Rapid 'technological lock in' and pathology - Is technology moving too fast?

The term "Lock In" as applied to Science and Technology refers to a technology which has been utilised for a certain amount of time and it has been determined that the technology is viable and cost effective. An analysis of the technological advancements in pathology over a period of time shows that the newer technologies in contrast to the older technologies are reaching a state of "Technological Lock In" much faster. Three different discoveries, the development of the autopsy as a research tool, the discovery of the microscope and immunohistochemistry illustrate how rapidly "Technological Lock In" is being achieved with the passage of time. Three probable scenarios are possible because of this rapid "Technological Lock In". Technology may continue to progress at the same pace (an ideal scenario), may plateau until pathologists accept and absorb new technologies or thirdly, develop very rapidly so that the technology may never reach pathology practice. What will the future be? How will technology influence the principles and practices of Pathology? Only time will tell.

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.

Bioshock: Biotechnology and Bioterrorism.

In the recent past, the threat of a global bioterrorist attack has increased dramatically. In addition to the already existing microorganisms and techniques, the recent explosion in biotechnology has considerably added to the arsenal of the bioterrorist. Molecular technologies are now available which can be used by committed bioterrorist groups to manipulate and modify microorganisms so as to make them increasingly infectious, virulent or treatment resistant for causing maximum casualties. Infectious diseases which are likely to be used as bioweapons are Anthrax, Botulism, Plague, Smallpox and Brucella. Molecular techniques like immunoassays and nucleic acid amplification are now available to detect bioattacks. This article discusses the threat of bioterrorism. It also evaluates the molecular diagnostic methods and the future of early containment of a bioterrorist attack using molecular techniques.

Genetic association of interleukin-1 haplotypes with gastritis and precancerous lesions in North Indians.

BACKGROUND: We evaluated the association of functional variants of IL-1 genes with the development of gastritis and precancerous lesions, which are known to be influenced by inflammatory response against Helicobacter pylori. METHODS: After upper gastrointestinal (GI) endoscopy, 120 patients with gastritis were tested for H. pylori infection using rapid urease test, modified Giemsa staining and IgG anti-CagA ELISA. All patients and 243 healthy controls were genotyped for IL-1B (-511 C/T) and IL-IRN (VNTR) genes using PCR-RFLP/PCR. RESULTS: IL-1B: (-511 C/T) genotype/allele were not associated with gastritis. IL-1RN 1/2 genotype carriers had susceptibility to gastritis (p=0.025, OR=1.7). Individuals with the IL-1RN 1/1 genotype (p=0.05, OR=0.65) and IL-1B -511*T-IL-1RN *1 haplotype were at low risk for gastritis (p=0.043, OR=0.72). High secretor haplotype combinations (C1-/T2+, C1-T1+ and T1+/T2+) did not influence neutrophilic infiltration, glandular atrophy or intestinal metaplasia. CONCLUSIONS: We identified that individuals with the IL-1RN 1/2 genotype had increased risk for gastritis. IL-1B -511*T-IL-1RN *1 (T1) haplotype carriers were at decreased risk for gastritis and no significant association was observed for precancerous lesions in North Indians.

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.

Blood Bank on Wheels : A Novel Concept.

The concept of supplying safe and screened blood to casualties in war has been a problem over the years. Using the equipments available in a Corp Blood Supply Unit, we describe a simple modification of a vehicle for blood supply and its potential use as a mobile blood bank.

Cytokine gene polymorphisms and the pathology of chronic gastritis.

INTRODUCTION: Helicobacter pylori (H. pylori) infection is associated with divergent clinical outcomes and these outcomes are largely influenced by the levels of cytokines in the gastric mucosa. The levels of these cytokines are dependant on cytokine gene polymorphisms. Pro-inflammatory cytokine polymorphisms are strongly associated with severe histological changes in the gastric mucosa in Caucasian populations. METHODS: In this study, we evaluated the role of cytokine gene polymorphisms in influencing the pathological severity of gastritis. 120 patients were evaluated. Cytokine gene polymorphisms of interleukin-1 (IL-1) beta, tumour necrosis factor alpha and the IL-1 receptor antagonist genes were done using polymerase chain reaction (PCR) restriction fragment length polymorphism and PCR variable number of tandem repeats markers typed on the deoxyribonucleic acid obtained from the peripheral blood. Histological analysis was done by using the revised Sydney system. RESULTS: There was no association between pro-inflammatory cytokine gene polymorphisms and severity of gastritis. CONCLUSION: This data suggests that high cytokine levels are not seen in the gastric mucosa in Indians in spite of H. pylori colonisation. IL-1 beta is a potent proinflammatory cytokine which causes a partial clearance of the organism as well as hypochlorhydria. Corporal hypochlorhydria causes a persistent colonisation by H. pylori followed by the development of gastric atrophy and later carcinoma. This lack of association with a pro-inflammatory polymorphism suggests that only low levels of IL-1 beta are present in the gastric mucosa. This causes a low clearance of the organism and a high incidence of duodenal ulceration because of hyperchlorhydria. However, it is protective against the development of gastric carcinoma. This would explain the "Indian Paradox" of the apparent discrepancy of a high degree of colonisation by H. pylori and a low incidence of gastric carcinoma in the Indian population.

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%).

The role of mast cells and eosinophils in chronic gastritis.

The role of mast cells and eosinophils in influencing the pathology of chronic gastritis remains unclear. We attempted to study the relationship between endoscopy and the mast cell and eosinophil infiltrate. We also studied the role of gene polymorphisms, Helicobacter pylori density and the CagA antibody status in influencing the mast cell and eosinophil infiltrate. One hundred and twenty consecutive patients were studied. Endoscopic evaluation was done and 3 antral biopsies were taken from each patient and were assessed for eosinophilic and mast cell infiltration, H. pylori density and the density of the other inflammatory cells as per the revised Sydney system. Cytokine gene polymorphisms (IL-1beta, IL-1RA and TNF-alpha) were done on the DNA extracted from the peripheral blood by PCR-RFLP. ELISA was done on the patients' serum for the anti-CagA antibody titres. Nodularity is strongly associated with the presence and density of eosinophils on biopsy (P < 0.05). Eosinophil density is strongly associated with the density of H. pylori, neutrophils, lymphocytes, plasma cells, atrophy, ulceration, foveolitis and lymphoid follicles. The mast cell density is not associated with any of the other histopathological variables. Gene polymorphisms and the CagA antibody titres have no relationship to the mast cell and eosinophil density. Eighty-one patients showed positive anti-CagA antibody titres but there was no association with the eosinophilic or the mast cell infiltrate. It is likely that eosinophilic infiltration is influenced by the H. pylori density but the CagA protein has no role to play in influencing the grade of the eosinophilic infiltrate in the Indian context. Cytokine gene proinflammatory polymorphisms have no role to play in influencing the eosinophilic or the mast cell response. It is likely that other mediators are involved in the inflammatory cell responses.