The heavy metals cadmium, lead and mercury in raw materials of animal origin: evaluation of data from practice.

Raw materials from animal origin are widely used in homoeopathy. Due to the lack of dedicated limits, the quality requirements for herbal drugs of the European Pharmacopoeia (Ph. Eur.) and/or the German Homoeopathic Pharmacopoeia (Homöopathisches Arzneibuch, HAB), including limits for heavy metals such as cadmium, lead and mercury, have been applied. A recent database evaluation shows that for some raw materials of animal origin the Ph. Eur. limits for herbal drugs cannot be met in practice. For this reason proposals for new limits for cadmium, lead and mercury are made based on recent experiences from the companies' daily practice. These specific limits are suggested to be included in the individual monographs of the Ph. Eur. or at least the German HAB, respectively, for Ambra grisea, Euspongia officinalis, Formica rufa and Sepia officinalis.

The occurrence of bromide in herbal drugs: is there a need for a Ph. Eur. limit?

This contribution provides an overview on the current legal requirements regarding limits for bromide and presents data on the actual bromide burden of commonly used herbal drugs. Evaluation of an extensive data base shows that results exceeding the limit of 50 mg/kg are found in specific plants which take up bromide to a high extent from the environment. Thus, positive findings of bromide in herbal drugs do not necessarily serve as a proof for methyl bromide treatment. Taking into account the ADI recommended by EMA and WHO, there are no toxicological concerns with regard to the intake of herbal teas, extracts or comminuted herbal drugs at therapeutic doses. Furthermore, the use of methyl bromide and other fumigants must be documented within the batch documentation. If stated in the batch documentation that no fumigation was carried out, it is not necessary to perform the test on bromide. In cases of a particular suspect and if toxicological concerns exist, additional testing can be performed in accordance with the limits set by Regulation (EC) No. 396/2005. For the above reasons, information obtained by performing the test on bromide is not significant for the assessment of quality. Therefore, it seems no longer necessary to maintain bromide in Ph. Eur. general chapter 2.8.13. Pesticide residues and it is recommended to delete it from Table 2.8.13.-1.

Evaluation of the risk of aflatoxin contamination in fresh medicinal plants.

Based on experimental results of aflatoxin analysis as well as information from literature, this contribution discusses the likelihood of aflatoxin contamination in fresh medicinal plants. As cultivation and collection of medicinal plants in accordance with Good Agricultural and Collection Practice (GACP) and the local climatic conditions minimise aflatoxin contamination and, as fresh raw material is normally processed immediately, aflatoxin contamination of fresh medicinal plants from Central European countries is extremely unlikely. As a result of the risk-based approach to aflatoxin testing, 3 options are proposed depending on the origin of the material and the plant parts used: no testing, skip lot testing or routine testing.

Study of the risk of heavy metal transfer to homoeopathic mother tinctures.

To assess the risk of heavy metal contamination of homoeopathic mother tinctures, 9 plant species and 1 fungus used in the manufacture of homoeopathic medicaments were investigated. Mother tinctures were prepared according to the manufacturing procedures described in the European Pharmacopoeia. The original herbal drug and the material processed during production were analysed for their cadmium (Cd), lead (Pb) and mercury (Hg) content. The plant components were harvested from 2 sites contaminated by different heavy metal exposure pathways and compared with reference material from Deutsche Homöopathie-Union (DHU). It was confirmed that in all cases a significant depletion of all heavy metals studied occurred during manufacture of the mother tincture, regardless of the starting material used. In all cases, most of the heavy metal content was retained in the press cake; low levels only were detected in the mother tincture. None of the mother tinctures of plant origin exceeded the required limits, not even those of plant starting materials originating from highly contaminated sites. Substantial heavy metal concentrations could only be detected in the mother tincture of the fungus Amanita muscaria, calculated from the dry weight of the starting material. According to the results obtained, a risk-based approach to heavy metal assessment is suggested where permanent control is focused on the heavy metals accumulating in organisms such as fungi.

Treatment of everolimus-resistant metastatic renal cell carcinoma with VEGF-targeted therapies.

BACKGROUND: Treatment of everolimus-resistant disease remains largely undefined in metastatic renal cell carcinoma (mRCC). We report on 40 patients (pts) who receive systemic treatment after failure of everolimus. PATIENTS AND METHODS: Forty pts received sunitinib (n=19), sorafenib (n=8), dovitinib (n=10) or bevacizumab/interferon (n=3) after failure of everolimus. Median progression-free survival (PFS), overall survival (OS) and best tumour response (according to Response Evaluation Criteria In Solid Tumors) were analysed retrospectively. Kaplan-Meier, log-rank test and Cox regression analyses were used to estimate or predict OS and PFS. RESULTS: Treatment of everolimus-resistant disease was associated with a PFS of 5.5 months. (range 0.4-22.3) and an objective partial remission (PR) in 4 pts (10%) and stable disease (SD) in 22 pts (55%). In univariate analyses, first-line treatment with sorafenib was the only variable to correlate with a prolonged PFS of treatment in everolimus-resistant disease (P=0.036). However, its significance as a predictive marker for subsequent therapy could not be verified in multivariate analyses. CONCLUSIONS: Vascular endothelial growth factor targeted therapy shows promising activity in everolimus-resistant metastatic renal cancer and warrants further studies.

[Introduction of interdisciplinary prostate cancer centers based on the recommendations of the German Cancer Society. A cost-benefit analysis 3 years after accreditation]. / Etablierung von interdisziplinären Prostatakrebszentren nach den Empfehlungen der DKG. Eine Kosten-Nutzen-Analyse 3 Jahre nach Zertifizierung.

The introduction of prostate cancer treatment centers according to the criteria of the German Cancer Society ("Deutsche Krebsgesellschaft", DKG) aims at improving the quality of care for patients with prostate cancer. Systematic analyses of the effects and costs are lacking as yet. Three years after certification of the Interdisciplinary Prostate Cancer Center at the Charité Hospital Berlin we observed a decrease in the rate of positive surgical margins (tumor stage pT2), but other parameters of treatment quality including patient satisfaction remained unchanged. A survey among urologists of the region showed a high acceptance of prostate cancer centers in general. The majority of participating urologists appreciated the work of the Charité center, in particular the treatment recommendations given by the center were mostly followed and the majority of urologists regularly use educational activities of the center. However, only 30% of the participating urologists confirmed short-term improvements in the quality of patient care. Yearly additional costs for the Charité prostate cancer center are estimated at 205,000 euro (precertification phase and certification) and 138,000 euro (monitoring phase), despite the initial drop in mean treatment costs per case (radical prostatectomy). The introduction of prostate cancer treatment centers certified by the DKG is cost intensive, increases in treatment efficiency notwithstanding. Short-term improvements in quality of care cannot be unequivocally demonstrated. Prostate cancer centers serve an important role in counseling and medical education and may thus help disseminate evidence-based treatment strategies.

[What is most important is what comes across : Urological guidelines from the target group's point of view]. / Entscheidend ist, was ankommt : Urologische Leitlinien aus Sicht der Zielgruppe.

BACKGROUND: Guidelines are developed to improve the quality of patient care. The effect of German urologic guidelines has not been evaluated so far. Therefore, we aimed to systematically investigate the acceptance, use, and quality of the published guidelines from a user's perspective. METHODS: A link to an online questionnaire concerning use and barriers to the application of guidelines was distributed via e-mail by the German Society of Urology (DGU). German urologists' opinions on differences in national guideline quality were evaluated regarding prostate cancer (PCA), bladder cancer, germ cell tumors (GCT), renal cell carcinomas, and erectile dysfunction. RESULTS: Four hundred sixty-seven German urologists participated. More than 90% of the participants considered guidelines to be helpful. The Internet as the main tool for guideline distribution was favored by 28.4%, followed by publication in Urologe A. The main barrier to guideline usage was attributed to the lack of up-to date clinical data. Guidelines for GCT scored best in all quality categories and reached the highest level of use (65.8%), and 40.5% of participating urologists considered the additional establishment of comprehensive care centers for GCT as more effective for quality improvement than guideline development alone. For the other urologic tumors, especially PCA, guideline development was favored as a tool for quality improvement. CONCLUSION: More than 90% of participating urologists accept clinical guidelines as useful instruments in clinical practice and for therapeutic decisions. Our results should be integrated into guideline dissemination and implementation strategies in order to achieve a higher degree of treatment conformation to guidelines.

Total synthesis and biological activities of (+)- and (-)-boscialin and their 1'-epimers.

Natural (-)-boscialin [(-)-1] has recently been described as one of the constituents of various medicinal plants. To obtain more material for investigations of its biological activities, we carried out the synthesis of (-)-1 and its isomers. Starting from the chiral building block 2, the key steps of the synthesis involved a regioselective reduction and a nucleophilic addition. The enantiomer of the natural product, (+)-boscialin [(+)-1], could be obtained via acid-catalyzed epimerization of hydroxyketone 4 to (+)-3. Starting the synthesis with (-)-3 led to (-)-boscialin [(-)-1] with the natural absolute configuration. In addition to (+)- and (-)-boscialin, the corresponding 1'-epimers (+)- and (-)-epiboscialin were also obtained. In vitro assays with (-)-boscialin [(-)-1] and its three stereoisomers were carried out to test for activity against microbes, parasites, and human fibroblasts. The investigations revealed activity against various microbes and against Trypanosoma brucei rhodesiense and also revealed cytotoxicity against human cancer cells.

A holistic model for moving toward excellence in chaotic times.

BACKGROUND: Staff development experts in a tertiary-care hospital were searching for a holistic approach to facilitating improved outcomes. METHOD: Staff development experts, clinical nurse specialists, and clinical managers developed a model that provides a framework for educators to integrate their energies with those of other leaders in order to create a holistic approach to the goal of achieving excellence. RESULTS: The model that is proposed links strategies for change with outcome evaluation. CONCLUSIONS: The model provides a conceptual lens that helps nurse leaders focus on organizational assessment, strategies to improve the work environment, and the evaluation of outcomes. The model is useful for guiding practice as well as research.