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Biomedical subjects

N Heaton

Publications and source records attributed to N Heaton.

At least 55 records · Page 3Linked to original sources
PubMed1997

N-acetylcysteine improves indocyanine green extraction and oxygen transport during hepatic dysfunction.

OBJECTIVES: To investigate whether the beneficial systemic hemodynamic effects of N-acetylcysteine, an agent that increases cyclic guanosine monophosphate (cGMP) concentration in fulminant hepatic failure, are present in a range of liver disorders and what concurrent effect this agent has on the hepatic-splanchnic circulation. SETTING: Liver Failure Unit, King's College Hospital, London, UK. PATIENTS: Fifteen patients with hepatic dysfunction who were mechanically ventilated, either after liver transplantation or during an acute or decompensated chronic liver disorder. INTERVENTIONS: Prostacyclin was administered at a continuous infusion rate of 5 ng/kg/min for 60 mins. After a washout period, the hemodynamic effects of this infusion were compared with the effects present during infusion of N-acetylcysteine at 150 mg/kg in 250 mL of 5% dextrose in water over 15 mins and then 50 mg/kg in 250 mL of 5% dextrose for 45 mins at an infusion rate of 62.5 mL/hr. MEASUREMENTS AND MAIN RESULTS: Following N-acetylcysteine infusion, the baseline oxygen delivery (DO2) increased from 667 +/- 154 to 751 +/- 166 (SD) mL/min/m2, and oxygen consumption (VO2) improved in 13 of 15 patients (150 +/- 30 to 169 +/- 25 mL/min/m2) (p< .01). Indocyanine green clearance, as determined by a fiberoptic physiologic monitoring system, also improved in 13 of 15 patients (7.3 +/- 4.2% to 11.8 +/- 4.0% [mean change 100%, 95% confidence interval 9 to 256]) (p = .002). Patients who were defined as responders in relation to systemic hemodynamics (VO2 of >10% from baseline [n = 6; 40%]) had a significantly lower baseline consumption compared with that of nonresponders (133 vs. 162 mL/min/m2, p = .04). No clear relationship between the increments in VO2 and indocyanine green clearance was observed (r2 = .21; p = .08). Prostacyclin resulted in moderate improvements in systemic DO2 (but not VO2) and a nonsignificant increase in indocyanine green clearance. CONCLUSION: N-acetylcysteine increases systemic VO2 in a proportion of patients with a wide variety of hepatic disorders. In addition, N-acetylcysteine elicits an improvement in indocyanine green clearance. These properties may be clinically useful in a range of critical illnesses where systemic or hepatic-splanchnic circulations are compromised.

Acetylcysteine↗
PubMed1997

Use of extracorporeal liver assist device and auxiliary liver transplantation in fulminant hepatic failure.

The case history of a 14-year-old boy with fulminant hepatic failure secondary to non-A, non-B hepatitis who fulfilled selection criteria for orthotopic liver transplantation is described. Two forms of liver support were used (extracorporeal liver assist device and an auxiliary partial orthotopic liver transplantation) to provide additional time to allow spontaneous recovery to occur. During the 66 h of extracorporeal haemoperfusion through the device, haemodynamic stability was maintained along with improvements in serum bilirubin (555 to 381 mumol/l), and international normalized ratio (INR) (3.7 to 2.9). Deterioration in these parameters was observed following cessation of treatment and 10 h later, after a donor liver had become available, an auxiliary transplant was performed. Clinical recovery, though initially slow, was eventually complete, with histopathological and scintigraphic evidence of full liver regeneration at 3 months. Withdrawal of his immunosuppressive drugs began at 6 months and was complete by 14 months after auxiliary transplantation. He has since remained well with normal liver function tests. Temporary liver support may provide additional time for spontaneous recovery of the native liver to occur in selected cases of fulminant hepatic failure, even when criteria are fulfilled for orthotopic liver grafting.

Adolescent↗
PubMed1997

Liver transplantation for extra hepatic biliary atresia.

Kasai portoenterostomy has transformed the prognosis for children with Extra Hepatic Biliary Atresia (EHBA). However, for children developing end stage liver disease following portoenterostomy, liver transplantation (OLT) is the treatment of choice. Between February 1989 and March 1996, 64 children with EHBA underwent 79 transplants (26 males, 38 females; median age 2.2 years, range 5 months-17 years; median weight 11.4 kg, range 5-65 kg). Of these, 58 (85%) had undergone previous portoenterostomy. Nineteen patients (30%) had gastrointestinal bleeding prior to OLT assessment. Mean serum bilirubin was 229 mumol/liter (range 11-801 muml/liter). Four children had associated polysplenia syndrome. Of the 79 transplants, 30 received whole and 41 reduced-size cadaveric grafts and 9 living related grafts. Eleven patients (17%) died, nine within one month of surgery. Thirteen patients were retransplanted once and one twice. There were 16 vascular complications (10 hepatic artery thrombosis, 3 portal vein thrombosis, 3 venous outflow obstruction) and 10 biliary complications (4 anastomotic leaks, 6 strictures). Ten patients (16%) had bowel perforation following the transplant. The 5 year actuarial patient and graft survival for this group is 84% and 69% respectively with normal physical and mental development in the majority. OLT provides satisfactory treatment for children with EHBA with end stage liver disease with long term survival in the majority.

Adolescent↗
PubMed1996

Liver transplantation for haemophiliacs with hepatitis C cirrhosis.

BACKGROUND: Experience of liver transplantation in haemophiliacs with end stage hepatitis C liver disease is limited and particularly difficult questions are raised when there is also HIV infection. AIMS: This is the first report in Great Britain to describe the operative replacement therapy and initial outcome in four haemophiliacs with end stage HCV cirrhosis. PATIENTS: Two patients had factor VIII, one had factor IX, and one had factor X deficiency. One patient had also contracted HIV infection from factor replacement but had no AIDS defining illnesses. METHODS: Intraoperatively patients were given either factor VIII infusions, factor IX bolus, or fresh frozen plasma, according to formulae devised to calculate exact clotting factor requirements. Baseline preoperative coagulation studies included prothrombin time, activated partial thromboplastin time, fibrinogen concentrations, and factor VIII, IX, and X concentrations. Factor concentrations were then assayed at 12, 24, 48, and 72 hours postoperatively. RESULTS: Postoperatively all patients had coagulation factor concentrations sustained within the normal ranges by 72 hours unsupported (137, 125, 95, 104 IU/dl), representing de novo synthesis by the graft. Transfusion requirements during the operative and immediate post-transplant period were no greater than those of patients without clotting disorders. Two patients had episodes of bleeding postoperatively, one of which was fatal, occurring at the site of a previous untreated subdural bleed. In both instances the bleeding occurred in the presence of normal concentrations of clotting factor. The remaining three patients are at 6, 6, and 12 months post-transplant and remarkably improved clinically with sustained factor concentrations. One patient has evidence of graft dysfunction from HCV recurrence and all have evidence of recurrent viraemia with HCV on polymerase chain reaction studies. CONCLUSIONS: Orthotopic liver transplantation should be considered in haemophiliac patients with end stage liver disease from hepatitis C infection with or without concomitant HIV infection. Their clinical condition is likely to be greatly improved by orthotopic liver transplantation and the haemophilia cured with only a small risk of severe graft dysfunction from recurrent HCV infection.

Adult↗
PubMed1995

Importance of concomitant viral infection during late acute liver allograft rejection.

We have determined accompanying events and reviewed the management and outcome of late acute cellular rejection episodes in 384 consecutive liver recipients. A significant proportion of patients experienced concomitant viral infection (group 1, n = 15 [41%]), with CMV infection comprising the largest group and smaller contributions from other viruses (CMV, 30%; HSV, 5%; EBV, 3%; varicella zoster virus, 3%). Thirteen (35%) patients (group 2) developed late rejection associated with low maintenance immunosuppression, and in a further 10 patients (group 3), no accompanying factor could be identified. Refractory rejection was higher in late compared with early rejection episodes in our series (29% vs. 9.2%, P < 0.05). Antiviral chemotherapy administered in rejection episodes with concomitant viral infection, either as sole treatment in cases with accompanying hepatitis or as adjunctive therapy to further supplemental immunosuppression in episodes of steroid-resistant rejection, controlled the rejection process in all treated patients.

Adolescent↗
PubMed1995

Centrilobular necrosis after orthotopic liver transplantation: a longitudinal clinicopathologic study in 71 patients.

Centrilobular necrosis (CLN) is a histological finding often encountered after orthotopic liver transplantation, but its pathogenesis is still unknown. In this study, the significance of CLN was assessed in a series of 227 consecutive liver transplantations performed between January 1989, and December 1991. Seventy-one patients (30.9%) showed CLN on at least one biopsy result, which were obtained because of an increase of aspartate aminotransferase activity. Their liver specimens were reviewed, and 19 histological features were recorded with particular attention given to lobular changes in acinar zone 3, to features commonly attributed to cellular and ductopenic rejection, and to changes suggestive of ischemia. CLN could first be observed either soon (within 4 days) or late (up to 3 years) after transplantation. Only 23 (32.4%) specimens had centrilobular necrosis affecting more than 75% of acinar zones 3. In 60 cases (84.5%) the lesion was limited to acinar zone 3. An important associated feature was sinusoidal congestion in 73.2% of cases. Fifty-one of 71 patients (71.8%) had histological features of cellular rejection before or at the time of CLN, and 13 of these progressed to ductopenic rejection versus 3 of the 156 patients without CLN (P < .0001). Nine patients had a recurrence of CLN, of whom 2 progressed to ductopenic rejection, a recurrence rate of 16.7% in this series. The survival of patients with CLN is worsened by associated ductopenic portal tracts compared with those without ductopenia (P = .0189-Mantel-Cox). This histological combination, irrespective of the serum bilirubin level, may warrant an early conversion to FK506-based immunosuppression.

Adult↗
PubMed1995

Effects of intraoperative N-acetylcysteine in orthotopic liver transplantation.

N-acetylcysteine (NAC) is an antioxidant agent which has been shown to benefit patients with fulminant hepatic failure. We have examined its effect in patients with chronic liver disease undergoing orthotopic liver transplantation by giving NAC during operation. In a prospective, randomized, double-blind, placebo-controlled study of 50 patients, NAC appeared to induce mild vasodilatation, improve oxygen delivery and consumption, and reduce base deficit, but data interpretation was difficult. There were no significant effects on mortality, morbidity or postoperative graft function.

Acetylcysteine↗
PubMed1995

Pretransplantation clinical status and outcome of emergency transplantation for acute liver failure.

Emergency transplantation for acute liver failure has a significantly inferior outcome than transplantations performed for elective indications. The severity of the pretransplantation clinical illness in this group will contribute to the reduced patient survival. We have reviewed the outcome of our first 100 consecutive adult patients who received transplants for acute liver failure and have evaluated and determined which recipient clinical parameters present on admission and at transplantation act as risk factors in early posttransplantation outcome. In patients who received transplants for nonacetaminophen-induced liver failure (n = 79), no static variable determinable on admission (including age, sex, year of transplantation, hospital admission to transplantation period, and fulminant or late-onset presentation) other than cause was predictive of 2-month patient survival. Fulminant Wilson's disease and idiosyncratic drug reactions with 2-month survival rates of 100% and 12.5%, respectively, had significantly different outcomes from other causes. By the time of transplantation, of four dynamic variables significant in a univariate analysis (serum creatinine, encephalopathy grade, Apache 111 and organ system failure scores, and P values < .05), only the creatinine level was an independent variable in a stepwise logistic regression for 2-month survival (r = .33). In patients who received transplants for acetaminophen hepatotoxicity (n = 21), overdose to hepatectomy period was the only significant static variable, with no parameter predictive of outcome present on admission.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaminophen↗
PubMed1994

Nitric oxide generation. A predictive parameter of acute allograft rejection.

The L-arginine:nitric oxide (NO) biosynthetic pathway has been proposed as an important mediator in host defense mechanisms and may therefore play a role in the acute allograft response. We have studied NO generation in liver allograft rejection and determined its value in immunological monitoring. Stable end products of this pathway have been determined serially in 50 primary liver recipients and compared with 2 known mediators and markers of acute allograft rejection (IL-2R positive lymphocytes and circulating TNF alpha). Plasma concentrations of acid-labile nitrosocompounds (NOx), which increased during acute allograft rejection (P < 0.0001), correlated with rejection severity and were reduced after administration of supplemental high dose glucocorticoids. Concentrations were significantly lower in nonrejection graft complications but were elevated during episodes of sepsis. Correlations between plasma NOx levels and circulating TNF-alpha (r = 0.451, P < 0.001) and IL-2R-positive lymphocytes in peripheral blood (r = 0.781, P < 0.001) were demonstrated. In a logistic analysis of these variables, plasma NOx was the most predictive parameter of an episode of acute cellular rejection. Nitric oxide generation in FK506-treated patients was lower compared with patients receiving a CsA-based immunosuppression regimen and was associated with a reduced frequency of acute rejection in the FK506 group. These data are consistent with a role for NO in the cellular alloantigen immune response and indicate that monitoring of plasma levels of NOx may be useful in the detection of acute allograft rejection.

Biomarkers↗
PubMed1994

Emergency liver transplantation after Kasai portoenterostomy.

Three patients with stable liver function after Kasai portoenterostomy developed acute liver failure secondary to liver necrosis. Doppler ultrasound at presentation revealed reversed diastolic hepatic arterial blood flow. Two patients survived after urgent liver transplantation. Liver necrosis should be suspected in children with chronic liver disease presenting with fever and rapidly deteriorating liver function.

Emergencies↗
PubMed1990

Elevated human chorionic gonadotrophin levels in a patient with pancreatic carcinoma presenting with a testicular metastasis.

Elevated levels of human chorionic gonadotrophin are associated with primary testicular tumours and usually indicate the presence of trophoblastic elements. Human chorionic gonadotrophin can also be secreted by extragonadal tumours which may metastasize to the testes. A patient is described presenting with a testicular tumour secreting human chorionic gonadotrophin which later proved to be a metastasis from a pancreatic adenocarcinoma. Up to 70% of malignant pancreatic tumours can secrete human chorionic gonadotrophin.

Adenocarcinoma↗