Breast screening programmes have facilitated more conservative approaches to the surgical and radiotherapy management of women diagnosed with breast cancer. This study investigated changes in shoulder movement after surgery for primary, operable breast cancer to determine the effect of elective physiotherapy intervention. Sixty-five women were randomly assigned to either the treatment (TG) or control group (CG) and assessments were completed preoperatively, at day 5 and at 1 month, 3, 6, 12 and 24 months postoperatively. The CG only received an exercise instruction booklet in comparison to the TG who received the Physiotherapy Management Care Plan (PMCP). Analyses of variance revealed that abduction returned to preoperative levels more quickly in the TG than in the CG. The TG women had 14 degrees more abduction at 3 months and 7 degrees at 24 months. Functional recovery at 1 month was greater in those randomised to the TG, with a dominant operated arm (OA) or receiving breast-conserving surgery. However, it was not possible to predict recovery over the 2 years postoperatively on the basis of an individual woman's recovery at 1 month postoperatively. The eventual recovery of abduction or flexion range of movement was not related to the dominance of the OA nor to the surgical procedure performed. The PMCP provided in the early postoperative period is effective in facilitating and maintaining the recovery of shoulder movement over the first 2 years after breast cancer surgery.

The development of secondary arm lymphoedema after the removal of axillary lymph nodes remains a potential problem for women with breast cancer. This study investigated the incidence of arm lymphoedema following axillary dissection to determine the effect of prospective monitoring and early physiotherapy intervention. Sixty-five women were randomly assigned to either the treatment (TG) or control group (CG) and assessments were made preoperatively, at day 5 and at 1, 3, 6, 12 and 24 months postoperatively. Three measurements were used for the detection of arm lymphoedema: arm circumferences (CIRC), arm volume (VOL) and multi-frequency bioimpedance (MFBIA). Clinically significant lymphoedema was confirmed by an increase of at least 200 ml from the preoperative difference between the two arms. Using this definition, the incidence of lymphoedema at 24 mo. was 21%, with a rate of 11% in the TG compared to 30% in the CG. The CIRC or MFBIA methods failed to detect lymphoedema in up to 50% of women who demonstrated an increase of at least 200 ml in the VOL of the operated arm compared to the unoperated arm. The physiotherapy intervention programme for the TG women included principles for lymphoedema risk minimisation and early management of this condition when it was identified. These strategies appear to reduce the development of secondary lymphoedema and alter its progression in comparison to the CG women. Monitoring of these women is continuing and will determine if these benefits are maintained over a longer period for women with early lymphoedema after breast cancer surgery.

SUMMARY1. Under conditions where heart rate, mean aortic pressure and enddiastolic pressure in the left ventricle are held constant, the intravenous infusion of isoprenaline is accompanied by large changes in dP/dt max in the left ventricle.2. Under similar conditions, during stepwise increments in the rate of infusion of isoprenaline the changes in dP/dt max (measured at a constant paced heart rate) were proportional to changes in the free (intrinsic) heart rate. It is concluded that dP/dt max is a quantitative index of inotropic changes in the left ventricle.3. In comparison to dP/dt max, three other variables which have been used to indicate inotropic changes in the heart (peak pressure in the left ventricle, duration of systole and stroke work at constant end-diastolic pressure), were shown to be unreliable indices of inotropic changes.4. Using dP/dt max to indicate inotropic changes, alteration in the heart rate while mean aortic pressure and end-diastolic pressure in the left ventricle were held constant, and in mean aortic pressure while heart rate and end-diastolic pressure in the left ventricle were held constant, were each shown to be accompanied by small inotropic changes in the heart.5. Under similar conditions, changes in end-diastolic pressure in the left ventricle alone were not accompanied by inotropic changes as indicated by dP/dt max.

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The generation of antitumour immunity depends on the nature of dendritic cell (DC) -tumour interactions. These have been studied mostly by using in vitro-derived DC which may not reflect the natural biology of DC in vivo. In breast cancer, only one report has compared blood DC at different stages and no longitudinal evaluation has been performed. Here we conducted three cross-sectional and one one-year longitudinal assessments of blood DC in patients with early (stage I/II, n ¼ 137) and advanced (stage IV, n ¼ 36) disease compared to healthy controls (n ¼ 66). Patients with advanced disease exhibit markedly reduced blood DC counts at diagnosis. Patients with early disease show minimally reduced counts at diagnosis but a prolonged period (1 year) of marked DC suppression after tumour resection. While differing in frequency, DC from both patients with early and advanced disease exhibit reduced expression of CD86 and HLA-DR and decreased immunostimulatory capacities. Finally, by comparing a range of clinically available maturation stimuli, we demonstrate that conditioning with soluble CD40L induces the highest level of maturation and improved T-cell priming. We conclude that although circulating DC are compromised by loco-regional and systemic breast cancer, they respond vigorously to ex vivo conditioning, thus enhancing their immunostimulatory capacity and potential for immunotherapy.

Dendritic cell (DC) defects are an important component of immunosuppression in cancer. Here, we assessed whether cancer could affect circulating DC populations and its correlation with tumor progression. The blood DC compartment was evaluated in 136 patients with breast cancer, prostate cancer, and malignant glioma. Phenotypic, quantitative, and functional analyses were performed at various stages of disease. Patients had significantly fewer circulating myeloid (CD11c+) and plasmacytoid (CD123+) DC, and a concurrent accumulation of CD11c(-)CD123(-) immature cells that expressed high levels of HLA-DR+ immature cells (DR(+)IC). Although DR(+)IC exhibited a limited expression of markers ascribed to mature hematopoietic lineages, expression of HLA-DR, CD40, and CD86 suggested a role as antigen-presenting cells. Nevertheless, DR(+)IC had reduced capacity to capture antigens and elicited poor proliferation and interferon-gamma secretion by T-lymphocytes. Importantly, increased numbers of DR(+)IC correlated with disease status. Patients with metastatic breast cancer showed a larger number of DR(+)IC in the circulation than patients with local/nodal disease. Similarly, in patients with fully resected glioma, the proportion of DR(+)IC in the blood increased when evaluation indicated tumor recurrence. Reduction of blood DC correlating with accumulation of a population of immature cells with poor immunologic function may be associated with increased immunodeficiency observed in cancer.

Introduction Dendritic cells (DCs) are key antigen-presenting cells that play an essential role in initiating and directing cellular and humoral immunity, including anti-tumor responses. Due to their critical role in cancer, induction of DC apoptosis may be one of the central mechanisms used by tumors to evade immune recognition.

SUMMARY1. Stimulation of left atrial receptors, by distension of the pulmonary vein/left atrial junctions, is known to cause a reflex increase in heart rate; the efferent pathway is known to be solely in the sympathetic nerves.2. In expectation of a concomitant positive inotropic response the effect of stimulating the left atrial receptors on the inotropic state of the left ventricle was studied, using as a known sensitive index of inotropic changes the maximal rate of rise of pressure in the left ventricle (dP/dt max).3. Stimulation of left atrial receptors resulted in an increase in heart rate but there were no significant concomitant changes in dP/dt max.4. It is concluded that activity in this discrete efferent pathway does not include an inotropic effect on the left ventricle and therefore the reflex involves only those sympathetic nerves which innervate the sinu-atrial node.5. The possible function of atrial receptors in the regulation of heart volumes is discussed.