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Biomedical subjects

H Barr

Publications and source records attributed to H Barr.

At least 19 recordsLinked to original sources
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↗
PubMed2004

Review article: screening and surveillance of Barrett's oesophagus: what is a cost-effective framework?

There is a strong association between symptomatic gastro-oesophageal reflux and oesophageal adenocarcinoma. With this in mind, the American College of Gastroenterology has recently revised its practice guidelines for the screening of patients with chronic gastro-oesophageal reflux disease (GERD) to identify those at risk of oesophageal adenocarcinoma, and recommends surveillance to identify curable oesophageal neoplasms in patients with established Barrett's oesophagus. Patients with chronic GERD symptoms, particularly those aged over 50 years, should undergo upper endoscopy. Patients found to have Barrett's oesophagus should be treated with acid suppression for GERD symptoms and then undergo regular surveillance endoscopy. Surveillance endoscopy every 3 years is recommended for those without dysplasia. For patients with verified low-grade dysplasia, yearly surveillance endoscopy is recommended. For those with focal high-grade dysplasia (defined as high-grade dysplastic changes involving fewer than five crypts), the condition may be followed with endoscopic surveillance performed at 3-month intervals. If there is verified, multifocal high-grade dysplasia, intervention (e.g. oesophagectomy) may be considered. Both observational and computer models suggest a benefit associated with screening and surveillance. Endoscopic screening and surveillance for Barrett's oesophagus compares favourably with mammography for the detection of breast cancer and other accepted medical practices.

Adenocarcinoma↗
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↗
PubMed2002

Medical applications of Raman spectroscopy: from proof of principle to clinical implementation.

Raman spectroscopy has recently been applied ex vivo and in vivo to address various biomedical issues such as the early detection of cancers, monitoring of the effect of various agents on the skin, determination of atherosclerotic plaque composition, and rapid identification of pathogenic microorganisms. This leap in the number of applications and the number of groups active in this field has been facilitated by several technological advancements in lasers, CCD detectors, and fiber-optic probes. However, most of the studies are still at the proof of concept stage. We present a discussion on the status of the field today, as well as the problems and issues that still need to be resolved to bring this technology to hospital settings (i.e., the medical laboratory, surgical suites, or clinics). Taken from the viewpoint of clinicians and medical analysts, the potential of Raman spectroscopic techniques as new tools for biomedical applications is discussed and a path is proposed for the clinical implementation of these techniques.

Arteriosclerosis↗
PubMed2001

Interprofessional education: effects on professional practice and health care outcomes.

BACKGROUND: As patient care becomes more complex, effective collaboration between health and social care professionals is required. However, evidence suggests that these professionals do not collaborate well together. Interprofessional education (IPE) offers a possible way forward in this area. OBJECTIVES: To assess the usefulness of IPE interventions compared to education in which the same professions were learning separately from one another. SEARCH STRATEGY: We searched the Cochrane Effective Practice and Organisation of Care Group specialised register, MEDLINE (1968 to 1998) and Cinahl (1982 to 1998). We also hand searched the Journal of Interprofessional Care (1992 to 1998), the Centre for the Advancement of Interprofessional Education Bulletin (1987 to 1998), conference proceedings, the 'grey literature' held by relevant organisations, and reference lists of articles. SELECTION CRITERIA: Randomised trials, controlled before and after studies and interrupted time series studies of IPE interventions designed to improve collaborative practice between health/social care practitioners and/or the health/well being of patients/clients. The participants included chiropodists/podiatrists, complementary therapists, dentists, dietitians, doctors/physicians, hygienists, psychologists, psychotherapists, midwives, nurses, pharmacists, physiotherapists, occupational therapists, radiographers, speech therapists and/or social workers. The outcomes included objectively measured or self reported (validated instrument) patient/client outcomes and reliable (objective or validated subjective) health care process measures. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the eligibility of potentially relevant studies. MAIN RESULTS: The total yield from the search strategy was 1042, of which 89 were retained for further consideration. However none of these studies met the inclusion criteria. REVIEWER'S CONCLUSIONS: Despite finding a large body of literature on the evaluation of IPE, these studies lacked the methodological rigour needed to begin to convincingly understand the impact of IPE on professional practice and/or health care outcomes.

Attitude of Health Personnel↗
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

The significance of cagA(+) Helicobacter pylori in reflux oesophagitis.

BACKGROUND: Helicobacter pylori is a gastroduodenal pathogen associated with ulceration, dyspepsia, and adenocarcinoma. Recent preliminary studies have suggested that H pylori may be protective for oesophageal adenocarcinoma. In addition, strains of H pylori identified by the presence of the cytotoxin associated gene A (cagA) are shown to have a significant inverse association with oesophageal adenocarcinoma. Given that cagA(+) H pylori may protect against oesophageal carcinoma, these strains may be protective for oesophagitis, a precursor of oesophageal carcinoma. AIMS: The aim of this study was to investigate the association between cagA(+) H pylori and endoscopically proved oesophagitis. PATIENTS: The study group included 1486 patients attending for routine upper gastrointestinal tract endoscopy. METHODS: At endoscopy the oesophagus was assessed for evidence of reflux disease and graded according to standard protocols. Culture and histology of gastric biopsy specimens determined H pylori status. The prevalence of cagA was identified by an antibody specific ELISA (Viva Diagnostika, Germany). RESULTS: H pylori was present in 663/1485 (45%) patients and in 120/312 (38%) patients with oesophagitis. Anti-CagA antibody was found in 499/640 (78%) H pylori positive patients. Similarly, anti-CagA antibody was found in 422/521 (81%) patients with a normal oesophagus and in 42/60 (70%) with mild, 24/35 (69%) with moderate, and 11/24 (46%) with severe oesophagitis. The risk of severe oesophagitis was significantly decreased for patients infected with cagA(+) H pylori after correction for confounding variables (odds ratio 0.57, 95% confidence interval 0.41-0.80; p=0.001). CONCLUSIONS: These results suggest that infection by cagA(+) H pylori may be protective for oesophageal disease.

Adult↗
PubMed2001

Sniffing out disease using the artificial nose.

Is there information in the odours that we emit and that circulate around us? More importantly, can doctors gain knowledge of disease by smelling their patients? Machines that emulate the mammalian nose have picked up the scent of several diseases and may drastically change diagnostic procedure.

Diagnostic Techniques and Procedures↗
PubMed2000

An intelligent rapid odour recognition model in discrimination of Helicobacter pylori and other gastroesophageal isolates in vitro.

Two series of experiments are reported which result in the discrimination between Helicobacter pylori and other bacterial gastroesophageal isolates using a newly developed odour generating system, an electronic nose and a hybrid intelligent odour recognition system. In the first series of experiments, after 5 h of growth (37 degrees C), 53 volatile 'sniffs' were collected over the headspace of complex broth cultures of the following clinical isolates: Staphylococcus aureus, Klebsiella sp., H. pylori, Enterococcus faecalis (10(7) ml(-1)), Mixed infection (Proteus mirabilis, Escherichia coli, and E. faecalis 3 x 10(6) ml each) and sterile cultures. Fifty-six normalised variables were extracted from 14 conductive polymer sensor responses and analysed by a 3-layer back propagation neural network (NN). The NN prediction rate achieved was 98% and the test data (37.7% of all data) was recognised correctly. Successful clustering of bacterial classes was also achieved by discriminant analysis (DA) of a normalised subset of sensor data. Cross-validation identified correctly seven 'unknown' samples. In the second series of experiments after 150 min of microaerobic growth at 37 degrees C, 24 volatile samples were collected over the headspace of H. pylori cultures in enriched (HPP) and normal (HP) media and 11 samples over sterile (N) cultures. Forty-eight sensor parameters were extracted from 12 sensor responses and analysed by a 3-layer NN previously optimised by a genetic algorithm (GA). GA-NN analysis achieved a 94% prediction rate of 'unknown' data. Additionally the 'genetically' selected 16 input neurones were used to perform DA-cross validation that showed a clear clustering of three groups and reclassified correctly nine 'sniffs'. It is concluded that the most important factors that govern the performance of an intelligent bacterial odour detection system are: (a) an odour generation mechanism, (b) a rapid odour delivery system similar to the mammalian olfactory system, (c) a gas sensor array of high reproducibility and (d) a hybrid intelligent model (expert system) which will enable the parallel use of GA-NNs and multivariate techniques.

Culture Media↗
PubMed2000

Raman spectroscopy for early detection of laryngeal malignancy: preliminary results.

OBJECTIVE: Raman spectroscopy, the analysis of scattered photons after monochromatic laser excitation, is well established in nonbiological sciences. Recently this method has been used to differentiate premalignant and malignant lesions from normal tissue. Its application for early diagnosis has been explored in a variety of sites (e.g., esophagus, cervix), but not, to date, in laryngeal cancer. The objective of this study was to perform a feasibility study of the use of Raman spectroscopy for early diagnosis of laryngeal malignancy. METHODS: Biopsy specimens were snap-frozen, and top sections were sent for histopathological analysis. Only homogenous samples with clearly defined pathological findings were used in this study: seven histologically normal samples, four exhibiting dysplasia, and four with carcinoma. Samples were defrosted and placed under a Renishaw (Wotton-Under-Edge, UK) System 1000 Raman microspectrometer for analysis. Between 5 and 12 spectra were acquired from each sample, with an excitation wavelength of 830 nm. Average characteristic spectra for each disease or condition were compared. Further multivariate statistical analysis of the data was carried out to evaluate and maximize the differences in the spectra for each disease or condition. RESULTS: The most visible differences in the spectra occur between 850 and 950 cm(-1) and 1,200 and 1,350 cm(-1). The later peaks are directly related to protein conformation and C-H bond stretch in nucleic acid bases. The relative intensity of the nucleic acid peak increases with progression to malignancy. Use of linear discriminant analysis made it possible to separate the spectra with disease to a greater degree of accuracy than using empirical peak ratio methods alone. Classification results obtained from cross-validation of the discriminant model showed prediction sensitivities of 83%, 76%, and 92% and specificities of 94%, 91%, and 90% for normal, dysplastic, and squamous cell carcinoma of the larynx, respectively. CONCLUSIONS: There was strong evidence to support spectral identification of malignancy and earlier abnormal changes. More substantive studies of the spectral differences between malignant and non-neoplastic tissue are warranted. Raman spectroscopy may become a useful adjunct to pathological diagnosis allowing directed or guided biopsies and assessment of adequacy of resection margins.

Adolescent↗
PubMed2000

Photodynamic therapy in gastrointestinal cancer: a realistic option?

Photodynamic therapy is now a useful and practical option of the local treatment of gastrointestinal cancers. There is increasing screening and surveillance of patients at risk of oesophageal and gastric cancers. The early detection of disease is often unhelpful if an elderly or frail patient needs to be subjected to radical resectional surgery. Photodynamic therapy can eradicate and cure early mucosal disease following a single endoscopic treatment. If the disease is more advanced good local control and palliation is often possible. Overall, palliation can often be achieved using simpler methods which are highly effective and not associated with the problems of prolonged photosensitisation. It is rapidly becoming clear that the ideal indication is for the treatment of dysplastic lesions in the oesophagus associated with columnar-lined oesophagus (Barrett's oesophagus). In these circumstances a heterogeneous field change often with multifocal dysplasia or cancer can be widely eradicated. Similar areas of squamous dysplasia in the upper oesophagus can be treated. At present a major complication of stricture formation is associated with the use of some photosensitisers. The treatment of cancer at the ampulla of Vater and choriocarcinoma is also proving very effective. The treatment can be performed at endoscopy and is well tolerated and safe.

Animals↗
PubMed2000

Barrett's esophagus: treatment with 5-aminolevulinic acid photodynamic therapy.

Barrett's esophagus has been identified as the premalignant precursor of esophageal adenocarcinoma. The eradication of metaplastic or dysplastic columnar-lined (Barrett's) esophagus may prevent progression to esophageal adenocarcinoma. 5-Aminolevulinic acid photodynamic therapy is a simple method for the mucosal ablation of the abnormal segment. Areas of metaplastic epithelium may remain buried after treatment and continued surveillance is necessary. Repeated treatments often are necessary but are very well tolerated with few complications.

Aminolevulinic Acid↗
PubMed1999

Induction of apoptosis by adenovirus E4orf4 protein is specific to transformed cells and requires an interaction with protein phosphatase 2A.

We previously have shown that adenovirus type 5 E4orf4 protein associates with protein phosphatase 2A (PP2A) and induces apoptosis in transformed cells in a p53-independent manner. Here we show that the interaction between E4orf4 and PP2A is required for induction of apoptosis by the viral protein. This conclusion is supported by a mutation analysis of E4orf4 protein, showing a correlation between the ability to bind PP2A and to induce apoptosis, and by the observation that transfection of an antisense construct of the PP2A-B55 subunit reduces expression of the PP2A-B55 subunit and inhibits induction of apoptosis by E4orf4, but not by p53. The mutant analysis also indicates that even a low level of interaction with PP2A is sufficient to initiate the E4orf4 apoptotic pathway. In addition, E4orf4 inhibits cellular transformation by various oncogenes, and this function is coupled to its ability to induce apoptosis. Furthermore, expression of oncogenes in primary cell cultures sensitizes these cells to induction of apoptosis by E4orf4. Our results suggest that E4orf4 is a potentially useful tool for cancer gene therapy.

Adenoviruses, Human↗