Time Interval and the Factors Associated with the Development of Asthma in Patients with Allergic Rhinitis

Rhinitis and asthma commonly coexist and studies have shown a positive association between rhinitis and asthma in both atopic and nonatopic adults. Longitudinal studies have shown that in many cases rhinitis precedes the onset of asthma. The aims of this study were to study the time interval for the development of asthma after the onset of rhinitis, to determine the proportion of patients in whom rhinitis precedes asthma, and to study the factors associated with the development of asthma in patients with allergic rhinitis compared to patients who continue to have allergic rhinitis alone. This was a cross-sectional study done at a tertiary care allergy center in Mysore, South India. It included consecutive patients between 2004 and 2006 with allergic rhinitis and/or asthma. We used a structured questionnaire, clinical evaluation, spirometry, and skin-prick testing. A total of 1,141 subjects were included in the study. Among them, 700 had allergic rhinitis for varying intervals before developing asthma and 355 had rhinitis without asthma. In subjects aged 20 years or younger, logistic regression analysis confirmed an independent association with a family history of allergic rhinitis and sensitization to house dust mites as risk factors and ever-used nasal steroids as protective against developing asthma in subjects with allergic rhinitis. In subjects older than 20 years, a family history of allergic rhinitis, atopy, and sensitization to house dust mites and trees were risk factors and ever-user of nasal steroids was protective. Rhinitis often preceded asthma and a high proportion of patients, both children and adults, developed asthma within 2 years after the onset of rhinitis. A family history of allergic rhinitis, atopy, and sensitization to house dust mites and trees are associated with the development of asthma in patients with allergic rhinitis.     

Pancreatic intraductal papillary mucinous neoplasm in a patient with Lynch syndrome

Intraductal papillary mucinous neoplasm (IPMN) is a mucin-producing epithelial neoplasm that carries a risk of progression to invasive pancreatic ductal adenocarcinoma. Lynch syndrome is an autosomal dominant condition caused by germline mutations in mismatch repair genes such as MSH2 that lead to microsatellite instability and increased risk of tumor formation. Although families with Lynch syndrome have an increased risk of pancreatic cancer, a clear connection between Lynch syndrome and IPMN has not been drawn. We present a report of a 58 year-old Caucasian woman with multiple cancers and a germline mutation of MSH2 consistent with Lynch syndrome. A screening abdominal computed tomography scan revealed a dilated main pancreatic duct and cystic ductular structure in the uncinate process that were consistent with IPMN of the main pancreatic duct on excision. Immunohistochemistry and polymerase chain reaction of the patient’s pancreas specimen did not reveal microsatellite instability or mismatch repair gene loss of expression or function. Our findings may be explained by the fact that loss of mismatch repair function and microsatellite instability is a late event in neoplastic transformation. Given the relative rarity of main duct IPMN, its appearance in the setting of somatic MSH2 mutation suggests that IPMN may fit into the constellation of Lynch syndrome related malignancies.     

Lack of Association Between Asthma and ABO Blood Group

ABO is the most important blood group system in transfusion and transplantation practices. Glycosyltransferases are controlled by the ABO system which is helpful in building oligosaccharide structures on the cell surface of erythrocytes and vascular endothelium and in the exocrine secretion system, including the respiratory tract. We analyzed the ABO blood group of 200 children and adults with asthma as well as that of 2000 healthy subjects as controls. The most common blood group among the patients and controls was “O” (43.5% and 43.6%, respectively), followed by B, A, and AB. In the distribution of different blood groups, nonsignificant difference between patients and controls was observed (p = 0.931). We conclude that ABO blood group status has a nonsignificant association with asthma among the population of Mysore, Karnataka, South India.     

A rare case of cutaneous kaposiform haemangioendothelioma

Kaposiform haemangioendothelioma is a rare vascular neoplasm with a wide anatomical distribution. We describe an unusual case arising in the post-auricular skin of a male infant overlying a ventriculoperitoneal shunt.     

1,N2-propanodeoxyguanosine adducts of the 1,3-butadiene metabolite, hydroxymethylvinyl ketone

1,3-Butadiene (BD) is a rodent and human carcinogen. While several epoxides formed during BD metabolism are mutagenic and may contribute to BD carcinogenicity, another proposed metabolite, hydroxymethylvinyl ketone (HMVK), could also be involved. A significant quantity of HMVK is likely to be formed since it is a proposed intermediate in the metabolism of 3-butene-1,2-diol (BD-diol) to 1,2-dihydroxy-4-(N-acetylcysteinyl)butane, the major mercapturic acid metabolite of BD in humans. In addition, BD-diol is a major BD metabolite in liver perfusion experiments in rodents. By analogy with other alpha,beta-unsaturated carbonyls, HMVK is likely to be mutagenic via formation of promutagenic 1,N(2)-propanodeoxyguanosine adducts. The objective of the current study was to investigate the formation of such adducts in vitro. The reaction between HMVK and dGuo yielded two major products shown to be identical by positive ion electrospray-MS, having protonated molecular ions with m/z consistent with HMVK-derived 1,N(2)-propanodeoxyguanosine (HMVK-dGuo). Rechromatography of each fraction yielded two fractions with retention times identical to those initially isolated, suggesting equilibration between two diastereomers. Two partially resolved sets of (1)H NMR signals were consistent with a 1:1 mixture of diastereomeric C-6-substituted adducts equilibrating slowly on an NMR time-scale. Following deglycosylation, C-6 substitution was verified by two-dimensional correlation NMR spectroscopy, indicating that the initial adducts were formed by Michael addition of dGuo-N1 to the terminal vinyl carbon followed by cyclization to the 1,N(2)-propano structure. Reactions with calf thymus DNA under physiological conditions yielded two sets of products. The first set had HPLC retention times and mass spectra identical to those of the previously characterized C-6-substituted HMVK-dGuo diastereomers. The second set had a molecular ion and fragmentation pattern identical to the C-6-substituted adducts and on this basis were assigned as the diastereomeric C-8 adducts. In addition to detecting HMVK-dGuo in treated DNA, the adducts were also present in control DNA. Overall, our research demonstrates that HMVK can form promutagenic DNA adducts and it therefore has the potential to play a role in BD-associated mutagenicity.