Exposure considerations in human safety assessment: Report from an EPAA Partners' Forum.

Understanding and estimating the exposure to a substance is one of the fundamental requirements for safe manufacture and use. Many approaches are taken to determine exposure to substances, mainly driven by potential use and regulatory need. There are many opportunities to improve and optimise the use of exposure information for chemical safety.

Use of New Approach Methodologies (NAMs) in regulatory decisions for chemical safety: Report from an EPAA Deep Dive Workshop.

New Approach Methodologies (NAMs) are considered to include any in vitro, in silico or chemistry-based method, as well as the strategies to implement them, that may provide information that could inform chemical safety assessment. Current chemical legislation in the European Union is limited in its acceptance of the widespread use of NAMs. The European Partnership for Alternative Approaches to Animal Testing (EPAA) therefore convened a 'Deep Dive Workshop' to explore the use of NAMs in chemical safety assessment, the aim of which was to support regulatory decisions, whilst intending to protect human health.

Reference Chemical Potency List (RCPL): A new tool for evaluating the accuracy of skin sensitisation potency measurements by New Approach Methodologies (NAMs).

Considerable progress has been made in the design of New Approach Methodologies (NAMs) for the hazard identification of skin sensitising chemicals. However, effective risk assessment requires accurate measurement of sensitising potency, and this has proven more difficult to achieve without recourse to animal tests. One important requirement for the development and adoption of novel approaches for this purpose is the availability of reliable databases for determining the accuracy with which sensitising potency can be predicted.

Switching a baby from IV levomethadone to IV fentanyl.

Methadone, or in Germany levomethadone, may be used for the treatment of iatrogenic opioid withdrawal syndrome in pediatric intensive care units. The limited literature on opioid rotation in children does not provide data for the switch from methadone to another opioid. We report switching a very ill preterm baby in an unstable condition from IV levomethadone to IV fentanyl identifying a possible conversion ratio of 6.

Finding synergies for the 3Rs - Repeated Dose Toxicity testing: Report from an EPAA Partners' Forum.

The European Partnership for Alternative Approaches to Animal Testing (EPAA) convened a Partners' Forum on repeated dose toxicity (RDT) testing to identify synergies between industrial sectors and stakeholders along with opportunities to progress these in existing research frameworks. Although RTD testing is not performed across all industrial sectors, the OECD accepted tests can provide a rich source of information and play a pivotal role for safety decisions relating to the use of chemicals. Currently there are no validated alternatives to repeated dose testing and a direct one-to-one replacement is not appropriate.

Finding synergies for 3Rs - Toxicokinetics and read-across: Report from an EPAA partners' Forum.

The European Partnership for Alternative Approaches to Animal Testing (EPAA) convened a Partners' Forum Toxicokinetics and Read-Across to provide an overview on research activities to develop in vitro toxicokinetics methods and physiologically-based kinetic (PBK) models and to find synergies to enhance use of toxicokinetic data to strengthen read-across. Currently, lacking toxicokinetic data often prevent the application of read-across. Preferably, toxicokinetic data should be generated using in vitro and in silico tools and anchored towards human relevance.

"Let's Bring Her Home First." Patient Characteristics and Place of Death in Specialized Pediatric Palliative Home Care.

Context: Specialized pediatric palliative home care (SPPHC) is the main pediatric palliative care structure in Germany. Detailed data on patient characteristics and care are sparse. Describing this population in terms of diagnoses and care needs is essential for further development of palliative care services for these patients.

Functional group analysis of starches reacted with urea-phosphoric acid-Correlation of wet chemical measures with FT Raman spectroscopy.

Because the degree of substitution (DS) of chemically modified starches strongly affects their physicochemical properties and applications, rapid techniques for its determination are crucial. In the present work, ammonium starch phosphates carbamates (SPC) were obtained by reacting starch with urea-phosphoric acid. DS of phosphate (DS), carbamate (DS), and ammonium groups (DS+) and contents of non-hydrolyzable amides (N) of SPC were determined using the vanadomolybdophosphoric acid and saponification methods, respectively.

[Thigh abscess as first manifestation of a sigma carcinoma].

Medical History: An extensive thigh abscess was the reason for a hospital admission of a 66 year old woman. Apart from that there were no other known preexisting diseases.

Investigations: The reason for the abscess was a perforated sigma carcinoma, which was incidentally found.

Survey of compartment syndrome of the lower extremity after gynecological operations.

Purpose: This study was aimed to investigate incidence, circumstances and consequences of acute compartment syndrome (CS) of the lower extremity after gynecological operations in lithotomy position by collecting data from departments of Obstetrics and Gynecology in Germany.

Design: Retrospective observational study.

Setting: Departments of Obstetrics and Gynecology in the area of North Rhine (Germany)

Methods: A 24-item questionnaire was sent to 168 gynecological departments.

Compartment syndrome after gynecologic operations: evidence from case reports and reviews.

Compartment syndrome (CS) of the lower leg is a rare but severe complication of operations in the lithotomy (LT) position after urologic, gynecologic and general surgery. A delay in diagnosis and treatment can lead to loss of function and even life-threatening complications. The pathophysiology is still not fully understood but it is believed that ischemia as a result of increased compartment pressure and decreased perfusion pressure may lead to CS.

18F-FDG-PET and histopathology in 131I-lipiodol treatment for primary liver cancer.

The diagnostic accuracy of 18F-FDG-PET (fluoro-2-deoxyglucose-positron emission tomography) remains questionable for primary hepatocellular carcinoma (HCC) but seems to be more promising for restaging and therapy control. Yet, there are no data on FDG-PET in 131I-lipiodol treatment for primary liver cancer. The aim of this study was to relate baseline FDG-PET findings to histologic data and to assess, for the first time, the role of repetitive FDG-PET imaging for follow-up of 131I-lipiodol treatment.

An unusual case of advanced bilateral male breast cancer.

Background: Breast cancer in men is an uncommon disease. Little is known about its etiology, clinical behavior, treatment, and outcome. Retrospective data indicate that stage- and age-matched male and female breast cancer is similar in presentation.

Single large inguinal lymph node metastasis in human papillomavirus-induced early invasive vulvar cancer of the anterior fourchette in two young women.

The incidence of human papillomavirus (HPV)-induced vulvar cancer in young women is increasing and often presents as microinvasive or early invasive tumors in a grade 3 vulvar intraepithelial neoplasia. So far, the risk of lymph node metastases in early invasive vulvar carcinoma (depth of invasion 1.1-2.

PRODH variants and risk for schizophrenia.

Schizophrenia is a common, devastating neuropsychiatric disorder whose etiology is largely unknown. Multiple studies in humans and in mouse and fly models suggest a role for proline and PRODH, the gene encoding the first enzyme in the pathway of proline catabolism, in contributing risk for schizophrenia. Other studies, however, reach contradictory conclusions.

New aspects of vulvar cancer: changes in localization and age of onset.

Objective: To characterize the changes in incidence, age of disease onset, tumor site and patients characteristics in women with invasive vulvar cancer in a German University Hospital unit over a 28-year period.

Methods: The clinical records for women treated for invasive vulvar cancer from 01/1980 until 06/2007 were analyzed. We performed a retrospective analysis for three 9-year periods: 1/1980 to 02/1989; 3/1989 to 04/1998 and 05/1998 to 06/2007.

Role of FDG-PET in the assessment of survival prognosis in melanoma.

Positron-emission tomography (PET) employing fluorodeoxyglucose (FDG) has proven to be a highly sensitive and specific diagnostic method in the staging and restaging of various neoplasms, including melanoma, complementing morphologic imaging. FDG uptake has been correlated with proliferation rate, and thus, the degree of malignancy of a given tumor (i.e.

Invasive breast cancer cells exhibit increased mobility of the actin-binding protein CapG.

The CapG protein, a Gelsolin-related actin-binding protein, is expressed at higher levels in breast cancer, especially in metastasizing breast cancer, than in normal breast epithelium. Furthermore, it is known that an increased expression of the CapG protein triggers an increase in cell motility. According to in vitro experiments, it was supposed that it is the nuclear fraction of the protein, which causes the increase in cell motility.

Comprehensive analysis of 130 multicentric intraepithelial female lower genital tract lesions by HPV typing and p16 expression profile.

Purpose: HPV associated cervical transformation is characterized by well-defined steps, including persistent HPV infection and deregulated oncogene expression. Recent studies have suggested that a number of lower genital tract lesions are clonally related to cervical lesions. In the current study, HPV infections and oncogene expression were assessed in a large series of patients with multicentric lower genital tract disease to analyze the transformation steps in extracervical disease.

Mesenchymal stem cells as a vehicle for targeted delivery of CRAds to lung metastases of breast carcinoma.

Purpose: Alternative and complementary therapeutic strategies need to be developed for metastatic breast cancer. Virotherapy is a novel therapeutic approach for the treatment of cancer in which the replicating virus itself is the anticancer agent. However, the success of virotherapy has been limited due to inefficient virus delivery to the tumor site.

Effect of human papillomavirus vaccines on vulvar, vaginal, and anal intraepithelial lesions and vulvar cancer.

Objective: Human papillomavirus (HPV) is a necessary cause for cervical cancer, and it has been associated with vulvar and vaginal cancer and vulvar (VIN) and vaginal (VaIN) and anal (AIN) intraepithelial neoplasia. We assessed the prevalence of HPV (and the types) to estimate the possible effect of a HPV vaccine on lower genital tract disease prevention.

Methods: Two hundred fifty-eight samples of VIN, VaIN, AIN, and vulvar cancer from 241 women were included in the study.

A case of a pT3, HPV 52-positive vulvar carcinoma in an 18-year-old woman.

Background: Vulvar carcinoma in young women is rare; so far, no case of an 18-year-old woman has been described. Here, we report a case with a T3 HPV 52-induced tumor 3 years after primary HPV contamination.

Case: An 18-year-old woman without risk factors complaining of dysuria and vulvar pain was treated several months for fungal infection before referred and diagnosed with a vulvar carcinoma located between clitoris and urethra.

Comparison of rapidly cycled tandem high-dose chemotherapy plus peripheral-blood stem-cell support versus dose-dense conventional chemotherapy for adjuvant treatment of high-risk breast cancer: results of a multicentre phase III trial.

Background: Breast cancer with extensive axillary-lymph-node involvement has a poor prognosis after conventional treatment. In trials with historical controls, high-dose chemotherapy produced improved outcomes. We compared an intensive double-cycle high-dose chemotherapy regimen with an accelerated conventionally dosed regimen in high-risk breast cancer in a multicentre trial.