Constipation Mimics: Differential Diagnosis and Approach to Management

Authors: Roger Farney, DO (Transitional Year Resident, San Antonio, TX) and Gillian Schmitz, MD (@GillianMD1, EM Attending Physician, San Antonio, TX) // Edited by: Alex Koyfman, MD (@EMHighAK) and Brit Long, MD (@long_brit)


Constipation is a common chief complaint in the emergency department (ED). Between the years 2006 to 2011, constipation related visits increased in frequency by 41.5% from 497,034 visits to 703,391 visits (1).  Constipation itself is not life threatening; however, it can be associated with or lead to a life-threatening disease. With the rise of acute ED visits for constipation, physicians may be misled in misdiagnosing a life-threatening disease that appears benign.  Therefore, emergency physicians must perform a well-rounded history and physical and maintain a broad differential in their evaluations.

Constipation can be caused by numerous etiologies; examples are listed below in the table:


A 60-year-old female presents to the ED with a complaint of having no bowel movements for the past 5 days and abdominal pain.  She has chronic issues with constipation but never goes this long without having a bowel movement.  She describes the pain as dull, located diffusely throughout the abdomen.  She also has new onset of nausea but denies any emesis. She denies fever, hematochezia, hematemesis, or dysuria. She has tried taking Miralax 1 capful daily at home for the past two days without resolution.  Further evaluation reveals a remote surgical history of a total hysterectomy and cholecystectomy. She currently takes Vicodin 5mg-325mg 1 tab every 6 hours for a left knee arthroscopy 7 days ago.

Her vital signs are: Temp 98, BP 135/87, HR 110, RR 16, Sp02 98% on room air.

Her abdominal exam reveals mild distension with well-healed surgical scars, high pitched bowel sounds in all quadrants, and moderate diffuse tenderness without guarding or rebound. The rest of the exam is normal.

Initially you suspect constipation due to her past history of similar episodes, and she has been taking Vicodin. However, based on the patient’s personal history and her abnormal abdominal exam, you have an increased suspicion for a more serious cause.  You perform a bedside ultrasound revealing dilated, fluid-filled bowel loops with bidirectional peristalsis. A CT with IV contrast is then performed, which confirms the diagnosis of small bowel obstruction. Surgery is consulted, and the patient is admitted for nonsurgical management of her small bowel obstruction.


Constipation has been traditionally defined in medicine as less than three bowel movements per week, but patients commonly define constipation with terms like abdominal pain, bloating, and straining during bowel movements (2). A useful tool to merge medical lexicon and patient understanding for functional constipation is the Rome criteria, which allows the physician to not just rely on stool frequency alone. The Rome criteria for constipation includes loose stools rarely occur without laxative use, and two or more of the following symptoms (3):

Besides the above-mentioned symptoms in the Rome criteria, patients can present with lower migrational abdominal pain, cramps, loss of appetite, nausea and vomiting, rectal bleeding, rectal pain, intermittent diarrhea, inability to pass flatus, and unexplained weight loss. Abdominal pain is the most common complaint in 66% of patients with constipation, and passing hard/infrequent stools is the second most common complaint at 46% (4).

Like many conditions, the most important aspect for evaluating constipation is merging patient history and physical exam.  Often the character and duration of symptoms along with personal and family history can significantly narrow the differential diagnosis.  Proper history will help to avoid missing red flags such as recent weight loss, rectal bleeding, peritoneal signs, fever, or neurological signs (5).  Part of the physical exam also includes a rectal exam with careful inspection and palpation for masses, hemorrhoids, fissures, and anal and perianal inflammation. The color and consistency of stool should be noted (6). Rectal exam should also include assessment for fecal impaction and rectal tone to assess for possible neurologic disorders (7).  In cases where there is no concern for organic causes or obstructions, labs and imaging are rarely needed. However, when organic causes cannot be excluded or if there is concern for obstruction, further testing and imaging is required.

Why Should an Emergency Physician be Aware of This?

We started with a brief discussion of constipation. As discussed, several dangerous diseases can cause constipation. An emergency physician must be diligent and always have a well-rounded differential diagnosis when a patient presents with constipation to the ED, especially if there are red flags for organic causes or obstruction.  With a thorough evaluation, one can uncover other diseases from non-organic and non-obstructive causes of constipation.


Appendicitis is one of the most common causes of acute abdominal pain requiring surgical treatment (9).  In the United States around 300,000 appendectomies are performed for acute appendicitis each year (2). Appendicitis is most common in the second decade of life, with a male predominance of 1.4:1 (10).  Textbook presentation is periumbilical pain that migrates to the RLQ of the abdomen. However, this presentation only occurs in about 50% of patients, and factors like age and anatomical position can create variable presentations. Common associated symptoms are anorexia, constipation, and subjective or objective fever (10).


Diverticulitis can be associated with bowel habit changes in 37%, with the most common change being constipation at 14% (11).  The most common complaint of diverticulitis is lower left sided abdominalpain. Other associated symptoms include nausea, vomiting, fever, leukocytosis, and diarrhea. The test of choice is CT of the abdomen and pelvis with intravenous contrast (2).  CT along with the history and physical exam will determine if the patient has complicated or uncomplicated diverticulitis. Complicated diverticulitis found on CT includes perforation, abscess, obstruction, and fistulization and should receive inpatient treatment (12).

  • Fever, constipation, and focal LLQ tenderness should increase the suspicion for diverticulitis.

Bowel Obstruction

The most common cause of small bowel obstruction is adhesions from previous abdominal surgeries, followed by hernias and malignancy.  Small bowel obstruction commonly presents with nausea, bilious vomiting, abdominal pain, and distension. Obstipation can occur which is the inability to pass gas or stool (13). Unfortunately, obstipation does not possess 100% sensitivity for obstruction. On physical exam the abdomen can be tympanic on percussion, and on auscultation high-pitched bowel sounds can be heard.  Large bowel obstructions are commonly caused by colon cancer, volvulus and diverticular disease (14).  Large bowel obstructions most commonly present with abdominal pain and distension, along with obstipation, but they rarely occur with nausea and vomiting.

  • Top 3 causes of SBO: Adhesions, Incarcerated hernias, and Malignancy.
  • Top 3 causes of LBO: Malignancy, Diverticulitis, and Volvulus.

Cauda Equina Syndrome

The adult spinal cord terminates at the level of L1-L2, and the terminal lumbar and sacral nerve roots form the cauda equina (15).  Cauda equina syndrome is a rare emergency neurological condition that is caused by compression of the lumbosacral nerve roots.  The most common causes are disk herniation, spinal stenosis, infection or trauma.  Patients with cauda equina syndrome usually present with one or more of these red flags: 1) severe low back pain, 2) saddle paresthesia 3) bladder, bowel and sexual dysfunction, or 4) lower limb weakness.  Patients may have an atonic bowel and develop severe constipation, which is believed to be the result of parasympathetic denervation of the sigmoid and rectum (17).  With a patient presenting with these symptoms, an emergent MRI with a neurosurgical consult for possible decompression is needed (16). Dexamethasone 10mg IV can help relieve pain and improve neurologic function by decreasing edema (2, 15).  In the ED obtaining a bladder scan/ultrasound to assess bladder volume is warranted to assess bladder volume.  Simple constipation should not present with weakness, saddle paresthesia, or urinary retention.

  • Lower extremity weakness or numbness and saddle paresthesias should raise suspicion for CES.


Megacolon, or dilation of the colon, can cause decreased peristalsis or bowel paralysis. It can be caused by a number of different disease processes. The average diameters of the cecum and sigmoid colon are 8.7 cm and 5.7 cm, respectively.  Megacolon refers to cecal dilatation greater than 12 cm and sigmoid dilatation greater than 6.5 cm (18).  Megacolon can be categorized into 2 categories: aganglionic and idiopathic.

Aganglionic megacolon is typically caused by underlying Hirschsprung’s disease or Chagas disease.  Hirschsprung’s is caused by migration failure of colonic ganglion cells during gestation. Typically it is diagnosed at birth; however, it can present later in adolescence, with the main symptoms being persistent constipation and abdominal pain (19).  Neonates can present with abdominal distension, poor feedings, and failure to pass meconium within 48 hours after birth.  A common finding on physical exam is explosive stool after rectal exam. In adolescents, the most common presentation will be a child who has chronic constipation, routinely has to use enemas or suppositories, and demonstrates slow growth and abdominal distension.  Definitive diagnosis is made with a rectal suction biopsy, which will show absence of ganglion cells in the submucosa.  Treatment includes removing the portion of the colon that is affected. With early treatment, the majority of the patients can live long and normal lives without adverse effects (19).

Chagas disease is caused by the protozoan Trypanosoma cruzi.  It typically affects the heart, nervous system, and digestive system. Chagas disease will cause degeneration of the enteric nervous system, but as opposed to Hirschsprung’s disease, it will affect the entire GI tract (21).

Idiopathic, or acquired megacolon usually affects adults and the elderly. It involves persistent lengthening and dilatation of the colon in absence of organic disease.  The pathophysiology is poorly understood in idiopathic megacolon. However, it has been suggested that psychiatric patients, the elderly, certain medications, and patients with redundancies in their colon are associated with increased risk.  In a review of 23 articles, the following diagnostic criteria for acquired megacolon were created: 1) exclusion of organic causes; 2) sigmoid diameter of 10 cm; 3) symptoms including constipation, distention, abdominal pain, and gastric distress (20). Initially conservative management is attempted, but if the patient develops a colonic volvulus or has intractable symptoms that affect quality of life, surgery is usually needed.

  • Physicians should be suspicious of megacolon with complaints of constipation and a sigmoid colon >6.5 cm.


Pregnancy causes significant anatomical and physiological changes in the female body.  Constipation occurs in approximately 11% to 38% of pregnant women (22).  These anatomic and physiologic changes can affect gut motility and stool consistency. Increased progesterone levels and decreased motilin levels increase water reabsorption from the intestines. The size of the enlarging uterus can cause decreased movement of stool (22). Primary treatment is increase dietary fiber, water intake, and daily exercise.

Bowel Perforation

Bowel perforation occurs from either full-thickness or partial-thickness bowel injuries. Perforation usually presents with sudden severe abdominal pain; the patient often knows the precise time of onset. Constipation is generally not a complaint with bowel perforation; however, chronic constipation and its mimics like appendicitis, diverticulitis, obstructions, and hernias can be risk factors for bowel perforation (26). There is a rare situation that is caused by a fecaloma from patients with chronic constipation that leads to ischemic necrosis of the intestinal wall.  Typically this affects the rectosigmoid colon, known as an idiopathic or a stercoral perforation (25). Bowel perforations are life-threatening situations that require urgent surgical intervention because leakage of intestinal contents into the abdominal cavity can lead to peritonitis, abscess, or development of sepsis (24).

  • If perforation is suspected, an upright CXR should be performed.


Hernias are defined as a protrusion, bulge, or projection of an organ or part of an organ thought the body wall that normally contains it. They are classified by their location, contents, and status of their contents (2).  Reducible hernias are soft and easily able to be put back through defect.  An incarcerated hernia is firm, painful, and not reducible. If an incarcerated hernia develops impaired blood flow, known as a strangulated hernia, it becomes a surgical emergency.  These are severely painful, and normally the patient is ill-appearing (27).

The prevalence of groin hernias in the U.S. is 5-10%, with indirect inguinal hernias being the most common type. Indirect inguinal hernias protrude through the internal inguinal ring, where the spermatic cord or round ligament exits the abdomen (28).  The origin of the sac lies lateral to the inferior epigastric artery.  Normally the internal inguinal ring closes during development, but a patent process vaginalis can increase the risk of developing a hernia. Direct inguinal hernias protrude medial to the inferior epigastric artery through Hesselbach’s triangle. Often this is due to weakness of the transversalis fascia and weakness in the abdominal wall musculature (28).  Femoral hernias protrude through the femoral ring, these are the least common however it has the highest association with complications. Femoral hernia’s present as emergencies with incarceration or strangulation about 40% of the time (23).

Typically, diagnosis can solely be from history and physical.  A common complaint is a painless or painful bulge in the abdominal area that is more noticeable with coughing or straining.  Dull pain or heaviness in the genital region can also be a common presentation with hernias. Constipation can be both a risk factor and a symptom of hernias. Bedside ultrasound may help differentiate between incarcerated and strangulated hernia. If no signs of strangulation on ultrasound, bedside attempts at reducing the hernia can be done (2).

  • Strangulated hernia is a surgical emergency as blood flow to the tissue is compromised.
  • Although they occur less frequently, femoral hernias have a higher incidence of becoming a surgical emergency.
  • Bedside ultrasound is a valuable tool that can quickly assist the emergency physician at bedside by differentiating between incarceration and strangulation.

Rectal Foreign Bodies

Rectal foreign body diagnosis can be a challenging task for an emergency physician. Patients are often embarrassed and may try to hide the true reason of why they presented to the ED. Typically patients will have complaints of abdominal pain, anorectal pain, bleeding, or the inability to pass gas or stool (2).

In up to 20% of cases, patients will not initiate concern of a rectal foreign body (29).  The most commonly found objects are typically household items but can include a wide variety of objects such as food, knives, sports equipment, sex toys, or drug packets. Plain radiograph of the abdomen will often be enough to show the object and the location, however CT scan is useful for radiolucent objects and detection of free air. Imaging is recommended before attempted removal to ensure no sharp objects are present. Removal of the object depends on the location and the object itself. If the object is made of glass, has sharp edges, the patient shows sign of peritonitis, or the object cannot be palpated with digital rectal exam, the patient will typically need surgery (2,30).  Transanal extraction in the ED should be attempted if the above mentioned has been excluded (2,30). The patient can be placed in a lithotomy position with reverse trendelenburg angulation. Mild sedation and proper lubrication will allow for greater extraction success.  Commonly used tools to grasp objects include obstetric forceps, Kocher clamps, and suction devices (2,30). Once the object is removed, a follow-up plan abdominal radiograph should be obtained to reassess for possible perforation (2,30).


Three major electrolyte disorders can lead to chronic organic constipation: hypomagnesemia, hypokalemia, and hypercalcemia (31). Hypomagnesemia and hypokalemia will typically occur together, as magnesium plays a role in potassium reabsorption in the kidneys (32).  ED physicians must not forget to obtain an ECG with severe hypokalemia, hypomagnesemia, and hypercalcemia, as they all can lead to fatal cardiac arrhythmias.  Look for T-wave flattening, QT shortening and prolongation, U waves, and ST depression on ECG (2). If asymptomatic and >2.5, potassium can be repleted orally. If symptomatic or <2.5, IV potassium should be administered (with oral repletion as well if the patient is able). In an asymptomatic patient with a magnesium level >1.6, PO magnesium can be given, as this should help relieve the patient’s constipation, otherwise IV magnesium can be given.  For patients who are found to be symptomatic with hypercalcemia, remember stone, bone, moans, and groans. Normal saline should be aggressively given to the patient (2).

  • Remember to order ECG with severe electrolyte abnormalities.


Hypothyroidism is caused by insufficient thyroid hormone; this can be secondary to a dysfunctional thyroid gland, absence of thyroid gland from treatment of Graves’ disease, or a central cause from the pituitary gland or hypothalamus.  Women have a higher rate of developing hypothyroidism (33).  Hypothyroidism can easily be diagnosed with a serum TSH and free T4 level. Signs and symptoms common with hypothyroidism include fatigue, cold intolerance, dry skin, weight gain, constipation, hair loss, facial periorbital edema, mental impairment, and bradycardia (33).

In a patient who presents to the ED with known hypothyroidism or with a clinical picture of hypothyroidism with new onset altered mental status and/or hypothermia, an emergency physician must consider myxedema coma. In comatose patients, the diagnosis should be considered with the following triad: hypothermia, hyponatremia, and hypercapnia (34).  Treatment consists of the following: thyroid hormone replacement (IV levothyroxine 4 mcg/kg), glucocorticoids (hydrocortisone 100 mg IV every 8 hours), and supportive care (electrolytes, passive rewarming, antibiotic therapy, fluids and vasopressors for hypotension) (2,33,34).

  • Hypothermia is common with myxedema crisis that a normal temperature highly suggests an underlying infection (2).

Inflammatory Bowel Disease

Inflammatory bowel diseases, which encompass Crohn’s disease and Ulcerative Colitis, are idiopathic diseases of the GI tract identified by a relapsing and remitting course (35). The distinction between the two diseases comes from their definitions. UC is defined as a diffuse inflammatory disease of unknown cause that continuously affects the colonic mucosa proximal from the rectum (36). Crohn’s is a chronic inflammatory disease of unknown cause, characterized by discontinuous transmural granulomatous inflammation (2,36). Unlike UC, Crohn’s can affect anywhere from the mouth to the anus, though the terminal ileum is the hallmark location.  While the diseases are typically associated with diarrhea and non-life threatening emergencies, their complications can become life-threatening.

Both UC and Crohn’s can develop strictures, secondary from repetitive episodes of inflammation and edema in the bowel wall (37).  Even though the strictures are usually benign, they can progress and cause severe bowel obstructions as a complication. Another major complication that can present as constipation in both diseases is malignancy. Patients with Crohn’s have a 3-fold higher incidence of developing malignancy, whereas patients with UC have a 10 to 30-fold higher incidence of malignancy (2). Generally when the diseases cause a complication like bowel obstruction, besides supportive care, an early consultation to surgery is recommended.

  • In patients presenting with abdominal pain and constipation with known history of UC or Crohn’s, bowel obstruction must be on the differential. 


-A patient presenting with constipation will often have a chief complaint of abdominal pain.

-Constipation itself is not life-threatening; however, it can lead to or represent a life-threatening disease.  An emergency physician must have a wide differential diagnosis to avoid misdiagnosis or attribution of symptoms to functional causes.

-It is up to the emergency physician to look for red flags. Weight loss, rectal bleeding, peritoneal signs, fever, neurological signs, and history of constipation that requires regular use of enemas are some of the red flags that can be obtained in a good history and physical exam.

Non-organic constipation should be treatable with dietary changes, increase in fiber and water intake, and short courses of medications such as polyethylene glycol after other causes have been ruled out.

References / Further Reading:

  1. Sommers T, Corban C, Sengupta N, et al. Emergency Department Burden of Constipation in the United States from 2006 to 2011. The Am J Gastroenterol. 2015;110(4): 572-579. doi:10.1038/ajg.2015.64.
  2. Stapczynski JS, Tintinalli JE. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 8th Edition. New York: McGraw-Hill Education; 2016.
  3. Shih DQ, Kwan LY. All Roads Lead to Rome: Update on Rome III Criteria and New Treatment Options. Gastroenterol Rep. 2007;1(2):56-65.
  4. Miller MK, Dowd MD, Fraker M. Emergency department management and short-term outcome of children with constipation. Pediatr Emerg Care. 2007 Jan, 23 (1): 1-4. doi: 1097/01.pec.0000248690.19305.a5.
  5. Beck DE. Evaluation and Management of Constipation. Ochsner J. 2008;8(1): 25-31.
  6. Arce DA, Ermocilla CA, Costa H. Evaluation of constipation. Am Fam Physician. 2002 Jun 1;65(11): 2283-90.
  7. McAninch S, Smithson III CC. Gastrointestinal Emergencies. In: Stone C, Humphries RL. eds. CURRENT Diagnosis & Treatment: Emergency Medicine, 8e New York, NY: McGraw-Hill; Accessed August 19, 2018.
  8. Shih DQ, Kwan LY. All Roads Lead to Rome: Update on Rome III Criteria and New Treatment Options. Gastroenterol Rep. 2007 Winter;1(2): 56-65.
  9. Cole MA, M. N. (2011). Evidence-based management of suspected appendicitis in the emergency department. Emerg Med Pract. 2011 Oct;13(10): 1-32.
  10. Humes DJ, Simpson J. Acute appendicitis. 2006 Sep 9;333(7567):530-534. doi:10.1136/bmj.38940.664363.AE.
  11. Textbook of Gastroenterology, Yamada T, Alpers DH, Kaplowitz N, et al (Eds), Lippincott Williams & Wilkins, Philadelphia, PA 2003.
  12. Janes SE, Meagher A, Frizelle FA. Management of diverticulitis. BMJ. 2006;332(7536):271-5.
  13. Baiu I, Hawn MT. Small Bowel Obstruction. JAMA. 2018;319(20):2146. doi:10.1001/jama.2018.5834
  14. Sule, Az, A Ajibade. “Adult Large Bowel Obstruction: A Review of Clinical Experience.” Ann Afr Med, 2011 Jan-Mar; 10(1):45-50. doi:10.4103/1596-3519.76586.
  15. Levis JT. Cauda Equina syndrome. West J Emerg Med. 2009 Feb;10(1):20.
  16. Gardner A, Gardner E, Morley T. Cauda equina syndrome: a review of the current clinical and medico-legal position. Eur Spine J. 2011 May;20(5):690-697. doi:10.1007/s00586-010-1668-3.
  17. Winge K, Rasmussen D, Werdelin LM. Constipation in neurological diseases. J Neurol, Neurosurg Psychiatry 2003 Jan;74:13-19.
  18. Bharucha AE, Phillips SF. Megacolon: Acute, Toxic, and Chronic. Curr Treat Options Gastroenterol.1999 Dec;2(6): 517-523.
  19. Kessmann J. Hirschsprung’s disease: diagnosis and management. Am Fam Physician. 2006 Oct 15;74(8): 1319-1322.
  20. Cuda T, Gunnarsson R, de Costa A. Symptoms and diagnostic criteria of acquired Megacolon – a systematic literature review. BMC Gastroenterol. 2018 Jan 31;18(1):25. doi:10.1186/s12876-018-0753-7.
  21. Ferreira-Santos R, Carril C. Acquired megacolon in Chagas’ disease. Dis Colon Rectum. 1964 Sep-Oct;7: 353-364. doi:10.1007/BF02616842.
  22. Trottier M, Erebara A, Bozzo P. Treating constipation during pregnancy. Can Fam Physician. 2012 Aug;58(8):836-838.
  23. Ruhl, C. E., J. E. Everhart. Risk Factors for Inguinal Hernia among Adults in the US Population. Am J Epidemiol. 2007 May15;165(10):1154-61. Doi 10.1093/aje/kwm011.
  24. Moore L.J., Moore F.A. Early Diagnosis and Evidence-Based Care of Surgical Sepsis. J Intensive Care Med. 2013 Mar;28(2): 107-17. Doi 10.1177/0885066611408690.
  25. Celayir MF, Köksal HM, Uludag M. Stercoral perforation of the rectosigmoid colon due to chronic constipation: A case report. Int J Surg Case Rep. 2017;40: 39-42. doi:10.1016/j.ijscr.2017.09.002.
  26. Re GL, Mantia FL, Picone D, Salerno S, Vernuccio F, Midiri M. Small Bowel Perforations: What the Radiologist Needs to Know. Seminars in Ultrasound, CT and MRI. 2016;37(1):23-30. Doi:10.1053/j.sult.2015.11.001.
  27. Jenkins JT, O’Dwyer PJ. Inguinal hernias. BMJ. 2008;336(7638):269-72.
  28. Öberg S, Andresen K, Rosenberg J. Etiology of Inguinal Hernias: A Comprehensive Review. Front Surg. 2017;4:52. Published 2017 Sep 22. doi:10.3389/fsurg.2017.00052
  29. Cologne KG, Ault GT. Rectal Foreign Bodies: What Is the Current Standard? Clin Colon Rectal Surg. 2012 Dec;25(4):214-218. doi:10.1055/s-0032-1329392.
  30. Kasotakis G, Roediger L, Mittal S. Rectal foreign bodies: A case report and review of the literature. Int J Surg Case Rep. doi: 2011;3(3):111-5.
  31. Childhood constipation: evaluation and management. Clin Colon Rectal Surg. 2005;18(2):120-7.
  32. Huang CL, Kuo E. Mechanism of hypokalemia in magnesium deficiency. J Am Soc Nephrol. 2007 Oct;18(10):2649-52. Epub 2007 Sep 5. Doi: 10.1681/ASN.2007070792.
  33. Kostoglou-Athanassiou I, Ntalles K. Hypothyroidism – new aspects of an old disease. Hippokratia. 2010;14(2):82-7.
  34. Kwaku MP, Burman KD. Myxedema Coma. J Intensive Care Med. 2007:22(4):224-231. Doi:10.1177/0885066607301361.
  35. Nimmons D, Limdi JK. Elderly patients and inflammatory bowel disease. World J Gastrointest Pharmacol Ther. 2016;7(1):51-65.
  36. Matsuoka K, Kobayashi T, Ueno F, et al. Evidence-based clinical practice guidelines for inflammatory bowel disease. J Gastroenterol. 2018;53(3):305-353.
  37. De Dombal FT, Watts JM, Watkinson G, Goligher JC. Local complications of ulcerative colitis: stricture, pseudopolyposis, and carcinoma of colon and rectum. Br Med J. 1966;1(5501):1442-7.

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