There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

다중혈관 관상동맥 환자에서 y-문합을 이용하여 양쪽 내흉동맥만을 사용한 우회술의 조기 성적

Osteoclasts are specialized cells derived from the monocyte/macrophage haematopoietic lineage that develop and adhere to bone matrix, then secrete acid and lytic enzymes that degrade it in a specialized, extracellular compartment. Discovery of the RANK signalling pathway in the osteoclast has provided insight into the mechanisms of osteoclastogenesis and activation of bone resorption, and how hormonal signals impact bone structure and mass. Further study of this pathway is providing the molecular basis for developing therapeutics to treat osteoporosis and other diseases of bone loss.

Osteoclast differentiation and activation

Background Sipuleucel-T, an autologous active cellular immunotherapy, has shown evidence of efficacy in reducing the risk of death among men with metastatic castration-resistant prostate cancer. Methods In this double-blind, placebo-controlled, multicenter phase 3 trial, we randomly assigned 512 patients in a 2:1 ratio to receive either sipuleucel-T (341 patients) or placebo (171 patients) administered intravenously every 2 weeks, for a total of three infusions. The primary end point was overall survival, analyzed by means of a stratified Cox regression model adjusted for baseline levels of serum prostate-specific antigen (PSA) and lactate dehydrogenase. Results In the sipuleucel-T group, there was a relative reduction of 22% in the risk of death as compared with the placebo group (hazard ratio, 0.78; 95% confidence interval [CI], 0.61 to 0.98; P = 0.03). This reduction represented a 4.1-month improvement in median survival (25.8 months in the sipuleucel-T group vs. 21.7 months in the placebo group). The 36-month survival probability was 31.7% in the sipuleucel-T group versus 23.0% in the placebo group. The treatment effect was also observed with the use of an unadjusted Cox model and a log-rank test (hazard ratio, 0.77; 95% CI, 0.61 to 0.97; P = 0.02) and after adjustment for use of docetaxel after the study therapy (hazard ratio, 0.78; 95% CI, 0.62 to 0.98; P = 0.03). The time to objective disease progression was similar in the two study groups. Immune responses to the immunizing antigen were observed in patients who received sipuleucel-T. Adverse events that were more frequently reported in the sipuleucel-T group than in the placebo group included chills, fever, and headache. Conclusions The use of sipuleucel-T prolonged overall survival among men with metastatic castration-resistant prostate cancer. No effect on the time to disease progression was observed. (Funded by Dendreon; ClinicalTrials.gov number, NCT00065442.)

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Sipuleucel-T immunotherapy for castration-resistant prostate cancer.

admission. This proportion could already be greater in some parts of the country and may increase if referrals of cases of self-poisoning increase faster than the facilities for their assessment and management. The provision of social work and psychiatric expertise in casualty departments may be one means of preventing unnecessary medical admissions without risk to the patients. Dr Blake's and Dr Bramble's figures do not demonstrate, however, that any advantage would attach to medical teams taking over assessment from psychiatrists except that, by implication, assessments would be completed sooner by staff working on the ward full time. What the figures actually suggest is that if assessment of overdoses were left to house doctors there would be an increase in admissions to psychiatric units (by 19°U), outpatients (by 5O°'), and referrals to social services (by 140o). So for house doctors to assess overdoses would provide no economy for the psychiatric or social services. The study does not tell us what the consequences would have been for the six patients who the psychiatrists would have admitted but to whom the house doctors would have offered outpatient appointments. E J SALTER

Vitamin D deficiency.

93 Background: Bone is the most common site of distant metastasis in patients with advanced breast cancer. Bone metastases (BMs) often lead to skeletal-related events (SREs) and may result in debilitating bone pain which impacts a patient’s quality of life. Bone targeting agents (BTAs) reduce the incidence of SREs and progression of pain due to BMs. This study aims to understand real world patients’ experience of bone pain and to assess BTAs treatment patterns. Methods: Data were extracted from the Adelphi Breast Cancer Disease-Specific Programme (DSP), a cross-sectional survey of 98 US oncologists conducted from February to May 2015 in the USA. Each physician completed comprehensive record forms capturing the following information about the next 12 patients being treated for advanced breast cancer: Presence of BMs, patient’s pain state at diagnosis of BMs, current pain state, time since diagnosis of BMs, current analgesic use and reasons for prescribing BTAs. Results: Bone pain was more prevalent (p < 0....

Bone targeting agent treatment patterns and the impact of bone metastases on patients with advanced breast cancer in the US.

Ectopic hormone production by non endocrine tumors

The efficacy, tolerability and immunomodulatory effects of CGP 19835A Lipid, a liposomal preparation containing a lipophilic derivative of muramyltripeptide, a drug experimentally known as a potent activator of the macrophage-monocyte system, were evaluated in patients with advanced non-small-cell lung cancer (NSCLC). The immunomodulator was administered intravenously weekly to 12 patients in 3 different dosages: 4mg (n = 4), 2mg (n = 5), and 1mg (n = 3). Adverse events suggesting macrophage activation were observed in almost all patients, despite the dosage used, and included fever, chills, asthenia, anorexia and weight loss. Serum levels of tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), neopterin, C-reactive protein and soluble IL-2 receptors were increased in accordance with clinical side effects. No objective antitumoral effect was observed in patients with bulky NSCLC. When given to these patients, CGP 19835A Lipid appeared to be effective in increasing serum TNF-α levels. This property could be investigated in order to potentiate anticancer chemotherapy.

A pilot study on a muramyltripeptide lipophilic derivative entrapped into liposomes (CGP 19835A lipid) in patients with advanced Non-Small-Cell Lung Cancer

272 Background: Patients with breast cancer and bone metastases often experience skeletal-related events (SREs) and pain, which can impact health-related quality of life (HRQoL). Denosumab is superior to zoledronic acid (ZA) in preventing SREs and more effective in delaying moderate or severe pain in patients with advanced breast cancer. We now describe the effect of denosumab or ZA treatment on HRQoL in these patients. Methods: Patients enrolled in this double-blind, double-dummy study were randomized to receive denosumab (120 mg SC) or ZA (4 mg IV) every 4 weeks. Patients completed the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire at baseline (BL), day 8, and each monthly visit to assess overall HRQoL. Higher scores (range 0 to 108) reflect a better HRQoL. Changes in HRQoL were summarized through month 18, when 30% of patients had died or dropped out due to disease progression or withdrawal of consent. Increases or decreases of ≥ 5 points in the FACT-G total score were considere...

Jean-Jacques Body

Papers

Bone targeting agent treatment patterns and the impact of bone metastases on patients with advanced breast cancer in the US.

Ectopic hormone production by non endocrine tumors

A pilot study on a muramyltripeptide lipophilic derivative entrapped into liposomes (CGP 19835A lipid) in patients with advanced Non-Small-Cell Lung Cancer

Effect of denosumab versus zoledronic acid on health-related quality of life in patients with metastatic breast cancer.

Stimulation of calcitonin secretion by an oral calcium load test in normal subjects and in idiopathic renal stone formers