University of Applied Sciences, Bioinformatics, Wiesenstrasse 14, D-35390 Giessen, Germany. uwe.hobohm2tg.fh-giessen.de
The phenomenon of spontaneous regression and remission from cancer has been observed by many physicians and was described in hundreds of publications. However, suggestive clues on cause or trigger are sparse and not substantiated by much experimental evidence. In this review, literature is surveyed and summarised and possible causes are discussed. At least in a larger fraction of cases a hefty feverish infection is linked with spontaneous regression in time and is investigated as putative trigger. Epidemiological and immunological evidence is put into perspective. An online forum to discuss the possible application of fever therapy in the future can be accessed at http://bioinfo.tg.fh-giessen.de/fever-and-cancer.
Latest citations:
Aina Zehnder,
Urs Fisch,
Andreas Hirt,
Felix K Niggli,
Arne Simon,
Hulya Ozsahin,
Luregn J Schlapbach,
Roland A Ammann
Department of Pediatrics, University of Bern, Bern, Switzerland.
BACKGROUND: Mannose-binding lectin (MBL) and MBL-associated serine protease-2 (MASP-2) are key components of the lectin pathway of complement activation. Their serum concentrations show a wide interindividual variability. This study investigated whether the concentration of MBL and MASP-2 is associated with prognosis in pediatric patients with cancer. METHODS: In this retrospective multicenter study, MBL and MASP-2 were measured by commercially available ELISA in frozen remnants of serum taken at diagnosis. Associations of overall survival (OS) and event-free survival (EFS) with MBL and MASP-2 were assessed by multivariate Cox regression accounting for prognostically relevant clinical variables. RESULTS: In the 372 patients studied, median serum concentration of MBL was 2,808 microg/L (range, 2-10,060) and 391 microg/L (46-2,771) for MASP-2. The estimated 4-year EFS was .60 (OS, .78). In the entire, heterogeneous sample, MBL and MASP-2 were not significantly associated with OS or EFS. In patients with hematologic malignancies, however, higher MASP-2 was associated with better EFS in a significant and clinically relevant way (hazard ratio per tenfold increase (HR), .22; 95% CI, .09- .54; P = .001). This was due to patients with lymphoma (HR, .11; 95% CI, .03- .47; P = .003), but less for those with acute leukemia (HR, .35; 95% CI, .11-1.15; P = .083). CONCLUSION: In this study, higher MASP-2 was associated with better EFS in pediatric patients with hematologic malignancies, especially lymphoma. Whether MASP-2 is an independent prognostic factor affecting risk stratification and anticancer therapy needs to be assessed in prospective, disease-specific studies.
Department of Pediatrics, Korea Cancer Center Hospital, 215-4, Gongneung-dong, Nowon-gu, Seoul, 139-706, South Korea.
The clinical impact of postoperative deep infection on survival remains controversial in osteosarcoma patients. The authors identified 31 osteosarcoma patients that developed a deep infection within 1 year of operation between 1990 and 2003, and compared clinicopathologic characteristics of 31 patients that developed an infection with those of 316 patients that did not. For survival analysis, 62 noninfected patients matched for prognostic factors such as histologic response, tumor size, and location were also selected. In infected patients, although it was not significant due to the small patient numbers, good response to preoperative chemotherapy and a proximal tibial location were frequently observed. No local recurrence developed in infected patients. Five-year overall and metastasis-free survival rates for the 31 infected patients were as high as 89% and 73%, respectively. However, after matching for clinical factors, no survival difference was noted between infected and noninfected patients. Deep infection has a multifaceted effect on patients. However, the present study suggests that the reported positive effect on survival is likely to be related to the clinical characteristics of infected patients rather than an antitumor effect due to the infection. Further investigations are needed to clarify the precise effects of infection.
The Ministry of Health, Goztepe Educational and Research Hospital, Pediatric Hematology and Oncology Department, Istanbul, Turkey. dryoruk@gmail.com
Spontaneous remission/regression of cancer is defined as partial or complete disappearance of malignant disease temporarily or permanently in the absence of medical treatment. This event is named as spontaneous regression for solid tumors and spontaneous remission for leukemia. The authors report the case of a girl aged 4 years and 3 months, who presented with mediastinal mass and leukemic findings in the bone marrow both of which reappeared after spontaneous regression and remission, respectively.
BACKGROUND: Despite neo-adjuvant chemotherapy osteosarcomas having significant mortality, recent studies have shown survival advantages following infections for some tumour types. This study investigates the effect of post-operative infection in patients treated for osteosarcoma using endoprosthetic replacement and neo-adjuvant chemotherapy. MATERIAL AND METHODS: A consecutive series of 547 patients underwent surgery between 1981 and 2001 for osteosarcoma. Patients were excluded from the study if over 60 years old at diagnosis (n = 14) as they would not routinely receive chemotherapy. Studies showed that 70% of deep infections occur within one year from reconstruction. Therefore landmark analysis was performed; all patients infected after 12 months of reconstruction were excluded (15 patients, 2.7%) and those who died within 12 months from diagnosis due to metastases were excluded (105 patients, 19.2%), leaving 412 patients. Any survival advantage of early infection was analysed by Kaplan-Meier survival analysis from this landmark point. RESULTS: Overall population survival was 65% at 10 years after landmarking. There were 41 patients (10%) who developed an infection within one year of implantation. These patients had significantly better survival (p = .017). The 10-year survival for patients with osteosarcoma with infection was 84.5% compared to 62.3% in the non-infected group after landmarking. There was no significant difference in the percentage post-chemotherapy specimen necrosis between the two groups (p = .36). Infection was an independent prognostic factor on cox regression analysis. CONCLUSIONS: There was evidence for increased survival after deep post-operative infection in osteosarcoma patients, in keeping with other research. The authors feel this warrants further investigation.
Åbo Akademi University, Department of Biochemistry and Pharmacy and Turku Immunology Centre, Turku, Finland; Turku Graduate School of Biomedical Sciences, Turku, Finland.
Oncolytic virotherapy is a promising form of gene therapy for cancer, employing nature's own agents to find and destroy malignant cells. The purpose of this review is to provide an introduction to this very topical field of research and to point out some of the current observations, insights and ideas circulating in the literature. We have strived to acknowledge as many different oncolytic viruses as possible to give a broader picture of targeting cancer using viruses. Some of the newest additions to the panel of oncolytic viruses include the avian adenovirus, foamy virus, myxoma virus, yaba-like disease virus, echovirus type 1, bovine herpesvirus 4, Saimiri virus, feline panleukopenia virus, Sendai virus and the non-human coronaviruses. Although promising, virotherapy still faces many obstacles that need to be addressed, including the emergence of virus-resistant tumor cells.
Other papers by authors:
Freiburg Center for Data Analysis and Modeling, Eckerstrasse 1, 79104 Freiburg, Germany.
Signal data from DNA-microarray ("chip") technology can be noisy; i.e., the signal variation of one gene on a series of repetitive chips can be substantial. It is becoming more and more recognized that a sufficient number of chip replicates has to be made in order to separate correct from incorrect signals. To reduce the systematic fraction of the noise deriving from pipetting errors, from different treatment of chips during hybridization, and from chip-to-chip manufacturing variability, normalization schemes are employed. We present here an iterative nonparametric nonlinear normalization scheme called simultaneous alternating conditional expectation (sACE), which is designed to maximize correlation between chip repeats in all-chip-against-all space. We tested sACE on 28 experiments with 158 Affymetrix one-color chips. The procedure should be equally applicable to other DNA-microarray technologies, e.g., two-color chips. We show that the reduction of noise compared to a simple normalization scheme like the widely used linear global normalization leads to fewer false-positive calls, i.e., to fewer genes which have to be laboriously confirmed by independent methods such as TaqMan or quantitative PCR.
F. Hoffmann-La Roche Ltd., Pharma Research, Basel, Switzerland. uwe.hobohm@roche.com
CONTEXT: A relationship between feverish infection and concurrent remission from cancer has been known about for a very long time. However, a systematic investigation of the phenomenon has not yet been made. OBJECTIVE: To bring together the isolated observations about the coincidence of spontaneous remissions with feverish infections and William Coley's seminal work, as a basis for devising an immunological hypothesis about the putative anti-cancer effect of fever. CONCLUSION: Fever induction under medical guidance may be considered as part of a therapy regimen for cancers of mesodermal origin.
Institute of Cell Biology, Biochemistry and Biotechnology, University of Bremen, D-28334 Bremen, Germany and the School of Technology and Science, Stavanger University College, P. O. Box 2557 Ullandhaug, N-4091 Stavanger, Norway.
The hypothesis of a common signal for heat shock (HS) and oxidative stress (OS) was analyzed in C6 cells with regard to the induction of heat shock proteins (Hsps). The synthesis rate and level of the strictly inducible Hsp68 was significantly higher after HS (44 degrees C) compared with OS (2 mm H2O2). This difference corresponded to higher and lower activation of the heat shock factor (HSF) by HS and OS, respectively. OS, on the other hand, showed stronger cytotoxicity compared with HS as indicated by drastic lipid peroxidation and inhibition of protein synthesis as well as of mitochondrial and endocytotic activity. Lactic dehydrogenase also revealed stronger inhibition of enzyme activity by OS than by HS as shown in cells and in vitro experiments. Conformational analysis of lactic dehydrogenase by the fluorophore 1-anilinonaphtalene-8-sulfonic acid, however, showed stronger exposure of hydrophobic domains after HS than after OS which correlates positively with the Hsp68 response. Treatment of cells with deoxyspergualin, which exhibits high affinity to Hsps, the putative inhibitors of HSF, strongly increased only OS-induced hsp68 expression. In conclusion, the results suggest that exposure of hydrophobic domains of cytosolic proteins represents the common first signal in the multistep activation pathway of HSF.
Gene Technologies, Basel, Switzerland.
Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry of protein samples from two-dimensional (2-D) gels in conjunction with protein sequence database searches is frequently used to identify proteins. Moreover, the automatic analysis of complete 2-D gels with hundreds and even thousands of protein spots ("proteome analysis") is possible, without human intervention, with the availability of highly accurate mass spectrometry instruments, and high-throughput facilities for preparation and handling of protein samples from 2-D gels. However, the lack of software for precise automatic analysis and annotation of mass spectra, as well as software for in-batch sequence database queries, is increasingly becoming a significant bottleneck for the proteomics work flow. In the present paper we outline an algorithm for reliable, accurate, and automatic evaluation of mass spectrometric data and database searches. We show here that simply selecting from the sequence database the protein that has the most matching fragment masses often leads to false-positive results. Reliable protein identification is dependent on several parameters: the accuracy of fragment mass determination, the number of masses submitted for query, the mass distribution of query masses, the number of masses matching between sample and database protein, the size of the sequence database, and the kind and number of modifications considered. Using these parameters, we derive a simple statistical estimation that can be used to calculate the probability of true-positive protein identification.
Scottish Cancer Trials Office, Medical School, University of Edinburgh, UK.
European Molecular Biology Laboratory, Heidelberg, Germany.
The sequence of the HIV Nef protein has no significant homology to other proteins in the SwissProt database, and experimental data concerning its function are sparse and contradictory. Using a novel protein sequence comparison method, we find similarities between different Nef sequences and the alpha chain of human MHC class I proteins. The possible biological implications of this finding are discussed.
Institut für Humangenetik, Universität Göttingen, Germany.
cDNA clones for the human Leydig insulin-like peptide (Ley I-L) have been isolated and characterized. The nucleotide sequence of the 743-bp cDNA includes an incomplete 7-bp 5'-noncoding region, an open reading frame of 393 bp, and a 343-bp 3'-noncoding region. By primer extension analysis, the transcription start site was determined as being 14-bp upstream of the translation start site. The underlying gene is expressed in the testis but not in other organs. From the cDNA sequence, it can be deduced that the Ley I-L protein is synthesized as a 131-amino-acid (aa) preproprotein and that it contains a 24-aa signal peptide. Comparison of the pro Ley I-L protein with members of the insulin-like hormone superfamily predicts that the biologically active hormone, after proteolytic processing of the C peptide, consists of a 31-aa long B chain and a 26-aa long A chain, and that it has a molecular weight of 6.25 kDa.
European Molecular Biology Laboratory, Heidelberg, Germany.
To reduce redundancy in the Protein Data Bank of 3D protein structures, which is caused by many homologous proteins in the data bank, we have selected a representative set of structures. The selection algorithm was designed to (1) select as many nonhomologous structures as possible, and (2) to select structures of good quality. The representative set may reduce time and effort in statistical analyses.
European Molecular Biology Laboratory, Heidelberg, Germany.
The identification of protein samples in minute quantities of protein samples, e.g., from two-dimensional polyacrylamide gel electrophoresis analysis, is an everyday problem in biology laboratories. Here we show that computer-assisted amino acid analysis can fulfill this task. Amino acid analysis data can be used to compare the amino acid composition of an unknown protein with protein compositions in a database (compositional search). Routine amino acid analysis data can, despite a certain margin of error, be used to identify a protein. Compared to protein sequencing, amino analysis is much cheaper, faster, and allows higher sample throughput. Thus, the method may replace protein sequencing as a first attempt in identification, provided a homolog can be found in the database.
European Molecular Biology Laboratory, Heidelberg, FRG.
The binding affinity between an antigenic peptide and its particular major histocompatibility complex (MHC) molecule seems to be largely determined by only a few residues. These residues have been called "anchors" because of their property of fitting into "pockets" inside the groove of the MHC molecule. To predict natural antigenic epitopes within a longer sequence, it therefore appears to be important to know the motif or pattern describing the anchors, i.e. the anchors amino acid residue preference and the distance between anchor residues. A large set of MHC class I-restricted peptides has been described. Peptide sequences vary in length and lack an obvious common sequence motif. For a list of peptides belonging to one type of MHC class I molecule, we describe a method to find the most prominent sequence motif with at least two anchor residues. Briefly, antigenic sequences are aligned, and two anchor positions are searched for, where all anchor residues share a high similarity. The alignments are scored according to the similarity of their anchor residues. We show that the motifs predicted for the MHC alleles A2.1, B27, Kb, Kd, Db are in substantial agreement with experimental data. We derive binding motifs for the MHC class I alleles HLA-A1, A11, B8, B14, H-2Ld and for the MHC class II alleles I-Ab and I-As. In some cases, higher scores were obtained by allowing a slight variation in the number of residues between anchors. Therefore, we support the view that the length of epitopes belonging to a particular class I MHC is not uniform. This method can be used to predict the natural short epitope inside longer antigenic peptides and to predict the epitopes anchor residues. Anchor motifs can be used to search for antigenic regions in sequences of infectious viruses, bacteria and parasites.
Latest similar papers:
University of Applied Sciences Giessen, Bioinformatics, D-35390 Giessen, Germany.
PDBselect (http://bioinfo.tg.fh-giessen.de/pdbselect/) is a list of representative protein chains with low mutual sequence identity selected from the protein data bank (PDB) to enable unbiased statistics. The list increased from 155 chains in 1992 to more than 4500 chains in 2009. PDBfilter-select is an online service to generate user-defined selections.
Monoclonal antibodies (MA) are an important group of drugs used in oncology. The objective of this study was to identify MAs used in oncology, and to describe their pharmacological characteristics. This literature review was based on database, index, and library collections. Eight MA were identified, out of which, 37.4% are immunoconjugated, 62.5% are recommended for hematological neoplasms, 75. % are diluted in saline solution and should not be mixed with other drugs, 100. % cause digestive side effects, and 87.5% affect the hematopoietic system. In order to guarantee MA's therapeutic efficacy and safety, professionals must fully understand their pharmacological characteristics.
Natural Killer (NK) cells are no longer considered as relatively unimportant bystander cells having the capacity to kill certain tumor and virus-infected cells in a mysterious way. During the last decade a significant progress has been made in understanding biology of NK cells in particular their mechanisms of recognition and killing of target cells. This progress has led to novel knowledge-based clinical applications of NK cells as immunotherapeutic tools in various disease settings, especially in bone marrow transplantation for leukemia patients. The potential of NK cell therapy for eradicating solid tumors has not been fully exploited. In this mini-review, we examine the rationale behind these therapies and discuss the problems confronting researchers in their usage as therapeutic agents.
Infectious Disease Division, Winthrop-University Hospital, 222 Station Plaza North, Suite 432, Mineola, NY, 11501, USA.
We proceeded with activated lymphocytes immunotherapy for 149 cancer patients, and hyperthermia therapy for 126 patients, and DC therapy for 20 patients in the past year. We were successful in two cases. Case 1: A metastatic pelvic cancer (unknown origin) patient treated with lymphocytes and hyperthermia therapy. She showed a drastic response. Case 2: A metastatic lymph node cancer patient treated with DC, lymphocytes and hyperthermia therapy. She showed a CR.
Colorectal Unit, Department of Surgery, Huddersfield Royal Infirmary, Huddersfield, UK.
INTRODUCTION: Spontaneous regression of cancer is an exceptional but well-documented biological event. Further understanding of this phenomenon and harnessing of the mechanisms involved will have significant preventative and therapeutic implications. DISCUSSION: In this review, the literature of spontaneous regression of colon or rectal cancer is reviewed from 1965 to 2005 to update reviews by Everson et al., Boyd and Challis et al. By adding to these, the author reports the entire series of colorectal cancer, which underwent documented spontaneous regression from 1900 to 2005. The demographic and pathologic characteristics, the details of regression and the outcome of reported cases are presented and discussed. Special emphasis is placed on identifying possible causes hypothesized by authors for occurrence of regression. Possible mechanisms operating to affect these regressions are also discussed.
Unidad de Enfermedades Infecciosas, Hospital Universitario 12 de Octubre, Madrid, Spain.
In order to take the best approach to infection in the oncohematologic patient with fever, it is important to know not only how profound the neutropenia is and how long the patient has had it, but also the characteristics of the underlying disease, the immunosuppressive therapy received and the type of hematopoietic stem/progenitor cell transplantation performed. Moreover, is important to consider if these patients have any personal or familial history of infectious diseases. All these aspects let us calculate the net state of immunosuppression and the risk of infection, and provide us with information about the most probable etiology in each case and the best prophylaxis and treatment. In this study we review the more important advances in chemotherapy in recent years that will make it necessary in the future to change our prophylactic guidelines for more effective prevention of infection in the oncohematologic patient.
IFR 89 Institut André Lwoff UPR 9045, 7 rue Guy Moquet, 94801 Villejuif, France yolene@noos.fr.
The history of science teaches that the greatest advances in the scientific domain have been achieved by bold thinkers who perceived new and fruitful approaches that others failed to notice. If one had taken the ideas of these scientific geniuses who have been the promoters of modern science and submitted them to committees of specialists, there is no doubt that the latter would have viewed them as extravagant and would have discarded them for the very reason of their originality and profundity; Louis de Broglie, Nobel Laureate, April 25, 1978 Scientists, these days, have a propensity for forgetting their forebears. However, on occasion, pioneer works are rediscovered that had been scorned, overlooked or forgotten, although reported by eminent scientists, including Nobel laureates, in first rate journals. The work is both provocative and visionary in scope. Some idea arose from theoretical considerations, others from experimental data. There are endless examples wherein key scientific breakthroughs have been neglected. The reasons for this oversight are multiple and complicated. Typically, the ideas are too advanced for the time, challenging the current dogma. Often, power interests come into play. As a result, these ideas do not grow, or quickly fall out of vogue, and have little immediate impact on the scientific community. Thanks to the persistence of a few open-minded individuals that keep alive some of the original claims, discarded ideas may be revisited. We wanted, in this thematic publication These Scholars who talk to the Wind, to revive some forgotten ground breaking discoveries that, in our opinion, deserve careful consideration. It leaves out far more than it includes. Many other important discoveries of long ago were not incorporated, not meaning they do not deserve any consideration. Although initially we did not wish to have authors advocating their owns works, we finally included some significant contributions by experienced researchers because we believed relating their own scientific achievement could be of interest for all of us. We also like to emphasize that the works we are presenting in this issue reflect the opinions of the authors not necessarily the ideas of the journal or of the guest editors. That is why the manuscripts were not peer-reviewed but nevertheless supported by peer-reviewed papers. One of the major intellectual weaknesses of contemporary scientists is their lack of historical perspective on scientific dogmatism. At the gut level, they believe that dogmatism and errors are definitely things of the past, when in fact the conditions for a confrontation of ideas, observations and interpretations are worse now than they were fifty years ago, the Web notwithstanding. They go ahead confidently, convinced that their training to "Modern Science'' is a guarantee against Error. They ignore the heritage from the past. This often leads to a redundant re-discovery of the past. Instead of analyzing the obstacle of scientific dogmatism each time it is overcome, scientists emphasize the triumphant march towards scientific truth. Such cases are thus erased from our collective memory and thus little progress is made. The unfortunate ''inside the box'' orthodox scientific mentality has already done great harm to the necessary scientific debate and has frozen many important, critical projects. It is becoming even socially counterproductive, when the work concerns major public health issues. So now, let us briefly introduce the different manuscripts which can be roughly arranged into four groups. The first group of articles revisits neglected (or rejected) works from distinguished scholars. Michel Laurent, Gilles Charvin (University Paris-Sud, Orsay, France) and Janine Guespin-Michel (faculté Sciences et techniques, Rouen, France) report the history of epigenesis and early forgotten thoughts of Max Delbrück back in 1949:''According to Delbrück, biological systems with identical genotypes may display different behaviors under particular external conditions. This difference is due to 'epigenetic' differences, which can be transmitted in the cell lineage in the absence of genetic modification. This hypothesis corresponds to a very early formulation of the general principle of phenotypic inheritance. The theoretical and mechanistic bases of this principle was described more than 20 years later, by Glansdorff and Prigogine''. John W. Porteous from the University of Aberdeen, UK, evokes Henrik Kacser, a pioneer in the idea of metabolic control analysis (MCA):''keenly aware of the intimate relation between genetics and biochemistry''. J. Porteous adds: ''there may be textbooks of elementary genetics that exposed students to MCA and the concepts that undergoing Kascer.... but I have yet to find one''. Harry Rubin from the University of California, Berkeley, USA, revisits Walter Elsasser,"an eminent theoretical physicist who devoted much of his spare time for over half a century to the development of a holistic theory of organisms. His ideas have either been coolly received or ignored by biologists, at least partly because of their purely formal character, although that is considered the sine qua non for theories in physical science''. HR reports ''a variety of experiments at the cellular level that illustrate Elsasser's principles... that hopefully will promote a dialog between theory and practice to facilitate development of a non-reductionist biology". Virginia A. Shepherd (University of NSW, Sydney, Australia) writes eloquently about a legendary figure in India, Jagadis Chandra Bose (1858-1937) an ingenious inventor and physicist, a pioneer in the fields of semi-conductor and microwave technology. As she mentioned:"In the West he is unknown or written off as crazy.../... In fact, it wasn't until 1992 that people, generally accepted that plants use electrical signaling as the predominant means of cell to cell communication". Richard C.A. Boyd (Brasenose College, Oxford, UK) unveils the critical contribution of Wilfred F. Widdas as a modern understanding of how membrane carriers function. RB describes ''what in the original paper Widdas actually did, analyses some aspects of why the work was so substantially ignored, to look at ways in which it was developed subsequently by a few other pioneers and finally how his 1952 paper has been triumphantly proven correct more than 50 years later''-''... the first atomic structures of transporters described last year". Michel Morange (ENS, Paris, France) introduces us to Henri Atlan's early writings."To appreciate the originality of Henri Atlan, and his role as a precursor", MM focuses "on Atlan's first book, Biological organization and the theory of information. His fame among the French- as well as English-reading public came from works published later, but we shall show that the main and most original ideas of Henri Atlan were already expressed in this book. In addition, the book exhibits the background for his ideas more than subsequent publications... Anticipations and obsolete models and visions are closely intermingled in Henri Atlan's ideas and writings, as they probably are in the work of every so-called 'precursor'". Victor Norris (faculté Sciences et techniques, Rouen, France) discusses three paradigms which are in the process of being shifted by Rosetta Natoli Reusch and her collaborators in the course of their investigations:''Reusch has also extended the importance of short chain poly-(R)-3-hydroxybutyrate to medicine by showing its likely involvement in atherogenic plaques and diabetes. And yet this opus has gone largely unnoticed''. In his manuscript Jonathan W. Yewdell (NIH/NIAID, Bethesda, USA) gives a personal testimony on Denys Wheatley's pioneered work in protein synthesis. Discussing about "The Nature We Have", JY remarks ''Nature does not care what we may or may not believe. Nature just is. It' s astounding how many scientists don't really get this..." The second group of articles deals with forgotten concepts or approaches that limped out through the last century with a few modest peaks of interest. Yet, data have continued to emerge which clearly suggests that these paradigms be re-examined. Edward J. Calabrese (University of Massachusetts, Amherst, USA) retraces the history of hormesis, a dose-response phenomenon characterized by a low dose stimulation and a high dose inhibition, propounded over a century ago. Despite its original ''institutional'' marginalization, the issue of the biological effect of low-level exposure to chemical or physical agents is now a main focus for toxicological assessment. Jacques de Certaines (Université de Rennes, France) in his essay "Is biomedical nuclear magnetic resonance limited by a revisitable paradigm in physics?":"i) points out the context of emergence of the Bloch and Purcell paradigm and its subsequent development, ii) evokes the vast extent of its applications in biomedicine and the limitations arising from the paradigm, and iii) describes the belated attempts to question this paradigm, along with their historical context and implications". The contribution by Vladimir L. Voeikov from Lomonosov Moscow State University, Russia, deals with the history of the problem of biological oxidation and how forgotten knowledge allows to explain most recent data on the universal regulatory functions of reactive oxygen species. VV reviews "the dramatic history of 'active oxygen', set out with the intention of showing that the most fundamental ideas of Lavoisier, Szent-Gyorgyi, and other outstanding scientists concerning the primary role of 'active oxygen' in bioenergetics might easily rekindle its potential to become a serious unifying biological principle". Marc Henry (Université Louis Pasteur, Strasbourg, France) reviews the status of water in living systems from philosophical and scientific viewpoints.(ABSTRACT TRUNCATED)
University Department of Dermatology and Venereology Zagreb University Hospital Center; Salata 4, HR-10000 Zagreb, Croatia ;branka@marli.hr.
Although the term 'evidence - based' has been recently introduced, the evidence based idea is very old indeed; in ancient world, Aristoteles placed a rule for all investigators of the time that they should support each of their statements with all available evidence. In 1991, Sackett defined the term evidence based medicine (EBM) as a conscientious, explicit and judicious use of current best evidence in making decisions about the care of individual patients. Some other authors define EBM as the best way of linking and integrating clinical research with clinical practice. Until now, our decisions on reaching the diagnosis and especially on the choice of therapy for our patients have been based on data acquired through our experience, from the experience of our colleagues, and from the routine at the particular medical institution. The best therapy for each individual patient is chosen according to these data. However, the problem is that this practice may be obsolete and too infrequently submitted to critical review. In the literature, this model of performance is called 'eminence based medicine'. The result of this approach is that patients are being differently treated at different hospitals, which means that not all patients have due access to the same conditions of medical treatment. EBM relies on the importance and value of research evidence, however, just the evidence is not enough to make a definitive decision, as it depends on the benefit to risk ratio, cost, physician's experience, and patient's preference. The most important evidence derives from reviews of controlled randomized trials conducted by different institutions. The most reliable sources of evidence are Cochrane Library (which also includes results of Cochrane Skin Group), Medline, Embase, secondary publications, primary publications, and national guidelines that should not be mistaken for EBM. As dermatologists, we are interested in evidence based dermatology in particular, which is defined as the use of EBM for people with skin problems. What is specific about the skin? Skin is a large and visible organ, however, it is not just an organ covering the body but a sensitive dynamic barrier between the outer world and internal organs. It is also a very important organ of social and sexual contact. All these facts probably are the reason why, unlike other organs where up to some 100 different diseases are usually described, dermatology textbooks list about 2000 different skin conditions. Skin manifestations can be caused by primary skin disease or some systemic diseases can have cutaneous manifestations. According to literature data, skin disorders affect about 20% of the general population at any time. As skin manifestations are readily visible, they can cause greater distress than other more serious but 'invisible' problems. As in other disciplines, the past few decades have seen an impressive increase in clinical research in dermatology. Yet, the problem is that the quality of randomized controlled trials in dermatology has not followed the progress in research. What could be the reasons for that? Here are some possible answers: there are not enough quality randomized controlled trials; in dermatology there are about 1000 very rare diseases with high mortality that could only be reviewed through international cooperation; skin changes are visible, giving patients an opportunity for self-monitoring and therapy modification; there are quite a number of studies reported in popular literature and providing wrong data and wrong picture; and a number of randomized studies are conducted by pharmaceutical industry, thus raising doubt about the realiability of data thus obtained. How could we make our contribution to solving these problems? The best way is to publisih results of our studies as well as interesting case reports substantiated by controlled data. Only the results published in publications with international relevance have a real value. And the last but not the least, we are proud to have a journal indexed in two relevant databases (Excerpta Medica/Embase and Excerpta Medica/Medline), which offers us an opportunity to inform the international scientific community on our researches as well as on diagnostic and therapeutic doubts and achievements.
