Subclinical cardiotoxicity following adjuvant dose-escalated FEC, high-dose chemotherapy, or CMF in breast cancer

We compared adjuvant chemotherapy-related myocardial damage by antimyosin scintigraphy in patients who received either nine cycles of FEC (fluorouracil, epirubicin and cyclophosphamide) where the doses of epirubicin and cyclophosphamide were escalated according to the leucocyte nadir (group I, n = 14), three cycles of FEC followed by high-dose chemotherapy with alkylating agents (CTCb) given with the support of peripheral blood stem cell transplantation (group II, n = 14), or six cycles of standard intravenous CMF (cyclophosphamide, methotrexate and fluorouracil; group III, n = 8). The cardiac uptake of In-111-antimyosin-Fab (R11D10) antibody was measured and the heart-to-lung ratio (HLR) calculated 8–36 months after the last dose of chemotherapy. Cardiac antimyosin antibody uptake was considerably higher among patients treated with nine cycles of dose-escalated FEC than among those who were treated with three cycles of FEC and high-dose CTCb (HLR, median 1.98; range 1.36–2.24 vs median 1.51; range 1.20–1.82;P< 0.001), or those treated with CMF (median 1.44; range 1.15–1.68;P< 0.001). The difference between groups II and III was not significant (P> 0.1). A linear association was found between the cumulative dose of epirubicin and the cardiac antimyosin uptake (P< 0.001). We conclude that subclinical cardiac damage caused by three cycles of conventional-dose FEC followed by one cycle of high-dose CTCb chemotherapy is small as compared with the damage caused by dose-escalated FEC. © 2000 Cancer Research Campaig

Novel Selective Estrogen Receptor Modulator Ameliorates Murine Colitis

Estrogen-receptor-mediated signaling has been suggested to decrease the inflammatory response in monocyte macrophages. Previously, we showed that a novel selective estrogen receptor modulator (SERM2) promotes anti-inflammatory phenotype of monocytes in vitro. In this study, we demonstrate the potential of SERM2 in amelioration of colitis. We utilized a dextran sodium sulfate (DSS)-induced colitis model in FVB/n mice to demonstrate the effects of orally administered SERM2 on the clinical status of the mice and the histopathological changes in the colon, as well as proportion of Mrc-1 positive macrophages. SERM2 nuclear receptor affinities were measured by radioligand binding assays. Orally administered, this compound significantly alleviated DSS-induced colitis in male mice and induced local estrogen receptor activation in the inflamed colon, as well as promoting anti-inflammatory cytokine expression and infiltration of anti-inflammatory monocytes. We show that this novel drug candidate has an affinity to estrogen receptors alpha and beta and progesterone receptors, but not to glucocorticoid receptor, thus expressing unique binding properties compared to other sex steroid receptor ligands. These results indicate that novel drug candidates to alleviate inflammatory conditions of the colon could be found among sex steroid receptor activating compounds

Development and validation of the short version of the Psychological General Well-Being Index (PGWB-S)

BACKGROUND: The PGWBI is a 22-item health-related Quality of Life (HRQoL) questionnaire developed in US which produces a self-perceived evaluation of psychological well-being expressed by a summary score. The PGWBI has been validated and used in many countries on large samples of the general population and on specific patient groups. Recently a study was carried out in Italy to reduce the number of items of the original questionnaire, yielding the creation of a shorter validated version of the questionnaire (PGWB-S). The purpose of the present paper is to describe the methods adopted and to report and discuss the relevance of results. METHODS: Data for this study were collected from 4 different population samples: two general population samples a student and a patient sample. On the basis of the results of the first (development) sample population, six relevant items were identified statistically from the original questionnaire and grouped to assemble a new summary scale. Following the newly created 6-item questionnaire was administered in three independent population samples. Descriptive statistics, correlation coefficients, univariate and multivariate regression analyses were used to compare the performance of the long and short questionnaire, within and between population samples and across relevant subgroups. A further independent sample extracted by an ongoing cancer clinical trial served as final validation step. RESULTS: Overall, the questionnaires were administered to 1443 subjects. Six items were selected by a step-wise approach to explain 90% of the variance of the summary measure of the original questionnaire. Response rates reached 100%, while missing items were not observed. University students (n = 400) showed the highest mean value of the summary measure (75.3); while the patient sample (n = 28) had the lowest score (71.5). The correlation coefficients between the summary measures and the single items according to the different studies were satisfactory, reaching the highest estimates in the student sample. The internal consistency showed high values of the Cronbach's alpha coefficient (range 0.80 – 0.92) for all three study samples, coming close to the value of the coefficient established for the original questionnaire (0.94). A cross-validation in an independent sample of 755 cancer patients confirmed the item selection procedure and amount of variance explained by the new shorter questionnaire (ranging from 90. 2 to 95.1 %, across age and sex strata). CONCLUSION: The newly identified PGWB-S showed good acceptability and validity for the use in various settings in Italy. The translation of the PGWB-S into different languages, and its use in other linguistic settings will add evidence about its cross-cultural validity

A high proliferation rate measured by cyclin A predicts a favourable chemotherapy response in soft tissue sarcoma patients

A small but not insignificant number of patients experience a prolonged survival after treatment of metastatic soft tissue sarcoma. This must be weighed against the majority of the patients who benefit little from the therapy, but nevertheless experience its side-effects. It would therefore be of utmost importance to be able to screen for those patients who respond to the treatment. Since proliferating cells are more sensitive to chemotherapy than non-proliferative cells, we measured the proliferation rate of the primary tumour of 55 soft tissue sarcoma patients with locally advanced or metastatic disease by determining the flow cytometric S phase fraction and immunohistochemical Ki-67 and cyclin A scores. S phase fraction or Ki-67 score did not predict chemotherapy response or progression-free survival. A high cyclin A score, however, correlated with a better chemotherapy response (P = 0.02) and longer progression-free survival time (P = 0.04). Our results suggest that a high cyclin A score predicts chemotherapy sensitivity. © 1999 Cancer Research Campaig

Multifractal characterization of stochastic resonance

We use a multifractal formalism to study the effect of stochastic resonance in a noisy bistable system driven by various input signals. To characterize the response of a stochastic bistable system we introduce a new measure based on the calculation of a singularity spectrum for a return time sequence. We use wavelet transform modulus maxima method for the singularity spectrum computations. It is shown that the degree of multifractality defined as a width of singularity spectrum can be successfully used as a measure of complexity both in the case of periodic and aperiodic (stochastic or chaotic) input signals. We show that in the case of periodic driving force singularity spectrum can change its structure qualitatively becoming monofractal in the regime of stochastic synchronization. This fact allows us to consider the degree of multifractality as a new measure of stochastic synchronization also. Moreover, our calculations have shown that the effect of stochastic resonance can be catched by this measure even from a very short return time sequence. We use also the proposed approach to characterize the noise-enhanced dynamics of a coupled stochastic neurons model.Comment: 10 pages, 21 EPS-figures, RevTe

European regulatory agenices should employ full time statisticians

No abstract available

Enhanced recovery after surgery: are we ready, and can we afford not to implement these pathways for patients undergoing radical cystectomy?

Enhanced recovery after surgery (ERAS) for radical cystectomy seems logical, but our study has shown a paucity in the level of clinical evidence. As part of the ERAS Society, we welcome global collaboration to collect evidence that will improve patient outcomes

What is known about the health and living conditions of the indigenous people of northern Scandinavia, the Sami?

The Sami are the indigenous ethnic population of northern Scandinavia. Their health condition is poorly known, although the knowledge has improved over the last decade.The aim was to review the current information on mortality, diseases, and risk factor exposure in the Swedish Sami population.Health-related research on Sami cohorts published in scientific journals and anthologies was used to compare the health condition among the Sami and the majority non-Sami population. When relevant, data from the Sami populations in Swedish were compared with corresponding data from Norwegian and Finnish Sami populations.Life expectancy and mortality patterns of the Sami are similar to those of the majority population. Small differences in incidences of cancer and cardiovascular diseases have been reported. The traditional Sami lifestyle seems to contain elements that reduce the risk to develop cancer and cardiovascular diseases, e.g. physical activity, diet rich in antioxidants and unsaturated fatty acids, and a strong cultural identity. Reindeer herding is an important cultural activity among the Sami and is associated with high risks for accidents. Pain in the lower back, neck, shoulders, elbows, and hands are frequent among both men and women in reindeer-herding families. For men, these symptoms are related to high exposure to terrain vehicles, particularly snowmobile, whereas for women psychosocial risk factors seem to more important, e.g. poor social support, high effort, low reward, and high economical responsibilities.Although the health condition of the Sami population appears to be rather similar to that of the general Swedish population, a number of specific health problems have been identified, especially among the reindeer-herding Sami. Most of these problems have their origin in marginalization and poor knowledge of the reindeer husbandry and the Sami culture in the majority population. It is suggested that the most sustainable measure to improve the health among the reindeer-herding Sami would be to improve the conditions of the reindeer husbandry and the Sami culture