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Biomedical subjects

N Stone

Publications and source records attributed to N Stone.

At least 37 records · Page 2Linked to original sources

Rural interprofessional education: promoting teamwork in primary health care education and practice.

In a climate of increasing incentives to work effectively within a primary health care team, the ability of various health care professionals to collaborate comes into focus. The principles of effective teamwork can be learned and this learning is most effectively achieved in the field under the supervision of experienced preceptors. It is also enhanced if learners have the opportunity to participate actively in the team and do so from undergraduate level. A 3 year project is underway in Victoria involving rural primary care placements for mixed groups of nursing and medical students. The students are educated in the field by medical and nursing tutors and preceptors who are currently working closely together. The learning objectives include understanding the principles of collaboration, teamwork and various roles in the health care team within a primary health care framework. The present paper describes the context for an evolving interprofessional education project in rural primary care, designed to promote collaboration. It outlines the policy underpinning the project's development. It provides a brief review of the associated evidence base, highlighting barriers to and enablers of interprofessional education. Lessons learnt during the implementation and evaluation of this project will guide efforts to extend the reach of interprofessional education across the primary health care sector.

Allied Health Personnel↗

The use of artificial intelligence technology to predict lymph node spread in men with clinically localized prostate carcinoma.

BACKGROUND: The current study assesses artificial intelligence methods to identify prostate carcinoma patients at low risk for lymph node spread. If patients can be assigned accurately to a low risk group, unnecessary lymph node dissections can be avoided, thereby reducing morbidity and costs. METHODS: A rule-derivation technology for simple decision-tree analysis was trained and validated using patient data from a large database (4,133 patients) to derive low risk cutoff values for Gleason sum and prostate specific antigen (PSA) level. An empiric analysis was used to derive a low risk cutoff value for clinical TNM stage. These cutoff values then were applied to 2 additional, smaller databases (227 and 330 patients, respectively) from separate institutions. RESULTS: The decision-tree protocol derived cutoff values of < or = 6 for Gleason sum and < or = 10.6 ng/mL for PSA. The empiric analysis yielded a clinical TNM stage low risk cutoff value of < or = T2a. When these cutoff values were applied to the larger database, 44% of patients were classified as being at low risk for lymph node metastases (0.8% false-negative rate). When the same cutoff values were applied to the smaller databases, between 11 and 43% of patients were classified as low risk with a false-negative rate of between 0.0 and 0.7%. CONCLUSIONS: The results of the current study indicate that a population of prostate carcinoma patients at low risk for lymph node metastases can be identified accurately using a simple decision algorithm that considers preoperative PSA, Gleason sum, and clinical TNM stage. The risk of lymph node metastases in these patients is < or = 1%; therefore, pelvic lymph node dissection may be avoided safely. The implications of these findings in surgical and nonsurgical treatment are significant.

Acid Phosphatase↗

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↗

Xeroderma pigmentosum: the role of phototesting.

We report three patients newly diagnosed as having xeroderma pigmentosum (XP). Previous photobiological studies have implicated ultraviolet (UV) B as the activating waveband in XP, causing a delayed and prolonged erythemal response. This characteristic reaction pattern has been used as a quick screening test in patients suspected of having XP, while awaiting confirmatory DNA repair studies. Two of our patients showed no abnormal erythemal responses, and one showed severe photosensitivity from 330 to 400 nm but normal UVB responses, with a peak erythema at 24 h. We conclude that the erythemal responses in XP are highly variable and cannot be considered as a reliable screening test in the diagnosis of XP.

Child↗

Patient and tumor characteristics of colon cancers with microsatellite instability: a population-based study.

Molecular screening for microsatellite instability (MSI) in colon cancers has been proposed to identify individuals with hereditary nonpolyposis colorectal cancer. To date, most reports of MSI in colorectal cancer have been based on studies of clinical case series or high-risk families. We examined the proportion of incident colon cancers in the general population that exhibit MSI by patient and tumor characteristics. We interviewed 201 colon cancer cases ascertained by the New Mexico Tumor Registry in the metropolitan Albuquerque area for demographic information, lifestyle factors, medical history, and family cancer history. Paired normal and tumor tissue specimens were obtained for each case. Three microsatellite markers were used; instability was defined as observed alteration at two or more loci. Overall, 37 of 201 (18%) colon cancers exhibited instability. MSI was more common among cases >70 years (26%) and most common among cases >80 years (38%). MSI was significantly associated with tumors in the proximal colon and with later stage and poor differentiation among cases >70 years. MSI was not associated with a history of polyps. Family history of colorectal cancer was associated with MSI only among cases <50 years. When all factors were analyzed jointly in a regression model, proximal subsite and poor differentiation remained significantly associated with MSI. One patient, whose tumor exhibited MSI, fulfilled the Amsterdam Criteria for hereditary nonpolyposis colorectal cancer. Our study provides a population-based estimate of MSI in colon tumors and a representative estimate of the proportion of colorectal cancer patients in the general population who consent to be interviewed for family cancer history and to have biological samples analyzed.

Adult↗

Toxic epidermal necrolysis and graft vs. host disease: a clinical spectrum but a diagnostic dilemma.

We describe a 53-year-old man who developed partial and full thickness skin loss associated with pyrexia, diarrhoea, liver, renal and bone marrow failure, during treatment for an aggressive B cell lymphoblastic lymphoma. The clinical features and histology were compatible with both toxic epidermal necrolysis and graft vs. host disease, causing a diagnostic and therapeutic dilemma. We discuss the possibility that methotrexate was the causative drug, with review of its cutaneous side-effects. Histologically our patient demonstrated the sparse dermal infiltrate with full thickness epidermal necrosis typical of toxic epidermal necrolysis and graft vs. host disease. We discuss this finding with respect to the pathogenesis of toxic epidermal necrolysis.

Antimetabolites, Antineoplastic↗

What determines geographical variation in rates of acceptance onto renal replacement therapy in England?

OBJECTIVE: To determine the independent effects of need and supply factors on the known geographical variation in acceptance rates onto renal replacement therapy (RRT) in England. METHODS: Data were obtained from all renal units in England on the characteristics of all cases aged 16 years and over, resident in England, who were accepted onto RRT in 1991 and 1992. Of these, 5715 (94.5%) had a valid postcode that could be matched to a census ward. Multilevel modelling using Poisson regression was used. The number of acceptances in each census ward within age bands 16-34, 35-64 and 65+ was the dependent variable. Independent effects modelled were: (1) individual factors (age, sex); (2) census ward need factors--ethnicity (expressed as the percentage of the ward population that was Asian or African-Caribbean), socio-economic deprivation--and supply factors--'access' to the nearest renal unit using crowfly and road travel time and distance, and services available to each ward expressed as number of haemodialysis stations per 100,000 catchment population of the nearest renal unit; (3) district health authority level effects. RESULTS: Age was a major determinant of acceptance, with a 7-fold higher rate in males aged over 64 years compared with younger men. Acceptance rates were lower in females, with a negative age-sex interaction in females aged over 64 years. The percentage of both Asian and African-Caribbean populations per ward was a highly significant positive determinant. Deprivation was also a significant determinant, best represented by a customised index. There was an inverse relation of acceptance with distance, especially road travel time. Other supply side variables had a significant effect though there was no independent district effect. There was some variation in the strength of these relationships by type of area (Greater London, urban and non-urban). CONCLUSIONS: Need and supply factors influence service use as expressed as acceptance onto RRT. Pressure to expand RRT services needs to be aimed at areas with large minority ethnic populations and those living far from existing units.

Adolescent↗

Beyond white light endoscopy--the prospect for endoscopic optical biopsy.

The most important factor in the successful treatment of cancer is early detection. This will be more likely to facilitate eradication of abnormal cells prior to systemic invasion. White light endoscopy has been an essential tool in medical diagnosis for a number of years. Direct endoscopic inspection of gastrointestinal organs has revolutionised diagnostic techniques, improving the targeting of biopsies of macroscopic morphological abnormalities. Recent technological developments are threatening a further revolution enabling the instantaneous and non-invasive diagnosis of microscopic tissue abnormalities in vivo. This is made possible by improving the level of information that can be obtained from the tissue. As well as the two-dimensional surface morphology image, which the traditional endoscope can view, new techniques enable structure at depth, i.e., the third-dimension, to be imaged in high resolution. Other advances enable the detection of biochemical changes in tissue that precede any changes in morphology, thus enabling earlier diagnosis of tissue abnormalities. This review details recent advances that have the greatest potential, for use in partnership with endoscopy, for the diagnosis of malignancy and pre-malignancy.

Biopsy↗

A novel F box protein, NFB42, is highly enriched in neurons and induces growth arrest.

NFB42 (neural F Box 42 kDa) is a novel gene product that is highly enriched in the nervous system. Its predicted protein contains an F box, a motif recently shown to couple cell cycle regulation to the proteasome pathway (Bai, C., Sen, P., Hofmann, K., Ma, L., Goebl, M., Harper, J. W., and Elledge, S. (1996) Cell 86, 263-274). NFB42 mRNA and protein are expressed in all major areas of the adult rat brain but are not detected in non-neural tissues. NFB42 protein is localized primarily to the cytoplasm of neurons and does not appear to be present in glia. The presence of an F box in NFB42 suggests that it may be involved in cell cycle regulation; however, its expression in postmitotic neurons indicates that it is not involved in regulating typical cell cycle events. In an initial attempt to characterize the function of this protein, NFB42 was transfected into N1E-115 neuroblastoma and Chinese hamster ovary cells. The expression of full-length NFB42, but not an F box deletion mutant, inhibits proliferation in both cell lines. Additional experiments demonstrate that NFB42 interacts with Skp1p, a component of the proteasome pathway, and deletion of the F box also inhibits this interaction. Overall, the expression pattern of NFB42, along with the presence of an F box domain and the ability to inhibit growth, suggests that it may play a role in maintaining neurons in a postmitotic state.

Amino Acid Sequence↗

Modelling the spatial distribution of teenage conception rates within Wessex.

This study attempts to determine which factors account for the spatial variation in teenage conception rates within the former Wessex Regional Health Authority and what factors account for the eventual outcomes of these conceptions. Postcoded data on all teenage conceptions from 1991 to 1994 were collected and related to census ward level information and indicators of accessibility to family planning services. The results show that the variation in teenage conception rates and conception outcomes is principally determined by the age of the teenager, deprivation levels, the presence of certain homogeneously distinct groups and the distance to the nearest youth-oriented family planning clinic.

Adolescent↗

High T cell responses to the glutamic acid decarboxylase (GAD) isoform 67 reflect a hyperimmune state that precedes the onset of insulin-dependent diabetes.

Pancreatic islet beta-cell destruction leading to insulin-dependent diabetes mellitus (IDDM) is an autoimmune T cell-mediated process. Peripheral blood T cells, which proliferate to islet antigens such as glutamic acid decarboxylase (GAD), (pro)insulin or tyrosine phosphatase IA-2, can be detected in at-risk, first degree relatives of people with IDDM. However, cross-sectional studies cannot define the relationship between T cell responses and progression to IDDM. Longitudinal studies were therefore undertaken on 50 at-risk, first degree relatives tested at least yearly for up to 4 years, during which time five developed IDDM. Peripheral blood T cell responses to a GAD67(aa208-404)-glutathione-S-transferase (GST) fusion protein, GST, insulin and tetanus toxoid were measured, together with antibodies to islet cells, GAD, insulin and IA-2. High levels of antibodies to GAD or insulin were generally associated with low T cell responses to these antigens. Relatives who developed IDDM were characterized by high levels of antibodies to insulin and/or islet cells, and high T cell responses to GAD67-GST and tetanus, but not insulin, in the 24 months before clinical diagnosis. Cross-sectionally, T cell responses to GAD67(aa208-404)-GST and to full-length GAD65-GST were highly correlated (r=0.75, P<0.002). In conclusion, increased cellular immunity to the mid region of GAD67 was a marker of late pre-clinical IDDM, but appears to reflect a more general, transient state of cellular immune hyperresponsiveness.

Adolescent↗

Breast abscess due to Corynebacterium striatum.

Corynebacterium striatum, a normal constituent of the skin flora, is rarely pathogenic. Previous reports of infection are few, and are mainly confined to immunosuppressed patients or those with indwelling prosthetic devices. We report a case in which the organism caused a recurrent breast abscess in a woman with normal immune function. The only previous reports of Corynebacterium striatum mastitis have been in cows.

Abscess↗