Search PubMed⌕ Search

Biomedical subjects

N C Fisher

Publications and source records attributed to N C Fisher.

At least 19 recordsLinked to original sources
PubMed2000

Endoscopy.

Explore the source record for details and available documents.

Procedural Sedation↗
PubMed2000

Targeted prophylaxis with amphotericin B lipid complex in liver transplantation.

The purpose of this study is to prospectively evaluate a strategy in which prophylaxis with amphotericin B lipid complex at 3 different dosages was targeted to liver transplant recipients at high risk for the development of invasive fungal infection (IFI). High risk was defined as a postoperative requirement for prolonged (>/=5 days) intensive care unit (ICU) treatment. Consecutive high-risk patients were administered prophylaxis with amphotericin B lipid complex from day 5 after orthotopic liver transplantation (OLT) until ICU discharge or death. The first 10 eligible patients were administered 5 mg/kg/d, the next 10 patients were administered 2.5 mg/kg/d, and a final 10 patients were administered 1 mg/kg/d. Drug safety and efficacy were assessed before each dosage reduction. During the study period, 130 adult patients underwent 137 OLTs. Thirty patients fulfilled the entry criteria and were administered prophylaxis with amphotericin B lipid complex. No patient developed proven IFI during prophylaxis. Cultures from normally sterile sites (blood and abdominal drain fluid) always showed negative results. All fungal isolates were sensitive in vitro to amphotericin B. There was no significant difference in colonization scores among the groups of patients administered different dosages of amphotericin B lipid complex. No death, serious adverse reaction, or nephrotoxicity was attributed to amphotericin B lipid complex. We conclude that prophylaxis with amphotericin B lipid complex targeted to patients requiring prolonged ICU treatment after OLT appears to be well tolerated and may prevent IFI. Our current policy is to use amphotericin B lipid complex, 1 mg/kg/d, as antifungal prophylaxis in this high-risk group.

Adult↗
PubMed2000

Massive hepatic fibrosis in Gaucher's disease: clinico-pathological and radiological features.

Hepatomegaly is frequent in patients with type 1 Gaucher's disease and is associated with infiltration of the liver with pathological macrophages. Most patients suffer no significant clinical consequences, but a few develop portal hypertension which may progress to parenchymal liver failure. We describe four patients with Gaucher's disease who have developed portal hypertension. We have reviewed their clinical histories and all available histological and radiological material. All had severe Gaucher's disease with multi-organ involvement, and had undergone splenectomy in childhood. Histologically, this advanced liver disease was characterized by a picture of extreme and advanced confluent fibrosis occupying the central region of the liver. This massive fibrosis is associated with characteristic radiological appearances. The liver histology in these cases is highly unusual and virtually unknown in other conditions. Our studies indicate that without specific treatment the liver disease is progressive and rapidly fatal. However, institution of enzyme replacement therapy with imiglucerase may have beneficial effects even when the condition is far advanced.

Adolescent↗
PubMed2000

Deficiency of natural anticoagulant proteins C, S, and antithrombin in portal vein thrombosis: a secondary phenomenon?

BACKGROUND: Hereditary deficiencies of natural anticoagulant proteins are implicated in the pathogenesis of portal vein thrombosis (PVT). Secondary deficiencies of these proteins have also been reported in PVT, making interpretation of concentrations difficult. AIMS: To characterise the coagulation profiles in adult patients with PVT and to investigate the possible mechanisms of natural anticoagulant protein deficiency. PATIENTS: Twenty nine adult patients with portal hypertension caused by PVT, and normal biochemical liver function tests. METHODS: Routine coagulation profiles and concentrations of proteins C, S, and antithrombin were measured; where indicated, corresponding concentrations in parents were also measured. Synchronous peripheral and hepatic or splenic vein concentrations were compared in seven patients undergoing interventional procedures, as were peripheral concentrations before and after shunt surgery in three patients. RESULTS: Deficiencies of one or more of the natural anticoagulant proteins occurred in 18 patients (62%), with six patients having combined deficiency of all three proteins. There were strong correlations between prothrombin and partial thromboplastin time ratios and concentrations of natural anticoagulant proteins. Family studies in nine cases of anticoagulant protein deficiency revealed possible hereditary deficiency in only three cases, and significantly lower concentrations of anticoagulant proteins in all PVT cases compared with parents. Levels of anticoagulant proteins tended to be lower in hepatic veins but higher in splenic veins compared with peripheral vein concentrations. Peripheral concentrations decreased after shunt surgery. CONCLUSIONS: Deficiency of natural anticoagulant proteins is common in PVT and is probably a secondary phenomenon in most cases, occurring as part of a global disturbance of coagulation variables. The mechanism for this remains unclear but may result from a combination of reduced hepatic blood flow and portosystemic shunting itself.

Adult↗
PubMed1999

Central venous cannulation in patients with liver disease and coagulopathy--a prospective audit.

OBJECTIVE: To determine the incidence of vascular complications associated with central venous cannulation in patients with liver disease and coagulopathy. DESIGN: A prospective audit of all cannulation episodes in patients with liver disease and a prothrombin (INR) more than 1.5 and/or platelet count of 150 x 10(9)/l or less. SETTING: A specialist liver unit between January 1996 and September 1997. PATIENTS: Patients with acute or chronic liver diseases and patients undergoing liver transplantation or other hepatobiliary surgery. MEASUREMENTS AND RESULTS: Vascular complications of central venous cannulation were classified as major (any haemodynamically significant haemorrhage) or minor (superficial oozing or haematoma). We recorded 658 cannulations (subclavian, 352, and internal jugular, 306). The median INR was 2.4 (range 1-16) in the subclavian group and 2.7 (1-17) in the internal jugular group (p < 0.05); median platelet counts were 81 x 10(9)/l (range 9-1088) and 83 x 10(9)/l (10-425), respectively (difference not significant). One patient developed a haemothorax after accidental subclavian artery puncture (INR was 1.5, platelets 68 and regional prostacyclin therapy was being given for haemofiltration). There were no other major vascular complications. Risk factors for minor vascular complications included internal jugular cannulation, more than one needle pass into the vein, failure to pass any guidewire, a high INR and low platelets for haematoma formation, and low platelets and heparin therapy for superficial oozing. CONCLUSIONS: The incidence of major vascular complications following central venous cannulation in patients with liver disease and coagulopathy was low in this audit. In liver disease the presence of a raised INR alone should not be considered a contra-indication to central venous cannulation.

Blood Coagulation Disorders↗
PubMed1999

Fungal infection and liposomal amphotericin B (AmBisome) therapy in liver transplantation: a 2 year review.

We reviewed the use of liposomal amphotericin B in 30 patients receiving therapy following liver transplantation over a 2 year period. Five of these patients were treated for presumed invasive aspergillosis: four of them died despite therapy, each having combined renal and respiratory failure at the time of diagnosis of presumed aspergillosis. Post-mortem examination of three of these patients confirmed the diagnosis of aspergillosis. Twenty-five patients were treated empirically; 11 died and supportive evidence for invasive fungal infection following commencement of therapy was found in only one case. Following liver transplantation, the use of liposomal amphotericin B following confirmation of aspergillus infection or for empirical therapy is of uncertain value, and strategies based on selective prophylaxis for high-risk cases may be preferable.

Amphotericin B↗
PubMed1999

Managing Budd-Chiari syndrome: a retrospective review of percutaneous hepatic vein angioplasty and surgical shunting.

BACKGROUND: The role of percutaneous hepatic vein angioplasty in the management of Budd-Chiari syndrome has not been well defined. Over a 10 year period at our unit, we have often used this technique in cases of short length hepatic vein stenosis or occlusion, reserving surgical mesocaval shunting for cases of diffuse hepatic vein occlusion or failed angioplasty. AIMS: To review the outcome of angioplasty and surgical shunting to define their respective roles. PATIENTS: All patients treated by angioplasty or surgical shunting for non-malignant hepatic vein obstruction over a ten year period from 1987 to 1996. METHODS: A case note review of pretreatment features and clinical outcome. RESULTS: Angioplasty was attempted in 21 patients with patent hepatic vein branches and was successful in 18; in three patients treatment was unsuccessful and these patients had surgical shunts. Fifteen patients were treated by surgical shunting only. Mortality according to definitive treatment was 3/18 following angioplasty and 8/18 following surgery; in most cases this reflected high risk status prior to treatment. Venous or shunt reocclusion rates were similar for both groups and were associated with subtherapeutic warfarin in half of these cases. Most surviving patients in both groups are asymptomatic although one surgical patient has chronic hepatic encephalopathy. CONCLUSION: With appropriate case selection, many patients with Budd-Chiari syndrome caused by short length hepatic vein stenosis or occlusion may be managed successfully by angioplasty alone. Medium term outcome is good following this procedure provided that anticoagulation is maintained. Further follow up is required to assess for definitive benefits but we suggest that this should be included as a valid initial approach in the algorithm for management of Budd-Chiari syndrome.

Adolescent↗
PubMed1999

Serum concentrations and peripheral secretion of the beta chemokines monocyte chemoattractant protein 1 and macrophage inflammatory protein 1alpha in alcoholic liver disease.

BACKGROUND: Alcoholic liver disease is associated with increased hepatic expression of monocyte chemoattractant protein 1 (MCP-1) and macrophage inflammatory protein 1alpha (MIP-1alpha). AIMS: To determine whether concentrations of chemokines in the peripheral circulation reflect disease activity, and whether chemokine secretion is restricted to the liver or is part of a systemic inflammatory response in alcoholic liver disease. PATIENTS: Fifty one patients with alcoholic liver disease and 12 healthy controls. METHODS: Peripheral vein (and hepatic vein in patients undergoing transjugular liver biopsy) chemokine concentrations were measured by ELISA. Chemokine secretion and transcription in isolated peripheral mononuclear cells were assessed using ELISA and in situ hybridisation in patients with severe alcoholic hepatitis. RESULTS: Serum MCP-1 concentrations were higher in alcoholic hepatitis compared with cirrhosis or healthy controls. MIP-1alpha concentrations were below the assay sensitivity in most patients. Serum MCP-1 concentrations correlated significantly with serum aspartate aminotransferase and creatinine. In severe alcoholic hepatitis, MCP-1 concentrations were higher in hepatic compared with peripheral veins; in mild alcoholic hepatitis there was no difference. Mononuclear cell secretion of both MCP-1 and MIP-1alpha was higher in severe alcoholic hepatitis compared with healthy controls, and chemokine mRNA was identified in monocytes. CONCLUSIONS: Serum MCP-1 concentrations are raised in alcoholic liver disease and reflect severity of hepatic inflammation. Monocyte secretion of both MCP-1 and MIP-1alpha is increased in severe alcoholic hepatitis. Both intrahepatic sources and peripheral mononuclear cells contribute to the raised serum MCP-1 concentrations.

Biomarkers↗
PubMed1998

Chronic renal failure following liver transplantation: a retrospective analysis.

BACKGROUND: Liver transplant recipients are at risk of chronic renal disease, principally as a result of nephrotoxicity of the commonly used immunosuppressive agents cyclosporine and tacrolimus. We have investigated the incidence of chronic renal failure and its risk factors in our transplant population, which was treated predominantly with cyclosporine. METHODS: A single-center retrospective study was done of 883 consecutive adult patients receiving a first liver transplant between 1982 and 1996. Potential risk factors for the development of chronic renal failure were recorded, including serial measurements of cyclosporine therapy and renal function. RESULTS: Severe chronic renal failure (serum creatinine level >250 microM/L for at least 6 months) developed in 25 patients, representing 4% of patients surviving 1 year or more. Twelve of these patients developed end-stage renal failure and mortality was 44%. The predominant cause of renal failure was cyclosporine nephrotoxicity. Serum creatinine as early as 3 months after surgery was strongly associated with the eventual development of severe chronic renal failure (P=0.001), and this group could be further subdivided into two groups with differing risk factors. The first group had early (<1 year) renal dysfunction, with older age (P=0.03), cytomegalovirus infection (P=0.03), need for perioperative renal replacement therapy (P=0.06), and regrafting (P=0.06) as risk factors for eventual renal failure; the second group had late-onset (>1 year) renal dysfunction, with cyclosporine levels at 1 month after surgery (P=0.007) and daily and cumulative cyclosporine dosage at 5 years (P=0.01 for both) as risk factors. CONCLUSIONS: With improved survival of liver transplant recipients, chronic renal failure has become an important cause of morbidity and is associated with a high mortality. Many patients at risk of severe chronic renal failure may be identified at an early stage. Treatment regimens that avoid or prevent cyclosporine-induced nephrotoxicity are urgently required for this population.

Adolescent↗
PubMed1998

Distinct patterns of chemokine expression are associated with leukocyte recruitment in alcoholic hepatitis and alcoholic cirrhosis.

Alcoholic liver disease is associated with three histologically distinct processes: steatosis (parenchymal fat accumulation), alcoholic hepatitis (characterized by parenchymal infiltration by neutrophil polymorphs), and alcoholic cirrhosis (in which chronic inflammation and fibrosis dominate). Chemokines are cytokines that promote subset-specific leukoycte recruitment to tissues and could therefore play a crucial role in determining which leukocyte subsets are recruited to the liver in alcoholic liver disease. This paper reports that chemokine expression is increased in the liver of patients with alcoholic liver disease and, moreover, that distinct patterns of chemokine expression are associated with the different inflammatory responses to alcohol. Interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1 alpha (MIP-1 alpha), and MIP-1 beta were all detected in the parenchyma at sites of inflammation in alcoholic hepatitis, whereas in alcoholic cirrhosis, chemokines were restricted to inflammatory cells and endothelium in the fibrous septa and portal tracts. In alcoholic hepatitis, chemokine transcription was localized to sinusoidal cells, leukocytes, and fibroblasts in areas of parenchymal inflammation, but hepatocytes, despite staining strongly for chemokine protein, were negative. In alcoholic cirrhosis, chemokine mRNA was detected in portal tract endothelium, leukocytes, and fibroblasts. Thus, alcoholic hepatitis and alcoholic cirrhosis are associated with distinct patterns of chemokine expression that are likely to be important factors in determining whether a patient develops acute parenchymal inflammation and alcoholic hepatitis, or chronic septal inflammation and alcoholic cirrhosis.

Chemokine CCL2↗
PubMed1998

A prospective, randomized controlled trial of sedation vs. no sedation in outpatient diagnostic upper gastrointestinal endoscopy.

BACKGROUND AND STUDY AIMS: The majority of gastrointestinal endoscopists in the United Kingdom routinely use intravenous sedation prior to diagnostic upper gastrointestinal endoscopy. We conducted a prospective, randomized controlled clinical trial to help determine whether the use of sedation influences the duration, safety, and tolerance of diagnostic upper gastrointestinal endoscopy. PATIENTS AND METHODS: Adults referred for outpatient diagnostic upper gastrointestinal endoscopy were invited to participate in the study. Patients with a history of previous upper gastrointestinal endoscopy or dysphagia were excluded. Patients were prospectively randomized to sedation with intravenous midazolam (5 mg for those under 65 years or 3 mg for those aged 65 or more), or no sedation. All patients were given topical oropharyngeal anaesthesia with 100 mg lignocaine spray. Outcome measures included duration of procedure, ease of procedure (as assessed by medical and nursing staff), tolerance of procedure (as assessed by patients), and incidence of complications. RESULTS: 100 patients were randomized to receive sedation or no sedation. The two groups were well matched for age, sex, and number of biopsies taken during the procedure. In the non-sedated group, the duration of endoscopy tended to be reduced and the procedure tended to be easier according to the endoscopists' assessment (neither of these observations was significant). The sedated group reported greater comfort for the procedure (P < 0.001), although both groups tolerated the procedure well, and the majority in both groups preferred to have any future procedure repeated in the same manner. There were no serious adverse events in either group. CONCLUSIONS: In patients who are willing to contemplate upper gastrointestinal endoscopy without sedation, the avoidance of sedation may lead to faster and easier endoscopies, without any increased risk of procedural difficulties or adverse events.

Adult↗
PubMed1998

Fungal colonisation and fluconazole therapy in acute liver disease.

BACKGROUND/AIMS: Fungal infection, particularly with Candida spp., has been identified as an important cause of morbidity and mortality in patients with acute liver failure. Fungal colonisation of superficial mucosal sites usually precedes invasive infection. We investigated colonisation patterns in patients with acute liver disease receiving fluconazole therapy in order to investigate the possibility of emergence of fluconazole-resistant C. albicans or other species. METHODS: During a 6-month study period, we studied all patients referred to our unit with acute liver disease by twice-weekly sampling and mycological analysis of specimens from superficial mucosal and other sites as appropriate. Patients were treated with prophylactic antimicrobials including 100 mg fluconazole daily in accordance with our usual protocol. RESULTS: Twenty-two patients with acute liver disease were studied, eight of whom underwent transplantation. Eighteen patients were colonised by fungi at presentation, and six developed secondary colonisation during fluconazole therapy. Four of these patients (all transplanted) became colonised by resistant species; one of these was Aspergillus fumigatus, which led to death. There were no other invasive fungal infections identified during the study period, and no fluconazole-resistant C. albicans were identified. CONCLUSIONS: Resistance to fluconazole is unlikely to develop in C. albicans during short-term fluconazole prophylaxis in acute liver disease, and in this study we did not find evidence of invasive disease from other Candida spp. during fluconazole therapy. However, in patients at particularly high risk, other strategies are required to prevent infection with Aspergillus spp.

Antifungal Agents↗