Common variants in NLRP2 and NLRP3 genes are strong prognostic factors for the outcome of HLA-identical sibling allogeneic stem cell transplantation

The inflammasomes are macromolecular cytosolic complexes involved in the production of interleukin-1beta (IL-1beta) and IL-18 in response to several pathogen-derived stimuli. Such interleukins have been implicated in the origin of severe allogeneic stem cell transplant (allo-SCT) complications. We analyzed the relationship between the interindividual variability in inflammasome protein-encoding genes in donors and patients and clinical outcome after allo-SCT. Fourteen common genetic variants in 5 genes of the inflammasome, namely, NLRP1, NLRP2, NLRP3, CARD8, and CASP5, were genotyped in 133 human leukocyte antigen-identical sibling pairs undergoing allo-SCT. In the multivariate analysis, donor variants in NLRP2 and NLRP3 were the most important prognostic factors for the clinical outcome after allo-SCT. Thus, donor TT genotype at rs10925027 in NLRP3 was associated with disease relapse (odds ratio (OR) = 6.3, P = 1 x 10(-7)), and donor GG genotype at rs1043684 in NLRP2 was associated with nonrelapse mortality (OR = 4.4, P = 6 x 10(-4)) and overall survival (OR = 3.1, P = .001). In addition, patient AA genotype at rs5862 in NLRP1 was associated with nonrelapse mortality (OR = 2.8, P = .005) and overall survival (OR = 2.0, P = .009). These results suggest that inflammasome genetic variants are important prognostic factors for the outcome of allo-SCT. If validated in larger studies, including unrelated allo-SCT, NLRPs genotype would become an important factor in donor selection.     

Prophylaxis of venous thromboembolism

The recommendations on venous thromboprophylaxis have been updated on the basis of current evidence reviewed by a multidisciplinary team. The problem has been approached with regard to its relevance in both surgical and nonsurgical patients. It should be noted that these recommendations were drawn up for use in Spain and, therefore, should be implemented with the drugs and therapeutic practices authorized and generally accepted in this country.     

Characterization of VHL promoter variants in patients suspected of Von Hippel-Lindau disease

Von Hippel-Lindau (VHL) disease is a hereditary tumor syndrome in which carriers are at an increased risk of developing a variety of tumors in multiple organ systems. A clinical diagnosis of VHL is determined by the presence of specific clinical manifestations while a molecular genetic diagnosis results from a pathogenic variant in the VHL gene. The majority of mutations occur in VHL coding exons and DNA analysis of these regions has a reported sensitivity of nearly 100%. However, rare variants in the VHL gene promoter may be detected in some cases of suspected VHL disease. We report two cases where VHL promoter variants were detected and describe the role of multi-step mRNA and protein analysis in the diagnostic evaluation of these cases.     

Bronchioloalveolar lavage in the diagnosis of CMV pneumonitis in lung transplant recipients: An immunocytochemical study

Cytomegalovirus (CMV) pneumonitis is a common opportunistic infection in lung transplant recipients. Its diagnosis usually rests on the identification of viral inclusions in lung parenchyma obtained by transbronchial biopsy, or by examination of the cytologic material obtained by bronchioloalveolar lavage (BAL). To determine whether the use of immunocytochemistry (ICC) increases the sensitivity of cytology in the diagnosis of CMV pneumonitis, we retrospectively selected 17 cases in which transbronchial biopsy and BAL were performed simultaneously, and had positive histology with negative cytology. Five negative controls were selected. The 22 slides were decolorized and restained with ICC for CMV. Of the 17 slides, nine (53%) showed cells with positive nuclear staining. All controls were negative. These results were then correlated with the number of infected cells present in the biopsy tissue, and the location of the cells (interstitial vs. intraalveolar). A good correlation was found between positive cytology and intraalveolar location of infected cells, and no correlation was seen between number of infected cells in the biopsy and the positive cytology. In summary, although histologic evaluation of lung parenchyma obtained by transbronchial biopsy is more sensitive for diagnosis of CMV pneumonitis, the sensitivity of the cytologic evaluation of BAL material can be increased by the use of ICC. The likelihood of positive ICC seems to be related to the presence of infected cells in the alveolar space rather than to the number of infected cells. Diagn. Cytopathol. 16:350–352, 1997. © 1997 Wiley-Liss, Inc.     

Detection of specific antibodies to pigeon serum and bloom antigens by enzyme linked immunosorbent assay in pigeon breeder's disease

BACKGROUND—Pigeon breeder's disease is an extrinsic allergic alveolitis in the lungs of sensitised people, caused by hypersensitivity reactions to inhaled pigeon antigens. Antigens from different sources of the animal are used for diagnostic purposes, with serum being the most widely used. Bloom is rarely used; very little is known of its antigenicity and diagnostic performance, particularly when used with the enzyme linked immunosorbent assay (ELISA) method, which is the most popular test as it permits measurement of the antibody response.
METHODS—To (a) standardise an ELISA for the measurement of specific IgG against pigeon serum and pigeon bloom extract; (b) to establish reference values for specific IgG in 73 non-exposed controls, (c) to show the presence of specific IgG against pigeon serum and bloom in serum samples of 17 patients with bird fancier's lung and 11 asymptomatic fanciers, and (d) to study the similarity of the two antigen sources by cross reactivity experiments.
RESULTS—Reference values of specific IgG were defined with the 97.5 percentile (367.9 U/ml for pigeon serum and 953.7 U/ml for pigeon bloom extract). Of symptomatic patients 100% had values higher than the cut off for both antigens. In asymptomatic fanciers values were higher than the cut off for pigeon serum in 45% and bloom extract in 54%. Cross reactivity experiments showed that the two antigens differed in antigenic content although some components may be common to both.
CONCLUSION—The ELISA methods used proved to be useful tools for evaluating specific IgG antibody responses against both antigens. The diagnostic performance of both ELISA methods performed with these antigen sources was similar, showing very high sensitivity but moderate specificity. Although some antigenic similarity was found between pigeon serum and bloom extract, cross reactivity studies showed that various antigens seemed to be specific to the bloom extract. However, the antigens responsible for pigeon breeder's disease seem to be present in both antigenic sources.


Keywords: antibodies; pigeons; ELISA     

Periapical and endodontic status of type 2 diabetic patients in Catalonia, Spain: a cross-sectional study

Introduction

The aim of this study was to investigate radiographically the prevalence of apical periodontitis (AP) and endodontic treatment in a sample of adult type II diabetic patients and control subjects.

Methods

In a cross-sectional study, the radiographic records of 50 adult patients reporting a history of well-controlled type 2 diabetes mellitus (DM) (study group) and 50 age- and sex-matched subjects who reported no history of DM (control group) were examined. Periapical status of all teeth was assessed using the periapical index score.

Results

The average number of teeth per patient in the diabetic and control groups was 21.9 and 24.6 teeth, respectively (P = .012). AP in one or more teeth was found in 37 diabetic patients (74%) and in 21 control subjects (42%) (odds ratio = 3.9, P = .002). One or more root-filled teeth were found in 35 (70%) and 25 (50%) of diabetic and control subjects, respectively (odds ratio = 2.3, P = .043). Among diabetic patients with root-filled teeth, 16 (46%) had AP affecting at least one treated tooth. Among controls with root-filled teeth, 6 (24%) had AP affecting at least one treated tooth (P > .05). Adjusting for teeth number, multivariate logistic regression analysis showed that periapical status (odds ratio = 3.3, P = .0071) and the number of root-filled teeth (odds ratio = 1.7; P = .0035) were significantly associated with diabetic status.

Conclusions

The results showed that in adult patients, type 2 DM is significantly associated with an increased prevalence of AP and endodontic treatment.