[Influence of ML-1 standardized mistletoe extract on the quality of life in head and neck cancer patients]. / Einfluss eines ML-1-normierten Mistelextraktes auf die Lebensqualität bei Patienten mit Kopf-Hals-Karzinomen.

BACKGROUND: ML-1 standardized mistletoe extracts have been recommended for increasing the health-related quality of life in cancer patients. PATIENTS AND METHODS: The EORTC questionnaire QLQ-C30((V2)) was given to a randomly chosen subgroup of 399 patients of a prospective, randomized, open, multi-center trial. A total of 200 patients from this trial were randomized for ML-1 treatment (1 ng/kg body weight ML-1 was injected subcutaneously twice weekly over a 60-week period. Treatment cycles of 12 weeks were followed by a break of 4 weeks (between weeks 12-16, 28-32, and 44-48)). The remaining 199 patients formed the control group. RESULTS: Patients completed questionnaires before the start of their treatments at week 0 and continued until week 156. The compliance rate was high: 3611 questionnaires were available, which equals a median of nine longitudinal measurements per patient between weeks 0 and 156. Analysis did not indicate any improvement in the quality of life for either group. A significant decrease in quality of life, however, was seen in patients undergoing radiotherapy. In these patients, the global state of health was reduced and four symptom scales were significantly worse. CONCLUSION: Our results demonstrated no improvement in the quality of life in head and neck cancer patients when treated with ML-1 extract.

Possession, use, and transfer of select agents and toxins--reconstructed replication competent forms of the 1918 pandemic influenza virus containing any portion of the coding regions of all eight gene segments. Interim final rule.

We are adding reconstructed replication competent forms of the 1918 pandemic influenza virus containing any portion of the coding regions of all eight gene segments to the list of HHS select agents and toxins. We are taking this action for several reasons. First the pandemic influenza virus of 1918-19 killed up to 50 million people worldwide, including an estimated 675,000 deaths in the United States. Also, the complete coding sequence for the 1918 pandemic influenza A H1N1 virus was recently identified, which will make it possible for those with knowledge of reverse genetics to reconstruct this virus. In addition, the first published study on a reconstructed 1918 pandemic influenza virus demonstrated the high virulence of this virus in cell culture, embryonated eggs, and in mice relative to other human influenza viruses. Therefore, we have determined that the reconstructed replication competent forms of the 1918 pandemic influenza virus containing any portion of the coding regions of all eight gene segments have the potential to pose a severe threat to public health and safety.

Mistletoe extracts standardized to mistletoe lectins in oncology: review on current status of preclinical research.

Since the identification and characterization of mistletoe lectins as pharmacologically active constituents at the end of the 1980s, research on mistletoe has made substantial advances. Mistletoe extracts are now available that are standardized in terms of the active mistletoe lectins (measured as mistletoe lectin I, ML I). This constitutes an indispensable precondition for reproducible investigations. Preclinical studies have shown that mistletoe extracts standardized in terms of ML I or pure ML I itself have highly potent cytotoxic and immunostimulating effects, predominantly on the cellular immune system. The immunostimulating effect is correlated with the apoptosis of immunologically active cells at low concentrations. Cytotoxic effects on tumor cells are likewise apoptosis-related, but at higher levels necrotic cell death predominates. Due to these properties, mistletoe extracts or pure ML I showed antitumoral activities in different animal models. The objective of this review is to present the current state of preclinical research on standardized mistletoe extracts which hence may be included in the category of rationalphytotherapy.

[Immunomodulating mistletoe therapy by lectin standardization: a double-edged sword?]. / Immunmodulierende Misteltherapie durch Lektinstandardisierung: Ein zweischneidiges Schwert?

Taking advantage of an unique, legally generous regulation, proprietary anthroposophic and phytotherapeutic mistletoe preparations are on the market in Germany. One constituent of the extract, the galactoside-specific lectin, is a potent biological response modifier in a very narrow low-dose range. Although the clinical implications of the lectin effects remain to be rigorously defined, this activity already prompted companies to eliminate the common batch-to-batch variations in favor of standardization, keeping the lectin content, which could otherwise vary drastically, purportedly constant. Based on literature data, immunomodulation by the lectin involves enhanced secretion of multifunctional proinflammatory cytokines such as IL-6. The apparently context-dependent ambivalence of their actions includes capacity to serve as autocrine and paracrine tumor growth and survival factors for a wide variety of tumor cell types in vitro and in vivo, as illustrated by the literature presented. The potential for clinical risks is indicated to be non-negligible, e.g. for lymphomas, advanced-stage melanomas and renal cell carcinomas. Moreover, negative effects of immunomodulatory lectin or extract treatment have already been reported. To reliably prove clinical efficacy and exclude lack of undesired side effects for each tumor class and stage, it is mandatory to evaluate the performance of this experimental therapy modality exclusively in relevant preclinical settings and strictly controlled clinical studies to obey the generally accepted rule: primum non nocere.

[Value of mistletoe lectin standardized mistletoe extract for evaluating antitumor properties]. / Zur Bedeutung eines auf Mistellektin eingestellten Mistelextraktes für den Nachweis antitumoraler Eigenschaften.

It could be shown from several experiments that carbohydrate-binding mistletoe lectins represent the pharmacologically active constituents of mistletoe extracts. On the basis of these findings, it was possible to develop an extract preparation standardized with respect to the mistletoe lectin concentration. This drug is the first mistletoe preparation that fulfills the criteria of the guidelines for the development of drugs (1) regarding its quality and stability of the active ingredients under certain storage conditions. The quality of this preparation has also been shown in several animal models to demonstrate antitumoral potencies.

Immunisation against ovine caseous lymphadenitis: comparison of Corynebacterium pseudotuberculosis vaccines with and without bacterial cells.

Sheep were immunised with Corynebacterium pseudotuberculosis vaccines prepared from cell-free toxoid or from toxoid with formalin-killed cells of C pseudotuberculosis added. Resistance of sheep to infection was tested 6 months after immunisation by inoculation with caseous lymphadenitis pus. The outcome was assessed 3 months later by slaughter and inspection of the sheep for lesions of caseous lymphadenitis. immunised sheep were adequately protected against infection as shown by a significant reduction in the number of sheep exhibiting lesions compared with control sheep, and by fewer abscesses in affected vaccinated sheep than in affected control sheep. The protective potency of the vaccines was not improved by the inclusion of cells of C pseudotuberculosis.

Biological standards and pharmacopoeias.

The use of standards in the control of biological substances is of particular importance because the potency of such substances cannot be adequately determined by physical or chemical means. For these substances, therefore, it is necessary to compare the activity or potency of a given quantity with that of a similar quantity of a standard or reference preparation to which a unitage has been assigned. In order to eliminate as far as possible the inherent variables in biological tests, especially in tests involving animals, the comparison between the standard and the unknown must be made in a single test. Furthermore it is essential that the biological activity of the standard has the same properties as those products for which the standard is used as a control. The master standards are the International Standards held by the World Health Organization and it is necessary to establish European or National Standards calibrated in International Units in order to conserve the stocks of the master standards. Criteria for the quality of preparations suitable as standards will be considered and some examples of their use will be presented.