Topographic genotyping of colorectal carcinoma: From a molecular carcinogenesis model to clinical relevance

Background: In recent years, as a result of refinement in molecular biology techniques, significant progress has been made in the understanding of colorectal carcinogenesis. Particular attention has been drawn to identification of genetic mutation that may predispose to colorectal carcinoma (familial syndromes) and may affect tumor behavior and prognosis (sporadic cases). Conclusions: Our method of topographic genotyping of human colonic carcinomas has shown a correlation between K-ras-2 and p53 mutations and stage- at diagnosis as well as long-term survival. Data from other investigators in this field confirm the importance of genetic analysis of human colorectal tumors. These findings are likely to impact management by allowing a more individualized therapeutic approach.     

Patient cytokine response in transfusion-associated sepsis.

Cytokine concentrations in plasma from patients transfused with packed erythrocytes contaminated with gram-negative bacilli were measured. Cytokine concentrations in posttransfusion plasma were significantly elevated. A difference in cytokine patterns between survivors and a nonsurvivor was observed.     

Alcoholism--North America and Asia. A comparison of population surveys with the Diagnostic Interview Schedule

The Diagnostic Interview Schedule (DIS) is a highly structured instrument that enables lay examiners to gather the clinical information necessary to generate psychiatric disorders according to the DSM-III, Feighner, and Research Diagnostic Criteria. It was developed originally as the diagnostic interview for the Epidemiologic Catchment Area (ECA) survey. Because it adheres to DSM-III and can be used by lay interviewers, thus making it practical for studies involving large samples, it has been used for other population surveys in North and South America, Europe, and Asia. This investigation compares the epidemiology of DSM-III-defined alcohol abuse and addiction in DIS-based population surveys cross-nationally (in St Louis, Mo; Edmonton, Canada; Puerto Rico; Taipei City, Taiwan; and South Korea). We found considerable variation in the lifetime prevalence of alcoholism but a similarity in the age of onset, the symptomatic expression, and the associated risk factors. We also found an inverse correlation between the prevalence of alcoholism and the strength of the association of the risk factors we examined. The work described herein demonstrates the utility of consistent definition and method in cross-cultural psychiatric research. The substantive findings have implications for the definition of alcoholism and for a better understanding of genetic and environmental interactions in its etiology.     

External resorption presenting as an intracoronal radiolucent lesion in a pre-eruptive tooth

A large intracoronal radiolucent lesion in an unerupted permanent molar was found during the routine assessment of a young male Caucasian prior to orthodontic treatment. The tooth was extracted. Histological examination indicated the lesion was caused by external resorption. The defect extended widely into the enamel and dentine, and was repaired in part by bone. The pulp chamber was not involved. The aetiology of these lesions is often obscure but in this case it appeared to have originated in the floor of two developmental pits on the occlusal surface of the tooth.     

Localisation of pseudohypoaldosteronism genes to chromosome 16p12.2- 13.11 and 12p13.1-pter by homozygosity mapping

Pseudohypoaldosteronism type 1 (PHA1, OMIM 264350) is a rare Mendelian disorder characterised by end-organ unresponsiveness to mineralocorticoids. Most steroid hormone insensitivity syndromes arise from mutations in the corresponding receptor, but available genetic evidence is against involvement of the mineralocorticoid receptor gene, MLR, in PHA1. A complete genome scan for PHA1 genes was undertaken using homozygosity mapping in 11 consanguineous families. Conclusive evidence of linkage with heterogeneity was obtained with a maximum two- locus admixture lod score of 9.9. The disease locus mapped to chromosome 16p12.2-13.11 in six families and to 12p13.1-pter in the other five families. The two chromosomal regions harbour genes for subunits of the amiloride-sensitive epithelial sodium channel: SCNN1B and SCNN1G on 16p and SCNN1A on 12p. Liddle's syndrome of hypertension and pseudoaldosteronism has been shown to arise from mutations in SCNN1B and SCNN1G. These results strongly suggest that PHA1 and Liddle's syndrome are allelic variants caused by mutations in genes encoding subunits of this sodium channel. These genes are of broad biological interest both in relation to sodium and water homeostasis in mammals and by virtue of their homology to the mec genes of Caenorhabditis elegans involved in mechanosensitivity and neuronal degeneration.      

Brain phantom: high-resolution imaging with SPECT and I-123

Inverse Monte Carlo (IMOC) is a unified reconstruction algorithm for single photon emission computed tomography (SPECT) that provides simultaneous compensation for attenuation and collimator divergence. IMOC was applied to the reconstruction of SPECT images of a brain phantom with iodine-123 and high-resolution collimation. Projection sets containing 80,000, 540,000, and 5.2 million counts were reconstructed. Comparison with filtered back-projection reconstructions showed that the IMOC reconstructions provided superior noise and resolution characteristics at all three photon densities. Results of this study indicate that IMOC may allow the use of high-resolution, low-sensitivity collimation for SPECT studies, which have traditionally provided photon yields too low for useful imaging.