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Biomedical subjects

C Kendall

Publications and source records attributed to C Kendall.

At least 19 recordsLinked to original sources

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↗

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↗

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↗

Levels of mercury in alligators (Alligator mississippiensis) collected along a transect through the Florida Everglades.

As part of a multi-agency study of alligator health, 28 American alligators (Alligator mississippiensis) were captured along a transect through the Florida Everglades in 1999. Liver and tail muscle tissues were sampled and analyzed on a wet weight basis for total mercury (THg) using cold-vapor atomic absorption spectrophotometry. All tissues had detectable concentrations of THg that ranged from 0.6 to 17 mg/kg in liver and from 0.1 to 1.8 mg/kg in tail muscle. THg was more concentrated in liver tissue than tail muscle, but levels were highly correlated between tissues. THg concentrations in tissue differed significantly among locations, with animals from Everglades National Park (ENP) having mean concentrations of THg in liver (10.4 mg/kg) and tail muscle (1.2 mg/kg) that were two-fold higher than basin-wide averages (4.9 and 0.64 mg/kg, respectively). The reasons for higher contamination of ENP alligators were unclear and could not be explained by differences in sex, length, weight or animal age. While delta15N values were positively correlated with THg concentrations in tail muscle, spatial patterns in isotopic composition did not explain the elevated THg levels in ENP alligators. Therefore, it appears that ENP alligators were more highly exposed to mercury in their environment than individuals in other areas. Comparisons to a previous survey by Yanochko et al. [Arch Environ Contam Toxicol 32 (1997) 323] suggest that mercury levels have declined in some Everglades alligators since 1994.

Age Factors↗

p53 Expression and keratinocyte hyperproliferation in middle ear cholesteatoma.

Keratinocytes in middle ear cholesteatoma have hyperproliferative properties. There is controversy regarding the role of p53 and its effect on cellular proliferation in cholesteatoma. This study was instituted to examine this. Cholesteatoma and deep meatal skin control specimens were analysed for MIB-1 (n = 7, controls = 7), a marker of cellular proliferation, and p53 (n = 17, controls = 17) expression by immunocytochemistry. Expression of p53 was minimal or absent in both cholesteatoma and controls (P = 0.2). MIB-1 expression was higher, but not significantly so, in cholesteatoma than in controls (P = 0.09). Our study has shown no significant p53 expression in cholesteatoma epithelium. This suggests that there is no dysfunction in the p53-mediated cell cycle control mechanisms in cholesteatoma.

Cell Division↗

Tandem zirconocene homologation-aldimine allylation.

[reaction: see text]. Hydrozirconation of internal and terminal alkynes followed by in situ transmetalation to dimethylzinc and treatment with diiodomethane leads to chain extended allylic organometallics. Addition to N-phosphinoyl or N-sulfonyl aldimines provides homoallylic amines in 48-87% yield and 3:2 to >20:1 diastereomeric ratios favoring anti-products.

Journal Article↗

Altered expression of apolipoprotein E, amyloid precursor protein and presenilin-1 is associated with chronic reactive gliosis in rat cortical tissue.

A major characteristic feature of Alzheimer's disease is the formation of compact, extracellular deposits of beta-amyloid (senile plaques). These deposits are surrounded by reactive astrocytes, microglia and dystrophic neurites. Mutations in three genes have been implicated in early-onset familial Alzheimer's disease. However, inflammatory changes and astrogliosis are also believed to play a role in Alzheimer's pathology. What is unclear is the extent to which these factors initiate or contribute to the disease progression. Previous rat studies demonstrated that heterotopic transplantation of foetal cortical tissue onto the midbrain of neonatal hosts resulted in sustained glial reactivity for many months. Similar changes were not seen in cortex-to-cortex grafts. Using this model of chronic cortical gliosis, we have now measured reactive changes in the levels of the key Alzheimer's disease proteins, namely the amyloid precursor protein, apolipoprotein E and presenilin-1. These changes were visualised immunohistochemically and were quantified by western blot analysis. We report here that chronic cortical gliosis in the rat results in a sustained increase in the levels of apolipoprotein E and total amyloid precursor protein. Reactive astrocytes in heterotopic cortical grafts were immunopositive for both of these proteins. Using a panel of amyloid precursor protein antibodies we demonstrate that chronic reactive gliosis is associated with alternative cleavage of the peptide. No significant changes in apolipoprotein E or amyloid precursor protein expression were seen in non-gliotic cortex-to-cortex transplants. Compared to host cortex, the levels of both N-terminal and C-terminal fragments of presenilin-1 were significantly lower in gliotic heterotopic grafts.The changes described here largely mirror those seen in the cerebral cortex of humans with Alzheimer's disease and are consistent with the proposal that astrogliosis may be an important factor in the pathogenesis of this disease.

Alzheimer Disease↗

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↗

From 'culture of dehumanization of childbirth' to 'childbirth as a transformative experience': changes in five municipalities in north-east Brazil.

Brazil has become a country known as having one of the most extreme examples of the consequences of the hospital-based medicalization of delivery care, while a model of humanization of birth was developed in the State of Ceará in the 1970s. The Government of Japan, through the Japanese International Cooperation Agency (JICA), collaborated with the Federal Ministry of Health of Brazil and the Government of the State of Ceará, in implementing the Maternal and Child Health Improvement Project in north-east Brazil (1996-2001). This project focused on 'humanization of childbirth', with training based intervention activities. Behavioral changes among health professionals who received the project's participatory type of training were described using rapid anthropological assessment procedure (RAP) survey results. Changes from 'a culture of dehumanization of childbirth' to 'childbirth as a transformative experience' were observed.

Brazil↗

Are p53 and MIB-1 overexpressed in cholesteatoma?

INTRODUCTION: There is controversy regarding the expression of p53 and MIB-1 in cholesteatoma.1 This study was instituted to study this. p53 is an intracellular protein which plays a critical role in control of the cell cycle at the G1 check point. MIB-1 is recognized as a marker of cellular proliferation. Using deep meatal skin controls, the question addressed was, 'are p52 and MIB-1 overexpressed in cholesteatoma'? METHOD: Immunocytochemistry using the avidin-biotin technique on frozen tissue sections with primary antibody to p53 (n = 17, controls = 17) and MIB (n = 17, controls = 7) was performed on cholesteatoma and deep meatal skin control specimens. Appropriate positive and negative controls were employed for each antibody. Slides were analysed in a blind fashion by two independent observers. Statistical analysis was performed using the Mann-Whitney test. RESULTS: Expression of p53 was minimal or absent in both cholesteatoma and controls. No significant difference in p53 expression was found between the two groups (P = 0.02). MIB-1 expression was higher in cholesteatoma than in controls, although this was not statistically significant (P = 0.09). CONCLUSION: This study did not demonstrate an increased expression of p53 cholesteatoma, indicating no evidence of a dysfunctional cell cycle. MIB-1 results showed a possible trend towards significance, which requires a more powerful study to evaluate this further. The probability that there is an increased rate of cellular proliferation in cholesteatoma, when compared to deep meatal skin controls, cannot be excluded.

Journal Article↗

Use of health status measures in patients with low back pain in clinical settings. Comparison of specific, generic and preference-based instruments.

OBJECTIVE: To evaluate the discriminative performance over time of specific, generic and preference-based instruments in patients with low back pain (LBP) in clinical settings. METHODS: Forty-six consecutive patients with LBP participated in the study. Self-response questionnaires were administered at baseline and 3 and 6 months, including the following instruments: Oswestry (specific for LBP), SF-36 (generic), EuroQol (EQ-5D) and Health Utilities Index (HUI) (preference-based). EQ-5D and HUI weights were derived from previously published evaluations in the general population. Patients were asked to compare their health status with their baseline health and were categorized on the basis of an ordinal scale as: (a) improved; (b) stable; or (c) worse. Changes in the instruments were evaluated by rescaling the instruments over the same scale interval and by estimating standardized effect sizes between two time points for the three categories of change. RESULTS: Thirty-seven patients (80%) completed both the baseline and the 3-month questionnaire and 34 the baseline and 6-month questionnaires (74%). Overall, at both time points, approximately half of the patients reported no changes in their health status. Correlations between instruments were generally low, suggesting that they measure different health domains. The scales which discriminated best between patients who improved and those who deteriorated at 3 months were the Oswestry, the HUI, the EQ-5D and the SF-36 bodily pain and emotional role subscales. The SF-36 subscales appeared to have a floor effect for those patients who had deteriorated. CONCLUSIONS: Most SF-36 subscales did not adequately reflect changes in the health status of patients with LBP, mostly for those who reported deterioration. Preference-derived quality-of-life scores appeared to discriminate among patients who improved and those who deteriorated, although not as consistently as the disease-specific measure (Oswestry). Additional research is needed to evaluate the role of generic measures of quality of life in the assessment of patients with LBP before they can be widely implemented in clinical settings or outcomes research.

Data Collection↗

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↗

Social network influences on reproductive health behaviors in urban northern Thailand.

Prevention approaches for reproductive health have evolved from an emphasis on individually focused models of behavior change to a recognition that risk reduction occurs within a context of social norms. Prevention programs can be improved by understanding how social structure influences sexual behavior and using that understanding to develop strategies for positive change. In a dynamic, urban context, communities are better conceptualized as informal networks of ties. These network structures may help to protect, or conversely, expose members to reproductive risk behaviors. Using data from a study of social and sexual networks conducted in northern Thailand, this article describes partner relations and social structure in the modern, urban context, and illustrates the links between individual, relational and structural properties and reproductive risk behaviors. Triangulation of ethnographic, survey and social network data collection and analytic tools provide an opportunity to interpret individual behaviors, meanings of relationships and structural properties of networks. Intervention approaches should build on existing networks, and address the complex meanings of romantic and sexual partnerships.

Community Networks↗

Networks of persons with syphilis and at risk for syphilis in Louisiana: evidence of core transmitters.

BACKGROUND AND OBJECTIVES: Differences in sociodemographic attributes and healthcare access may explain differences in regional sexually transmitted disease rates but don't fully explain why syphilis persists disproportionately in certain populations. GOAL OF THIS STUDY: To understand the behavioral epidemiology of syphilis, we conducted a social network analysis of persons with syphilis and their contacts and developed and applied a definition of core transmitters. STUDY DESIGN: We interviewed 10 index persons with primary or secondary untreated syphilis and 80 of their named sexual and social contacts. RESULTS: Fourteen (16%) of 90 interviewed persons met the definition of core transmitters, 9 of whom had past or current syphilis. The other interviewed persons had only moderately risky behaviors. Seventy-eight (42%) of the network sexual contacts were connected directly or indirectly to a core transmitter. CONCLUSION: This analysis suggests that syphilis transmission is maintained by a community with a small percentage of high-risk persons centrally placed amidst a larger group with moderately risky behavior.

Adult↗

Implementation of condom social marketing in Louisiana, 1993 to 1996.

OBJECTIVES: This article describes the implementation and impact of the first statewide condom social marketing intervention in the United States. METHODS: A statewide social marketing program made condoms freely available in 93 public health clinics, 39 community mental health centers, 29 substance abuse treatment sites, and more than 1000 businesses in neighborhoods with high rates of sexually transmitted diseases (STDs) and HIV. Surveys about condom use were conducted annually. RESULTS: Between 1994 and 1996, more than 33 million condoms were distributed without significant opposition. Over time, self-reported condom use at the last sexual encounter increased among African American women (from 28% in 1994 to 36% in 1996), particularly African American women with 2 or more sex partners (from 30% to 48%). Condom use at the last sexual encounter increased among African American men (from 40% in 1994 to an average of 54% in 1996). The number of reported sex partners did not increase. CONCLUSIONS: Condom social marketing can be successfully implemented in the United States. The widespread availability of free condoms is associated with increased condom use, particularly among persons at high risk for STDs and HIV.

Adolescent↗