (more commonly called the  coffee bean sign;  also  bent inner tube sign ) is a  radiologic sign  observed on  abdominal radiographs  that indicates the presence of a  sigmoid volvulus , a form of bowel obstruction. It is seen as an area of hyperlucency resembling a coffee bean. [ 1 ]  The opposed walls of adjacent bowel loops form the central cleft while the two sides of the bean represent gas‐filled segments of dilated bowel that form an inverted U‐shape. [ 2 ]  Air-fluid levels may also be seen in the segments of dilated bowel. [ 1 ]


This  medical  diagnostic article is a  stub . You can help Wikipedia by  expanding it .


Cystica profunda  is a rare disease of the gut lining. It is characterized by formation of  mucin   cysts  in the muscle layers of the gut lining, and it can occur anywhere along the  gastrointestinal tract . [ citation needed ]


When the condition occurs in the stomach, it may be termed  gastritis cystica profunda , and in the small intestine,  enteritis cystica profunda . [ 1 ]


When it occurs in the  colon , it is termed  colitis cystica profunda . Colitis cystica profunda is benign, but it may mimic a tumor. [ 2 ]   When it occurs in the rectum it may be termed  colitis cystica  profunda , or termed  proctitis cystica profunda . Some consider this synonymous, or closely related to  solitary rectal ulcer syndrome , a consequence of  internal rectal intussusception . [ citation needed ]


It can have benign columnar epithelium and mucosal cysts deep to the muscularis mucosa on microscopy. Hence it can be mistaken for an invasive adenocarcinoma. [ citation needed ]


This article about an endocrine, nutritional, or metabolic disease is a  stub . You can help Wikipedia by  expanding it .


The  De Simone Formulation  is a  probiotic  formula and manufacturing method developed by Claudio De Simone. [ 1 ]


The De Simone Formulation has been  clinically studied  for a variety of health conditions since the 1990s [ 2 ]  but it has been researched the most for its efficacy in the medical management of chronic intestinal conditions including  irritable bowel syndrome  (IBS) [ 3 ] [ 4 ]  and  inflammatory bowel disease  (IBD). [ 5 ] [ 6 ] [ 7 ] [ 8 ]


The De Simone Formulation has been the subject of lawsuits. In the United States, the 4th U.S. Circuit Court of Appeals upheld a  false advertising  verdict against the makers of the VSL#3 probiotic in February 2021 stating there was enough evidence to support a jury's November 2018 finding that the makers of VSL#3 had quote "reverse-engineered an imperfect copy" of De Simone's signature probiotic formulation that was sold under the brand name VSL#3 through May 2016 after he withdrew from their joint venture, VSL Pharmaceuticals Inc. According to the lawsuit, his departure was as a result of being pressured to substitute cheaper bacteria in the manufacturing process to lower production costs and raise profits. [ 9 ]  Court action states that De Simone apparently refused. [ 10 ]  The makers of VSL#3 were ordered to pay De Simone and ExeGi Pharma a combined total of $18 million (USD) in damages. [ 11 ] [ 12 ]


The Court also issued a permanent  injunction  intended to prevent claims, implied or stated, of continuity between the two different formulations.  The court also cited public health and wellbeing concerns, when they blocked the makers of VSL#3 from linking their product with the original De Simone Formulation by referring to  clinical studies  that were executed using the De Simone Formulation prior to May 2016. [ 13 ]


On August 1, 2019, the American Gastroenterology Association (AGA), the medical association of gastroenterologists in the United States, issued a correction regarding the De Simone Formulation and VSL#3.  AGA's correction stated it had referenced studies referenced in its 2019 Technical Review on the Management of Mild-to-Moderate Ulcerative Colitis that were based on the probiotic formulation previously know by the brand name VSL#3 before May 2016, but was now known by the formulation name 'De Simone Formulation'. [ 14 ] [ 15 ]


On January 24, 2022, the European Crohn's and Colitis Organization (ECCO) issued a letter to the editor of Oxford Academic's Journal of Crohn's and Colitis (JCC) stating that as a result of a court injunction, the ECCO must provide a clarification note for changes relating to VSL#3 and the De Simone Formulation in their articles that reference or studied these probiotics. [ 16 ]


Intestinal desmosis  is a medical condition implicated in gut motility disorder and chronic  constipation . Desmosis can be observed as the absence of the  tendinous  plexus layer and connective tissue fibers. [ 1 ] [ 2 ]


The absence of the tendinous plexus layer was first described in 1998 by Meier-Ruge. [ 3 ]


Desmosis is implicated in disturbed gut  motility . [ 4 ]  Normal  peristalsis  depends upon the interaction between muscles, nerve cells and tendinous connective tissue. A malfunction of any of these leads to intestinal motility disorders. Patients with desmosis demonstrate chronic constipation.


Desmosis may be congenital (aplastic form) or acquired (atrophic form). [ 5 ]


The  aplastic [ 5 ]  form is rare. Typical clinical findings are hypoperistalsis, and pseudo-obstruction. These are found in premature infants, associated with low birth weight.


The  atrophic [ 6 ]  form is more frequent. Inflammation of the muscularis propria releases  enzymes  including  collagenases  which destroy the connective tissue of the bowel wall. Primarily newborns and small children are affected, although this manifestation can also be found in adults. The most common location is the colon with a necrotizing enterocolitis as well as  Crohn Disease  and  diverticulitis . If the taenia are also affected, the disease is defined as complete atrophic desmosis, all other forms without involvement of the taenia are referred to as incomplete. Clinically, patients demonstrate chronic  constipation .


As proposed by Giuseppe Martucciello, [ 7 ]  microscopic diagnosis requires laparoscopic intestinal full-thickness biopsies from colon. Histological findings are absence of the tendinous plexus layer and connective tissue fibers in longitudinal and circular muscle layer. [ 2 ]


Proton pump inhibitors  (PPIs) block the gastric  hydrogen potassium ATPase  (H + /K +  ATPase) and inhibit gastric acid secretion. These drugs have emerged as the treatment of choice for acid-related diseases, including  gastroesophageal reflux disease  (GERD) and  peptic ulcer disease .
PPIs also can bind to other types of proton pumps such as  those that occur in cancer cells and are finding applications in the reduction of cancer cell acid efflux and reduction of chemotherapy drug resistance.


Evidence emerged by the end of the 1970s that the newly discovered proton pump (H + /K +  ATPase) in the secretory membrane of the  parietal cell  was the final step in acid secretion. [ 1 ]  Literature from anaesthetic screenings led attention to the potential antiviral compound pyridylthioacetamide which after further examination pointed the focus on an anti-secretory compound with unknown mechanisms of action called  timoprazole . [ 2 ] [ 3 ] [ 4 ]  Timoprazole is a pyridylmethylsulfinyl  benzimidazole  and appealed due to its simple chemical structure and its surprisingly high level of anti-secretory activity. [ 5 ]


Optimization of substituted benzimidazoles and their antisecretory effects were studied on the newly discovered proton pump to obtain higher  pKa  values of the  pyridine , thereby facilitating accumulation within the parietal cell and increasing the rate of acid-mediated conversion to the active mediate. As a result of such optimization the first proton pump inhibiting drug,  omeprazole , was released on the market. [ 4 ] [ 6 ]
Other PPIs like  lansoprazole  and  pantoprazole  would follow in its footsteps, claiming their share of a flourishing market, after their own course of development. [ citation needed ]


PPIs can be divided into two groups based on their basic structure. Although all members have a  substituted  pyridine part, one group has linked to various benzimidazoles, whereas the other has linked to a substituted imidazopyridine. All marketed PPIs (omeprazole, lansoprazole, pantoprazole) are in the benzimidazole group. [ citation needed ]


Proton pump inhibitors are  prodrugs  and their actual inhibitory form is somewhat controversial. In acidic solution, the  sulfenic acid  is isolated before reaction with one or more cysteines accessible from the  luminar  surface of the  enzyme , a tetracyclic sulfenamide. This is a planar molecule thus any enantiomer of a PPI loses stereospecifity upon activation. [ 7 ]


The effectiveness of these drugs derives from two factors: their target, the H + /K +  ATPase which is responsible for the last step in acid secretion; therefore, their action on acid secretion is independent of the stimulus to acid secretion, of  histamine ,  acetylcholine , or other yet to be discovered stimulants. In addition, their mechanism of action involves  covalent binding  of the activated drug to the enzyme, resulting in a duration of action that exceeds their plasma  half-life . [ 7 ] [ 8 ]


Acid secretion by the human  stomach  results in a median  diurnal   pH  of 1.4. This very large (>10 6 -fold) H +   gradient  is generated by the gastric H + /K +  ATPase which is an ATP-driven proton pump. Hydrolysis of one ATP molecule is used to catalyse the electroneutral exchange of two luminal  potassium  ions for two  cytoplasmic   protons  through the gastric membrane. [ 9 ]


The proton pump, H + /K +  ATPase is a α,β-heterodimeric enzyme. The  catalytic  α subunit has ten  transmembrane  segments with a cluster of intramembranal  carboxylic   amino acids  located in the middle of the transmembrane segments TM4, TM5, TM6 and TM8. The β subunit has one transmembrane segment with  N terminus  in cytoplasmic region. The  extracellular   domain  of the β subunit contains six or seven  N -linked  glycosylation  sites which is important for the enzyme assembly, maturation and sorting. [ 10 ]


The ion transport is accomplished by cyclical conformational changes of the enzyme between its two main  reaction  states, E1 and E2. The cytoplasmic-open E1 and luminal-open E2 states have high affinity for H +  and K + . [ 9 ]  The expulsion of the proton at 160  mM  (pH 0.8)  concentration  results from movement of  lysine  791 into the  ion  binding site in the E2P configuration. [ 10 ]


In the year 1975, timoprazole was found to inhibit acid secretion irrespective of stimulus, extracellular or intracellular. [ 7 ]  Studies on timoprazole revealed enlargement of the  thyroid gland  due to  inhibition  of  iodine  uptake as well as  atrophy  of the  thymus  gland. A literature search showed that some  substituted  mercapto-benzimidazoles had no effect on iodine uptake and introduction of such substituents into timoprazole resulted in an elimination of the toxic effects, without reducing the antisecretory effect. [ 6 ]  A derivative of timoprazole, omeprazole, was discovered in 1979, and was the first of a new class of drug that control acid secretion in the stomach, a proton pump inhibitor (PPI). [ 11 ] [ 12 ]  Addition of 5-methoxy-substitution to the benzimidazole moiety of omeprazole was also made and gave the compound much more stability at neutral pH. [ 6 ]  In 1980, an Investigational New Drug (IND) application was filed and omeprazole was taken into Phase III human trials in 1982. [ 6 ]  A new approach for the treatment of acid-related diseases was introduced, and omeprazole was quickly shown to be clinically superior to the  histamine H 2  receptor antagonists , and was launched in 1988 as Losec in Europe, and in 1990 as Prilosec in the United States. In 1996, Losec became the world's biggest ever selling pharmaceutical, and by 2004 over 800 million patients had been treated with the drug worldwide. During the 1980s, about 40 other companies entered the PPIs area, but few achieved market success:  Takeda  with lansoprazole, Byk Gulden (now  Nycomed ) with pantoprazole, and  Eisai  with rabeprazole, all of which were analogues of omeprazole. [ 7 ] [ 8 ]


The story of pantoprazole's discovery is a good example of the stepwise development of PPIs. The main focus of modification of timoprazole was the benzimidazole part of its structure. Addition of a  trifluoromethyl  group to the benzimidazole  moiety  led to a series of very active compounds with varying solution-stability. In general fluoro substituents were found to block  metabolism  at the point where they were attached. Later the more balanced fluoroalkoxy substituent, instead of the highly  lipophilic  and strongly electron-withdrawing trifluoromethyl substituent, led to highly active compounds with supposed longer half-lives and higher solution stability. [ 5 ]


It was realized that activity was somehow linked to instability in solution and then came to the conclusion that the cyclic sulfenamides, formed in acidic conditions, were the active principle of the PPIs. Finally, it was understood that seemingly small alterations in the backbone of timoprazole led nowhere, and focus had to be centered on the substituents on the backbone. However, necessary intramolecular rearrangement of the benzimidazole into sulfenamide posed severe  geometric  constraints. Optimal compounds would be those that were stable at neutral pH but were quickly activated at low pH. [ 5 ]


A clear-cut design of active inhibitors was still not possible because in the complex multi-step chemistry the influence of a substituent on each step in the cascade could be different, and therefore not predictable for the overall rate of the prerequisite acid activation. Smith Kline and French, that entered into collaboration with Byk Gulden mid-1984, greatly assisted in determining criteria for further development. From 1985, the aim was to identify a compound with good stability at neutral pH, sustaining this higher level of stability down to pH 5 but being rapidly activateable at lower pHs, combined with a high level of H + /K +  ATPase inhibition. [ 13 ]  From the numerous already synthesized and tested compounds that fulfilled these criteria the most promising candidates were pantoprazole and its salt, pantoprazole sodium. [ 5 ]


In 1986 pantoprazole sodium sesquihydrate was synthesized and from 1987 onwards the development of pantoprazole was switched to the sodium salt which is more stable and has better compatibility with other excipients used in the drug formulation. [ citation needed ]


Pantoprazole was identified after nearly seven years of research and registered for clinical use after a further seven years of development, and finally reached its first market in 1994 in Germany. During the course of the studies on pantoprazole, more than 650 PPIs had been synthesized and evaluated. [ 5 ]  Pantoprazole obtained high selection criteria in its development process — especially concerning the favorable low potential for interaction with other drugs. Good solubility of pantoprazole and a very high solution stability allowed it to become the first marketed PPI for intravenous use in critical care patients. [ 5 ]


Omeprazole showed an inter-individual variability and therefore a significant number of patients with acid-related disorders required higher or multiple doses to achieve symptom relief and healing. Astra started a new research program in 1987 to identify a new analogue to omeprazole with less interpatient variability. Only one compound proved superior to omeprazole and that was the ( S )-(−)-isomer, esomeprazole, which was developed as the magnesium salt. Esomeprazole magnesium (brand name Nexium) received its first approval in 2000 and provided more pronounced inhibition of acid secretion and less inter-patient variation compared to omeprazole. In 2004, Nexium had already been used to treat over 200 million patients. [ 7 ] [ 8 ]


Omeprazole was the first PPI on the market, in 1988. It is a 1:1 racemate drug with a backbone structure of timoprazole, but substituted with two methoxy and two methyl groups. One of the methoxy group is at position 6 of the bensoimidazole and the other at position 4 of the pyridine and the methyl groups are at position 3 and 5 of the pyridine.
Omeprazole is available as enteric-coated  tablets ,  capsules , chewable tablets,  powder  for oral  suspensions  and powder for  intravenous injection . [ citation needed ]


Lansoprazole was the second of the PPI drugs to reach the market, being launched in Europe in 1991 and the US in 1995.
It has no substitutions at the benzimidazole  but two substituents on the pyridine, methyl group at position 3 and a trifluoroethoxy group at position 4. The drug is a 1:1  racemate  of the  enantiomers  dexlansoprazole and levolansoprazole. It is available in gastroresistant capsules and tablets as well as chewable tablets. [ citation needed ]


Pantoprazole was the third PPI and was introduced to the German market in 1994.
It has a difluoroalkoxy sidegroup on the benzimidazole part and two methoxy groups in position 3 and 4 on the pyridine.
Pantoprazole was first prepared in April 1985 by a small group of scale-up chemists. It is a dimethoxy-substituted pyridine bound to a fluoroalkoxy substituted benzimidazole. [ 5 ]
Pantoprazole sodium is available as gastroresistant or delayed release tablets and as lyophilized powder for intravenous use.


Rabeprazole is a novel benzimidazole compound on market, since 1999 in USA. It is similar to lansoprazole in having no substituents on its benzimidazole part and a methyl group at site 3 on the pyridine, the only difference is the methoxypropoxy substitution at site 4 instead of the trifluoroethoxy group on lansoprazole.
Rabeprazole is marketed as rabeprazole sodium salt. It is available as enteric-coated tablets. [ citation needed ]


In 2001 esomeprazole was launched in USA, as a follow-up of omeprazoles patent.
Esomeprazole is the ( S )-(−)-enantiomer of omeprazole and provides higher  bioavailability  and improved  efficacy , in terms of stomach acid control, over the ( R )-(+)-enantiomer of omeprazole. In theory, by using pure esomeprazole the effects on the proton pump will be equal in all patients, eliminating the "poor metabolizer effect" of the racemate omeprazole. It is available as delayed-release capsules or tablets and as esomeprazole sodium for intravenous injection/infusion. Oral esomeprazole preparations are enteric-coated, due to the rapid degradation of the drug in the acidic condition of the stomach. This is achieved by formulating capsules using the multiple-unit pellet system.
Although the ( S )-(−)- isomer  is more potent in humans, the ( R )-(+)-isomer is more potent in testings of rats, while the enantiomers are equipotent in dogs. [ 14 ]


Dexlansoprazole was launched as a follow up of lansoprazole in 2009.
Dexlansoprazole is an ( R )-(+)-enantiomer of lansoprazole, marketed as Dexilant. After oral appliance of the racemic lansoprazole, the circulating drug is 80% dexlansoprazole. Moreover, both enantiomers have similar effects on the proton pump. [ 15 ]  Consequently, the main advantage of Dexilant is not the fact that it is an enantiopure substance. The advantage is the pharmaceutical formulation of the drug, which is based on a dual release technology, with the first quick release producing a  blood plasma  peak concentration about one hour after application, and the second retarded release producing another peak about four hours later. [ 16 ]


Tenatoprazole (TU-199), an  imidazopyridine  proton pump inhibitor, is a novel compound that has been designed as a new chemical entity with a substantially prolonged plasma half-life (7 hours), but otherwise has similar activity as other PPIs. [ 17 ]


The difference in the structural backbone of tenatoprazole compared to benzimidazole PPIs, is its imidazo[4,5-b]pyridine moiety, which reduces the rate of metabolism, allowing a longer plasma residence time but also decreases the pKa of the fused imidazole  N  as compared to the current PPIs. [ 18 ]  Tenatoprazole has the same substituents as omeprazole, the methoxy groups at position 6 on the imidazopyridine and at position 4 on the pyridine part as well as two methyl groups at position 3 and 5 on the pyridine.


The bioavailability of tenatoprazole is double for the ( S )-(−)-tenatoprazole sodium salt  hydrate  form when compared to the free form in dogs. This increased bioavailability is due to differences in the  crystal structure  and  hydrophobic  nature of the two forms, and therefore its more likely to be marketed as the pure ( S )-(−)-enantiomer. [ citation needed ]


The disulfide binding of the inhibitor takes place in the luminal sector of the H + /K +  ATPase were 2 mol of inhibitor is bound per 1 mol of active site H + /K +  ATPase. [ 19 ] [ 20 ]
All PPIs react with cysteine 813 in the loop between TM5 and TM6 on the H + /K +  ATPase, fixing the enzyme in the E2 configuration. Omeprazole reacts with cysteine 813 and 892. Rabeprazole binds to cysteine 813 and both 892 and 321. Lansoprazole reacts with cysteine 813 and cysteine 321, whereas pantoprazole and tenatoprazole react with cysteine 813 and 822. [ 18 ] [ 21 ] [ 22 ] [ 23 ]
 Reaction  with cysteine 822 confers a rather special property to the covalently inhibited enzyme, namely  irreversibility  to  reducing  agents. The likely first step is binding of the prodrug protonated on the pyridine of the compound with cysteine 813. Then the second proton is added with acid transport by the H + /K +  ATPase, and the compound is activated. Recent data suggest the hydrated sulfenic acid to be the reactive species forming directly from the mono-protonated benzimidazole bound on the surface of the pump. [ 7 ]


Even though consumption of food stimulates acid secretion and acid secretion activates PPIs, PPIs cannot inhibit all pumps. About 70% of pump enzyme is inhibited, as PPIs have a short half-life and not all pump enzymes are activated. It takes about 3 days to reach steady-state inhibition of acid secretion, as a balance is struck between covalent inhibition of active pumps, subsequent stimulation of inactive pumps after the drug has been eliminated from the blood, and  de novo  synthesis of new pumps. [ 8 ]


Although the drugs omeprazole, lansoprazole, pantoprazole, and rabeprazole share common structure and mode of action, each differs somewhat in its clinical pharmacology. [ 24 ]
Differing pyridine and benzimidazole substituents result in small, but potentially significant different physical and chemical properties.
Direct comparison of pantoprazole sodium with other anti-secretory drugs showed that it was significantly more effective than H 2 -receptor antagonists and either equivalent or better than other clinically used PPIs. [ 5 ]  Another study states rabeprazole undergoes activation over a greater pH range than omeprazole, lansoprazole, and pantoprazole, and converts to the sulphenamide form more rapidly than any of these three drugs. [ 23 ]
Most oral PPI preparations are enteric-coated, due to the rapid degradation of the drugs in the acidic conditions of the stomach. For example omeprazole is unstable in acid with a half-life of 2 min at pH 1–3, but is significantly more stable at pH 7 (half-life ca. 20 h).
The acid protective coating prevents conversion to the active principle in the lumen of the stomach, which then will react with any available sulfhydryl group in food and will not penetrate to the lumen of the secretory canaliculus [ 10 ]


The oral bioavailability of PPIs is high; 77% for pantoprazole, 80–90% for lansoprazole and 89% for esomeprazole. All the PPIs except tenatoprazole are rapidly metabolized in the liver by CYP enzymes, mostly by  CYP2C19  and  CYP3A4 . PPIs are sensitive to CYP enzymes and have different pharmacokinetic profiles. Studies comparing the efficacy of PPIs indicate that esomeprazole and tenatoprazole have stronger acid suppression, with a longer period of intragastric pH (pH > 4). [ 25 ] [ 26 ] [ 27 ] [ 28 ] [ 29 ]


Studies of the effect of tenatoprazole on acid secretion in  in vivo  animal models, such as pylorus-ligated rats and acute gastric fistula rats, demonstrated a 2- to 4-fold more potent inhibitory activity compared with omeprazole. A more potent inhibitory activity was also shown in several models of induced gastric lesions. [ 30 ]  In Asian as well as Caucasian healthy subjects, tenatoprazole exhibited a seven-fold longer half-life than the existing H + /K +  ATPase inhibitors. [ 31 ]  It is thus hypothesized that a longer half-life results in a more prolonged inhibition of gastric acid secretion, especially during the night.
A strong relationship has been stated between the degree and duration of gastric acid inhibition, as measured by monitoring of the 24-hour intragastric pH in pharmacodynamic studies, and the rate of healing and symptom relief reported.
A clinical study showed that nocturnal acid breakthrough duration was significantly shorter for 40 mg of tenatoprazole than for 40 mg of esomeprazole, with the conclusion that tenatoprazole was significantly more potent than esomeprazole during the night. Although, the therapeutic relevance of this pharmacological advantage deserves further study. [ 17 ]


PPIs have been used successfully in triple-therapy regiments with  clarithromycin  and  amoxicillin  for the  eradication of  Helicobacter pylori  with no significant difference between different PPI-based regimens. [ 10 ]


Despite the fact that PPIs have revolutionized the treatment of  GERD , there is still room for improvement in the speed of onset of acid suppression as well as mode of action that is independent of an acidic environment and also better inhibition of the proton pump. [ 8 ]  Therefore, a new class of PPIs,  potassium-competitive acid blockers  (P-CABs) or  acid pump antagonists  (APAs), have been under development the past years and will most likely be the next generation of drugs that suppress gastric activity. [ 32 ]  These new agents can in a reversible and competitive fashion inhibit the final step in the gastric acid secretion with respect to K +  binding to the parietal cell gastric H + /K +  ATPase. That is, they block the action of the H + /K +  ATPase by binding to or near the site of the K +  channel. Since the binding is competitive and reversible these agents have the potential to achieve faster inhibition of acid secretion and longer duration of action compared to PPIs, resulting in quicker symptom relief and healing. [ 33 ] [ 34 ]  The  imidazopyridine -based compound SCH28080 was the prototype of this class, and turned out to be hepatotoxic. [ 35 ]  Newer agents that are currently in development include  CS-526 ,  linaprazan ,  soraprazan  and  revaprazan  in which the latter have reached clinical trials. Studies remain to determine whether these or other related compounds can become useful. [ 34 ] [ 36 ]  In June 2006,  Yuhan  obtained approval from the Korean FDA for the use of  revaprazan  (brand name Revanex) in the treatment of gastritis. [ 37 ]


Vonoprazan  is a newer agent with a faster and longer lasting action, first marketed in Japan, then in Russia, and in 2023 was approved for use in the US. It is still being trialed in the UK. [ 38 ]


Dolichocolon  is an abnormally long  large intestine . [ 1 ]  It should not be confused with an abnormally wide large intestine, which is called a  megacolon . [ citation needed ]


Dolichocolon may predispose to abnormal rotation (see  volvulus ) and interposition between the diaphragm and the liver (see  Chilaiditi syndrome ). It is more commonly seen in the  elderly , some psychiatric patients or in institutionalised individuals. It is not, however, a part of normal aging. The exact cause remains unknown. Dolichocolon is often an incidental finding on  abdominal X-rays  or  colonoscopy . It is not by itself a disease and as such requires no treatment. The term is from  ancient Greek   dolichos , the long distance in running, and  colon .


Endoanal ultrasound  is a type of medical investigation which images the structures of the  anal canal . [ 1 ]


It is used in the investigation of some anorectal symptoms, e.g.  fecal incontinence  or  obstructed defecation . [ 2 ]


This article related to  medical imaging  is a  stub . You can help Wikipedia by  expanding it .


An  endoclip  is a metallic mechanical device used in  endoscopy  in order to close two mucosal surfaces without the need for surgery and  suturing .  Its function is similar to a  suture  in gross surgical applications, as it is used to join together two disjointed surfaces, but, can be applied through the channel of an endoscope under direct visualization.  Endoclips have found use in treating  gastrointestinal bleeding  (both in the  upper  and  lower GI tract ), in preventing bleeding after therapeutic procedures such as  polypectomy , and in closing  gastrointestinal perforations .  Many forms of endoclips exist of different shapes and sizes, including two and three prong devices, which can be administered using single use and reloadable systems, and may or may not open and close to facilitate placement.


The endoclip was first described by Hayashi and Kudoh in 1975, [ 1 ]   and was termed the "staunch clip".  Initial attempts to incorporate the clip into applications in endoscopy (such as clipping bleeding  blood vessels ) were limited by the applicator system of the clip. [ 1 ]   However, by 1988, an easy to use applicator delivery system was developed, and a functional reloadable endoclip system was described. [ 2 ]   This consisted of a stainless steel clip (of size approximately 6 mm long and 1.2 mm wide at the prongs) with a metal deployment device (that could be used to insert the clip into the endoscopic camera, and deployed outside the camera) enclosed in a plastic sheath. [ 1 ]   These clips were initially reloadable. [ citation needed ]


Endoclips in use today have a variety of additional shapes and sizes than the original.  Clips with two and three prongs (TriClip,  Cook Medical [ 3 ] ) have been described and used for various applications. [ 4 ]   Rotatable clips have been devised to improve localization of deployment. [ 5 ]   Also, clips that open and close (as opposed to single-deployment) have also been developed (Resolution Clip,  Boston Scientific [ 6 ] ), and also facilitate the appropriate location of deployment. [ 7 ]


When a treatable lesion is identified on  endoscopy  (such as a bleeding vessel), an endoclip can be inserted through the channel of the endoscope until the sheathed clip is visible on the endoscopic image, and the handle for deployment handed to the  nurse  assistant.  The clip is unsheathed by retraction at the handle, positioned, and "fired" by the assistant to treat the lesion. [ citation needed ]


Endoclips have found a primary application in  hemostasis  (or the stopping of bleeding) during  endoscopy  of the upper (through  gastroscopy ) or lower (through  colonoscopy ) gastrointestinal tract. [ 1 ]   Many bleeding lesions have been successfully clipped, including bleeding  peptic ulcers , [ 4 ]   Mallory-Weiss tears  of the  esophagus , [ 8 ]   Dieulafoy's lesions , [ 9 ]   stomach tumours , [ 10 ]  and bleeding after  removal of polyps . [ 11 ]   Bleeding peptic ulcers require endoscopic treatment if they show evidence of high risk stigmata of re-bleeding, such as evidence of active bleeding or oozing on  endoscopy  or the presence of a visible blood vessel around the ulcer. [ 12 ] [ 13 ]   The alternatives to endoscopic clipping of peptic ulcers are thermal therapy (such as  electrocautery  to burn the vessel causing the bleeding), or injection of  epinephrine  to constrict the blood vessel.  Comparative studies between endoclips and thermal therapy make the point that endoclips cause less trauma to the  mucosa  around the ulcer than electrocautery, [ 14 ]  but no definitive advantage to either approach has reached consensus by  gastroenterologists . [ 15 ] [ 16 ]


Endoclips have also found an application in preventing bleeding when performing complicated endoscopic procedures.  For example, prophylactic clipping of the base of a polyp has been found to be useful in preventing post- polypectomy  bleeding, especially in high-risk patients or patients on  anticoagulant  medications. [ 17 ]   In addition, clips can be used to close  gastrointestinal perforations  that may have been caused by complicated therapeutic endoscopy procedures, such as  polypectomy , or by the endoscopic procedure itself. [ 18 ]   Clips have also been used to secure the placement of endoscopic  feeding tubes , [ 19 ]  and to orient the  bile duct  to assist with  endoscopic retrograde cholangiopancreatography , a procedure used to image to bile duct. [ 20 ]


Endoclips have been seen to dislodge between 1 and 3 weeks from deployment, [ 21 ]  although lengthy clip retention intervals of as high as 26 months have been reported. [ 1 ] [ 9 ]   Endoclips are believed to be safe and no major complications (such as perforation or impaction) have been reported with them, although concern has been raised about blocking the outflow of the bile duct if clips are deployed in the  duodenum . [ 1 ]


An  endoscopy unit  refers to a dedicated area where medical procedures are performed with  endoscopes , which are cameras used to visualize structures within the body, such as the  digestive tract  and  genitourinary system .  Endoscopy units may be located within a  hospital , incorporated within other medical care centres, or may be stand-alone in nature.


In the early days of endoscopy, when fewer procedures were carried out, facilities such as  operating theatres  tended to be used; as the number of procedures carried out and the complexity of the procedures and equipment increased, the need for specialised rooms and staff became apparent. [ 1 ]


An endoscopy unit consists of the following components: trained and accredited endoscopists (which are usually  gastroenterologists  or  surgeons ); trained nursing and additional staff; endoscopes and other equipment; preparation, procedural and recovery areas; a disinfection and cleaning area for equipment; emergency equipment and personnel; and, a program for quality assurance.  [ 2 ]   Procedures performed within an endoscopy unit may include gastrointestinal endoscopy (such as  gastroscopy ,  colonoscopy ,  ERCP , and  endoscopic ultrasound ),  bronchoscopy ,  cystoscopy , or other more specialized procedures.  Endoscopy units may be part of a hospital, where emergency procedures may be performed on ill patients admitted to hospital; however, most endoscopies are performed on ambulatory patients in the outpatient setting. [ citation needed ]


Endoscopy units consist of a number of areas: [ citation needed ]


These are the rooms where the endoscopic procedures are performed.


Procedure rooms should to contain: [ citation needed ]


Procedure rooms should be at least 200 square feet (19 m 2 ) in size, and hospitals should have at least two procedure rooms. Larger endoscopy units should contain one procedure room per 1,000 to 1,500 procedures performed annually. [ 3 ]


Since a number of patients undergoing endoscopy receive sedation, and a few emergency patients may be unstable, there must be an area available for the observation of patients until they have recovered. These areas also need to have piped oxygen, full monitoring facilities (including pulse oximetry), suction,  resuscitation equipment  and emergency drugs. [ 3 ]


An  enema , also known as a  clyster , is an injection of fluid into the rectum or into  lower bowel  by way of the  rectum . [ 1 ]  The word  enema  can also refer to the liquid injected, [ 2 ] [ 3 ]  as well as to a device for administering such an injection. [ 4 ]


In standard medicine, the most frequent uses of enemas are to relieve constipation and for bowel cleansing before a medical examination or procedure; [ 5 ]  also, they are employed as a  lower gastrointestinal series  (also called a barium enema), [ 6 ]  to treat  traveler's diarrhea , [ 7 ]  as a vehicle for the administration of food, water or medicine, as a stimulant to the general system, as a local application and, more rarely, as a means of reducing body temperature, [ 1 ]  as treatment for  encopresis , and as a form of  rehydration therapy  (proctoclysis) in patients for whom  intravenous therapy  is not applicable. [ 8 ]


The principal medical usages of enemas are:


As  bowel  stimulants, enemas are employed for the same purposes as orally administered  laxatives : to relieve  constipation ; to treat  fecal impaction ; to empty the colon prior to a medical procedure such as a  colonoscopy . When oral laxatives are not indicated or are not sufficiently effective, enemas may be a sensible and necessary measure. [ 9 ]


A large volume enema [ 10 ]  can be given to cleanse as much of the colon as possible of feces. [ 11 ] [ 12 ]  However, a low enema is generally useful only for stool in the rectum, not in the intestinal tract. [ 13 ]


Such enemas' mechanism consists of the volume of the liquid causing a rapid expansion of the intestinal tract in conjunction with, in the case of certain solutions, irritation of the intestinal  mucosa  which stimulates peristalsis and lubricates the stool to encourage a bowel movement. [ 14 ]  An enema's efficacy depends on several factors including the volume injected and the temperature and the contents of the infusion. [ 9 ]  In order for the enema to be effective the patient should retain the solution for five to ten minutes, as tolerated. [ 5 ] [ 14 ]  or, as some nursing textbooks recommend, for five to fifteen minutes or as long as possible. [ 15 ]


For emptying the entire colon as much as feasible [ 12 ]  deeper and higher enemas are utilized to reach large sections of the colon. [ 9 ]  The colon dilates and expands when a large volume of liquid is injected into it, and the colon reacts to that sudden expansion with general contractions,  peristalsis , propelling its contents toward the rectum. [ 5 ]


Soapsuds enema  is a frequently used synonym for a large volume enema (although soap is not necessary for effectivity). [ 5 ]


For relieving occasional constipation, a large volume enema may be used in a home setting, although for recurring or severe cases of constipation medical care may be required. [ 5 ]


Plain water can be used, simply functioning mechanically to expand the colon, thus prompting evacuation.


Normal saline  is least irritating to the colon. Like plain water, it simply functions mechanically to expand the colon, but having a neutral concentration gradient, it neither draws  electrolytes  from the body, as happens with plain water, nor draws water into the colon, as occurs with phosphates. Thus, a salt water solution can be used when a longer period of retention is desired, such as to soften an impaction.


Castile soap  is commonly added because its irritation of the colon's lining increases the urgency to defecate. [ 15 ]  However, liquid handsoaps and detergents should not be used. [ 5 ]


Glycerol  is a specific bowel mucosa irritant serving to induce peristalsis via a  hyperosmotic effect . [ 16 ]  It is used in a dilute solution, e.g., 5%. [ 17 ]


Equal parts of milk and molasses heated together to slightly above normal body temperature have been used. [ 18 ]  Neither the milk sugars and proteins nor the molasses are absorbed in the lower intestine, thus keeping the water from the enema in the intestine. [ 19 ]  Studies have shown that milk and molasses enemas have a low complication rate when used in the  emergency department [ 20 ]  and are safe and effective with minimal side effects. [ 21 ]


Mineral oil  functions as a lubricant and stool softener, but may have side effects including rectal skin irritation and leakage of oil. [ 22 ]


ATC code A06   Drugs for constipation  is a therapeutic subgroup of the  Anatomical Therapeutic Chemical Classification System , a system of alphanumeric codes developed by the  World Health Organization  (WHO) for the classification of  drugs  and other medical products. [ 23 ] [ 24 ] [ 25 ]  Subgroup A06 is part of the anatomical group  A  Alimentary tract and metabolism . [ 26 ]


Codes for  veterinary  use ( ATCvet codes ) can be created by placing the letter Q in front of the human ATC code: for example,  QA06 . [ 27 ]   National issues of the ATC classification may include additional codes not present in this list, which follows the WHO version.


In alphabetical order


In alphabetical order of the original brand names


Klyx contains  docusate sodium  1 mg/mL and sorbitol solution (70%)(crystallising) 357 mg/mL and is used for faecal impaction or constipation or for colon evacuation prior medical procedures, [ 44 ]  developed by  Ferring B.V.


Micralax (not to be confused with MICROLAX®) [ 45 ]


MICROLAX®  (not to be confused with Micralax) combines the action of  sodium citrate , a peptidising agent which can displace bound water present in the faeces, with sodium alkyl sulphoacetate, a wetting agent, and with glycerol, an anal mucosa irritant and hyperosmotic. However, also sold under the name "Micralax", is a preparation containing  sorbitol  rather than glycerol; [ 46 ]  which was initially tested in preparation for  sigmoidoscopy . [ 47 ]


Micolette Micro-enema® contains 45 mg sodium lauryl sulphoacetate, 450 mg per 5 ml sodium citrate BP, and 625 mg glycerol BP [ 48 ]  and is a small volume stimulant enema suitable where large-volume enemas are contra-indicated. [ 28 ]


TAI , also termed  retrograde irrigation , is designed to assist evacuation using a water enema [ 49 ]  as a treatment for persons with bowel dysfunction, including  fecal incontinence  or constipation, especially  obstructed defecation . By regularly emptying the bowel using transanal irrigation, [ 50 ]  controlled bowel function is often re-established to a high degree, thus enabling development of a consistent bowel routine. [ 50 ]   Its effectiveness varies considerably, some individuals experiencing complete control of incontinence but others reporting little or no benefit. [ 49 ]


An international consensus on when and how to use transanal irrigation for people with bowel problems was published in 2013, offering practitioners a clear, comprehensive and simple guide to practice for the emerging therapeutic area of transanal irrigation. [ 50 ]


The term  retrograde irrigation  distinguishes this procedure from the  Malone antegrade continence enema , where irrigation fluid is introduced into the colon proximal to the anus via a surgically created irrigation port. [ 51 ]


Patients who have a bowel disability, a medical condition which impairs control of  defecation , e.g., fecal incontinence or constipation, [ 52 ]  can use bowel management techniques to choose a predictable time and place to evacuate. [ 52 ]  Without bowel management, such persons might either suffer from the feeling of not getting relief, or they might soil themselves. [ 52 ]


While simple techniques might include a controlled  diet  and establishing a toilet routine, [ 52 ]  a daily enema can be taken to empty the colon, thus preventing unwanted and uncontrolled bowel movements that day. [ 53 ]


In a  lower gastrointestinal series  an enema that may contain  barium sulfate  powder or a water-soluble  contrast agent  is used in the  radiological  imaging of the bowel. Called a  barium enema , such enemas are sometimes the only practical way to  view  the colon in a relatively safe manner. [ 6 ]


Failure to expel all of the barium may cause constipation or possible impaction [ 54 ]  and a patient who has no bowel movement for more than two days or is unable to pass gas rectally should promptly inform a physician and may require an enema or laxative. [ 55 ]


The administration of substances into the bloodstream. This may be done in situations where it is undesirable or impossible to deliver a medication by mouth, such as  antiemetics  given to reduce  nausea  (though not many antiemetics are delivered by enema). Additionally, several anti-angiogenic agents, which work better without digestion, can be safely administered via a gentle enema.


The topical administration of medications into the rectum, such as  corticosteroids  and  mesalazine  used in the treatment of  inflammatory bowel disease . Administration by enema avoids having the medication pass through the entire  gastrointestinal tract , therefore simplifying the delivery of the medication to the affected area and limiting the amount that is absorbed into the bloodstream.


Rectal corticosteroid enemas are sometimes used to treat mild or moderate ulcerative colitis. They also may be used along with systemic (oral or injection) corticosteroids or other medicines to treat severe disease or mild to moderate disease that has spread too far to be treated effectively by medicine inserted into the rectum alone.


Improper administration of an enema can cause electrolyte imbalance (with repeated enemas) or ruptures to the bowel or rectal tissues which can be unnoticed as the rectum is insensitive to pain, [ 66 ]  resulting in internal  bleeding . However, these occurrences are rare in healthy,  sober  adults. Internal bleeding or rupture may leave the individual exposed to infections from intestinal bacteria. Blood resulting from tears in the colon may not always be visible, but can be distinguished if the feces are unusually dark or have a red hue. If intestinal rupture is suspected, medical assistance should be obtained immediately. [ 14 ]  Frequent use of enemas can cause laxative dependency. [ 67 ]


The enema tube and solution may stimulate the  vagus nerve , which may trigger an  arrhythmia  such as  bradycardia .


Enemas should not be used if there is an undiagnosed  abdominal pain  since the peristalsis of the bowel can cause an inflamed  appendix  to  rupture .


There are arguments both for and against colonic irrigation in people with  diverticulitis ,  ulcerative colitis ,  Crohn's disease , severe or internal  hemorrhoids  or  tumors  in the rectum or  colon , and its usage is not recommended soon after bowel  surgery  (unless directed by one's  health care provider ). Regular treatments should be avoided by people with  heart disease  or  kidney failure . Colonics are inappropriate for people with bowel, rectal or anal  pathologies  where the pathology contributes to the risk of  bowel perforation . [ 68 ]


Recent research has shown that ozone water, which is sometimes used in enemas, can immediately cause  microscopic colitis . [ 69 ]


A recent case series [ 70 ]  of 11 patients with five deaths illustrated the danger of phosphate enemas in high-risk patients.


Enema  entered the English language c. 1675 from Latin in which, in the 15th century, [ 3 ]  it was first used in the sense of a rectal injection, [ 2 ]  from Greek ἔνεμα (énema), "injection", itself from ἐνιέναι (enienai) "to send in, inject", from ἐν (en), "in" + ἱέναι (hienai), "to send, throw". [ 71 ]


Clyster  entered the English language in the late 14th century from Old French or Latin, from Greek κλυστήρ (klyster), "syringe", itself from κλύζειν (klyzein), "to wash out", [ 72 ]  also spelled  glister  in the 18th century, [ 73 ]  is a generally archaic word used more particularly for enemas administered using a  clyster syringe .


The first mention of the enema in medical literature is in the Ancient Egyptian  Ebers Papyrus  ( c.  1550  BCE). One of the many types of medical specialists was a Nery-Pehuyt, the Shepherd of the Anus. Many medications were administered by enemas. [ 74 ]  There was a Keeper of the Royal Rectum [ 75 ]  who may have primarily been the pharaoh's enema maker. The god  Thoth , according to Egyptian mythology, invented the enema. [ 76 ]


In parts of Africa the  calabash  gourd is used traditionally to administer enemas. On the Ivory Coast the narrow neck of the gourd filled with water is inserted the patient's rectum and the contents are then injected by means of an attendant's forcible oral inflation, or, alternatively, a patient may self-administer the enema by using suction to create a negative pressure in the gourd, placing a finger at the opening, and then upon anal insertion, removing the finger to allow atmospheric pressure to effect the flow. In South Africa,  Bhaca  people used an ox horn to administer enemas. [ 77 ]  Along the upper Congo River an enema apparatus is made by making a hole in one end of the gourd for filling it, and using a resin to attach a hollow cane to the gourd's neck. The cane is inserted into the anus of the patient who is in a posture that allows gravity to effect infusion of the fluid. [ 78 ]


The  Olmec  from their middle preclassic period (10th through 7th centuries BCE) through the Spanish Conquest used trance-inducing substances ceremonially, and these were ingested via, among other routes, enemas administered using jars.


As further described below in  religious rituals , the  Maya  in their late classic age (7th through 10th centuries CE) used enemas for, at least, ritual purposes, Mayan sculpture and ceramics from that period depicting scenes in which, injected by syringes made of gourd and clay, ritual hallucinogenic enemas were taken. [ 79 ]  In the Xibalban court of the God D, whose worship included ritual cult paraphernal, the Maya illustrated the use of a characteristic enema bulb syringe by female attendants administering clysters ritually. [ 80 ] [ 81 ]


For combating illness and discomfort of the digestive tract, the Mayan also employed enemas, as documented during the colonial period, e.g., in the  Florentine Codex . [ 79 ]


The  indigenous peoples of North America  employed  tobacco smoke enemas  to stimulate respiration, injecting the smoke using a rectal tube. [ 82 ] [ 83 ]


A rubber bag connected with a conical nozzle, at an early period, was in use among the  indigenous peoples of South America   as an enema syringe, [ 84 ]  and the rubber enema bag with a connecting tube and ivory tip remained in use by them while in Europe a syringe was still the usual means for conducting an enema. [ 85 ]


In Babylonia, by 600 BCE, enemas were in use, although it appears that initially they were in use because of a belief that the demon of disease would, by means of an enema, be driven out of the body. [ 86 ]  Babylonian and Assyrian tablets c. 600 BCE bear cuneiform inscriptions referring to enemas. [ 87 ]


In China, c. 200 CE,  Zhang Zhongjing  was the first to employ enemas. "Secure a large pig's bile and mix with a small quantity of vinegar. Insert a bamboo tube three or four inches long into the rectum and inject the mixture" are his directions, according to  Wu Lien-teh . [ 88 ]


In India, in the fifth century BCE,  Sushruta  enumerates the enema syringe among 121 surgical instruments described. Early Indian physicians' enema apparatus consisted of a tube of bamboo, ivory, or horn attached to the scrotum of a deer, goat, or ox. [ 86 ]


In Persia,  Avicenna  (980–1037 A. D.) is credited with the introduction of the "clyster-purse" or collapsible portion of an enema outfit made from ox skin or silk cloth and emptied by squeezing with the hands. [ 87 ]


Hippocrates  (460–370 BCE) frequently mentions enemas, e.g., "if the previous food which the patient has recently eaten should not have gone down, give an enema if the patient be strong and in the prime of life, but if he be weak, a suppository should be administered, should the bowels be not well moved on their own accord." [ 89 ]


In the first century BCE the  Greek physician   Asclepiades of Bithynia  wrote "Treatment consists merely of three elements: drink, food, and the enema". [ 90 ]  Also, he contended that indigestion is caused by particles of food that are too big and his prescribed treatment was proper amounts of food and wine followed by an enema which would remove the improper food doing the damage. [ 91 ]


In the second century CE the Greek physician  Soranus  prescribed, among other  techniques , enemas as a safe  abortion  method, [ 92 ]  and the Greek philosopher  Celsus  recommended an enema of pearl barley in milk or rose oil with butter as a nutrient for those with dysentery and unable to eat, [ 93 ]  and also Galen mentions enemas in several contexts. [ 61 ]


In medieval times appear the first illustrations of enema equipment in the  Western world , a clyster syringe consisting of a tube attached to a pump action bulb made of a pig bladder. [ citation needed ]
A simple piston  syringe  clyster was in use from the 15th through 19th centuries. This device had its rectal nozzle connected to a syringe with a plunger rather than to a bulb. [ citation needed ]


Beginning in the 17th century enema apparatus was chiefly designed for self-administration at home and many were French as enemas enjoyed wide usage in France. [ 93 ]


In 1694  François Mauriceau  in his early-modern treatise,  The Diseases of Women with Child,  records that both midwives and man-midwives commonly administered clysters to labouring mothers just prior to their delivery. [ 94 ]


Clysters were administered for symptoms of constipation and, with more questionable effectiveness, stomach aches and other illnesses. [ when? ] [ citation needed ] [ 95 ]


In 1753 an enema bag prepared from a pig's or beef's bladder attached to a tube was described by Johann Jacob Woyts as an alternative to a syringe. [ 96 ]


In the 18th century Europeans began emulating the  indigenous peoples of North America's  use of tobacco smoke enemas to resuscitate drowned people. [ 97 ]  Tobacco resuscitation kits consisting of a pair of bellows and a tube were provided by the Royal Humane Society of London and placed at various points along the Thames. [ 93 ]  Furthermore, these enemas came to be employed for headaches, respiratory failure, colds, hernias, abdominal cramps, typhoid fever, and cholera outbreaks. [ 97 ]


Clysters were a favourite medical treatment in the  bourgeoisie  and  nobility  of the Western world up to the 19th century. As medical knowledge was fairly limited at the time, purgative clysters were used for a wide variety of  ailments , the foremost of which were  stomach aches  and constipation. [ 9 ]


According to  the duc de Saint-Simon , clysters were so popular at the court of King  Louis XIV of France  that  the duchess of Burgundy  had her servant give her a clyster in front of the King (her modesty being preserved by an adequate posture) before going to the  comedy . However, he also mentions the astonishment of the King and Mme de Maintenon that she should take it before them. [ 98 ]