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Biomedical subjects

K Linde

Publications and source records attributed to K Linde.

At least 73 records · Page 4Linked to original sources
PubMed1996

St John's wort for depression--an overview and meta-analysis of randomised clinical trials.

OBJECTIVE: To investigate if extracts of Hypericum perforatum (St John's wort) are more effective than placebo in the treatment of depression, are as effective as standard antidepressive treatment, and have fewer side effects than standard antidepressant drugs. DESIGN: Systematic review and meta-analysis of trials revealed by searches. TRIALS: 23 randomised trials including a total of 1757 outpatients with mainly mild or moderately severe depressive disorders: 15 (14 testing single preparations and one a combination with other plant extracts) were placebo controlled, and eight (six testing single preparations and two combinations) compared hypericum with another drug treatment. MAIN OUTCOME MEASURES: A pooled estimate of the responder rate ratio (responder rate in treatment group/responder rate in control group), and numbers of patients reporting and dropping out for side effects. RESULTS: Hypericum extracts were significantly superior to placebo (ratio = 2.67; 95% confidence interval 1.78 to 4.01) and similarly effective as standard antidepressants (single preparations 1.10; 0.93 to 1.31, combinations 1.52; 0.78 to 2.94). There were two (0.8%) drop outs for side effects with hypericum and seven (3.0%) with standard antidepressant drugs. Side effects occurred in 50 (19.8%) patients on hypericum and 84 (52.8%) patients on standard antidepressants. CONCLUSION: There is evidence that extracts of hypericum are more effective than placebo for the treatment of mild to moderately severe depressive disorders. Further studies comparing extracts with standard antidepressants in well defined groups of patients and comparing different extracts and doses are needed.

Antidepressive Agents↗
PubMed1996

Completeness of reporting of trials published in languages other than English: implications for conduct and reporting of systematic reviews.

BACKGROUND: Lately, the number of systematic reviews published has increased substantially. Many systematic reviews exclude trials published in languages other than English. However, there is little empirical evidence to support this action. We looked for differences in the completeness of reporting between trials published in other languages and those published in English, to see whether the exclusion of trials published in other languages is justified. METHODS: We compared completeness of reporting, design characteristics, and analytical approaches of 133 randomised controlled trials (RCTs) published in English between 1989 and 1994 and 96 published in French, German, Italian, or Spanish during the same time. RCTs were identified by hand searching of journals (seven in English and six in the other languages). FINDINGS: We found no significant differences between trials published in English and other-language trials for any single item in the completeness of reporting scale (randomisation, double-blinding, withdrawals), or for the overall score (percentage of maximum possible score 51.0% for trials in English, 46.2% for trials in other languages; 95% CI for difference -1.1 to 10.5). Other-language trials were more likely than English-language trials to have adult participants, to use two or more interventions, and to compare two or more active treatments without an untreated control group. Trials in other languages were less likely to report a clearly prespecified primary outcome or any rationale for sample size estimation. INTERPRETATION: These results provide evidence for inclusion of all trial reports, irrespective of the language in which they are published, in systematic reviews. Their inclusion is likely to increase precision and may reduce systematic errors. We hope that our findings will prove useful to those developing guidelines and policies for the conduct of reporting of systematic reviews.

Adult↗
PubMed1995

The efficacy of a live Listeria monocytogenes combined serotype 1/2a and serotype 4b vaccine.

In each of two experiments, sheep and lambs were vaccinated by a subcutaneous injection of a test vaccine (consisting of a combined serotype 1/2a and serotype 4b live Listeria monocytogenes culture) and challenged 16 days later with a mixture of the homologous wild strains. After challenge, the mortality rate of vaccinated sheep was 28.1% and that of controls 71.9%; that of lambs was 25.0%, although these had been inoculated with the LD70 dose. Furthermore, in each of two field trials in Listeria-infected flocks, primiparous pregnant ewes were vaccinated. In the first field trial, 3 or 110 lambs died of listeriosis of those born of vaccinated (n = 564) or unvaccinated (n = 3345) ewes, respectively. In the second, the perinatal mortality rate of lambs born of vaccinated or unvaccinated ewes was 7.6 or 30.3%, respectively, and the mean birth weight of lambs born of vaccinated or control ewes was 2.2 or 1.8 kg, respectively; the mean milk production of vaccinated ewes was 106 and that of controls 83 l; no Listeria was isolated from milk samples of vaccinated ewes. It is concluded that the vaccine is efficacious for the protection of sheep from listeriosis.

Animals↗
PubMed1995

Results of five randomized studies on the immunomodulatory activity of preparations of Echinacea.

This article describes and discusses five placebo-controlled randomized studies investigating the immunomodulatory activity of preparations containing extracts of Echinacea in healthy volunteers. A total of 134 (18 female and 116 male) healthy volunteers between 18 and 40 years of age were studied. Two studies tested intravenous homeopathic complex preparations containing Echinacea angustifolia D1 (study 1) and D4 (study 5). Two studies (2 and 3a) tested oral alcoholic extracts of roots of E. purpurea, one study an extract of E. pallida roots (study 3b), and one study an extract of E. purpurea herb (study 4). Test and placebo preparations were applied for four (study 5) or five (studies 1-4) consecutive days. The primary outcome measure for immunomodulatory activity was the relative phagocytic activity of polymorphonuclear neutrophil granulocytes (PNG), measured in studies 1 and 2 with a microscopic method and in studies 3, 4, and 5 with two different cytometric methods. The secondary outcome measure was the number of leukocytes in peripheral venous blood. Safety was assessed by a screening program of blood and other objective parameters as well as by documentation of all subjective side effects. In studies 1 and 2 the phagocytic activity of PNG was significantly enhanced compared with placebo [maximal stimulation 22.7% (95% confidence interval 17.5-27.9%) and 54.0% (8.4-99.6%), respectively], while in the other studies no significant effects were observed. Analysis of intragroup differences revealed significant changes in phagocytic activity during the observation periods in five test and three control groups. Leukocyte number was not influenced significantly in any study. Side effects due to the test preparations could not be detected. Our studies provide evidence for immunomodulatory activity of the homeopathic combination tested in study 1 and the E. purpureae radix extract tested in study 2. The negative results of the other three studies are difficult to interpret due to the different methods for measuring phagocytosis, the relevant changes in phagocytic activity within most placebo and treatment groups during the observation period, and the small sample sizes. Future studies should be performed on patients rather than healthy volunteers and use standardized or chemically defined monopreparations of Echinacea.

Adjuvants, Immunologic↗
PubMed1995

The integration of natural healing procedures into research and teaching at German universities.

This article describes the activities of the "Münchener Modell," a project for "Integration of Natural Healing Procedures into Research and Teaching" at the Ludwig-Maximilian University in Munich. Its objective is to improve research and teaching of Natural Healing Procedures (NHPs) and to provide the infrastructural and conceptual prerequisites for the establishment of an independent academic institution. In the years 1989 to 1992 the project organized three 1-year pregraduate courses of NHPs for medical students. Parts of the courses have now been integrated in the regular undergraduate education. In 1993 a quality assurance project for postgraduate education was piloted. In a network of clinics using NHPs a comprehensive quality assurance project including observational studies and controlled clinical trials has been implemented and piloted. For evaluating the actual state of knowledge in a transparent way the project performs systematic reviews of published research. Further clinical-experimental research is being done in the area of immunomodulation with natural products.

Complementary Therapies↗
PubMed1994

Critical review and meta-analysis of serial agitated dilutions in experimental toxicology.

1. We conducted an overview and quantitative meta-analysis of all experimental literature on the protective effects of serial agitated dilutions (SADs) of toxin preparations. 2. Articles were systematically collected and evaluated for scientific quality using pre-defined methodological criteria and then independently analysed for validity. 3. We found 105 publications exploring the effects of SAD preparations in toxicological systems. 4. The quality of evidence in these studies was low with only 43% achieving one half of the maximum possible quality score and only 31% reported in a fashion that permitted reevaluation of the data. 5. Very few studies were independently replicated using comparable models. 6. Among the high quality studies, positive effects were reported 50% more often than negative effects. 7. Four of 5 outcomes meeting quality and comparability criteria for meta-analysis showed positive effects from SAD preparations. 8. Average percent protection over controls in these preparations was 19.7 (95%Cl 6.2-33.2). 9. Further research with special attention to methodological detail and independent replication should be done.

Animals↗
PubMed1993

Shigella flexneri 2a and sonnei I vaccine with two attenuating markers: construction, tolerability and immunogenicity in 143 children aged 3-17 years.

The vaccine candidates were constructed through stepwise incorporation of weakly attenuated purine auxotrophy with subsequent rifampicin resistance (RNA polymerase) mutation to yield optimal attenuation. These strains showed a maintained invasiveness for conjunctival epithelia. Therefore, while not causing keratoconjunctivitis, they were excreted for a short but marked period and provided partial protection in the Sereny test. Children tolerated the maximum dose of 1-3 x 10(9) colony-forming units (c.f.u.) of lyophilized vaccine without side effects. This total dose distributed among three oral inoculations, induced coproantibodies in 70% of recipients during the first three months. However, the single application of this total dose for primary immunization or booster proved to be more efficient: 90% of the subjects had markedly elevated titres for not less than six months.

Administration, Oral↗
PubMed1992

Prophylaxis of Salmonella abortus ovis-induced abortion of sheep by a Salmonella typhimurium live vaccine.

A Salmonella typhimurium live vaccine with optimal level of attenuation for sheep, constructed by means of 'metabolic drift' mutations, was tested for its efficacy in preventing Salmonella abortus ovis-induced abortions. In two field trials in Kirgiziya, 78,000 to 100,000 first delivery sheep received a fully tolerated single dose of 10(9) c.f.u. live vaccine 2 months before to 4 months after insemination. Alternatively, they were immunized twice with commercial inactivated S. abortus ovis vaccine, or they served as non-immunized controls. The S. abortus ovis-induced abortion frequency in the controls was greater than or equal to 30%, in sheep immunized with inactivated vaccine greater than or equal to 11%. In flocks immunized with live vaccine, the S. abortus ovis-induced abortion frequency did not exceed 0.1%. Thus, use of 'metabolic drift' mutations for construction of stable vaccine strains optimally attenuated for the particular host species proved to be relevant to practice.

Abortion, Veterinary↗
PubMed1992

Humoral and cell-mediated immunity in mice after immunization with live oral vaccines of Salmonella typhimurium: auxotrophic mutants with two attenuating markers.

Persistence and clearance of the vaccinal strains, humoral and cell-mediated immune response and protective immunity were assessed in ICR mice, immunized intraperitoneally or intragastrically with double-marker auxotrophic mutants of Salmonella typhimurium strains 1771 and 3334 (his-pur-). Strain 3334 possesses in addition the antiepidemic Hst (high sensitivity to tensides) marker which confers decreased survival in the gut and environment. The results showed that the strains are not overattenuated. They revealed preserved multiplication capacity, established carrier state for 28-30 days and induced humoral and cell-mediated immunity as measured by passive haemolysis and microagglutination or footpad swelling tests, respectively. The immune response was determined by biological features of the strains. Strain 1771 induced synthesis of O- and H-antibodies 7-11 days earlier than strain 3334. Footpad reactions appeared 3-4 days after immunization and a week before the serum antibodies. Cell-mediated immunity showed clear correlation with the protection against challenge with a virulent strain. The present results suggest that the double-marker auxotrophic mutants of S. typhimurium might prove very useful in the development of a live vaccine in further studies on livestock.

Administration, Oral↗
PubMed1992

Testosterone increases serum 1,25-dihydroxyvitamin D and insulin-like growth factor-I in hypogonadal men.

The short-term metabolic effects of testosterone treatment on circulating levels of 1,25-dihydroxyvitamin D and insulin-like growth factor-I (IGF-I) were studied in 13 hypogonadal men. The study group included 11 men with Klinefelter's syndrome, with varying degree of androgen deficiency, and two men with secondary hypogonadism. Pretreatment levels of 1,25-dihydroxyvitamin D, vitamin D-binding protein and IGF-binding protein-I were all within the normal range. The levels of IGF-I were lower than normal in 5/11 of the Klinefelter patients and in one patient with GH-deficiency. Testosterone treatment increased circulating total 1,25-dihydroxyvitamin D significantly from 75 +/- 4 pmol l-1 (mean +/- SEM) to 86 +/- 4 (P less than 0.01) and the free 1,25-dihydroxyvitamin D-index from 1.95 +/- 0.11 to 2.39 +/- 0.12 (P less than 0.01). Serum levels of IGF-I increased from 117 +/- 22 micrograms/l to 143 +/- 23 (P less than 0.01) during androgen treatment. No significant effects on levels of IGF-binding protein-I were seen. It is concluded that androgen therapy increases the availability of 1,25-dihydroxyvitamin D and the level of IGF-I, which may be important links in the action of testosterone.

Adolescent↗
PubMed1991

Stable Listeria monocytogenes live vaccine candidate strains with graded attenuation on the mouse model.

Metabolic drift (antibiotics resistance) mutations were used to construct stable two (and three) marker vaccine candidate strains of the predominant Listeria monocytogenes serotypes 1/2a and 4b by stepwise selection. Derived from wild-type strains, spontaneous chromosomal streptomycin-resistant clones with their i.p. LD50 elevated from less than or equal to 10(5.0) c.f.u. to approximately 10(6.1) c.f.u. were used in the second step to isolate the rifampicin-resistant mutants with i.p. LD50 values ranging from 10(6.6) to 10(7.4). On i.p. immunization with fully tolerated doses (less than or equal to 1% LD50), these potential vaccine strains were found to protect not less than 95% of the mice against a lethal (approximately 100 LD50) challenge with the homologous wild-type strain. Further elevation of the i.p. LD50 to greater than 10(8.3) c.f.u. by means of a third attenuating fosfomycin-resistance marker resulted in overattenuation and reduced protective capacity.

Animals↗
PubMed1991

Technological aspect of the production of live dysentery vaccines for oral administration.

An experimental technology for the production of live freeze-dried vaccines prepared from attenuated Shigella flexneri 2a and Shigella sonnei I strains was developed. It is based on the cultivation of bacterial strains in a fermentor under conditions which ensure high yields. The strains grow in S-form, their antigenic structure is preserved and they remain non-virulent. The attenuating markers are stable. The freeze-dried vaccines retain good immunogenicity when applied intra-intestinally to rats.

Administration, Oral↗
PubMed1990

Stable Salmonella live vaccine strains with two or more attenuating mutations and any desired level of attenuation.

Mutants optimally attenuated for highly susceptible hosts and protecting after a single oral vaccination are often overattenuated for host species being less susceptible. Therefore, to select vaccine strains optimally attenuated for the particular host species it is essential that a range of mutants with graded levels of attenuation be provided so as to permit lesser susceptibility to be compensated for by a correspondingly lower level of attenuation. This, while guaranteeing the stability through two-marker or multi-marker attenuation, can be suitably accomplished by slightly to moderately virulence-reducing mutations. Aspartic acid auxotrophy and, in particular, 'metabolic drift' mutations, possibly by additionally incorporating antiepidemic markers, are adopted for the mouse model to demonstrate stepwise production of S. typhimurium and S. typhi vaccine candidate strains with graded attenuation or any level of attenuation desirable. It is emphasized that this basic approach is relevant to practice.

Animals↗
PubMed1990

Live Shigella flexneri 2a and Shigella sonnei I vaccine candidate strains with two attenuating markers. I. Construction of vaccine candidate strains with retained invasiveness but reduced intracellular multiplication.

Live Shigella flexneri 2a and Shigella sonnei Phase I vaccine candidate strains with two virulence-reducing markers were constructed through stepwise incorporation of weakly attenuating purine auxotrophy with subsequent rifampicin-resistance (RNA polymerase) mutation to yield optimal attenuation. These vaccine candidate strains showed an unaltered plasmid profile; did not cause keratoconjunctivitis in the Sereny test, while being excreted for a short but still marked period and providing partial protection from wild-strain infection; exhibited for guinea-pig conjunctival epithelia, HeLa cells and rat enterocytes a maintained invasiveness with reduced intracellular multiplication with little, if any, reversible cell damage; and produced, just as their ultrasonic lysates, no exudative reaction in the rabbit gut loop test.

Animals↗
PubMed1990

Live Shigella flexneri 2a and Shigella sonnei I vaccine candidate strains with two attenuating markers. II. Preliminary results of vaccination of adult volunteers and children aged 2-17 years.

Shigella flexneri 2a and Shigella sonnei I vaccine candidate strains were tested for tolerance in 14 adults as well as for tolerance and immunogenicity in children aged 2-17 years. For fresh culture material, the limit for side effects fading within 36 h such as meteorism, loose stools, tenesmus and slight temperature, and tolerated by volunteers was 3 x 10(9) colony-forming units (c.f.u.). Excretion of vaccine strain germs for 2-3 days was observed only at doses of 10(10) c.f.u. and greater (2-3 x 10(10)). Children tolerated up to the maximum dose of 1-3 x 10(9) c.f.u. of the lyophilized vaccine without side effects. No vaccine strain germs were found in faeces, antigen being detected for 4-5 days. The total dose of 1-3 x 10(9) c.f.u. being distributed among three oral inoculations at intervals of 1-2 days induced coproantibodies in 70% of the vaccinees during the first 3 months, and in 30-40% up to 6 months. In contrast, the single application of this total dose for primary immunization, or booster after 10 months, proved to be more efficient. Ninety per cent of the subjects had markedly elevated titres for not less than 6 months.

Adolescent↗
PubMed1990

Potential Shigella flexneri 2a and Shigella sonnei I live vaccinal strains. Characterization of immunogenicity in animal models.

Rats and rabbits were immunized intraintestinally with different doses of virulent and nonvirulent live Shigella flexneri 2a and Shigella sonnei I strains. The nonvirulent strains had one or two attenuating markers. The period of excretion with the faeces of the bacteria and of their polysaccharide antigens, the proliferation of antigen-binding and antibody-producing cells in the spleens and gut-associated lymphoid tissues and the levels of antibodies in sera and faeces were studied. Attenuated strains S. flexneri 2a 77 and S. sonnei I 3359 induced the most potent and long lasting local immune response.

Animals↗
PubMed1990

Modulating the microbial colonization of the gastrointestinal tract by oral administration of defined Escherichia coli strains. III. Lipopolysaccharide-specific IgA in the intestine after oral administration of Escherichia coli.

The assumption that local immunologic mechanisms are responsible for findings on the specific microbial colonization of the gastrointestinal tract of mice, is confirmed by results described in the present communication. Quantitative examination of intestinal lavage fluids after oral administration of germs by ELISA showed that (i) there is a critical dose above which a significant increase of IgA synthesis is observable; (ii) low antibody levels could be detected already in the untreated control group. It may be assumed that--regardless of the biological characteristics of the administered strain, namely, substrate and receptor competition--the stimulability of local immunity provides against permanent monocolonization with displacement of the autochthonous Enterobacteriaceae in adult and immunocompetent hosts.

Administration, Oral↗