Increased adipogenesis and myelopoiesis in the bone marrow of SAMP6, a murine model of defective osteoblastogenesis and low turnover osteopenia.

Bone formation and hematopoiesis are anatomically juxtaposed and share common regulatory mechanisms. However, little is known about the interrelationship between these two processes. We have previously shown that the senescence accelerated mouse-P6 (SAMP6) exhibits decreased osteoblastogenesis in the bone marrow that is temporally linked with a low rate of bone formation and decreased bone mineral density. Here we report that in contrast to decreased osteoblastogenesis, ex vivo bone marrow cultures from SAMP6 mice exhibited an increase in the number of colony-forming unit adipocytes, as well as an increase in the number of fully differentiated marrow adipocytes, compared with SAMR1 (nonosteopenic) controls. Further, long-term bone marrow cultures from SAMP6 produced an adherent stromal layer more rapidly, generated significantly more myeloid progenitors and produced more IL-6 and colony-stimulating activity. Consistent with this, the number of myeloid cells in freshly isolated marrow from SAMP6 mice was increased, as was the number of granulocytes in peripheral blood. The evidence that SAMP6 mice exhibit decreased osteoblastogenesis, and increased adipogenesis and myelopoiesis, strongly suggests that a switch in the differentiation program of multipotential mesenchymal progenitors may underlie the abnormal phenotype manifested in the skeleton and other tissues of these animals. Moreover, these observations support the contention for the existence of a reciprocal relationship between osteoblastogenesis and adipogenesis that may explain the association of decreased bone formation and the resulting osteopenia with the increased adiposity of the marrow seen with advancing age in animals and humans.

Morphological characterization of stromal cell types in hematopoietically active long-term murine bone marrow cultures.

Accurate histological evaluation of stromal morphology is very difficult in cultures incubated in plastic flasks. Employing glass flasketts, we were able to characterize the morphology and immunocytochemistry of four marrow stromal cell types in a functionally intact microenvironment of murine long-term bone marrow cultures (LTBMCs). Fibroblastoid cells stained positively for collagen Type I and III, negatively for von Willebrand factor (vWf), the mouse macrophage F4/80 antigen, and the Bandeiraea simplicifolia lectin I isolectin B4 (BSL I-B4). Endothelial cells stained positively for vWf antigen and lectin BSL I-B4 but negatively for collagen Types I and III and for F4/80 antigen. Fat-containing cells had a dense, ovaloid, indented nucleus and fat-containing vacuoles. Macrophages were strongly positive for the F4/80 antigen and stained weakly with BSL I-B4. Between the fourth and ninth weeks after culture initiation, fibroblastoid and endothelial cells remained constant, between 21 +/- 2% and 24 +/- 2% and between 3 +/- 0.3% and 4 +/- 0.4%, respectively, of the total stromal cell population. By contrast, the percentage of fat-containing cells decreased significantly from 26 +/- 3% at Week 4 to 17 +/- 2% at Week 9, and macrophages increased significantly from 49 +/- 1% at Week 4 to 57 +/- 1% at Week 9. This characterization of the stromal cell types in functionally intact LTBMCs should assist in the study of the complex interactions among the marrow stroma, cytokine production, and hematopoiesis.

Effects of unprocessed and processed cardiopulmonary bypass blood retransfused into patients after cardiac surgery.

BACKGROUND: The aim of this prospective study was to compare the effect of autologous unprocessed to processed residual cardiopulmonary bypass blood (CPB) on patients' laboratory and clinical parameters and outcome. METHODS: 20 patients undergoing elective coronary artery bypass surgery were randomized to receive either unprocessed CPB blood (control group) or processed CPB blood employing the Continuous AutoTransfusion System (CATS; Fresenius, Bad Homburg, Germany). We have shown that this method eliminated >93% of activated mediators. Serial laboratory parameters including complement activation, coagulation factors and the stimulation of IL-6 and IL-8 were compared with clinical side effects and patients' outcome. RESULTS: Compared to control patients, retransfusion of unprocessed CBP blood significantly increased heparin, free plasma hemoglobin and D-Dimers. Postoperatively, three patients in the control group and two patients in the CATS group required prolonged mechanical ventilation or developed infections associated respectively with elevated C3a (desArg) or IL-6 concentration. CONCLUSIONS: CATS-processing of CPB blood provided a high-quality red blood cell concentrate, resulting in a reduced load of retransfused activated mediators.

[Dr. Sklenar's Kombucha mushroom infusion--a biological cancer therapy. Documentation No. 18]. / Teepilz Kombucha nach Dr. med. Sklenar--eine biologische Krebstherapie. Dokumentation Nr. 18.

Kombucha, a fungal infusion, is a 'symbiotic mixture' of bacteria, yeasts, tea and sugar. A number of components are listed, but exact analyses are not published. On the basis of 'thorough detoxification', Kombucha is claimed to be a prophylactic and therapeutic agent in countless diseases, such as rheumatism, intestinal disorders, ageing and cancer. All 'stages of the Sklenar blood picture' have to be treated with Kombucha Drink, Kombucha Drops, coli preparations and Gelum oral-rd for a period of months. A litre-bottle costs 13 DM, the blood analysis 150 Sfr. In the 1960's Dr. R. Sklenar developed a 'biological cancer therapy with Kombucha as the main agent' and his own system of diagnosing cancer. Sklenar's diagnosis of cancer is based on iris diagnosis and demonstration of the causative organism by means of a 'Blood picture according to Dr. Sklenar'. He claims, on one hand, that cancer is only one of the many metabolic diseases and, on the other, that viruses, in his view parasitic microorganisms in general, are responsible for the pathogenesis of cancer. No preclinical and nor investigations are available, as 'success has proved him (Dr. Sklenar) to be right'. The seven 'case histories' described have no solid medical data. There is so far no evidence to support the claim that Kombucha offers 'effective biological treatment of cancer'.

[Are paramedical means and methods justified in the treatment of breast carcinoma?]. / Haben paramedizinische Mittel und Methoden in der Behandlung des Mammakarzinoms eine Rechtfertigung?

In industrial countries breast cancer is the second frequent malignancy of women. The often metastasizing (65 to 70%) and long-lasting illness leads patients in more than 50% to paramedical treatments. An analysis of the unproven methods and the remedies concerning the effectiveness against breast cancer is done: mistletoe preparations, nutrition directions, organotherapy (cell therapy, cytoplasmatic and thymus therapy), enzyme-preparations and further paramedical remedies and methods. In the last part, the discussion covers the findings of the 'Gesellschaft für Biologische Krebsabwehr', which presumes that biological remedies will lead to a turn in cancer treatment. An exact analysis of the paramedical literature shows that the quoted successes of paramedical treatment are nearly parallel to the successes of 'ortho-medical' therapies, which are not mentioned at all or only on incidentally.

[Autologous tumor therapy]. / Autologe Tumortherapie.

The dermatologist from Munich developed three differently called therapies; however, they basically show the same theory. They are the treatment with transoptin, tumor identification training for autologous immunocompetent cells (TI-TAI), and the autologous target cytokine (ATC) therapy. The ATC therapy is supposed to have a positive effect on all cancers and immunodeficiencies. Side effects are denied, although oncologists have noticed fatigue, fever, pain, lymphopenia, leukocytosis and others. The dermatologist supposedly establishes tumor cell and leukocyte cultures from blood and mixes them later on. The cytokines (ATC), produced by the lymphocytes, are harvested in 40 ampules and then subcutaneously injected. One cycle with the ATC therapy costs around 3000 DM. The dermatologist believes that tumor cells can only be immunologically identified during the dividing phase. He stimulates the cultured tumor cells to divide. At the same time he adds the autologous immunocompetent cells which should be trained to identify tumor cells and to produce cytokines. The dermatologist uses many terms unconventionally and imprecisely. The in-vitro training of lymphocytes for tumor defense with the method of the dermatologist is experimentally unproven. The production of the ATC preparations is kept secret. Also unclear are the mechanisms of action and the clinical efficacy. Besides neologisms, the dermatologist does not offer any scientific or clinical facts for his therapy of cancers.

[Helixor--mistletoe preparation for cancer therapy. Documentation No. 19]. / Helixor--Mistelpräparate für die Krebstherapie. Dokumentation Nr. 19.

Helixor is an aqueous cold extract from fresh mistletoe, obtained from fir, pine and apple trees. A number of components with different possible effects were isolated: lectins, viscotoxins, alkaloids, etc. "Oncological therapy" and "stimulation of the bone marrow" are given as the main fields of indication. Pregnancy, hyperthyroidism and intolerances are given as contraindications. Depending on the type and the stage of the tumour, treatment based on a specific rhythmic schedule should be carried out for a period ranging from five years to a lifetime. A 7-ampoule pack costs 37 to 44 DM. Local inflammatory reactions occur as side effects. Fever is desirable. Helixor was developed by the Section for Leukemia and Cancer Therapy of the Gemein-schaft Fischermühle e. V. in Rosenfeld, FRG, and has been used since about 1968. It is produced and distributed by Helixor Heilmittel GmbH & Co. The origin of anticancer treatment with Helixor, a mistletoe preparation, is the anthroposophical medicine. In addition, Helixor supposedly bridges the dramatic gap between conventional and natural treatment of cancer in that it exerts both a selective cancerostatic and an immunostimulatory effect. Hardly any research has been done on the pharmacodynamics, the pharmacokinetics and the toxicity of the total extract Helixor. In vitro studies reveal a cytostatic effect on individual cell lines; animal experiments with freshly pressed juice are contradictory. Specific effects of Helixor on the immune system and its actual bearing on the tumour process have so far not been unequivocally elucidated. The three clinical-historical comparative studies contain methodological errors. They do not provide evidence of the clinical efficacy against tumours.(ABSTRACT TRUNCATED AT 250 WORDS)

[Cancer treatment using Dr. Moerman's diet and therapy. Documentation No. 24]. / Krebsheilung durch die Dr.-Moerman-Diät und -Therapie. Dokumentation Nr. 24.

For prophylaxis of cancer and treatment of manifest cancer Morerman recommends as the basis of his therapy a lactovegetable diet and, in addition, the '8 essential substances': vitamins A, B, C and E, iodine, sulfur, iron and citric acid. At a later stage he also recommends supplementary vitamin D and selenium. The most important aspect is the change in dietary habits required by the diet prescribed by Moerman and the ingestion of the '8 essential substances' in the form of conventional preparations. The daily cost of treatment of a prostatic cancer, for instance, ranges from about Fr. 3.- to Fr. 6.-. Side effects are not mentioned. The diet and therapy were developed by the Dutch physician Dr Moerman (1893-1988) as long ago as the 1930s. The promoters are the iridiologist J. Landman, the nutritional consultant E. Wannee and the writer R. Jochems. All three have written a book on Moerman. In Switzerland, the Lifecare Association endeavours to disseminate this form of therapy. A chronic deficiency of the '8 essential substances' is said to lead to metabolic disturbances, structural and behavioural anomalies of the regeneration tissue and alkalosis, which is claimed to be a fertile soil for the 'symbionts' that can transform healthy cells into cancer cells. Moerman came to this conclusion on the basis of his observations of pigeons. By means of a lactovegetable diet and substitution of the '8 essential substances', this metabolic disorder is said to be reversible, thus robbing the 'symbionts' of their growth medium. The results of the experiments with pigeons have, as far as we know, never been published.(ABSTRACT TRUNCATED AT 250 WORDS)

[The "Lifecare Concept" of "ecological cancer prevention". Report No. 29]. / Das "Lifecare-Konzept" der "ökologischen Krebsverhütung". Dokumentation Nr. 29.

The Lifecare concept of ecological cancer prevention is summarized in the Lifecare Fitness Checkup and contains: Lifecare questionnaire, Lifecare age test using Vincent's bioelectronic method. Lifecare reform programme according to Kousmine and a whole food, fresh fruit and vegetable diet in accordance with the nutritional pyramid, personal health counselling based on the Lifecare philosophy and ecological holistic medicine. Subjects are tested and supervised by a Lifecare doctor who has been admitted to the Lifecare Association. Only the prophylactic Lifecare testing and supervising would require roughly one physician per 1000 subjects. In 1982, the equipment costs were DM 13,000.- and the test DM 150.-. The Lifecare Association was founded as a non-profit organization in 1986 with its headquarters in Zurich. Mrs. T. Büchi-von Arx is the initiator of the Lifecare Association, Dr. Lietha is founding president, and the current president is Dr. M. Vogel, Lugano. The main promotors are named as Dr. h.c. A. Vogel and Bioforce Ltd. The association promotes a Lifecare philosophy on the basis of ecological holistic medicine, which itself is based on the terrain theory. It is maintained that the cause of degenerative diseases such as cancer and rheumatism is an alteration in the terrain brought about by over-acidification of the tissue resulting from metabolic disturbances. Vincent's bioelectronic test supposedly enables changes in the terrain to be detected even before the subject becomes manifestly ill. The aim is to exclude ecological toxins. Apparently the terrain can be normalized by a diet rich in vital substances. No scientific investigations are available on the hypothetical Lifecare concept of ecological cancer prevention.(ABSTRACT TRUNCATED AT 250 WORDS)

[M. von Ardenne's multi-step cancer therapy and variations--universally applicable in oncology? Documentation No.23]. / Krebs-Mehrschritt-Therapie nach M. von Ardenne und Varianten--universell einsetzbar in der Onkologie? Dokumentation Nr. 23.

M. von Ardenne advances 2 concepts for the treatment of cancer: the Multistep-Cancer-Therapy (MCT) and the O2-Multistep-Immunostimulation (O2-MIS). Since the properties of cancer tissues postulated by. M. von Ardenne are considered common to all malignant tumours, MCT and O2-MIS can be employed in any type of malignancy. These concepts are recommended for cancer therapy and prophylaxis. The 1989 concept consists of the combination of O2-MIS (thymus) for 18 days followed by MCT on the 19th day. O2-MIS can be done on an outpatient basis, whereas MCT must be carried out in hospital. An investment of 5000 to 10,000 Fr. is needed to provide O2-MIS in a medical practice. In 1959, Prof. Dr. h. c. mult. M. von Ardenne transferred from research in the field of physics to cancer research. He published the basic concept of MCT in 1965, from which the Oxygen-Multistep-Therapy (SMT) and the O2-MIS were later derived. Most of the proponents are found in the former Federal Republic of Germany, where the SMT-Society is responsible for the dissemination of the ideas and apparatus. The mechanism of action of MCT consists of the irreversible occlusion of tumor blood vessels as a result of "elective over-acidification of the cancer cells and tumour tissue by stimulating the aerobic fermentation metabolism of cancer cells discovered by O. Warburg in 1924". O2-MIS, on the other hand, works by potentiating non-specific defences. Contrary to his claims, von Ardenne has so far been unable to demonstrate a reproducible efficacy either for the MCT or for O2-MIS against cancer in man. Despite a supposedly large number of patients treated, no clinical trials have yet been published.(ABSTRACT TRUNCATED AT 250 WORDS)

[Vysorel/Isorel--cancer drug from Viscum album. Documentation No.20]. / Vysorel/Isorel--Krebstherapeutikum aus Viscum album. Dokumentation Nr. 20.

Vysorel/Isorel is an aqueous extract from fresh mistletoe (viscum album). A number of components with different possible effects have been isolated, but exact analyses of the preparation have not been published. One ampoule 'Stärke 60' of 1 ml contains the extract of 60 mg mistletoe. Vysorel/Isorel is recommended in all malignant diseases, in 'precancerous' conditions and for prevention of relapse. Vysorel/Isorel is supposed to be taken subcutaneously according to a rhythmic schedule. Drug costs for one year in precancerous conditions are approximately 900 DM, for prevention of recurrence approximately 1800 DM, in the case of inoperable tumour approximately 3800 DM. Vysorel/Isorel is also a product of the anthroposophical medicine according to R. Steiner. It is marketed by Novipharm GmbH as Isorel in Austria and as Vysorel in the Federal Republic of Germany. The clinical efficacy of Vysorel/Isorel is derived from the demonstration of proteins from mistletoe (so-called 'Vester's Protein') with cancerostatic activity in vitro. No preclinical or clinical investigations are available. None of the 33 case histories suggests that Vysorel/Isorel is effective in the treatment of malignant diseases. Vysorel/Isorel is not registered in Switzerland at the IKS. It has been permitted in Austria since 1983 and in Germany since 1986.

[GELUM oral-rd: blood pH regulator and oxygen activator. Documentation No.27]. / GELUM oral-rd: Blut-pH-Regulator und Sauerstoffaktivator. Dokumentation Nr. 27.

GELUM oral-rd contains a potassium iron phosphate-potassium iron citrate complex, lactic acid and vitamins. It is recommended in oxygen deficiency states, tissue and tumour diseases and more recently as an adjunct to tumour therapy. The recommended dosage is 20 drops three times daily, to be taken for 5 to 10 years following cancer surgery. No side effects are stated. The daily cost of treatment is DM - .60 to DM 1.35. Manufacturer: Laboratorium pharmazeutischer Erzeugnisse Dr. Elten und Sohn was founded in 1938 and was renamed Dreluso Pharmazeutika Dr. Elten & Sohn in 1948, Oldendorf, FRG. Malignancies require a pathological alkaline milieu for growth; the associated increase in oxygen deficiency is caused by an unbalanced diet and carcinogens. GELUM oral-rd restores an optimum milieu and at the same time activates the lymph system, thereby providing the basis for all other tumour therapies. In transplant tumours and in Meth-A mouse fibrosarcoma, only prophylactic administration of GELUM oral-rd lengthened survival time or reduced tumour induction. Lymph node hyperplasia and giant cells in the spleen, occurring only in the pretreated animals, are also interpreted as nonspecific activation of the body's defence system. The clinical investigations are more anecdotal in nature, and the basic documentation and case studies are inadequate. In the prospective, randomized trial in 72 patients suffering from carcinoma of the gastrointestinal tract, the conclusion of efficacy is questionable on account of the incongruence between the group receiving the active drug and the control group. GELUM oral-rd is not registered in Switzerland at the IKS.

[Factor AF2--the 4th column in tumor therapy. Documentation No.22]. / Factor AF2--die vierte Säule in der Tumortherapie. Dokumentation Nr. 22.

Factor AF2 is an extract from the spleen and liver of sheep embryos and lambs. The product contains biotechnologically produced, chromatographically uniform, molecularly standardized polypeptides, glycopeptides, glycolipids and nucleotides, deproteinized and free of pyrogens'. Factor AF2 is intended mainly for use in 'supportive antitumour therapy', as a 'biological antiemetic and analgesic'. The proposed duration of treatment is usually more than six months. The dosage varies considerably according to the indication. The average daily costs are, therefore, between DM 4.- (prevention of recurrence) and DM 107.- (adjuvant to chemotherapy). Allergic reactions have been reported in 'rare cases'. Factor AF2 was developed in the forties by Guarnieri in Rome. Since 1984, Factor AF2 is 'biotechnologically' produced and as a 'biological response modifier' (BRM) in the oncotherapy distributed by Biosyn Arzneimittel GmbH, Stuttgart. Dr. rer. nat. T. Stiefel and Dr. rer. nat. H. Porcher are the representatives of Biosyn Arzneimittel GmbH. In the past, both worked with Vitorgan Arzneimittel GmbH (cytoplasmatic therapy according to Theurer). It is claimed that Factor AF2 contains 'immunomodulating and immunorestorative biomolecules' assignable to the BRM group. Terms and investigations from current immunological research are applied to Factor AF2. No preclinical investigations are available which demonstrate any cytostatic effect of Factor AF2. In vivo, no effects were observed on the transplanted meth-A-sarcoma in mice.(ABSTRACT TRUNCATED AT 250 WORDS)

[Mexican medicinal plants and Grüninger's diet. Documentation No.25]. / Mexikanische Medizinalpflanzen und Diät nach Grüninger. Dokumentation Nr. 25.

A decoction is prepared from 14 Mexican medicinal plants. This phytotherapy is supplemented by a special diet ('food with a high nutritional value') and nutritional supplements such as lactoferment, enzyme preparations (e.g. Wobenzym), co-enzymes (e.g. Becozym forte) Ossopulvit, vitamin C, iron preparations and raw melasses. The following indications are mentioned: all stages of cancer, following surgery, during radiotherapy or chemotherapy in order to alleviate side effects and stimulate the immune system and hematopoiesis, detoxification in all other diseases. The initial fasting period is followed by a diet, phytotherapy and the ingestion of nutritional supplements. The only side effects are caused by tumour degradation products as a result of excessively rapid tumour degradation. The documentation brochure costs Fr. 30.-. The patient pays what he likes for the tea bag of a cure. F.A. Grüninger is a chemist living in the Bernese Oberland (Switzerland). He spends most of his time in Mexico, where he himself collects the individual plants. According to Grüninger, cancer is an intoxication of the entire body as a result of an inappropriate diet (demineralized, poor in cellulose, high in hormone levels). The intoxication in counteracted by fasting, phytotherapy and dietary measures. Only subjective statements are available about the Mexican medicinal plants. Toxicity studies in rats revealed no signs of toxicity. There are no preclinical or clinical data in man.

[Iscucin--mistletoe preparations for the pre- and postoperative treatment of malignancies. Documentation No. 21]. / Iscucin--Mistelpräparate für die prä- und die postoperative Malignombehandlung. Dokumentation Nr. 21.

Iscucin-Viscum preparations contain mistletoe from eight different host-trees and are produced according to a particular 'rhythmic' procedure and additionally 'potentialized'. Sterilization should be achieved by the addition of oligodynamic silver. The indications given are: precancerous conditions, postoperative tumour prevention, operable tumours, and inoperable tumours. Each of the eight preparations (according to host-tree) has its own list of indications. Iscucin is supposed to be injected close to the tumour between 5 and 7 p. m.; the dosage and the frequency depend on body temperature. The annual costs of Iscucin treatment are DM 140.- to 280.-, not including doctor's visits, homeopathic drugs and special diet. Koehler began to develop Iscucin in 1958 on the basis of a personal communication of Steiner made in 1924. It is produced and distributed by Wala-Heilmittel GmbH, Eckwälden. Most Wala publications have been written by H. H. Vogel, the medical advisor of Wala. Vogel combines Fromme's mesenchymal theories with the anthroposophical ideas on carcinoma development in that he designates the mesenchyma as the organic vehicle of the 'ethereal body' (Atherleib). Carcinomas develop on depletion of the mesenchymal forces; mistletoe, on the other hand, activates the mesenchyma. No preclinical or clinical investigations are available. However, the performance of controlled clinical studies is hardly possible, since the supportive measures considered to be essential cannot be applied according to a specific schedule. Iscucin is not registered in Switzerland at the IKS.