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Biomedical subjects

N D Heaton

Publications and source records attributed to N D Heaton.

At least 91 records · Page 5Linked to original sources

Patterns of portal vein occlusion and their aetiological significance.

Clinical and angiographic findings in 53 patients with portal vein occlusion were reviewed to determine the relationship between the pattern of venous occlusion and its aetiology. Five major patterns were identified. Group 1 comprised three children with idiopathic intrahepatic portal vein occlusion alone (hepatoportal sclerosis). Those in group 2 (25 patients), with occlusion of the main portal vein, accounted for almost half the total number and for most of those with a probable congenital aetiology. The ten patients in group 3 had angiographic occlusion and collateralization of the main portal and superior mesenteric veins. Intra-abdominal sepsis, other than that from pancreatic disease, was associated with this pattern of venous occlusion in which the splenic vein is spared. No patients with isolated portal and splenic vein occlusion (group 4) were recorded. Widespread thrombosis throughout the portal venous system (group 5; 15 patients) had a multifactorial aetiology but was typically observed in hypercoagulable states that were also associated with hepatic vein occlusion or other deep vein thromboses.

Adolescent↗

The use of percutaneous transluminal angioplasty in hepatic artery stenosis after transplantation.

Graft ischemia following liver transplantation is associated with a high incidence of morbidity and mortality. The present report concerns a group of seven patients in whom an anastomotic stenosis of the hepatic artery was identified. Three patients had unexplained allograft dysfunction at a median time of 28 days (range 13-64 days), and 3 had a biliary leak at a median time of 42 days after liver transplantation (range 35-270 days). In one patient the stenosis was diagnosed by routine Doppler ultrasound one week after transplant. Management was by percutaneous transluminal angioplasty at a median time of 35 days (range 13-270 days) after transplantation. After angioplasty there was a marked improvement in clinical appearance, liver function, and liver histology in 5 of the 7 patients. Those patients who had a biliary leak subsequently developed strictures that eventually required biliary tract reconstruction (hepaticojejunostomy) in two and retransplantation in one. Percutaneous transluminal angioplasty is an effective way of improving arterial blood flow in cases of anastomotic stenosis, reducing the likelihood of complete occlusion by thrombosis. If recognized early and treated promptly ischemic changes in the graft can resolve and the development of biliary strictures may be avoided.

Adult↗

Development of techniques for obtaining monodispersed human islet cells.

The aim of this study was to develop techniques to obtain monodispersed, human islet cells in large quantities, since these constitute a potentially transplantable beta cell mass with which to treat established type 1 diabetes, as well as provide the most appropriate substrate for studying the immune pathogenesis of the disease. Human islets were isolated from the pancreas of beating-heart organ donors by collagenase digestion. Enzymatic (collagenase types II, IV, V, and XI, trypsin, DNAse, and hyaluronidase) and chemical (EDTA and EGTA) conditions were then used to find the optimum requirements for digestion of intact human islets into their constituent cells. The combination of trypsin with EDTA provided the highest yield of monodispersed islet cells (963 cells/islet) and highest viability (88%). DNAse with EGTA gave high yields (710 cells/islet) but viability was low (55%). Lower yields and viability were obtained using collagenase types II, IV, V, and XI (47-243 cells/islet; viability 45-62%), hyaluronidase (410 cells/islet; 75% viability), and EDTA alone (253 cells/islet; viability 43%). Human islet cells monodispersed using trypsin 0.125 mg/ml in 0.1 mM EDTA retained an insulin secretory response to glucose, and had intact surface class I MHC molecules when analyzed immediately after digestion by flow cytofluorimetry. Our results indicate that functionally intact, single, human islet cells may be obtained in abundance, and provide a potential substrate for islet cell transplantation in the treatment of patients with type 1 diabetes.

Cell Separation↗

Orthotopic liver transplantation for acute hepatic failure in children.

Thirty children received 35 liver transplants for fulminant or late-onset liver failure between March 1988 and May 1993. Aetiology included non-A non-B hepatitis in 12, Wilson's disease in 8, drug-induced hepatic failure in 6, hepatitis B in 1, hepatitis A in 1, tyrosinaemia in 1 and congenital haemochromatosis in 1. Three patients were retransplanted, one each for hepatic artery thrombosis, non-A non-B graft reinfection, and chronic rejection. Two of these three patients received a third transplant for chronic rejection and hepatic artery thrombosis. One patient in the retransplant group survived. Overall, graft and patient survival at a mean follow-up of 17 months were 49% and 57%, respectively. Mortality was related to vascular complications in three patients (hepatic venous obstruction, portal vein thrombosis and hepatic artery thrombosis). Two patients died of primary sepsis (cerebral aspergillosis and cytomegalovirus (CMV) pneumonitis in association with graft-versus-host disease). Systemic sepsis and multiorgan failure was documented as a cause of death in four children and sepsis in association with chronic rejection in a further three patients. One child died of respiratory failure 4 weeks after transplantation. Mortality in eight children less than 2 years was 75% and this was significantly greater than for older children (P < 0.003, Mantel Cox). Earlier referral, even in the absence of a definitive diagnosis and particularly in children under 2 years is advisable and may improve survival.

Adolescent↗

Incidence of haemorrhoids and anorectal varices in children with portal hypertension.

A prospective study of 60 children with portal hypertension showed a significant incidence of haemorrhoids (33 per cent), anorectal varices (35 per cent) and external anal varices (15 per cent). Four children (7 per cent) complained of anorectal symptoms. A comparison of extrahepatic with intrahepatic disease showed that the former was associated with a higher incidence of both haemorrhoids and anorectal varices (57 versus 26 per cent and 64 versus 26 per cent respectively). The occurrence and severity of haemorrhoids was related to the number of previous oesophageal sclerotherapy sessions (P = 0.001). Problems relating to anorectal pathology were unusual, but treatment with haemorrhoidal sclerotherapy or banding was satisfactory for the symptomatic patients.

Adolescent↗

Orthotopic liver transplantation for hepatic complications of Wilson's disease.

Thirteen orthotopic liver transplantations were performed in 12 patients for hepatic complications of Wilson's disease between May 1988 and July 1992. Ten patients had fulminant hepatic failure and two chronic liver disease. One patient underwent retransplantation for liver abscess secondary to hepatic artery thrombosis. Nine patients survive at a median follow-up of 18 (range 6-31) months. Three patients have died: two from multiple organ failure and sepsis, one from B cell lymphoma. Postoperative complications included bleeding requiring laparotomy in two patients, renal impairment in five, bacterial septicaemia in three, fungal sepsis in two and acute cellular rejection in six. The nine surviving patients are well with normal liver function test results.

Adolescent↗

Complications and limitations of injection sclerotherapy in portal hypertension.

Injection sclerotherapy is now the accepted first line treatment for bleeding oesophageal varices, although it is associated with an impressive list of rare complications. The main problem concerns the strategy for uncontrollable or recurrent bleeding. Patients with uncontrolled bleeding may be referred for surgery after considerable blood loss and are then extremely difficult to assess. The effects of blood loss on liver function can lead to an unduly pessimistic assessment of liver status. An effective choice of emergency surgical procedure may require considerable surgical expertise. Oesophageal transection and devascularisation are satisfactory for many patients with oesophageal varices secondary to cirrhosis and should nearly always control bleeding. Difficulties arise in patients who are grossly obese and in those who have undergone extensive surgery in the upper abdomen. Problems may also be encountered in those treated by repeated sclerotherapy, which may have caused severe inflammatory change and thickening around the lower oesophagus and upper stomach. We believe that an emergency mesocaval shunt using either a vein graft or a synthetic material such as polytetrafluoroethylene is the procedure of choice for this difficult group of very sick patients. The surgical exposure is satisfactory and not unduly prolonged in even the largest patients and the technique does not interfere with any subsequent transplant operation. There is a greater choice in the management of the patient with less urgent bleeding from recurrent varices after sclerotherapy. Repeat sclerotherapy may be effective for small oesophageal varices while liver transplantation may be indicated in the patient with deteriorating liver function. A selective distal splenorenal shunt should be considered for patients with intact splenic and left renal veins and a mesocaval vein graft for the remainder. We would therefore suggest that surgery should still be considered for the management of portal hypertension, particularly in the following circumstances: (1) Uncontrollable bleeding during the initial course of sclerotherapy; (2) Life threatening haemorrhage from recurrent varices; (3) Bleeding from ectopic varices not accessible to sclerotherapy; (4) Uncontrollable bleeding from oesophageal ulceration secondary to injection sclerotherapy; (5) Severe, symptomatic hypersplenism; (6) For patients who live in communities remote from blood transfusion facilities and adequate medical care. The management of the complications of portal hypertension continues to pose problems. We believe that the best results should come from a combined management approach using injection sclerotherapy as primary treatment and surgery for complications and for haemorrhage from unusual anatomical sites.

Esophageal and Gastric Varices↗

Gangrene of the anterior abdominal wall after orthotopic liver transplantation: invasive cutaneous candidiasis.

Fungal infections following liver transplantation are not uncommon and may be life-threatening. Superficial candidal infections of the bronchus, oesophagus and urinary tract are the most common mode of presentation. Invasive cutaneous and subcutaneous candidiasis is, however, very rare. We report two patients with invasive cutaneous and subcutaneous candidiasis after orthotopic liver transplantation.

Abdominal Muscles↗

Liver transplantation for fulminant hepatic failure and late-onset hepatic failure in children.

The mortality rate of fulminant hepatic failure (FHF) and late-onset hepatic failure (LOHF) in childhood has remained between 70 and 95 per cent despite recent improvements in medical therapy. Liver transplantation has become an important therapeutic option in adults with this condition but has been performed infrequently in children. Between March 1988 and August 1991, 12 children aged between 1 month and 14 years with FHF or LOHF received 13 liver transplants. The aetiology was viral hepatitis in eight children (non-A non-B in six, A in two), drug hepatotoxicity (carbamazepine) in two, autoimmune hepatitis in one and congenital haemochromatosis in one. Reduced-size livers were used for ten of the 13 transplants. Morbidity after operation included infective complications and abdominal bleeding. Two patients died from graft versus host disease, one from brain aspergillosis and another from graft infarction after portal vein thrombosis. Eight patients survive after a median follow-up of 18 months. Liver transplantation should be the therapeutic choice for children with FHF and LOHF for whom the chances of recovery are poor.

Adolescent↗

Liver transplantation for fulminant liver failure in children.

The mortality rate of fulminant hepatic failure (FHF) in childhood has remained between 70% and 95% despite recent improvements in medical therapy. Liver transplantation has become an important therapeutic option in adults with this entity, but has been infrequently performed in children. Many children do not receive transplants because of the rapid progression of the illness and the lack of suitable donor livers. We present our experience in liver transplantation in children with FHF. Between March 1988 and December 1989, seven children aged between 15 months and 12 years received eight liver transplants. The aetiology of FHF was viral hepatitis in five and drug hepatotoxicity (carbamazepine) in two. Five of our patients were in grade III-IV coma. Reduced-sized livers were used in six of the eight transplants. The post-operative morbidity included viral and fungal infections, and abdominal bleeding. Two patients died from graft-versus-host disease and one from brain aspergillosis. Four patients (57%) survived a median follow-up of 15 months. Liver transplantation should be the therapeutic option in children with FHF where the chances of medical recovery are poor.

Child↗

Symptomatic hemorrhoids and anorectal varices in children with portal hypertension.

There have been few reports of the anorectal problems encountered in children with portal hypertension. We report the incidence of anorectal symptoms in a retrospective study of 189 children treated by injection sclerotherapy for esophageal varices secondary to portal hypertension. Anorectal symptoms, proctoscopic findings and treatment have been recorded in this group. The incidence of symptomatic hemorrhoids and rectal varices was 4.2%. Hemorrhoids are rare in children and the increased incidence can be assumed to be secondary to portal hypertension. Treatment is advised only for symptomatic patients and injection sclerotherapy is satisfactory for the majority.

Child↗

The late presentation of postero-lateral congenital diaphragmatic hernias.

Four patients presenting after the neonatal period with a combination of respiratory and gastro-intestinal symptoms and signs which point to the diagnosis of congenital postero-lateral diaphragmatic hernias are discussed. Late presentation is more common than previously acknowledged. Early correct diagnosis and treatment are associated with an excellent clinical outcome.

Adult↗

Spontaneous perforation of the bile duct in infants.

Spontaneous perforation of the bile duct is a rare but well documented condition of infants. Six infants are described, five presenting within 2 months of birth without apparent antecedent factors and one associated with an 'acquired' type I biliary atresia at 8 months. All infants underwent definitive surgery, which included decompression of the biliary tree with cholecystenterostomy or T tube drainage. There was no morbidity or mortality associated with such surgical intervention.

Anastomosis, Roux-en-Y↗