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Biomedical subjects

S D Heys

Publications and source records attributed to S D Heys.

At least 19 recordsLinked to original sources
PubMed2002

Folate and breast cancer: the role of polymorphisms in methylenetetrahydrofolate reductase (MTHFR).

Evidence is growing that low folate status may be a factor in the aetiology of several cancers, including breast cancer. The methylenetetrahydrofolate reductase gene (MTHFR), which has a key role in folate metabolism, is polymorphic. We report a case-control study of two functional polymorphisms in MTHFR, dietary folate intake and breast cancer. Sixty-two cases with invasive breast cancer and sixty-six general practice controls participated. Women reporting the highest dietary folate intake had non-significantly reduced breast cancer risk (odds ratio (OR) = 0.49, 95% confidence interval (CI) 0.20-1.20). Risk was significantly lower for the 1298CC genotype compared to AA (OR = 0.24, 95% CI 0.06-0.97). Relative to compound wild-type subjects, compound heterozygotes had moderately reduced risk (OR = 0.47, 95% CI 0.11-1.92) and homozygote variants (677TT and/or 1298CC) greater reduced risk (OR = 0.26, 95% CI 0.07-0.96); the trend was statistically significant. Patterns in risk with regard to genotype and folate combinations are broadly similar those reported for colorectal neoplasia. The roles of MTHFR and folate in breast cancer aetiology are likely to be complex.

Aged↗
PubMed2002

Breast cancer in women aged 35 and under: prognosis and survival.

BACKGROUND: Breast cancer comprises 22% of all cancers occurring in females but only 2% of cases occur in women aged 35 years and less. The presentation, behaviour and prognosis of breast cancer in such women, when compared with older women, are unclear and conflicting results have been reported. This study has audited clinical and pathological features in patients aged 35 years and under with breast cancer. METHODS: One hundred and thirteen patients were identified. The details of clinical staging, local and distant disease recurrence and overall survival were obtained for all patients. Histological sections of tumours were examined for type, grade, size, presence of surrounding intraductal carcinoma, presence of vascular space invasion, lymph node involvement and oestrogen receptor (ER) status. RESULTS: Histological examination of the tumours revealed that 94% were invasive ductal carcinoma. In 73% of the cases the tumours were grade 3, 49% of patients who underwent axillary surgery had lymph node involvement and 20% of tumours expressed ERs. The overall 5-year survival was 64%. Predictors of a poorer survival (univariate analysis) were: increasing tumour size, absence of ERs, presence of lymphovascular space invasion, axillary lymph node involvement and detectable metastases at the initial presentation. Multivariate analysis revealed that only lymphovascular space invasion was an independent predictor of a poor survival. CONCLUSION: Breast cancer in young (< or = 35 years) women is biologically aggressive, compared with older women. Factors predicting survival and overall survival rates, however, were comparable with those previously reported for older women with breast cancer.

Adult↗
PubMed2001

Fatty acid regulation of protein kinase C isoforms in prostate cancer cells.

Polyunsaturated fatty acids influence the aetiology of prostate cancer. Their effects on cellular mechanisms regulating prostate tumorigenesis are unclear. Using prostate cancer cells (LNCaP), we determined effects of n-9-OA, n-6-LA, and n-3-EPA on total PKC and its isoforms in relation to cell proliferation and PSA production. PKC-alpha, delta, gamma, iota, mu, and zeta were present in LNCaP cells; PKC-beta, epsilon, eta, and theta isoforms were not. PKC-alpha was detected only in cytosol; PKC-delta, iota, gamma, and mu were present in cytosol and in membranes. Fatty acids increased cell proliferation, total PKC activity and elicited pro-proliferative effects on specific PKC isoforms (PKC-delta and -iota). EPA and LA increased total PKC activity and reduced membrane-abundance of PKC-delta. OA reduced cytosolic and membrane PKC-delta. Only EPA reduced PKC-gamma membrane abundance. Fatty acids enhanced cytosolic PKC-iota abundance but only EPA and to a lesser extent LA increased its membrane content. Changes in PKC-delta, -iota, and -gamma did not affect PSA production.

Cell Division↗
PubMed2001

What is achieved by mammographic surveillance after breast conservation treatment for breast cancer?

BACKGROUND: After breast conservation surgery for breast cancer, patients are followed up by regular clinical examination and mammography, at intervals which vary according to local practice. However, the optimum interval remains unclear with current guidelines suggesting mammography should be carried out every 1 to 2 years. This study has investigated this aspect and, in particular, whether mammography or clinical examination or both allowed an early detection of recurrence of the disease in the conserved breast. METHODS: A total of 695 patients who had undergone breast conservation surgery were identified from a database of prospectively recorded data during the period 1990 to 1995. Clinical examination and annual mammography were performed in accordance with local protocol. The results of clinical examination, mammography, and local recurrence rates were evaluated. RESULTS: A total of 2,181 mammograms were undertaken in the 695 patients studied. Local recurrence of disease in the conserved breast occurred in 21 patients (3%), at a mean follow-up of 3.5 years. The first identification of tumor recurrence was by clinical examination in 11 patients with local recurrence, and by the surveillance mammography in the other 10 patients with local recurrence. Overall, mammography detected the local recurrence in 13 of 20 (65%) patients who underwent this examination. In the other patients, the recurrence was detected on clinical examination only. In addition, in 52 patients, mammography was falsely positive, giving a false positive rate of 2.3%. Contralateral cancers in the opposite breast were detected in 2 patients. CONCLUSIONS: The detection of local disease after breast conservation surgery requires both clinical examination and mammography. In the context of our follow-up policy, in 52% of patients with local recurrence, this was first identified by clinical examination. Disease recurrence was identified in the other 48% of patients by mammographic surveillance. Overall, mammography will identify or confirm local recurrence in two thirds of women. However, in a small number of cases (2.3% in our series) mammography will give false positive results. New imaging modalities to assist in the diagnosis of local recurrence of disease after breast conservation surgery are required.

Adult↗
PubMed2000

Distal proctocolitis and n-3 polyunsaturated fatty acids (n-3 PUFAs): the mucosal effect in situ.

It has been postulated that patients with ulcerative colitis (UC) have altered reactivity of gut-associated lymphoid tissue. In such cases there is intense infiltration of the mucosa with immune competent cells and associated tissue damage. We have shown previously that the dietary supplementation with the n-3 polyunsaturated fatty acids (n-3 PUFAs), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) results in significant systemic immune suppression. The aim of this study, therefore, was to evaluate the in situ effect of n-3 PUFAs on distal proctocolitis. Each patient received either fish oil extract (EPA 3.2 g, DHA 2.4 g) (n = 9) or sunflower oil (n = 9) daily in a double blind manner for six months. Monthly assessment included: (1) disease activity using clinical, sigmoidoscopic, and histological scores and (2) immunohistochemical analysis (immunoglobulins, CD profiles) of rectal biopsy specimens (before and after six months supplementation) using monoclonal antibodies and quantitative computer-assisted video image analysis. Prior to receiving supplementation, patients with proctocolitis (n = 18) showed significantly higher numbers of cells expressing CD3 (pan T cells) and HLA-DR and IgM containing cells compared with non-colitic controls (n = 8). Six months supplementation with n-3 PUFAs resulted in significant reduction in the number of cells expressing CD3 and HLA and the percentage of cells containing IgM. There was no significant change in the CD20 nor the percentage of IgG or IgA containing cells in either group of patients with procto-colitis. In patients receiving n-3 PUFA supplementation, there was improvement in the disease activity and histological scores, compared with pretreatment evaluation. This study has demonstrated both evidence of suppression of in situ immune reactivity and concurrent reduction in disease activity in patients with proctocolitis receiving n-3 PUFA supplementation. This may have important implication for therapy in patients with ulcerative colitis.

Animals↗
PubMed2000

Distal procto-colitis and n-3 polyunsaturated fatty acids: the mechanism(s) of natural cytotoxicity inhibition.

BACKGROUND: Altered natural killer (NK) and lymphokine-activated killer (LAK) cell activities have been reported with ulcerative colitis (UC). Previously, we have shown that in patients with UC, the n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), specifically inhibit natural cytotoxicity with clinical improvement in disease activity. The aim of this study therefore was to evaluate the possible mechanism(s) involved in this inhibition, and in particular the alteration of production of interleukin 2 (IL2) and the arachidonic acid metabolite leukotriene B4 (LTB4), both known to modulate NK cell activity. MATERIALS AND METHODS: Each patient with procto-colitis received either fish oil extract (EPA 3.2 g, DHA 2.4 g; n = 9) or placebo (n = 9) daily for 6 months. Monthly assessment included disease activity using clinical and sigmoidoscopic scores. Peripheral blood mononuclear (PBMN) cells were isolated and NK cell cytotoxic activity in vitro was measured. Monthly serum samples were analysed for LTB4, IL2 and soluble IL2 receptors (sIL2R). RESULTS: The n-3 PUFAs group had significantly reduced NK cell activity, compared with the placebo group (P < 0.05, Mann-Whitney U-test). In the n-3 PUFA group, incubation of PBMN cells for 72 h with recombinant interleukin 2 (rIL2) reversed the NK inhibition. In patients with active proctocolitis, serum levels of LTB4 correlated positively with NK cell cytotoxicity (r = 0.873, P < 0.05, Kendall's correlation coefficient). After six months of n-3 PUFAs supplementation, serum levels of LTB4 were undetectable with concurrent significant reduction in NK cell cytotoxic activity. The latter was associated with significant reduction of serum IL2 and sIL2R levels (P < 0.05). CONCLUSION: This study has demonstrated both evidence of suppression of immune reactivity and concurrent reduction in disease activity in patients with proctocolitis receiving n-3 PUFAs supplementation. This may have important implications for therapy in patients with UC.

Cytotoxicity, Immunologic↗
PubMed2000

Positron emission tomography using [(18)F]-fluorodeoxy-D-glucose to predict the pathologic response of breast cancer to primary chemotherapy.

PURPOSE: To determine whether [(18)F]-fluorodeoxy-D-glucose ([(18)F]-FDG) positron emission tomography (PET) can predict the pathologic response of primary and metastatic breast cancer to chemotherapy. PATIENTS AND METHODS: Thirty patients with noninflammatory, large (> 3 cm), or locally advanced breast cancers received eight doses of primary chemotherapy. Dynamic PET imaging was performed immediately before the first, second, and fifth doses and after the last dose of treatment. Primary tumors and involved axillary lymph nodes were identified, and the [(18)F]-FDG uptake values were calculated (expressed as semiquantitative dose uptake ratio [DUR] and influx constant [K]). Pathologic response was determined after chemotherapy by evaluation of surgical resection specimens. RESULTS: Thirty-one primary breast lesions were identified. The mean pretreatment DUR values of the eight lesions that achieved a complete microscopic pathologic response were significantly (P =.037) higher than those from less responsive lesions. The mean reduction in DUR after the first pulse of chemotherapy was significantly greater in lesions that achieved a partial (P =.013), complete macroscopic (P =.003), or complete microscopic (P =.001) pathologic response. PET after a single pulse of chemotherapy was able to predict complete pathologic response with a sensitivity of 90% and a specificity of 74%. Eleven patients had pathologic evidence of lymph node metastases. Mean pretreatment DUR values in the metastatic lesions that responded did not differ significantly from those that failed to respond (P =.076). However, mean pretreatment K values were significantly higher in ultimately responsive cancers (P =.037). The mean change in DUR and K after the first pulse of chemotherapy was significantly greater in responding lesions (DUR, P =.038; K, P =.012). CONCLUSION: [(18)F]-FDG PET imaging of primary and metastatic breast cancer after a single pulse of chemotherapy may be of value in the prediction of pathologic treatment response.

Adult↗
PubMed2000

Current and potential chemotherapeutic agents used for induction chemotherapy in the treatment of breast cancer.

A substantial proportion of breast cancers are large (<3 cm) or locally advanced (T3, T4, TXN2) at the time of initial presentation. The therapeutic goals that must be achieved in patients with such cancers are to obtain adequate local disease control so that surgery can be performed and to abolish occult distant metastases therefore improving survival. Over the past three decades conventional adjuvant chemotherapy regimens have been employed pre-operatively (neo-adjuvant or primary chemotherapy) to achieve these goals. Studies have now shown that the survival of patients who receive neo-adjuvant chemotherapy is comparable to that of those who receive the same chemotherapy regimen following surgery. It is also apparent that although clinical tumour response rates to neo-adjuvant chemotherapy may be high there is considerable scope for improvement in the corresponding pathological tumour response. Furthermore, data from major studies that have comprehensively evaluated the use of pre-operative chemotherapy now indicates that the pathological response of breast cancers following treatment is of far greater prognostic importance than the clinical response. Recent interests has focoused, therefore, on the implementation of more prolonged or dose intensive chemotherapy regimens with the aims of improving pathological response to treatment and ultimately overall survival. Newer antineoplastic agents are also becoming available that may be used alone or in combination with conventional therapies in order that tumor response may be improved. This review describes current and potential therapeutic agents that may be used for the induction therapy of breast cancer.

Antibiotics, Antineoplastic↗
PubMed2000

Alterations in polyamine catabolic enzymes in human breast cancer tissue.

High concentrations of acetyl polyamines have been observed in human breast cancer compared with the equivalent normal tissue, however, no explanation as to the reason for the increases has been proposed. In this study, we show that changes in the enzymes responsible for the breakdown of acetyl polyamines occur in breast cancer tissue. Spermidine/spermine N1-acetyltransferase, the first and rate-limiting enzyme in polyamine catabolism, is increased in the tumor tissue whereas polyamine oxidase (PAO) is decreased. The changes in PAO correlate with prognostic factors, and activity decreases as the size and histological grade of tumors increase. The metabolism of polyamines by PAO generates locally high concentrations of hydrogen peroxide, a known inducer of apoptosis; thus, low PAO activity may contribute to the low level of apoptosis seen in tumor cells. Therefore, drugs that induce PAO activity may be a novel means of attacking tumor cells.

Acetylation↗
PubMed2000

Apoptosis and prognosis in cancer: rationale and relevance.

Apoptosis is the biological process by which cells in tissues undergo programmed death. This process is morphologically identifiable and characterised by light and electron microscopy. However, the biological mechanisms underlying this process, as yet, are poorly understood and in need of elucidation. As apoptotic tumour cells can be identified and counted by light microscopy, there has been interest in the application of the enumeration of apoptosis in malignant growths as a putative prognostic marker. This review outlines the rationale for and discusses the relevance of using such an approach in clinical practice.

Animals↗
PubMed2000

Peri-operative nutritional support: controversies and debates.

BACKGROUND: Malnutrition continues to be a significant problem in patients undergoing surgery. The relationship between a poor nutritional status and subsequent post-operative morbidity and mortality is well recognised. It is logical, therefore, that malnourished patients should be given nutritional supplementation in the peri-operative period. However, the benefits of this approach have been debated and as we enter the new millennium there are many questions regarding then role of peri-operative nutritional support that remain unanswered. AIMS: This review aims to determine how we decide which patients are malnourished, which patients require nutritional support and what are the benefits, by what route (enteral or parenteral), and for how long should nuritional support be given are there key nutrients which should be given. RESULTS: Nutritional status can be assessed routinely in all patients, with clear definitions of undernutrition, overnutrition and nutritional risk indices being applicable to surgical practice. Peri-operative parenteral nutritional support does benefit patients who are malnourished but they should receive at least 7 to 10 days of support before surgery. The theoretical benefits of enteral nutrition are clear but whether or not this translates into clinical benefits remains contentious. Nutritional support supplemented with key nutrients does seem to be advantageous by reducing the risk of septic post-operative complications and reducing overall stay in hospital. CONCLUSION: Patients most likely to benefit from peri-operative nutritional support can be defined. Enteral nutritional support has advantages over parenteral nutrition and the administration of key nutrients has clinical benefits.

Enteral Nutrition↗
PubMed1999

Minimal modulation of lymphocyte and natural killer cell subsets following minimal access surgery.

BACKGROUND: Trauma, whether accidental or surgically induced, is known to cause significant modulation of the cell-mediated immune response. Minimal access surgery (MAS) has been shown to improve postoperative recovery and enhance rehabilitation. The degree of immunosuppression resulting from two MAS techniques was studied and compared by measuring the circulating T lymphocyte and natural killer (NK) cell subsets. METHOD: This investigation was a randomized prospective study of patients admitted to the Professorial Surgical Unit, Aberdeen Royal Infirmary for elective cholecystectomy. Two methods of MAS were studied-laparoscopy and minilaparotomy. RESULTS: Laparoscopy was found to cause significantly less reduction in the number of cells expressing T lymphocyte phenotypic surface markers (CD2, CD3, CD8, CD4:CD8 ratio), activation markers (CD71 and HLA-DR), and NK cell subsets (CD11b, CD16, CD56 and CD57), when compared with the minilaparotomy technique. CONCLUSIONS: These data show that host defences are less suppressed after laparoscopic cholecystectomy, and this may have important implications for the use of laparoscopic techniques in major surgical resections, especially for malignant disease.

Adult↗
PubMed1999

Minimal access surgery for cholelithiasis induces an attenuated acute phase response.

BACKGROUND: Some benefits of laparoscopic (LC) and minilaparotomy (MC) cholecystectomy may reflect attenuation of the acute phase response. The authors examined components of this response. METHODS: Patients were randomized to LC (n = 11) or MC (n = 11). C-reactive protein (CRP), alpha-1-antitrypsin (AAT), retinol-binding protein (RBP), transferrin, and albumin were measured preoperatively and on postoperative days 1, 2, 4, and 7. Interleukin-1 receptor antagonist (IL-1ra), IL-6, and tumor necrosis factor (TNF-alpha) were measured more frequently perioperatively. Peak expiratory flow rate, forced expiratory volume in 1 second, and forced vital capacity were measured daily. RESULTS: The IL-6 increase was more persistent and marked in the MC patients from hour 8 to day 7 postoperatively (P < 0.05). Alterations in CRP, AAT, and albumin were similar. Postoperative deficits of respiratory function correlated with the magnitude of acute phase protein alteration. CONCLUSIONS: Minimal access surgery induces an acute phase response that is less prominent after a laparoscopic technique.

Acute-Phase Proteins↗