Anti-citrullinated-protein-antibody-specific intravenous immunoglobulin attenuates collagen-induced arthritis in mice.

Administration of intravenous immunoglobulin (IVIg) is a recognized safe and efficient immunomodulation therapy for many autoimmune diseases. Anti-idiotypic antibody binding to pathogenic autoantibodies was proposed as one of the mechanisms attributed to the protective activity of IVIg in autoimmunity. The aim of this study was to fractionate the anti-anti-citrullinated protein anti-idiotypic-antibodies (anti-ACPA) from an IVIg preparation and to test it as a treatment for collagen-induced arthritis in mice. IVIg was loaded onto an ACPA column. The eluted fraction was defined as ACPA-specific-IVIg (ACPA-sIVIg). Collagen-induced-arthritis (CIA) was induced in mice. Mice were treated weekly with ACPA-sIVIg, low-dose-IVIg, high-dose-IVIg and phosphate-buffered saline (PBS). Sera-ACPA titres, anti-collagen anitbodies and cytokine levels were analysed by enzyme-linked immunosorbent assay (ELISA); antibody-forming-cell activity by enzyme-linked imunospot (ELISPOT) assay; and expansion of regulatory T cell (Treg ) population by fluorescence activated cell sorter (FACS). ACPA-sIVIg inhibited ACPA binding to citrullinated-peptides (CCP) in vitro 100 times more efficiently than the IVIg compound. ACPA-sIVIg was significantly more effective than the IVIg-preparation in attenuating the development of collagen-induced arthritis. Splenocytes from CIA mice treated with ACPA-sIVIg reduced the ACPA and anti-collagen-antibody titres, including the number of anti-collagen and ACPA antibody-forming cells. In parallel, splenocytes from ACPA-sIVIg treated mice secreted higher levels of anti-inflammatory cytokines and lower proinflammatory cytokines. The ACPA-sIVIg inhibitory potential was accompanied with expansion of the Treg population. Low-dose IVIg did not affect the humoral and cellular response in the CIA mice in comparison to the PBS-treated mice. Based on our results, IVIg may be considered as a safe compound for treating patients with rheumatoid arthritis by neutralizing pathogenic autoantibodies, reducing proinflammatory cytokines and expanding the Treg population.

Width of the extended facial recess: a numerical study of ultrahigh-resolution computed tomography and its implications in minimally invasive otologic surgery.

BACKGROUND: Methods of minimally invasive computer-assisted otologic surgery lag behind other fields. The reason seems to be the extremely small dimensions of the corridors between important structures in the temporal bone and the fact that these structures are encased in bony frameworks, are obscured before drilling, and are not movable. The extended facial recess is a surgical pass to the tympanic cavity. It is bounded medially by the facial nerve and laterally by the tympanic annulus, and varies among individuals. For computer-assisted, minimally invasive temporal bone surgery, high-resolution definition is critically important. AIMS: To determine the width of the extended facial recess and evaluate the computerized findings as a pre- and intraoperative aid to otologic surgery planning. METHODS: Bilateral temporal bone high-resolution computed tomographic images of 100 male and 100 female patients were measured twice at five levels (caudal to cephalic), first using a window-independent algorithm (extended facial recess, full-width at half-maximum), implemented in a computed tomographic image-processing workstation, and then manually with calipers on the same axial computed tomographic images. RESULTS: As expected, the extended facial recess, full-width at half-maximum method yielded the widest values superiorly (4.15 +/- 0.41 mm in the female patients and 4.32 +/- 0.54 mm in the male patients). From this level down, the extended facial recess, full-width at half-maximum method yielded values that tapered gradually to 2.50 +/- 0.56 mm in the female patients and 2.42 +/- 0.46 mm in the male patients at the most interior level. The manual method (extended facial recess, computed tomographic images) yielded a significantly higher value than that obtained with the objective, window-independent method at all levels, and at some levels was higher by as much as one-third. At Level 2, which corresponded roughly to the round window, the extended facial recess was 4.00 +/- 0.65 in the female study group and 4.11 +/- 0.67 mm in the male study group. CONCLUSION: Image processing methods such as extended facial recess, full-width at half-maximum method might lead to fine tuning and thus improvement of computer-assisted otologic surgery. Before clinical application and complete dependence on these automated methods during otologic surgery, their reliability should be further validated.

Volume of mastoid pneumatization: three-dimensional reconstruction with ultrahigh-resolution computed tomography.

The volume of the mastoid air cell system was measured in 69 patients with normal middle ears. All patients underwent axial ultrahigh-resolution computed tomography. Mastoid pneumatization was marked on each axial slice, and 3-dimensional reconstruction was performed. The volumes were measured with a volumetric algorithm. A polyethylene tubing phantom with a density similar to that of bone on computed tomography was devised. The polyethylene tubing was tied in a particular fashion so as to create interconnecting air spaces with a known volume. The phantom was scanned with the imaging parameters used for scanning the temporal bone. The air in the tubing was marked, and 3-dimensional reconstruction for the marked phantom air was performed. The volume of the interconnecting air spaces was measured and found to be identical to its known volume, thereby verifying the accuracy of the method used. The mean mastoid volume was 6.61 cm3. The smallest volume measured was 1.3 cm3, and the largest was 12.7 cm3. The importance of this technique lies in its high accuracy, ease of use, and ability to directly correlate mastoid size and clinical findings.

[Silicone gel-filled breast implants and breast cancer--an update and safety].

Silicone gel-filled breast implants have long been an important method of breast reconstruction and breast augmentation. In 1992, the Food and Drug Administration (FDA), implemented a voluntary but strongly urged moratorium on the sale and use of silicone gel-filled breast implants. This was due to previous anecdotal reports regarding possible health hazards associated with these types of implants, including the emergence of breast cancer. The FDA allowed the use of silicone gel-filled breast implants for post-mastectomy reconstruction, and also in a small number of breast augmentation patients who were willing to enroll in a long-term prospective study. In this article, we review the current available literature that failed to produce any evidence associating the use of silicone breast implants with the increased risk of breast cancer.

Stenosis in antiphospholipid syndrome: a new finding with clinical implications.

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by a variety of clinical manifestations. Recent studies suggest arterial stenosis is involved in APS. Furthermore, arterial stenosis may be a relevant and treatable cause for hypertension, renal, CNS and gastrointestinal manifestations of APS. Our objective was to overview the published data regarding arterial stenosis in APS--the clinical presentation, diagnosis, suggested therapies and the possible mechanisms. We searched PUBMED (1951-2006) reference lists for the role of arterial stenosis in APS. APS patients might present with arterial stenosis. Its recognition has important diagnostic and therapeutic implications. Articles suggest that anticoagulation treatment with INR above three may reverse the artery stenosis and achieve subsequent clinical improvement. Currently, there are no specific guidelines for the management of APS patients with arterial stenosis. The exact mechanism of arterial stenosis in APS patients remains unclear.

Stress-induced osteolysis of distal clavicle: imaging patterns and treatment using CT-guided injection.

Osteolysis of distal clavicle (ODC) may occur in patients who experience repeated stress or microtrauma to the shoulder. This entity has clinical and radiological findings similar to post-traumatic ODC. We describe a case of successful treatment of stress-induced ODC with CT-guided injection of corticosteroid and anesthetic drug into the acromioclavicular joint.

How accurate is helical CT volumetric assessment in renal tumors?

The aim of this study was to evaluate the accuracy of tumor size measurement on CT studies of renal tumors. Sixteen patients with tumors of the kidneys were imaged by helical CT prior to surgery. Assessment of tumor volume was made by two radiologists on the CT images with the summation of area method, then compared with the resected specimen water displacement volume. Intra- and interobserver agreement for CT measurements were also assessed. There were substantial differences between the CT volume measurement compared with the tumor post-operative volume (mean of differences 30.05+/-91.6, 95%CI: 31.45-91.55). The inter- and intraobservation agreements for tumor measurement by CT was found to be satisfactory (ANOVA: p < 0.0001; t-test: p < 0.05). The CT volumetric measurement by area summation is a method with good inter- and intraexamination reproducibility but not an accurate technique for tumor volume assessment.

Pyknodysostosis: imaging and laboratory observations.

Pyknodysostosis is a rare form of sclerosing bone dysplasia with autosomal recessive inheritance. Affected members of two families were assessed as follows: three patients underwent densitometry measurements and bone scans; four patients underwent magnetic resonance imaging (MRI) and an immunological investigation, as well as a detailed endocrinological and biochemical laboratory review. Densitometry measurements revealed values of up to 291% of age-matched normal controls; this increased bone density was mainly in the trabecular bone and not in the cortical bone. The MRI showed the cortex to be of normal thickness, whereas the increase in trabecular bone limited the space within the medullary canal. Bone scans and single photon emission computerized tomography in three patients showed an increased uptake of [99mTc]methylene diphosphonate of up to 538% of age-matched controls, which reflected the increased bone density. Monocyte function tests demonstrated a normal phagocytic capacity, but their killing activity was impaired. Interleukin-1 secretion was also impaired, which may point to the pathogenesis of the disease, in view of its function as an osteoclast activator and its role in bone resorption.

Multiple autoantibodies in patients with silicone breast implants.

Diverse immunologic abnormalities have been described in women who received silicone breast implants. However, most studies have focused on either a limited number of patients or a small panel of autoantibodies. We report the analysis of 20 autoantibodies in 116 women with implants and 134 controls. The patients ranged from 26- to 66-years-old, with a mean of 45.7 +/- 8.3 years; breast prostheses were in place for a mean of 15 +/- 5.6 years, with a range of 4 to 30, the chief complaints of the 116 patients included polyarthralgias, fatigue, myalgias, morning stiffness, and decreased memory. All 250 sera were tested blindly using a panel of 20 autoantigens including SS-A, SS-B, RNP, cardiolipin (CL), collagen types I, II and IV, phosphatidylserine (PS), myeloperoxidase (MPO), sulfatides (sulf), thyroglobulin (TG), gangliosides (GDIa;GM2), proteinase-3 (PR3), Jo-1, Sm, HPRPP-ribosomal phosphate, histones (H2AH2B), Scl-70 and glomerular basement membrane (NC-1). Values from individual patients were considered positive only when greater than 3 SD above the control mean. There was a statistically significant greater frequency of autoantibodies in women with implants for 15 of the 20 autoantigens; these were particularly striking for anti-H2AH2B, HPRPP, SS-A, SS-B, Scl-70, CL, PS, GM2, and NC-1. Many patients harbored several autoantibodies; 20% had four autoantibodies; 8% had six autoantibodies. The association of autoantibodies and implants suggests an adjuvant action of silicon/silicone byproducts.

Oxidized low-density lipoprotein (Ox-LDL) but not LDL aggravates the manifestations of experimental antiphospholipid syndrome (APS).

Ox-LDL is thought to play a major role in atherogenesis. The mechanisms mediating the deleterious influences of Ox-LDL include foam cell formation and cell cytotoxicity. The production of anti-Ox-LDL antibodies results in the formation of immune complexes which are taken up at enhanced rate by macrophages, leading to foam cell formation. APS is characterized by repeated venous and arterial thromboembolic phenomena, recurrent fetal loss and thrombocytopenia, associated with the presence of antibodies to negatively charged phospholipids (aPL) (i.e. cardiolipin, phosphatidylserine). Phospholipids bear structural resemblance to LDL, and several studies have indeed proved that aPL display cross-reactivity with anti-Ox-LDL antibodies. In this study we assessed the capacity of oxidized and native forms of LDL to aggravate the clinical picture of experimentally induced APS in naive mice. Mice were actively immunized intradermally with anticardiolipin antibodies and developed a clinical picture resembling APS in humans. Subsequently, the mice were infused with either Ox-LDL, native LDL or PBS, and similar regimens were applied to controls. APS mice infused with Ox-LDL were found to exhibit a significantly more severe form of the disease in comparison with native LDL- and PBS-infused mice, expressed by lower platelet counts (261,000/mm3, 535,000/mm3 and 455,000/mm3, respectively), longer activated partial thromboplastin time (aPTT) (99 +/- 12 s, 63 +/- 8 s and 74 +/- 8 s, respectively) and higher fetal resorption rates (72.7%, 34.4% and 32.6%, respectively). The results of this study show that Ox-LDL, compared with native LDL, aggravates the clinical manifestations of experimental APS and suggest that cross-reactivity of Ox-LDL with phospholipids may provide a pathogenic explanation for this effect.

Mycoplasma-pneumoniae-induced thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura (TTP) is a fatal disease characterized by widespread platelet aggregation, hemolytic anemia and fever with renal and neurological involvement. Different factors have been associated with the development of TTP, e.g. infections, pregnancy, chemotherapy, drug therapy and bone marrow transplantation. Recent data imply that all these different causes may induce the disease by decreasing the activity of the plasma von Willebrand factor-cleaving protease resulting in unusually large von Willebrand factor multimers that later on initiate the cascade of TTP. In this communication, we present a unique association between infection with Mycoplasma pneumoniae and TTP. We believe that the emergence of antibodies that cross-react with Mycoplasma and the protease might elucidate in this case the pathogenesis of TTP.