Incidence of cutaneous squamous cell carcinoma in a New Zealand population of chronic lymphocytic leukaemia patients.

BACKGROUND: Chronic lymphocytic leukaemia (CLL) is associated with an increased incidence and aggressiveness of skin cancers, particularly cutaneous squamous cell carcinoma (cSCC), but little is known about cSCC incidence in Australasian CLL patients. AIM: In this retrospective study, we analysed the incidence of cSCC in patients seen at a tertiary hospital in New Zealand (NZ). METHODS: We retrospectively assessed the clinical history and histology data of CLL patients (n = 371) who presented to the Haematology Department, Christchurch Hospital, NZ during the period 1996-2015. Baseline characteristics, incidence of second cancers, treatment details and overall survival were analysed. RESULTS: During follow-up (median = 11.8 years), 221 second cancers were recorded in 88 patients. Of these cancers, 185 were cSCC, removed from 61 patients. In 56% of these patients, >1 cSCC was removed, and the majority of cSCC occurred following the treatment for CLL. The cumulative incidence of a first cSCC was 11% at 5 years, whereas the cumulative incidence of a subsequent cSCC was 88% at 5 years. The incidence of cSCC in male patients was threefold higher than that reported for the general NZ population. CONCLUSION: NZ CLL patients have a high incidence of cSCC relative to the levels observed in the general population, which are themselves among the highest in the world. The careful monitoring of CLL patients is warranted, particularly those who have a progressive disease or have had a first cSCC removed.

Chronic lymphocytic leukaemia cells become both activated and immunosuppressive following interaction with CD3 and CD28 stimulated PBMC.

Chronic lymphocytic leukaemia (CLL) is associated with immunosuppression. The activation of CLL cells induced by interaction with other cell types, particularly activated T-cells, within the tumour micro-environment is thought to be important for CLL progression. However it is unclear whether activated CLL cells (CLL(Act)) have immunosuppressive capacity. We report that co-culture of CLL cells with normal PBMC in the context of CD3/CD28 T-cell activation generates CLL(Act) with increased CD38 expression that are capable of suppressing the proliferative responses of both CD4+ and CD8+ T-cells. The suppression required cell contact but did not involve induction of T-cell apoptosis.

Differential expression of CD32 isoforms following alloactivation of human T cells.

Receptors for the Fc region of immunoglobulin G (IgG) (Fc gamma Rs) exist in three main forms: membrane bound, soluble and cytoplasmic. The function of cytoplasmic Fc gamma Rs is poorly understood. We have previously demonstrated cytoplasmic Fc gamma RII (cCD32) within most normal human peripheral blood lymphocytes (PBL), including T cells. In this study we have investigated the hypothesis that following lymphocyte activation, up-regulation of cCD32 occurs, resulting in increased expression at the cell surface. Normal PBL were activated in vitro using a two-way mixed lymphocyte reaction (MLR) and expression of CD32 monitored by flow cytometry and by immunoperoxidase staining using specific monoclonal antibodies and aggregated mouse IgG subclasses. Furthermore, we designed oligonucleotide probes specific for the three main isoforms of CD32 and looked for changes in mRNA expression throughout the MLR using an in situ hybridization technique. Increased surface expression of CD32 was found on both activated human T and B lymphocytes, but this was found only in the early stages of the MLR, on days 3 and 4, and was virtually absent by day 7. An inverse relationship between cell surface expression of CD32 and mRNA for the IIb isoforms was noted with strong mRNA expression for IIb isoforms occurring in the later stages of the MLR (days 6-7) when interleukin-2R (IL-2R)-positive T cells were predominant. A soluble IgG binding factor (soluble CD32?) was also detected in the MLR culture supernatant. These observations provide support for the hypothesis that synthesis of IIb isoforms of CD32 occurs following alloantigen activation of human T lymphocytes.

Demonstration of cytoplasmic CD32 (Fc gamma RII) within human lymphocytes following microwave treatment.

We have recently described a cytoplasmic from of CD32 (Fc gamma RII) within the vast majority of normal human peripheral blood lymphocytes (PBL) including T cells. The function of cytoplasmic CD32 is not known. These flow cytometric studies were conducted using single cell suspensions of PBL that had been pre-fixed and permeabilized using methanol/triton-X-100. In this study we have attempted to visualize cytoplasmic CD32 by immunocytochemistry using normal PBL processed in various ways and have also looked for CD32 within tissue lymphocytes. Weak cytoplasmic CD32 staining was observed in paraffin sections of normal lymphocytes but only when sections were microwave treated. The intensity of staining for CD32 did however, appear to be much stronger within infiltrating lymphocytes found in autoimmune diseases or in rejecting allografts: an observation that suggests that up-regulation of cytoplasmic CD32 may occur when T cells become activated in vivo. Microwave treatment of PBL suspensions was shown to disrupt the outer cell membrane, thus effectively permeabilizing the cell and allowing for the detection of cytoplasmic components, like CD32, by flow cytometry. Microwave treatment may, therefore, afford an alternative method for cell permeabilization and may prove to be a useful method for the study of cytoplasmic molecules in cell suspensions and in paraffin-embedded tissues.

Expectations, experiences and satisfaction with labour.

Emotional, medical and control aspects of labour were explored in 81 primiparous women. Expectations were assessed antenatally and compared with postnatal reports of experiences. Expectations of positive emotions were significantly greater than experience while negative emotional expectations were paralleled by experience. There was a major discrepancy between expectations and experiences of the occurrence of interventions, with the proportion of women expecting interventions being greatly exceeded by those actually undergoing such experiences. In addition, expectations concerning personal control together with the use and efficacy of breathing and relaxation exercises in labour were elevated in relation to experience. Positive emotional expectations were strong predictors of positive emotional experiences and unrelated to negative emotional expectations. Expectations in general were positively related to experience but the strength of the association was weak. Personal satisfaction (i.e. satisfaction with self) in labour was strongly associated with the ability to control panic and other aspects of personal control. The ability to control panic was mainly influenced by the use of exercises. Attenders and non-attenders at antenatal preparation classes showed no significant differences in their experiences or personal satisfaction levels. Possible explanations for this absence of impact are discussed together with issues concerning the relevance of psychological theory to midwifery practice and the need for greater integration.