Frozen section analysis of esophageal endoscopic mucosal resection specimens in the real-time management of Barrett's esophagus.

BACKGROUND & AIMS: The aim of this study was to assess the validity of frozen section analysis of endoscopic mucosal resection (EMR) specimens from Barrett's esophagus as compared with permanent sections for the detection of neoplasia. Frozen sections help to give immediate feedback for surgical procedures. It has not been determined whether EMR can be adequately interpreted by using frozen sections to aid endoscopists in completely resecting neoplastic lesions. METHODS: EMR specimens from Barrett's esophagus with high-grade dysplasia (HGD) and/or carcinoma were tested by frozen section. Pathologists evaluated EMR specimens for the depth of invasion as well as the appearance of clear margins of resection. The kappa statistic was calculated to assess the degree of agreement between the frozen section and permanent section diagnoses. RESULTS: Twenty-three consecutive patients underwent 30 EMRs with frozen section diagnosis. Frozen section revealed a carcinoma in 7 specimens (23%) and dysplasia in 20 (66%). Permanent sections found carcinoma in 8 specimens (26%), dysplasia in 19 specimens (63%), and normal or nondysplastic Barrett's esophagus in the remainder. The kappa statistic for the depth of invasion of EMR specimens was 0.93 (near perfect agreement). The kappa statistic for the margins of the EMR specimens was 0.80 (excellent agreement). CONCLUSIONS: This study indicated that frozen section analysis of esophageal EMR specimens is valid as compared with permanent section. This technique might allow rapid evaluation about the degree and depth of involvement of cancers. This allows physicians to make decisions regarding further therapy if margins are involved or decrease the use of EMR for histologically benign-appearing lesions.     

Effect of naringin on bone cells.

Statin, a HMG-CoA reductase inhibitor, was shown to increase BMP-2 gene expression for bone formation, by blocking the mevalonate pathway in cholesterol production. We investigated the effect of naringin, a flavonoid available commonly in citrus fruits, which was also a HMG-CoA reductase inhibitor, in UMR 106 osteoblastic cell line in vitro. The control group consisted of cells cultured without any intervention for different time intervals (24 h, 48 h, and 72 h), whereas the experimental (naringin) group consisted of cells cultured with naringin of different concentrations (0.001 micromol/L, 0.01 micromol/L, and 0.1 micromol/L) for the same time intervals of the control. Colorimetric Tetrazolium (MTT) assay, total protein content assay, and alkaline phosphatase activity were used to measure the cellular activities. Results for the naringin group showed an increase in MTT assay compared with the control and the effect was dose dependent. At high concentration (0.1 micromol), the increases ranged from 60% to 80%. In the total protein content assay, naringin also showed an increase compared with control and the effect was also dose dependent. At high concentration (0.1 micromol), the increases ranged from 9% to 20%. In the alkaline phosphatase activity assay, naringin at high concentration (0.1 micromol) significantly increased the activity up to 20%. In conclusion, naringin significantly increased bone cell activities in vitro. This is the first study specifically attempted to investigate the effect of naringin on bone cell activities. Besides statin, this provided another example of mevalonate pathway blockage in the cholesterol production pathway by HMG-CoA reductase inhibition will increase the bone cell activities.     

Radiosensitivity of mouse skin epithelial cell line established in serum-free culture: an alternative to animal use.

A cultured line of murine skin epithelial cells was established to investigate the potential use of cultured cells as an alternative to animal use in radiation research. C3Hf/Sed newborn mouse skin cells have been successfully cultured in serum- and Ca(2+)-free medium with no terminal differentiation to keratinized cells. Presently, more than 25 passages have passed with no loss of stem cell capability. The radiosensitivity and repair of sublethal and potentially lethal radiation damages were investigated in this epithelial cell line. The population cell doubling time was 25 +/- 2.9 hr at 37 degrees C. The clonal growth of epithelial cells after irradiation was performed in the serum-free medium in the presence of lethally irradiated skin fibroblasts. Single dose survival curves of exponentially growing epithelial cells were investigated from the seventh to the twenty-third passages, and no significant changes in radiosensitivity and doubling time were found. The confluent epithelial cells also showed an identical sensitivity to radiation. The alpha/beta ratios of survival curves fitted by the linear quadratic model were 6.1 +/- 1.0 and 5.9 +/- 1.3 Gy for cells in exponential and confluent phases, respectively. The survival curve of epithelial cells left in confluence for 8 hr after irradiation showed a smaller beta value than that of cells plated immediately after irradiation with a resultant alpha/beta ratio of 9.5 +/- 3.8 Gy. This alpha/beta ratio was identical to those found in many animal experiments, suggesting a potential use of this cell line as an alternative to animal use. The magnitude of repair of sublethal damage following 6 Gy was greater than that following 3.9 Gy. Survival curves were also obtained following twice-a-day irradiations with no sign of rapid repopulation. These results are discussed by comparing with published in vivo and in vitro data.     

APOE epsilon3 gene transfer attenuates brain damage after experimental stroke.

Apolipoprotein E (apoE, protein; APOE, gene) is the major lipid-transport protein in the brain and plays an important role in modulating the outcome and regenerative processes after acute brain injury. The aim of the present study was to determine if gene transfer of the epsilon3 form of APOE improves outcome in a murine model of transient focal cerebral ischaemia. Mice received an intrastriatal injection of vehicle, a second-generation adenoviral vector containing the green fluorescent protein gene (Ad-GFP) or a vector containing the APOE epsilon3 gene (Ad-APOE) 3 days before 60 mins focal ischaemia. Green fluorescent protein expression was observed in cells throughout the striatum and subcortical white matter indicating successful gene transfer and expression. ApoE levels in the brain were significantly increased after Ad-APOE compared with Ad-GFP or vehicle treatment. Ad-APOE treatment reduced the volume of ischaemic damage by 50% compared with Ad-GFP or vehicle treatment (13+/-3 versus 29+/-4 versus 27+/-5 mm(3)). The extent of postischaemic apoE immunoreactivity was enhanced in Ad-APOE compared with Ad-GFP or vehicle treated mice. These results show the ability of APOE gene transfer to markedly improve outcome after cerebral ischaemia and suggest that modulating apoE levels may be a potential strategy in human stroke therapy.     

Improved bioavailability and clinical response in patients with chronic liver disease following the administration of a spironolactone: β-cyclodextrin complex

Aims To compare the absorption and clinical effect of spironolactone from an inclusion complex with β-cyclodextrin (SP-COMP) to Aldactone tablets (ALD) in chronic liver disease.
Methods Patients, admitted with chronic liver disease, completed a randomized crossover steady state study. They received their spironolactone dose as either daily SP-COMP or ALD for 7 days. Serial blood samples were drawn over a 24  h period from day 7 of each therapy. Accurate fluid balance was recorded on days 5–7 and 12–14. Thirteen (six females) whose mean (s.d.) age and weight was 58.4(9.3) years and 74.3(19.0)  kg completed the study.
Results The mean (95% confidence limits) relative bioavailability for SP-COMP (compared with ALD) from steady state serum concentrations of canrenone, 6β-hydroxyl 7α-thiomethyl spironolactone and 7α-thiomethyl spironolactone was 310.0 (265.4, 336.7), 233.4(212.9, 250.8) and 254.8(230.8, 279.0)%, respectively. Improvements in clinical status and fluid balance occurred over the last 3 days of SP-COMP with a mean (s.d.) net loss, in fluid balance, of 1370(860)ml compared with a gain of 228(936)ml during ALD.
Conclusions Better absorption of spironolactone from the spironolactone: β-cyclodextrin complex formulation should lead to a reduction in dosage and perhaps a more consistent effect in patients with chronic liver disease.     

Allergic contact dermatitis from grasses

This study attempts to demonstrate the existence of allergic contact dermatitis from grass, and to develop a patch test series to screen patients with grass intolerance. 6 common grass species from lawns and military training areas were collected. Solvent extracts of polar. non-polar and volatile fractions were prepared and used for patch testing in 20 control subjects and 46 patients with a history of grass intolerance. The 20 control had negative responses to patch testing. 5 out of 46 patients had positive patch tests to Axonopus compressus (carpet grass). Ischaenmum muticum (sea-shore centipede grass). Imperata evlindrica (lalang). Panicum maximum (Guinea grass) and Pennisetum purpureum (elephant grass). Reactions to the non-polar fraction for all 5 species were noted. This study demonstrates the existence of allergic contact dermatitis from various common species of grass. In our series, this is seen in 11% of those with a history of grass intolerance.     

Fundus biomicroscopy: a comparison of four methods

Funduscopic examination utilizing the biomicroscope is extremely valuable in the detection, diagnosis, and management of ocular disease. A variety of lenses are currently available for detailed examination of the posterior vitreous cavity and the retina. This paper discusses the optical principles and the various attributes of four lenses relative to magnification, field of view, clinical application and ease of use.     

Retrovirus-induced immunodeficiency in mice exacerbates gastrointestinal candidiasis.

Dysfunction of neutrophils in patients infected with human immunodeficiency virus is at least partly responsible for secondary microbial diseases in these individuals, including invasive gastrointestinal (GI) candidiasis. Immunoregulatory disturbances associated with the development of AIDS in human immunodeficiency virus-infected patients exacerbates Candida albicans infection of the upper GI tract and frequently leads to oropharyngeal and esophageal candidiasis. In this article, we present the first report of a murine model of invasive GI candidiasis associated with an AIDS-related murine immunodeficiency syndrome that results from infection of C57BL/6 mice with a previously described retrovirus complex (LP-BM5). Mice of the inbred strain were infected with C. albicans by oral-intragastric inoculation as infants and with the retrovirus by the intraperitoneal route 30 days later. Control mice of the same strain were infected with C. albicans as above and subsequently infected with the avirulent, ecotropic helper virus (MBI-5). Animals were killed 90 days after retroviral challenge. Total and differential blood cell counts, CD4+ T-cell counts in the spleen, and the histopathology of the gastric mucosa of experimental and control animals were determined. The virulent LP-BM5-infected animals developed murine AIDS and showed eruptive and suppurative lesions, with associated C. albicans mainly in regions of the cardial-atrium fold of the stomach. Well-defined abscesses with entrapped C. albicans hyphae were observed in the region of the cardial-atrium fold of control mice. A significant increase in the number of C. albicans CFU in homogenized and plated segments of the GI tract was recognized in mice with murine AIDS versus the control animals. The murine model of GI candidiasis reported here permits examination of the nature of C. albicans interaction with the gastric mucosa both in the immunocompetent host under conditions in which the yeast exists predominantly as a commensal organism and in the immunosuppressed host during progressive stages of AIDS induced by a retroviral infection.