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Biomedical subjects

N Stone

Publications and source records attributed to N Stone.

At least 19 recordsLinked to original sources
PubMed2007

Optical adjuncts for enhanced colonoscopic diagnosis.

BACKGROUND: Optical techniques using previously unexploited properties of light interaction with tissue may be valuable in the detection, diagnosis and staging of colorectal neoplasia. METHODS: A Medline search (1990 to present) was conducted on optical diagnostics in the detection of colorectal neoplasia. The reference list of each identified article was reviewed for further relevant papers. RESULTS AND CONCLUSION: Chromoendoscopy is the only optical adjunct to colonoscopy that has been tested in large randomized clinical trials. It improves the detection of small and flat colorectal adenomas, and of neoplasia in chronic ulcerative colitis and hereditary non-polyposis colorectal cancer. All other techniques are the subject of ongoing research and the practicality of population screening with any of the methods has yet to be established. Optical techniques may, however, permit immediate clinical diagnosis, removing the need for histological analysis. They may also improve the diagnosis of early colonic neoplasia.

Colonoscopy↗
PubMed2006

Coulomb blockade anisotropic magnetoresistance effect in a (Ga,Mn)As single-electron transistor.

We observe low-field hysteretic magnetoresistance in a (Ga,Mn)As single-electron transistor which can exceed 3 orders of magnitude. The sign and size of the magnetoresistance signal are controlled by the gate voltage. Experimental data are interpreted in terms of electrochemical shifts associated with magnetization rotations. This Coulomb blockade anisotropic magnetoresistance is distinct from previously observed anisotropic magnetoresistance effects as it occurs when the anisotropy in a band structure derived parameter is comparable to an independent scale, the single-electron charging energy. Effective kinetic-exchange model calculations in (Ga,Mn)As show chemical potential anisotropies consistent with experiment and ab initio calculations in transition metal systems suggest that this generic effect persists to high temperatures in metal ferromagnets with strong spin-orbit coupling.

Journal Article↗
PubMed2006

How, not just if, condoms are used: the timing of condom application and removal during vaginal sex among young people in England.

OBJECTIVE: To assess the prevalence of, and factors associated with, vaginal penetration before condom application and following condom removal among young people in education in England. METHOD: A large cross sectional survey (n = 1373) was conducted in educational establishments in England and sexual event diaries were completed by a subsample of young people over a 6 month period. RESULTS: Of the 375 survey respondents who reported having used a condom on the most recent occasion of vaginal sex, 6% had applied the condom after penetration and 6% had continued penetration after condom removal. Of the 74 diary respondents, 31% applied a condom late and 9% removed a condom early at least once over a 6 month period. The odds of "imperfect" condom use were found to decrease with overall consistency of condom use, confidence in correct condom use, positive reported relationship with mother, non-use of other contraception, and desire to use a condom. CONCLUSION: Given that late application and early removal of condoms fail to maximise their effectiveness as a method of STI prevention, it is important to address "imperfect" condom use and the factors associated with such use in public health policies and programmes. It is essential that young people understand the importance of using condoms consistently and correctly, and are also equipped with the skills and knowledge to do so.

Adolescent↗
PubMed2006

Raman spectroscopy: elucidation of biochemical changes in carcinogenesis of oesophagus.

Several techniques are under development to diagnose oesophageal adenocarcinoma at an earlier stage. We have demonstrated the potential of Raman spectroscopy, an optical diagnostic technique, for the identification and classification of malignant changes. However, there is no clear recognition of the biochemical changes that distinguish between the different stages of disease. Our aim is to understand these changes through Raman mapping studies. Raman spectral mapping was used to analyse 20-microm sections of tissue from 29 snap-frozen oesophageal biopsies. Contiguous haematoxylin and eosin sections were reviewed by a consultant pathologist. Principal component analysis was used to identify the major differences between the spectra across each map. Pseudocolour score maps were generated and the peaks of corresponding loads identified enabling visualisation of the biochemical changes associated with malignancy. Changes were noted in the distribution of DNA, glycogen, lipids and proteins. The mean spectra obtained from selected regions demonstrate increased levels of glycogen in the squamous area compared with increased DNA levels in the abnormal region. Raman spectroscopy is a highly sensitive and specific technique for demonstration of biochemical changes in the carcinogenesis of Barrett's oesophagus. There is potential for in vivo application for real-time endoscopic optical diagnosis.

Adenocarcinoma↗
PubMed2006

Estimating population size of endangered brush-tailed rock-wallaby (Petrogale penicillata) colonies using faecal DNA.

The brush-tailed rock-wallaby (Petrogale penicillata) is an endangered species in southeastern Australia and many of the remaining populations are declining. The steep rocky habitat and shy nature of the species make it difficult to obtain data on population parameters such as abundance and recruitment. Faecal pellet counts from scat plots are commonly used to monitor population trends but these are imprecise and difficult to relate to absolute population size. We conducted a noninvasive genetic sampling 'mark-recapture' study over a 2-year period to identify individuals from faecal DNA samples and estimate the population size of four brush-tailed rock-wallaby colonies located in Wollemi National Park, New South Wales. Scat plots in rock-wallaby colonies were used as sample collection points for this study. Two separate population estimates were carried out for three of the colonies to determine if we could detect recruitment and changes in population size. We determined that there was one large colony of an estimated 67 individuals (95% confidence interval: 55-91) and three smaller colonies. Monitoring of the smaller colonies also detected possible population size increases in all three. Our results indicate that faecal DNA analysis may be a promising method for estimating and monitoring population trends in this species particularly when used with a traditional field survey method.

Animals↗
PubMed2005

The use of Raman spectroscopy to differentiate between different prostatic adenocarcinoma cell lines.

Raman spectroscopy (RS) is an optical technique that provides an objective method of pathological diagnosis based on the molecular composition of tissue. Studies have shown that the technique can accurately identify and grade prostatic adenocarcinoma (CaP) in vitro. This study aimed to determine whether RS was able to differentiate between CaP cell lines of varying degrees of biological aggressiveness. Raman spectra were measured from two well-differentiated, androgen-sensitive cell lines (LNCaP and PCa 2b) and two poorly differentiated, androgen-insensitive cell lines (DU145 and PC 3). Principal component analysis was used to study the molecular differences that exist between cell lines and, in conjunction with linear discriminant analysis, was applied to 200 spectra to construct a diagnostic algorithm capable of differentiating between the different cell lines. The algorithm was able to identify the cell line of each individual cell with an overall sensitivity of 98% and a specificity of 99%. The results further demonstrate the ability of RS to differentiate between CaP samples of varying biological aggressiveness. RS shows promise for application in the diagnosis and grading of CaP in clinical practise as well as providing molecular information on CaP samples in a research setting.

Adenocarcinoma↗
PubMed2005

Assessment of fiberoptic near-infrared raman spectroscopy for diagnosis of bladder and prostate cancer.

OBJECTIVES: To determine whether a fiberoptic Raman system, suitable for in vivo use, is able to differentiate between benign and malignant bladder and prostate pathologic findings in vitro. Raman spectroscopy is an optical technique that provides a measure of the molecular composition of tissue by analyzing the way that tissue scatters laser light. Laboratory studies have shown that the technique can be used to identify and characterize transitional cell carcinoma and prostate adenocarcinoma in vitro. METHODS: A total of 220 Raman spectra were recorded from 29 snap-frozen bladder samples collected at cystoscopic procedures, and 197 Raman spectra were recorded from 38 snap-frozen prostate samples collected at transurethral resection of the prostate. The spectra were correlated with the histologic features and used to construct separate diagnostic algorithms for the bladder and prostate. These algorithms were tested as to their ability to determine the pathologic finding of a sample from its Raman spectrum. RESULTS: The bladder algorithm was able to differentiate benign samples (normal and cystitis) from malignant samples (transitional cell carcinoma), with an overall accuracy of 84%. The prostate algorithm was able to differentiate benign samples (benign prostatic hyperplasia and prostatitis) from malignant samples (prostate cancer), with an overall accuracy of 86%. CONCLUSIONS: The results of this study have demonstrated that the clinical Raman system can provide an accurate and objective method to diagnose prostate and bladder cancer in vitro. Because the Raman probe is suitable for use during endoscopic, laparoscopic, or open procedures, this work paves the way for in vivo studies.

Adenocarcinoma↗
PubMed2004

The use of Raman spectroscopy to identify and characterize transitional cell carcinoma in vitro.

OBJECTIVE: To determine whether Raman spectroscopy can be used to differentiate between normal, inflammatory and malignant bladder pathologies in vitro, and secondly if it can used to grade and stage transitional cell carcinoma (TCC). MATERIALS AND METHODS: In all, 1525 Raman spectra were measured from 75 bladder samples comprising normal bladder, cystitis, carcinoma in situ (CIS), TCC and adenocarcinoma. Multivariate analysis was applied to the spectral dataset to construct diagnostic algorithms; these were then tested for their ability to determine the histological diagnosis of each sample from its Raman spectrum. RESULTS: The diagnostic algorithms could be used to accurately differentiate among the pathological groups, in particular, a three-group algorithm differentiated among normal bladder, cystitis and TCC/CIS with sensitivities and specificities of > 90%. Algorithms could also accurately characterize TCC in terms of splitting them into low (G1/G2) or high (G3) grade and superficial (pTa) or invasive (pT1/pT2) stage. CONCLUSION: Raman spectroscopy can be used to accurately identify and grade/stage TCC in vitro. The technique therefore shows promise for use as an objective method to assist the pathologist in assessing bladder pathologies. Raman spectroscopy also has potential to provide immediate pathological diagnoses during surgical procedures. Following the promising results of this in vitro study, in vivo cystoscopic studies are planned.

Aged↗
PubMed2004

Effects of CaCl2 and MgCl2 on Fourier transform infrared spectra of lung cancer cells.

The cations Ca2+ and Mg2+ are two important factors in the growth and maintenance of living cells. The addition of Ca2+ to living cells can cause a change in the three-dimensional (3D) structure of calcium binding proteins. Therefore, we decided to study whether the addition of CaCl2 and MgCl2 to three in vitro growing lung cancer cell lines could cause changes that could be measured by Fourier Transform Infrared Spectroscopy. The addition of CaCl2 or MgCl2 to lung cancer cells caused an increase in absorbance of the trough at 1410 cm(-1). This translated into an inversion of the 1410/1395 cm(-1) ratio following the addition of CaCl2 or MgCl2 for all three lung cancer cell lines. Also, the amide I peak shifted from around 1631 cm(-1) to lower wavenumbers when CaCl2 or MgCl2 was added to cancer cells. Furthermore, the addition of these two substances caused a shift of the peak between 3290 and 3395 cm(-1). Finally, while the addition of CaCl2 to lung cancer cells was associated with an increased cell death, this was not the case following the addition of MgCl2. This would confirm that the changes seen in the spectra of all three cell lines are due to metabolic and ionic shifts rather than cell death.

Apoptosis↗
PubMed2003

The use of Raman spectroscopy to identify and grade prostatic adenocarcinoma in vitro.

Raman spectroscopy is an optical technique, which provides a measure of the molecular composition of tissue. Raman spectra were recorded in vitro from both benign and malignant prostate biopsies, and used to construct a diagnostic algorithm. The algorithm was able to correctly identify each pathological group studied with an overall accuracy of 89%. The technique shows promise as a method for objectively grading prostate cancer.

Adenocarcinoma↗
PubMed2003

Raman spectral mapping in the assessment of axillary lymph nodes in breast cancer.

This paper is the first reported description of Raman Spectroscopy in the assessment of axillary lymph nodes in breast cancer patients. Raman Spectroscopy is an inelastic scattering spectroscopic technique appropriate for the assessment of unprocessed complex biological tissues. Spectra represent biochemical signatures of the tissue under scrutiny. The described method of Raman spectral mapping produces false-color spectral images of lymph node sections. These can be compared with standard histopathology slides and white light images of nodal tissue. This method has the potential to allow the detailed biochemical assessment of heterogeneous lymph node features, and to contribute towards the development of an optical diagnostic tool for use in a clinical setting.

Breast Neoplasms↗
PubMed2001

Clinical staging of prostate cancer: reproducibility and clarification of issues.

The American Joint Committee on Cancer (AJCC) staging system for prostate cancer adopted in 1992 is based on tumor-node-metastasis (TNM) designations. It has been widely accepted for use in local and advanced disease. The purpose of this study was to assess reproducibility of staging among observers and to help clarify staging issues. Twelve prostate cancer cases were sent to 20 physicians with special expertise in prostate cancer including eight urologists, eight radiation oncologists, and four medical oncologists. Physicians were asked to assign a stage based on the 1992 AJCC clinical staging. The most frequently reported stage assigned to each case was taken to be the consensus. Agreement was the percentage of physicians who reported that particular stage. Seventy-five percent of the physicians responded. The overall agreement for assignment of T stage was 63.9%. Differences were found by specialty for inclusion of available information in designating a T stage. The overall agreement for N stage was 73.8%. The most common designation was Nx regardless of availability of a computed tomography scan. The overall agreement for M stage was 76.6%. Without a bone scan the most common designation was Mx regardless of Gleason grade or prostate-specific antigen (PSA). A frequent comment was that PSA was more indicative of disease extent than current clinical staging. The reproducibility of the 1992 clinical AJCC staging is poor even among experts in the field. This problem arises primarily from disagreement regarding which studies are included in assigning a stage. Some of these difficulties are addressed in the 1997 revision. However, the clinical staging does not address the true biological significance of disease in many instances.

Humans↗
PubMed2001

Review article: the potential role for photodynamic therapy in the management of upper gastrointestinal disease.

Photodynamic therapy involves the activation of an exogenously administered, or an endogenously generated, photosensitizer with light to produce localized tissue destruction. It is an attractive, predominantly endoscopic technique for the palliation of advanced upper gastrointestinal cancer and the eradication of early neoplastic and pre-neoplastic lesions. The nature of the biological response allowing safe healing and the exploitation of tissue threshold effects mean that adjacent tissue damage can be minimized. This review used a database of 368 papers. The nature of the photosensitizer is critical to the depth of tissue damage and the risk of adjacent tissue damage and stricture formation. The generation of protoporphyrin IX following administration of 5-aminolaevulinic acid has proved useful for the treatment of high-grade dysplasia in Barrett's oesophagus. A double-blind randomized placebo controlled trial has confirmed that it is a safe and effective method for the ablation of low-grade dysplasia. The treatment of more advanced lesions requires exogenously administered photo-sensitizers. However, recent data indicate that the neoplastic potential remains in some patients and continued follow-up is necessary. Photodynamic therapy can be used to eradicate early neoplasia and palliate advanced cancer, but caution is required before a definitive cure can be claimed.

Barrett Esophagus↗
PubMed2001

Trends in Gleason score for prostate cancer diagnosed between 1983 and 1993.

PURPOSE: During the 1980s and 1990s the number, incidence rate and proportion of moderately differentiated prostate cancer cases ascertained by population based cancer registries increased substantially. The increase is thought to have resulted from the widespread use of prostate specific antigen (PSA) for screening because it occurred coincidentally with the introduction of PSA for early detection of prostate cancer. We investigate this increase in a population based study. MATERIALS AND METHODS: To report the trends in tumor grade we conducted a blinded, standardized pathological study and reviewed medial records of a stratified random sample of cases diagnosed before and after the introduction of PSA (1983 to 1984 and 1992 to 1993). Archival tumor biopsy specimens or transurethral resection of the prostate specimens were reviewed for the diagnosis of cancer and assignment of Gleason score. Medical records were reviewed to determine the method of prostate cancer detection for each case. RESULTS: We found a small but statistically insignificant shift in the distribution of Gleason scores assigned after review of biopsy or transurethral resection specimens. The proportion of Gleason score 2, 3 and 4 tumors decreased, and the proportion of 7, 8, 9 and 10 tumors as a group did not change. The shifts in Gleason score resulted in a slight statistically nonsignificant increase in mean Gleason score. There was a significant shift in the method of detection from predominately incidental detection in the earlier period to predominately screen detection in the later period. Because the proportion of screen detected tumors increased and they had a significantly higher mean Gleason score than incidentally detected tumors within each interval, the overall mean Gleason score increased. CONCLUSIONS: After a standardized pathological review a small shift in the distribution of Gleason scores occurred resulting in a small increase in mean Gleason score between 1983 and 1984, and 1992 and 1993. There was little change in the proportion of Gleason score 7, 8, 9 and 10 tumors between the 2 periods.

Adenocarcinoma↗
PubMed2001

Caspase-mediated cleavage of the TIAM1 guanine nucleotide exchange factor during apoptosis.

Rho family GTPases Rac and Cdc42 are pivotal regulators of apoptosis in multiple cell types. However, little is known about the mechanism by which these GTPases are regulated in response to apoptotic stimuli. Here, we demonstrate that TIAM1, a Rac-specific guanine nucleotide exchange factor, is cleaved by caspases during apoptosis. TIAM1 cleavage occurs in multiple cell lines in response to diverse apoptotic stimuli such as ceramide, Fas, and serum deprivation. Processing occurs at residue 993 of TIAM1 and removes the NH(2)-terminal of TIAM's two pleckstrin homology domains, leaving a stable fragment containing the Dbl homology and COOH-terminal pleckstrin homology domains. This leads to functional inactivation of TIAM1, as determined by failure of the cleavage product to stimulate GTP loading of Rac in vivo. Furthermore, this product is defective in signaling to two independent Rac effectors, c-Jun NH(2)-terminal kinase and serum response factor. Finally, we demonstrate that in cells treated with ceramide, cleavage of TIAM1 coincided with the inactivation of endogenous Rac. These results reveal a novel mechanism for regulating guanine nucleotide exchange factor activity and GTPase-mediated signaling pathways.

3T3 Cells↗