Phenotype and management of patients with familial adenomatous polyposis in Hong Kong: perspective of the Hereditary Gastrointestinal Cancer Registry.

OBJECTIVES: To report on the phenotypic spectrum and clinical management of Chinese patients suffering from the rare autosomal dominant colorectal cancer syndrome of familial adenomatous polyposis. DESIGN: Analysis of prospectively collected data from the database of a regional registry. SETTING: The Hereditary Gastrointestinal Cancer Registry, Hong Kong. PARTICIPANTS: One hundred and eight patients with proven familial adenomatous polyposis from 36 local Chinese families with the condition recruited to the Registry from 1995 to 2001. INTERVENTIONS: Screening programme for at-risk family members, prophylactic surgery at presymptomatic diagnosis, and surveillance programme for extracolonic lesions in affected individuals. MAIN OUTCOME MEASURES: Rate of colorectal cancer, type of surgical treatment, spectrum of extracolonic lesions, and management of the syndrome. RESULTS: Fifty patients suffered from colorectal cancer with a mortality rate of 78.0%. The strategy of presymptomatic diagnosis by screening and appropriate prophylactic surgery reduced the incidence of colorectal cancer. Affected individuals were prone to develop potentially serious extracolonic lesions including thyroid cancer (5.7%), desmoid tumour (15.7%), gastroduodenal adenomas (7.1%), duodenal microadenoma (17.1%), and pouch polyposis (17.4%). CONCLUSIONS: Screening and prophylactic surgery are effective ways to prevent colorectal cancer for patients with familial adenomatous polyposis. Lifelong regular surveillance is necessary to detect and manage extracolonic lesions. A dedicated registry is essential to coordinate clinical management and to compile data for furthering knowledge of this rare but complex syndrome.published_or_final_versio

Assessment and in vivo scoring of murine experimental autoimmune uveoretinitis using optical coherence tomography

Despite advances in clinical imaging and grading our understanding of retinal immune responses and their morphological correlates in experimental autoimmune uveoretinitis (EAU), has been hindered by the requirement for post-mortem histology. To date, monitoring changes occurring during EAU disease progression and evaluating the effect of therapeutic intervention in real time has not been possible. We wanted to establish whether optical coherence tomography (OCT) could detect intraretinal changes during inflammation and to determine its utility as a tool for accurate scoring of EAU. EAU was induced in C57BL/6J mice and animals evaluated after 15, 26, 36 and 60 days. At each time-point, contemporaneous Spectralis-OCT scanning, topical endoscopic fundal imaging (TEFI), fundus fluorescein angiography (FFA) and CD45-immunolabelled histology were performed. OCT features were further characterised on retinal flat-mounts using immunohistochemistry and 3D reconstruction. Optic disc swelling and vitreous opacities detected by OCT corresponded to CD45+ cell infiltration on histology. Vasculitis identified by FFA and OCT matched perivascular myeloid and T-cell infiltrates and could be differentiated from unaffected vessels. Evolution of these changes could be followed over time in the same eye. Retinal folds were visible and found to encapsulate mixed populations of activated myeloid cells, T-cells and microglia. Using these features, an OCT-based EAU scoring system was developed, with significant correlation to validated histological (Pearson r(2) = 0.6392, P<0.0001, n = 31 eyes) and TEFI based scoring systems (r(2) = 0.6784, P<0.0001). OCT distinguishes the fundamental features of murine EAU in vivo, permits dynamic assessment of intraretinal changes and can be used to score disease severity. As a result, it allows tissue synchronisation with subsequent cellular and functional assessment and greater efficiency of animal usage. By relating OCT signals with immunohistochemistry in EAU, our findings offer the opportunity to inform the interpretation of OCT changes in human uveitis

Pulmonary artery sarcoma diagnosed by endobronchial ultrasound-guided transbronchial needle aspiration

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Microwave enhanced ion-cut silicon layer transfer

Microwave heating has been used to decrease the time required for exfoliation of thin single-crystalline silicon layers onto insulator substrates using ion-cut processing. Samples exfoliated in a 2.45 GHz, 1300 W cavity applicator microwave system saw a decrease in incubation times as compared to conventional anneal processes. Rutherford backscattering spectrometry, cross sectional scanning electron microscopy, cross sectional transmission electron microscopy, and selective aperture electron diffraction were used to determine the transferred layer thickness and crystalline quality. The surface quality was determined by atomic force microscopy. Hall measurements were used to determine electrical properties as a function of radiation repair anneal times. Results of physical and electrical characterizations demonstrate that the end products of microwave enhanced ion-cut processing do not appreciably differ from those using more traditional means of exfoliation. © 2007 American Institute of Physics

Reading Single DNA with DNA Polymerase Followed by Atomic Force Microscopy

The importance of DNA sequencing in the life sciences and personalized medicine is continually increasing. Single-molecule sequencing methods have been developed to analyze DNA directly without the need for amplification. Here, we present a new approach to sequencing single DNA molecules using atomic force microscopy (AFM). In our approach, four surface conjugated nucleotides were examined sequentially with a DNA polymerase immobilized AFM tip. By observing the specific rupture events upon examination of a matching nucleotide, we could determine the template base bound in the polymerase&apos;s active site. The subsequent incorporation of the complementary base in solution enabled the next base to be read. Additionally, we observed that the DNA polymerase could incorporate the surface-conjugated dGTP when the applied force was controlled by employing the force-clamp mode.X1114Ysciescopu

The Novel CYP2A6 Inhibitor, DLCI-1, Decreases Nicotine Self-Administration in Mice.

During tobacco and e-cigarette use, nicotine is mainly metabolized in the human liver by cytochrome P450 2A6 (CYP2A6). Given that a slower CYP2A6 metabolism has been associated with less vulnerability to develop nicotine dependence, the current studies sought to validate a novel CYP2A6 inhibitor, (5-(4-ethylpyridin-3-yl)thiophen-2-yl)methanamine (DLCI-1), for its effects on intravenous nicotine self-administration. Male and female mice were trained to self-administer nicotine across daily sessions. Once stable responding was achieved, DLCI-1 or vehicle control was administered prior to nicotine sessions. We found that the lower 25 mg/kg and moderate 50 mg/kg doses of DLCI-1 induced a significant decrease in nicotine intake for both males and females. DLCI-1 was further shown to be more effective than a moderate 1 mg/kg dose of bupropion on reducing nicotine intake and did not exert the adverse behavioral effects found with a high 75 mg/kg dose of bupropion. Although mice treated with DLCI-1 self-administered significantly less nicotine, similar nicotine-mediated behavioral effects on locomotion were observed. Together, along with the analysis of nicotine metabolites during self-administration, these findings support the contention that blocking hepatic nicotine metabolism would allow for similar activation of nicotinic acetylcholine receptors at lower nicotine doses. Moreover, these effects of DLCI-1 were specific to nicotine self-administration, as DLCI-1 did not result in any behavioral changes during food self-administration. Taken together, these studies validate DLCI-1 as a novel compound to decrease nicotine consumption, which may thereby promote tobacco and nicotine product cessation. SIGNIFICANCE STATEMENT: Current pharmacological approaches for nicotine and tobacco cessation have only been able to achieve limited efficaciousness in promoting long-term abstinence. In this work, we characterize the effects of a novel compound, (5-(4-ethylpyridin-3-yl)thiophen-2-yl)methanamine (DLCI-1), which inhibits the main enzyme that metabolizes nicotine, and we report a significant decrease in intravenous nicotine self-administration in male and female mice, supporting the potential of DLCI-1 as a novel tobacco cessation pharmacotherapeutic

Stability of Mine Car Motion in Curves of Invariable and Variable Radii

We discuss our experiences adapting three recent algorithms for maximum common (connected) subgraph problems to exploit multi-core parallelism. These algorithms do not easily lend themselves to parallel search, as the search trees are extremely irregular, making balanced work distribution hard, and runtimes are very sensitive to value-ordering heuristic behaviour. Nonetheless, our results show that each algorithm can be parallelised successfully, with the threaded algorithms we create being clearly better than the sequential ones. We then look in more detail at the results, and discuss how speedups should be measured for this kind of algorithm. Because of the difficulty in quantifying an average speedup when so-called anomalous speedups (superlinear and sublinear) are common, we propose a new measure called aggregate speedup

Plasma hydrogenation of strained Si/SiGe/Si heterostructure for layer transfer without ion implantation

We have developed an innovative approach without the use of ion implantation to transfer a high-quality thin Si layer for the fabrication of silicon-on-insulator wafers. The technique uses a buried strained SiGe layer, a few nanometers in thickness, to provide H trapping centers. In conjunction with H plasma hydrogenation, lift-off of the top Si layer can be realized with cleavage occurring at the depth of the strained SiGe layer. This technique avoids irradiation damage within the top Si layer that typically results from ion implantation used to create H trapping regions in the conventional ion-cut method. We explain the strain-facilitated layer transfer as being due to preferential vacancy aggregation within the strained layer and subsequent trapping of hydrogen, which lead to cracking in a well controlled manner. © 2005 American Institute of Physics

Studies on the clinical significance of nonesterified and total cholesterol in urine

Gas-liquid chromatographic determinations of nonesterified and total urinary cholesterol were performed in 137 normals, 264 patients with various internal diseases without evidence of neoplasias or diseases of the kidney or urinary tract, 497 patients with malignancies and 236 patients with diseases of the kidney, urinary tract infections or prostatic adenoma with residual urine. A normal range (mean±2 SD) of 0.2–2.2 mg/24 hours nonesterified cholesterol (NEC) and of 0.3–3.0 mg/24 hours total cholesterol (TC) was calculated. Values of urinary cholesterol excretion were independent of age and sex and did not correlate with cholesterol levels in plasma. Patients with various internal diseases, without evidence of neoplasias nor diseases of the kidney or obstruction of the urinary tract, showed normal urinary cholesterol excretions, as did patients with infections of the urinary tract. However, elevated urinary cholesterol was found in patients with diseases of the kidney or urinary tract obstruction (prostatic adenoma with residual urine), malignant diseases of the urogenital tract and metastasing carcinoma of the breast. In patients with other malignant diseases urinary cholesterol was usually normal. Lesions of the urothelial cell membranes are considered to be the most likely cause of urinary cholesterol hyperexcretion. The clinical value of urinary cholesterol determinations as a possible screening test for urogenital carcinomas in unselected populations is limited by lacking specificity, expensive methodology and low prevalence of the mentioned carcinomas, although elevated urinary cholesterol excretions have been observed in early clinical stages of urogenital cancers