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Biomedical subjects

S D Heys

Publications and source records attributed to S D Heys.

At least 73 records · Page 4Linked to original sources
PubMed1997

Dietary supplementation with L-arginine: modulation of tumour-infiltrating lymphocytes in patients with colorectal cancer.

BACKGROUND: Dietary supplementation with L-arginine enhances natural cytotoxicity in peripheral blood lymphocytes but its effect on infiltrating lymphoreticular cells within a tumour microenvironment is unknown. The effects of dietary supplementation with L-arginine on tumour-infiltrating lymphocytes (TILs) in patients with colorectal cancer were evaluated. METHODS: Eighteen patients received either a standard hospital diet (controls) or a standard diet supplemented with 30 g per day of L-arginine for 3 days before surgery. Tumour biopsies were taken at surgery and lymphocyte subsets (CD antigens) and macrophages examined immunohistochemically. RESULTS: Tumours from patients receiving L-arginine contained increased numbers of specific cell subsets within the tumour which expressed CD16 (P = 0.004) and CD56 (P = 0.001) surface markers, when compared with tumours from control patients. There were no differences in the total number of T and B cells, T helper and T suppressor cells. CONCLUSION: Dietary supplementation with L-arginine significantly alter the spectrum of TILs in human colorectal cancers in vivo. These findings have important implications for new strategies in anticancer treatment.

Aged↗
PubMed1997

Cognitive performance and mood after a weekend on call in a surgical unit.

BACKGROUND: Considerable interest and concern have been expressed about junior doctors' hours. This study was carried out to evaluate the emotional and cognitive effects of a weekend on call in a surgical ward. METHODS: Ten surgical house officers were assessed, in counterbalanced design, on four Monday mornings, twice after a weekend off duty and twice after a weekend on call. Cognitive functioning was assessed using the Cognitive Drug Research computerized cognitive assessment system, and emotional state was evaluated by means of the Aberdeen Mood Rating Scale. RESULTS: Following a weekend on call, significant impairment in concentration, speed and power was observed, and the doctors felt less confident, less energetic and more confused. Impaired attention, working memory, long-term memory and confusion were most closely correlated with number of hours worked on Sunday, and tiredness and confusion were related to number of hours slept. CONCLUSION: A weekend on call has significant deleterious effects on cognitive performance and mood. The findings have implications for staffing levels and the design of duty rosters.

Affect↗
PubMed1997

Expression of growth factor receptors is not a prognostic indicator in young patients with colorectal cancer.

Growth factor receptor expression has been shown to be of prognostic significance in certain cancers, but its relevance in young patients with colorectal cancer is unknown. The aim of this study, therefore, is to determine the prognostic relevance of growth factor receptor expression [c-erbB-2, epidermal growth factor receptor (EGFR) and transforming growth factor beta receptor (TGF beta R)] in such patients. Ninety-two patients were evaluated. They were staged using the Jass staging system and the presence of metastases. The expression of EGFR and TGF beta R and the protein production of c-erbB-2 were detected using standard immunohistochemical techniques. The expression of EGFR and TGF beta R and the presence of the c-erbB-2 protein product were not identified as independent prognostic factors for survival. Furthermore, their expression did not correlate with established prognostic indicators such as Jass staging, the presence of extramural vascular invasion and the degree of tumour differentiation.

Biomarkers, Tumor↗
PubMed1996

Natural killer cells and cancer.

BACKGROUND: Natural cytotoxicity, mediated by natural killer (NK) cells and cell with lymphokine-activated killer (LAK) activity, is believed to play an important role in host anti-cancer mechanisms. METHODS: The authors critically review recent publications on the role of natural cytotoxicity in patients with cancer. RESULTS: In patients with cancer, several studies have noted variations in the numbers and activity of NK and cells with LAK activity in different body compartments. NK cell activity in the peripheral blood lymphocytes (PBLs) is higher than that found in lymph nodes and within tumors, and this appears to be due to the presence of suppressor factors. The natural cytotoxicity of PBLs in patients with different types of cancers varies. However, there appears to be a trend for natural cytotoxicity to be reduced in certain cancer patients, possibly related to tumor volume or dissemination. Anti-cancer treatments (e.g., surgery, hormonal modulation, radiotherapy and chemotherapy) can also result in suppression of natural cytotoxicity, although the long-term effect on response to treatment and development of metastases is at present unknown. CONCLUSIONS: NK and LAK cells, through the use of immune biologic modifiers, have been demonstrated to have a therapeutic role in the treatment of human cancers. Further studies are required to determine the optimal dosages and combinations of chemotherapeutic agents, the timing of surgery, and the adjuvant use of immune biologic response modifiers. An increasing awareness and understanding of this field, may allow for the future development of anti-cancer therapies.

Cytotoxicity, Immunologic↗
PubMed1996

Nutritional pharmacology and malignant disease: a therapeutic modality in patients with cancer.

It is now established that certain nutrients have a significant effect on cellular metabolism and growth, tissue repair and regeneration, and modulation of host defences. So far, however, potential clinical benefits have been difficult to demonstrate. Nevertheless, the use of nutrients in combinations seems to have promise and may be associated with a reduction in infectious complications and length of hospital stay. Nutritional pharmacology in the future may be able to improve tumour response to chemotherapy and may minimize the metabolic effect of cachexia.

Animals↗
PubMed1996

Male breast cancer: clinico-pathological features, immunocytochemical characteristics and prognosis.

A series of 30 cases of male breast cancer in the North-East of Scotland is reviewed. The aims of the study were to document clinico-pathological and immunocytochemical features (available for 25) of these patients and to establish which factors could predict prognosis. Tumours were studied for the expression of oestrogen receptors (ERs), the oestrogen-dependent proteins pS2 and cathepsin D, the oncoprotein products of c-erb-B2 and the p53 tumour-suppressor-gene derived protein. Clinico-pathological features documented were in agreement with those reported by other authors. The overall 5-year survival was 53%. Tumour grade and lymph-node status influenced prognosis. In this series, 64% of the tumours expressed ERs, 50% pS2, 46% cathepsin D, 42% the c-erb-B2 transmembrane oncoprotein and 54% p53. In contrast to female breast cancer, the presence of either substantial amounts of ERs or the oestrogen-dependent protein pS2 correlated with poorer prognosis in males. This correlation has not previously been documented.

Breast Neoplasms, Male↗
PubMed1996

The cognitive effects of recombinant interleukin-2 (rIL-2) therapy: a controlled clinical trial using computerised assessments.

It has been suggested that patients undergoing treatment with recombinant interleukin-2 (rIL-2) may develop cognitive impairment. To evaluate these effects, 17 patients with advanced colorectal cancer took part in a randomised, parallel group study of rIL-2 with chemotherapy (5-fluorouracil and leucovorin) and chemotherapy alone. Assessments were carried out daily whilst patients were in hospital and regularly between cycles of treatment using state-of-the-art computerised cognitive assessment, as well as traditional psychometric tests. Rigorous discontinuation criteria were applied to ensure that the effect of time-related variables did not influence the results. One patient developed repeated transient psychotic episodes associated with rIL-2 infusions and another regularly became confused. Computerised cognitive assessments revealed that immunochemotherapy produced significant impairment in various tasks, especially reaction time, picture recognition and vigilance. These effects were not due to sleep deprivation or pyrexia. For most patients, cognitive functioning was restored to the baseline level within 10 days following the cessation of rIL-2. In conclusion, during infusions of rIL-2, some patients experience severe confusion and amnesia which resembles some of the major cognitive impairments associated with dementias such as Alzheimer's disease. Computerised cognitive assessment using the Cognitive Drug Research system provides a feasible, sensitive and reliable method of evaluating cognitive changes in patients with cancer. It could usefully be included in quality of life assessments in clinical trials where treatment-related cognitive changes need to be evaluated.

Aged↗
PubMed1996

Lymphangitis carcinomatosa: a literature review.

Intrathoracic metastases occur in 30-40% of patients with malignant disease. In this group 6-8% have lymphangitis carcinomatosa. This review examines the pathogenesis, investigation and treatment of lymphangitis carcinomatosa. The 40-49 years age group is most commonly affected. In 46% of patients respiratory symptoms are the initial presentation of the underlying carcinoma. The most common underlying primary tumours are breast (33%), stomach (29%) and lung cancers (17%). Approximately 50% die within 3 months of their first respiratory symptoms but those with a prostatic primary carcinoma may have good remission with adjuvant hormonal therapy.

Adult↗
PubMed1996

A novel diagnostic index for use in the breast clinic.

The diagnostic accuracy of clinical examination, mammography, ultrasonography and fine needle aspiration (FNA) cytology in discriminating between benign and malignant breast lesions has been retrospectively assessed in 603 patients who attended the Professorial Breast Clinic and then underwent surgical biopsy, in Aberdeen Royal Infirmary, between January 1989 and September 1992. In this series of patients, FNA cytology gave the highest overall prediction of malignancy (92.6%) with a sensitivity of 87% and a specificity of 98%, whilst ultrasonography gave the lowest correct overall prediction (75.6%), with a sensitivity of 70% and a specificity of 79%. Using all the available findings (clinical examination, mammography, ultrasonography, FNA) as well as the patients' age, a stepwise logistic discriminant analysis was used to derive a mathematical equation for use as a novel diagnostic index. Weighted scores, derived from each variable, were used in the discriminant equation to predict the likelihood of malignancy in patients of different ages (>90%). For young patients (<35 years) the discriminant analysis predicted the diagnosis in 98% of women correctly. Quadruple assessment provides an opportunity for establishing the likely diagnosis in most patients the same day they visit the Breast Clinic. The diagnostic index, currently being evaluated prospectively in our breast clinic, may be a further aid to establishing a correct diagnosis.

Adult↗
PubMed1995

Interleukin 2 receptor expression and interleukin 2 localisation in human solid tumor cells in situ and in vitro: evidence for a direct role in the regulation of tumour cell proliferation.

Frozen sections of 52 human solid tumours (38 malignant and 14 benign) of varied histogenesis were immunohistochemically stained with well characterised monoclonal antibodies (MAbs) to human interleukin 2 (IL-2) and the alpha and beta chains of its receptor (R). In all malignant specimens, the tumour cells expressed the IL-2R beta subunit (p75) but not the IL-2R alpha subunit (CD25). In 36 of 38 malignant tumours examined, there was conspicuous staining for IL-2 in the tumour cell nuclei/nucleoli and perinuclear cytoplasm. In the human solid tumour cell lines G361 (melanoma), A549 (lung), MCF-7 (breast) and WiDR (colorectal), both subunits of the IL-2R appeared to be expressed, although the alpha subunit only weakly. Exogenous addition of human recombinant (r) interleukin 2 altered cell numbers in 3 of the 4 cell lines (WiDR was refractory). When grown in the absence of exogenously added rIL-2, IL-2 staining was observed in all cell lines. The pattern of distribution was similar to that exhibited by the tumour cells in situ (i.e., a nuclear/nucleolar localisation). In G361 melanoma cells, this IL-2 staining was present in proliferating cells but disappeared as the cultures approached confluence. Addition of an IL-2R beta subunit blocking antibody to growing G361 cultures (grown in the absence of rIL-2) resulted in a significant reduction in cell numbers. We propose, therefore, that the presence of immunoreactive IL-2 and IL-2R expression is characteristic of human malignant cells and that IL-2 may play a role in the autocrine stimulation of proliferation of malignant cells, such as G361 melanoma cells.

Cell Division↗
PubMed1995

Modulation of the cytokine and acute-phase response to major surgery by recombinant interleukin-2.

Major surgery suppresses host immune reactivity through alterations in monocyte and T cell-derived cytokine, eicosanoid and acute-phase protein release. Recombinant interleukin (IL) 2 augments T lymphocyte and monocyte activity in vitro. Eighteen patients, with localized colorectal cancer, were randomized to receive either recombinant IL-2 or placebo for 3 days by subcutaneous injection before surgery. Serum levels of IL-1 beta, IL-6, tumour necrosis factor alpha, soluble IL-2 receptor, C-reactive protein (CRP) and albumin were measured, and T lymphocyte surface expression of HLA-DR and CD25 and neutrophil phagocytosis were determined, before and for 21 days after surgery. Significant augmentation of IL-6, CRP and soluble IL-2 receptor production, enhanced expression of activation markers and increased neutrophil activity were found. Recombinant IL-2 may have a role in ameliorating the immunosuppression found after major surgery.

Acute-Phase Reaction↗
PubMed1995

A phase III study of recombinant interleukin-2, 5-fluorouracil and leucovorin versus 5-fluorouracil and leucovorin in patients with unresectable or metastatic colorectal carcinoma.

135 patients with locally advanced or metastatic colorectal cancer were entered into a phase III trial evaluating the efficacy of chemoimmunotherapy [recombinant interleukin 2 (rIL2)/5-fluorouracil (5-FU) and leucovorin (LV)] versus chemotherapy alone (5-FU/LV). A cycle of chemoimmunotherapy comprised a constant intravenous infusion of rIL2 at a dose of 18 x 10(6) U/m2/24 h for 120 h, followed by three bolus injections of 5-FU (600 mg/m2) and LV (25 mg/m2) at weekly intervals. Patients receiving chemotherapy alone received 5-FU/LV at the same dose at weekly intervals for 6 weeks followed by a rest period of 2 weeks, constituting one cycle of therapy. A maximum of 6 months therapy was given in both arms of the study. The response rates (complete and partial responses) were 17% in patients receiving rIL2/5-FU/LV versus 16% in those in the 5-FU/LV arm of the study. Median survival and progression-free survival were comparable for the two groups of patients, although there was a trend for a prolongation of survival in patients receiving chemoimmunotherapy compared with chemotherapy alone, beyond 12 months. Retrospective subgroup analyses revealed a significantly increased survival in poor prognosis patients (ECOG 1) treated with rIL2/5-FU/LV when compared to those receiving chemotherapy alone. Therefore, further studies evaluating the dose and duration of chemoimmunotherapy in patients with metastatic colorectal cancer seem warranted.

Adult↗
PubMed1995

Polyadenylic-polyuridylic acid enhances the natural cell-mediated cytotoxicity in patients with breast cancer undergoing mastectomy.

BACKGROUND: Surgical procedures suppress host antitumor defense mechanisms, which may increase the risk of metastatic tumor dissemination. We have evaluated the effects of the biologic response modifier polyadenylic-polyuridylic acid (PAPU) on natural cytotoxicity in patients with breast cancer undergoing operation. METHODS: PAPU (150 mg) or placebo was given intravenously during the perioperative period (preoperative, days -1 and 0; postoperative, days 1, 3, 5, 7, and 14). The function (chromium release assay) and number (flow cytometry) of natural killer (NK) cells were measured before operation (days -2 and -1), on the day of operation (day 0), and after operation (days 1, 2, 4, 6, and 18). RESULTS: Surgical procedures suppressed NK cell cytotoxicity in the placebo group on postoperative days 1 (p < 0.001), 4, 6, and 18 (p < 0.05), whereas inhibition on postoperative day 2 failed to reach significance. PAPU abolished this immunosuppression after operation. The NK cell activity was elevated when compared with the control group; it was significant (p < 0.05) on postoperative days 1, 2, 4, 6, and 18. Surgical procedures also reduced circulating NK cell numbers during the first postoperative week in the placebo group; the decrease was statistically significant on day 4. The decrease in NK cell numbers in the PAPU group was insignificant. CONCLUSIONS: PAPU prevented the decrease in the circulating number and cytotoxic activity of NK cells that occurred after operation and enhanced NK cell cytotoxicity. This may have important implications for patients with cancer undergoing major operation.

Adult↗
PubMed1995

Interleukin-2 (IL-2) augments host cellular immune reactivity in the perioperative period in patients with malignant disease.

Major surgery impairs cellular and humoral immunity, in particular natural cytotoxicity, and this may facilitate the dissemination of tumour cells in the peri-operative period. Recombinant interleukin-2 (rIL-2) has been used to modulate peri-operative immune function. Eighteen patients were randomized to receive either rIL-2 or placebo for three days, as a subcutaneous injection, prior to surgical resection for colorectal cancer. Natural cytotoxicity (natural killer (NK) and lymphokine-activated killer (LAK) cell activity), monocyte phagocytosis and immune cell surface activation marker (CD14+HLA-DR) expression were assessed during therapy and for up to 21 days after surgery. rIL-2 therapy enhanced both NK and LAK cell-mediated cytotoxicity and augmented circulating lymphocyte CD16+ and CD56+ cell subset populations. Circulating monocyte phagocytosis was also increased. Hence, rIL-2 may be used to enhance immune function in the peri-operative period in patients undergoing curative cancer surgery.

Adult↗
PubMed1995

Synthetic polyribonucleotides: current role and potential use in oncological practice.

Polyadenylic-polyuridylic acid (PAPU) has a wide range of effects on various immunological cells and functions. It has been shown to enhance cellular and humoral immunity, in particular anti-cancer host defences, in both animals and man. In a small number of clinical trials (breast and stomach cancers) it appears to have a beneficial adjuvant effect, in terms of prolongation of disease-free and overall survival. Side effects with PAPU are minimal. The precise mode of action of PAPU is unclear and the most beneficial therapeutic regimen has yet to be established. PAPU, therefore, merits further careful consideration and evaluation. This article reviews its present status and considers further priority areas for investigation.

Animals↗