Gastrointestinal Diseases

Gastrointestinal (GI) Bleeding

Gastrointestinal (GI) bleed may present as occult or overt bleed. Upper GI bl+eed is defined as bleeding from any site from pharynx to duodenojejunal (DJ) flexure or more specifically upto ligament of Trietz and usually presents as haemaetemesis or melena (black, tarry, sticky, foul smelling stools). Bleeding from GIT distal to DJ flexure is called lower GI bleed. Presence of identifiable fresh/altered blood in stool is called haematochezia. Minimum of 60 ml of blood is required in the stomach to produce melena. Black stools may be seen in patients taking iron, charcoal or bismuth salts.

Treatment

Acute GI bleed is an emergency and needs active management. An assessment of activity and severity of bleed should be done immediately.

Nonpharmacological

• Maintain vital signs (blood pressure, airways, respiration, temperature).
• Insert a large bore IV cannula and send the blood samples for Hb, TLC, platelets, coagulation profile, renal and liver function tests, blood grouping and cross-matching.
• Start IV fluids like normal saline/ Ringer’s lactate/ haemacoel.
• Severity of GI bleed is assessed as mild (patient has tachycardia but blood pressure is maintained), moderate (tachycardia with postural hypotension, tachypnoea, sweating, cold skin) and severe (hypotension and shock)
• Replace the blood as soon as available if moderate to severe bleed or active bleed.

Pharmacological

1. Inj. Ranitidine 300 mg IV infusion/24 hours started if non-variceal upper GI bleed suspected (patient with known peptic ulcer or reflux disease, taking NSAIDs)
2. If variceal bleed is suspected (chronic alcoholic, jaundice, splenomegaly, dilated abdominal veins, ascites, encephalopathy)
   Inj. Octreotide 50 mcg IV immediately followed by 25 mcg/hour infusion
   Or
   Inj. Terlipressin 1-2 mg IV given 4-6 hourly.
   Or
   Inj. Vasopressin 20 IU in 200 ml of normal saline over 20 min.
   Maintenance dose is given as 100 units in 50 ml of 5% dextrose given as 0.2-0.9 units/min (6-27 ml/h) in the next 24 hours. Avoid in ischaaemic heart disease (IHD). Nitroglycerine drip can also be used along with this if systolic BP is >90 mmHg.

Follow up

Monitor pulse, blood pressure and urine output and activity of bleed. Presence of identifiable blood/clots per rectum in a patient with upper GI bleed indicates a severe ongoing bleed and need for very active management.

Transfer patient urgently (see also shock) (after starting the above treatment) to a higher center for further investigations and treatment if uncontrolled bleed, severe bleed, poor urine output and shock.

References

1. Gastrointestinal Bleeding. In: Harrison’s Principles of Internal Medicine. Braunwald E., Fauci AS, Kasper DL et al (eds), 15th Edition, 2001, McGraw Hill Company Inc., New York, pp 252-254.
2. Gastrointestinal Bleeding. In: Emerg Med Clin North Am, Talbot-Steer JK et al (eds), 1996, 14, pp 173-184.

Chronic Pancreatitis

1. Cap. Pancreoflat 2 capsules to be taken during the meal and 2 capsules after the meal.
2. Cap. Omeprazole 20 mg twice a day to be taken 30 min before meals.
   Or
   Cap. Lansoprazole 30 mg twice a day.
   Or
   Tab. Pantoprazole 40 mg twice a day.
3. Tab. Diclofenac 50 mg to be taken as and when required for pain.
4. If diabetes not controlled with diet, for drug therapy (see section on diabetes mellitus – Diabetes mellitus, in children & retinopathy).

Patient education

1. Patient should be regularly followed up for appearance of any specific nutrient deficiency, especially deficiency of fat soluble vitamins and adequate supplements should be given if required.
2. Patient should be explained about giving up alcohol consumption and may require behavioural therapy.

References

Acute and chronic pancreatitis. In: Harrison’s Principles of Internal Medicine. Braunwald E., Fauci AS, Kasper DL et al (eds), 15th Edition, 2001, McGraw Hill Company Inc., New York, pp 1792-1804.

Acute Pancreatitis

• Infusion Dextran saline – 1 L
• Infusion Dextran – 1 L
• Inj. Potassium chloride (KCl) 60-80 mmol (20 mmol added to 50 ml of IV fluid)

If signs of hypovolemia: Add Haemacoel 500 ml – 1000 L.

• Nasogastric tube aspiration – if evidence of paralytic ileum, abdominal distension and vomiting.
• Send blood for complete blood count, amylase, KFT, LFT, blood sugar, serum triglycerides and arterial blood gases. Repeat these test at 48 hours, early if indicated. Oral intake start after 48-72 hours depending upon appearance of bowel sound and relief in pain.
• Fats should be avoided until acute phase settles.

Pharmacological

1. Inj. Diclofenac sodium 50 mg IM 2-3 times a day.
2. If pain is not relieved

Inj. Tramodol 50 mg IM, repeated 6-8 hourly if needed. Patient with severe necrotizing pancreatitis (as diagnosed by contrast enhanced CT) should be managed by a specialist.

Patient education

• Avoid alcohol in patients with gall stones, avoid fatty food and explain the patient about need of early gall bladder removal.

References

1. Approach to the patient with pancreatic disease. In: Harrison’s Principles of Internal Medicine. Braunwald E., Fauci AS, Kasper DL et al (eds), 15th Edition, 2001, McGraw Hill Company Inc., New York, pp 1788-1792.
2. Acute and Chronic Pancreatitis. In: Harrison’s Principles of Internal Medicine. Braunwald E., Fauci AS, Kasper DL et al (eds), 15th Edition, 2001, McGraw Hill Company Inc., New York, pp 1792-1798.

Pyogenic Liver Abscess

• Drainage- percutaneus catheter or open surgical- remains the mainstay of treatment
• If patient is toxic, should be kept nil by mouth and given IV fluids as per requirement

Pharmacological

Initial empirical treatment should include broad-spectrum antibiotic(s)

1. Inj. Ceftriaxone 1-2g IV 2 times a day
2. Inj. Gentamicin 3mg/kg/day IV in 3 divided doses
3. If source of abscess is intra-abdominal sepsis add Inj. Metronidazole 500mg IV 3 times a day should be added

Follow up

• Monitor for clinical improvement and modify the therapy based on culture sensitivity report
• Abscess should always be drained
• Surgery considered if no improvement with medical treatment and percutaneus drainage in 4-7 days.

Patient education

• Avoid taking alcohol while on treatment with metronidazole.
• Stress the need for adopting hygienic precautions regarding food intake to prevent enteric infection

References

Intraabdominal Infections and Abscesses, In: Harrison’s Principles of Internal Medicine. Braunwald E., Fauci AS, Kasper DL et al (eds), 15th Edition, 2001, McGraw Hill Company Inc., New York, pp 829-834.

Amoebic Liver Abscess (ALA)

1. Tab. Metronidazole 800 mg 3 times a day for 7-10 days
   Or
   Tab. Tinidazole 600 mg 2 times a day for 7-10 days
2. If patient is very toxic
   Inj. Metronidazole 500mg given 8 hourly until patient improves. Switch over to oral therapy whenever possible.

Indications for aspiration of amoebic liver abscess:

1. If doubt about possibility of pyogenic abscess
2. No improvement with medical treatment in 72 hours
3. Impending rupture of abscess- one very close to the surface of liver
4. Left lobe abscess if large, to prevent rupture in to pericardium

Follow up

• Monitor the patient for resolution of symptoms with medical treatment and aspirate if any indication.
• Abscess cavity may persist for several weeks even after cure of infection. Therefore, frequent ultrasonographic examinations are un-necessary unless patient develops symptoms. May be repeated after 4-6 weeks after the patient becomes asymptomatic.
• After treatment with metronidazole, Tab. Diloxanide furoate 500 mg 3 times a day for 1 week may be given specially if patient is in nonendemic area.

Patient education

• Avoid taking alcohol while on treatment with metronidazole.
• Stress the need for adopting hygienic precautions regarding food intake to prevent enteric infections.

References

Amebiasis and Infection with Free Living Ameba. In: Harrison’s Principles of Internal Medicine. Braunwald E., Fauci AS, Kasper DL et al (eds), 15th Edition, 2001, McGraw Hill Company Inc., New York, pp 1199-1203.

Ulcerative Colitis

Salient features

• Patient may present in acute stage with bloody diarrhoea, may be associated with systemic symptoms of low to moderate fever, backache, arthralgias.
• The diagnosis is confirmed by sigmoidoscopic examination and mucosal biopsies.
• The disease almost always involves rectum and rest of the colon may be involved to variable length.
• Acute disease is graded as mild (2-4 stool/day), moderate (4-6 stools/day) or severe (> 6 stools/day). During remission patient may be asymptomatic or may have extra-intestinal symptoms.

Treatment

Aim of the treatment include induction of remission in acute stage and then maintenance of remission.

Nonpharmacological

There is no specific dietary restriction but patient may avoid any food if the patient is uncomfortable.

Pharmacological

A. Mild to moderate acute ulcerative colitis (distal/left colonic involvement)

1. Tab. Sulphasalazine 1 g 3-4 times a day.
   Or
   Tab. Mesalazine 800 mg 3-4 times a day.
   Or
   Tab. Olsalazine 1-3 g/day in divided doses.
2. Prednisolone phosphate enema, 20 mg in saline 100 ml 1-2 time a day.
   Or
   Hydrocortisone enema 100-125 mg in 100 ml saline 1-2 times a day. (to be prepared fresh)
   Or
   If disease limited to rectum, Hydrocortisone foam 125 mg 1-2 times a day.

B. Moderate to severe or extensive acute disease

1. Start (1) as above.
2. Tab. Prednisolone 20-60 mg/day in single or divided doses.

Follow up
If the symptoms do not improve or worsen, patient will need hospitalization.

C. Acute severe disease with systemic symptoms (requires hospitalization under the care of specialist)

1. Inj. Hydrocortisone 100 mg IV 4 times a day.
   Or
   Inj. Dexamethasone 4 mg IV 3-4 times a day.
2. Patient should be kept ‘nil by mouth’ and should be given adequate intravenous fluids and electrolytes.
3. Blood transfusion to be given as per requirement.
4. Patient switched over to oral steroids and amino-salicylates to be started as in A (1) as soon as patient is allowed to take orally.

If patient fails to respond to steroids, refer the patient to gastroenterologist for immunosuppressive therapy or surgery.

Once the remission is induced, steroids are tapered slowly over 4-6 weeks period. For acute attack, there is no use of giving steroids for more than 12 weeks.

Follow up
Close clinical/biochemical/radiological monitoring is required for any complications like toxic megacolon/perforation.

D. Maintenance of remission

1. Any of the drug used in A(1) should be given life long.

Patient education

• Patient should be followed up at 6 monthly interval and maintenance treatment should be continued.
• In any patient who has disease for more than 10 years, a regular sigmoidoscopy and rectal biopsy should be done at 6 monthly interval to look for any dysplasia and total colonoscopic examination should be done at 2-3 year interval.
• Patient should be explained about chronic nature of the disease and continuation of maintenance treatment for life long with regular follow up and risk of colonic cancer after 10 years of onset of disease.

References

Irritable Bowel Syndrome. In: Harrison’s Principles of Internal Medicine. Braunwald E., Fauci AS, Kasper DLet al (eds), 15th Edition, 2001, McGraw Hill Company Inc., New York, pp 1679-1692.

Chronic Diarrhoea

1. Tab. Norfloxacin 400 mg 2 times a day.
   Or
   Tab. Ciprofloxacin 500 mg 2 times a day.
   Or
   Cap. Doxycycline 100 mg 2 times a day.
   Or
   If the above mentioned drugs are contraindicated
   Tab. Cotrimoxazole 960 mg 2 times a day.
2. Tab. Folic acid 5 mg 2 times a day.

• Well balanced diet including all major & minor nutrients should be taken.
• Patient should be advised to follow general hygienic measures regarding eating habits.
• To come back for review if there is no clinical improvement in 3-4 weeks of treatment.

References

Disorders of Absorption. In: Harrison’s Principles of Internal Medicine. Braunwald E., Fauci AS, Kasper DL et al (eds), 15th Edition, 2001, McGraw Hill Company Inc., New York, pp 1665-1679.

Acute Diarrhoea/Gastroenteritis

1. Indicated only in very ill patients with systemic symptoms associated with bloody diarrhoea, traveler’s diarrhoea or in cholera infection Tab. Ciprofloxacin 500 mg 2 times a day for 3-5 days.
2. In amoebic dysentery
   Tab. Metronidazole 800 mg 3 times a day for 7 days.
   Or
   Tab. Tinidazole 600 mg 2 times a day for 7 days.
   In acute Giardia infection
   Tab. Metronidazole 400 mg 3 times a day for 3 days.

Indications for hospitalization
Patients with clinical signs of dehydration specially young children or elderly, suspected cholera, immunosuppressed patients and those with severe systemic symptoms.

Patient education

• Patients should be instructed to continue taking adequate fluids even if it initially causes slight increase in frequency of stools due to increased gastro-colic reflex.
• They should report to the physician if they are not able to retain any fluid taken orally and develop significant decrease in urine output.

References

1. Gastroenteritis. In: Management of Common GI Problems. R Guan, J Kang and H Ng (eds), 1995, Medimedia Asia Pvt Ltd., Singapore, pp 68-75.
2. Diarrhoea & Constipation. In: Harrison’s Principles of Internal Medicine. Braunwald E., Fauci AS, Kasper DL et al (eds), 15th Edition, 2001, McGraw Hill Company Inc., New York, pp 241-250.

Irritable Bowel Syndrome (IBS)

1. Tab. Mebavarine hydrochloride 270 mg 3 times a day given for long term
   Or
   Tab. Drotavarine 40-80 mg 3 times a day
   Or
   Tab. Propanthaline hydrochloride 15 mg 3 times a day
2. In individuals complaining of symptoms suggestive of depression
   Tab. Amitriptyline 25 mg at bed time or 2 times a day
3. In case of severe diarrhoea, if symptoms are not controlled by above drugs, give Tab./Cap. Loperamide hydrochloride 2-4 mg daily for several days/weeks depending upon the clinical response.

• Explain the chronic nature of symptoms
• Patient should try to find out correlation of symptom with certain food item, specially milk ingestion and should avoid these.
• Stressful situation also worsen symptom. Relaxing exercises like yoga may help.

1. Irritable Bowel Syndrome. In: Medicine International, Jewell DP & Thillainaygam A. (eds), Vol. 22, 1998, The Medicine Publishing Co. Oxford, UK, pp 102-104
2. Clinical approach to Irritable Bowel Syndrome. In: Approach to patient with Chronic GI disorders, 1999, pp 323-29.
3. Irritable Bowel Syndrome. In: Harrison’s Principles of Internal Medicine. Braunwald E., Fauci AS, Kasper DL et al (eds), 15th Edition, 2001, McGraw Hill Company Inc., New York, pp 1692-1694.

Constipation

• Reassurance since many patients with normal stools and in pregnancy imagine that they are constipated.
• High fibre diet and increased intake of fluid with decrease in consumption of caffeinated drinks.
• Retraining of bowels (avoiding suppression of urge to defecate, making a regular habit).
• Bulk forming agents like ‘isapghula husk’ or ‘psyllium seeds’ also help to relieve mild constipation.
• Regular physical exercise such as walk for 1/2 to 1 hour daily and abdominal exercises.

Pharmacological (Usually required for moderate to severe constipation)

1. Lactulose Soln 15-20 ml orally at night.
   Or
   Susp. Magnesium sulphate 15-20 ml at night.
   Or
   Tab. Sodium picosulphate 10 mg at night.
   Or
   Isotonic polyethylene glycol (PEG) electrolyte solution 125-250 ml.
   Any of these may be given 2-4 times a week. Some patients may require treatment for several weeks or months if there is no improvement.
2. Tab. Mosapride 5 mg 2 or 3 times a day. In some patients may be required for several weeks.
3. Phosphate enemas to be used on as & when required basis in patients having acute problem with severe constipation or sub-acute intestinal obstruction.

Follow up

• If patient continues to have severe constipation or symptoms worsen, refer the patient to a specialist for investigations to rule out secondary causes.
• Recent unexplained constipation (not acute) in an elderly person whose bowel habits were always regular should be investigated.
• Acute constipation especially when the patient is vomiting, has not passed even wind and appears ill, suspect GIT obstruction and refer immediately to a higher centre.

Patient education

1. Do not use purgative frequently to treat constipation as it may form a habit
2. Do not use purgatives to treat constipation with fever and following heart attack. A suppository or simple enema is preferred.
3. In pregnancy ispaghula is preferred.

Reference

1. Constipation. In: Harrison’s Principles of Internal Medicine. Braunwald E, Fauci AS, Kasper DL et al (eds), 15th Edition, 2001, McGraw Hill Company Inc., New York, pp 248-250.
2. Medicine International. Jewell DP & Thillainayagam (eds). The Medicine Publishing Co. Oxford, UK

Vomiting

Nausea is the unpleasant feeling that one is going to vomit. Vomiting is the forceful expulsion of the gastric contents due to involuntary contraction of abdominal musculature and simultaneous relaxation of gastric fundus and lower oesophageal sphincter. Regurgitation is spitting up of the gastric contents without associated nausea or forceful contraction of abdominal musculature.

Causes of vomiting

1. Central (due to stimulation of vomiting center)-neurological diseases, raised intracranial pressure, vestibular system disorders, drugs and toxins, any acute severe pain, toxic or metabolic disorders like ketoacidosis, systemic infections, radiation exposure, pregnancy and psychogenic vomiting.
2. Peripheral-obstructive lesion of GIT, acute gastritis or gastroenteritis, severe upper GI bleed etc.

Treatment

Nonpharmacological

• Acute gastroenteritis is usually self-limiting. Advise the patient to take sips of cold water/ORS.
• Prevent motion sickness by avoiding heavy meal before travel.
• Give rest to the injured part to prevent severe pain.

Pharmacological

Treat the underlying cause (medically or surgically).

Hospitalize the patient to give IV fluids if dehydrated. Start oral fluids as soon as patient can tolerate. Appropriate analgesics if patient has severe pain.

• For symptomatic relief -
  In acute vomiting in the absence of obstruction to GIT or other organic cause, give
  Inj. Metoclopramide 10 mg IV and repeat after 6 hours, if needed.
  Or
  Inj. Prochlorperazine 5 mg IM, repeated after 4-6 hours, if needed.
• In patients with recurrent vomiting due to gastroperesis (as in diabetes), non-ulcer dyspepsia, give
  Tab. Mosapride 5 mg 3 times a day.
  Or
  Tab. Domperidone 10 mg 3 times a day.
  Or
  Tab. Metoclopramide 10 mg 3 times a day.
• To prevent motion sickness, give
  Tab. Cyclizine 50 mg upto 3 times daily. In children: 6-12 years 25 mg upto 3 times daily to be taken half an hour before starting journey.

Patient education

• Advise the patient to prevent food poisoning, not to take drugs like pain killers frequently
• Patient should be encouraged to take small sips of liquids at short intervals to prevent dehydration.

References

1. Nausea, Vomitings and Indigestion. In: Harrison’s Principles of Internal Medicine. Braunwald E., Fauci AS, Kasper DL et al (eds), 15th Edition, 2001, McGraw Hill Company Inc., New York, pp 236-239.

Peptic Ulcer

1. Tab. Omeprazole 20 mg 2 times a day.
2. Tab. Clarithromycin 500 mg 2 times a day.
3. Cap. Amoxycillin 1 g 3 times a day.

• Patient should avoid frequent use of unsupervised pain killers. If these are required on long term basis, a safer drug should be taken in consultation with a doctor.
• Smoking should be stopped
• There is no role of bland diet or drinking cold milk in the treatment of peptic ulcer.

References

1. Peptic Ulcer disease and Related Disorders. In: Harrison’s Principles of Internal Medicine. Braunwald E., Fauci AS, Kasper DL et al (eds), 15th Edition, 2001, McGraw Hill Company Inc., New York, pp 1649-1665.
2. Gastritis and PepticUlcer. In: Medicine International. Jewell
   DP & Thillainayagam (eds), 1998, The Medicine Publishing Co. Oxford, UK, pp 11-15.

Gastro-Oesophageal Reflux Disease

1. Antacid Gel (with or without alginate) 10-15 ml or 2-3 tablets (chewed) taken 4-6 times a day ½ to 1 hour after meals may be given for a long time depending upon patients symptoms. If no relief add (2) and/or (3)
   Tab. Domeperidone 10 mg 3 times a day 30 minutes before meals for 4-6 weeks or even for longer if needed.
   Or
2. Tab. Mosapride 5 mg 3 times a day 30 minutes before meals for 4-6 weeks or longer if needed.
3. Tab. Ranitidine 150 mg 2 times a day 30 minutes before meals for 4-6 weeks.

Follow up

Ranitidine courses may be repeated or continued for several months if patient relapses while on antacids or Domeperidone/Mosapride.

Moderate- to- severe gastro-oesophageal reflux disease (endoscopically proved erosive oesophagitis)

1. Cap. Omeprazole 20 mg once daily 30 minutes before meals for 4 weeks, followed by further 4-8 weeks if not fully healed.
   Or
   Cap. Lansoprazole 30 mg 2 times a day 30 minutes before meals for 3 months
   Or
   Tab. Pentoprazole 40 mg 2 times a day 30 minutes before meals for 3 months.

Follow up

Repeat endoscopy after 3 months to confirm healing of oesophagitis. If healed, continue maintenance treatment as in mild reflux disease or single daily dose of 10-20 mg Omeprazole (or any other PPIs). Refer to the specialist if no or inadequate response

Patient education

• Explain about chronic nature of the illness, role of weight reduction and early small night time meal
• Wearing tight clothes around the abdomen may also increase the reflux.

Reference

1. Management of GERD in Adults. In: Approach to Patients with Chronic Gastrointestinal Disorder’. E Corazziari (ed), 1999, Messaggi s.r.l. Milano Itali, pp 255-69.
2. Oesophageal symptoms and Motility Disorders. In: Medicine International. Jewell DP & Thillainayagam (eds), 1998, The Medicine Publishing Co. Oxford, UK pp 1-6.
3. Nausea, Vomiting and Indigestion. In: Harrison’s Principles of Internal Medicine. Braunwald E., Fauci AS, Kasper DL et al (eds), 15th Edition, 2001, Mc-Graw Hill Companies Inc., New York, pp 236-240.
4. Disease of the Oesophagus. In: Harrison’s Principles of Internal Medicine. Braunwald E., Fauci AS, Kasper DL et al (eds), 15th Edition, 2001, Mc-Graw Hill Companies Inc., New York, pp 1642-1649.
5. Gastrooesophageal reflux disease. In: Harrison’s Principles of Internal Medicine. Braunwald E., Fauci AS, Kasper DL et al (eds), 15th Edition, 2001, Mc-Graw Hill Companies Inc., New York, pp 1645-1647.

Dyspepsia

• Avoid precipitating factors.

References

1. Functional Dyspepsia: Clinical Management. In: Approach to patients with Chronic Gastrointestinal Disorder. E Corazziari (ed), 1999, Messaggi SRL Milano Itali, pp 255-69.
2. Nausea, Vomiting and Indigestion. In: Harison’s Principles of Internal Medicine. Braunwald E., Fauci AS, Kasper DL et al (eds), 15th Edition, 2001, McGraw Hill Company Inc., New York, pp 236-240.

Acute Oro-Pharyngo-Oesophageal Candidiasis

1. Inflammatory disorders. In: Harrison’sPrinciples of Internal Medicine. Braunwald E., Fauci AS, Kasper DL et al (eds), 15th Edition, 2001, McGraw Hill Company Inc., New York, pp 1647-1649.
2. Oropharyngeal Anti-infective Drugs. British National Formulary, 2002; pp 530.

Recurrent Oral Aphthous Ulcers

Salient features

• Single or multiple 1-15 mm size painful ulcers surrounded by erythematous mucosa occurring repeatedly any where in the oral mucosa (lip, tongue, soft palate or oropharynx). Usually heal in 1-2 weeks time.
• Rule out secondary causes like malabsorption syndrome, inflammatory bowel disease, Behcet’s disease and recurrent trauma from tooth/denture and treat accordingly

Treatment

Nonpharmacological

Oral hygiene (repeated mouth wash with plain water specially after eating any thing).

Pharmacological

1. Symptomatic treatment with application of any gel containing local anaesthetic before taking meals.
2. Only in severe cases with large multiple ulcers.
   Pellets Hydrocortisone 5 mg to be kept on the ulcer and sucked every 4 hours for 3-5 days.
   Or
   Tab. Prednisolone 0.5 mg/kg/day in a single dose for 3-5 days.

• Maintain good oral hygiene.
• Avoid precipitating factors, if any.

References

Oral Manifestation of Disease. In: Harrison’s Principles of Internal Medicine. Braunwald E., Fauci AS, Kasper DL et al (eds), 15th Edition, 2001, McGraw Hill Company Inc., New York, pp 193-199.