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Biomedical subjects

E McDermott

Publications and source records attributed to E McDermott.

At least 19 recordsLinked to original sources
PubMed2006

Making sense of dying: a review of narratives written since 1950 by people facing death from cancer and other diseases.

UNLABELLED: This article reviews a sample of narratives written since 1950 by people knowingly facing death as a result of cancer and other diseases, in order to compare experiences and show how these relate to wider changes in practice in end of life care. METHODS: A bibliographic search of libraries, archives, journals and internet sources located English spoken literature, including books, poems, newspapers, journal articles, diaries, and internet postings of writings by people facing terminal disease. Bibliometric and qualitative content analysis explored changing authorship, experiences, purpose in writing, and reported the impact on readers. RESULTS: The initial search located a wide range of published and unpublished narratives, to which inclusion/exclusion criteria were applied, yielding 148 narratives by different authors since 1950. A purposive sub-sample of 63 of these narratives was reviewed. DISCUSSION: Over the last half century there have been changes in both the volume of available literature and patterns of writing about end of life experience. Therapeutic benefits of writing are reported as a way of making sense of dying combined with a strong sense of purpose in sharing the story. There is a clear awareness of social needs when dying, along with issues of communication with medical staff, symptom control, realities of suffering, and spiritual aspects of dying. Differences are found in the nature and style of writing about cancer in comparison to other illnesses.

Attitude to Death↗
PubMed2005

Ets2 transcription factor in normal and neoplastic human breast tissue.

The Ets family of transcription factors regulate the expression of multiple genes involved in tumour formation and progression. The aim of this work was to test the hypothesis that the expression of Ets2 in breast cancers was associated with parameters of tumour progression and metastasis. Using reverse-transcriptase polymerase chain reaction (RT-PCR), Ets2 mRNA was detected in 69% of 181 breast carcinomas, 63% of 43 fibroadenomas and 47% of 43 specimens of normal breast tissue. Levels were significantly higher in carcinomas compared with normal breast tissue (P = 0.006). Using Western blotting, Ets2 protein was found to migrate as two bands with molecular masses of 52 kDa (p52) and 54kDa (p54). Levels of both proteins were significantly higher in the carcinomas compared with both fibroadenomas (P = 0.0001) and normal breast tissue (P = 0.0001). In the carcinomas, a significant relationship was found between the p52 and p54 form of Ets2 (r = 0.51, P < 0.0001; Spearman correlation). Also, in the carcinomas, a significant correlation was found between both forms of Ets2 protein and urokinase plasminogen activator (uPA) (for p52, r = 0.43, P = 0.0005, n = 68; for p54, r = 0.50, P = 0.0001, n = 68). As Ets2 binding sites are present on the uPA promoter, Ets2 may be one of the transcription factors regulating uPA expression in human breast cancer.

Blotting, Western↗
PubMed2005

Investigation into the effects of the novel antipsychotic ziprasidone on weight gain and reproductive function in female rats.

Weight gain and sexual dysfunction are serious side effects of certain antipsychotic drugs. Ziprasidone, a novel antipsychotic with a unique receptor binding profile, is reported to have a low propensity for such side effects. Previous results from this laboratory have demonstrated substantial weight gain following sub-chronic treatment with olanzapine and risperidone. Risperidone induced weight gain and markedly impaired reproductive function while olanzapine induced weight gain, without affecting reproductive function. The aim of this study was to investigate effects of ziprasidone on weight gain and reproductive function in female rats. Ziprasidone (1 and 2.5 mg/kg i.p.) or vehicle was administered once daily for 28 days and body weight, food and water intake measured, in addition to histological examination of vaginal lavage to determine the stage of the oestrous cycle. On day 28, the rats were sacrificed and the uterine weights recorded, intra-abdominal fat weight and plasma prolactin levels measured. Ziprasidone failed to induce significant weight gain during weeks 1-3, however, significant weight gain was observed on day 28 at 2.5 mg/kg (p < 0.05). Ziprasidone had no effect on food intake at any time point. A significant reduction in water intake (p < 0.05) was observed during the first week of treatment with 2.5 mg/kg ziprasidone. Ziprasidone had no effect on intra-abdominal fat weight, wet or dry uterine weight or plasma prolactin levels. All ziprasidone treated animals displayed a normal four-day oestrous cycle. This study is the first to report that ziprasidone is without effect on reproductive function or ingestive behaviour in the rat.

Analysis of Variance↗
PubMed2005

Expression of survivin and its splice variants survivin-2B and survivin-DeltaEx3 in breast cancer.

Alternative splicing of survivin mRNA gives rise to multiple isoforms, that is, survivin and 3 splice variants, survivin-2B, survivin-3B and survivin-DeltaEx3. The aim of this study was to compare the expression of survivin, survivin-2B and survivin-DeltaEx3 in normal breast tissue, fibroadenomas, primary breast cancer and axillary nodal metastases. Survivin, survivin-2B and survivin-DeltaEx3 mRNA were measured using semiquantitative RT-PCR. In the primary carcinomas, we related mRNA for each form of survivin to both survivin protein and apoptosis. For each type of breast tissue, survivin was the predominant form detected, being present in 146 out of 156 (93.6%) primary breast carcinomas, 11 out of 11 (100%) axillary nodal metastases, 21 out of 31 (67.7%) fibroadenomas and five out of 22 (22.7%) specimens of normal breast tissue. Levels of the three forms of survivin were significantly higher in the carcinomas compared to normal breast tissue (P < 0.0001). Levels of both survivin-2B and survivin-DeltaEx3 but not survivin were significantly higher in nodal metastases than primary carcinomas. Survivin mRNA levels correlated significantly with survivin protein. Finally, both survivin and survivin-DeltaEx3 but not survivin-2B correlated positively with apoptosis. Although survivin, survivin-2B and survivin-DeltaEx3 were all detected in both malignant and nonmalignant breast tissue, the predominant form was survivin. Our results suggest that the different forms of survivin may have different roles in apoptosis in breast cancer.

Alternative Splicing↗
PubMed2005

Measurement of plasminogen activator system components in plasma and tumor tissue extracts obtained from patients with breast cancer: an EORTC Receptor and Biomarker Group collaboration.

The plasminogen activator (PA) system comprises the 2 serine proteases, urokinase PA (uPA) and tissue PA (tPA), the 2 serpin inhibitors, PAI-1 and PAI-2 and the uPA receptor (uPAR; CD87). High levels of uPA, PAI-1, uPA-PAI-1 complex and uPAR in breast cancer tissue are associated with poor prognosis, while high levels of tPA or PAI-2 correlate with good prognosis. In this study, pre-operative plasma levels of uPA, PAI-1, uPAR, tPA, uPA-PAI-1 complex, and tPA-PAI-1 complex were measured in patients with benign (n=103) and malignant breast disease (n=113) by immunoenzymatic assays (ELISA). While plasma antigen levels of uPA, PAI-1, uPA-PAI-1 complex and uPAR were not significantly different in the 2 groups, antigen levels of tPA and tPA-PAI-1 complex were significantly higher in patients with breast carcinoma compared to the control group. In plasma from the breast cancer patients, uPA levels correlated weakly but significantly with those of tPA (r=0.20, p=0.035) and uPAR (r=0.208, p=0.028). tPA levels correlated strongly with tPA-PAI-1 complex (r=0.972, p=0.0001) while uPA-PAI-1 levels were significantly associated with PAI-1 levels (r=0.534, p<0.0001), tPA levels (r=0.348, p=0.0003) and tPA-PAI-1 levels (r=0.356, p=0.002). However, no significant correlation was found between plasma and tumor tissue levels of uPA, PAI-1, uPA-PAI-1 complex, tPA or tPA-PAI-1. Our findings indicate that determination of these factors in plasma do not reflect their concentration in tumor tissue. Therefore, measurement of PA components in blood cannot be recommended for assessing prognosis in breast cancer.

Biomarkers, Tumor↗
PubMed2004

Overexpression of the Ets-1 transcription factor in human breast cancer.

The Ets family of transcription factors regulate expression of multiple genes involved in tumour progression. The aim of this study was to investigate the expression of Ets-1 in a large panel of human breast cancers and relate its levels to the parameters of tumour progression and metastasis. Using RT-PCR, Ets-1 mRNA was detected in 30 out of 42 (71%) fibroadenomas and 131 out of 179 (73%) primary breast carcinomas. Similarly, levels of Ets-1 mRNA were not significantly different in fibroadenomas and primary breast carcinomas. Using Western blotting, four forms of the Ets-1 protein were detected, that is, p33, p42, p51 and p52. Levels of both p51 and p52 but not p33 and p42 were present at significantly higher levels in the carcinomas compared to the fibroadenomas (for p51, P<0.007; for p52, P<0.02; Mann-Whitney U-test). Levels of p52, p51 and p33 correlated significantly with uPA protein levels (P<0.01), while only levels of p52 correlated significantly with HER-2/neu protein levels (P<0.01). Using immunohistochemistry, Ets-1 was found predominantly in tumour cells, but was also detected in some stromal cells surrounding tumour islands. We conclude that, while at the mRNA level, Ets-1 was found at similar levels in fibroadenomas and primary breast carcinomas, higher protein levels were detected in the cancers compared to the benign specimens. Since p52, p51 and p33 correlate with uPA levels, these forms of Ets-1 may play a role in breast cancer metastasis.

Biomarkers, Tumor↗
PubMed2004

Needle-localised biopsy of impalpable breast lesions: a novel adjunct to surgical technique and specimen mammography.

Successful screening programmes have resulted in the more frequent detection of early impalpable breast tumours. Effective surgical management of impalpable lesions demands a precise approach to excision which is currently aided by radiologically guided needle-localisation of the lesion prior to operative removal. The surgical specimen procured is most commonly evaluated for tumour presence by specimen mammography intra-operatively or by histological analysis. The latter is more accurate but requires lengthy laboratory processing, which may result in re-operation if the primary excision is inadequate. Although advocated as the standard of care, specimen mammography remains an imperfect technique. In this article we describe a piece of surgical apparatus which attempts to address some of the concerns associated with specimen mammography. It is an inexpensive compression device which reduces operative time, avoids portable fluoroscopy, increased radiation and the necessity for specialised equipment

Biopsy, Needle↗
PubMed2003

Predictive testing for BRCA1 and 2 mutations: a male contribution.

BACKGROUND: Management strategies for women carrying BRCA1 and 2 mutations are becoming clearer and predictive testing for a known family mutation is commonly undertaken. Implications for men are not as clear and they participate less frequently. PATIENTS AND METHODS: Twenty-six men from 10 extended families underwent predictive testing. Their motivation, reaction and outcome were studied. Subjects had appropriate pre- and post-test counselling. Informed consent was obtained before predictive testing for known deleterious mutations. DNA analysis followed standard procedures. RESULTS: Eighteen tested positive and eight negative. Four had adverse psychological reactions and three reneged on their commitments to impart results. The spouse of another man had an adverse psychological reaction to the disclosure of his positive result. Two, already suffering from prostate cancer, were phenocopies and paternal lineage transmission was unexpectedly determined in another. Risk was removed from 33 offspring and confirmed for 56. CONCLUSIONS: Complex themes associated with genetic testing are confirmed and the spectrum extended. Men appear to understand the importance of participating in this process. Methods of avoiding adverse reactions merit further study along with other aspects of the process.

Adult↗
PubMed2002

Anti-human epidermal growth factor receptor 2 monoclonal antibody therapy for breast cancer.

BACKGROUND: Advances in molecular biology and improved understanding of tumour biology have led to the development of novel treatments for cancer. Trastuzumab (Herceptin; Genentech, San Francisco, California, USA) is a monoclonal antibody directed against human epidermal growth factor receptor (HER) 2 protein, which is overexpressed in a wide variety of human cancers, including 20-30 per cent of human breast cancers. HER-2 plays an important role in oncogenic transformation, tumorigenesis and metastatic spread. Overexpression is associated with a poor prognosis and predicts a poor response to several treatment modalities. METHOD: Literature relating to the monoclonal antibody was identified by a Medline literature search and by cross-referencing from the references of seminal articles on the subject. Four major clinical trials were identified and reviewed. RESULTS AND CONCLUSION: In clinical trials approximately 15-20 per cent of patients with HER-2-overexpressing tumours benefited from treatment with trastuzumab. In sensitive patients the antibody appeared to have intrinsic anticancer activity when given as a single agent. In combination chemotherapy it appeared to act synergistically with other agents. Ongoing research is evaluating trastuzumab in combination with numerous standard chemotherapy regimens and with other novel chemotherapeutic agents. Clinical trials have also revealed several serious side-effects of monoclonal antibody therapy. Most notable is an unpredictable cardiotoxicity, especially when used in combination with anthracycline-based chemotherapy regimens.

Anthracyclines↗
PubMed2001

Granulomatous appendicitis revisited: report of a case.

BACKGROUND: Isolated granulomatous appendicitis is uncommon and previously was considered to be a form of localised Crohn's disease. However more recent series have noted that relapse is rare after appendicectomy and concluded that the condition is a distinct entity unrelated to Crohn's disease. Following a case of granulomatous appendicitis at St. Vincent's University Hospital Dublin, the condition was reviewed and the results are detailed herein. METHODS: A case of granulomatous appendicitis is presented with discussion of 4 previous cases encountered in our practice and the literature is reviewed. RESULTS: The clinical presentation was sub-acute appendicitis with a mass palpable in the right iliac fossa. At operation an enlarged, inflamed appendix with a broad base was noted and appendicectomy performed. Histopathology showed numerous granulomata on microscopic examination. The yersinia serology tests were negative. Review of computerised histopathology records in the hospital for the last 7 years showed 4 additional cases of granulomatous appendicitis. This is a total of 5 of 1,615 appendectomies (an incidence of 0.31%). In all cases, the post-operative course was uneventful and the patients have had no further complaints. CONCLUSION: This small series provides further evidence that granulomatous appendicitis is a distinct clinical entity unrelated to Crohn's disease and is cured by appendicectomy. It should be suspected when there is a sub-acute onset of appendicitis and an enlarged, broad-based appendix is found at operation.

Acute Disease↗
PubMed2001

17Beta-estradiol stimulates mineralized bone nodule formation when added intermittently to SaOS-2 cells.

It is now well established that estrogen inhibits bone resorption. However, its effect on bone formation remains controversial. We studied the effect of 17beta-estradiol (E2) on mineralized bone nodule formation in long-term cultures of osteosarcoma SaOS-2 cells. We showed that SaOS-2 cells formed mineralized nodules which under electron microscopy revealed a bone structure with active osteoblasts, entrapped osteocytes, extracellular collagen fibrils and hydroxyapatite deposits, making this system a valid model to study bone formation in vitro. Intermittent addition of E2 for 6 hours during a 48-hour cycle of changes of medium, starting from day 3, resulted in a dose-dependent stimulation of mineralized bone nodule number and area, as well as alkaline phosphatase activity. In conclusion, we report for the first time a stimulatory effect of E2 on mineralized bone nodule formation in human osteoblasts in culture.

Alkaline Phosphatase↗
PubMed2000

Metalloproteinases: role in breast carcinogenesis, invasion and metastasis.

The matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases. Their primary function is degradation of proteins in the extracellular matrix. Currently, at least 19 members of this family are known to exist. Based on substrate specificity and domain organization, the MMPs can be loosely divided into four main groups: the interstitial collagenases, gelatinases, stromelysins and membrane-type MMPs. Recent data from model systems suggest that MMPs are involved in breast cancer initiation, invasion and metastasis. Consistent with their role in breast cancer progression, high levels of at least two MMPs (MMP-2 and stromelysin-3) have been found to correlate with poor prognosis in patients with breast cancer. Because MMPs are apparently involved in breast cancer initiation and dissemination, inhibition of these proteinases may be of value both in preventing breast cancer and in blocking metastasis of established tumours

Apoptosis↗
PubMed2000

Increased gelatinase-A and gelatinase-B activities in malignant vs. benign breast tumors.

Matrix metalloproteinases (MMP) types 2 and 9 (also known as gelatinase A and B) are thought to be causally involved in cancer invasion and metastasis. In normal as well as in malignant tissue, both these MMPs occur in multiple forms such as inactive precursors, active enzymes and enzyme-inhibitor complexes. Using newly developed quantitative activity assays, the levels of active MMP-2, total (active and activatable) MMP-2 and total MMP-9 were found to be significantly higher in breast carcinomas than in fibroadenomas. In addition, active MMP-2 and MMP-9 were detected more frequently in malignant than in benign breast carcinoma. These new quantitative activity assays are likely to be of use in studying the mechanism of action of both MMP-2 and -9, assessing their potential prognostic value in different cancers and in the design of MMP inhibitors for preventing cancer metastasis.

Breast Neoplasms↗
PubMed2000

High levels of TIMP-2 correlate with adverse prognosis in breast cancer.

TIMP-2 is an endogenous inhibitor of MMPs. Most data from model systems suggest that high levels of this inhibitor prevent metastasis. In human breast cancers, however, we show that high levels of TIMP-2 correlate with both shortened disease-free interval and overall survival. In primary breast cancers, TIMP-2 levels showed no significant relationship with either tumor size or axillary node status but correlated inversely with estrogen receptor levels. TIMP-2 levels also correlated significantly with those for TIMP-1. We conclude that high levels of endogenous TIMP-2, like other protease inhibitors such as PAI-1 and TIMP-1, correlate with progression of human breast cancer.

Biomarkers, Tumor↗
PubMed1999

High levels of tissue inhibitor of metalloproteinase-1 predict poor outcome in patients with breast cancer.

Studies from model systems suggest that matrix metalloproteinases (MMPs) are causally involved in tumor progression while tissue inhibitors of MMPs (TIMPs) prevent this progression. Here, we show that concentrations of TIMP-1 are significantly higher in breast carcinomas than in fibroadenomas. In primary breast cancers, TIMP-1 concentrations increased with increasing tumor size but showed an inverse relationship with estrogen receptor concentrations. In primary breast cancers also, TIMP-1 levels were weakly but significantly correlated with those for MMP-1, proMMP-2, active MMP-2, MMP-3 and proMMP-9. Contrary to what might be expected from published data on model systems, high concentrations of TIMP-1 predicted a poor outcome in patients with breast cancer. We conclude that in human breast cancer, endogenous TIMP-1 does not inhibit tumor progression but may enhance the process.

Biomarkers, Tumor↗
PubMed1999

Production and inhibition of the gelatinolytic matrix metalloproteinases in a human model of vein graft stenosis.

OBJECTIVES: human vein graft stenoses are caused by intimal hyperplasia, a process which is characterised by extensive degradation and accumulation of extracellular matrix. This study investigated the role of the matrix metalloproteinases (MMPs) - the principal physiological mediators of extracellular matrix degradation - in the development of intimal hyperplasia in cultured human long saphenous vein. DESIGN: experimental study. MATERIALS AND METHODS: paired venous segments with the endothelium intact or denuded were cultured in standard conditions for 14 days. At the termination of culture, MMPs were extracted from one half of the tissue, whilst the remainder of the vein was prepared for histological examination. RESULTS: stereologic analysis revealed that the endothelium intact veins developed a significantly thicker neointima when compared to the denuded venous segments (20 micron v. 0 micron, p=0.006). Quantification of MMPs by substrate gel enzymography demonstrated that the development of a neointima was associated with increased production of the gelatinolytic MMP-9 (p=0. 03) in intact veins. Immunocytochemistry showed that the MMP-9 localised to the internal elastic lumina, which suggested a role in facilitating smooth-muscle-cell migration into the intima. The role of MMPs-2 and -9 in intimal hyperplasia was further investigated by culturing intact venous segments with a therapeutic concentration of doxycycline--a potent MMP inhibitor. These experiments demonstrated that a therapeutic dose of doxycycline significantly reduced neointimal thickness (control 21 micron, doxycycline 10 mg/l-5.5 micron), in conjunction with a significant reduction in the production of MMP-9. CONCLUSIONS: these data suggest that elevated levels of MMPs may play a significant role in the development of human intimal hyperplasia and that inhibition of these enzymes may offer a potential therapeutic strategy for the prevention of hyperplastic lesions.

Anti-Bacterial Agents↗