Acute basophilic leukemia with an intense erythroblastic reaction

A patient is presented who had acute basophilic leukaemia with intense erythroblastic reaction. The patient, a 66 year-old man, complained of general malaise, increased abdominal perimeter and melena. Leucocytosis, as well as severe anaemia and thrombocytopenia, were found in his peripheral blood. Basophils were present in all maturation stages, along with 7% blast-cells showing basophilic stippling, and there were 210 erythroblasts per 100 white cells. Erythropoietic hyperplasia (75%) was found in the bone-marrow aspirate, without dyserythropoietic signs; the PAS-stain reaction was negative. Of the non-erythroid cells, 63% were basophils and 34% blast-cells, some of them showing basophilic stippling plus metachromasia for tholuidin-blue, positivity for omegaexonuclease and negativity for peroxidase stains. The diagnosis of acute basophilic leukaemia was confirmed upon demonstration of basophilic stippling in the ultrastructural study of the blast-cells. The patient developed acute liver failure and renal insufficiency which led him to death. The basis of the diagnosis of acute basophilic leukaemia is discussed, as well as the differential diagnosis with other conditions presenting with basophilia and the probably reactive erythroblastic increase appearing in this case.     

Efficient 5''-end labeling of oligonucleotides containing self-complementary sequences

BACKGROUND: Auxiliary liver transplantation offers an alternative method to conventional transplantation in acute liver failure. It is especially challenging for children because lifelong immunosuppression may be avoided. However, experience with this procedure is rare and there is controversy about whether to place the graft orthotopically or heterotopically. METHODS: We present the case of a 3-year-old boy with acute liver failure due to non-ABC hepatitis complicated by aplastic anemia who underwent auxiliary liver transplantation. Segments 2 and 3 of the graft were implanted heterotopically in the right lower abdomen. RESULTS: Good liver function was immediately restored. Aplastic anemia resolved 3 weeks after transplantation. Immunosuppressive therapy was discontinued after 14 months, and the graft was left to atrophy. Thirty-nine months after transplantation the boy is alive and well with normal liver function tests and normal blood cell counts. CONCLUSIONS: Heterotopic auxiliary liver transplantation allowed recovery of the native liver in a child with acute liver failure and aplastic anemia due to non-ABC hepatitis.     

Liver transplantation in acute liver failure

Acute hepatic failure is characterized by jaundice and hepatic encephalopathy within eight weeks after the onset of disease. Although acute hepatic failure is a rare occurrence, its rapid progression and high mortality (50 to 90%, depending on the etiology of disease) necessitate immediate intervention. In the absence of causal therapy, orthotopic liver transplantation is currently the only definitive and effective means of treating acute hepatic failure in Europe, acute hepatic failure accounts for 11% of all liver transplantations. At the University department of transplantation surgery in Vienna a total of 27 patients with acute hepatic failure underwent 31 liver transplantations in the last 10 years (1.1.1987 to 31.12.1996). Twenty (74%) of the 27 patients survived the acute event and were discharged from hospital in good general condition after a median postoperative stay of 25 days (range 14-81 days). Seven patients (26%) died between the first and 34th postoperative day (median 26 days) in the intensive care unit, although all potential modern options of intensive care and surgery were used. The causes of death were irreversible cerebral edema (n = 3), multiple organ failure due to bacterial sepsis (n = 3) and uncontrollable haemolysis (n = 1). With a 3-year graft survival rate of 70% the 3-year patient survival rate was 74%. A retrospective analysis of our patients revealed that the postoperative graft function and the incidence of re-transplantation were significant prognostic factors (p < 0.05) for survival following orthotopic liver transplantation for acute hepatic failure. In the absence of further prognostically relevant preoperative indices and in consideration of the potentially fulminant progression of disease, we strongly recommend that any patient, in whom acute hepatic failure is suspected, is immediately transferred to a specialized center with experience both in the conservative treatment of acute hepatic failure and emergency liver transplantation.     

Doxycycline hyclate treatment of experimental canine ehrlichiosis followed by challenge inoculation with two Ehrlichia canis strains

These is increasing evidence to suggest that central noradrenergic mechanisms may contribute to the central nervous system manifestations of acute liver failure. To further elucidate this possibility, extracellular brain concentrations of the monoamines, noradrenaline (NA), dopamine (DA), and serotonin, were measured by high-performance liquid chromatography with electrochemical detection in microdialysates from the extracellular compartment of frontal cortex in rats with acute (ischemic) liver failure at various times during the progression of encephalopathy and brain edema, as well as in obligate control groups of animals. In addition, binding sites for the noradrenergic receptor subtype ligands, [3H]-prazosin (alpha1 sites), [3H]-RX821002 (alpha2 sites), and [125]I-iodopindolol (beta sites), were assessed using quantitative receptor autoradiography in regions of the brains of rats at coma stage of acute liver failure and of control groups of animals. Coma stages of encephalopathy in acute liver failure were associated with selectively increased noradrenaline concentrations (P < .05) and a concomitant selective loss of alpha1 and beta1 sites in frontal cortex and thalamus. These findings add to a growing body of evidence that central noradrenergic function is modified in acute liver failure and suggest that alpha1/beta1 receptor-mediated noradrenergic mechanisms may play a role in the pathogenesis of brain edema and encephalopathy in this condition.     

Reactivated fulminant hepatitis B virus replication after bone marrow transplantation: clinical course and possible treatment with ganciclovir

A female chronic hepatitis B virus carrier (HBV-DNA negative) suffered from simultaneous hepatitis B virus and cytomegalovirus reactivation after in vivo T cell depletion preceding transplantation of an in vitro T cell depleted marrow graft for treatment of acute leukaemia. Interstitial pneumonia developing after bone marrow transplantation was successfully treated with ganciclovir (day 13 until day 46). The initially unnoticed extensive hepatitis B virus replication finally led to clinical hepatitis (day 85) and liver failure (day 96). Liver transplantation was performed, but the patient died from septicaemia. Retrospective analysis of hepatitis B virus DNA revealed that the HBV replication started immediately after T cell depletion and was completely suppressed during ganciclovir administration. Screening for HBV-DNA seems to be mandatory in comparable cases, and antiviral chemotherapy should be seriously considered.     

Quantitative electroencephalography and regional cerebral blood flow: discriminant analysis between Alzheimer''s patients and healthy controls

Acute liver failure represents one of the most challenging conditions in gastroenterology. In most cases, there is no effective therapy making supportive intensive care the most important management tool. These patients frequently develop multi-organ failure, placing them at risk of systemic infections, cerebral edema, hemodynamic instability, coagulopathy and various renal and metabolic complications. Successful management of the patient with acute liver failure requires an understanding of the pathophysiology and management of these complications. An overview of acute liver failure and its most common complications is presented.     

Two antipeptide monoclonal antibodies that recognize adhesive sequences in fibrinogen: identification of antigenic determinants and unrelated sequences using synthetic combinatorial libraries

Fulminant hepatic failure is infrequently seen as a consequence of acute congestive heart failure. Recognition of this entity is important as treatment directed towards heart failure should help resolve the liver failure. A case of fulminant hepatic failure due to previously unrecognized cardiomyopathy is presented. A liver transplantation was being considered for fulminant hepatic failure until hemodynamic monitoring studies demonstrated that, in fact, the patient had severe cardiomyopathy. Treatment directed at his cardiomyopathy resolved the liver failure. Therefore, prompt recognition of such a phenomenon would enable early institution of appropriate therapeutic measures with the hope of clinical benefit to the patient.     

Probable diltiazem-induced acute interstitial nephritis

OBJECTIVE: To describe a case of acute interstitial nephritis (AIN) probably related to administration of diltiazem. CASE SUMMARY: A 53-year-old white man presented to the hospital experiencing abdominal pain radiating to both renal fossae, as well as dysuria. Diltiazem and atenolol had been prescribed to treat an episode of precordial pain associated with effort. An erythematous maculopapular rash developed approximately 2 hours after administration of a single dose of diltiazem, and acute renal failure, associated with elevated liver function test results, developed 6 days later. DISCUSSION: To the best of our knowledge, this is the third reported case of acute renal failure believed to be induced by diltiazem. In all cases, there was an obvious temporal relationship between administration of diltiazem and the onset of acute renal failure. Previous reports failed to discuss a probable pathogenic mechanism. AIN is the most likely etiology of acute renal failure in our patient. Favorable resolution with no relapse, the presence of the skin rash, and the liver sequelae suggest a common immunoallergic mechanism. CONCLUSIONS: Healthcare professionals should consider diltiazem-induced AIN in the differential diagnosis of a patient taking diltiazem who develops acute renal failure.     

Novel strategies for liver support in acute liver failure

At present, the treatment of a patient in acute liver failure is based upon scrupulous intensive care. In those patients whose condition deteriorates, emergency liver transplantation must be considered. There would be great benefit if it were possible to provide treatment which would stabilise the condition of a patient in acute liver failure. Thus, there is great incentive to develop a means of artificial liver support. Over many years, a considerable array of therapeutic strategies has been investigated. These can be considered in four main categories: plasma exchange, haemofiltration, extra-corporeal liver assist devices (ELAD), extra-corporeal liver perfusion (ECLP). Finally, the role of xenotransplantation is considered.     

Elevation of intracranial pressure following transjugular intrahepatic portosystemic stent-shunt for variceal haemorrhage

Increased intracranial pressure and cerebral oedema in patients with chronic liver disease is rare and is more typical of acute liver failure. Transjugular intrahepatic portosystemic stent-shunt is being increasingly used in the management of uncontrolled variceal haemorrhage in patients with cirrhosis. In our institution, a total of 160 patients has undergone transjugular intrahepatic porto-systemic stent-shunt for variceal haemorrhage; 56 of these procedures were emergencies for uncontrolled variceal haemorrhage. Four of these 56 patients developed features of acute liver failure, with marked deterioration in liver function tests and elevated intracranial pressure. This unusual but important complication of transjugular intrahepatic portosystemic stent-shunt has not been reported in the literature previously, and may have important consequences both for clinical practice and in the provision of further clues to understanding the pathogenesis of increased intracranial pressure in patients with liver diseases.     

The non-random distribution of point mutations in leukaemia and myelodysplasia--a possible pointer to their aetiology

A conventional and a computer search of the literature yielded 627 sequenced point mutations in the ras and p53 genes in 575 patients with leukaemia and myelodysplasia (MDS) out of a total of 4214 investigated. ras Mutations predominated in myeloid leukaemia and were more common in the disease in relapse than at presentation. There was no clinical, or haematological difference or difference in survival between ras positive and ras negative patients with acute myeloid leukaemia (AML) in adults or children, but ras mutations carried a poorer prognosis in childhood acute lymphocytic leukaemia and an increased risk of leukaemia in MDS. p53 mutations predominated in lymphoid leukaemia and were several fold more frequent in leukaemia in relapse than in the de novo disease, were associated with loss of the normal p53 allele (monosomy 17) in > 50% of cases and carried a poor prognosis in AML, MDS and chronic lymphatic leukaemia and a 3.8-fold increase risk of death in T cell acute lymphocytic leukaemia. There were 163 transitions for every 100 transversions, the expected number being ca 50. Consideration of the molecular mechanisms by which nitrous acid produces transitions allows transitions resulting from the deamination of cytosine to be distinguished from those resulting from the deamination of adenine. The former constitute 84.67% and the latter 15.33% of the 372 transitions present. Again purine-->pyrimidine and pyrimidine-->purine transversions form 80.35 and 19.65%, respectively, of the 228 transversions present. The possible bearing of this highly non-random distribution on the aetiology of point mutations in leukaemia and myelodysplasia is discussed.     

Use of transjugular intrahepatic portosystemic shunt as a bridge to transplantation in fulminant hepatic failure due to Budd-Chiari syndrome

We report a case of fulminant hepatic failure in a 55-yr-old man due to Budd-Chiari syndrome in the setting of polycythemia rubra vera. The patient presented with acute hepatic failure, which rapidly progressed to grade IV hepatic encephalopathy. Placement of a transjugular intrahepatic portosystemic shunt resulted in marked improvement of the encephalopathy and stabilized the liver failure. Subsequently, he underwent successful nonemergent orthotopic liver transplantation. Transjugular intrahepatic portosystemic shunt placement is a safe, effective, therapeutic option to bridge patients with fulminant Budd-Chiari to liver transplantation.     

Acute monocytic leukaemia in a HIV-seropositive man

Individuals infected with the human immunodeficiency virus (HIV) have been reported to develop a number of malignant neoplasms. We recently treated an HIV patient who had acute monocytic leukaemia which was first evident in the skin. To our knowledge, this is the first report of a case of acute monocytic leukaemia occurring in a HIV-infected person.     

Liver transplantation in Europe for patients with acute liver failure

Approximately 11% of all liver transplants performed in Europe are for acute liver failure, with one-year patient survival rates ranging between 50% and 75%. This review summarizes the selection, perioperative management, and outcome of patients transplanted for acute liver failure, with particular reference to the experience at the H?pital Paul Brousse in Paris and at King's College Hospital, London. In both centers, the decision to proceed to liver transplantation is based on criteria that predict a survival of less than 20% with medical management alone. Infectious complications and cerebral edema remain the most common causes of death, and highlight the importance of intensive monitoring and early treatment of perioperative complications. In selected patients, auxiliary partial orthotopic liver transplantation may be a therapeutic option, with the potential for native liver generation and eventual immunosuppression withdrawal in approximately two-thirds of patients.     

The management of abnormalities of hemostasis in acute liver failure

The liver is the primary site of synthesis of most coagulation and fibrinolytic proteins, and also plays a role in the clearance of hemostasis factors and their degradation products. In acute liver failure, these functions are severely disturbed, and the risk of hemorrhage is increased. Following a brief summary of the physiology of hemostasis, this review describes the nature and frequency of hemostatic abnormalities in acute liver failure. These abnormalities include quantitative and qualitative platelet defects, impaired synthesis and clearance of the coagulation factors and related inhibitory proteins, and enhanced fibrinolysis. Disseminated intravascular coagulation may also play a role, although this syndrome is difficult to distinguish from changes due to the failure of hepatic synthesis and clearance alone. At present, management options are limited to support with blood products, although pharmacological manipulation of the coagulation and fibrinolytic systems represent a potential area for future study.     

Total quality in tubing glass manufacturing

We studied four patients who presented a striking elevation of blood transaminases suggesting acute hepatitis. The post mortem histological examination of the liver revealed centrolobular necrosis that is commonly diagnosed as ischaemic hepatitis. The liver necrosis arose from heart failure which was worsened by an acute anaemia in one patient and by a severe hypoxemia, due to respiratory failure, in another. In three subjects there was evidence of disseminated intravascular coagulation that may be responsible for aggravating the condition of liver hypoxia. The authors also review the literature on the various aspects of ischaemic hepatitis.     

Hepatocyte liver-assist systems--a clinical update

Liver failure is a serious problem that affects thousands of people in the United States each year. Other than liver transplantation, a supportive therapy has been unavailable for patients with liver failure that is refractory to medical treatment. An apparent solution to this problem is a hepatocyte liver-assist system. Such a system is composed of mammalian hepatocytes loaded in a mechanical apparatus, such as a hollow fiber cartridge. During extracorporeal perfusion of the system, the hepatocytes provide metabolic function to the patient with liver failure. At least two extracorporeal hepatocyte systems have shown promise in human clinical trials of acute liver failure. In fact, one system has gained approval from the Food and Drug Administration for testing in a randomized multicenter clinical trial. In this article, key issues of clinical testing are reviewed, and major contributions and questions that remain unresolved are emphasized.     

Varicella-zoster virus infection associated with acute liver failure

Although acute liver failure due to the varicella-zoster virus is rare, it is frequently fatal. Immunologic impairment is a significant predisposing factor. Classic symptoms at presentation are rash, abdominal pain, and fever. After some days patients go on to develop full-blown liver failure. The diagnosis can be confirmed by histological examination and electron microscopy with fluorescent staining, immunohistochemistry, and in situ hybridization of the liver. In cases of high suspicion, acyclovir therapy should not be delayed.     

Critical illness myopathy unrelated to corticosteroids or neuromuscular blocking agents

Acute myopathy occurs in critically ill patients, receiving neuromuscular blocking agents or corticosteroids during intensive care hospitalisation. We report three patients with acute quadriplegic myopathy, two of whom were not exposed to corticosteroids or neuromuscular blocking agents. The first of these latter two patients had a history of generalised anoxia with coma related to surgery, complicated by multiple organ failure and sepsis. The second patient, suffering from acute leukaemia, developed sepsis and acute respiratory distress syndrome with the need for mechanical ventilation in the intensive care unit. Electrophysiological studies and muscle biopsy findings were consistent with the diagnosis of critical illness myopathy with loss of myosin filaments. Selective loss of myosin was confirmed by biochemical analysis of muscle. These findings demonstrate that acute myopathy with loss of myosin filaments may occur in patients with severe systemic illness without exposure to corticosteroids or neuromuscular blocking agents.     

Case-control study of childhood leukaemia and cancer in Scotland: findings for neonatal intramuscular vitamin K

OBJECTIVE: To test the hypothesis of an association between neonatal intramuscular vitamin K and childhood leukaemia and other cancers. DESIGN: Population based case-control study with data abstracted from hospital records. SETTING: Scotland. SUBJECTS: Children aged 0-14 years resident in Scotland from 1991-4 and diagnosed with leukaemia (150), lymphomas (46), central nervous system tumours (79), a range of other solid tumours (142), and a subset of acute lymphoblastic leukaemia (129). Controls were 777 children matched for age and sex, providing 417 matched sets (360 triplets and 57 pairs) for analysis. MAIN OUTCOME MEASURE: Odds ratios for the risk of childhood leukaemia and cancer and intramuscular vitamin K versus a combined group of oral doses, none, and no record. Results are given for information recorded in medical notes and data supplemented by hospital policy. RESULTS: Odds ratios based on medical record abstractions showed no significant positive association for leukaemias (odds ratio 1.30; 95% confidence interval 0.83 to 2.03), acute lymphoblastic leukaemia (1.21; 0.74 to 1.97), lymphomas (1.06; 0.46 to 2.42), central nervous system tumours (0.74; 0.40 to 1.34), and other solid tumours (0.59; 0.37 to 0.96). There was no association with acute lymphoblastic leukaemia in children aged 1 to 6 years. Imputation of exposure from hospital policy gave similar results. Adjustment for deprivation and type of delivery moved risk estimates closer to unity for all major diagnostic groups. CONCLUSIONS: The observation of an increased risk of childhood leukaemia and cancer associated with intramuscular vitamin K is not confirmed by this independent population based study.