Interpretation of hypertransaminasemia

Raised serum level of transaminases aspartate (aminotransferase and alanine aminotransferase) is a frequent situation in medical practice. It is considered as moderate when the level is under 10 times normal and as chronic when it lasts for more than 6 months. The most common etiologies for chronically elevated transaminases are alcohol use, viral hepatitis, liver steatosis, diabetes, obesity and medications. Many non invasive tests, including history, physical examination, blood tests (markers for hepatitis A and B, muscular enzymes), and imaging procedures (abdominal ultrasonography) are usually done and lead to a correct diagnosis in 80% of patients. When the diagnosis cannot be determined non invasively a liver biopsy is recommended in order to make diagnosis, to evaluate the prognosis and to start an adapted treatment.     

Expressed isolated integrin beta1 subunit cytodomain induces endothelial cell death secondary to detachment

Expression of isolated beta integrin cytoplasmic domains in cultured endothelial cells was reported to induce cell detachment and death. To test whether cell death was the cause or the consequence of cell detachment, we expressed isolated integrin beta1 cytoplasmic and transmembrane domains (CH1) in cultured human umbilical vein endothelial cells (HUVEC), and monitored detachment, viability, caspase activation and signaling. CH1 expression induced dose-dependent cell detachment. At 24 h over 90% of CH1-expressing HUVEC were detached but largely viable (>85%). No evidence of pro-caspase-8,-3, and PARP cleavage or suppression of phosphorylation of ERK, PKB and Ikappa-B was observed. The caspase inhibitor z-VAD did not prevent cell detachment. At 48 h, however, CH1-expressing cells were over 50% dead. As a comparison trypsin-mediated detachment resulted in a time-dependent cell death, paralleled by caspase-3 activation and suppression of ERK, PKB and Ikappa-B phosphoyrylation at 24 h or later after detachment. HUVEC stimulation with agents that strengthen integrin-mediated adhesion (i.e. PMA, the Src inhibitor PP2 and COMP-Ang1) did not prevent CH1-induced detachment. Expression of CH1 in rat carotid artery endothelial cells in vivo caused endothelial cell detachment and increased nuclear DNA fragmentation among detached cells. A construct lacking the integrin cytoplasmic domain (CH2) had no effect on adhesion and cell viability in vitro and in vivo. These results demonstrate that isolated beta1 cytoplasmic domain expression induces caspase-independent detachment of viable endothelial cells and that death is secondary to detachment (i.e. anoikis). They also reveal an essential role for integrins in the adhesion and survival of quiescent endothelial cells in vivo.     

Organizational aspects of organ harvesting in France

Organ transplantation of kidneys, liver, heart, lungs and pancreas is a routine practice in numerous French surgical centers with very good long-term results. Tissue transplantation of cornea, blood vessels, bone, and cardiac valves has also shown its efficacity and these tissues should be harvested whenever possible. Brain death is defined as the complete and irreversible destruction of the brain stem and cerebral cortex. The diagnosis of brain death is largely clinical but must be confirmed by EEG and cerebral arteriography. The Law of Caillavet has established the concept of "presumed consent" and has defined the judicial framework to permit organ harvesting. Nevertheless, there is still a high level of refusal of organ donation (in a third of cases) by the family of the decedent. At local and regional levels, control and coordination are provided by trained teams in liaison with the French Establishment for Transplantation (Etablissement fran?ais de greffes). The number of organ harvests grows steadily (18/million inhabitants in 2001) yet remains insufficient to meet the needs of the ever lengthening list of patients awaiting transplant. The profile of potential donors has also changed with time and poses increasing problems with regard to the quality of harvested organs.     

Profile of antimicrobial resistance of agents causing urinary tract infections in children

OBJECTIVE: The management of urinary tract infection in children faces the problem of the emergence of resistant strains to antibiotics. The aim of this study is to precise the frequency of the different germs and their susceptibility to antibiotics. METHODS: We report a retrospective study concerning 200 cases of urinary tract infection hospitalised in the paediatric department of Monastir between January 1995 and December 2000. There were 58 boys and 142 girls aged between two months and 14 years with a mean age of 5 years. The frequency of urinary tract infection is 1.85%. RESULTS: The most common causative agent is Escherichia coli in 75.5% of cases, followed by Proteus mirabilis (10%) then by Klebsiella pneumoniae (6%). Escherichia coli is predominant in girls, whereas Proteus mirabilis and Klebsiella pneumoniae are likely encountred in boys. Of all the strains, 96% are resistant to ampicillin, amoxicillin and cefalotin, 67% to amoxicillin + clavulanic acid and 34% to cotrimoxazole. A resistance to ampicillin, amoxicillin and cefalotin is noted in 96% of the germs. The resistance is of 67% for amoxicillin + clavulanic-acid and of 34% for cotrimoxazole. However, third generation cephalosporins and aminoglycosides remain usually active on the majority of strains incriminated in these infections a part from Pseudomonas.     

Spontaneous rupture of non-tumoral kidneys in patients with end stage renal failure: risks and management

OBJECTIVES: To determine the risks and treatment modalities of spontaneous subcapsular or perinephric bleeding in end stage renal patients. METHODS: 8 patients with end stage renal failure developed a spontaneous hemorrhage of one of their native kidneys and were referred to our institution. They were all men. Six of them presented an acquired renal cystic disease. Symptoms included sudden abdominal pain in 7 patients, vomiting in 2 and hematuria in 1. Symptoms were always associated with a hemoglobin decrease. Four patients were receiving oral anticoagulants for various reasons and one had thrombopenia. Bleeding was confirmed by computerized tomography and nephrectomy undertaken in all cases. RESULTS: 3 patients died in the immediate post-operative period. Histologic findings confirmed bleeding and did not find any other abnormality than those related to renal insufficiency (cysts and atrophy). CONCLUSION: Renal rupture should be considered in case of unexplained distress or sudden fall of the hemoglobin especially when patients are on anticoagulants. Surgery is our preferred treatment because of the frequency of unrevealed tumours and the potential mortality of massive hematomas.     

Prevalence of autoantibodies in the course of Gaucher disease type 1: A multicenter study comparing Gaucher disease patients to healthy subjects

Objectives

Type 1 Gaucher disease may be related to the presence of autoantibodies. Their clinical significance is questioned.Primary endpoint was to compare the prevalence of autoantibodies in type 1 Gaucher disease patients with healthy subjects, seeking correlations with autoimmune characteristics. Secondary endpoints were to determine whether patients with autoantibodies reported autoimmunity-related symptoms and if genotype, splenectomy or treatment influenced autoantibodies presence.

The impact of out‐of‐pocket health expenditure on household impoverishment: Evidence from Morocco

Health financing in Morocco relies mainly on out‐of‐pocket (OoP) payments. World Health Organization (WHO) has shown that these payments can expose households to catastrophic health expenditure (hereinafter CHE) and impoverish them. The study examines the financial burden of OoP health payments on Moroccan households. Two approaches—that developed by Wagstaff and Doeslear and the one advocated by WHO—are adopted to estimate the extent of CHE. These show that 1.77% of households incurred CHE at the 40% threshold for nonfood expenditure. At the 10% threshold for total consumption expenditure, 12.8% of households incurred CHE. We find that these OoP payments have made 1.11% of Moroccan households poorer. In analyzing the determinants of CHE, we estimated an ordered probit model. It appears that any of (a) hospitalization, (b) presence of an elderly person in the household, or (c) the level of poverty increases significantly the likelihood of health expenditure becoming catastrophic. On the other hand, we find that coverage by health insurance protects against CHE.     

Effect of donor CTLA-4 alleles and haplotypes on graft-versus-host disease occurrence in Tunisian patients receiving a human leukocyte antigen-identical sibling hematopoietic stem cell transplant

The CTLA-4 genetic variation, such as single nucleotide polymorphisms (SNPs) may be critical and can affect the functional activity of cells that initiate the graft-versus-host disease (GVHD) effects. The aim of this study is to examine the effect of donor CTLA-4 alleles and haplotypes for the -318C>T and the 49A>G polymorphisms on the occurrence of GVHD in Tunisians recipients of HSCs. A total of 112 patients and their 112 respective sibling donors of HSCs were enrolled in this study. All patients had either grades 0-I or grades II-IV acute GVHD, or chronic GVHD. The SNPs genotyping assay was performed using sets of sequence specific primers (SSP-PCR). The single marker association analysis showed that the 49G allele, in a genetic recessive model, may be a potential risk factor only for the chronic GVHD (p = 0.032, odds ratio [OR] = 2.58, 95% confidence interval = 1.05-6.32). The haplotypes analyses showed that the CTLA-4 -318C49G nucleotide combination is significantly associated with the incidence of chronic GVHD (p = 0.043, χ2 = 3.27). Donor CTLA-4 -318C49G haplotype may be a significant risk factor for developing chronic GVHD after allo-stem cell transplantation. We suppose that donor T cells expressing this haplotype in a homozygous state have higher proliferation than those expressing other haplotypes, especially after recognition of the recipient's minor histocompatibility antigens.