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ID PMID Title PublicationDate abstract
17888600 Preventive effect of Ophiopogon japonicus polysaccharides on an autoallergic mouse model f 2007 Nov 1 AIM OF STUDY: Sjogren's syndrome (SS) is an autoimmune disorder characterized by lymphocytic infiltration of salivary and lacrimal glands leading to xerostomia and keratoconjunctivitis sicca. Evidence has accumulated suggesting that a Th1/Th2 cytokine imbalance has a role in the pathogenesis of SS. Currently, only palliative treatment is available. Ophiopogon japonicus, a common Chinese herbal, has been used to treat sicca-associated disorders in traditional Chinese medicine for centuries. MATERIALS AND METHOD: In this study, we constructed an autoallergic mouse model for SS by immunizing C57BL/6 mouse with submandibular gland (SMG) autoantigen. At the same time, Ophiopogon japonicus polysaccharides (OJP) was administered and hydroxychloroquine was served as positive control. During the 4 weeks' experiment, salivary flow rates were determined every week, body weight, food and water intake were measured every 2 days. After death, serum were collected for IFN-gamma and IL-4 ELISA analysis and the IFN-gamma/IL-4 was calculated, SMG and spleen were harvested for organ index calculation, and part of SMG was examined for histological changes. RESULTS: Results showed that immunization with SMG autoantigen induced decreased salivary flow and body weight, increased water intake, SMG index, spleen index, IFN-gamma level and IFN-gamma/IL-4 ratio compared with the normal group. However, administration of the OJP could improve these data and the pathological changes of SMG with respect to the model mice, especially the high-dose of OJP group. CONCLUSIONS: Thus, this study provided a basis for the use of Ophiopogon japonicus in SS.
17703372 Parotid gland involvement, the presenting sign of high grade non-Hodgkin lymphoma in two p 2007 Oct Increased risk of haematological malignancies has been described in Gaucher disease patients; however, high-grade lymphoma has been rarely observed. We report two patients with Gaucher disease and sicca syndrome diagnosed with aggressive lymphoma involving the parotid gland. A 29-year-old woman with Gaucher disease developed tumour of the left parotid gland. She reported chronic arthralgias, xerostomia and xerophthalmia. Parotid gland biopsy disclosed diffuse large B-cell lymphoma. No lymphadenopathy was found. Bone biopsy revealed focal lymphomatous infiltration consistent with stage IV disease. MACOP-B chemotherapy regimen (cyclophosphamide, adriamycin, methotrexate, bleomycin, vincristine, prednisone) resulted in complete remission for 15 years. A 76-year-old patient with Gaucher disease suffered from dry-mouth feeling. He developed a left parotid gland tumour. CT scan disclosed diffuse lymphadenopathy, pleural effusion and multiple lung nodules. A cervical lymph node biopsy revealed mantle cell lymphoma. Fine-needle aspiration of the parotid gland showed lymphoma cells. Immunochemotherapy with fludarabine, cyclophosphamide and rituximab resulted in complete remission. Accumulation of the glucocerebroside in Gaucher disease activates macrophages, inducing release of pro-inflammatory cytokines which may be involved in the pathogenesis of second malignancy. Patients with Gaucher disease bear an increased risk of haematological malignancies; however, aggressive lymphoma has been described only occasionally. In both our patients the presenting sign of lymphoma was tumour of the parotid gland. The patients suffered from sicca syndrome, which increases risk for developing lymphoma. The underlying Gaucher disease and sicca syndrome might be implicated as immunological triggers for lymphoma occurrence and its propensity for the parotid gland in these patients.
17417148 [A new approach for better comprehension of diseases of the ocular surface]. 2007 Mar The mechanistic view of dry eye disease aims at completing the classic etiological approach that classifies the disease as parallel ocular surface disorders leading to lacrimal film impairment and dry eye. This approach proposes two levels of ocular surface impairment (with standard etiologies, previously validated in the NEI/Industry workshop), which may not be independent diseases but rather risk factors and/or ways to enter a self-stimulated biological process involving the ocular surface. All external disorders proposed in this model, although unlikely to be fully exhaustive, are classical mechanisms considered to be causes of tear film impairment and ocular surface damage, by tear instability and evaporation, tear hyposecretion, or both. These mechanisms, sometimes alone--when severe or becoming chronic or repeatedly present on the ocular surface and when two or more are present--may cause the patient to enter the self-stimulated loop. Tear film instability/imbalance can be considered as the key point of dry eye disease. It will cause local or diffuse hyperosmolarity of the tear film and therefore of superficial epithelial cells of the cornea and/or conjunctiva, stimulating epithelial cells and resident inflammatory cells. Cell damage in the cornea and conjunctiva, by means of apoptosis and direct mechanical and/or osmotic stress, will stimulate the reflex neurosensory arc, in turn stimulating lacrimal gland and neurogenic inflammation, with inflammatory cytokine release, MMP activation, and inflammatory involvement of the conjunctival epithelium. Goblet cell loss is thus directly related to chronic inflammation and surface cell apoptosis subsequent to cell hyperosmolarity and chronic damage, resulting in further tear film instability/imbalance. On the other hand, bacterial changes and an imbalance resulting from specific diseases or from tear film abnormalities may trigger release of endotoxins, lipopolysaccharides, and/or lipase activation, causing eyelid inflammation, meibomian gland dysfunction, and lipidic changes, directly influencing tear film stability and favoring tear evaporation. The lipidic hypothesis therefore participates in the vicious circle as a parallel, independent, or complementary loop. This mechanistic approach proposes a synthetic combination of mechanisms previously validated independently, with two levels of ocular surface impairment, a first level including many possible acute or chronic causes that favor or trigger the imbalance and can be reversible if correctly and specifically managed when possible, and the further involvement of a series of biological cascades centered by tear film imbalance and inflammatory stimulation, finally acting as an independent vicious circle, however the patient entered the loop. Clinically, this approach may explain examples of dry eye syndrome occurring after ocular surgery, contact lens wear, chronic allergy or systemic or topical drugs, and the long-lasting effect even though all causal factors have been removed or have disappeared. This model should be considered as a basis for further reflection on biological mechanisms that could be even more complex but individually constitute potential leads for targeting therapeutic strategies to allow patients to leave the loop even though the triggering factors are still present or can only be attenuated, such as in Sjögren syndrome or ocular rosacea. It also should be considered a complement to more classic etiological and severity classifications aimed at understanding and classifying the large number of diseases that may cause dry eye disease and better assessing the major impairment it causes on the patient's quality of life.
18384647 Permeation of blood-borne IL15 across the blood-brain barrier and the effect of LPS. 2008 Jul Interleukin15 (IL 15) is a proinflammatory cytokine with elevated concentrations in autoimmune diseases involving the periphery (e.g. rheumatoid arthritis) and CNS (e.g. multiple sclerosis). Its interactions with the blood-brain barrier (BBB) were studied in normal and lipopolysaccharide (LPS)-treated mice. (125)I-IL15 remained intact for at least 10 min after i.v. injection and reached CNS parenchyma with regional differences between brain and spinal cord. Both in vivo and in situ brain perfusion of (125)I-IL15 showed that its permeation of the BBB was non-saturable. LPS induced a significant increase of IL15 uptake by the brain and spinal cord, partly related to a higher general permeability of the BBB. The results suggest that the BBB is an interface for blood-borne IL15 to interact with the CNS in the basal state and during inflammation.
16331857 TNF blockade: an inflammatory issue. 2006 Tumor necrosis factor (TNF), initially discovered as a result of its antitumor activity, has now been shown to mediate tumor initiation, promotion, and metastasis. In addition, dysregulation of TNF has been implicated in a wide variety of inflammatory diseases including rheumatoid arthritis, Crohn's disease, multiple sclerosis, psoriasis, scleroderma, atopic dermatitis, systemic lupus erythematosus, type II diabetes, atherosclerosis, myocardial infarction, osteoporosis, and autoimmune deficiency disease. TNF, however, is a critical component of effective immune surveillance and is required for proper proliferation and function of NK cells, T cells, B cells, macrophages, and dendritic cells. TNF activity can be blocked, either by using antibodies (Remicade and Humira) or soluble TNF receptor (Enbrel), for the symptoms of arthritis and Crohn's disease to be alleviated, but at the same time, such treatment increases the risk of infections, certain type of cancers, and cardiotoxicity. Thus blockers of TNF that are safe and yet efficacious are urgently needed. Some evidence suggests that while the transmembrane form of TNF has beneficial effects, soluble TNF mediates toxicity. In most cells, TNF mediates its effects through activation of caspases, NF-kappaB, AP-1, c-jun N-terminal kinase, p38 MAPK, and p44/p42 MAPK. Agents that can differentially regulate TNF expression or TNF signaling can be pharmacologically safe and effective therapeutics. Our laboratory has identified numerous such agents from natural sources. These are discussed further in detail.
17081464 [Influence of preoperative range of motion on the early clinical outcome of total knee art 2006 Aug 15 OBJECTIVE: To retrospectively analyze the influence of preoperative range of motion (ROM) and maximal flexion degree on the early clinical outcome of total knee arthroplasty (TKA). METHODS: From January 2000 to December 2003, 97 knees of 65 patients that were underwent total knee arthroplasty with Scorpio posterior-stabilized knee prosthesis were reviewed. There were 55 osteoarthritis patients (81 knees), and 10 rheumatoid arthritis (16 knees). Thirty-three patients were underwent unilateral TKA, 32 patients were underwent bilateral TKA. According to the preoperative ROM of knee, these patients were divided into two groups, one 90 degrees (range, 95 degrees - 140 degrees ). Finally the clinical outcomes of two groups (include ROM, maximal flexion degree, KSS score and function score) were evaluated. Three days later after operation, continuous passive motion (CPM) and active functional exercise of the knee were begun, and the wound healed well in all patients. All these operations were primary total knee arthroplasty. RESULTS: The patients were followed up for average 2 years 5 months (range, 10 months to 3 years 8 months). The average ROM of knee was improved to 101.6 degrees (range, 40 degrees - 140 degrees ) after operation from 84.2 degrees (range, 5 degrees - 140 degrees ) before operation (P = 0.000); the average maximal flexion degree was decreased from 103.5 degrees (range, 25 degrees - 140 degrees ) before operation to 101.6 degrees (range, 40 degrees - 140 degrees ) after operation (P = 0.439); KSS of knee joint was improved to 78.8 points after operation (range, 50 - 95 points) from 19.5 points (-24 - 62 points) before operation (P = 0.000). There was statistically difference between the clinical outcomes (ROM, maximal flexion degree, KSS score and function score) in the two groups before and after operation. Those knees with good preoperative ROM tend to lose flexion, while those with poor preoperative ROM gain flexion after TKA. No revision and deep infection happened. CONCLUSIONS: TKA is a complex operation, the clinical outcome of TKA is mainly determined by the good operation skill, abundant clinical experience and the familiarity with the prosthesis of the surgeon. At the same conditions such as same surgeon, same prosthesis and same physical therapy, preoperative range of motion of knee influence on the early clinical outcome of total knee arthroplasty, knees that have good preoperative ROM have better clinical outcomes postoperatively than those with poor preoperative ROM.
16879746 Characterisation of the immune response to type I collagen in scleroderma. 2006 This study was conducted to examine the frequency, phenotype, and functional profile of T lymphocytes that proliferate in response to type I collagen (CI) in patients with scleroderma (SSc). Peripheral blood mononuclear cells (PBMCs) from SSc patients, healthy controls, and rheumatoid arthritis disease controls were labeled with carboxy-fluorescein diacetate, succinimidyl ester (CFSE), cultured with or without antigen (bovine CI) for 14 days, and analysed by flow cytometry. Surface markers of proliferating cells were identified by multi-color flow cytometry. T-cell lines were derived after sorting for proliferating T cells (CFSElow). Cytokine expression in CI-responsive T cells was detected by intracellular staining/flow cytometry and by multiplex cytokine bead assay (Bio-Plex). A T-cell proliferative response to CI was detected in 8 of 25 (32%) SSc patients, but was infrequent in healthy or disease controls (3.6%; p = 0.009). The proliferating T cells expressed a CD4+, activated (CD25+), memory (CD45RO+) phenotype. Proliferation to CI did not correlate with disease duration or extent of skin involvement. T-cell lines were generated using in vitro CI stimulation to study the functional profile of these cells. Following activation of CI-reactive T cells, we detected intracellular interferon (IFN)-gamma but not interleukin (IL)-4 by flow cytometry. Supernatants from the T-cell lines generated in vitro contained IL-2, IFN-gamma, GM-CSF (granulocyte macrophage-colony-stimulating factor), and tumour necrosis factor-alpha, but little or no IL-4 and IL-10, suggesting that CI-responsive T cells express a predominantly Th1 cytokine pattern. In conclusion, circulating memory CD4 T cells that proliferate to CI are present in a subset of patients with SSc, but are infrequent in healthy or disease controls.
19111972 Transthoracic ultrasound in the evaluation of pulmonary fibrosis: our experience. 2009 May The purpose of this study was to identify the ultrasonographic features of mild, moderate and severe pulmonary fibrosis. Between December 2005 and November 2007, transthoracic ultrasonography (US) was performed by a single operator with specific training in lung sonography on 84 consecutive patients (51 males and 33 females, aged 46 to 73 y) with pulmonary fibrosis. The obtained data were compared with those from a sample of 162 healthy subjects (78 men and 84 women, aged 18 to 76 y). The disease was idiopathic (biopsy confirmed) in 53/84 cases (63%). In the remaining (all histologically confirmed) cases, it was associated with systemic sclerosis (n = 18), rheumatoid arthritis (n = 4), mixed connective tissue disease (n = 4), Sjogren syndrome (n = 4), polymyositis (n = 2) or primary biliary cirrhosis (n = 1). Disease severity was classified as mild, moderate or severe based on clinical findings and the results of standard chest radiography, high-resolution computed tomography and pulmonary function tests. Pulmonary fibrosis was associated with the following US findings: (1) fragmented, irregular thickening (micro3 mm) of the "pleural line" distributed over the whole surface of the lung, especially in the lower posterior lobe (observed in all 84 patients); (2) subpleural cysts (seen in 57/84 (68%) cases of moderate-severe disease); (3) reduction or absence of the physiological "gliding sign" related to disease severity (observed in 33/84 to 39% cases); and (4) increased number of horizontal (and to a lesser extent vertical) reverberation artifacts (seen in 41 patients with advanced fibrosis, 34% of the total series). All abnormalities were detected in both lungs. Although lung biopsy is still the gold standard for diagnosis of interstitial lung disease, transthoracic ultrasound can document early and late-stage changes associated with this disease.
19048257 Hyperuricemia and its related factors in an urban population, Izmir, Turkey. 2009 Jun The aim of this study was to examine the prevalence of hyperuricemia and its associated factors in an urban area of Izmir, located in western Turkey. Our study group was selected by computerized sampling from the participants of a larger population-based study searching for the prevalence of rheumatoid arthritis in Balcova and Narlidere districts of Izmir. A total of 132 subjects (69 women and 63 men) were included in this study. Serum uric acid, glucose, creatinine and lipid levels were studied. Body composition along with body fat percentage was determined anthropometrically. A total of 16 subjects had hyperuricemia (4 women and 12 men). The overall prevalence of hyperuricemia was 12.1% and the mean uric acid level was 4.9 +/- 1.3 mg/dl. Males had significantly higher uric acid levels than females (P < 0.05; 5.5 +/- 1.3 vs. 4.3 +/- 1.1 mg/dl, respectively). The prevalence of hypertension, diabetes, obesity and metabolic syndrome was 24.4, 5.3, 28 and 26.5%, respectively. There was no gouty subject. Sum of skinfold thickness (SFT) measurements and creatinine levels were the independent predictors of hyperuricemia (beta = 0.45, 0.47, respectively). Uric acid measurement is important not only for inflammatory rheumatic disorders but also for predicting metabolic syndrome and related coronary artery disease. There is sex difference in uric acid levels in favor of women most probably explained by gonadal hormones. Hyperuricemia is significantly predicted by anthropometric measure of SFT which is a simple clinical screening method along with creatinine levels.
19000786 A review of the current use of rituximab in autoimmune diseases. 2009 Jan Rituximab is a human/murine chimeric monoclonal antibody primarily used for treating non-Hodgkin's B-cell lymphoma. Recently it has also been used in the treatment of several autoimmune diseases. A literature review was conducted to determine the efficacy of rituximab in the treatment of some of these autoimmune diseases. Multiple mechanisms proposed for the rituximab mediated B cell depletion are also discussed. The efficacy of rituximab is well-established and it is FDA approved for treatment of Rheumatoid arthritis. In this review, data on the use of rituximab is presented from 92 studies involving 1197 patients with the following diseases: systemic lupus erythematosus, idiopathic thrombocytopenic purpura, anti-neutrophil cytoplasmic antibody associated vasculitis, Grave's disease, autoimmune hemolytic anemia, pemphigus vulgaris, hemophilia A, cold agglutinin disease, Sjogren's syndrome, graft vs. host disease, thrombotic thrombocytopenic purpura, cryoglobulinemia, IgM mediated neuropathy, multiple sclerosis, neuromyelitis optica, idiopathic membranous nephropathy, dermatomyositis, and opsoclonus myoclonus. The efficacy varies among different autoimmune diseases. The cumulative data would suggest that in the vast majority of studies in this review, RTX has a beneficial role in their treatment. While rituximab is very effective in the depletion of B cells, current research suggests it may also influence other cells of the immune system by re-establishing immune homeostasis and tolerance. The safety profile of RTX reveals that most reactions are infusion related. In patients with autoimmune diseases the incidence of serious and severe side effects is low. Systemic infection still remains a major concern and may result in death.
18823786 Aldehydic components of cinnamon bark extract suppresses RANKL-induced osteoclastogenesis 2008 Oct 15 Several major bone diseases are directly attributable to bone loss, including osteoporosis, bone metastasis, and rheumatoid arthritis. The nuclear factor of activated T cell 1 (NFATc1), a transcription factor, has recently been shown to play an essential role in osteoclastogenesis. In this study, we found that of several herbs, Cinnamomum zeylanicum (C. zeylanicum) exhibited the strong inhibitory effects on osteoclastogenesis and that its mechanism of action involves the suppression of NFATc1-mediated signal transduction. C. zeylanicum dose-dependently inhibited osteoclast-like cell formation at concentrations of 12.5-50 microg/ml without affecting cell viability. Resorption pit assays have shown that C. zeylanicum also inhibits the bone-resorbing activity of mature osteoclasts. Treatment with C. zeylanicum inhibited the receptor activator of nuclear factor-kappaB ligand (RANKL)-induced NFATc1 and c-fos expression. Additionally, C. zeylanicum moderately inhibited phosphorylation of IkappaB-alpha, suggesting that the c-fos/NFATc1 pathway, rather than the nuclear factor-kappaB (NF-kappaB) pathway, is the primary target of C. zeylanicum during RANKL-induced osteoclastogenesis. Using an HPLC-DAD system, we identified three major peaks for four characteristic components in the C. zeylanicum extract and identified an unknown peak as 2-methoxycinnamaldehyde via HPLC and a 2D-COSY (1)H NMR study. We identified cinnamaldehyde and 2-methoxycinnamaldehyde as active components reducing osteoclast-like cell formation and inhibiting NFATc1 expression. Notably, in a resorption pit assay, 2-methoxycinnamaldehyde exhibited remarkable inhibition rates of 95% at 2 microM on bone resorption. In summary, this study points to the conclusion that C. zeylanicum inhibits RANKL-induced osteoclastogenesis. This finding raises prospects for the development of a novel approach in the treatment of osteopenic disease.
18785312 Abnormal antinuclear antibody titers are less common than generally assumed in established 2008 Oct OBJECTIVE: To evaluate antinuclear antibody (ANA) tests in established cases of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) by indirect immunofluorescence microscopy (F-ANA) and enzyme-immunoassays detecting antinucleosomal antibodies (ANSA-EIA). METHODS: Sera from 50 patients with SLE and 65 patients with RA were analyzed regarding abnormal concentrations of F-ANA (serum dilution>or=1:200=95th percentile among 300 healthy blood donors). The sera were also analyzed with 2 commercial ANSA-EIA kits. RESULTS: An abnormal F-ANA titer occurred in 76% of the SLE sera compared to 23% in RA, and was not related to present use of antirheumatic drugs. At dilution 1:50, 84% of the SLE sera were F-ANA-positive compared to 20% of healthy women. Forty percent and 56%, respectively, of the SLE sera tested positive in the 2 ANSA-EIA kits. By the most sensitive assay, 96% of the ANSA-positive SLE sera produced a homogenous (chromosomal) F-ANA staining pattern compared to 18% of the ANSA-negative SLE sera. Ten of the 15 F-ANA-positive RA sera (63%) generated homogenous F-ANA staining and 13 (20%) tested positive in the most sensitive ANSA-EIA, but with no correlation to the F-ANA staining pattern. CONCLUSION: The sensitivity of F-ANA at an abnormal titer was surprisingly low (76%) in established cases of SLE. ANSA occurred in 56% of the SLE sera, but also in a fair number (20%) of RA sera. Practically all ANSA-positive SLE sera were identified by chromosomal F-ANA staining. We conclude that the antigen-specific antinucleosomal EIA does not have high enough diagnostic specificity to justify use of this analysis for routine diagnostic purposes.
20641534 N-4-[(18)F]Fluorobenzoyl-c(RGDyK). 2004 Integrins are a family of heterodimeric glycoproteins on cell surfaces that mediate diverse biological events involving cell-cell and cell-matrix interactions (1). Integrins consist of an α and a β subunit and are important for cell adhesion and signal transduction. α(v)β(3) integrin is the most prominent receptor affecting tumor growth, tumor invasiveness, metastasis, tumor-induced angiogenesis, inflammation, osteoporosis, and rheumatoid arthritis (2-7). Expression of α(v)β(3) integrin is strong on tumor cells and activated endothelial cells, whereas expression is weak on resting endothelial cells and most normal tissues. α(v)β(3) antagonists are being studied as antitumor and antiangiogenic agents and the agonists as angiogenic agents for coronary angiogenesis (6, 8, 9). A tripeptide sequence consisting of Arg-Gly-Asp (RGD) has been identified as a recognition motif used by extracellular matrix proteins (vitronectin, fibrinogen, laminin, and collagen) to bind to a variety of integrins, including α(v)β(3). Various radiolabeled antagonists have been introduced for imaging of tumors and tumor angiogenesis (10). Most of the cyclic RGD peptides are monomeric and composed of five amino acids. Haubner et al. (11) reported that various cyclic RGD peptides exhibit selective inhibition of binding to α(v)β(3) (IC(50), 7-40 nM) but not to α(v)β(5) (IC(50), 600-4,000 nM) or α(IIb)β(3) (IC(50), 700-5,000 nM) integrin. [(18)F]FB-c(RGDyK) was synthesized to study in vivo biodistribution of the tracer in tumor-bearing mice. [(18)F]FB-c(RGDyK) was found to have high accumulation in tumors, but it also had a high tumor washout and biliary excretion into the gallbladder and intestines (12). A dimeric analog was also synthesized as [(18)F]FB-E[c(RGDyK)](2), which was shown to have higher tumor uptake than the monomer and predominantly renal excretion (13).
17621549 Transcriptional activation of MMP-13 by periodontal pathogenic LPS requires p38 MAP kinase 2007 Matrix metalloprotease-13 (MMP-13) is induced by pro-inflammatory cytokines and increased expression is associated with a number of pathological conditions such as tumor metastasis, osteoarthritis, rheumatoid arthritis and periodontal diseases. MMP-13 gene regulation and the signal transduction pathways activated in response to bacterial LPS are largely unknown. In these studies, the role of the mitogen-activated protein kinase (MAPK) pathways in the regulation of MMP-13 induced by lipopolysaccharide was investigated. Lipopolysaccharide from Escherichia coli and Actinobacillus actinomycetemcomitans significantly (P < 0.05) increased MMP-13 steady-state mRNA (average of 27% and 46% increase, respectively) in murine periodontal ligament fibroblasts. MMP-13 mRNA induction was significantly reduced by inhibition of p38 MAP kinase. Immunoblot analysis indicated that p38 signaling was required for LPS-induced MMP-13 expression. Lipopolysaccharide induced proximal promoter reporter (-660/+32 mMMP-13) gene activity required p38 signaling. Collectively, these results indicate that lipopolysaccharide-induced murine MMP-13 is regulated by p38 signaling through a transcriptional mechanism.
17610605 Pyoderma gangrenosum: clinical presentation and outcome in 18 cases and review of the lite 2007 Jul BACKGROUND: Pyoderma gangrenosum (PG) is an idiopathic ulcerative neutrophilic inflammatory skin disease characterized by variable clinical presentation and outcome. Because its incidence is low, no prospective randomized controlled trials and only a few large case studies on PG have been reported. OBSERVATIONS: We demonstrate the clinical presentation and outcome in 18 cases with severe and chronic PG. In our 18 patients, the female/male ratio was 3.5:1, the mean onset age was 53.1 yrs (range 23-78); six cases (33%) had associated diseases (inflammatory bowel disease [n = 2, 11%], monoclonal gammopathy [n = 2, 11%], rheumatoid arthritis [n = 1, 6%], diabetes mellitus [n = 1, 6%]). Anatomic locations involved were lower leg (n = 14, 78%), abdomen (n = 5, 28%), arm (n = 3, 17%), breast (n = 2, 11%), and buttocks (n = 1,6%). Five patients (28%) had multiple lesions (n > or = 2). Immunosuppressive monotherapies (n = 3, 17%) and polytherapies (n = 15, 83%) were used. 13 patients (72%) showed complete remission (mean duration to complete remission: 1.29 yrs), three patients (17%) persistent disease (mean duration: 8 yrs), contact was lost to one patient (6%) and one patient died (6%). CONCLUSION: Our observations add to the growing body of evidence that PG responds in most cases to systemic immunosuppressive treatment, with corticosteroids and cyclosporine representing first-line therapies. Besides reporting the clinical outcome in our 18 patients, we review the literature and discuss treatment recommendations that take additional factors including associated conditions, disease severity and localization of lesions into consideration.
17600819 Lymphoma risk in inflammatory bowel disease: is it the disease or its treatment? 2007 Oct With the increasingly widespread use of immunosuppressive and biologic agents for the treatment of Crohn's disease and ulcerative colitis come concerns about potential long-term consequences of such therapies. Disentangling the potential confounding effects of the underlying disease, its extent, severity, duration, and behavior, and concomitant medical therapy has proven to be exceedingly difficult. Unlike the case in rheumatoid arthritis, the overwhelming preponderance of population-based evidence suggests that a diagnosis of inflammatory bowel disease (IBD) is not associated with an increased relative risk of lymphoma. However, well-designed studies that evaluate the potential modifying effect of IBD severity have yet to be performed. Although the results from hospital- and population-based studies have conflicted, the results of a recent meta-analysis suggest that patients receiving purine analogs for the treatment of IBD have a lymphoma risk approximately 4-fold higher than expected. Analyses of lymphoma risk in patients receiving biologic agents directed against tumor necrosis factor-alpha are confounded by concomitant use of immunosuppressive agents in most of these patients. Nevertheless, there may be a small but real risk of lymphoma associated with these therapies. Although the relative risk of lymphoma may be elevated in association with some of the medical therapies used in the treatment of IBD, this absolute risk is low. Weighing the potential risk of lymphoma associated with select medical therapies against the risk of undertreating IBD will help physicians and patients to make more informed decisions pertaining to the medical management of IBD.
17450072 Utility of flexion-extension radiographs in evaluating the degenerative cervical spine. 2007 Apr 20 STUDY DESIGN: Retrospective cohort of 258 consecutive patients. OBJECTIVE: The purpose of this study is to determine the: (1) percentage of flexion-extension radiographs that revealed pathology not appreciated on neutral radiographs in the nontrauma population, and (2) frequency that these views led to a change in the management of these patients. SUMMARY OF BACKGROUND DATA: The utility of flexion-extension radiographs in the evaluation of the spine trauma or preoperative patient is well accepted, but the role of dynamic radiographs in the degenerative population is not well defined. METHODS: Consecutive patients presenting with axial cervical, upper extremity radicular, or myelopathic symptoms underwent upright anteroposterior, neutral lateral, and flexion-extension lateral radiographs. Patients with recent trauma, rheumatoid arthritis, prior cervical fracture, prior cervical surgery, inadequate radiographs, or congenital anomalies were excluded. Three observers reviewed all radiographs after determining the best measurement method by a priori analysis of interobserver reliability. RESULTS: Listhesis was observed on 23 of the neutral lateral images; 6 of these were found to have changes between flexion and extension (2-4 mm). Two patients (1%) had spondylolisthesis on flexion-extension radiographs not visualized on neutral lateral radiographs. A subsequent review of these patients' charts revealed no change in management based on these findings. CONCLUSIONS: Cervical flexion-extension radiographs are a method of assessing potential instability. In the degenerative population studied here, 1% had spondylolisthesis noted only on the flexion-extension images, and 3% had a change in spondylolisthesis. None of these, however, led to a changes in clinical management. These data, in conjunction with the extra cost and radiation exposure associated with additional views, led us to no longer regard dynamic radiographs as a useful part of the initial imaging for the patient with degenerative cervical conditions.
16958136 Inhibitors of CXCR4 affect the migration and fate of CXCR4+ progenitors in the developing 2006 Nov Chemokines and their receptors play major roles in numerous physiological and pathological processes during development and disease. CXCR4 is the most abundantly expressed chemokine receptor during development. In contrast to other chemokine receptors, CXCR4 binds and is activated exclusively by its ligand stromal derived factor-1 (SDF-1) or CXCL12. SDF-1 signaling has a wide range of effects on CXCR4-expressing cells depending on the cell type ranging from cell growth to adhesion, chemotaxis, and migration. CXCR4 also serves as a co-receptor for HIV-1 entry into T-cells and has been implicated in the pathogenesis of rheumatoid arthritis and cancer growth and invasion. Numerous inhibitors and antagonists of CXCR4 have been produced and are being tested for their efficiency to target its role in pathogenesis. Our initial expression analysis revealed that CXCR4 is expressed by the migrating myogenic and angiogenic precursors in the developing chick limb. In this study, we used the most specific peptidic inhibitors of CXCR4, T140 and its analog TN14003, to analyse the effect of blocking CXCR4/SDF-1 signaling on the undetermined bioptent migratory progenitors in the developing chick limb. Our results point to defects in migration and an altered differentiation program of these CXCR4-expressing progenitor pool in the limb.
15657943 Effect of D-penicillamine on rat lung elastin cross-linking during the perinatal period. 2006 Mar This study was designed to clarify the effects of D-penicillamine (DPA), a drug used for treatment of various pathological events, on lung elastin formation and maturation of the newborn in the perinatal period. The investigation was conducted on 20 newborn rats bred from 40 female and six male rats. DPA doses 400 mg kg(-1) day(-1) and physiological saline were given intraperitoneally (i.p) to experimental and control groups. To assess newborn maturation, their body and lung weights were determined. Serum Cu levels were measured by atomic absorption spectroscopy and ceruloplasmin (Cp) activities were measured spectrophotometrically. Newborn lung tissue elastin, desmosine (DES) and isodesmosine (IDES) levels were measured by HPLC. The results showed that DPA treatment caused loss of skin elasticity and reduction in body and lung weight in newborns of the experimental group. The serum Cu levels and Cp activity were found to be significantly lower in both maternal and newborn of the experimental groups compared with the control group. The lung DES, IDES and elastin values of newborns in the experimental group were decreased compared with the control group. In conclusion, our results indicate that 400 mg kg(-1) day(-1) DPA, a dose that is used in the treatment of Wilson's disease, rheumatoid arthritis and cystinuria, caused the retardation of newborn maturation, a decrease in DES-IDES cross-links and levels of lung elastin of offspring in the perinatal period. Another conclusion to be drawn from this study is that even low levels of Cu depletion due to DPA administration induces a change in cross-linking in lung elastin during the perinatal period.
18591874 Design and development of hydroxypropyl methycellulose (HPMC) based polymeric films of met 2008 Jul The present investigation was aimed to evaluate the possibility of using different concentrations and polymeric grades of hydroxypropyl methylcellulose (K4M, K15M and K100M) for transdermal delivery of methotrexate, an immunosuppressant drug for rheumatoid arthritis. The matrix films were evaluated for their physicochemical characterization followed by in vitro and in vivo evaluation. Selected formulations were subjected for their in vivo studies on healthy rabbits following balanced incomplete block design. The relevance of difference in the in vitro dissolution rate profile and pharmacokinetic parameters (C(max), t(max), AUC((s)), t(1/2), K(el), and MRT) were evaluated statistically. The thickness and weight of the patch increased with the increase in polymeric grade and content. Fourier transform infrared spectroscopy and differential scanning calorimetry results confirm that there is no interaction between drug and polymer used. X-ray diffraction study reveals an amorphous state of drug in the matrix films. The in vitro drug release followed Higuchi kinetics (r=0.972-997; p<0.001) as its coefficient of correlation values predominates over zero order and first order release kinetics. In vitro dissolution profiles and pharmacokinetic parameters showed a significant difference between test products (p<0.01), but not within test products. A quantitatively good correlation was found between per cent of drug absorbed from the transdermal patches and AUC((s)). A significant in vitro/in vivo correlation was observed when per cent drug released was correlated with serum drug concentration. Out of the various formulations made, the selected formulations are better in their in vitro dissolution and pharmacokinetic characteristics and thus hold potential for transdermal delivery.