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Biomedical subjects

Linda Snell

Publications and source records attributed to Linda Snell.

13 recordsLinked to original sources
PubMed2006

Breast tissue banking: collection, handling, storage, and release of tissue for breast cancer research.

A "tumor bank" provides a resource tool that can efficiently address the limitations of other tissue resources, such as clinical archives and research study collections. A tumor bank allows formal accreditation of ethics and security procedures, and through a dedicated management, processing, storage, retrieval, and release structure, can provide selected and preassembled material and data for research and discovery. This chapter describes the design, operating protocols, and methods for processing, storage, and release of the Manitoba Breast Tumor Bank.

Animals↗
PubMed2005

Reviewers' perceptions of the peer review process for a medical education journal.

AIMS: To explore the review process from the reviewers' perspective, including perceptions of the time taken to carry out a review, barriers to and facilitators of the review process, benefits of reviewing, opinions about blinded versus transparent reviews, how the process of reviewing might be made easier, and to assess reviewers' experience of, and training in, the peer review process. SUBJECTS: Reviewers for Medical Education invited to review over a 5-month period between 1st June and 31st October 2002 (n = 221). METHODS: Postal questionnaire accompanying a request to review a manuscript. RESULTS: The overall response rate was 64.7% (the response rate of those completing and returning a manuscript review and a questionnaire was 87%); 30% were first-time reviewers for Medical Education, although the majority (87%) reviewed for other journals. The average time spent on the current review was just over 3 hours (184.3 minutes, median 162 minutes, range 30-810 minutes), which was stated to be about the same time as usual for the majority. Only 14% of respondents had received formal training in reviewing, although 66% said they would like such training. A total of 79.5% said they would have liked to seek a colleague's opinion, and 90% wished to receive other reviewers' comments. A wide range of problems with the review process were encountered, and the main way in which it was felt it could be made easier was to make the process electronic. Nearly three quarters of respondents said they would be happy to sign their reviews. Acting as a reviewer was seen as a professional responsibility and as an opportunity for learning. CONCLUSIONS: This study provides useful insights into the process of review from the reviewer's perspective. Reviewers spend a substantial amount of time on each paper. Many referees feel their reviews would benefit if they had formal training in the review process, received feedback on their reviews, or were able to ask colleagues for opinions on the paper being reviewed. Most reviewers would be willing to sign their reviews and feel that the process should be transparent. These results may help inform discussions about how to better prepare peer reviewers for their job.

Education, Medical, Undergraduate↗
PubMed2005

Faculty development for teaching and evaluating professionalism: from programme design to curriculum change.

INTRODUCTION: The recent emphasis on the teaching and evaluation of professionalism for medical students and residents has placed significant demands on medicine's educational institutions. The traditional method of transmitting professional values by role modelling is no longer adequate, and professionalism must be taught explicitly and evaluated effectively. However, many faculty members do not possess the requisite knowledge and skills to teach this content area and faculty development is therefore required. PROGRAMME DESCRIPTION: A systematic, integrated faculty development programme was designed to support the teaching and evaluation of professionalism at our institution. The programme consisted of think tanks to promote consensus and "buy-in", and workshops to convey core content, examine teaching strategies and evaluation methods, and promote reflection and self-awareness. PROGRAMME EVALUATION: The programme was evaluated using a CIPP (context, input, process, product) analysis. The institution supported this initiative and local expertise was available. A total of 152 faculty members, with key educational responsibilities, attended 1 or more faculty development activities. Faculty participation resulted in agreement on the cognitive base and attributes of professionalism, consensus on the importance of teaching and evaluating professionalism, and self-reported changes in teaching practices. This initiative also led to the development of new methods of evaluation, site-specific activities and curriculum change. DISCUSSION: A faculty development programme designed to support the teaching and evaluation of professionalism can lead to self-reported changes in teaching and practice as well as new educational initiatives. It can also help to develop more knowledgeable faculty members, who will, it is hoped, become more effective role models.

Curriculum↗
PubMed2005

Death related to albendazole-induced pancytopenia: case report and review.

Albendazole is a benzimidazole with wide spectrum coverage as an antiparasitic drug. Reported side effects have been minimal. We report the case of a patient who died with severe prolonged pancytopenia beginning during the third week of therapy for a pulmonary echinococcal cyst. This case was a 68-year-old man who presented with a large cystic lung mass. His medical history was significant for Child-Pugh class B cirrhosis. A prolonged course of albendazole was initiated. Two weeks later, the patient presented in septic shock with severe pancytopenia. The patient was initially resuscitated, but died after 10 days with no marrow recovery. Autopsy was consistent with albendazole-induced pancytopenia. This is the third human case of pancytopenia and the first death reported in relation to albendazole-induced pancytopenia. Neutropenia seems to be related more to higher dosage and longer duration of use. Albendazole sulfoxide peak dose and half life are significantly prolonged by liver disease and concomitant administration of certain drugs. The severity and duration of albendazole-induced pancytopenia in this case was likely related to the underlying liver disease. Frequent serial monitoring of blood counts and cessation of medication with any evidence of marrow toxicity in such patients is warranted.

Aged↗
PubMed2004

Phospho-serine-118 estrogen receptor-alpha expression is associated with better disease outcome in women treated with tamoxifen.

PURPOSE: The purpose of this research was to determine whether estrogen receptor alpha specifically phosphorylated at Ser(118) is associated with clinical outcome in primary breast tumors from estrogen receptor-positive and node-negative breast cancer patients. EXPERIMENTAL DESIGN: Estrogen receptor alpha specifically phosphorylated at Ser(118) was determined by immunohistochemistry in 117 primary breast tumors from node-negative patients who were subsequently treated with adjuvant tamoxifen. The relationship of estrogen receptor alpha specifically phosphorylated at Ser(118) expression to disease-free survival and overall survival was determined. RESULTS: Estrogen receptor alpha specifically phosphorylated at Ser(118) was limited to estrogen receptor alpha ligand binding assay-positive tumors and among this subset was expressed in 70 (62%) of these tumors. Estrogen receptor alpha specifically phosphorylated at Ser(118) expression was more frequently observed in progesterone receptor-positive tumors compared with progesterone receptor-negative tumors (chi(2) test, P = 0.012, n = 113). A significant correlation was also seen between estrogen receptor alpha specifically phosphorylated at Ser(118) and progesterone receptor levels (Spearman r = 0.236, P = 0.0118, n = 113). Kaplan-Meier outcome analysis showed that patients whose primary tumors expressed estrogen receptor alpha specifically phosphorylated at Ser(118) had a longer disease-free survival (P = 0.0018, n = 113) and a trend toward better overall survival, but this was not statistically significant. Among the subset of progesterone receptor-positive tumors, progesterone receptor-positive/estrogen receptor alpha specifically phosphorylated at Ser(118)-positive patients had a significantly longer disease-free survival that progesterone receptor-positive/estrogen receptor alpha specifically phosphorylated at Ser(118)-negative patients (P = 0.0041). CONCLUSIONS: Our data suggest that estrogen receptor alpha specifically phosphorylated at Ser(118) is a marker of a functional, intact ligand-dependent estrogen receptor signaling pathway in breast cancer and that estrogen receptor alpha specifically phosphorylated at Ser(118) status has the potential to provide a more precise biomarker of responsiveness to endocrine therapy in conjunction with estrogen receptor alpha and progesterone receptor status.

Antineoplastic Agents, Hormonal↗
PubMed2004

S100A7 (psoriasin) expression is associated with aggressive features and alteration of Jab1 in ductal carcinoma in situ of the breast.

INTRODUCTION: The S100A7 (psoriasin) gene is highly expressed in ductal carcinoma in situ (DCIS) of the breast and can be downregulated in invasive carcinoma. Persistent S100A7 expression in invasive carcinoma is associated with a worse prognosis, and this effect may be mediated in part through interaction with the multifunctional cell signaling protein Jab1. METHODS: In order to investigate the relationship between S100A7 and progression from DCIS to invasive carcinoma, we studied S100A7 expression in 136 patients with DCIS (including 46 patients with associated invasive carcinoma) by immunohistochemistry. RESULTS: S100A7 expression was present in 63 out of 136 (46%) of DCIS lesions and was associated with estrogen receptor negative status (P = 0.0002), higher nuclear grade (P < 0.0001), necrosis (P < 0.0001) and inflammation (P < 0.0001). S100A7 status was no different between DCIS with and DCIS without an invasive component, but higher levels of S100A7 were present in DCIS associated with invasive carcinoma (P < 0.004). Analysis of a subset of cases showed that S100A7 expression was also associated with an increase in nuclear Jab1 (n = 43; P = 0.0019) and reduced p27kip1 (n = 47; P = 0.0168). In cases of DCIS associated with invasive carcinoma, there was also a significant reduction in S100A7 between in situ and invasive components (n = 46; P < 0.0001). In pure DCIS cases treated by local excision, there was no difference in frequency of S100A7 expression between patients with recurrence of DCIS (n = 9) and those without (n = 36). CONCLUSION: The findings reported here suggest that, although S100A7 may not be a marker for recurrence of DCIS, it is associated with poor prognostic markers in DCIS and may influence progression of breast carcinoma through its interaction with and influence on Jab1.

Breast Neoplasms↗
PubMed2004

Phospho-serine-118 estrogen receptor-alpha detection in human breast tumors in vivo.

PURPOSE: To determine whether estrogen receptor (ER)-alpha specifically phosphorylated at Ser(118) is detectable in multiple human breast cancer biopsy samples. To gain insight into possible roles for P-Ser(118)-ERalpha in human breast cancer in vivo. EXPERIMENTAL DESIGN: A specific antibody for P-Ser(118)-ERalpha was validated for immunohistochemistry (IHC), and Western blot analysis confirmed IHC results. IHC was used to determine the relationship of P-Ser(118)-ERalpha to known prognostic markers and active mitogen-activated protein kinase (MAPK; erk1/2) expression. RESULTS: P-Ser(118)-ERalpha was significantly correlated with the expression of total ER, determined by ligand binding assay (r = 0.442, P = 0.002), but not with progesterone receptor expression or nodal status. P-Ser(118)-ERalpha was inversely correlated with histological grade (r = -0.34, P = 0.023), reflecting a similar trend for total ER (r = -0.287, P = 0.056). Categorical contingency analysis confirmed that P-Ser(118)-ERalpha was more frequently associated with lower than higher grade breast tumors (P = 0.038). In addition P-Ser(118)-ERalpha was significantly associated with detection of active MAPK (Erk1/2; Spearman r = 0.649, P < 0.0001; Fisher's exact test, P = 0.0004). CONCLUSIONS: P-Ser(118)-ERalpha detection is associated with a more differentiated phenotype and other markers of good prognosis in human breast cancer. P-Ser(118)-ERalpha is correlated with active MAPK in human breast tumor biopsies, suggesting the possibility that active MAPK either directly or indirectly has a role in the regulation of P-Ser(118)-ERalpha expression in vivo. These data provide evidence for a role of P-Ser(118)-ERalpha in human breast cancer in vivo.

Biomarkers, Tumor↗
PubMed2004

Orienting teaching toward the learning process.

Based on developments in educational psychology from the late 1980s, the authors present a model of an approach to teaching. Students' learning processes were analyzed to determine teacher functions. The learning-oriented teaching (LOT) model aims at following and guiding the learning process. The main characteristics of the model are (1) the components of learning: cognition (what to learn), affect (why learn), and metacognition (how to learn); and (2) the amount of guidance students need. If education aims at fostering one's ability to function independently in society, an important general objective should be that one learns how to fully and independently regulate his or her own learning; i.e., the ability to pursue one's professional life independently. This implies a transition from external guidance (from the teacher) through shared guidance (by the student together with the teacher) to internal guidance (by the student alone). This transition pertains not only to the cognitive component of learning (content) but also to the affective component (motives) and the metacognitive component (learning strategies). This model reflects a philosophy of internalization of the teacher's functions in a way that allows optimal independent learning after graduation. The model can be shown as a two-dimensional chart of learning components versus levels of guidance. It is further elaborated from learners' and teachers' perspectives. Examples of curriculum structure and teachers' activities are given to illustrate the model. Implications for curriculum development, course development, individual teaching moments, and educational research are discussed.

Cognition↗
PubMed2003

Psoriasin (S100A7) expression is altered during skin tumorigenesis.

BACKGROUND: Psoriasin (S100A7) expression has previously been associated with psoriasiform hyperplasia as well as with tumor progression in breast cancer. Its expression profile for different stages of skin lesions is unknown. The aim of this study was to determine the relationship between psoriasin (S100A7) and tumor progression in skin. METHODS: Psoriasin was assessed by immunohistochemistry and levels of expression determined by semi-quantitative scoring in skin biopsies from 50 patients. The cohort included normal skin, actinic keratosis, squamous carcinoma in-situ, invasive squamous cell carcinoma, and basal cell carcinoma. RESULTS: In normal skin, psoriasin was rarely detected in epidermis but was expressed in underlying adnexae. In abnormal epidermis psoriasin was frequently expressed in abnormal keratinocytes in actinic keratosis, in-situ and invasive squamous cell carcinoma, but was rarely observed in the basal epidermal layer or in superficial or invasive basal cell carcinoma. The highest levels of expression were seen within squamous carcinoma in-situ. Significantly reduced levels of expression were observed in both unmatched (p = 0.0001) and matched (p < 0.004) invasive squamous cell carcinoma. Psoriasin expression within abnormal squamous lesions correlated with mitotic count (r = 0.54, p = 0.0036), however no significant relation was found with the intensity of dermal inflammatory cell infiltrates assessed within each pathology. CONCLUSION: These results suggest that altered psoriasin expression occurs in abnormal epidermis and that downregulation may be related to the onset of invasion in squamous cell carcinoma in skin.

Biomarkers, Tumor↗
PubMed2002

Activated mitogen-activated protein kinase expression during human breast tumorigenesis and breast cancer progression.

PURPOSE: The purpose of this study is to address the hypothesis that activatedmitogen-activated protein kinase (MAPK; extracellular signal-regulated kinases 1 and 2) has a role in breast tumorigenesis, breast cancer progression, and the development of tamoxifen resistance. EXPERIMENTAL DESIGN: H-score analysis and a specific antibody for the immunohistochemical detection of activated MAPK in formalin-fixed, paraffin-embedded tissue sections were used to compare expression in: (a) human breast tumors and their matched adjacent normal breast tissue; (b) primary human breast tumors and their matched lymph node metastases; and (c) primary breast tumors from patients who later proved to be sensitive or resistant to tamoxifen treatment. RESULTS: Active MAPK expression was detected in 48% of primary human breast tumors and was significantly increased in tumors compared with adjacent normal breast (Wilcoxon test, P = 0.027). A significant positive association (chi(2), P = 0.02; n = 55) was obtained between active MAPK and the presence of lymph node metastases. Moreover, increased active MAPK (Wilcoxon test, P = 0.0098) was found in concurrent lymph node metastases compared with primary breast tumors. No significant difference in active MAPK was found in primary tumors of patients who later responded to tamoxifen or did not respond to tamoxifen. CONCLUSIONS: These data suggest that active MAPK is a marker of breast cancer metastasis and has a role in the metastatic process. However, active MAPK is unlikely to be a marker of endocrine sensitivity or involved in de novo tamoxifen resistance.

Blotting, Western↗
PubMed2002

Analysis of gene expression in ductal carcinoma in situ of the breast.

PURPOSE: The risk of recurrence and progression of ductal carcinoma in situ (DCIS) of the breast is best designated by morphological indicators, including the presence of necrosis. Our purpose was to identify molecular alterations underlying progression of DCIS. EXPERIMENTAL DESIGN: We have compared gene expression within a cohort of six cases of DCIS with necrosis (DCIS(necrosis+)) and four cases without necrosis (DCIS(necrosis-)) using microdissection and cDNA microarray. RESULTS: A set of 69 cDNAs from a group of 1,181 was identified that were consistently differentially expressed. Among this set, the mRNA for angio-associated migratory cell protein and a serine threonine protein kinase, nuclear Dbf2 related, were consistently higher in DCIS(necrosis+) and were also found to be overexpressed in the T47D breast cancer cell line subjected to hypoxia. Further study of angio-associated migratory cell protein by quantitative reverse transcriptase-PCR and in situ hybridization analysis of 37 cases of DCIS confirmed higher mRNA expression in DCIS(necrosis+) (P = 0.0095). CONCLUSIONS: This study shows that although levels of gene expression are mostly similar between morphologically different DCIS, consistent differences in expression of a subset of genes can be identified between DCIS with and without necrosis.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Small group learning in the final year of a medical degree: a quantitative and qualitative evaluation.

The new undergraduate medical curriculum in Manchester uses problem-based learning (PBL) throughout the course. However, the major difference from other PBL schools is that in years 3 & 4 (phase 2) the students can use clinical experience when discussing the paper cases. The process is then developed further in year 5 (phase 3), in which there are no set PBL 'triggers' and students bring their own cases to the groups for discussion. In this study, we have explored what happens in the phase 3 (year 5) group sessions and how the students view them. A questionnaire and focus groups were used to generate data, from which a model was developed of what happens in a 'good' group session. The data suggest that most groups run on a case-presentation and discussion format, most commonly about clinical management and diagnosis. Students want tutors to act as an expert resource and to be flexible in allowing students to direct the discussions. University guidance about the group sessions was not generally used.

Journal Article↗