Journal of the Royal Society of Medicine Volume 83 December 1990
Gastrointestinal complications of the haemolytic
D C G Crabbe mcs'
J T Broklebank Fcp2
uraemic
R D Spicer FRcs1
773
syndrome
yndom
Departments of
'Paediatric Surgery and 2Nephrology, St James' University Hospital, Leeds Keywords: haemolytic uraemic syndrome; intestinal ischaemia; acute renal failure
Paper read to Section of
Summary
The haemolytic uraemic syndrome (HUS) is a well recognized cause of acute renal failure in children. Gastrointestinal involvement is common, and may result in rectal bleeding which can be an important. presenting symptom. Previous publications have stressed the importance of correct diagnosis to avoid unnecessary surgery. Occasionally serious gastrointestinal complications do occur. We present five children with life-threatening gastrointestinal complications of the HUS and discuss the indications for laparotomy. Introduction The haemolytic uraemic syndrome (HUS) is an important cause of acute renal failure in children. The syndrome was first described by Gasser et al. in 19551, and comprises of three important features: uraemia, thrombocytopaenia and a microangiopathic haemolytic anaemia2. Whilst HUS is a heterogeneous entity, the classical form is typically presaged by a gastroenteritic illness accompanied by rectal bleeding. The colitis is generally regarded as a relatively trivial component of the illness, although it may provide an important first clue to the correct diagnosis. Sixty-two patients have been treated in Leeds for the HUS between 1984 and 1989. There were two deaths in this group; one from neurological involvement and the other, mentioned in this report, from a colonic perforation. It is our clinical impression that the severity of the colitis is increasing. Despite this, there are few reports of serious gastrointestinal complications in the literature. In our series of patients we have treated five patients for lifethreatening GI complications of the syndrome. These five cases are presented and the indications for surgical intervention in the HUS are discussed. Case reports
Paediatrics, 24 November 1989
Figure 1. Case 2. Histological section of the resected colon showing submucosal haemorrhage and occlusion of small vessels in the colonic wall by fibrin. H&E stain, high power
Case 2 A previously fit 5-year-old girl initially presented with a 36-h history of colicky abdominal pain and vomiting. Oii the fourth day, of her illness she developed bloodstained diarrhoea and became anuric. She was referred to Leeds for dialysis. On arrival, her abdomen was distended, silent and generally tender. Initial investigations revealed an elevated plasma urea 15.4 mmol/l, plasma creatinine 291 Amol/l, a leucocytosis 32x iO0/1 and a thrombocytopaenia 50x108/1; Peritoneal dialysis was begun through a catheter inserted percutaneously. This was not successful: -the effluent was persistently bloodstained and. slow to drain, despite correction of the thrombocytopaenia. The patient was haemodialysed. The abdominal signs remained worrying and she underwent a laparotomy on the 5th day of her illness. At laparotomy, there was a bloody ascites. The transverse and descending colon was haemorrhagic and oedematous. A Hartmann's resection was performed. Her postoperative recovery wat complicated by hypertension, convulsions and persistent hyperglycaemia. She remains on subcutaneous insulin. Her colostomy has since been closed and her renal function has returned to normal. Histological examination of the colon revealed submucosal haemorrhage with
Case
occlusion of mucosal vessels with fibrin (Figure 1).
A previously fit 15-month-old boy presented with a 3-day history of diarrhoea, latterly bloodstained. He became anuric the day after admission to hospital and suffered a number of grand mal seizures. He was referred to Leeds for dialysis. On arrival, the child was comatose. The abdomen was silent, distended but not tender. Initial investigations showed a raised creatinine 341 pmoIl, urea 13.2 mmod/l, haemogiobin 10.8 g/dl, platelet count 20x1091/l, white cell ount 32.1x1(9/L. A chest radiograph showed signs of pulm ry oedema. A peritoneal dialysis catheter was inserted percutaneously. Unfortunately, dialysis was unsatisfactory: the dialysate remained bloodstained and would not drainadequately.The infant's condition failed to improve. He required artificial ventilation and suffered an asystohic cardiac arrest 24 h after admission, from which he could not be resuscitated. Postmortem examination demonstrated generalized pertonitis. The distal transverse and descending colon was necrotic with a perforation at the splenic flexure.
Case 3 -A 4-year-old girl, diagnosed diabetic one year previously, managed on subcutaneous insulin. She presented with a 3-day -history of diarrhoea and vomiting. The day after admission she began to pass blood per rectum hid became oliguric. Fragmented ery reidtihedon a blood film and stool cultures subsequ grew a producing strain ofE. coli 057. Her renal filure tially managed by peritoneal dialysi thrugh Xaieho catheter. This was difficult due to persistent cath blockage, ee an omentectomy. She was referred to Lee4- 0-4O-0768/90 on the 14th day of her illness for haemodialysis. The 12O773 following day she had a massive haematemesis and passed 0 1990copiousmelaena. After rwuscitation and upper GI endoscopy The Royal sh&'came to laparotomy where a bleeding posterior duodenal Society of ulcer was underrun. Medicine
774
Journal of the Royal Society of Medicine Volume 83 December 1990
Case 4. Operative photograph showing the sricture in the descending colon identified on barium enemaI
Figure 2.
Case 4 A previously fit 2-year-old girl presented with a 4-day history of bloody diarrhoea and abdominal pain. She was initially treated with corticosteroids for a presumptive diagnosis of ulcerative colitis. She did not improve and became oliguric 3 days later. On admission she was generally oedematous. Tenderness localized to the left hypochondrium was noted on abdominal examination. Investigations on admision showed elevated plasma urea, 30.4 mmol/l, and creatinine, 364 i&mol/l. She was anaemic, 6.6 g/dl, thrombocytopaenic, 24x 1091/1 and there was a leucocytous, 26.7x109/L. Peritoneal dialysis was begun and, after initial problems with a hydrothorax, her renal function recovered completely. She was discharged home one month after presentation. Her convalescence was complicated by persitent constipation and colicky abdominal pain. This failed to respond to conservative measures. A barium enema showed a tight stricture in the descending colon. This was resected 45 days after the onset of her illness after which she made an uncomplicated recovery. Figure 2 shows the colonic stricture at the time of her laparotomy. Case 5 This previously healthy 5-year-old girl presented with a 5-day history of abdominal pain, intermittent rectal prolapse and rectal bleeding. She became uraemic 4 days later and had a grand mal convulsion. She was transferred to Leeds for dialysis. She required paralysis and ventilation for intractable seizures. Her renal fimction improved over the following 10 days. However, at the time ofher discharge from hospital she was felt to have sustained profound cerebral damage from the seizures. She eventually made a complete neurological recovery. She represented exactly one year after her original illness with an intestinal obstruction. At laparotomy a short stricture was resected from the transverse colon. She remains well. Histological examination of the resected specimen showed a chronic fibrous stricture (Figure 3).
Figure 3. Case 5. Histologial section through the colonic stricture showing chronic fibrosis. H&E stain, high power
Discussion The diagnosis of HUS can be difficult. The initial presentation may be with peritoneal signs miicking acute appendicitis or an intussusception3'4. Failure to recognize the uraemia may lead to an unnecessary laparotomy. A therapeutic dilemma still exists once the correct diagnosis has been made: peritoneal signs are common in HUS. They may be difficult to interpret in an unconscious child, and masked by peritoneal dialysis. The general impression is that serious gastrointestinal complications are uncommon in HUS. In Gianantonio's series of 678 cases there were no major gastrointestinal problems documented5. Segmental colonic gangrene6 and stricture formation7 have, however, been recorded in the literature and our cases represent further examples of these complications. In view of the relative rarity of serious intestinal complications compared with the frequency of peritoneal signs in the acute phase of HUS, it is difficult to be dogmatic about the indications for surgery. In our series of cases, peritoneal dialysis was technically unsatisfactory in both children with acute colonic complications. The dialysate was persistently bloodstained, despite correction ofthrombocytopaenia, and drained slowly. It is our routine practice to send samples of dialysate for bacterial culture daily during the acute phase of the illness. Cell counts were of limited value, as the dialysates were frankly haemorrhagic, and the results of culture arrived too late to be of clinical value. Based on our experience, we would now advise early laparotomy in the patient with HUS, who has signs of peritoneal irritation, and a persistently bloodstained dialysate. Similarly, we would normally anticipate considerable clinical improvement within 24 h of the start of dialysis. Failure to improve in a patient with worrying peritoneal signs should again indicate the need for surgical exploration. Haemodialysis should be considered in children with worrying abdominal signs at presentation. Although technically more difficult than peritoneal dialysis in young children, haemodialysis will permit repeated clinical examination of an abdomen which is not distended with dialysate. After making the decision to proceed with laparotomy, the surgeon may be faced with a decision about resection of the colon. A colonic perforation obviously necessitates resection but the usual situation is an oedematous haemorrhagic thick-walled colon. HUS is now regarded as a toxaemic illness. The pathogenesis is thought to involve endothelial cell damage by the verocytotoxin produced by E. coli. The resulting microangiopathy is responsible for the haematological abnormalities and the ischaemic damage to the target organs. Removal of the source of the toxin, ie colonic resection, is a logical step. We have felt that primary anastomosis of the colon is unsafe in this situation and would therefore advise a Hartman's procedure. It is interesting to note that we were only able to isolate a verocytotoxin producing strain of E. coli from one- of our cases. Late st ricture formation after HUS is uncommon; our two cases illustrate differing time courses for the development of strictures. Persistent abdominal pain in the convalescent phase of the HUS requires investigation by contrast radiology. Once stricture formation has been identified conservative treatment appears to have little role.
Journal of the Royal Society of Medicine Volume 83 December 1990
The final recommendation from our series of patients is the routine use of H2-receptor antagonists as prophylaxis against stress ulceration. We have not encountered upper GI bleeding since starting this policy. Achnowledgment: We thank Mr D F M Thomas for permission to report case 4. References 1 Gasser C, Gauthier E, Steck A, et al HamolytischUramisch Syndrome: Bilaterale Nierenrindennekrosen bei Akuten Erworbenen Hamolytischen Anamien. Schweiz Med Wochenschr 1955;38:905 2 Editorial. Unravelling HUS. Lancet 1987;ii:1437 3 Edmonson MB, Chesney RW. Hemolytic-uremic syndrome confused with acute appendicitis. Arch Surg 1978;113:754
Forthcoming events New Ideas on Common Retinal Disorders 13-14 December 1990, San Francisco, California Further details from: Extended Programs in Medical Education, Room C-124, University of California School of Medicine, San Francisco, CA 94143-0742, USA
(Tel: 4154251) 3rd International Congress on Trace Elements in Medicine and Biology: Chromium and Trace Elements in Endocrinology 15-18 January 1991, Les Deux Alpes, France Further details from: Arlette Alcaraz, Laboratoire de Biochimie C, CHRU de Grenoble, BP217 X, 38043 Grenoble Cedex, France (Tel: 76 42 81 21) MRCP Part II Courses Five-day Clinical 11-15 February 1991, Royal Free Hospital, London Further details from: Dr D Geraint James, Royal Free Hospital, Pond Street, London NW3 2QG (Tel: 071-794 0550, ext 3931) Colorectal Disease in 1991: An International Exchange of Medical and Surgical Concepts 14-16 February 1991, Ft Lauderdale Florida Further details firom: The Cleveland Clinic Educational Foundation, Department of Continuing Education, Euclid Avenue, TT-31, Cleveland, OH 44195-5241, USA(Tel: 1 800 762 8173) Recent Advances in Neurology 15-17 February 1991, San Francisco, California Further details firom: (se entry for 13-14 December 1990) 11th Instructional Course on TnDitus and its Management 24-27 March 1991, Nottingham University Further details firom: Mrs J P Willoughby, Course Secretary, MRC Istute of HearingResearch, Universty of Notinghaim, University Park, Nottingham NG7 2RD (Tel: 0602 223431; Fax: 0602 423710)
4 Smith CD, Schuster SR, Gruppe WE, et aL Hemolyticuremic syndrome: a diagnostic and therapeutic dilemma for the surgeon. J Pediatr Suirg 1978;13:597 5 Gianantonio CA, Vitacco M, Mendilaharzu F, et aL The hemolytic-uremic syndome. Nephron 1973;11:174 6 Schwartz DL, Becker JM, So BB, et aL Segmental colonic gangrene: a surgical emergency in the hemolytic-uremic syndrome. Pediatrics 1978;62:54 7 Sawaf H, Sharp MJ, Youn KJ, et aL Ischemic colitis and stricture after hemolytic-uremic syndrome. Pediatrics 1978;61:315
(Accepted 3 July 1990. Correspondence to Mr D C G Crabbe, University Department of Pathology, The Royal Victoria Infirmary, Newcastle upon Tyne NEI 4LP)
The Food Network: Achieving a healthy diet by the year 2000 19-20 March 1991, Royal College of Physicians, London Further details firom: Conference Secretariat: Conference Associates & Services Ltd BDA/HEA, Congress House, 55 New Cavendish Street, London WlM 7RE (Tel: 071486 0631; Fax: 071-935 7559) Spring Meeting of the British Association of Oral and MaxiMofacial Surgeons 12 April 1991, Brighton A joint meeting with the British Society for the Study of Orthodontics and will take the form of a Festschrift to celebrate the contributions of the late Mr John Hovell to the specialties of oral and maxillofacial surgery and orthodontics. Further details from: John C Lowry, Honorary Secretary, British Association of Oral and Maxillofacial Surgeons, Royal College of Surgeons of England, 35/43 Lincoln's Inn Fields, London WC2A 3PN 24th Annual Advances and Controversies in Clinical Pediatrics 16-18 May 1991, San Francisco, California Further details from: (see entry for 13-14 December 1990) Thyroid '1 4-5 July 1991, Newcastle upon Tyne Further details firom: Dr Petros Perros, Department of Medicine, The Medical School, University of Newcastle, Newcastle NE2 4HH Autumn Meeting of the British Association of Oral and Maxillofacial Surgeons 27-29 September 1991, Harrogate Conference Centre Further details from: John C Lowry, Honorary Secretary, British Aciation of Oral and Maxillofacial Surgeons, Royal College of Surgeons of England, 35/43 Lincoln's Inn Fields, London WC2A 3PN 3rd International Conference on SLE 13-15 April 1992, Queen Elizabeth II Conference Centre, London Further details from: Dr Graham Hughes or Mrs Denzil Fletcher, Rheumatology Department, St Thomas' Hospital, London SE1 7EH (Tel and Fax: 071-633 9422)
775
Gastrointestinal complications of the haemolytic
D C G Crabbe mcs'
J T Broklebank Fcp2
uraemic
R D Spicer FRcs1
773
syndrome
yndom
Departments of
'Paediatric Surgery and 2Nephrology, St James' University Hospital, Leeds Keywords: haemolytic uraemic syndrome; intestinal ischaemia; acute renal failure
Paper read to Section of
Summary
The haemolytic uraemic syndrome (HUS) is a well recognized cause of acute renal failure in children. Gastrointestinal involvement is common, and may result in rectal bleeding which can be an important. presenting symptom. Previous publications have stressed the importance of correct diagnosis to avoid unnecessary surgery. Occasionally serious gastrointestinal complications do occur. We present five children with life-threatening gastrointestinal complications of the HUS and discuss the indications for laparotomy. Introduction The haemolytic uraemic syndrome (HUS) is an important cause of acute renal failure in children. The syndrome was first described by Gasser et al. in 19551, and comprises of three important features: uraemia, thrombocytopaenia and a microangiopathic haemolytic anaemia2. Whilst HUS is a heterogeneous entity, the classical form is typically presaged by a gastroenteritic illness accompanied by rectal bleeding. The colitis is generally regarded as a relatively trivial component of the illness, although it may provide an important first clue to the correct diagnosis. Sixty-two patients have been treated in Leeds for the HUS between 1984 and 1989. There were two deaths in this group; one from neurological involvement and the other, mentioned in this report, from a colonic perforation. It is our clinical impression that the severity of the colitis is increasing. Despite this, there are few reports of serious gastrointestinal complications in the literature. In our series of patients we have treated five patients for lifethreatening GI complications of the syndrome. These five cases are presented and the indications for surgical intervention in the HUS are discussed. Case reports
Paediatrics, 24 November 1989
Figure 1. Case 2. Histological section of the resected colon showing submucosal haemorrhage and occlusion of small vessels in the colonic wall by fibrin. H&E stain, high power
Case 2 A previously fit 5-year-old girl initially presented with a 36-h history of colicky abdominal pain and vomiting. Oii the fourth day, of her illness she developed bloodstained diarrhoea and became anuric. She was referred to Leeds for dialysis. On arrival, her abdomen was distended, silent and generally tender. Initial investigations revealed an elevated plasma urea 15.4 mmol/l, plasma creatinine 291 Amol/l, a leucocytosis 32x iO0/1 and a thrombocytopaenia 50x108/1; Peritoneal dialysis was begun through a catheter inserted percutaneously. This was not successful: -the effluent was persistently bloodstained and. slow to drain, despite correction of the thrombocytopaenia. The patient was haemodialysed. The abdominal signs remained worrying and she underwent a laparotomy on the 5th day of her illness. At laparotomy, there was a bloody ascites. The transverse and descending colon was haemorrhagic and oedematous. A Hartmann's resection was performed. Her postoperative recovery wat complicated by hypertension, convulsions and persistent hyperglycaemia. She remains on subcutaneous insulin. Her colostomy has since been closed and her renal function has returned to normal. Histological examination of the colon revealed submucosal haemorrhage with
Case
occlusion of mucosal vessels with fibrin (Figure 1).
A previously fit 15-month-old boy presented with a 3-day history of diarrhoea, latterly bloodstained. He became anuric the day after admission to hospital and suffered a number of grand mal seizures. He was referred to Leeds for dialysis. On arrival, the child was comatose. The abdomen was silent, distended but not tender. Initial investigations showed a raised creatinine 341 pmoIl, urea 13.2 mmod/l, haemogiobin 10.8 g/dl, platelet count 20x1091/l, white cell ount 32.1x1(9/L. A chest radiograph showed signs of pulm ry oedema. A peritoneal dialysis catheter was inserted percutaneously. Unfortunately, dialysis was unsatisfactory: the dialysate remained bloodstained and would not drainadequately.The infant's condition failed to improve. He required artificial ventilation and suffered an asystohic cardiac arrest 24 h after admission, from which he could not be resuscitated. Postmortem examination demonstrated generalized pertonitis. The distal transverse and descending colon was necrotic with a perforation at the splenic flexure.
Case 3 -A 4-year-old girl, diagnosed diabetic one year previously, managed on subcutaneous insulin. She presented with a 3-day -history of diarrhoea and vomiting. The day after admission she began to pass blood per rectum hid became oliguric. Fragmented ery reidtihedon a blood film and stool cultures subsequ grew a producing strain ofE. coli 057. Her renal filure tially managed by peritoneal dialysi thrugh Xaieho catheter. This was difficult due to persistent cath blockage, ee an omentectomy. She was referred to Lee4- 0-4O-0768/90 on the 14th day of her illness for haemodialysis. The 12O773 following day she had a massive haematemesis and passed 0 1990copiousmelaena. After rwuscitation and upper GI endoscopy The Royal sh&'came to laparotomy where a bleeding posterior duodenal Society of ulcer was underrun. Medicine
774
Journal of the Royal Society of Medicine Volume 83 December 1990
Case 4. Operative photograph showing the sricture in the descending colon identified on barium enemaI
Figure 2.
Case 4 A previously fit 2-year-old girl presented with a 4-day history of bloody diarrhoea and abdominal pain. She was initially treated with corticosteroids for a presumptive diagnosis of ulcerative colitis. She did not improve and became oliguric 3 days later. On admission she was generally oedematous. Tenderness localized to the left hypochondrium was noted on abdominal examination. Investigations on admision showed elevated plasma urea, 30.4 mmol/l, and creatinine, 364 i&mol/l. She was anaemic, 6.6 g/dl, thrombocytopaenic, 24x 1091/1 and there was a leucocytous, 26.7x109/L. Peritoneal dialysis was begun and, after initial problems with a hydrothorax, her renal function recovered completely. She was discharged home one month after presentation. Her convalescence was complicated by persitent constipation and colicky abdominal pain. This failed to respond to conservative measures. A barium enema showed a tight stricture in the descending colon. This was resected 45 days after the onset of her illness after which she made an uncomplicated recovery. Figure 2 shows the colonic stricture at the time of her laparotomy. Case 5 This previously healthy 5-year-old girl presented with a 5-day history of abdominal pain, intermittent rectal prolapse and rectal bleeding. She became uraemic 4 days later and had a grand mal convulsion. She was transferred to Leeds for dialysis. She required paralysis and ventilation for intractable seizures. Her renal fimction improved over the following 10 days. However, at the time ofher discharge from hospital she was felt to have sustained profound cerebral damage from the seizures. She eventually made a complete neurological recovery. She represented exactly one year after her original illness with an intestinal obstruction. At laparotomy a short stricture was resected from the transverse colon. She remains well. Histological examination of the resected specimen showed a chronic fibrous stricture (Figure 3).
Figure 3. Case 5. Histologial section through the colonic stricture showing chronic fibrosis. H&E stain, high power
Discussion The diagnosis of HUS can be difficult. The initial presentation may be with peritoneal signs miicking acute appendicitis or an intussusception3'4. Failure to recognize the uraemia may lead to an unnecessary laparotomy. A therapeutic dilemma still exists once the correct diagnosis has been made: peritoneal signs are common in HUS. They may be difficult to interpret in an unconscious child, and masked by peritoneal dialysis. The general impression is that serious gastrointestinal complications are uncommon in HUS. In Gianantonio's series of 678 cases there were no major gastrointestinal problems documented5. Segmental colonic gangrene6 and stricture formation7 have, however, been recorded in the literature and our cases represent further examples of these complications. In view of the relative rarity of serious intestinal complications compared with the frequency of peritoneal signs in the acute phase of HUS, it is difficult to be dogmatic about the indications for surgery. In our series of cases, peritoneal dialysis was technically unsatisfactory in both children with acute colonic complications. The dialysate was persistently bloodstained, despite correction ofthrombocytopaenia, and drained slowly. It is our routine practice to send samples of dialysate for bacterial culture daily during the acute phase of the illness. Cell counts were of limited value, as the dialysates were frankly haemorrhagic, and the results of culture arrived too late to be of clinical value. Based on our experience, we would now advise early laparotomy in the patient with HUS, who has signs of peritoneal irritation, and a persistently bloodstained dialysate. Similarly, we would normally anticipate considerable clinical improvement within 24 h of the start of dialysis. Failure to improve in a patient with worrying peritoneal signs should again indicate the need for surgical exploration. Haemodialysis should be considered in children with worrying abdominal signs at presentation. Although technically more difficult than peritoneal dialysis in young children, haemodialysis will permit repeated clinical examination of an abdomen which is not distended with dialysate. After making the decision to proceed with laparotomy, the surgeon may be faced with a decision about resection of the colon. A colonic perforation obviously necessitates resection but the usual situation is an oedematous haemorrhagic thick-walled colon. HUS is now regarded as a toxaemic illness. The pathogenesis is thought to involve endothelial cell damage by the verocytotoxin produced by E. coli. The resulting microangiopathy is responsible for the haematological abnormalities and the ischaemic damage to the target organs. Removal of the source of the toxin, ie colonic resection, is a logical step. We have felt that primary anastomosis of the colon is unsafe in this situation and would therefore advise a Hartman's procedure. It is interesting to note that we were only able to isolate a verocytotoxin producing strain of E. coli from one- of our cases. Late st ricture formation after HUS is uncommon; our two cases illustrate differing time courses for the development of strictures. Persistent abdominal pain in the convalescent phase of the HUS requires investigation by contrast radiology. Once stricture formation has been identified conservative treatment appears to have little role.
Journal of the Royal Society of Medicine Volume 83 December 1990
The final recommendation from our series of patients is the routine use of H2-receptor antagonists as prophylaxis against stress ulceration. We have not encountered upper GI bleeding since starting this policy. Achnowledgment: We thank Mr D F M Thomas for permission to report case 4. References 1 Gasser C, Gauthier E, Steck A, et al HamolytischUramisch Syndrome: Bilaterale Nierenrindennekrosen bei Akuten Erworbenen Hamolytischen Anamien. Schweiz Med Wochenschr 1955;38:905 2 Editorial. Unravelling HUS. Lancet 1987;ii:1437 3 Edmonson MB, Chesney RW. Hemolytic-uremic syndrome confused with acute appendicitis. Arch Surg 1978;113:754
Forthcoming events New Ideas on Common Retinal Disorders 13-14 December 1990, San Francisco, California Further details from: Extended Programs in Medical Education, Room C-124, University of California School of Medicine, San Francisco, CA 94143-0742, USA
(Tel: 4154251) 3rd International Congress on Trace Elements in Medicine and Biology: Chromium and Trace Elements in Endocrinology 15-18 January 1991, Les Deux Alpes, France Further details from: Arlette Alcaraz, Laboratoire de Biochimie C, CHRU de Grenoble, BP217 X, 38043 Grenoble Cedex, France (Tel: 76 42 81 21) MRCP Part II Courses Five-day Clinical 11-15 February 1991, Royal Free Hospital, London Further details from: Dr D Geraint James, Royal Free Hospital, Pond Street, London NW3 2QG (Tel: 071-794 0550, ext 3931) Colorectal Disease in 1991: An International Exchange of Medical and Surgical Concepts 14-16 February 1991, Ft Lauderdale Florida Further details firom: The Cleveland Clinic Educational Foundation, Department of Continuing Education, Euclid Avenue, TT-31, Cleveland, OH 44195-5241, USA(Tel: 1 800 762 8173) Recent Advances in Neurology 15-17 February 1991, San Francisco, California Further details firom: (se entry for 13-14 December 1990) 11th Instructional Course on TnDitus and its Management 24-27 March 1991, Nottingham University Further details firom: Mrs J P Willoughby, Course Secretary, MRC Istute of HearingResearch, Universty of Notinghaim, University Park, Nottingham NG7 2RD (Tel: 0602 223431; Fax: 0602 423710)
4 Smith CD, Schuster SR, Gruppe WE, et aL Hemolyticuremic syndrome: a diagnostic and therapeutic dilemma for the surgeon. J Pediatr Suirg 1978;13:597 5 Gianantonio CA, Vitacco M, Mendilaharzu F, et aL The hemolytic-uremic syndome. Nephron 1973;11:174 6 Schwartz DL, Becker JM, So BB, et aL Segmental colonic gangrene: a surgical emergency in the hemolytic-uremic syndrome. Pediatrics 1978;62:54 7 Sawaf H, Sharp MJ, Youn KJ, et aL Ischemic colitis and stricture after hemolytic-uremic syndrome. Pediatrics 1978;61:315
(Accepted 3 July 1990. Correspondence to Mr D C G Crabbe, University Department of Pathology, The Royal Victoria Infirmary, Newcastle upon Tyne NEI 4LP)
The Food Network: Achieving a healthy diet by the year 2000 19-20 March 1991, Royal College of Physicians, London Further details firom: Conference Secretariat: Conference Associates & Services Ltd BDA/HEA, Congress House, 55 New Cavendish Street, London WlM 7RE (Tel: 071486 0631; Fax: 071-935 7559) Spring Meeting of the British Association of Oral and MaxiMofacial Surgeons 12 April 1991, Brighton A joint meeting with the British Society for the Study of Orthodontics and will take the form of a Festschrift to celebrate the contributions of the late Mr John Hovell to the specialties of oral and maxillofacial surgery and orthodontics. Further details from: John C Lowry, Honorary Secretary, British Association of Oral and Maxillofacial Surgeons, Royal College of Surgeons of England, 35/43 Lincoln's Inn Fields, London WC2A 3PN 24th Annual Advances and Controversies in Clinical Pediatrics 16-18 May 1991, San Francisco, California Further details from: (see entry for 13-14 December 1990) Thyroid '1 4-5 July 1991, Newcastle upon Tyne Further details firom: Dr Petros Perros, Department of Medicine, The Medical School, University of Newcastle, Newcastle NE2 4HH Autumn Meeting of the British Association of Oral and Maxillofacial Surgeons 27-29 September 1991, Harrogate Conference Centre Further details from: John C Lowry, Honorary Secretary, British Aciation of Oral and Maxillofacial Surgeons, Royal College of Surgeons of England, 35/43 Lincoln's Inn Fields, London WC2A 3PN 3rd International Conference on SLE 13-15 April 1992, Queen Elizabeth II Conference Centre, London Further details from: Dr Graham Hughes or Mrs Denzil Fletcher, Rheumatology Department, St Thomas' Hospital, London SE1 7EH (Tel and Fax: 071-633 9422)
775
