Re: interview with Denis O'Mullane.
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Biomedical subjects
Publications and source records attributed to Noel Walsh.
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BACKGROUND: There is evidence that depression impairs natural killer cell activity (NKA); this could have implications for anti-tumour immunity. Our aim was to examine the role of the hypothalamic-pituitary-adrenal (HPA) axis in suppressing NKA in a population of patients with early breast cancer, screened for depression. Secondary aims were to study the relationship between psychological, endocrine and immune variables and baseline tumour characteristics. METHOD: A cross-sectional population of female patients (n=55) with early breast cancer was sampled prior to primary surgery. Structured interview and psychometric instruments measured psychological distress. Flow cytometry was used to enumerate NK cells and lymphocytes were cryopreserved for use in a 51Cr-release assay, to estimate NKA. Midnight and three early morning saliva samples were collected to measure free cortisol levels. Tumour characteristics were obtained from hospital laboratory data. RESULTS: A high rate of psychological morbidity (40%) was observed in the population. NKA was reduced in those with past or current psychiatric illness compared to those without (344 v. 553 LU20 and 455 v. 569 LU20 respectively, p < 0.05 for both). Cortisol was not related to psychological status but was modestly positively correlated to NKA. A positive correlation was observed between the Fighting Spirit subscale of the Mental Adjustment to Cancer Scale and tumour size (r=0.383, p=0.012). CONCLUSIONS: Our data support the evidence that psychological morbidity is associated with immune dysfunction; however, the most obvious candidate mediator of this effect, the HPA axis, does not appear responsible for this effect. Possible reasons for this are discussed.
BACKGROUND: Evidence exists that prognosis in breast cancer may be related to the timing of primary surgery. Fluctuations in natural killer (NK) cells and/or their sensitivity to surgical stress hormones could mediate this phenomenon. We sought to establish, firstly, if there are any numerical or functional changes in NK cells during the course of the menstrual cycle and, secondly, if their prior in vitro incubation with cortisol and adrenaline produced functional change that was more pronounced at a particular point in the cycle. SUBJECTS AND METHODS: Normally menstruating females (n = 10) were sampled at two points (mid-follicular and mid-luteal) during two cycles. NK cell numbers were determined by flow cytometry. Natural killer cell activity (NKA) (unstimulated and following a 2-hour pre-incubation with cortisol and adrenaline) was determined using chromium-51 release assays from peripheral blood mononuclear cells (PBMCs) prepared from cryopreserved samples from the second cycle. RESULTS: NK cell numbers (expressed as a percentage of a standard lymphgate) were significantly higher at the mid-luteal point compared to the mid-follicular point (8.45 +/- 3.71 vs. 6.85 +/- 2.80, p < 0.05, data pooled from both cycles). Corresponding changes in NKA were observed, although these did not reach statistical significance. The mean inhibitory effects of cortisol (67%) and adrenaline (12%) on NKA were significant, but this phenomenon was uninfluenced by cycle point. CONCLUSION: This study supports the role of menstrual cycle-induced alterations in NK cells as a putative mediator of improved survival when surgery for breast cancer is carried out in the follicular phase. However there is no evidence of the cyclical sensitivity of NK cells to the principal surgical stress hormones.