Association of Toll-like receptor-4 (Asp299Gly and Thr399Ileu) gene polymorphisms with gastritis and precancerous lesions

A Toll-like receptor-4 (TLR-4) Asp299Gly and Thr399Ileu substitution reduces responsiveness to Helicobacter pylori (H. pylori) lipopolysaccharide. CagA+ strains of H. pylori are known to be associated with gastroduodenal diseases. Therefore we aimed to evaluate association of TLR-4 substitutions and CagA seropositivity with gastritis and precancerous lesions in a northern Indian population. After upper gastrointestinal endoscopy, 130 rapid urease test (RUT)-positive patients with nonulcer dyspepsia (NUD) were included. Patients with NUD were also screened for H. pylori infection using modified Giemsa staining and anti-CagA IgG enzyme-linked immunoabsorbent assay. All patients and 200 asymptomatic control subjects were genotyped for TLR-4 substitutions using polymerase chain reaction-restriction fragment length polymorphism. We observed that frequencies of TLR-4 Asp299Gly variants were comparable between patients and control subjects, and also between positive and negative groups of precancerous lesions in patients. Frequencies of TLR-4 399Ileu allele (8% vs 3%, p = 0.008) and Asp299-Ileu399 haplotype (6.5% vs 3%, p = 0.022) were higher in patients than in control subjects at risk for gastritis (OR = 2.6 and 2.5, respectively). TLR-4 399Ileu allele carriers had higher risk for plasma cell infiltration (p = 0.023, OR = 10.6) that led to atrophy (p = 0.028, OR = 4.2) and intestinal metaplasia (p = 0.009, OR = 4.7). CagA positivity was more frequently associated with lymphoid follicle formation (p = 0.033, OR = 2.53). In conclusion TLR-4 Thr399Ileu substitution may be a risk factor for gastritis and precancerous lesions. CagA positivity may be a risk factor for lymphoid follicle development but not for other precancerous lesions in a northern Indian population.     

Clinico-pathological profile of pediatric lymphadenopathy

Objective : To study the clinico-pathological profile of significant pediatric peripheral lymphadenopathy and to arrive at an etiological diagnosis.Methods : Prospective study in a tertiary care hospital setting. One hundred consecutive children reporting to pediatric OPD from 1 January 1995 to 31 December 1998, aged 1 month to 12 years were studied.Results : The commonest aetiology diagnosed was tubercular lymphadenitis in 35% cases, followed by chronic tonsillopharyngitis in 15% cases. Lymphomas, AIDS and infectious mononucleosis constituted 3,2 and 1 cases each. Aetiology could not be ascertained in 44 (44%) children even after detailed haematological, microbiological, radiological and serological investigations. FNAC’s sensitivity and specificity as compared to ’gold standard of excision lymph node biopsy was 94% and 100% respectively.Conclusion : Tubercular lymphadenitis was the commonest treatable entity of significant pediatric peripheral lymphadenopathy. A majority of the cases even after thorough evaluation, remained undiagnosed. FNAC as a diagnostic modality is almost as sensitive and as specific as excision lymph node biopsy when an adequate aspirate is examined by expert eyes.     

Ameloblastic Carcinoma of the mandible

Odontogenic carcinomas are rare lesions arising from dental embryogenic residues and have been designated by a variety of terms like malignant ameloblastoma, ameloblastic carcinoma, metastatic ameloblastoma or primary intra-alveolar epidermoid carcinoma. Ameloblastic carcinoma combines the histological features of ameloblastoma with cytological atypia, even in the absence of metastasis. The lesion has been reported to arise either from the odontogenic cyst or the ameloblastoma. Majority originate de novo and the remaining are malignant transformation of an ameloblastoma.     

Risk of lymphoid follicle development in patients with chronic antral gastritis: role of endoscopic features, histopathological parameters, CagA status and interleukin-1 gene polymorphisms

Objective: Helicobacter pylori infection causes gastritis, lymphoid follicle formation and development of MALT lymphoma. We evaluated endoscopic, histological, serological and genetic risk factors associated with lymphoid follicle development in gastritis. Materials and methods: After upper GI endoscopy, 3 antral biopsies were taken from 120 patients for histological examination. H. pylori was diagnosed using rapid urease test (RUT), modified Giemsa stain and IgG anti-CagA ELISA. Genotyping of IL-1B (−511C/T) and IL-1RN (86 bp VNTR) genes were performed by PCR-RFLP/PCR. Results: In 120 patients, 45 (37.5%) showed presence of lymphoid follicles in antral gastric mucosa. H. pylori was positive by modified Giemsa stain (26%) RUT (50%) and anti-CagA IgG in 67.5%, The presence of nodularity (p = 0.030), neutrophilic infiltration (p = 0.010), lymphocytic infiltration (p = 0.002), glandular atrophy (p = 0.0001), glandular shortening (p = 0.001), fibrosis (p = 0.0001), plasma cells (p = 0.007), eosinophils (p = 0.012), anti-CagA antibodies (p = 0.003) and H. pylori density (p = 0.020) were associated with risk (odds ratio = 11.5, 3.8, 11.0, 8.4, 3.8, 4.6, 5.8, 16.0, 10.8 and 2.8 respectively) of lymphoid follicle. However, IL-1 gene polymorphisms did not influence lymphoid follicle development Conclusion: The presence of modularity, lymphocytic infiltration, glandular atrophy, glandular shortening, fibrosis, plasma cells, eosinophils and anti-CagA IgG antibodies are risk factors for lymphoid follicle development in patients with gastritis. Received 21 February 2007; returned for revision 11 June 2007; accepted by C. Kasserra 31 July 2007     

Vitamin D Deficiency After Oral Retinoid Therapy for Ichthyosis

Oral retinoids are being increasingly used to treat ichthyotic disorders in children. We report on two children with ichthyotic disorders who developed unusual manifestations after they were started on oral retinoids. The first case is a 10‐year‐old girl with nonbullous ichthyosiform erythroderma and the second is a 2‐year‐old girl with lamellar ichthyosis. The child with ichthyosiform erythroderma developed features of rickets within months of initiation of systemic retinoids. Her baseline examination before initiation of oral retinoids was normal. The second patient with lamellar ichthyosis was found to have low vitamin D levels after 6 months of retinoid therapy, and prompt supplementation reversed the levels in 2 months. These cases are being reported to bring attention to the probable need for initiation of vitamin D supplementation with systemic retinoid therapy in ichthyotic disorders in children.     

Status of HFE mutation in thalassemia syndromes in north India

Hereditary hemochromatosis is an autosomal recessive and most commonly inherited single gene disorder among Caucasians, with a prevalence of 5 per 1,000 and a carrier frequency of 1 in 10. Two point mutations were described and are referred as C282Y and H63D. In the present study, we have analyzed 729 north Indian samples for C282Y and H63D mutations. Of these, no allele of the C282Y mutation was seen, while 3 homozygous and 43 heterozygous for the H63D mutation were seen in the patients of thalassemia group. However, 47 cases were found heterozygous for the H63D mutation among the normal groups (11.16%).