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Biomedical subjects

R Scheer

Publications and source records attributed to R Scheer.

16 recordsLinked to original sources

Demonstration of antibodies to the chitin-binding mistletoe lectin (cbML) in tumor patients before and during therapy with an aqueous mistletoe extract.

Mistletoe extracts exert immunomodulatory properties in vivo and in vitro, and these effects have been related mainly to mistletoe lectin 1 (ML-1). Recently, a new chitin-binding mistletoe lectin (cbML) has been isolated and structurally characterized in these extracts. Aim of the present study was, therefore, to evaluate whether this cbML also affects immunocompetent cells and can for instance activate B-cells to produce anti-cbML-specific antibodies. Sera from patients with different tumors who were treated with the mistletoe extract ABNOBAviscum Mali (AM) 4 for at least 18 weeks were analysed before therapy and after 3, 6, 9, 12, 18, and 24 weeks. Sera were tested by ELISA against ML-1, -3, and cbML, isolated from a single mistletoe plant collected from an apple tree (Malus domestica). Eight of the 26 patients (31%) had IgG anti-cbML antibodies already before therapy, while only four had anti-ML-1 and -3 antibodies. Of the 18 anti-cbML negative patients before therapy 54% developed these antibodies during therapy, and there was a significant increase in anti-cbML antibody titers. In contrast, anti-ML-1 or -3-antibodies developed in almost 100% of the 25 patients being negative before therapy. These data indicate that cbML can induce immunological responses in patients treated with mistletoe extracts, although it seems to have lower antigenicity. Interestingly, anti-cbML antibodies can be observed in a low incidence also in individuals, not having yet received mistletoe therapy.

Adjuvants, Immunologic↗

The feasibility of measuring three-dimensional facial morphology in children.

OBJECTIVE: An investigation to determine the feasibility of measuring soft tissue morphology in children using a three-dimensional laser-scanning device. DESIGN: Prospective clinical trial. SETTING AND SAMPLE POPULATION: University of Wales, College of Medicine and one secondary school in the South Wales region. Sixty live subjects (30 adults, 30 children) were recruited in the study. EXPERIMENTAL VARIABLES: Laser scanned images of the subjects were obtained under a reproducible and controlled environment with two Minolta Vivid 900 (Osaka, Japan) optical laser-scanning devices assembled as a stereo-pair. A set of left and right scanned images was taken for each subject and each scan took an average of 2.5 s. These scanned images were processed and merged to form a composite three-dimensional soft tissue reproduction of the subjects using commercially available reverse modelling software. OUTCOME MEASURE: The shell deviations between left and right scan of each patient were recorded and analysed for differences. These differences determined whether the subjects could remain still during the time of the scans. RESULTS: The results showed that the mean differences between shell deviations for the adult scans and children scans were 0.25 +/- 0.09 and 0.30 +/- 0.09 mm, respectively. Paired t-tests showed that the mean error between subject groups was 0.05 +/- 0.15 mm indicating that there was no difference between the two subject groups (p = 0.18). CONCLUSION: The technique as described is clinically reproducible for children and adults and can be used for studies assessing facial changes due to growth or clinical intervention.

Adult↗

Induction of antibodies to viscotoxins A1, A2, A3, and B in tumour patients during therapy with an aqueous mistletoe extract.

Mistletoe extracts exert immunomodulatory properties on immunocompetent cells of the innate as well as the specific immune system. These effects have been mainly ascribed to mistletoe lectin 1 (ML-1) present in most of the extracts. However, it became evident that also other components of these extracts may induce immunological reactions, and especially viscotoxins (VT) may be of relevance. Aim of the study was, therefore, to evaluate whether VT like ML-1 could activate B-cells and lead to the production of VT-specific antibodies. Sera from 26 patients with different tumours who were treated with the mistletoe extract ABNOBAviscum Mali (AM) 4 for at least 18 weeks were analysed before therapy and after 3, 6, 9, 12, and 18 weeks. Sera were tested by ELISA against the four viscotoxins A1, A2, A3, B, as well as against ML-1. Within the observation period twenty-four (92%) of the 26 patients developed antibodies to at least one of the four VT and 25 (96%) to ML-1. In most instances, anti-VT antibodies appeared after 6-9 weeks of treatment. The antibodies were predominantly of the IgG type belonging preferentially to the IgG1 and IgG3 subclass. IgE antibodies were found only to VT-B and to ML-1. There was no relation between the development of antibodies to VT and ML-1, and also cross-reactivity could be excluded with high probability. These data indicate that not only ML-1 but also VT induce immunological responses in patients treated with mistletoe extracts. Whether there is any relationship to the postulated anti-tumour effect of mistletoe extracts has, however, still to be evaluated.

Adjuvants, Immunologic↗

Effects of a mistletoe preparation with defined lectin content on chronic hepatitis C: an individually controlled cohort study.

Despite advances in the therapy of chronic hepatitis C for some hepatitis C virus (HCV) genotypes interferon and ribavirin combination therapy is effective in less than 50% of patients. Abnobaviscum Quercus (AQ) is a mistletoe preparation containing defined amounts of mistletoe lectins (ML). It has shown immunomodulatory properties in vitro and in vivo. In small clinical trials AQ resulted, within an anthroposophical treatment concept, in a biochemical or virological response in up to 40% of patients with chronic hepatitis C. In order to evaluate the effect of this preparation we conducted an individually controlled cohort study. 25 patients with chronic hepatitis C (mean duration 147 +/- 80 months) and elevated alanine aminotransferase (ALT) levels were included in the study. As control they were observed for 6 months pre-treatment. This pre-treatment period was followed by 6 months of active treatment in which the mistletoe preparation was subcutaneously injected three times a week. Main outcome parameters were normalization of ALT and viral load. Hepatitis C associated signs and symptoms like tiredness, fullness in the right upper abdomen and musculoskeletal pain were assessed monthly in a standardized questionnaire. All 25 patients completed the study and most of the patients wanted to continue treatment. Mean duration of treatment was 9.1 months. None of the patients had complete or partial normalization of ALT or HCV RNA levels during pre-treatment or treatment period. Mean ALT did not change during the study. Tiredness, fullness in the right upper abdomen and musculoskeletal pain were present in 18, 8 and 4 patients respectively. They significantly improved within two months of treatment. A significant eosinophilia (p=0.0001) occurred between month 2 and 6 during treatment. 9 month treatment with a ML containing mistletoe preparation has no effect on viral load or ALT as markers of activity in patients with chronic hepatitis C. However, frequency and intensity of clinical signs and symptoms in our patients decreased significantly, similar to reports of improved quality of life in tumour patients treated with such preparations. A significant eosinophilia suggests that ML containing mistletoe preparations induce a T-helper 2 immune response.

Adjuvants, Immunologic↗

[The effect of mistletoe lectins on the limulus amebocyte lysate test].

Former reports about too high and from batch to batch changing endotoxin contents in mistletoe preparations and phytopharmaceuticals for parenteral administration correlated with clinically observed side effects led to investigations of the endotoxin content of ABNOBA-viscum. For that purpose the endotoxin levels of the raw materials, the equipment and the production steps were observed by using the limulus amebocyte lysate (LAL) test. The mean value found in the preparation containing the highest available concentration (dilution level 2 containing 15 mg of plant extract from 20 mg of fresh mistletoe in 1 ml) came to 66.7 endotoxin units (EU) per ml, corresponding to about one fifth of the commonly accepted limit value of 350 EU/ml, the human pyrogenic dose. Depending on their dilution level, lower concentrated preparations led also to lower LAL test results. It could be proved that lectins contained in mistletoe preparations cause false positive LAL tests. Such results implicate false too high contents of endotoxin. Different lysates, i.e. Limusate, Pyrogel, Pyrogent, and Pyroquant showed approximately the same results. Microbiological and LAL test results indicate that only 10% of the total amount of the LAL test result was caused by endotoxins. So it is necessary to form a new estimation of the former results of determination of the endotoxin content of mistletoe preparations.

Animals↗

Serum concentration and dose-response relationships for carprofen in rheumatoid arthritis.

Thirty-eight patients with active, definite, or classical rheumatoid arthritis were tested in a double-blind, 3-week-per-arm, multiple-crossover, randomized, block-design comparison of 100, 300, 600, and 800 mg/day carprofen given b.i.d. A linear dose-response relationship was demonstrated for six of nine efficacy measures (p less than 0.052). A plasma concentration to therapeutic response relationship was shown just before or 1 to 2 hours after a dose (p less than 0.05) for seven efficacy parameters for the patients with at least three serum carprofen concentrations. By nonparametric analysis, with the patients divided into three equal groups, the percent of responders rose from 38.1% to 50% to 59.1%. Sixty-nine percent of patients responded when carprofen concentrations were greater than 10 micrograms/ml, whereas only 9% responded when they were below 1.9 micrograms/ml. Although only seven patients had limiting side effects, there was a tendency toward a dose-toxicity relationship through 600 mg daily carprofen.

Adult↗

[Microbial growth in mixed-bed ion exchange columns].

The microbial growth in ion-exchange columns of Christ GmbH Leonberg (Germany) was studied under differing water processing conditions. Continuous processing led to the same or slightly higher microbial counts in the product water compared to the feed water. Feeding the considerably contaminated column with slightly contaminated water (less than 40 CFU/100 ml) also didn't prevent microbial growth in the column. If water was withdrawn on demand only, an overnight no-demand period with closed inlet of the column led to considerable microbial growth, raising the microbial counts of the product water to well above the feed water level. But lower microbial counts were found in the product water than in the feed water by tightly closing the outlet of the column and hereby keeping the column at the same pressure as exists in the piping system. This was observed in several months long experiments operating with disinfected as well as freshly regenerated resin. The passage through a column of freshly regenerated resin led to a germ reduction of approximately 2 powers of ten and to an elimination of pyrogens.

Bacteria↗

Alteration of cortical orientation selectivity: importance of asymmetric input.

Rearing cats so that each of the two eyes sees stripes of a different orientation alters the orientation preference of visual cortex cells. This result can be obtained by rearing the cats in striped cylinders or with goggles attached to their faces, but a tighter control of orientation preference is achieved by the goggles.

Animals↗

Anticancer activity of a lectin-rich mistletoe extract injected intratumorally into human pancreatic cancer xenografts.

BACKGROUND: In single case observations, tumour remissions after intratumoral injections of mistletoe extracts have been described. MATERIALS AND METHODS: We investigated the antitumour activity of intratumorally (i.t.)-injected lectin-rich mistletoe extract at different dosages and i.t.-injected mistletoe lectin I in comparison to intravenous (i.v.) Gemcitabine and i.t. treatment with placebo in a human pancreatic cancer xenograft. RESULTS: In a preliminary dose-response experiment, the most marked tumour inhibition was induced when mistletoe extract was given at 8 mg/kg body weight (BW) and mistletoe lectin I at 5.3 microg/kg BW. In a second experiment, bi-weekly i.t. injections of mistletoe extract over 8 weeks resulted in a very high antitumour activity with an optimal T/C value (=median relative tumour volume of the test group vs. the control) of 0.4% combined with 3/8 partial and 3/8 complete remissions. Gemcitabine was less active with 2/8 partial and 1/8 complete remissions and an optimal TIC of 4.6%. CONCLUSION: I.t.-injected lectin-rich mistletoe extract should be further evaluated in patients with inoperable locally advanced pancreatic cancer.

Adenocarcinoma↗