Josef Beuth

Impact of complementary oral enzyme application on the postoperative treatment results of breast cancer patients--results of an epidemiological multicentre retrolective cohort study.

Purpose: To evaluate the impact of postoperative treatment with an oral enzyme (OE) preparation given complementary to an antineoplastic therapy in patients with breast cancer. Methods: The design of this epidemiological study was a retrolective cohort analysis with parallel groups. Design and conduct of the study were performed to current standards for prospective, controlled clinical trials. A cohort of 2339 breast cancer patients undergoing surgical intervention and radio-, chemo- or hormonal therapy were studied in 216 centres. Of the 2339 patients, 1283 received complementary treatment with OE and 1056 did not receive OE. Patients with other complementary medications were excluded and the final analysis was performed with the data from 649 patients, of whom 239 (37%) were additionally treated with OE (test group) and 410 (63%) without OE (control group). The median follow-up time for the test group was 485 days and for the control group 213 days. The primary endpoint of the study was to determine whether complementary treatment with OE can reduce typical disease- or therapy-associated signs and symptoms (gastrointestinal symptoms, mental symptoms, dyspnoea, headache, tumour pain, cachexia, skin disorders, infections, and side effects associated with the antineoplastic therapy) in patients with breast cancer. Imbalances for causal effects (covariates) were adjusted for by means of the propensity score. Outcome analysis was performed by estimating the linear regression between change in symptom score and propensity score with all data and using this regression line to calculate the change in symptom score which would be expected for each patient. Tumour-associated events (recurrence, metastasis, and death) were evaluated in terms of the number of events observed and time to event. The safety of treatment with OE was analysed in terms of the number and severity of adverse events, their duration, treatment and outcome. Results: For all symptoms except tumour pain, the adjusted mean improvement in symptom scores was larger in the test group than in the control group. The adjusted difference was statistically significant for all symptoms, except tumour pain and infections. The results show that the typical disease- and therapy-associated signs and symptoms in patients on complementary therapy with OE during postoperative treatment were significantly less. For 75% of the test group and 55% of the control group the physician recorded “no signs and symptoms”. A clear reduction in the side effects of radiotherapy and chemotherapy was documented in 74% of the test group and 55% of the control group. Analysis of survival, recurrence, and metastasis demonstrated a reduced number of events in the test group. There was evidence of a beneficial influence of OE on time to event, although the median observation time was too short in these breast cancer patients to draw definite conclusions. The safety component was judged in 98% of the test group and 76% of the control group as “very good” or “good”. In the total sample of 2339 patients, the rate of OE-associated adverse reactions was 3.2%. All side effects were mild to moderate gastrointestinal symptoms. Conclusion: Complementary treatment of breast cancer patients with OE improves the quality of life by reducing signs and symptoms of the disease and the side effects of adjuvant antineoplastic therapies. This epidemiological retrolective cohort analysis provides evidence that the patients may also gain benefit by a prolongation of the time to event for cancer recurrence, metastasis and survival. OE was generally well tolerated.

Proteolytic enzyme therapy in evidence-based complementary oncology: fact or fiction?

Systemic enzyme therapy was recently subjected to experimental investigations and to rigorous clinical studies in cancer patients. The designs of the relevant clinical cohort studies followed the guidelines of Good Epidemiological Practice and represent level IIB in evidence-based medicine (EBM). Scientifically sound experimental in vitro and in vivo investigations are far advanced and document promising immunological, anti-inflammatory, anti-infectious, and antitumor/antimetastatic activities of proteolytic enzyme mixtures (containing trypsin, chymotrypsin, and papain) or bromelain. EBM level II clinical studies, which are accepted by the European Union to show safety and efficacy of medical treatments, were performed to evaluate the benefit of complementary systemic enzyme therapy in cancer patients suffering from breast and colorectal cancers and plasmacytoma. These studies demonstrated that systemic enzyme therapy significantly decreased tumor-induced and therapy-induced side effects and complaints such as nausea, gastrointestinal complaints, fatigue, weight loss, and restlessness and obviously stabilized the quality of life. For plasmacytoma patients, complementary systemic enzyme therapy was shown to increase the response rates, the duration of remissions, and the overall survival times. These promising data resulted in an “orphan drug status” designation for a systemic enzyme product, which should motivate further studies on this complementary treatment.

Besonderheiten der implantatassoziierten Infektion in der orthopädischen Chirurgie

ZusammenfassungDer zunehmende Einsatz von Implantatmaterialien führt zu einem Anstieg des Infektionsrisikos in der modernen Orthopädie. Ist ein Implantatmaterial erst einmal infiziert werden, muss—da die Pathophysiologie dieser speziellen Art von Infektion zu einer relativen Unempfindlichkeit konventioneller Antibiotikatherapien führt—in der Regel das Material explantiert werden. Die Folgen sowohl für den Patienten als auch für unser Gesundheitssystem sind gravierend.Mindestens ein Drittel der Infektionen lässt sich durch striktes hygienisches Arbeiten verhindern. Aufgrund auch geringster Inokulationsmengen als Basis für eine Materialkolonisation und -infektion muss von einem großen Anteil „physiologischer Infektionen“ ausgegangen werden. Deshalb ist die Entwicklung infektionsresistenter Implantatmaterialien eine medizinische Notwendigkeit. Moderne Konzepte solcher Materialien beinhalten antimikrobielle „Drug-delivery-Systeme“, welche in der Lage sind, unphysiologisch hohe Konzentrationen antimikrobieller Substanzen in die Mirkoumgebung des Implantats abzugeben, um damit die phänotypische Resistenz adhärenter Mikroorganismen zu überlisten.AbstractOne of the most important risk factors in orthopedic surgery is implant-associated infection. Adhesion and colonization mediated implant infections are extremely resistant to antibiotics and host defences and frequently persist until the biomaterial or foreign body is removed, which is standard therapy. Tissue damage caused by surgery and foreign body implantation increases the susceptibility to infections, activates host defences and stimulates the generation of inflammatory mediators including radicals that are further aggravated by bacterial activity and toxins.Nearly one third of implant-related infections can be prevented by strictly following established infection control guidelines. However, a significant number of implant-associated infections remains. The escape of bacteria from host defence and antibiotic therapy makes the development of infection-resistant materials as antimicrobial drug delivery systems feasible. This concept consists of the sustained delivery of antimicrobial drugs into the local microenvironment of implants avoiding systemic side effects exceeding usual systemic concentrations by magnitudes of order.

Proinflammatory Responses to Lipo-oligosaccharide of Neisseria meningitidis Immunotype Strains in Relation to Virulence and Disease

Inflammatory responses to lipo-oligosaccharide (LOS) contribute to the severity of meningococcal disease. Strains that express the L(3,7,9) LOS immunotypes are isolated from the majority of patients, but other immunotypes are isolated predominantly from carriers. Inflammatory responses elicited from a human monocytic cell line (THP-1) that had been pretreated with vitamin D3 (VD3) were compared after stimulation with purified LOSs from standard immunotype strains. The neutralizing effects of normal human serum and serum from mice immunized with strain B:2a:P1.5,2:L3 were compared. LOSs of immunotypes L3, L7, L8, and L9 induced significantly higher levels of tumor necrosis factor-alpha and interleukin-6, compared with other immunotypes. Normal human serum neutralized the proinflammatory responses to LOSs of all immunotypes tested. Immune mouse serum neutralized inflammatory responses against LOSs from immunotypes with epitopes cross-reactive with L(3,7,9) moieties. Antibodies found in normal human serum and immune mouse serum to the oligosaccharide, core, and lipid A moieties of meningococcal endotoxin contribute to neutralizing activity.

Lectin mediated adhesion of Streptococcus pneumoniae and its specific inhibition in vitro and in vivo

According to our hypothesis, bacterial lectins play an important role in the organotropy of infectious diseases which is analogous to the metastasis of tumor cells. As a model for proving this, we investigated the specific lectin of Streptococcus pneumoniae, which has N-acetyl-D-glucosamine/D-galactose (GlcNAc-Gal) specificity. In vitro, after incubation with Streptococcus pneumoniae, cryotome sections of various organs from Balb/c-mice showed remarkable quantitative differences of bacterial adhesion to the organ cells. Whereas lungs and meninges were closely settled with bacteria, attachment to other organs (e.g. liver, spleen, brain) was lacking. In vitro lectin-blocking by GlcNAc completely prevented the adherence of Streptococcus pneumoniae to lungs and meninges. Other non-related carbohydrates (e.g. D-mannose, D-xylose) showed no effect. During in vivo experiments with Balb/c-mice, intratracheal application of Streptococcus pneumoniae led to a diffuse settlement of the lung. However, bacterial lectin-blocking with intratracheal GlcNAc administration completely inhibited adhesion to the organ cells of the lung. Therefore blocking of bacterial adhesins with competitive specific monosaccharides can completely prevent bacterial adhesion processes, a fact, which opens therapeutical aspects.

Evidence-Based Complementary Medicine in Breast Cancer Therapy.

Complementary medicine is currently widely debated by the oncologic community, because the required scientific proof of safety and effectiveness for most of the therapeutic approaches has not yet been met with definite results. In the past years, basic research and clinical evaluation of defined complementary therapeutic concepts in oncology have been intensified in an attempt to integrate these procedures into evidencebased medicine. According to definition, scientificallybased therapies of complementary medicine cannot replace the wellstudied conventional cancerdestructive therapies such as surgery, chemotherapy, radiotherapy, or hormone therapy. Complementary approaches in oncology that are recommended as an addition to standard cancerdestructive therapies claim to optimize this therapy. A great body of data emerging from scientifically sound clinical trials prove that defined complementary procedures are beneficial for the patients.

Respiratory burst of human polymorphonuclear leukocytes in response to the galactoside-specific mistletoe lectin

The phagocytic activity of human polymorphonuclear leukocytes (PMNLs) towards Staphylococcus aureus Cowan 1 was evaluated in chemiluminescence assays. As to check its activating ability, galactoside-specific mistletoe lectin (ML-1) was coincubated with PMNLs which were then challenged with S. aureus. Statistically significant (p < 0.001) chemiluminescent response (correlating with phagocytic activity) could be demonstrated at optimal experimental condition, viz: 1 x 10(6) PMNLs incubated with 0.005 ng ML-1 for 30 and 60 minutes before S. aureus challenge. Other experimental schedules (different timing and PMNL/ML-1 concentrations) did not present with statistically relevant changes in chemiluminescent response. These studies suggest that optimal ML-1 concentrations enhance the phagocytic activity of PMNLs which might be of benefit in thus treated patients as to prevent (or lower the rate of) infections under antineoplastic therapy.

Effect of Immunomodulation with Galactoside-specific Mistletoe Lectin on Experimental Listeriosis*

BALB/c-mice (n = 10 per experimental group) were intravenously infected with 5 x 10(4) and 5 x 10(5) viable cells of Listeria monocytogenes SLCC 4013. About 50-80 h after this challenge, all mice of the untreated control groups succumbed to their infection. Pretreatment of experimental animals on the optimal immunoactive schedule with the galactoside-specific mistletoe lectin (ML-1; 1 ng/kg body weight; days 1, 4, 5, 6 before challenge), however, evidently reduced the lethality of listerial infection (survival rate 60%).

Bedarf erkennen, gezielt verwenden

Ausgleichen, was fehlt — auf Basis dieser Theorie nehmen heute viele gesundheitsbewusste Menschen präventiv Nahrungsergänzungsmittel ein. Die Diskussion um den Nutzen dieser Maßnahme reißt nicht ab. Was dabei aber immer wieder deutlich wird: Besteht tatsächlich ein erhöhter Bedarf, wie in der Schwangerschaft oder bei Krebspatienten, kann das Konzept der Nahrungsergänzung ein sinnvolles sein.

Komplementäre Therapie aus der Sicht von Krebspatientinnen

«Deine Medizin sei deine Nahrung und deine Nahrung sei deine Medizin». Dieser Satz stammt nicht etwa aus einem der bekannten «Ernährung bei Krebs»-Bücher, sondern wird Hippokrates von Kos (460 – 370 v. Chr.), dem berühmtesten Arzt der Antike, dem «Vater der Heilkunde» und dem «Begründer der Medizin als Wissenschaft» zugeschrieben. Würde man sich weiter mit Hippokrates und einem antiken Werk mit großer Nachwirkung, dem «Corpus Hippocraticum», befassen, so stieße man auf erstaunliche Dinge: «Licht und Luft, Entgiftung, Entschlackung, Entsäuerung, richtiges Essen und Trinken, Aktivität und Entspannung» und die «stetige Übung in Gelassenheit» sollen in ihrer Gesamtheit den Schlüssel zu Gesundheit und Glück bereit stellen. Heute findet man diese alten komplexen Gesundheitsempfehlungen neben einer großen Anzahl weiterer Möglichkeiten unter dem Sammelbegriff «Komplementärmedizin» (lat. complementum = Ergänzung) oder «komplementäre Therapie» oder auch «komplementärmedizinische Maßnahmen» wieder. Die Palette ergänzender Maßnahmen umfasst mittlerweile nicht nur die bekannte Homöopathie und Akupunktur, sondern erstreckt sich auf über 200 verschiedene Methoden – von der Traditionellen Chinesischen Medizin über die Misteltherapie und Anthroposophie bis hin zur Meditation, dem Qi Gong oder der Tanztherapie. Einige dieser Behandlungen stellen inzwischen einen Teil der Standardtherapie dar, so dass neben der reinen Schulmedizin auch Bewegungsund Atemoder Ernährungstherapie oft zum Behandlungsplan gehören. Die Übergänge zwischen Schulmedizin und Komplementärmedizin sind fließend geworden. Was gestern noch unter den Begriff «komplementär» fiel, ist heute Teil der Schulmedizin, seit kleinere Studien die Wirksamkeit einiger komplementärer Maßnahmen belegt haben.