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ID PMID Title PublicationDate abstract
18395519 Soluble tissue factor has unique angiogenic activities that selectively promote migration 2008 Jun 6 The level of circulating tissue factor (TF) is up-regulated in human angiogenesis-related malignancies. However, whether circulating TF has angiogenic activities has not been determined. Soluble TF (sTF) is the main domain of circulating TF. Here, using cell migration, wound healing, and tubule formation assays, human recombinant sTF was found to significantly promote the migration and differentiation of endothelial cells. The stress fiber formation and rearrangement induced by sTF observed through immunofluorescence microscope may be responsible for the stimulatory migration effect of sTF. Nevertheless, sTF had no effects on endothelial cell proliferation. Interestingly, sTF can be internalized by endothelial cells, which implies a novel mechanism for sTF in angiogenesis. These results suggest that sTF has unique angiogenic activities and may serve as a potential therapeutic target to treat diseases associated with angiogenesis such as cancer and rheumatoid arthritis.
18391558 The impact of physical illness on sexual dysfunction. 2008 Sexuality is the ultimate union of mind and body. Sexual dysfunction is often the first manifestation of physical illness but is often not inquired about on routine review of symptoms. This is, in large part, due to the health care providers' lack of knowledge in diagnosis and treatment of sexual impairment as well as their discomfort with this sensitive topic. However, sexual well-being is an important determinant of quality of life and many medically ill patients find sexual intimacy to be an essential mode of communication with their partners. This chapter attempts to methodically delineate physical illnesses causing sexual dysfunction by organ system. Neurologic, endocrinologic, cardiovascular and pelvic illnesses are discussed as to their impact on sexual health. Diagnostic and established treatment strategies are also reviewed. Breast cancer, rheumatoid arthritis and psoriasis are touched upon. Although not a disease, pregnancy and its unique impact on sexuality is also discussed. Not only the disease itself but the treatment prescribed may also cause sexual impairment. Thus, a separate section on medications that impair sexual functioning is presented. A table of common medications as a quick reference to their effects on each stage of the sexual cycle is also provided.
18220943 Tetracyclines and pulmonary inflammation. 2007 Dec Tetracycline and its derivatives, such as chlortetracycline, oxytetracycline, minocycline, doxycycline, methacycline and lymecycline, are naturally occurring or semi-synthetic polyketide compounds that exhibit a well known broad-spectrum antibacterial activity that interferes with prokaryotic protein synthesis at the ribosome level. In addition to this well known antibacterial activity these compounds also exhibit a variety of additional, less well known properties. Among them are separate and distinct anti-inflammatory properties. Tetracycline and related compounds have been shown to be effective chemotherapeutic agents in a wide variety of chronic inflammatory diseases and conditions. These include periodontitis, rosacea, acne, auto-immune diseases such as rheumatoid arthritis and protection of the central nervous system against trauma and neurodegenerative diseases such as stroke, multiple sclerosis and Parkinson disease. Tetracycline and related compounds appear to be beneficial for treatment of several chronic inflammatory airway diseases. Among them are asthma, bronchiectasis, acute respiratory distress syndrome, chemical induced lung damage and cystic fibrosis. The clinical use of tetracycline-type drugs in treatment of chronic airway inflammation is becoming a topic of intense interest. Recent findings in this area have led to an understanding of the myriad physiological, cellular and molecular mechanisms of the inflammatory response and how this response may be controlled to limit damage to host cells and tissues. This review presents a brief summary of the recent research in the area of tetracycline and its derivatives in control of pulmonary inflammation.
18094932 No changes in infliximab levels in blood stored for preoperative autologous blood donation 2008 Rheumatoid arthritis (RA) patients requiring total joint arthroplasties under administration of infliximab, which may remain in donated blood if preoperative autologous blood donation (PABD) is undertaken for the surgery, may risk infection. We clarified infliximab hemokinetics in blood stored for such patients. A 20-ml blood sample was obtained from each of the ten RA patients receiving infliximab at just after administration and at 2 and 4 weeks following the administration of infliximab, mixed with 2.8 ml citrate-phosphate-dextrose-adenine (CPDA-1) and stored at 4-6 degrees C. Plasma levels of infliximab in the stored blood were measured just after-mixture with CPDA-1, and at 2 and 4 weeks following the start of storage. Serum levels were also measured just before infliximab administration and at each phlebotomy. The plasma infliximab levels in the stored blood remained close to their original serum levels at the time of each corresponding phlebotomy, only somewhat influenced by dilution of CPDA-1, and sustained for 4 weeks following the start of storage, unlike in vivo, where levels decreased. This suggests that in order to prevent side effects, the later after infusion of infliximab the phlebotomy occurs, the better, and that the amount of stored blood transfusion should be consistent with that of blood loss.
18062589 [Spondylodiscitis as cause of unexplained fever]. 2007 Nov 10 An 83-year-old woman was admitted to hospital with complaints of fever, abdominal pain and other complaints suggesting urosepsis. Additional analyses did not reveal the cause of her complaints. After cessation of antibiotic therapy, there was a spontaneous decrease in the infection parameters and she was subsequently discharged. Two and a half months later she was presented in our hospital with low back pain with radiating to the legs. MRI showed signs ofa spondylodiscitis at the level of LIII-LIV existing for some time. Finally, a gram-positive streptococcus infection was found and she was treated with antibiotics for 13 weeks. 6 months later she was free of symptoms. A 57-year-old man was admitted to the intensive care with a double-sided olecranon bursitis and sepsis. An endocarditis caused by Staphylococcus aureus was thought to be the cause of the sepsis and the patient was treated with surgical intervention and antibiotics. Because of persistent sepsis, different CT-scans were performed, and after one and a half months an extensive spondylodiscitis with abscess formation was diagnosed and subsequently treated surgically. A delay in diagnosing spondylodiscitis is the rule rather the exception. The diagnosis should be considered in any patient with localised back pain, especially when accompanied by fever, high ESR, and the presence of risk factors such as high age, diabetes mellitus, immunosuppression, and/or rheumatoid arthritis.
18044200 [Operative treatment for carpal tunnel syndrome]. 2007 Nov Carpal tunnel syndrome is an entrapment neuropathy where the median nerve is compressed inside of the carpal canal. Causes of this syndrome include repetitive strain, wrist fracture, rheumatoid arthritis, space-occupying lesion, dialysis-related amyloidosis, diabetes mellitus, and in addition, cases with no apparent cause. Similar symptoms such as numbness, sensory disturbance of the median nerve distribution area and weakness of thenar muscles also occur in patients who suffer from cervical diseases. In cases where the patient suffers from both carpal tunnel syndrome and cervical disease, the patient's complaints may not disappear if treatment is only performed for one of them. Therefore, accurate diagnosis of the cause of the symptoms, using electrophysiological test results and/or carpal canal pressure measurement results is essential to the successful treatment of such patients. The purpose of operative treatments for carpal tunnel syndrome is to decompress the median nerve. A variety of operative treatment techniques, i.e., standard open procedure, minimum incision open procedure, one-portal or two-portal endoscopic procedures, etc., are used. Every procedure has different conditions such as equipment used, operative hand positions, location and size of skin incisions, blind ways or no blind ways, approaches to target tissues, tourniquet usage and others. I developed the world's first endoscopic operative procedure for carpal tunnel syndrome using the Universal Subcutaneous Endoscope (USE) system in 1986 and I have operated on over 7,300 hands during these last 20 years. My technique has been proven by pre- and postoperative carpal canal pressure and intraneural median nerve pressure measurement results as an evidence-based medicine. Before an operative method is chosen, the most important thing to consider is whether or not it will safely and completely achieve the purpose as evidence-based medicine with minimal invasion of the patient.
17987290 First hip arthroplasty register in Italy: 55,000 cases and 7 year follow-up. 2009 Apr The Register for Orthopaedic Prosthetic Implantation (RIPO) has been prospectively collecting data on hip prostheses performed in all the orthopaedic units in the region Emilia-Romagna since January 2000. The register aims to determine the characteristics of patients, evaluate the effectiveness of prostheses, and allow internal audit. Adherence to the register is compulsory (93% capture). By 31 December 2006 the register contained data on 35,041 primary total hip arthroplasty (THA), 14,613 hemiarthoplasties, and 5,878 revisions. All prosthetic components are registered on an individual basis. Survival analysis is done following the Kaplan Meier method. Cumulative survival rate at 7 years is 96.8% (95% CI: 96.4-97.1%) for THA and 97.6% (97.0-98.3%) for hemiarthroplasties. Multivariate analysis verified that survival of the THA is affected by pathology, where the worst conditions are rheumatoid arthritis, femoral neck fracture, and sequelae of coxitis or Paget's disease. Results are comparable to other major registers of Northern Europe and Australia.
17896975 Small molecule CXCR4 chemokine receptor antagonists: developing drug candidates. 2007 Chemokine receptors are a target of growing interest for new therapeutic drugs, as their role in multiple disease states has been demonstrated. The CXCR4/ CXCL12 pairing has been implicated in HIV and cancer, as well as chronic inflammatory diseases, including asthma and rheumatoid arthritis. HIV uses CXCR4 or CCR5 receptors in the key binding step of the infection process, leading to the idea that drugs could be developed to block this interaction. Cancer metastasis has also been linked to cellular communication via the chemokine pathways and hence, receptor antagonists could potentially inhibit this important pathway of disease progression. A wealth of data concerning small molecule CXCR4 receptor antagonists has been generated over the last few years, as a variety of these small molecules have been tested, and the understanding of structure activity relationships has improved. Here, we review the developing area of small molecule CXCR4 antagonists and the rapidly increasing amount of data from biological studies. Both peptidic and non-peptidic compounds have been investigated. In particular, we focus on AMD3100 and bismacrocyclic analogues, the most extensively studied class of CXCR4 antagonists, and the recent developments in this area.
17712817 Cannabis, pain, and sleep: lessons from therapeutic clinical trials of Sativex, a cannabis 2007 Aug Cannabis sativa L. has been utilized for treatment of pain and sleep disorders since ancient times. This review examines modern studies on effects of Delta9-tetrahydrocannabinol (THC) and cannabidiol (CBD) on sleep. It goes on to report new information on the effects on sleep in the context of medical treatment of neuropathic pain and symptoms of multiple sclerosis, employing standardized oromucosal cannabis-based medicines containing primarily THC, CBD, or a 1 : 1 combination of the two (Sativex). Sleep-laboratory results indicate a mild activating effect of CBD, and slight residual sedation with THC-predominant extracts. Experience to date with Sativex in numerous Phase I-III studies in 2000 subjects with 1000 patient years of exposure demonstrate marked improvement in subjective sleep parameters in patients with a wide variety of pain conditions including multiple sclerosis, peripheral neuropathic pain, intractable cancer pain, and rheumatoid arthritis, with an acceptable adverse event profile. No tolerance to the benefit of Sativex on pain or sleep, nor need for dosage increases have been noted in safety extension studies of up to four years, wherein 40-50% of subjects attained good or very good sleep quality, a key source of disability in chronic pain syndromes that may contribute to patients' quality of life.
17644055 Pylephlebitis and mesenteric thrombophlebitis in sigmoid diverticulitis: medical approach, 2007 Dec A 57-year-old woman presented with fever, vomiting and arthralgia, with a history of rheumatoid arthritis. Laboratory tests showed leucocytes, anaemia and elevation of C-reactive-protein (CRP). Blood cultures were positive for Gram negative bacteria and Streptococcus viridans. Patient underwent abdominal Computed Tomography (CT) scan revealing sigmoid acute diverticulitis with peridiverticular abscesses and thrombophlebitis within the inferior mesenteric and portal veins. She started antibiotic and anticoagulant therapy. After 20 days, a second CT revealed a thrombosis involving the superior mesenteric vein also. After 22 days of therapy the patient was discharged with the resolution of the septic status. Two months after discharge the patient underwent left hemicolectomy for a histopathologically documented diverticulitis with an uneventful postoperative course. This is a description of a rare association of septic thrombosis within the portal, inferior mesenteric and superior mesenteric veins during acute sigmoid diverticulitis with abdominal abscesses. Our therapeutic strategy was a first line medical approach and delayed surgery.
17346153 The Janus face of CD4+CD25+ regulatory T cells in cancer and autoimmunity. 2007 Regulatory T cells (Treg) encompass a heterogeneous family of T cells implicated in maintenance of tolerance to self antigens. Treg cells might be qualitatively and/or quantitatively deficient in human autoimmune diseases, including multiple sclerosis, graft versus host disease, systemic lupus erythematosus, type I diabetes, and rheumatoid arthritis. In animal models of autoimmunity, infusion of ex vivo-expanded Treg cells and/or in vivo enhancement of Treg cell suppressor function by pharmacological agents and cytokines attenuate disease manifestations and restore tolerance. However, Treg cells represent a double-edged sword, as Treg cells with specificity for tumour-associated antigens contribute to cancer pathogenesis and progression. In vivo depletion of Treg cells by monoclonal antibodies and/or selected drugs is an encouraging therapeutic strategy which improves tumour eradication in animal models of cancer. In addition, elimination and/or functional inactivation of Treg cells might boost anti-tumour immunity in tumour-bearing hosts receiving anti-cancer vaccination. The present review discusses Treg cell manipulation as a novel therapeutic strategy in cancer and autoimmunity, conditions characterised by a common regulatory basis.
17112645 Small cell neuroendocrine carcinoma of the sinonasal region. A propose of a case. 2007 Dec We describe a 70-year-old man with rheumatoid arthritis and pulmonary fibrosis who presented with a month's history of pain in the left lateronasal region and inferior eyelid. On examination there was left exophthalmos, difficulty in coordinating eye movements, inflammation, erythema, and pain. Computed tomography showed a 3 cm mass in the left posterior ethmoid region, a biopsy specimen from which showed a small cell neuroendocrine tumour. He refused operation and was treated unsuccessfully with four cycles of cisplatin and etoposide.
17078510 [Adjuvants--essential components of new generation vaccines]. 2006 Adjuvants are essential components of vaccines that augment an immunological reaction of organism. New vaccines based on recombinant proteins and DNA, are more save than traditional vaccines but they are less immunogenic. Therefore, there is an urgent need for the development of new, improved vaccine adjuvants. There are two classes of adjuvants: vaccine delivery systems (e.g. emulsions, microparticles, immune-stimulating complexes ISCOMs, liposomes) and immunostimulatory adjuvants (e.g. lipopolysaccharide, monophosphoryl lipid A, CpG DNA, or muramylpeptides). The discovery of more potent and safer adjuvants may allow to development better prophylactic and therapeutic vaccines against chronic infectious (e.g., HSV, HIV, HCV, HBV, HPV, or Helicobacter pylori) and noninfectious diseases as multiple sclerosis, insulin-dependent diabetes, rheumatoid arthritis, allergy and tumors (e.g., melanoma, breast, or colon cancer).
17073673 The role of HLA promoters in autoimmunity. 2006 Population studies reveal HLA class I and class II gene polymorphisms associated with all the common chronic autoimmune diseases, notably spondylarthropathies, rheumatoid arthritis, multiple sclerosis and type I diabetes. We here discuss the exceptionally high levels of nucleotide diversity in the MHC region likely to reflect not only balancing selection acting on the epitope binding sites but also natural selection operating on the promoter region. The latter possibility is supported by functional studies with promoters, higher levels of diversity in the promoters of class II than class I genes and the relatively high frequency of single nucleotide polymorphisms around transcription factor binding sites. This, we argue, reflects the need for an appropriate level of signalling at the immunological synapse. We here summarise our knowledge of HLA promoter polymorphisms and how these translate into differential expression, T cell polarisation and inflammation. We discuss current strategies for pharmaceutical intervention in HLA expression.
17060363 Factors masking HMGB1 in human serum and plasma. 2007 Jan High mobility group box 1 protein (HMGB1) is a ubiquitously expressed architectural chromosomal protein. Recently, it has become obvious that HMGB1 can also act as a proinflammatory mediator when actively secreted during cell activation or passively released from necrotic cells. HMGB1 appears to play an important role in the pathogenesis of diseases, including sepsis and rheumatoid arthritis. However, easy, sensitive, and reliable detection systems are required to investigate the clinical significance of HMGB1 in clinical samples for diagnosis and prognosis of diseases. Here, we describe sensitive ELISAs for the detection of HMGB1 in cell culture medium and cell lysates. However, these assays failed to reliably quantitate HMGB1 in serum and plasma when compared with immunoblot analysis. We found that serum/plasma components bind to HMGB1 and interfere with its detection by ELISA systems. In most serum/plasma samples investigated, including those from healthy individuals, we detected IgG antibodies binding to HMGB1. The titers of these antibodies correlated with the capacity of sera to interfere with the detection of recombinant HMGB1 by ELISA. Furthermore, HMGB1 coimmunoprecipitated with several proteins including IgG1, as identified by mass spectrometry. These HMGB1 interacting proteins are currently characterized and may contribute to complex formation, masking, and possibly, modulation of cytokine activity of HMGB1.
17056024 Serum soluble Fas levels in patients with autoimmune rheumatic diseases. 2007 Jan OBJECTIVE: The role of the serum soluble Fas (sFAS) system is unclear in diagnosis of several autoimmune rheumatic diseases although there are present contradictory reports on the levels of serum sFas. We therefore assessed levels of sFAS in serum of patients with autoimmune rheumatic diseases. PATIENTS AND METHODS: We analyzed sFas levels and their relationship to clinical and laboratory data in patients with systemic lupus erythematosus (SLE, n=32), rheumatoid arthritis (RA, n=28), Sjögren's syndrome (SS, n=20) systemic sclerosis (SSc, n=21), polymyositis/dermatomyositis (PM/DM, n=15). Patients with osteoarthritis (OA, n=20) and healthy volunteers (n=20) were used as controls. Serum levels of sFAS were determined by ELISA. sFas levels greater than mean (normals)+2 SD were considered as elevated. RESULTS: The mean sFas values were found higher in RA, PM/DM and OA than in control although no differences were found in SSc and SS patients. The mean sFas levels in SLE patients were lower than healthy controls. Elevated sFas rates in RA, PM/DM and SS were found to be 21.4%, 60%, 10% higher than in healthy controls, respectively. sFas levels in SLE and SSc did not differ from control values. Mean sFas levels did not show significant difference between active and inactive patients in all disease groups except PM/DM, RA and OA. No correlations of sFas with relevant disease subsets, laboratory findings and treatment modalities were found. CONCLUSIONS: The findings indicate that the serum sFas molecule may provide a useful additional marker for presence and assessment of disease in patients with RA and PM/DM.
16887405 Pulmonary adverse events of anti-tumor necrosis factor-alpha antibody therapy. 2006 Aug It is well established that anti-tumor necrosis factor-alpha (TNFalpha) antibody is an efficacious disease-modifying drug for rheumatoid arthritis and Crohn's disease. Unfortunately, its long-term use can be associated with ominous pulmonary adverse events, most notably mycobacterial and fungal lung infections. To this end, reactivation of latent tuberculosis infection represents a serious concern of anti-TNFalpha antibody therapy. Given the anticipated increase in the approved indications for these drugs, community-based physicians should be made aware of these events for implementation of better patient selection for anti-TNFalpha antibody therapy and initiation of appropriate measures once these adverse events are observed. This review will address this issue by outlining: 1) the role of TNFalpha in host inflammatory response to injury, particularly during mycobacterial and fungal infections; 2) the salutary effects of anti-TNFalpha antibody therapy in human diseases; and 3) the ominous pulmonary adverse events associated with these drugs.
16887087 [Acute abdomen secondary to spontaneous uterine rupture associated with pyometra]. 2006 Mar A 71-year-old female with rheumatoid arthritis and chronic use of corticosteroids presented to the emergency room with 2 weeks of urinary symptoms, abdominal pain and a mass located in hypo-mesogastrium and both flanks. An X-ray film of the abdomen showed that bowels were displaced by the mass. Laboratory studies showed thrombocytosis (549,000/mm(3)) and leukocytosis (41,800/mm(3)). Several hours after her arrival the patient developed acute abdomen and surgery was indicated. A urinary catheter drained 2100 ml of urine and the abdominal mass was reduced in size but did not disappear. Surgery demonstrated that the urinary bladder covered the fundus and the anterior face of the uterus, where extensive necrosis and a 3-cm perforation were found; 400 ml of foul-smelling pus was drained from the uterine cavity. Due to necrosis, a hysterectomy was performed. The histopathological report indicated necrosis, atrophic cervicitis and endometritis; pus culture developed Escherichia coli and Proteus vulgaris. Despite administration of broad-spectrum antibiotics, the patient developed severe sepsis and died 11 days postoperatively. During a literature review, only one similar case was found. Acute abdomen due to uterine perforation secondary to pyometra and associated with chronic use of corticosteroids is a rare complication.
16857607 Fever of unknown origin in adults: evaluation of 144 cases in a non-university hospital. 2006 The spectrum of diseases found in series of fever of unknown origin shows variation in relation to selection bias; particularly, selection of the most difficult cases in tertiary reference university centres. We present a series of 144 patients presenting to a non-university hospital between 1999 and 2005 (secondary level of the health care system) with a community-acquired fever of unknown origin. In 37 cases (25.7%), the reason for fever could not be explained. Among the 107 patients with a final diagnosis (74.3%), non-infectious inflammatory disorders represented the most prevalent category (35.5%), surpassing infections (30.8%), miscellaneous causes (20.6%) and malignancies (13.5%). 13 entities accounted for over 68% of diagnoses (sinusitis and occult dental infections, Q fever, Epstein-Barr virus and cytomegalovirus infections, lymphoma, colo-rectal adenocarcinoma, adult-onset Still disease, systemic lupus erythematosus, giant cell arteritis and/or polymyalgia rheumatica, rheumatoid arthritis, polyarteritis nodosa, factitious fever and habitual hyperthermia). As demonstrated in other studies, non-infectious inflammatory diseases emerge as the most prevalent diagnostic category. Giant cell arteritis and polymyalgia rheumatica were particularly frequent in the elderly. Epstein-Barr virus and cytomegalovirus infections and habitual hyperthermia were particularly frequent in the youngest patients. There were no major differences in repartition of diagnostic categories between this series and historical university series.
16842190 Novel targets for antiinflammatory and antiarthritic agents. 2006 Inflammation is a complex pathological condition associated with exaggerated human immune system involving various activated immune cells and bio-molecules. Treatment of inflammatory diseases particularly chronic inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease etc. has been a big challenge for scientists as there are no safe drugs available for cure. Current therapeutic approaches to the treatment of inflammatory diseases are centered on cycloxygenase (both COX-1 and 2) proinflammatory enzymes but present available drugs of this category are associated with undesirable gastrointestinal and cardiovascular side effects. Recent scientific advents draw out the secrets of inflammation cache and understanding the involvement of several factors acting as stimulators or inhibitors thus opening new avenues for drug discoveries. Several bio-molecules such as proinflammatory cytokines, components of signal transduction and matrix degrading enzymes resolve inflammatory responses, might be new targets for treatment of chronic inflammatory diseases. This review gathers recent advances in drug research focusing interleukin-1, TNF-alpha, p38 kinase, c-Jun N-terminal kinase MAP kinase, NFkappaB, and matrix metalloproteinases. The biological roles of these inflammatory mediators are clearly understood thus offering new targets for design of novel inhibitors for incurable inflammatory diseases. This also provides an overview of the current nonsteroidal antiinflammatory agents.