142
sometimes lead to healing. Thus, some locally advanced breast carcinomas can be widely excised and the chest wall reconstructed with myocutaneous flaps; radiotherapy reduces bleeding and discharge and can cleanse large areas of tumour, even when given in palliative doses; and in sensitive tumours, hormone therapy and chemotherapy can lead to
surprising improvements. For tumours that are resistant to all therapeutic measures, local palliation is all that can be offered. Daily nursing care will reduce the risk of infection; deodorisers and ventilation may improve the smell but are seldom enough on their own; and daily charcoal dressings, which adsorb the volatile fatty-acids, are sometimes sufficient to control the fetor.4 Topical honey and icing sugar have also been suggested,5,6 and are thought to act by adsorption and by the creation of a hyperosmolar environment that precludes bacterial growth. However, the sterility of honey cannot be guaranteedand neither agent is practical to use. The deodorising effect of metronidazole was first reported in 19808 and these initial observations were subsequently confirmed.9-11 Controlled studies have shown a correlation between a reduction in smell and the eradication of anaerobic infection.9 Unfortunately, continuous therapy is required because the organisms soon regrow when treatment is stopped. In addition, metronidazole can cause nausea and long-term use is associated with neuropathy. The ban on alcohol that is necessary during metronidazole treatment may be distressing for some patients. Although clindamycin is an effective alternative2 it must also be taken systemically and is effective only for as long as therapy continues. To avoid these difficulties, Allwood et al have experimented with topical metronidazole for accessible tumours. 12 Initial trials with dressings soaked in metronidazole injection preparation, although effective for bed sores13 and diabetic ulcers, were not totally successful in treating smelly tumours because absorption was poor. It was therefore decided to incorporate the metronidazole in an 0-8% gel formulation for use with daily dressings. A trial in 68 hospice patients with smelly tumours showed that it was totally effective in 50% and reasonably effective in a further 46%, having no effect in only 3 patients. Many staff commented that this treatment compared favourably with previous therapy, including oral metronidazole.14 The gel has now been licensed in the UK and is a valuable addition to the treatment options available for a most unpleasant aspect of malignant disease. 1. Altemeier WA. The cause of the putrid odor of perforated appendicitis with peritonitis. Ann Surg 1938; 107: 634-36. 2. Brusis T, Luckhaupt H. Fetor from ulcerated head and neck tumors. Ann Otol Rhinol Laryngol 1989; 98: 615-17. 3. Rotimi VO, Durosinmi-etti FA. The bacteriology of infected malignant ulcers. J Clin Pathol 1984; 37: 592-95. 4. Beckett R, Coombes TJ, Frost MR, et al. Charcoal cloth and malodorous wounds. Lancet 1980; ii; 594. 5. Thomlinson RH. Kitchen remedy for necrotic malignant breast ulcers. Lancet 1980; ii: 707. 6. Keast-Butler J. Honey for necrotic malignant breast ulcers. Lancet 1980; ii: 809. 7. Mossel DAA. Honey for necrotic malignant breast ulcers. Lancet 1980; ii: 1091. 8. Ashford RFU. Plant GT, Maher J, et al. Metronidazole in smelly tumours. Lancet 1980; i: 874-75. 9. Ashford RFU, Plant G, Maher J, Teare L. Double-blind trial of metronidazole in malodorous ulcerating tumours. Lancet 1984; i: 1232-33. 10. Sparrow G, Minton M, Rubens RD, Simmons NA, Aubrey C. Metronidazole in smelly tumours. Lancet 1980; i: 1185.
11. Dankurt
J, Holloway Y, Bouma J, Van de Vergh J, Wolfthers, BG. Metronidazole in smelly gynaecological tumours. Lancet 1981; ii: 1295. 12. Allwood M, McHutchinson DI. Commercial version of metronidazole gel. Pharmaceutical J 1987; April 18: 504. 13. Gomolin IH, Brandt JL. Topical metronidazole therapy for pressure sores for geriatric patients. J Am Geriatric Soc 1983; 31: 710-12. 14. Newman V, Allwood M, Oakes RA. The use of metronidazole gel to control the smell of malodorous lesions. Palliative Med 1989; 3: 303-05.
ABO INCOMPATIBILITY AND PLATELET TRANSFUSION That transfusion of platelets can arrest bleeding caused by thrombocytopenia has been known for more than 75 years, but until lately this was an uncommon form of treatment. Then aggressive, potentially curative treatment schedules for malignant diseases, especially leukaemia and lymphoma, called for intensive support, including the provision of large amounts of platelets for transfusion. Transfusion services rose to the challenge, with increased production of single donor and apheresis harvested material and with increased understanding of optimum conditions for storage and handling. Nonetheless, the demand for platelets is heavy, increasing, and, in the short term, often unpredictable. Need platelets be from ABO identical or compatible donors? Is Rh compatibility important? These factors may have a bearing on the efficacy and morbidity of platelet transfusion. There are three aspects to consider-the platelets themselves; red cell contamination of platelet preparations; and the donor plasma. ABH antigens are expressed on the platelet surface; Rh antigens are not present. There is some evidence that transfusion of ABO incompatible platelets results in a poorer response, both clinically and in post-transfusion increments. Not surprisingly, responses are poorer in those who receive
multiple incompatible transfusions.1,2 Moreover, persistent use of ABO incompatible platelets may stimulate plateletspecific antibodies, leading to refractoriness. Group B platelets may be preferable to group A in an incompatible transfusion. However, at least one recent large prospective study showed that ABO incompatibility was not a significant variable in a multivariate analysis of factors likely to cause a poor response to HLA-matched platelet transfusion. The extent of red cell contamination will vary with the technique used to prepare material for transfusion but can be sufficient to immunise susceptible individuals against Rh. A retrospective study of Rh(D)-negative patients who received multiple transfusions of platelets from Rh(D) positive donors found that anti-D developed in 8% notwithstanding the immunosuppression associated with the underlying diagnoses and treatments.4 Patients may be harmed by ABO incompatible platelet transfusions when the donor has unexpectedly possessed an especially potent isoagglutinin and sufficient donor plasma has been transfused to cause an acute haemolytic reaction in the -
recipient. 5-7 These three drawbacks can obviously be avoided by exclusive use of ABO compatible material for platelet transfusion, but such a policy inevitably results in wastage of a scarce product that has a short shelf-life and is subject to unpredictable demand. Adoption of a policy of ignoring ABO groups reduced wastage from 19% to 5% in one UK region, but careful study of the consequences in patients receiving incompatible platelets led subsequently to a reversal of this approach.1
143
The Rh problem can most easily be solved by giving an6-D immunoglobulin to D-negative recipients of platelets from D-positive donors if immunisation could cause difficulties--eg, in women of childbearing age. High-titre isoagglutinins can be detected by donor screening or by some sort of reverse crossmatch procedure. The latter would be labour intensive and a cumbersome way of preventing a very uncommon complication. Platelet transfusion is highly effective treatment and has become an indispensible adjunct to many forms of chemotherapy and to marrow transplantation. It is also very safe. Whilst ABO compatibility is desirable, it is better to transfuse incompatible platelets than none at all. In long-term support however, compatible material probably causes fewer difficulties. Increased use of single donor, machine-harvested material from panels of regular platelet donors makes screening of sera for high-titre isoagglutinins an additional safeguard for transfusion centres to apply. 1. Carr R, Jenkins JA, Chapman DM, et al. Transfusion of ABOmismatched platelets reduces wastage but increases early refractoriness. British Blood Transfusion Society VI I Annual Meeting,
Durham, 1989 (abstr). 2. Lee EJ, Schiffer CA. ABO incompatibility can influence the results of platelet transfusion. Results ofa randomised trial. Transfusion 1989; 29: 384-89. 3.McFarland JG, Anderson AJ, Slichter SJ. Factors influencing the transfusion response to HLA-selected apheresis donor platelets in patients refractory to random platelet concentrates. Br J Haematol
1989; 73: 380-86. 4. Goldfinger D, McGinnis MH. Rh incompatible platelet transfusionrisks and consequences of sensitizing immunosuppressed patients. N Engl J Med 1971; 284: 942-44. 5. Pierce RN, Reich LM, Mayer K. Hemolysis following platelet transfusion from ABO-incompatible donors. Transfusion 1985; 25: 60-62. 6. Resi MD, Coovadia AS. Transfusion of ABO-incompatible platelets causing severe haemolytic reaction. Clin Lab Haematol 1989; 11: 237-40. 7. Winter PM, Amon M, Hocker P. Febrile transfusion reaction caused by ABO-incompatible platelet transfusion. Infusionstherapie 1988; 15: 251-53.
HOT DRINKS AND PEPTIC ULCERS To the uninitiated, the link between eating habits and peptic disease seems obvious and rational. However, even a brief acquaintance with the subject shows that any such relation is elusive. There is no convincing evidence that the type of
food, frequency of meals, or their size is causally related to peptic ulceration.12 Although dietary modifications will worsen or improve symptoms in some patients with ulcer and non-ulcer dyspepsia, the natural history of the disease is not apparently so affected. Alcohol, caffeine-containing beverages, and cola-type drinks are all secretagogues and may influence the patient’s dyspeptic symptoms, but none has been proven to cause or aggravate peptic ulceration.1,2 Thermal irritation was first suggested as a cause of peptic ulcer more than a century ago, when mucosal haemorrhages and erosions were observed in dogs that had been fed gruel at 62°C.3 Subsequent animal experiments either gave similar results4-6 or showed no such lesions;’ in none of these studies was peptic ulceration recorded. Fewer experiments have been conducted in man, who alone in the animal kingdom chooses to eat food hotter or colder than in its natural condition. Most attention has been directed to hot food and drinks. The typical preferred temperature of hot drinks by normal subjects is around 60°C.6,8,10 Solid food
can be tolerated at higher temperatures because of its lower thermal conductivity.6 Substances that are ingested quickly lose their heat during transit from the lips to the stomach; cooling is more rapid for liquids than for solids.6 Complex systems have been devised to allow measurement of intraluminal temperature changes in the upper alimentary tract during and after ingestion of hot food and drinks. 11 Normal ranges have yet to be established, but published examples indicate that food eaten at 60°C falls to 50°C in the lower oesophagus and gastric body but to less than 40°C in the gastric antrum and duodenum; within the stomach, food temperature falls by about 1°C per minute.11 Although 19th century physicians12.13 taught that patients with gastric ulcer had a preference for hot drinks, this was no more than a clinical impression. Edwards and Edwards9 in 1955 reported that dyspeptic patients with histological gastritis took their drinks hotter than did those without gastritis. This study was somewhat flawed by the long and variable interval (up to three years) between the demonstration of gastritis and the testing of preferred drink temperature. More recently Pearson and McCloy1O have conducted a similar survey in 59 patients with endoscopically proven disorders and in 65 symptom-free controls. The patients with peptic disease chose to drink their tea or coffee 6°C hotter than did controls (median 62°C vs 56°C). Those with oesophageal disease (63’5°C) and gastric disease (63°C) preferred hotter drinks than did those with duodenal disease (60-5°C). These observations were not influenced by sex, age, or smoking habits. Although the difference between the median values of patients and controls was statistically significant, the overlap was such that most of the chosen temperatures for all those tested fell between 53°C and 66°C. Interpretation of these latest findings is difficult, and the researchers’ enthusiasm for a causal relation is unlikely to be widely shared. It would be interesting to know the differences in intraluminal temperatures in the various groups and whether temperature had any effect on acid secretion, mucus, cell kinetics, and Helicobacter pylori.
1. Richardson CH. Gastric ulcer. In: Sleisenger MH, Fordtran JS, eds. Gastrointestinal disease. 4th ed. Philadelphia: W. B. Saunders, 1989: 879-909. 2. Soll AH. Duodenal ulcer and drug therapy. In: Sleisenger MH, Fordtran JS, eds. Gastrointestinal disease. Philadelphia: W. B. Saunders, 1989: 814-79.
3. Decker J. Experimenteller Beitrag zur Aetiologie der Magengeschwure. Berl Klin Wchnschr 1987; 24: 369-71. 4. Ivy AC, Farrell JI. Experimental production of achylia gastrica in dogs. Proc Soc Exp Biol NY 1926; 23: 752. 5. Dyer HM, Kelly MG, Dunn TB. Effect of administration of hot water, acids, alkalies, mecholyl chloride or atropine sulfate upon gastric mucosa of mice. J Natl Cancer Inst 1946; 7: 67-70. 6. Davis RE, Ivy AC. Thermal irritation in gastric disease. Cancer 1949; 2: 138-42. 7. Lewis JH cited
by Wells HG, Slye M, Holmes HF. Comparative pathology of cancer of alimentary canal. Am J Cancer 1938; 33: 223-38. 8. Hunt JN. The temperature of choice for hot drinks: a comparison of men and women. Guys Hosp Rep 1947; 96: 60-63. 9. Edwards FC, Edwards JH. Tea drinking and gastritis. Lancet 1956; ii: 543-45. 10. Pearson RC,
McCloy RF. Preference for hot drinks is associated with peptic disease. Gut 1989; 30: 1201-05. 11. Pearson RC, McCloy RF, Cutler WC, Levitt JR, Richards B, Vickery JC. Multichannel digital recording of intraluminal temperature in the upper gastrointestinal tract of man: techniques and analyses. Clin Phys Physiol Meas 1988; 9: 243-48. 12. Lauder Brunton T. Disorders of digestion. London: Macmillan, 1886: 65. 13. Ewald CA. Lectures on disease of the digestive organs. Vol 1. Lectures on digestion. (Translation by Saundby R.) London: New Sydenham Society, 1891.
sometimes lead to healing. Thus, some locally advanced breast carcinomas can be widely excised and the chest wall reconstructed with myocutaneous flaps; radiotherapy reduces bleeding and discharge and can cleanse large areas of tumour, even when given in palliative doses; and in sensitive tumours, hormone therapy and chemotherapy can lead to
surprising improvements. For tumours that are resistant to all therapeutic measures, local palliation is all that can be offered. Daily nursing care will reduce the risk of infection; deodorisers and ventilation may improve the smell but are seldom enough on their own; and daily charcoal dressings, which adsorb the volatile fatty-acids, are sometimes sufficient to control the fetor.4 Topical honey and icing sugar have also been suggested,5,6 and are thought to act by adsorption and by the creation of a hyperosmolar environment that precludes bacterial growth. However, the sterility of honey cannot be guaranteedand neither agent is practical to use. The deodorising effect of metronidazole was first reported in 19808 and these initial observations were subsequently confirmed.9-11 Controlled studies have shown a correlation between a reduction in smell and the eradication of anaerobic infection.9 Unfortunately, continuous therapy is required because the organisms soon regrow when treatment is stopped. In addition, metronidazole can cause nausea and long-term use is associated with neuropathy. The ban on alcohol that is necessary during metronidazole treatment may be distressing for some patients. Although clindamycin is an effective alternative2 it must also be taken systemically and is effective only for as long as therapy continues. To avoid these difficulties, Allwood et al have experimented with topical metronidazole for accessible tumours. 12 Initial trials with dressings soaked in metronidazole injection preparation, although effective for bed sores13 and diabetic ulcers, were not totally successful in treating smelly tumours because absorption was poor. It was therefore decided to incorporate the metronidazole in an 0-8% gel formulation for use with daily dressings. A trial in 68 hospice patients with smelly tumours showed that it was totally effective in 50% and reasonably effective in a further 46%, having no effect in only 3 patients. Many staff commented that this treatment compared favourably with previous therapy, including oral metronidazole.14 The gel has now been licensed in the UK and is a valuable addition to the treatment options available for a most unpleasant aspect of malignant disease. 1. Altemeier WA. The cause of the putrid odor of perforated appendicitis with peritonitis. Ann Surg 1938; 107: 634-36. 2. Brusis T, Luckhaupt H. Fetor from ulcerated head and neck tumors. Ann Otol Rhinol Laryngol 1989; 98: 615-17. 3. Rotimi VO, Durosinmi-etti FA. The bacteriology of infected malignant ulcers. J Clin Pathol 1984; 37: 592-95. 4. Beckett R, Coombes TJ, Frost MR, et al. Charcoal cloth and malodorous wounds. Lancet 1980; ii; 594. 5. Thomlinson RH. Kitchen remedy for necrotic malignant breast ulcers. Lancet 1980; ii: 707. 6. Keast-Butler J. Honey for necrotic malignant breast ulcers. Lancet 1980; ii: 809. 7. Mossel DAA. Honey for necrotic malignant breast ulcers. Lancet 1980; ii: 1091. 8. Ashford RFU. Plant GT, Maher J, et al. Metronidazole in smelly tumours. Lancet 1980; i: 874-75. 9. Ashford RFU, Plant G, Maher J, Teare L. Double-blind trial of metronidazole in malodorous ulcerating tumours. Lancet 1984; i: 1232-33. 10. Sparrow G, Minton M, Rubens RD, Simmons NA, Aubrey C. Metronidazole in smelly tumours. Lancet 1980; i: 1185.
11. Dankurt
J, Holloway Y, Bouma J, Van de Vergh J, Wolfthers, BG. Metronidazole in smelly gynaecological tumours. Lancet 1981; ii: 1295. 12. Allwood M, McHutchinson DI. Commercial version of metronidazole gel. Pharmaceutical J 1987; April 18: 504. 13. Gomolin IH, Brandt JL. Topical metronidazole therapy for pressure sores for geriatric patients. J Am Geriatric Soc 1983; 31: 710-12. 14. Newman V, Allwood M, Oakes RA. The use of metronidazole gel to control the smell of malodorous lesions. Palliative Med 1989; 3: 303-05.
ABO INCOMPATIBILITY AND PLATELET TRANSFUSION That transfusion of platelets can arrest bleeding caused by thrombocytopenia has been known for more than 75 years, but until lately this was an uncommon form of treatment. Then aggressive, potentially curative treatment schedules for malignant diseases, especially leukaemia and lymphoma, called for intensive support, including the provision of large amounts of platelets for transfusion. Transfusion services rose to the challenge, with increased production of single donor and apheresis harvested material and with increased understanding of optimum conditions for storage and handling. Nonetheless, the demand for platelets is heavy, increasing, and, in the short term, often unpredictable. Need platelets be from ABO identical or compatible donors? Is Rh compatibility important? These factors may have a bearing on the efficacy and morbidity of platelet transfusion. There are three aspects to consider-the platelets themselves; red cell contamination of platelet preparations; and the donor plasma. ABH antigens are expressed on the platelet surface; Rh antigens are not present. There is some evidence that transfusion of ABO incompatible platelets results in a poorer response, both clinically and in post-transfusion increments. Not surprisingly, responses are poorer in those who receive
multiple incompatible transfusions.1,2 Moreover, persistent use of ABO incompatible platelets may stimulate plateletspecific antibodies, leading to refractoriness. Group B platelets may be preferable to group A in an incompatible transfusion. However, at least one recent large prospective study showed that ABO incompatibility was not a significant variable in a multivariate analysis of factors likely to cause a poor response to HLA-matched platelet transfusion. The extent of red cell contamination will vary with the technique used to prepare material for transfusion but can be sufficient to immunise susceptible individuals against Rh. A retrospective study of Rh(D)-negative patients who received multiple transfusions of platelets from Rh(D) positive donors found that anti-D developed in 8% notwithstanding the immunosuppression associated with the underlying diagnoses and treatments.4 Patients may be harmed by ABO incompatible platelet transfusions when the donor has unexpectedly possessed an especially potent isoagglutinin and sufficient donor plasma has been transfused to cause an acute haemolytic reaction in the -
recipient. 5-7 These three drawbacks can obviously be avoided by exclusive use of ABO compatible material for platelet transfusion, but such a policy inevitably results in wastage of a scarce product that has a short shelf-life and is subject to unpredictable demand. Adoption of a policy of ignoring ABO groups reduced wastage from 19% to 5% in one UK region, but careful study of the consequences in patients receiving incompatible platelets led subsequently to a reversal of this approach.1
143
The Rh problem can most easily be solved by giving an6-D immunoglobulin to D-negative recipients of platelets from D-positive donors if immunisation could cause difficulties--eg, in women of childbearing age. High-titre isoagglutinins can be detected by donor screening or by some sort of reverse crossmatch procedure. The latter would be labour intensive and a cumbersome way of preventing a very uncommon complication. Platelet transfusion is highly effective treatment and has become an indispensible adjunct to many forms of chemotherapy and to marrow transplantation. It is also very safe. Whilst ABO compatibility is desirable, it is better to transfuse incompatible platelets than none at all. In long-term support however, compatible material probably causes fewer difficulties. Increased use of single donor, machine-harvested material from panels of regular platelet donors makes screening of sera for high-titre isoagglutinins an additional safeguard for transfusion centres to apply. 1. Carr R, Jenkins JA, Chapman DM, et al. Transfusion of ABOmismatched platelets reduces wastage but increases early refractoriness. British Blood Transfusion Society VI I Annual Meeting,
Durham, 1989 (abstr). 2. Lee EJ, Schiffer CA. ABO incompatibility can influence the results of platelet transfusion. Results ofa randomised trial. Transfusion 1989; 29: 384-89. 3.McFarland JG, Anderson AJ, Slichter SJ. Factors influencing the transfusion response to HLA-selected apheresis donor platelets in patients refractory to random platelet concentrates. Br J Haematol
1989; 73: 380-86. 4. Goldfinger D, McGinnis MH. Rh incompatible platelet transfusionrisks and consequences of sensitizing immunosuppressed patients. N Engl J Med 1971; 284: 942-44. 5. Pierce RN, Reich LM, Mayer K. Hemolysis following platelet transfusion from ABO-incompatible donors. Transfusion 1985; 25: 60-62. 6. Resi MD, Coovadia AS. Transfusion of ABO-incompatible platelets causing severe haemolytic reaction. Clin Lab Haematol 1989; 11: 237-40. 7. Winter PM, Amon M, Hocker P. Febrile transfusion reaction caused by ABO-incompatible platelet transfusion. Infusionstherapie 1988; 15: 251-53.
HOT DRINKS AND PEPTIC ULCERS To the uninitiated, the link between eating habits and peptic disease seems obvious and rational. However, even a brief acquaintance with the subject shows that any such relation is elusive. There is no convincing evidence that the type of
food, frequency of meals, or their size is causally related to peptic ulceration.12 Although dietary modifications will worsen or improve symptoms in some patients with ulcer and non-ulcer dyspepsia, the natural history of the disease is not apparently so affected. Alcohol, caffeine-containing beverages, and cola-type drinks are all secretagogues and may influence the patient’s dyspeptic symptoms, but none has been proven to cause or aggravate peptic ulceration.1,2 Thermal irritation was first suggested as a cause of peptic ulcer more than a century ago, when mucosal haemorrhages and erosions were observed in dogs that had been fed gruel at 62°C.3 Subsequent animal experiments either gave similar results4-6 or showed no such lesions;’ in none of these studies was peptic ulceration recorded. Fewer experiments have been conducted in man, who alone in the animal kingdom chooses to eat food hotter or colder than in its natural condition. Most attention has been directed to hot food and drinks. The typical preferred temperature of hot drinks by normal subjects is around 60°C.6,8,10 Solid food
can be tolerated at higher temperatures because of its lower thermal conductivity.6 Substances that are ingested quickly lose their heat during transit from the lips to the stomach; cooling is more rapid for liquids than for solids.6 Complex systems have been devised to allow measurement of intraluminal temperature changes in the upper alimentary tract during and after ingestion of hot food and drinks. 11 Normal ranges have yet to be established, but published examples indicate that food eaten at 60°C falls to 50°C in the lower oesophagus and gastric body but to less than 40°C in the gastric antrum and duodenum; within the stomach, food temperature falls by about 1°C per minute.11 Although 19th century physicians12.13 taught that patients with gastric ulcer had a preference for hot drinks, this was no more than a clinical impression. Edwards and Edwards9 in 1955 reported that dyspeptic patients with histological gastritis took their drinks hotter than did those without gastritis. This study was somewhat flawed by the long and variable interval (up to three years) between the demonstration of gastritis and the testing of preferred drink temperature. More recently Pearson and McCloy1O have conducted a similar survey in 59 patients with endoscopically proven disorders and in 65 symptom-free controls. The patients with peptic disease chose to drink their tea or coffee 6°C hotter than did controls (median 62°C vs 56°C). Those with oesophageal disease (63’5°C) and gastric disease (63°C) preferred hotter drinks than did those with duodenal disease (60-5°C). These observations were not influenced by sex, age, or smoking habits. Although the difference between the median values of patients and controls was statistically significant, the overlap was such that most of the chosen temperatures for all those tested fell between 53°C and 66°C. Interpretation of these latest findings is difficult, and the researchers’ enthusiasm for a causal relation is unlikely to be widely shared. It would be interesting to know the differences in intraluminal temperatures in the various groups and whether temperature had any effect on acid secretion, mucus, cell kinetics, and Helicobacter pylori.
1. Richardson CH. Gastric ulcer. In: Sleisenger MH, Fordtran JS, eds. Gastrointestinal disease. 4th ed. Philadelphia: W. B. Saunders, 1989: 879-909. 2. Soll AH. Duodenal ulcer and drug therapy. In: Sleisenger MH, Fordtran JS, eds. Gastrointestinal disease. Philadelphia: W. B. Saunders, 1989: 814-79.
3. Decker J. Experimenteller Beitrag zur Aetiologie der Magengeschwure. Berl Klin Wchnschr 1987; 24: 369-71. 4. Ivy AC, Farrell JI. Experimental production of achylia gastrica in dogs. Proc Soc Exp Biol NY 1926; 23: 752. 5. Dyer HM, Kelly MG, Dunn TB. Effect of administration of hot water, acids, alkalies, mecholyl chloride or atropine sulfate upon gastric mucosa of mice. J Natl Cancer Inst 1946; 7: 67-70. 6. Davis RE, Ivy AC. Thermal irritation in gastric disease. Cancer 1949; 2: 138-42. 7. Lewis JH cited
by Wells HG, Slye M, Holmes HF. Comparative pathology of cancer of alimentary canal. Am J Cancer 1938; 33: 223-38. 8. Hunt JN. The temperature of choice for hot drinks: a comparison of men and women. Guys Hosp Rep 1947; 96: 60-63. 9. Edwards FC, Edwards JH. Tea drinking and gastritis. Lancet 1956; ii: 543-45. 10. Pearson RC,
McCloy RF. Preference for hot drinks is associated with peptic disease. Gut 1989; 30: 1201-05. 11. Pearson RC, McCloy RF, Cutler WC, Levitt JR, Richards B, Vickery JC. Multichannel digital recording of intraluminal temperature in the upper gastrointestinal tract of man: techniques and analyses. Clin Phys Physiol Meas 1988; 9: 243-48. 12. Lauder Brunton T. Disorders of digestion. London: Macmillan, 1886: 65. 13. Ewald CA. Lectures on disease of the digestive organs. Vol 1. Lectures on digestion. (Translation by Saundby R.) London: New Sydenham Society, 1891.
