Sports and Leisure Time Physical Activity During Pregnancy in Nulliparous Women

To describe patterns of leisure time physical activity during pregnancy in relation to pre-pregnancy leisure time physical activity, socio-demographic characteristics, fertility history, and lifestyle factors. 4,718 nulliparous with singleton pregnancy and intended spontaneous vaginal delivery were included in the study at gestational week 33 from May 2004 to July 2005. Information was provided by self-administered questionnaires. Leisure time physical activity was categorised into four categories: competitive sport, moderate-to-heavy, light or sedentary. In this population of nulliparous women, 4% participated in competitive sport, 25% in moderate-to-heavy activities, 66% in light activities, and 5% in sedentary activities in the year prior to pregnancy. Physical activity before pregnancy was statistically significantly associated with age, pre-pregnancy BMI, chronic diseases, number of years at school, and smoking habits. The proportion of women who took part in competitive sports, and moderate-to-heavy activities decreased over the three trimesters of pregnancy. The proportion of women with light physical activity was stable during pregnancy while the proportion of women with sedentary activity increased from 6% to 29%. During the third trimester women performing competitive sports or moderate-to-heavy activities before pregnancy continued to have a higher level of physical activity than women with light activities or sedentary activities before pregnancy. In general the intensity and time spent on exercise decreased during pregnancy. Women with the highest level of exercise prior to pregnancy continued to be the most active during pregnancy. Among women with sedentary activities before pregnancy one-fourth changed to light activity during pregnancy.     

Langerhans cell markers CD1a and CD207 are the most rapidly responding genes in lesional psoriatic skin following adalimumab treatment

TNFα‐, IL‐23‐ and IL‐17‐targeting drugs are highly effective in the treatment of psoriasis. However, the precise molecular mechanism remains unknown. In psoriatic skin, the presence of Langerhans cells (LCs) is reduced, but the role of LC is poorly understood. The purpose of this study was to investigate the impact of TNFα and IL‐23/IL‐17 on the presence of LC in the skin during treatment. Therefore, psoriatic skin was investigated before and after 4 days of adalimumab or ustekinumab treatment. Furthermore, TNFα and IL‐17A stimulation was investigated in an ex vivo model of epidermis and dermis from healthy normal skin kept in cultures at an air‐liquid interphase for 4 days. In a gene array analysis, we found that the two LC markers, CD1a and CD207, were among the most up‐ or downregulated genes in psoriatic skin after anti‐TNFα therapy. Validation showed that both mRNA expression and protein level followed the same pattern and became significantly upregulated after 4 days of treatment. No changes were seen after ustekinumab treatment. In the ex vivo skin model, a decrease in the CD1a level was seen after TNFα stimulation and it was caused by LC migration from epidermis. No response in LC migration was seen after IL‐17A stimulation. Taken together, we demonstrated that changes in the LC level in epidermis precede the histological and clinical changes during adalimumab treatment in psoriatic skin. Furthermore, TNFα plays a prominent role in orchestrating LC migration in the skin. This seems not to be the true for the IL‐23/IL‐17A pathway.     

Antikörpertherapie in klinischer und präklinischer Anwendung bei gastrointestinalen Karzinomen

The clinical and preclinical applications of new antitumor agents for the treatment of gastrointestinal cancer is a field undergoing continuous progress. The antibody derived apoptosis of tumor cells represents an ideal target in cancer therapy. However, the actual effectiveness of and tolerance to antibodies does not yet allow for a convincing clinical application. Modifications in the production of antibodies, such as humanisation, chimerisation or the establishment of totally human antibodies, provide hope for higher selectivity and less side effects in the future. Through the development of targeted therapy with antibodies against epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF), as well as the combination with new cytotoxic agents, the median overall survival in colorectal cancer patients has been significantly improved over the next few years. In particular, the survival of patients with advanced colorectal cancer could be increased by more than 2 years, almost doubling that found with the classical 5-FU regimen. Thus, the use of chemotherapy and antibodies in the treatment of gastrointestinal cancer means that this has become not only more effective, particularly for patients with metastases, but also much more complex. Bevacizumab and cetuximab are excellent examples for a selectively targeted therapy in first and second-line therapy for metastatic colorectal cancer.     

Tumor progression in waiting time for radiotherapy in head and neck cancer.

INTRODUCTION: Waiting-time prior to radiotherapy is a well-known problem. This study aims to determine the impact of time on tumor growth in a patient population with squamous-cell carcinoma of the head and neck (SCCHN). MATERIAL AND METHODS: In a consecutive cohort, all patients with both a diagnostic scan and a treatment-planning scan were identified. In total 648 patients were seen, and 414 treated with primary radiotherapy. Ninety-five had two scans and 61 sets were eligible for comparison. Endpoints were change in tumor volume, tumor volume doubling time (TVD) and disease progression measured by TNM-classification and RECIST criteria. RESULTS: Median interval between eligible scans was 28 (5-95) days. Thirty-eight (62%) had measurable increase in tumor volume, median 46% (6-495%). For all patients TVD was median 99 days, but for the half of patients with fastest growing tumors TVD was 30 days (15-41). Tumor volume increase was significantly correlated to time and histological differentiation. Twelve (20%) developed new lymph-node metastasis and 10 (16%) progressed in TNM-classification. Evaluated by RECIST criteria 18 (30%) patients had progressive disease. INTERPRETATION: This study shows a negative impact of waiting time in patients with SCCHN. Within an average time of 4 weeks the majority of the patients developed significant signs of tumor progression. It was not possible to define a threshold for acceptable time intervals in order to avoid volume changes, or to define a subgroup that has no negative impact of delay.