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ID PMID Title PublicationDate abstract
19292412 Wound necrosis after total knee arthroplasty. 2008 Aug Quickly evolutive skin necrosis and deep infection after total knee arthroplasty (TKA) are not uncommon. Several predisposing factors, such as immunosuppression, malnutrition, steroid use, rheumatoid arthritis, multiple scars, and vascular disease can be involved in the onset of wound complications, as well as long tourniquet time and early knee flexion. Skin necrosis after TKA can be treated in different ways, including local wound care, debridement, and soft tissue coverage with muscle or skin grafts. This article presents a rare case of skin necrosis occurring in a patient without any other apparent risk factor after TKA. A 78-year-old woman affected by primary osteoarthritis of the right knee who had no comorbidities and who had already undergone TKA for primary osteoarthritis on the left knee underwent a cemented TKA. Three days postoperatively, she developed a fever and wound problems, which soon after turned into skin necrosis. This complication was first treated surgically with a debridement of the wound with antibiotic therapy and local wound care, then with vacuum-assisted closure (Kinetic Concepts Inc, San Antonio, Texas) therapy and soft tissue coverage using skin grafting. She had a complete recovery in the next 3 months; the skin grafting was well tolerated and the range of motion and functional outcome were good.
19084694 [Wells' cellulitis and bacterial necrotizing cellulitis induced by anakinra]. 2008 Dec BACKGROUND: Anakinra is a recombinant form of the naturally occurring human interleukin-1 receptor antagonist. It is used in the treatment of rheumatoid arthritis. The most frequent side effects are injection site reactions, which seem to have a toxic mechanism. PATIENTS AND METHODS: We report two unusual cases of injection site reactions with anakinra: a woman presented Wells' cellulitis of the thigh and a man developed serious bacterial cellulitis distinguished by deep necrosis at the site of the latest anakinra subcutaneous injection. DISCUSSION: The cases are examples of serious side effects that can occur during treatment with anakinra and underline the need for careful use of this new biological agent.
19053834 Engineering stabilized vascular endothelial growth factor-A antagonists: synthesis, struct 2008 Dec 25 Cyclotides are plant derived mini-proteins with compact folded structures and exceptional stability. Their stability derives from a head-to-tail cyclized backbone coupled with a cystine knot arrangement of three-conserved disulfide bonds. Taking advantage of this stable framework we developed novel VEGF-A antagonists by grafting a peptide epitope involved in VEGF-A antagonism onto the stable cyclotide framework. Antagonists of this kind have potential therapeutic applications in diseases where angiogenesis is an important component of disease progression, including cancer and rheumatoid arthritis. A grafted analogue showed biological activity in an in vitro VEGF-A antagonism assay at low micromolar concentration and the in vitro stability of the target epitope was markedly increased using this approach. In general, the stabilization of bioactive peptide epitopes is a significant problem in medicinal chemistry and in the current study we have provided insight into one approach to stabilize these peptides in a biological environment.
18930854 Solubility and dissolution improvement of Rofecoxib using solid dispersion technique. 2008 Oct Rofecoxib (RXB) is a potent and selective cyclo-oxygenase-2 (COX-2) inhibitor, highly effective in the treatment of various pains, inflammatory condition, post-operative pain, rheumatoid arthritis, other musculo-skeletal and joint disorders. Although they are completely absorbed upon oral administration, the peak plasma concentration is reached 2-3 hours after oral ingestion. The reason for delay being slow rate of absorption due to poor aqueous solubility. An attempt has been made to enhance solubility and dissolution of rofecoxib by solid dispersion(SD) technique using various hydrophilic excipients like PEG 4000, PEG 6000, PVP at different ratios by melting method and solvent evaporation method. The prepared SD of RXB were characterized to various physico-chemical properties and in vitro drug dissolution studies in 0.1N HCl with 0.25% SLS (pH 1.1) media for a period of 90 min using USP XXIII electro lab 8 basket tab dissolution test apparatus using paddle. The result of study indicated that there was no drug-polymer interaction found. The drug dissolution was found to enhance percent in PEG 4000, PEG 6000 and PVP, after 90 mins of dissolution study 79.02%, 88.02%, 98.57% respectively. On comparison of various polymers used at varied concentrations PVP at 75:25 ratio by fusion method was found to be best suitable for the enhancement of dissolution and solubility of RXB.
18728615 Endoscopic transnasal transclival odontoidectomy: a new approach to decompression: technic 2008 Jul OBJECTIVE: Endoscopic transnasal transclival resection of the odontoid process is less invasive than the standard transoral odontoidectomy. In this article, we describe our techniques, which are less invasive but provide successful decompression. CLINICAL PRESENTATION: From September 2004 to April 2007, three consecutive patients with basilar invagination and instability in the craniovertebral junction were enrolled. The causes for the invagination and instability included rheumatoid arthritis in two patients and trauma in one patient, and all patients presented with myelopathy and quadriparesis before intervention. INTERVENTION: All three patients underwent an endoscopic transnasal transclival approach for anterior decompression and resection of the displaced odontoid process and pannus to decompress the underlying medulla. Subsequently, they received occipitocervical fixation by lateral mass screws and bone fusion to ensure stability. Remarkable neurological recovery was observed after surgery in all patients, and no adverse effects were noted. CONCLUSION: Compared with the standard transoral approach, the transnasal transclival endoscopic approach for decompressing basilar invagination is a feasible and effective alternative that avoids common disadvantages like prolonged intubation, excessive tongue retraction, and the need for palatal incision.
18694850 Treatment of rheumatic diseases in patients with HCV and HIV infection. 2008 Dec A wide variety of rheumatic diseases has been documented in the presence of hepatitis C virus (HCV) infection and in human immunodeficiency virus (HIV) infection. In this conditions, physicians are refrained from using corticosteroids and/or immunosuppressants agents because of the risk of favouring viral replication and the progression of the underlying viral disease. In the present review we have focused our attention on the possible role of cyclosporine A (CsA), anti-Tumour Necrosis Factor (TNF) alpha agents in the treatment of HIV or HCV infected autoimmune patients. The results drown from the literature and from our personal experience confirm the safety of CsA and anti-TNF alpha agents, in terms of viral load and liver toxicity. A limited experience also suggest that both therapies can be given in combination in rheumatoid arthritis patients without increasing the risk of adverse events.
18556968 Insulin receptor autoimmunity and insulin resistance. 2008 Apr The frequency of insulin receptor autoantibodies (IR-ab) was determined among adolescents and young adults with documented insulin resistance syndrome (IRS) with and without concomitant autoimmunity. The study population was comprised of 61 patients with obesity, acanthosis nigricans and insulin resistance (simple IRS); 12 with IRS and other autoimmune problems (lupus erythematosus, rheumatoid arthritis, dermatomyositis) (type B insulin resistance); six with autoimmune polyglandular syndrome type 2; and 40 healthy controls. Using our newly developed radiobinding assay system, we found no control positive while 25% of the patients with type B IRS (3/12) were positive, as expected. However, we found that 9.8% of the patients with simple IRS (6/61) were also reproducibly positive. All the latter patients with positive IR-ab were female with ovarian hyperandrogenism. The phenotype of those affected was otherwise unremarkably different from those without IR-ab. Our findings suggest that autoimmunity to insulin receptors may be causal in IRS especially for females with ovarian hyperandrogenism, and that IR-ab may be found in IRS besides those previously defined by the type B phenotype. Determining the level of IR-ab in childhood onset IRS may provide mechanistic insights into the genesis of insulin resistance and lead to novel treatment approaches.
18537779 Limb-length measurement in total hip arthroplasty using a calipers dual pin retractor. 2008 BACKGROUND: Limb-length inequality is not uncommon after total hip arthroplasty (THA) and may cause subjective problems for patients. During THA a stable reference point must be established to determine changes in leg length. Several methods have been useful in minimizing the incidence and magnitude of this problem. The equalization of leg-length discrepancy during THA can be achieved through the use of a simple measuring device, the calipers dual pin retractor (CDPR). MATERIALS AND METHODS: The CDPR was developed to establish a fixed point on the pelvis that would remain constant throughout the procedure and from which the distance to the greater trochanter could be measured prior to dislocation of the hip. Limb lengths were measured in 56 patients undergoing primary THA, between 2004 and 2006. The CDPR was used in all cases. RESULTS: The preoperative diagnoses were osteoarthritis in 44 patients, osteonecrosis in five, and rheumatoid arthritis in seven. Average postoperative limb-length inequality was 4.2 mm. None of the patients had to use shoe lifts for equalization of limb lengths or complained of limb-length inequality. CONCLUSION: This method of measurement is beneficial with most THA approaches, and the technique is helpful for minimizing limb-length inequality during THA.
18508462 Dipeptidyl peptidase IV (DPP IV) and related molecules in type 2 diabetes. 2008 May 1 Dipeptidyl peptidase IV (DPP IV) is a widely distributed physiological enzyme that can be found solubilized in blood, or membrane-anchored in tissues. DPP IV and related dipeptidase enzymes cleave a wide range of physiological peptides and have been associated with several disease processes including Crohn's disease, chronic liver disease, osteoporosis, multiple sclerosis, eating disorders, rheumatoid arthritis, cancer, and of direct relevance to this review, type 2 diabetes. Here, we place particular emphasis on two peptide substrates of DPP IV with insulin-releasing and antidiabetic actions namely, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). The rationale for inhibiting DPP IV activity in type 2 diabetes is that it decreases peptide cleavage and thereby enhances endogenous incretin hormone activity. A multitude of novel DPP IV inhibitor compounds have now been developed and tested. Here we examine the information available on DPP IV and related enzymes, review recent preclinical and clinical data for DPP IV inhibitors, and assess their clinical significance.
18503132 Plasma viscosity: a forgotten variable. 2008 Evaluation of plasma viscosity has been underutilized in the clinical practice. Plasma viscosity is determined by water-content and macromolecular components. Plasma is a highly concentrated protein solution, therefore weak protein-protein interactions can play a role that is not characterized by electrophoresis. The effect of a protein on plasma viscosity depends on its molecular weight and structure. The less spheroid shape, the higher molecular weight, the higher aggregating capacity, and the higher temperature or pH sensitivity a protein has, the higher plasma viscosity results. Plasma is a Newtonian fluid, its viscosity does not depend on flow characteristics, therefore it is simple to measure, especially in capillary viscosimeters. Its normal value is 1.10-1.30 mPa s at 37 degrees C and independent of age and gender. The measurement has high stability and accuracy, thus little alterations may be pathologically important. Inflammations, tissue injuries resulting in plasma protein changes can increase its value with high sensitivity, though low specificity. It can increase in parallel with erythrocyte sedimentation rate (ESR), but it is not influenced by hematocrit (anemia, polycytemia), or time to analysis. Based on these favorable features, in 1942 plasma viscosity was recommended to substitute ESR. In hyperviscosity syndromes plasma viscosity is better in follow-up than ESR. In rheumatoid arthritis, its sensitivity and specificity are better than that of ESR or C-reactive protein. Plasma fibrinogen concentration and plasma viscosity are elevated in unstable angina pectoris and stroke and their higher values are associated with higher rate of major adverse clinical events. Elevation of plasma viscosity correlates to the progression of coronary and peripheral artery diseases. In conclusion, plasma viscosity should be measured routinely in medical practice.
18431583 [Longitudinal effects of structured patient education programs for vasculitis patients]. 2008 May According to the literature it is known that structured standardized patient education represents an effective additional treatment in patients with chronic diseases. Positive effects in the reduction of disease activity and depression have been shown for rheumatoid arthritis, systemic lupus erythematodes, and diabetes mellitus. An interdisciplinary approach for providing information was developed for patients with primary systemic vasculitides (PSV) in the vasculitis center in Bad Bramstedt. The contents of the seminars were revised and condensed into five modules. To evaluate the new form of the program a documentation system was designed. Patients were trained in closed groups (n=10-15) and completed the questionnaires at baseline, 4 weeks, 6 and 12 months following participation. A total of 102 patients in 10 closed groups showed a statistically significant increase in their knowledge in the three aspects of medicine, therapy and side effects, nutrition and physiotherapy. Health-related quality of life in all dimensions increased considerably. Both self-efficacy and the patient-assessed health status improved. The standardized structured education program for vasculitis patients provides an additional treatment in the interdisciplinary care of vasculitis.
18361936 Association of MYO9B haplotype with type 1 diabetes. 2008 Feb MYO9B (myosin IXB) polymorphisms were associated with celiac disease and ulcerative colitis susceptibility, presumably through alteration of the intestinal permeability. Recently this gene was also associated with several diseases with an autoimmune component, such as rheumatoid arthritis and systemic lupus erythematosus. We aimed to test, for the first time, the potential role of MYO9B polymorphisms in type 1 diabetes (T1D), an autoimmune condition preceded by changes in intestinal barrier integrity. Three previously associated MYO9B polymorphisms (rs962917, rs2279003, and rs2305764) were studied in 316 T1D patients and 706 ethnically matched controls. Minor alleles of those polymorphisms were more frequent in diabetic patients than in controls and the haplotype carrying major alleles in those positions, rs962917*G/rs2279003*C/rs2305764*G, significantly reduced the risk of T1D in the Spanish population (p = 0.004; OR [95% confidence interval] = 0.68 [0.52-0.90]). Our data suggest an involvement of this MYO9B chromosomal region in T1D predisposition, indicating extensive influence on autoimmune diseases.
18334181 [Kinoids: a novel generation of specific immune therapy against cytokines]. 2008 Mar The abnormal cytokine release in the stromal microenvironment of pathologic tissues, contributes to the pathogenesis of viral infections such as AIDS, cancer and auto-immune diseases. Neovacs developed therapeutic vaccines, named Kinoids, which induce anti-cytokine Antibodies. Kinoids are non toxic but immunogenic cytokine derivatives. Kinoid immunizations induce high titre of neutralizing Abs to the corresponding cytokine, is well tolerated and experimentally effective. In transgenic mice expressing huTNFalpha, the TNFalpha kinoid decreases clinical signs of Rheumatoid Arthritis and in mice challenged with syngenic CT26 tumor cell line huVEGF kinoid inhibits lung metastases. After validation by clinical trials, kinoid vaccines could represent a second generation of specific immune therapy to be used to combat ectopic cytokines.
18314371 Endothelial progenitor cells and rheumatic disorders. 2008 Mar In human adults, new blood vessels may form via endothelial sprouting from pre-existing endothelial cells/angioblasts (angiogenesis) or via the recruitment of circulating endothelial progenitor cells (EPCs) (vasculogenesis). EPCs are a population of bone marrow-derived cells able to differentiate into mature endothelial cells and participating in the formation of new blood vessels. The molecular phenotype of EPCs and processes leading to their mobilization from bone marrow and homing to neovascularization sites remain unclear. There is still debate regarding methods for their quantification and isolation. In the field of rheumatology, EPCs have been studied in multiple myeloma and inflammatory rheumatic disorders. In myeloma, data suggest that EPCs could be reliable biomarkers of tumor angiogenesis, growth and antiangiogenic therapy efficacy. Recent studies suggest that EPCs are involved in synovial vascularization, and may contribute to the increased cardiovascular morbidity and mortality in rheumatoid arthritis, known features of this disease. In systemic lupus erythematosus, preliminary data suggest that EPCs are decreased. Results available in systemic sclerosis are consistent with the hypothesis that EPCs are recruited during active disease; however, their levels may be depleted as the disease progresses and under chronic ischemic conditions. EPCs are important in vasculogenesis, and may be involved in other systemic features of inflammatory rheumatic disorders.
18294265 Development of Crohn's disease following anti-tumour necrosis factor therapy (etanercept). 2008 Nov Inhibition of tumour necrosis factor (TNF)-alpha is effective in the treatment of rheumatoid arthritis and other inflammatory rheumatic diseases. Anti-TNF antibodies such as infliximab, etanercept and adalimumab are commonly used. There are structural and functional differences among these agents. We describe development of Crohn's disease in a patient with ankylosing spondylitis receiving anti-TNF therapy. This case suggests that the appearance of gastrointestinal symptoms in patients on anti-TNF therapy must be evaluated to find out whether this is a new onset or an exacerbation of underlying inflammatory bowel disease.
18289518 Leptin beyond body weight regulation--current concepts concerning its role in immune funct 2008 Mar Leptin, a 16 kDa non-glycosylated polypeptide produced primarily by adipocytes and released into the systemic circulation, exerts a multitude of regulatory functions including energy utilization and storage, regulation of various endocrine axes, bone metabolism, and thermoregulation. In addition to leptin's best known role as regulator of energy homeostasis, several studies indicate that leptin plays a pivotal role in immune and inflammatory response. Because of its dual nature as a hormone and cytokine, leptin can be nowadays considered the link between neuroendocrine and immune system. The increase in leptin production that occurs during infections and inflammatory processes strongly suggests that this adipokine is a part of the cytokines network which governs inflammatory/immune response and host defence mechanisms. Indeed, leptin plays a relevant role in inflammatory processes involving either innate or adaptive immune responses. Several studies have implicated leptin in the pathogenesis of autoimmune inflammatory conditions such as encephalomyelitis, type I diabetes, bowel inflammation and also articular degenerative diseases such as rheumatoid arthritis and osteoarthritis. Although the mechanisms by which leptin exerts its action as modulator of inflammatory/immune response are likely to be more complex than predicted and far to be completely depicted, there is a general consensus about its pivotal role as pro-inflammatory and immune-modulating agent. Here, we review the most recent advances on leptin biology with a particular attention to its adipokine facet, even though its role as metabolic hormone will be also addressed.
18216569 Therapeutic keratoplasty for corneal perforation: clinical results and complications. 2008 Feb PURPOSE: To report the clinical results, postoperative progress, and complications after therapeutic keratoplasty for corneal perforation. METHODS: Twenty consecutive eyes (20 patients) that underwent therapeutic keratoplasty between December 2003 and May 2006 were included. The eyes were evaluated retrospectively for the cause of the corneal perforation, the type of surgical technique and intraoperative complications, anatomic cure rates, graft clarity, visual prognosis, and postoperative complications. RESULTS: The causes of corneal perforation were herpetic keratitis (n = 5), bacterial ulcer (n = 1), fungal ulcer (n = 1), neurotrophic ulcer (n = 3), rheumatoid arthritis (n = 2), Mooren ulcer (n = 2), Terrien marginal corneal degeneration (n = 1), keratoconus (n = 1), and Wegener granulomatosis (n = 1). In 3 cases, the etiology was unknown. Six cases had a previous history of corneal transplantation. Anatomic cures were obtained in 16 (80%) of 20 eyes after the first transplantation procedure. Visual acuity (VA) equal to or better than the preoperative level was achieved in 17 (85%) of 20 eyes. The graft transparency rate was 67% in 15 eyes that underwent central penetrating keratoplasty with fresh donor tissue. Major postoperative complications included cataract (n = 6), glaucoma (n = 4), and recurrent disease (n = 3). CONCLUSIONS: Keratoplasty is valuable for maintaining the ocular integrity and VA. In cases with severe preoperative inflammation of the anterior segment, it is difficult to achieve transparency after the first graft.
18207621 Gold stimulates Ca2+ entry into and subsequent suicidal death of erythrocytes. 2008 Feb 28 The suicidal death of erythrocytes, eryptosis, is characterized by cell shrinkage and cell membrane scrambling leading to phosphatidylserine exposure at the erythrocyte surface. Erythrocyte cell membrane scrambling is stimulated by increase of cytosolic Ca2+ concentration ([Ca2+](i)) and formation of ceramide. Phosphatidylserine (PS) exposing cells are rapidly cleared from circulating blood. Ca2+ entry and/or ceramide formation and thus eryptosis are triggered by lead, mercury, aluminium, and copper ions. The present study explored whether eryptosis could be similarly triggered by exposure to gold. To this end, erythrocytes from healthy volunteers were exposed to AuCl and phosphatidylserine exposure (annexin V binding), cell volume (forward scatter), [Ca2+](i) (Fluo3-dependent fluorescence), and ceramide formation (anti-ceramide-FITC fluorescence) were determined by flow cytometry. Exposure of erythrocytes to low concentrations of AuCl (> or =0.75microg/ml) increased [Ca2+](i) but did not affect ceramide formation. AuCl at concentrations > or =0.5microg/ml significantly increased the number of PS exposing erythrocytes and decreased forward scatter at low concentrations of AuCl pointing to cell shrinkage. Aurothiomalate (> or =1microg/ml), a gold containing drug effective against rheumatoid arthritis, similarly triggered PS exposure of erythrocytes. The present observations disclose a novel action of gold, which may well contribute to side effects during treatment with gold preparations.
18165173 Ex vivo measurement of calpain activation in human peripheral blood lymphocytes by detecti 2007 Limited proteolysis of multiple intracellular proteins by endogenous Ca-dependent cysteine proteases--calpains--is an important regulatory mechanism for cell proliferation, apoptosis etc. Its importance for cellular functions is stressed by existence of endogenous calpain inhibitors--calpastatins. The calpain-calpastatin system within living cells is in a fragile balance, which depends on both partners. The interdependence of calpain--a protease--and calpastatin--an endogenous inhibitor and at the same time a substrate for this enzyme makes any assessment of actual activity of this enzyme in the cells very difficult. In this work we made an attempt to estimate and compare the activity of calpain in human peripheral blood lymphocytes by assessing the levels of limited proteolysis of calpastatin in these cells by western blot, while at the same time the levels of calpain protein inside these cells was measured by flow cytometry. Our results indicate that it is possible to compare (semi-quantitatively) the activities of calpain in peripheral blood CD4+ and CD19+ lymphocytes from various donors that way. Preliminary results showed that calpain activity is increased in the CD4+ T cells isolated from peripheral blood of rheumatoid arthritis patients as compared to control lymphocytes. Extremely high intrinsic activity of calpain was detected in chronic lymphocytic leukemia (CD19+) cells. All this confirms the detection of immunoreactive products of calpastatin as a good maker of endogenous calpain activity.
18021515 Disease-specific quality indicators, guidelines, and outcome measures in systemic lupus er 2007 Nov The assessment of quality of care is becoming increasingly important, but as yet no standard set of measures to assess quality has been developed. The ACR Quality Measures Committee has selected the following areas of study to develop quality indicators: diagnostic/classification criteria, outcome measures/response criteria, treatment guidelines/management recommendations, definition of quality indicators, and definition of data collection systems. The aim of the present review is to evaluate existing guidelines and outcome measures concerning disease/activity monitoring, autoantibody and laboratory assessment, outcomes, and therapy in systemic lupus erythematosus (SLE) that could be used to define disease-specific quality indicators. Much data is available in the literature that could serve to define a starter set of quality indicators for SLE. Monitoring issues are discussed in the ACR and EULAR recommendations. As far as therapy is concerned, the ACR has provided indicators for rheumatoid arthritis that could also be applied to SLE, as well as indications for anti-malarial monitoring. The outcomes measures most frequently used in SLE are damage and death, but organ-specific definitions of outcome and response are being evaluated. The development of quality measures for SLE is just beginning; existing information could serve to construct a starter set of indicators such as the one proposed here. Certainly much progress will be made in the near future. A practical, user-friendly tool for physicians that will help them deliver high quality care to populations is also needed.