Acute infectious epiglottitis in children and adults: annual incidence and mortality

The incidence and mortality of acute epiglottitis were retrospectively analysed covering a 12-year period, 1975-1987. The diagnosis was made by the laryngoscopic findings in 95% of patients. Based on 902 hospitalized patients, a mean annual incidence of 4.9 cases per 100,000 children and adults was found. Although adult patients predominated (60%), the incidence was far higher in children, 13.8 per 100,000 compared with 3.9 per 100,000 in adults. Two peaks in incidence were identified, one for the youngest children, and the second for young adults (15-29 years). Over the years the incidence varied little in adults, but decreased significantly in children over the last 6 years studied. The data presented indicate acute epiglottitis to be a more frequent disorder than previously believed but with less risk of a fatal outcome. The mortality rate was below 1% in children and adults and the annual incidence of death from acute epiglottitis was estimated at 0.5 cases per million. The primary admission of these patients to ENT units seems to be the single factor having the most powerful impact on mortality.     

Diagnosis of gastrointestinal stromal tumors: A consensus approach

As a result of major recent advances in understanding the biology of gastrointestinal stromal tumors (GISTs), specifically recognition of the central role of activating KIT mutations and associated KIT protein expression in these lesions, and the development of novel and effective therapy for GISTs using the receptor tyrosine kinase inhibitor STI-571, these tumors have become the focus of considerable attention by pathologists, clinicians, and patients. Stromal/mesenchymal tumors of the gastrointestinal tract have long been a source of confusion and controversy with regard to classification, line(s) of differentiation, and prognostication. Characterization of the KIT pathway and its phenotypic implications has helped to resolve some but not all of these issues. Given the now critical role of accurate and reproducible pathologic diagnosis in ensuring appropriate treatment for patients with GIST, the National Institutes of Health convened a GIST workshop in April 2001 with the goal of developing a consensus approach to diagnosis and morphologic prognostication. Key elements of the consensus, as described herein, are the defining role of KIT immunopositivity in diagnosis and a proposed scheme for estimating metastatic risk in these lesions, based on tumor size and mitotic count, recognizing that it is probably unwise to use the definitive term "benign" for any GIST, at least at the present time.     

Digital detection of genetic mutations using SPC-sequencing

Deletion or insertion mutations lead to a frameshift that causes misalignment between wild-type and mutated allele sequences, making it difficult to identify such mutations unambiguously by using electrophoresis-based DNA sequencing. We have previously established the feasibility of an accurate DNA sequencing method using solid-phase capturable (SPC) dideoxynucleotides and MALDI-TOF mass spectrometry on synthetic templates, an approach we refer to as SPC-sequencing. Here, we report the application of SPC-sequencing in characterizing frameshift mutations by using the detection of the BRCA1 gene mutations 185delAG and 5382insC as examples. In this method, Sanger DNA sequencing fragments are generated in one tube by using biotinylated dideoxynucleotides. The sequencing fragments carrying a biotin moiety at the 3' end are captured on a streptavidin-coated solid phase to eliminate excess primer, primer dimers, and false stops. Only correctly terminated DNA fragments are captured, subsequently released, and analyzed by mass spectrometry to obtain digital DNA sequencing data. This method produces distinct doublet mass peaks at each point in the mass spectrum beyond the mutation site, facilitating the accurate characterization of the mutation. We have compared SPC-sequencing with electrophoresis-based sequencing in characterizing the above BRCA1 mutations, demonstrating the significant advantage offered by SPC-sequencing for the accurate identification of frameshift mutations.     

Stromal tumors of the gastrointestinal tract: myogenic or neurogenic?

Because of the recent controversy over the histogenesis of gastrointestinal stromal tumors, 170 gastrointestinal tract tumors appearing to be of smooth muscle type with routine stains were studied immunohistochemically. Five percent were positive for S-100 ("neural") protein. These findings are compared with several recent studies. We conclude that only a small minority of gastrointestinal tract stromal tumors are neurogenic and that most are probably of smooth muscle type.     

Eroded Polypoid Hyperplasia of the Rectosigmoid

We studied histologic sections and clinical data from six patients with multiple rectosigmoid polyps that could not be readily classified. Features common to all were: 1) numerous polyps restricted to the rectosigmoid colon without evidence of polyposis or gastrointestinal disease elsewhere, 2) severe clinical symptoms mimicking inflammatory bowel disease, 3) no family history of polyposis or evidence of infection and 4) histology showing minimally inflamed polypoid hyperplastic mucosa with surface erosions or pseudomembranes. Three patients underwent colectomies; three showed a response to oral steroids. One had rectal prolapse. Although reminiscent of inflammatory cloacogenic polyps or solitary rectal ulcer syndrome, the polyps extended into the sigmoid colon, were quite numerous, and showed only mild smooth muscle insinuation in the lamina propria. Whether these lesions are due to occult prolapse or are an unusual manifestation of inflammatory bowel disease remains unclear.     

Early chronic lead exposure reduces exploratory activity in young C57BL/6J mice

Research has suggested that chronic low‐level lead exposure diminishes neurocognitive function in children. Tests that are sensitive to behavioral effects at lowest levels of lead exposure are needed for the development of animal models. In this study we investigated the effects of chronic low‐level lead exposure on exploratory activity (unbaited nose poke task), exploratory ambulation (open field task) and motor coordination (Rotarod task) in pre‐adolescent mice. C57BL/6J pups were exposed to 0 ppm (controls), 30 ppm (low‐dose) or 230 ppm (high‐dose) lead acetate via dams’ drinking water administered from birth to postnatal day 28, to achieve a range of blood lead levels (BLLs) from not detectable to 14.84 µg dl^–1). At postnatal day 28, mice completed behavioral testing and were killed (n = 61). BLLs were determined by inductively coupled plasma mass spectrometry. The effects of lead exposure on behavior were tested using generalized linear mixed model analyses with BLL, sex and the interaction as fixed effects, and litter as the random effect. BLL predicted decreased exploratory activity and no threshold of effect was apparent. As BLL increased, nose pokes decreased. The C57BL/6J mouse is a useful model for examining effects of early chronic low‐level lead exposure on behavior. In the C57BL/6J mouse, the unbaited nose poke task is sensitive to the effects of early chronic low‐level lead exposure. This is the first animal study to show behavioral effects in pre‐adolescent lead‐exposed mice with BLL below 5 µg dl^–1. Copyright © 2014 John Wiley & Sons, Ltd.     

Changes in the microvasculature with age

The microvasculature of various organs of the rat and of the mesentery of the cat were examined for histochemical changes as a function of age, using the periodic acid-Schiff (PAS) reaction. Arterioles, minute arteries, and nonmuscular venules were histochemically unchanged to approximately 17 months of age in the rat and 8 years in the cat. Subsequently, focal areas of PAS-positive material developed in the media of arterioles and small arteries and increased in extent and severity with age. The adventitia of nonmuscular venules normally stains slightly positive due to the mucopolysaccharide coating of collagen fibers. With age this adventitial layer becomes more intensely PAS-positive. In the 26-month-old rat and 19-year-old cat, the media of arterioles and small arteries were extensively hyalinized. Lesions of arteriosclerosis were not present. These observations, in consort with prior observations of others in various mammals, indicate that there is a regular systematic alteration of various elements of the microcirculation with age. A possible relationship between these anatomical changes and tissue exchange is considered.     

Serum selenium and colonic neoplastic risk

BACKGROUND: Selenium deficiency has been associated with cancer risk in several organs. This association was investigated in neoplasia of the colorectum. DESIGN: A case-control study is reported with two patient series, colorectal cancer and colorectal adenomatous polyps, and a control group found to be free of colorectal neoplasia. Diagnosis was determined by colonoscopy and histologic review of suspected neoplasms. Serum drawn at the time of colonoscopy was subsequently assayed for selenium content, and quartiles based on selenium were defined. Crude and adjusted odds ratios with 95 percent confidence intervals for adenoma related to selenium were calculated, controlling for known or suspected risk factors including gender, age, race, body mass index, family history, tobacco use, alcohol consumption, serum beta carotene, serum alpha tocopherol, and serum ferritin. RESULTS: There were 138 controls who had no neoplastic disease, 139 adenoma patients, and 25 cancer patients. For adenoma,comparing higher quartiles of selenium to the first (lowest selenium), the adjusted odds ratio for the second quartile was 1.7 (95 percent confidence interval, 0.8–3.7), the third quartile was 1.4 (0.7–3.2), and the fourth (highest selenium) quartile was 1.8 (0.9–4). The odds ratios for cancer patients were 0.8 for the second quartile, 1 for the third quartile, and 1.7 for the fourth quartile. CONCLUSION: No trend could be detected toward a protective effect of higher levels of serum selenium for colonic benign or malignant tumors.Supported by grants from The American Society of Colon and Rectal Surgeons Research Foundation, the Department of Clinical Investigation of Walter Reed Army Medical Center, and Public Health Service Grant CA 36978.Address reprint requests to Dr. Nelson: 1740 West Taylor, Room 2204, M/C 957, Chicago, Illinois 60612.     

Early chronic low-level lead exposure produces glomerular hypertrophy in young C57BL/6J mice

Early chronic lead exposure continues to pose serious health risks for children, particularly those living in lower socioeconomic environments. This study examined effects on developing glomeruli in young C57BL/6J mice exposed to low (30 ppm), higher (330 ppm) or no lead via dams’ drinking water from birth to sacrifice on post-natal day 28. Low-level lead exposed mice [BLL mean (SD); 3.19 (0.70) μg/dL] had an increase in glomerular volume but no change in podocyte number compared to control mice [0.03 (0.01) μg/dL]. Higher-level lead exposed mice [14.68 (2.74) μg/dL] had no change in either glomerular volume or podocyte number. The increase in glomerular volume was explained by increases in glomerular capillary and mesangial volumes with no change in podocyte volume. Early chronic lead exposure yielding very low blood lead levels alters glomerular development in pre-adolescent animals.     

Acute wound repair in an aged animal: a model for accelerated aging of the microvasculature?

This study of wound repair in the aged rat is based on increased carbohydrate content of various proteins which occurs with aging and is readily seen in the microvasculature (MV). We have used the periodic acid-Schiff (PAS) reaction to identify histochemically the carbohydrate moiety of the glycoproteins found in these blood vessels. In the young rat, as in other young vertebrates, elements of the MV are PAS negative and become increasingly PAS+ beyond the half life span. During acute wound repair in an old animal, the new capillaries and venules are PAS- 2 weeks after injury, moderately PAS+ at 4 weeks, and intensely PAS+ at 8 weeks. Arterioles are present and PAS+ at 6 weeks, and intensively positive at 8 weeks, comparable to vessels remote from the wound site. The MV in wound repair in a young animal remains PAS- throughout healing. Rapid aging of the microvasculature in wound repair in an old animal reproduces histochemically the aging which occurs progressively during the prior 24 months. These histochemical changes may result from successive enzymatic and nonenzymatic glycosylation of the various basement membrane proteins in the microvasculature in both normal aging and wound repair in the aged animal. The latter may serve as a model for study of accelerated aging.