The ability to predict the outcome in acute tubular necrosis (ATN) remains elusive despite considerable efforts. Accurate prediction is a crucial priority and has large economical and ethical implications, mainly to judge when treatment is futile and further efforts only prolong miserable agony. To analyze the influence of risk factors in the prognosis of ATN, we applied, in an initial phase, a prospective protocol of demographic data, cause of renal failure, diuresis, need of dialysis and clinical conditions in 228 patients using multiple linear and logistic regression models. In a control phase with 100 consecutive patients, we checked the accuracy of the results previously obtained, evaluating further the overall population of 328 patients in a synthetic phase. Finally, the validation of the equations obtained was verified in 25 patients from another hospital. As a complement of this 4-phase study, detailed statistical comparisons between both linear and logistic multiple regression models were undertaken. Correlation between probability of death obtained with equations from the initial phase applied to control patients and real evolution of these patients, survival or death, was excellent. The study of the synthetic phase revealed coma, assisted respiration, hypotension, oliguria and jaundice as having an independent positive influence on mortality and nephrotoxic etiology and normal consciousness on good prognosis. For the linear model, the same cut-off point of discriminant score (0.9) above which there were no chances for survival could be established in the 4 phases. With the logistic model, it only was found at later phases. The multiple linear was better than the logistic regression model in terms of better correlation with real mortality, better sensitivity and specificity intervals, easier use of discriminant cut-off point and better adjustment of distribution of standardized residuals to expected normal function. Early prognosis of ATN is possible and can be given using simple clinical features. A discriminant score allows to distinguish patients without chances for survival. The multiple linear is better than the logistic regression model in the prediction of the outcome in ATN.

Multiple factors still influence the high rate of mortality in acute tubular necrosis. Trying to analyze the influence of each risk factor present in an individual patient and the possible interdependence between these factors, as well as to obtain an early prognosis, we have applied a forward analysis to demographic data, acute renal failure origin, need of dialysis, diuresis and clinical conditions in 228 patients, using a multiple linear regression model contained in a computer package. Based on this approach we have found that three variables: deep neurological coma, persistent blood hypotension and assisted respiration have significant influence on mortality. Also, a regression equation was obtained which could be applied as a discriminant score to patient prognosis. This score, calculated with the three aforementioned variables and oliguria when the nephrologist sees the patient for the first time, allows an easy and early prognosis in each patient with acute tubular necrosis.

Anticardiolipin antibodies are autoantibodies clinically associated with hypercoagulability. Systemic thrombosis and thrombosis of the vascular access for haemodialysis coexist with immunoregulation abnormalities in end-stage renal disease (ESRD). The aim of the present study was to analyse the incidence of thrombotic episodes and the presence of anticardiolipin antibodies and lupus anticoagulant in 73 patients with ESRD--51 on haemodialysis and 22 on conservative treatment. Four (18%) patients on conservative treatment had IgG-anticardiolipin, three of them also having lupus anticoagulant. Sixteen (31%) patients on haemodialysis showed IgG-anticardiolipin and 11 (22%) lupus anticoagulant; overall, 19 (37%) patients on haemodialysis had IgG-anticardiolipin and/or lupus anticoagulant. This greater incidence in haemodialysis was associated with a more frequent use of cuprophane membranes (68% versus 34%, P less than 0.05). Six patients with ESRD--one on conservative treatment--met criteria for the diagnosis of primary antiphospholipid syndrome, clinically characterised by thrombosis of the vascular access. IgG-anticardiolipin and/or lupus anticoagulant are frequently found in ESRD and their incidence increases with haemodialysis, probably due to some kind of membrane bioincompatibility. IgG-anticardiolipin and lupus anticoagulant can be associated with thrombotic episodes, being constituents of an ESRD-related antiphospholipid syndrome.

Nijmegen breakage syndrome (NBS) is a genetic disorder characterized by immunodeficiency, microcephaly, and "bird-like" facies. NBS shares some clinical features with ataxia telangiectasia (AT), including increased sensitivity to ionizing radiation, increased spontaneous and induced chromosome fragility, and strong predisposition to lymphoid cancers. The mutated gene that results in NBS codes for a novel double-stranded DNA break repair protein, named nibrin. In the present work, a Spanish NBS patient was extensively characterized at the immunological and the molecular DNA levels. He showed low CD3 ؉ -cell numbers and an abnormal low CD4؉ naive cell/CD4 ؉ memory cell ratio, previously described in AT patients and also described in the present report in the NBS patient. The proliferative response of peripheral blood lymphocytes in vitro to mitogens is deficient in NBS patients, but the possible link among NBS mutations and the abnormal immune response is still unknown.Nijmegen breakage syndrome (NBS) is a rare, autosomal recessive disorder characterized by microcephaly, immunodeficiency, and a predisposition to cancer (27). It shares some striking clinical and cellular similarities to the genetic disease ataxia telangiectasia (AT), and for this reason, NBS has been classified as a variant of AT (12). However, NBS patients have neither ataxia nor telangiectasia, and microcephaly is absent from AT patients (25, 27). The serum ␣-fetoprotein concentration is within the normal range in NBS patients, in contrast to AT patients, about 90% of whom are found to have elevated serum ␣-fetoprotein concentrations (31). In addition, different defective genes in patients with AT and NBS have been identified (3,23,28) and have been mapped in chromosomes 11q23 (8) and 8q21-24, respectively (22), which demonstrates that NBS is a genetic entity distinct from AT.Patients with both NBS and AT display chromosome instability, hypersensitivity to ionizing radiation, and a lack of DNA replication delay in response to radiation, which is governed, in normal cells, by the protein kinase C (PKC)-mediated upregulation of tumor suppresor protein p53 (9,13,14,15,18). These similarities suggest that ATM and nibrin, the proteins responsible for AT and NBS, respectively, may play a role in common functions, which appear to be defective in both diseases.Both ATM and nibrin participate in the processing of double-stranded breaks in DNA (3, 25). It has recently been shown that nibrin, in particular, forms a trimolecular complex, together with Rad50 (a protein similar to those required for the structural maintenance of chromosomes) and Mre11 (with both structural and catalytic activities, including single-stranded DNA endonuclease and double-stranded DNA exonuclease activities). The complex participates in the repair of doublestranded DNA breaks induced by radiation, and the Mre11 hyperphosphorylation observed after DNA damage is dependent on the presence of intact nibrin (6, 7). Recently, it has been shown that the phosphorylation of nibrin induced ...

SUMMARYLeucocyte adhesion de®ciency (LAD) is an autosomal-recessive genetic disease that is characterized clinically by severe bacterial infections and caused by mutations in the CD18 gene that codes for the b 2 integrin subunit. A patient with a severe LAD phenotype was studied and the molecular basis of the disease was identi®ed as a single homozygous defect in a Herpes virus saimiri (HVS)-transformed T-cell line. The defect identi®ed involves a deletion of 171 bp in the cDNA that encodes part of the proteic extracellular domain. This genetic abnormality was further studied at the genomic DNA level and found to consist of a deletion of 169 bp (from x37 of intron 4 to +132 of exon 5), which abolishes the normal splicing and results in the total skipping of exon 5. The 171-bp shortened`inframe' mRNA not only resulted in the absence of CD18 expression on the cell surface but also in its absence in the cytoplasm of HVS T-cell lines. Functionally, the LAD-derived HVS T-cell lines showed a severe, selective T-cell activation impairment in the CD2 (but not in the CD3) pathway. This defect was not reversible when exogenous interleukin-2 (IL-2) was added, suggesting that there is also a functional interaction of the lymphocyte function-associated antigen-1 (LFA-1) protein in the CD2 signal transduction pathway in human T cells, as has been previously reported in mice and in the human Papillon±Lefe Ávre syndrome. Thus, HVS transformation is not only a suitable model for T-cell immunode®ciency studies and characterization, but is also a good system for investigating the immune system in pathological conditions. It may also be used in the future in cellular models for in vitro gene-therapy trials.