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ID PMID Title PublicationDate abstract
16446596 Alendronate in bone cement: fatigue life degraded by liquid, not by powder. 2006 Apr Bisphosphonates have the potential to reduce osteolysis, a phenomenon that has been postulated to play a key role in aseptic loosening of total joint replacements. Bisphosphonates may contribute to the in vivo longevity of total joint replacements. Some authors have suggested there are decreases in flexural strength and flexural modulus of the cured cement when a liquid form of disodium pamidronate is added to a commercially available acrylic bone cement (Palacos R). We proposed that it is comparatively easier to blend a bisphosphonate in powder form into an acrylic bone cement than it is when the drug is in liquid form; and that the cement's fatigue life is decreased when the bisphosphonate is added in liquid rather than in solid form. The bisphosphonate and bone cement used were alendronate sodium and Cemex XL, respectively. The fatigue tests were done using phosphate buffered saline solution at 37 degrees +/- 1 degrees C. The data supported both hypotheses. Our findings should guide orthopaedic surgeons when using bisphosphonate-impregnated acrylic bone cements in total joint replacements. Bisphosphonates are endogenous pyrophosphate analogs in which a carbon atom replaces the central oxygen atom. These therapeutic agents may be classified into nitrogen and non-nitrogen containing types. Some examples are alendronate, pamidronate, ibandronate, risedronate, etidronate, clodronate, and zoledronate. There are many targets and mechanisms of action of this family of drugs, therefore making them efficacious against diverse clinical conditions such as osteoporosis, periprosthetic bone loss subsequent to total joint replacement, tumor cell proliferation, apoptosis and angiogenesis, Charcot neuroarthropathy, rheumatoid arthritis, ankylosing spondylitis and spondyloarthropathies, and arterial calcification. It has been proposed that some bisphosphonates are effective against the mechanisms that have been suggested as being implicated in aseptic loosening of total joint replacements, these being osteoclast-mediated bone resorption and wear particle-induced osteolysis. A meta-analysis of randomized controlled trials showed that alendronate and pamidronate had beneficial effects maintaining periprosthetic bone for as much as 1 year after a total joint replacement.
16402109 The role of inflammation in CNS injury and disease. 2006 Jan For many years, the central nervous system (CNS) was considered to be 'immune privileged', neither susceptible to nor contributing to inflammation. It is now appreciated that the CNS does exhibit features of inflammation, and in response to injury, infection or disease, resident CNS cells generate inflammatory mediators, including proinflammatory cytokines, prostaglandins, free radicals and complement, which in turn induce chemokines and adhesion molecules, recruit immune cells, and activate glial cells. Much of the key evidence demonstrating that inflammation and inflammatory mediators contribute to acute, chronic and psychiatric CNS disorders is summarised in this review. However, inflammatory mediators may have dual roles, with detrimental acute effects but beneficial effects in long-term repair and recovery, leading to complications in their application as novel therapies. These may be avoided in acute diseases in which treatment administration might be relatively short-term. Targeting interleukin (IL)-1 is a promising novel therapy for stroke and traumatic brain injury, the naturally occurring antagonist (IL-1ra) being well tolerated by rheumatoid arthritis patients. Chronic disorders represent a greater therapeutic challenge, a problem highlighted in Alzheimer's disease (AD); significant data suggested that anti-inflammatory agents might reduce the probability of developing AD, or slow its progression, but prospective clinical trials of nonsteroidal anti-inflammatory drugs or cyclooxygenase inhibitors have been disappointing. The complex interplay between inflammatory mediators, ageing, genetic background, and environmental factors may ultimately regulate the outcome of acute CNS injury and progression of chronic neurodegeneration, and be critical for development of effective therapies for CNS diseases.
16355400 Expression of peptidylarginine deiminase type 4 (PAD4) in various tumors. 2006 Mar Peptidylarginine deiminase type 4 (PAD4/PADI4) posttranslationally converts peptidylarginine to citrulline, in a process known as citrullination. Evidence suggests that PAD4 plays an essential role in pathogenesis of rheumatoid arthritis (RA). RA synovium has many features in common with tumor tissues, including abnormal cell proliferation, extensive fibrin deposition, high coagulation activity, and extreme angiogenesis. The purpose of the present study was to investigate expression of PAD4 in various tumor tissues. Immunohistochemistry indicated that PAD4 had significant expression in many tumor tissues, especially various adenocarcinoma. Western blotting with anti PAD4 antibody and immunostaining with anti citrulline antibody confirmed the expression of the enzyme in these tumors. Furthermore, our immunohistochemistry also detected co-location of PAD4 with cytokeratin (CK), a well-known tumor marker for oncological study in many tumors. Western blot analysis also detected citrulline signals in CK extracted from the tumors. In addition, CK 8, 18, and 19 following in vitro citrullination resisted to the digestion of caspase. The results further confirm the expression of PAD4 in the tumors and support that PAD4 may contribute to the disrupted apoptosis of tumors by caspase-mediated cleavage of CK. Double immunofluorescent labeling detected co-location of PAD4 with CD34, a cell marker of heamatopoietic progenitor cells (HPC) in bone marrow and other normal tissues, as well as in some fibroblast-like cells at stroma region of tumors, but not in the tumor cells. The findings imply that PAD4 is initially expressed in CD34(+) cells of bone marrow and then distributed in derives of the multi-potent progenitor cells in diverse tissues. The development of tumor cells expressing PAD4 is possibly associated with abnormal proliferation of CD34(+) stem cells.
16341055 Examination of seven candidate regions for multiple sclerosis: strong evidence of linkage 2006 Jan Multiple sclerosis (MS) is a debilitating neuroimmunological and neurodegenerative disease with a strong genetic component. Numerous studies have failed to consistently identify genes that confer disease susceptibility except for association with HLA-DR. Seven non-HLA regions (1q, 2q, 9q, 13q, 16q, 18p and 19q) identified in a recent genomic screen were investigated by genotyping approximately 20 single-nucleotide polymorphisms (SNPs) at approximately 1 Mb intervals. Non-parametric multipoint analyses identified a peak LOD* score of 2.99 for the 1q44 region and substantially narrowed the linkage peak to approximately 7 Mb. Ordered subset analyses (OSA) identified significant LOD score increases for 2q35 and 18p11 when ranking families by HLA-DR status and identified a significant LOD score increase in region 2q35 when ranking families by linkage to chromosome 1q44. 1q44 is particularly interesting because of linkage evidence for this region in studies of both rheumatoid arthritis and systemic lupus erythematosus.
18785423 Changes in length of the first ray with two different first MTP fusion techniques: a cadav 2008 Jul BACKGROUND: First metatarsophalangeal joint (MTP) fusions are performed as salvage procedures for a variety of conditions ranging from osteoarthritis, rheumatoid arthritis, hallux valgus, and failed first MTP arthroplasty. A number of bone preparation techniques have been described to fuse the first MTP joint, with varying degrees of success. The aim of this study was to characterize and compare the average shortening of the first ray with a conical reamer fusion technique versus flat bone cut technique. MATERIALS AND METHODS: Six paired cadaver feet were divided into two groups with one foot from each pair in each group. Preoperative first ray lengths were measured radiographically. Each group then underwent arthrodesis of first MTP joint with one of two different bone cut techniques: flat cuts or conical reaming. The postoperative lengths of the first rays were measured and the data analyzed using a two-tailed Student's t-tests. RESULTS: The average shortening that occurred in both groups after the procedure was 7.1 mm for the flat cut group (Group I) and 5.7 mm for the machined conical reaming group (Group II). Comparing both groups, there was no statistically significant difference in the shortening between the groups. CONCLUSION: Both flat bone cut and conically reamed techniques caused shortening of the first ray after first MTP fusion. However, there was no statistically significant difference in the postprocedure lengths of the first ray between the two groups. CLINICAL RELEVANCE: Neither technique is more likely to lead to transfer metatarsalgia since the shortening was similar.
18780753 AMBIENCE: a novel approach and efficient algorithm for identifying informative genetic and 2008 Oct We developed a computationally efficient algorithm AMBIENCE, for identifying the informative variables involved in gene-gene (GGI) and gene-environment interactions (GEI) that are associated with disease phenotypes. The AMBIENCE algorithm uses a novel information theoretic metric called phenotype-associated information (PAI) to search for combinations of genetic variants and environmental variables associated with the disease phenotype. The PAI-based AMBIENCE algorithm effectively and efficiently detected GEI in simulated data sets of varying size and complexity, including the 10K simulated rheumatoid arthritis data set from Genetic Analysis Workshop 15. The method was also successfully used to detect GGI in a Crohn's disease data set. The performance of the AMBIENCE algorithm was compared to the multifactor dimensionality reduction (MDR), generalized MDR (GMDR), and pedigree disequilibrium test (PDT) methods. Furthermore, we assessed the computational speed of AMBIENCE for detecting GGI and GEI for data sets varying in size from 100 to 10(5) variables. Our results demonstrate that the AMBIENCE information theoretic algorithm is useful for analyzing a diverse range of epidemiologic data sets containing evidence for GGI and GEI.
18680514 The microsatellite, macrophage migration inhibitory factor -794, may influence gene expres 2008 Aug Polymorphisms within the gene encoding macrophage migration inhibitory factor (MIF) have been associated with susceptibility to inflammatory diseases such as rheumatoid arthritis and increased risk of developing sepsis. We investigated the effects of the MIF-173G>C polymorphism and the MIF-794 CATT microsatellite on MIF expression. These are in moderate linkage disequilibrium. Mononuclear cells from healthy donors were stimulated with bacterial pathogens associated with sepsis (Streptococcus pneumoniae or Escherichia coli ). MIF mRNA and protein levels were measured by real-time polymerase chain reaction and ELISA, respectively. Carriage of the C allele of MIF-173G>C or the 7 CATT repeat of the MIF-794 microsatellite correlated with lower basal and stimulated MIF mRNA levels. However, levels of intracellular and extracellular MIF protein were similar. This discordance between effects on MIF mRNA and protein was not explained by differential effects of genotype on stability of MIF mRNA (detected by actinomycin D mRNA chase). Gel shift assays revealed no differences in the profile of nuclear proteins from mononuclear cells bound by the G and C alleles of MIF-173G>C, but alleles at the microsatellite marker showed differential binding. Our data suggest that the MIF-794 CATT microsatellite influences transcription by differential binding of nuclear transcription factors. This may impact on inflammatory processes.
18626671 Molecular docking guided 3D-QSAR CoMFA analysis of N-4-Pyrimidinyl-1H-indazol-4-amine inhi 2008 Oct Inhibition of leukocyte-specific protein tyrosine kinase (Lck) activity offers one of the approaches for the treatment of T-cell mediated inflammatory disorders including rheumatoid arthritis, transplant rejection and inflammatory bowel disease. To explore the relationship between the structures of the N-4 Pyrimidinyl-1H-indazol-4-amines and their Lck inhibition, 3D-QSAR study using CoMFA analysis have been performed on a dataset of 42 molecules. The bioactive conformation of the template molecule, selected as the most potent molecule 23 from the series was obtained by performing molecular docking at the ATP binding site of Lck, which is then used to build the rest of the molecules in the series. The constructed CoMFA model is robust with r(2)(cv) of 0.603 and conventional r2 of 0.983. The predictive power of the developed model was obtained using a test set of 10 molecules, giving predictive correlation coefficient of 0.921. CoMFA contour analysis was performed to obtain useful information about the structural requirements for the Lck inhibitors which could be utilized in its future design.
18393924 Monoclonal antibodies: new therapeutic agents for autoimmune hemolytic anemia? 2008 Mar Conventional treatment of autoimmune hemolytic anemia (AIHA) comprises corticosteroids and splenectomy and/or other immunosuppressive drugs for refractory/relapsed patients. Monoclonal antibodies (MoAbs) rituximab and alemtuzumab have gained widespread acceptance in the management of B-cell malignancies. More recently, they have been used to treat a number of autoantibody-mediated diseases, such as both idiopathic and secondary AIHA, with encouraging results. Herein we report an overview of the medical literature on the use of MoAbs to treat AIHA. The therapeutic mechanism of action of rituximab in the treatment of autoimmune diseases such as rheumatoid arthritis and lupus is currently a subject of considerable investigation. We have proposed that cell-associated IgG immune complexes, generated by the binding of rituximab to CD20 on B cells, may serve as decoys that attract FcgammaR-expressing effector cells and downregulate effector cell pathogenic action, thus reducing inflammation and tissue destruction in these diseases. We briefly review evidence that suggests that this immune complex decoy hypothesis plays a role in the therapeutic action of rituximab in AIHA, and we propose new measurements that should allow for a more complete evaluation of the importance of this mechanism in AIHA.
18387938 Anti-serum albumin domain antibodies for extending the half-lives of short lived drugs. 2008 May We have used phage display to isolate a range of human domain antibodies (dAbs) that bind to mouse, rat and/or human serum albumin (SA) and can be expressed at very high levels in bacterial, yeast or mammalian cell culture. In contrast to non-SA-binding dAbs, which have terminal half-lives of less than 45 min, the half-lives of these 12 kDa 'AlbudAbs' can match the half-life of SA itself. To demonstrate the use of AlbudAbs for extending the half-lives of therapeutic drugs, we created a fusion of the interleukin-1 receptor antagonist (IL-1ra) with an AlbudAb. Soluble IL-1ra is potent inhibitor of IL-1 signalling that is approved for the treatment of rheumatoid arthritis but has a relatively short in vivo half-life. Here we show that although the AlbudAb/IL-1ra fusion has a similar in vitro potency, its in vivo efficacy can be dramatically improved due to its extended serum half-life. AlbudAbs could potentially be used to generate a range of long half-life versions of many different drugs in order to improve their dosing regimen and/or clinical effect.
18342093 [AA amyloidosis: a little-known complication of chronic leg ulcer]. 2008 Feb INTRODUCTION: AA amyloidosis, secondary to inflammatory chronic diseases like rheumatoid arthritis, is often complicated by renal failure. Chronic inflammatory dermatoses constitute rare causes of AA amyloidosis. CASE-REPORT: We describe two cases of AA amyloidosis discovered after renal failure in patients presenting leg ulcers for several years. AL amyloidosis was suspected in both cases because of a history of monoclonal gammopathy in one patient and of plasmocytoma in the other. The diagnosis of AA amyloidosis was confirmed on renal histology through the detection of AA antibodies in amyloid deposits. No extrarenal amyloidosis was seen in either patient and there were no inflammatory diseases other than chronic leg ulcers. DISCUSSION: AA amyloidosis is caused by serum amyloid protein A (SAA), a reactive inflammatory protein. AA amyloidosis is thus caused by chronic inflammatory diseases, but only rarely by cutaneous inflammatory diseases. To our knowledge, the literature contains only seven other published cases of AA amyloidosis secondary to chronic leg ulcers. A review of the literature does not indicate whether cure of ulcers has any effect on the accompanying renal failure. We imagine that AA amyloidosis secondary to leg ulcer is in fact under-diagnosed. However, since the first specific treatment for AA amyloidosis is currently being evaluated by the Food and Drug Administration, it is essential that this serious complication of chronic leg ulcers be widely recognised.
18253767 Inhibition of cathepsin B by Au(I) complexes: a kinetic and computational study. 2008 May Gold(I) compounds have been used in the treatment of rheumatoid arthritis for over 80 years, but the biological targets and the structure-activity relationships of these drugs are not well understood. Of particular interest is the molecular mechanism behind the antiarthritic activity of the orally available drug triethylphosphine(2,3,4,6-tetra-O-acetyl-beta-l-D-thiopyranosato-S) gold(I) (auranofin, Ridaura). The cathepsin family of lysosomal, cysteine-dependent enzymes is an attractive biological target of Au(I) and is inhibited by auranofin and auranofin analogs with reasonable potency. Here we employ a combination of experimental and computational investigations into the effect of changes in the phosphine ligand of auranofin on its in vitro inhibition of cathepsin B. Sequential replacement of the ethyl substituents of triethylphosphine by phenyl groups leads to increasing potency in the resultant Au(I) complexes, due in large part to favorable interactions of the more sterically bulky Au(I)-PR3 fragments with the enzyme active site.
18227910 Acupuncture for chronic pain in Japan: a review. 2007 Dec Many Japanese reports of acupuncture and moxibustion for chronic pain are not listed in medical databases such as Medline. Therefore, they are not easily accessible to researchers outside of Japan. To complement existing reviews of acupuncture and moxibustion for chronic pain and to provide more detailed discussion and analysis, we did a literature search using 'Igaku Chuo Zasshi Wed' (Japana Centra Revuo Medicina) and 'Citation Information by National Institute of Information' covering the period 1978-2006. Original articles and case reports of acupuncture and moxibustion treatment of chronic pain were included. Animal studies, surveys, and news articles were excluded. Two independent reviewers extracted data from located articles in a pre-defined structured way, and assessed the likelihood of causality in each case. We located 57 papers written in Japanese (20 full papers, 37 case reports). Conditions examined were headache (12 trials), chronic low back pain (9 trials), rheumatoid arthritis (8 trials), temporomandibular dysfunction (8 trials), katakori (8 trials) and others (12 trials). While 23 were described as clinical control trials (CCTs), 11 employed a quasi-random method. Applying the 5-point Jadad quality assessment scoring system, the mean score was 1.5 +/- 1.3 (SD). Eleven (52%) of the CCTs were conducted to determine a more effective procedure for acupuncture; these compared a certain type of acupuncture with another type of acupuncture or specific additional points. In particular, the trigger point acupuncture was widely used to treat chronic low back pain in Japan. Many reports of chronic pain treatment by acupuncture and moxibustion are listed in Japanese databases. From the data, we conclude that there is limited evidence that acupuncture is more effective than no treatment, and inconclusive evidence that trigger point acupuncture is more effective than placebo, sham acupuncture or standard care.
18078761 Bornyl (3,4,5-trihydroxy)-cinnamate--an optimized human neutrophil elastase inhibitor desi 2008 Mar 1 Human neutrophil elastase (HNE), a serine protease, is involved in the regulation of inflammatory processes and controlled by endogenous proteinase inhibitors. Abnormally high levels of HNE can cause degradation of healthy tissues contributing to inflammatory diseases such as rheumatoid arthritis, and also psoriasis and delayed wound healing. In continuation of our research on HNE inhibitors we have used the recently developed binding mode model for a group of cinnamic acid derivative elastase inhibitors and created bornyl (3,4,5-trihydroxy)-cinnamate. This ligand exhibited improved binding affinity predicted by means of free energy calculations. An organic synthesis scheme for the ligand was developed and its inhibitory activity was tested toward the isolated enzyme. Its IC(50) value was found to be three times lower than that of similar compounds, which is in line with the computational result showing the high potential of free energy calculations as a tool in drug development.
17961971 FCRL3 -169CT functional polymorphism in type 1 diabetes and autoimmunity traits. 2008 Mar A functional variant located in the promoter region of the Fc receptor like 3 gene (FCRL3, -169CT variant) has been recently shown to be associated with several autoimmune diseases in the Japanese population. Following the concept of shared genetic determinants between autoimmune diseases, we tested this variant for association to Type 1 diabetes (T1D) and T1D-related phenotypes in two independent settings: a family-based association study (French and US families) and a case-control study (French population). We found suggestive evidence for association of the FCRL3 -169CC genotype, corresponding to the susceptibility genotype for rheumatoid arthritis, with an increased risk of additional autoimmunity markers (OR=1.97, P=0.01) and of other autoimmune diseases (OR=1.75, P=0.05). However, there was no evidence of association of this variant with T1D in these cohorts, separately and combined, nor in subgroups of patients defined based on their major T1D risk factors at HLA-DRB1, insulin and PTPN22. Hence, this variant may help define subgroups of T1D patients with contrasted risk of other autoimmune diseases.
17908371 An evaluation of the association between systemic inflammation--as measured by C-reactive 2007 Nov OBJECTIVE: To evaluate the association between inflammatory status, as measured by C-reactive protein (CRP), during inpatient admission and subsequent inpatient outcome and associated resource use. METHODS: Probabilistic record linkage was used to match hospital episode data, laboratory reports and mortality statistics in a large urban population of 424,000 people in South Wales, UK. Inpatient mortality, length of stay, emergency readmissions and subsequent 1-year hospital bed day occupancy were assessed as a function of CRP status. RESULTS: Between 2001 and 2005, in total there were 432,272 CRP observations from 98,505 people; 69,593 admissions had at least one CRP measurement, affecting 47,100 individual patients. Across all ICD-10 primary diagnoses, CRP was acutely high (> 10 mg/L) in three-quarters of admissions. Acutely high CRP was associated with an eight-fold increase in risk of hospital mortality (p < 0.001) and a doubling of length of stay (p < 0.001) compared to normal CRP levels, after standardising for age and gender. Across the range of observed maximum CRP values measured during admissions (1 mg/L to > 400 mg/L) the likelihood of emergency readmission within 28 days of discharge increased by 50% (p < 0.001), and the predicted number of subsequent bed days occupied in the year following discharge increased by 30-58% across the range of CRP measurement (p = 0.004). CONCLUSIONS: CRP has been found to be clearly associated with hospital resource use. Furthermore, CRP also predicted in-hospital mortality. This may imply that better management of systemic inflammation would result in resource savings in inflammatory diseases such as rheumatoid arthritis.
17906611 B-cell lymphoproliferation in chronic inflammatory rheumatic diseases. 2007 Oct Patients with chronic inflammatory rheumatic diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and especially primary Sjögren's syndrome (SS), are at higher risk than the general population of developing B-cell non-Hodgkin lymphoma (NHL). Analyses of the association between various lymphoma subtypes and specific disease entities suggest that this association might be mediated by disease-specific mechanisms, as well as by mechanisms unique to lymphoma subtype. These specific associations can provide important information about abnormal B-cell stimulation in these conditions. Patients with primary SS, SLE and RA are at high risk of developing diffuse large B-cell lymphomas, a group of high-grade NHLs with remarkable heterogeneity. Patients with primary SS are at particularly high risk of developing marginal-zone B-cell lymphomas. The risk factors of lymphoma development in primary SS seem to be closely related to the underlying mechanisms of abnormal stimulation and/or impaired censoring mechanisms of B cells. In patients with RA and SLE, more intense disease activity and/or long-lasting disease might be indications of a higher risk of lymphoma development. This Review will focus on the risk of lymphoma, common and disease-specific mechanisms of B-cell lymphoma development, and on the clinical consequences of lymphoma in patients with inflammatory rheumatic diseases.
17897055 Macrophage migration inhibitory factor: a therapeutic target across inflammatory diseases. 2007 Sep Macrophage migration inhibitory factor (MIF), a cytokine originally reported in the 1960s as the prototypic T lymphokine, has emerged in recent years as a key factor regulating inflammatory responses. Both by directly activating immune cells, and by participating in activation entrained by other stimuli, MIF is important in innate and adaptive immune responses as well as tissue-specific mechanisms of damage. As a consequence of its involvement in multiple stages of the immune-inflammatory response, MIF has the potential to be involved in the pathogenesis of a range of immune-mediated inflammatory diseases affecting multiple organ systems. Diseases in which a role for MIF has been strongly validated include rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, atherosclerosis, asthma, inflammatory liver disease, and most recently systemic lupus erythematosus. Recent data have provided mechanisms of action for MIF which further support its suitability as a therapeutic target. Finally, MIF has a unique relationship with glucocorticoids, acting to counter-regulate their anti-inflammatory effects, such that MIF antagonist therapy may be a direct route to 'steroid-sparing'. Methods of targeting MIF therapeutically have also emerged in recent years, based on the unique protein structure of MIF which affords opportunities for direct antagonism by small molecules, as well as by protein therapeutics such as monoclonal antibodies. Clinical trials of MIF antagonist therapies are likely before the end of the current decade.
17598662 [The case of multiple brain abscesses conservatively treated]. 2007 Feb We report the case of patient with rheumatoid arthritis treated by sulfasalazin. He was hospitalized because of general erythrodermia and diarrhoea with dysproteinemia. The consciousness disturbances and the meningitis syndrome occured in the course of disease. The findings of cerebrospinal fluid suggested viral meningitis and encephalitis. The treatment was started. After short-term improvement, the focal neurological deficits and the consciousness disturbances appeared again. The examinations of the computed tomography and the magnetic resonance image suggested inflammatory or neoplasmatic process. The inflammatory process seemed to be more probable and antibiotic treatment was administered. The following CT and MRI findings confirmed inflammatory changes of brain tissue and abscess formation tendency. After the neurosurgeon consultation the conservatively treatment was continued. The 2 month therapy achieved a successful outcome. We report this case because of the difficulties of diagnostic and treatment choices and the 50% mortality connected with the multiple brain abscesses. It seems that in our case the bacterial infection was secondary to the viral encephalomeningitis. We couldn't find the primary focus of bacterial infection, although the infection cause was undoubtedly hematogenous (abscesses location on the boundaries of cerebral cortex and white matter). There is no evident therapeutic standards and the choice of the best treatment is still under discussion. However, neuroimagining techniques are very useful in the correct diagnosis and optimal treatment.
17532798 An immunohistochemical study of the triangular fibrocartilage complex of the wrist: region 2007 Jul The triangular fibrocartilage complex (TFCC) transmits load from the wrist to the ulna and stabilizes the distal radioulnar joint. Damage to it is a major cause of wrist pain. Although its basic structure is well established, little is known of its molecular composition. We have analysed the immunohistochemical labelling pattern of the extracellular matrix of the articular disc and the meniscal homologue of the TFCC in nine elderly individuals (age range 69-96 years), using a panel of monoclonal antibodies directed against collagens, glycosaminoglycans, proteoglycans and cartilage oligomeric matrix protein (COMP). Although many of the molecules (types I, III and VI collagen, chondroitin 4 sulphate, dermatan sulphate and keratan sulphate, the oversulphated epitope of chondroitin 6 sulphate, versican and COMP) were found in all parts of the TFCC, aggrecan, link protein and type II collagen were restricted to the articular disc and to entheses. They were thus not a feature of the meniscal homologue. The shift in tissue phenotype within the TFCC, from a fibrocartilaginous articular disc to a more fibrous meniscal homologue, correlates with biomechanical data suggesting that the radial region is stiff and subject to considerable stress concentration. The presence of aggrecan, link protein and type II collagen in the articular disc could explain why the TFCC is destroyed in rheumatoid arthritis, given that it has been suggested that autoimmunity to these antigens results in the destruction of articular cartilage. The differential distribution of aggrecan within the TFCC is likely to be reflected by regional differences in water content and mobility on the radial and ulnar side. This needs to be taken into account in the design of improved MRI protocols for visualizing this ulnocarpal complex of the wrist.