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Anterior thoracoscopic epiphysiodesis in the treatment of a crankshaft phenomenon.

We report our first performance of a multiple anterior thoracoscopic epiphysiodesis in the treatment of a crankshaft phenomenon. In the last 2 years, video-assisted thoracoscopy has been introduced as a new therapeutic technique in the field of spinal diseases. Its use has been most documented in the treatment of vertebral abscesses and disc herniations, while its performance in treating deformities is less known. The patient in our case was an 11-year-old boy with a 7-year history of aggressive left thoracic idiopathic scoliosis that had previously needed three subcutaneous instrumentations and finally a Cotrel-Dubousset-instrumented arthrodesis. Following these operations, a continuous clinical and radiographical evolution of the curve was recorded and an anterior T6-T11 video-assisted thoracoscopic epiphysiodesis was therefore performed. The patient did not need postoperative narcotics; Argyle chest tubes were removed after 48h with only 150ml of serohaematic drainage, no blood transfusion was required. One year after the intervention, we found a well-consolidated T6-T11 arthrodesis with no evolution of the deformity. The endoscopic technique allowed us to perform an extensive anterior arthrodesis using only three small incisions, with a reduction of bed-confinement to 3 days and reduced postthoracotomy pain.

Arthrodesis↗

Osteoporosis: the evolution of a scientific term.

Coined in French in the early 1820s as a mere description of a pathological state of the bone, the term 'osteoporosis' made its way into the English medical vocabulary only in the twentieth century. Unlike other medical concepts, which have not been substantially altered by progress in medical research, the definition of osteoporosis has constantly reflected the state of knowledge on the phenomenon itself. Over its 170 years of evolution, this definition has continuously sought to maintain a difficult balance between physiological and clinical criteria. Even at present, while the 1990 Consensus Conference definition (centering mainly on physiological deterioration) merely implies the clinical aspect through the notions of fragility and fracture risk, others advocate restriction of the term to the clinical consequences of osteopenia. How will the concept of osteoporosis develop in the future? This article, which deals with the origin of the term and its successive definitions, is offered as a basis for further discussion on this subject of high topicality.

France↗

Statin therapy in cardiovascular diseases other than atherosclerosis.

Statins are drugs that inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, thereby blocking the synthesis of cholesterol. Since being discovered in Japan in the mid 1970s, statins have been widely used to lower low-density lipoprotein cholesterol. However, analysis of cardiovascular research has revealed other important effects beyond changes in lipid parameters, referred to as pleiotropic effects. This paper focuses on the effects of statins as anti-ischemic agents with improvement in endothelial function, along with studies on valvular aortic stenosis, atrial fibrillation, heart failure, peripheral arterial disease, and cancer. As the evolution of statin research continues, there appear to be new potential benefits from statins to be found in many facets of cardiovascular disease.

Atherosclerosis↗

Mycobacteria and other environmental organisms as immunomodulators for immunoregulatory disorders.

In the rich, developed parts of the world there has been a steady and simultaneous increase in at least three groups of disease: (1) allergies, (2) inflammatory bowel diseases (IBD; e.g. Crohn's disease and ulcerative colitis) and (3) autoimmunity (e.g. type 1 diabetes and multiple sclerosis). Because the medical world is so compartmentalised it was some time before the connection between these increases was noticed and understood. There is now evidence that the simultaneous increase in these diseases of immunodysregulation is at least partly attributable to malfunction of regulatory T cells (Treg). This paper provides an overview of relevant work in each of these fields of medicine (though with emphasis on the allergic disorders), and concludes that the increasing failure of Treg is a consequence of diminished exposure to certain micro-organisms that are "old friends", because of their continuous presence throughout mammalian evolution. These organisms, which include saprophytic mycobacteria, helminths and lactobacilli, are recognised by the innate immune system as harmless, and as adjuvants for Treg induction. Polymorphisms of components of the innate immune system such as TLR2 and NOD2 appear to define subsets of the population that will develop immunoregulatory disorders when living in the modern environment. A further role of the "old friends" and of the Treg that they induce might be to maintain the levels of regulatory IL-10 secreting macrophages and antigen-presenting cells, which are depleted in asthma and Crohn's disease. These concepts are leading to novel therapies based on harmless organisms or their components. Phase I/II clinical trials have yielded some statistically significant results, and phase II trials are in progress.

Adjuvants, Immunologic↗

MR imaging of the brain: tumors.

The radiologic modality that most likely provides the imaging information needed in a patient suspected of having a brain tumor is MR imaging. A brain tumor can be reliably ruled out if the MR examination is performed properly and experts interpret the results as negative. If there is a tumor, however, its exact location and topography must be determined. Important for therapy and prognosis are also tumor properties such as histologic type and grade, as well as effects on adjacent brain structures. Although potentially a noninvasive method of in vivo neuropathology, MR is still far from being sufficiently specific, as dissimilar lesions may look the same despite the use of refined imaging protocols. The evolution of MR imaging continues, however, making further methodologic improvement likely. Presently, advanced methods, such as diffusion- and perfusion-weighted MR imaging, functional MR imaging, neuronavigation based on MR imaging data, and the use of MR imaging during surgery (intraoperative MR imaging), influence the way patients are treated. Likewise, follow-up imaging (monitoring) of tumor patients by MR has become more effective, and experience has shown how to distinguish reactive changes from recurrent tumor. In the future, MR imaging may gain importance in the development of novel therapeutic concepts.

Adult↗

High-resolution comparative physical mapping of mouse chromosome 10 in the region of homology with human chromosome 21.

Comparative mapping of human and mouse chromosomes can be used to predict locations of homologous loci between the species, provides the substrate to examine the process of chromosomal evolution, and facilitates the continuing development of mouse genetic models for human disorders. A YAC contig of the region of mouse Chromosome (Chr) 10 (MMU10) that demonstrates conserved linkage with the distal portion of human Chr 21 (HSA21) has been constructed. The contig contains all known genes mapped in both species, defines the proximal region of homology between MMU10 and HSA22, and contains the evolutionary junction between HSA21 and HSA22 on MMU10. It consists of 23 YACs and 2 PACs, and covers 3.2 Mb of MMU10. The average marker density for this region is 1 marker/69 kb. Nine of 22 expressed sequences are mapped here for the first time in mouse, and two are newly characterized expressed sequences. The contig also contains 12 simple sequence repeats (SSRs) and 16 YAC and PAC endclone markers. YAC fragmentation analysis was used to create a physical map for the proximal 2.2 Mb of the contig. Cloning of the corresponding region of HSA21 has proven difficult, and the mouse contig includes segments absent from previously described sequence ready maps of HSA21.

Animals↗

The evolution of legislation to regulate pediatric clinical trials: Present and continuing challenges.

Children suffer from many of the same diseases as adults and are often treated with the same agents. However, it was not until 1997 that legislation mandating studies in children was introduced in the United States. A 2000 International Conference on Harmonisation (ICH) Guidance on the Clinical Investigation of Medicinal Products in the Pediatric Population intended to encourage and facilitate timely pediatric clinical trials detailed critical issues in pediatric drug development and ways to ethically study the safety and efficacy of drugs in the unique and vulnerable pediatric population. In 2005, there is draft legislation in Europe. In Japan, pediatric data are not currently required although studies in pediatric populations are encouraged. This chapter describes the history of legislation on the study of drugs in the pediatric population and details present and continuing challenges for the child, parent/guardian, manufacturer and health authority.

Child↗

Use of potentiated antibiotics in wound management.

Prevention or resolution of microbial colonization of wounds is critical to rapid and uneventful healing. The use and misuse of antimicrobial agents continues to support the evolution of multidrug resistant organisms that can cause severe or life-threatening infections. Chelating agents have been shown to potentiate the effects of antimicrobial compounds. The third generation chelating agent. Tricide has been shown to be effective against many multidrug resistant pathogens, prevents pathogens from development resistance to the antimicrobials with which it is mixed and substantially reduces the amount of antimicrobials needed to kill bacteria and fungi.

Animals↗

Functional characterization of the rice kaurene synthase-like gene family.

The rice (Oryza sativa) genome contains a family of kaurene synthase-like genes (OsKSL) presumably involved in diterpenoid biosynthesis. While a number of OsKSL enzymes have been functionally characterized, several have not been previously investigated, and the gene family has not been broadly analyzed. Here we report cloning of several OsKSL genes and functional characterization of the encoded enzymes. In particular, we have verified the expected production of ent-kaur-16-ene by the gibberellin phytohormone biosynthesis associated OsKS1 and demonstrated that OsKSL3 is a pseudo-gene, while OsKSL5 and OsKSL6 produce ent-(iso)kaur-15-ene. Similar to previous reports, we found that our sub-species variant of OsKSL7 produces ent-cassa-12,15-diene, OsKSL10 produces ent-(sandaraco)pimar-8(14),15-diene, and OsKSL8 largely syn-stemar-13-ene, although we also identified syn-stemod-12-ene as an alternative product formed in approximately 20% of the reactions catalyzed by OsKSL8. Along with our previous reports identifying OsKSL4 as a syn-pimara-7,15-diene synthase and OsKSL11 as a syn-stemod-13(17)-ene synthase, this essentially completes biochemical characterization of the OsKSL gene family, enabling broader analyses. For example, because several OsKSL enzymes are involved in phytoalexin biosynthesis and their gene transcription is inducible, promoter analysis was used to identify a pair of specifically conserved motifs that may be involved in transcriptional up-regulation during the rice plant defense response. Also examined is the continuing process of gene evolution in the OsKSL gene family, which is particularly interesting in the context of very recently reported data indicating that a japonica sub-species variant of OsKSL5 produces ent-pimara-8(14),15-diene, rather than the ent-(iso)kaur-15-ene produced by the indica sub-species variant analyzed here.

Alkyl and Aryl Transferases↗

Reduction of infarct size by the early use of intravenous timolol in acute myocardial infarction. International Collaborative Study Group.

One hundred forty-four patients admitted to the hospital within 4 hours after the onset of symptoms of suspected acute myocardial infarction (AMI) were randomly assigned to either intravenous timolol treatment or to matching placebo. Infarct evolution was assessed by continuous vectorcardiography and CK release. Timolol reduced myocardial ischemia and infarct size as measured by an accelerated reduction in ST-vector magnitude, a significant reduction in maximal cumulative CK release (29.5%) and significantly smaller changes in QRS-vector parameters (20 to 25%). Furthermore, the predicted CK release and maximal QRS-vector change for a given initial ST-vector magnitude was significantly reduced by timolol. The drug regimen also caused a significant reduction in pain and the need for analgesic medication.

Administration, Oral↗

Film drainage between two captive drops: PEO-water in silicon oil.

An experimental study of the deformation and drainage of a Newtonian liquid film trapped between two drops is performed for the cases of a constant and slightly rising interaction force. Series of polyethylene oxide (PEO) water solutions are used for the dispersed and polydimethylsiloxane (PDMS) for the continuous phase. The film evolution is observed by an interferometric technique. Experimental data for the film thinning rate and for the film profile allow quantitative comparison with the available drainage models.

Journal Article↗

Proteomics: applications in basic and applied biology.

The rapid evolution of proteomics has continued during the past year, with a series of innovations in the core technologies of two-dimensional electrophoresis and mass spectrometry, and a diversity of productive research programmes. Well-annotated proteomics databases are now emerging in a number of fields to provide a platform for systematic research, with particularly promising progress in clinical applications such as cardiology and oncology. Large-scale quantitative research, comparable in power and sensitivity to that achieved for gene expression, is thus becoming a reality at the protein level.

Databases, Factual↗

Recent developments in linker design and application.

The linker connecting the solid support and the substrate is critical to the ultimate success of a solid-phase synthesis. The evolution of linker constructs continues, offering new approaches to the analysis, release and deconvolution of resin-bound material and allowing entry to new structural motifs.

Combinatorial Chemistry Techniques↗

Cis-preferential LINE-1 reverse transcriptase activity in ribonucleoprotein particles.

LINE-1 retrotransposons (L1s) constitute approximately 17% of human DNA, and their activity continues to affect genome evolution. Retrotransposition-competent human L1s encode two proteins required for their mobility (ORF1p and ORF2p); however, biochemical activities associated with ORF2p have been difficult to detect in cells. Here, we show for the first time the colocalization of L1 RNA, ORF1p and ORF2p to a putative ribonucleoprotein retrotransposition intermediate. We further demonstrate that ORF2p preferentially uses its encoding RNA as a template for reverse transcription. Thus, our data provide the first biochemical evidence supporting the cis-preferential action of the L1 reverse transcriptase.

Base Sequence↗

Reduction of infarct size with the early use of timolol in acute myocardial infarction.

One hundred forty-four patients admitted to the hospital within four hours after onset of symptoms of myocardial infarction were randomly assigned to either intravenous timolol treatment or to placebo. Timolol was given intravenously for the first 24 hours and orally thereafter for the duration of hospitalization. Infarct evolution was assessed by continuous vectorcardiography and creatine kinase release. The timolol group had reduced myocardial ischemia and infarct size as measured by an accelerated reduction of ST-vector magnitude, a significant reduction of maximal cumulative creatine kinase release (29.5 per cent), and significantly smaller changes in QRS-vector variables (20 to 25 per cent). Furthermore, the predicted creatine kinase release and maximal QRS-vector change for a given initial ST-vector magnitude was significantly reduced in the timolol group. Timolol was also associated with significant reductions in pain and need for analgesics and was well tolerated overall. This study supports the use of intravenous timolol in the early phase of suspected myocardial infarction to limit infarct size.

Administration, Oral↗

Tick-borne encephalitis in eastern France.

Each y a few cases of TBE infection are described in Alsace, France which lies at the occidental limit of the endemic zone of tick-borne encephalitis (TBE). Hence we carried out a retrospective epidemiological and clinical study of TBE infection in Alsace. Data were collected from serological results sent to the Institut de Virologie (Université Louis Pasteur) in Strasbourg. All samples positive for specific IgM against TBE were retained. The physician in charge of each patient was asked to provide clinical, epidemiological and biological data and with his agreement the medical file was referred to us. Since 1968, 64 cases of TBE infection, occurring between April and November, had been described. In 56% of cases, flu-like symptoms preceded neurological symptoms. Most patients had meningitis (54%) or meningoencephalitis (34%). There was no death due to TBE. Two areas were more highly endemic for the disease: the Guebwiller valley in low mountain country and the Neuhof forest, near Strasbourg in the plain of Alsace. In the last 2 y of the study, a third zone seemed to emerge, in the Munster valley. This epidemiological survey revealed the existence in Alsace of 2 endemic zones of TBE with a third zone possibly emerging in the last few y. The survey must be continued to follow the evolution of the disease.

Adult↗

Molecular characterization of macrolide resistance mechanisms among Streptococcus pneumoniae and Streptococcus pyogenes isolated from the PROTEKT 1999-2000 study.

In this study, the distribution of macrolide resistance mechanisms was determined for isolates of Streptococcus pneumoniae and Streptococcus pyogenes obtained from the PROTEKT 1999-2000 study (a global, longitudinal study of the antibacterial susceptibility of bacterial pathogens associated with community-acquired lower respiratory tract infections). The global macrolide resistance mechanism distribution results for 1043 macrolide-resistant S. pneumoniae isolates collected from 25 countries were as follows: 35.3% mef(A), 56.2% erm(B), 6.8% both mef(A) and erm(B), 0.2% erm(A) subclass erm(TR) and 1.5% negative for mechanisms tested. Mechanisms of macrolide resistance were found to vary widely between countries and different geographical regions with mef(A) predominating in North America and erm(B) in Europe. Approximation of genotype from macrolide MIC without molecular determination of the mechanism of resistance resulted in an error of 10.2% (106 isolates). Overall, for 143 macrolide-resistant S. pyogenes isolates, 46.1% of the isolates tested were mef(A), 30.8% were erm(B), 23.1% were erm(A) subclass erm(TR) and no isolates were negative for all the genetic markers tested. Again, the distribution varied widely between countries and geographical regions. This study provides valuable baseline data for the continued monitoring of the evolution of macrolide resistance development in these important respiratory tract pathogens. The ketolide telithromycin retained excellent anti-pneumococcal activity irrespective of macrolide resistance mechanism, having a MIC(90) of 0.25, 0.5 and 0.5 mg/L against mef(A), erm(B) and mef(A)+erm(B) macrolide-resistant S. pneumoniae, respectively. It also exhibited potent activity against S. pyogenes that had become resistant to macrolides via either mef(A), (MIC(90 )0.5 mg/L) or erm(TR), (MIC(90) 0.03 mg/L).

Anti-Bacterial Agents↗

The evolutionary history of quorum-sensing systems in bacteria.

Communication among bacterial cells through quorum-sensing (QS) systems is used to regulate ecologically and medically important traits, including virulence to hosts. QS is widespread in bacteria; it has been demonstrated experimentally in diverse phylogenetic groups, and homologs to the implicated genes have been discovered in a large proportion of sequenced bacterial genomes. The widespread distribution of the underlying gene families (LuxI/R and LuxS) raises the questions of how often QS genes have been transferred among bacterial lineages and the extent to which genes in the same QS system exchange partners or coevolve. Phylogenetic analyses of the relevant gene families show that the genes annotated as LuxI/R inducer and receptor elements comprise two families with virtually no homology between them and with one family restricted to the gamma-Proteobacteria and the other more widely distributed. Within bacterial phyla, trees for the LuxS and the two LuxI/R families show broad agreement with the ribosomal RNA tree, suggesting that these systems have been continually present during the evolution of groups such as the Proteobacteria and the Firmicutes. However, lateral transfer can be inferred for some genes (e.g., from Firmicutes to some distantly related lineages for LuxS). In general, the inducer/receptor elements in the LuxI/R systems have evolved together with little exchange of partners, although loss or replacement of partners has occurred in several lineages of gamma-Proteobacteria, the group for which sampling is most intensive in current databases. For instance, in Pseudomonas aeruginosa, a transferred QS system has been incorporated into the pathway of a native one. Gene phylogenies for the main LuxI/R family in Pseudomonas species imply a complex history of lateral transfer, ancestral duplication, and gene loss within the genus.

Bacteria↗