The autoimmune/inflammatory syndrome induced by adjuvants (ASIA)/Shoenfeld’s syndrome: descriptive analysis of 300 patients from the international ASIA syndrome registry

Clinical Rheumatology - The autoimmune/inflammatory syndrome induced by adjuvants (ASIA) is a recently identified condition in which the exposure to an adjuvant leads to an aberrant autoimmune...     

The distinctive profile of risk factors of nasopharyngeal carcinoma in comparison with other head and neck cancer types

Background

Nasopharyngeal carcinoma (NPC) and other head and neck cancer (HNCA) types show a great epidemiological variation in different regions of the world. NPC has multifactorial etiology and many interacting risk factors are involved in NPC development mainly Epstein Barr virus (EBV). There is a need to scrutinize the complicated network of risk factors affecting NPC and how far they are different from that of other HNCA types.

Methods

122 HNCA patients and 100 control subjects were studied in the region of the Middle East. Three types of HNCA were involved in our study, NPC, carcinoma of larynx (CL), and hypopharyngeal carcinoma (HPC). The risk factors studied were the level of EBV serum IgG and IgA antibodies measured by ELISA, age, sex, smoking, alcohol intake, histology, and family history of the disease.

Results

EBV serum level of IgG and IgA antibodies was higher in NPC than CL, HPC, and control groups (p < 0.01). NPC was associated with lymphoepithelioma (LE) tumors, males, regular alcohol intake, and regular smoking while CL and HPC were not (p < 0.05). CL and HPC were associated with SCC tumors (p < 0.05). Furthermore, NPC, unlike CL and HPC groups, was not affected by the positive family history of HNCA (p > 0.05). The serum levels of EBV IgG and IgA antibodies were higher in LE tumors, regular smokers, younger patients, and negative family history groups of NPC patients than SCC tumors, non-regular smokers, older patients and positive family history groups respectively (p < 0.05) while this was not found in the regular alcoholics (p > 0.05).

Conclusion

It was concluded that risk factors of NPC deviate much from that of other HNCA. EBV, smoking, alcohol intake, LE tumors, male patient, and age > 54 years were hot risk factors of NPC while SCC and positive family history of the disease were not. Earlier incidence, smoking, LE tumors, and negative family history of the disease in NPC patients were associated much clearly with EBV. It is proposed that determining the correct risk factors of NPC is vital in assigning the correct risk groups of NPC which helps the early detection and screening of NPC.     

Human MSH2 binds to trinucleotide repeat DNA structures associated with neurodegenerative diseases

The expansion of trinucleotide repeat sequences is associated with several neurodegenerative diseases. The mechanism of this expansion is unknown but may involve slipped-strand structures where adjacent rather than perfect complementary sequences of a trinucleotide repeat become paired. Here, we have studied the interaction of the human mismatch repair protein MSH2 with slipped-strand structures formed from a triplet repeat sequence in order to address the possible role of MSH2 in trinucleotide expansion. Genomic clones of the myotonic dystrophy locus containing disease-relevant lengths of (CTG)n x (CAG)n triplet repeats were examined. We have constructed two types of slipped-strand structures by annealing complementary strands of DNA containing: (i) equal numbers of trinucleotide repeats (homoduplex slipped structures or S-DNA) or (ii) different numbers of repeats (heteroduplex slipped intermediates or SI-DNA). SI-DNAs having an excess of either CTG or CAG repeats were structurally distinct and could be separated electrophoretically and studied individually. Using a band-shift assay, the MSH2 was shown to bind to both S-DNA and SI-DNA in a structure- specific manner. The affinity of MSH2 increased with the length of the repeat sequence. Furthermore, MSH2 bound preferentially to looped-out CAG repeat sequences, implicating a strand asymmetry in MSH2 recognition. Our results are consistent with the idea that MSH2 may participate in trinucleotide repeat expansion via its role in repair and/or recombination.      

Hypersensitivity pneumonitis: evaluation with CT

Thirteen chest radiographs and computed tomographic (CT) scans obtained from 11 patients with hypersensitivity pneumonitis were reviewed. The CT findings were correlated with open lung biopsy findings in seven patients. The two patients with acute hypersensitivity pneumonitis showed air-space opacification on CT scans. An open lung biopsy, done in one of these patients, demonstrated noncaseating granulomas and filling of the air spaces with macrophages. The nine patients with subacute hypersensitivity pneumonitis showed small, rounded opacities and patchy air-space opacification on CT scans. These findings reflected the histologic findings, which consisted of interstitial pneumonitis, cellular bronchiolitis, and small, noncaseating granulomas. The six patients with symptoms for 12 months or longer also showed irregular linear opacities on CT scans, corresponding to areas of fibrosis. CT scans were superior to radiographs in helping to assess the type and extent of abnormalities, and high-resolution CT scans were superior to conventional CT scans.     

Prognostic significance of thrombocytosis in idiopathic sideroblastic anemia

In order to determine the prognostic significance of thrombocytosis in idiopathic sideroblastic anemia, the clinical courses of 17 patients were reviewed. Six patients (36%) had thrombocytosis, and none developed acute leukemia. Nine patients (53%) had normal platelet counts, and one developed acute leukemia. Two patients (12%) were thrombocytopenic, and one died of acute leukemia. There was little correlation between survival and platelet count. Sixty-three additional case reports of idiopathic sideroblastic anemia were collected from the literature. Analysis of those patients and the patients in the present study documented transformation to acute leukemia in 5 of 9 (56%) thrombocytopenic patients, 4 of 54 (7.4%) patients with normal platelet counts, and 0 of 17 patients with thrombocytosis (p less than 0.05). Therefore patients with idiopathic sideroblastic anemia and thrombocytosis appear to have a decreased likelihood of leukemic transformation.