Pulmonary malakoplakia: a report of two cases

Malakoplakia of lung is an unusual condition that has been reported to occur in association with immunocompromised state, particularly in those with acquired immunodeficiency syndrome. We present two cases of pulmonary malakoplakia in immunocompetent individuals. The diagnosis was made on histopathological examination of surgically resected specimen.     

Intraductal papillary mucinous neoplasm of the pancreas with loss of mismatch repair in a patient with Lynch syndrome

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a precancerous lesion with a well-described progression to carcinoma. This case report describes a 61-year-old woman with a history significant for multiple cancers and a confirmed germline mutation of MSH2, a mismatch repair gene responsible for Lynch syndrome, who was also found to have an IPMN of the pancreas. Phenotypic manifestations of Lynch syndrome in this patient included multiple adenomas and adenocarcinomas of the colon and also several other Lynch syndrome-associated cancers. The patient's adenocarcinoma of the colon and IPMN of the pancreas showed identical immunohistochemical staining profiles with loss of expression of MSH2 and MSH6 proteins and high levels of microsatellite instability. The immunohistochemical staining and microsatellite instability patterns of the adenocarcinoma of the colon and IPMN gives strong evidence to support the consideration of IPMN as part of the spectrum of lesions found in Lynch syndrome.     

ORIGINAL ARTICLE: Treatment with Adalimumab (Humira®) and Intravenous Immunoglobulin Improves Pregnancy Rates in Women Undergoing IVF*

Problem The purpose of this study was to investigate whether treatment with TNF‐α inhibitors and/or intravenous immunoglobulin (IVIG) increases in vitro fertilization (IVF) success rates among young (<38 years) women with infertility and T helper 1/T helper 2 cytokine elevation. Method of study Seventy‐five sub‐fertile women with Th1/Th2 cytokine elevation were divided into four groups: Group I: Forty‐one patients using both IVIG and Adalimumab (Humira^®), Group II: Twenty‐three patients using IVIG, Group III: Six patients using Humira^®, and Group IV: Five patients using no IVIG or Humira^®. Results The implantation rate (number of gestational sacs per embryo transferred, with an average of two embryos transferred by cycle) was 59% (50/85), 47% (21/45), 31% (4/13) and 0% (0/9) for groups I, II, III and IV respectively. The clinical pregnancy rate (fetal heart activity per IVF cycle started) was 80% (33/41), 57% (13/23), 50% (3/6) and 0% (0/5) and the live birth rate was 73% (30/41), 52% (12/23), 50% (3/6) and 0% (0/5) respectively. There was a significant improvement in implantation, clinical pregnancy and live birth rates for group I versus group IV (P = 0.0007, 0.0009, and 0.003, respectively) and for group II versus group IV (P = 0.009, 0.04 and 0.05, respectively). Conclusion The use of a TNF‐α inhibitor and IVIG significantly improves IVF outcome in young infertile women with Th1/Th2 cytokine elevation.     

EGLN1 involvement in high-altitude adaptation revealed through genetic analysis of extreme constitution types defined in Ayurveda

It is being realized that identification of subgroups within normal controls corresponding to contrasting disease susceptibility is likely to lead to more effective predictive marker discovery. We have previously used the Ayurvedic concept of Prakriti, which relates to phenotypic differences in normal individuals, including response to external environment as well as susceptibility to diseases, to explore molecular differences between three contrasting Prakriti types: Vata, Pitta, and Kapha. EGLN1 was one among 251 differentially expressed genes between the Prakriti types. In the present study, we report a link between high-altitude adaptation and common variations rs479200 (C/T) and rs480902 (T/C) in the EGLN1 gene. Furthermore, the TT genotype of rs479200, which was more frequent in Kapha types and correlated with higher expression of EGLN1, was associated with patients suffering from high-altitude pulmonary edema, whereas it was present at a significantly lower frequency in Pitta and nearly absent in natives of high altitude. Analysis of Human Genome Diversity Panel-Centre d'Etude du Polymorphisme Humain (HGDP-CEPH) and Indian Genome Variation Consortium panels showed that disparate genetic lineages at high altitudes share the same ancestral allele (T) of rs480902 that is overrepresented in Pitta and positively correlated with altitude globally (P < 0.001), including in India. Thus, EGLN1 polymorphisms are associated with high-altitude adaptation, and a genotype rare in highlanders but overrepresented in a subgroup of normal lowlanders discernable by Ayurveda may confer increased risk for high-altitude pulmonary edema.     

Linkage analysis of chromosome 4 in families with familial pancreatic cancer

BACKGROUND: Approximately 10% of pancreatic ductal adenocarcinomas have a familial basis. While a small portion of this familial clustering can be explained by inherited mutations in known genes (BRCA2, p16/CDKN2A, PRSS1, and STK11), the genetic basis for the majority of this familial clustering remains unknown. In addition, a pancreatic cancer susceptibility locus has been reported to be linked to chromosome 4q32-34 in a single family having a high penetrance of early-onset pancreatic ductal adenocarcinoma and pancreatic insufficiency. The goal of this study is to determine if linkage to chromosome 4q exists in our series of well-characterized families with idiopathic familial pancreatic cancer enrolled in the Pancreatic Cancer Genetic Epidemiology Consortium (PACGENE). METHODS: Parametric and nonparametric linkage analyses were performed using 21 microsatellite markers on chromosome 4 on affected individuals with pancreatic cancer from 42 familial pancreatic cancer kindreds. RESULTS: Markov Chain Monte Carlo parametric and nonparametric linkage analyses using SIMWALK2 as well as nonparametric linkage analysis using MERLIN did not provide strong evidence of linkage in this region (LOD < 1.0). Only one family provided a multipoint LOD score of >0.5 adjacent to the reported region. CONCLUSIONS: Our results do not support linkage to the 4q32-34 region in the majority of our familial pancreatic cancer kindreds. However, because multiple pancreatic cancer susceptibility genes are likely to exist, it is possible that a subset of the families in this study may be linked to this region.