Correlation of metalloproteinase-2 and -9 with proinflammatory cytokines interleukin-1b, interleukin-12 and the interleukin-1 receptor antagonist in patients with chronic uveitis.

PURPOSE: Matrix metalloproteinases have been shown to play a role in active uveitis. Transcription of MMPs is induced by a number of growth factors and cytokines. This study investigates the role of MMPs in chronic uveitis and correlates the amounts of MMP-2 and -9 in intraocular samples to the intraocular levels of proinflammatory cytokines (Interleukin-1 [IL-1], Interleukin-12 [IL-12] and Interleukin-1 receptor antagonist [IL-1ra]). METHODS: Aqueous humor of 16 patients was collected during surgical or diagnostic procedures (control group: cataract patients). MMP-2 and -9 were measured using zymography. IL-1beta, IL-12 and IL-1ra were evaluated by ELISA. RESULTS: We found MMP-2 and -9 in all of our uveitis patients. In the control group only MMP-2 was seen. Higher levels of MMP-2 and -9 were found in patients with higher activity of uveitis (p < 0.014 for MMP-2, p < 0.0054 for MMP-9). The amounts of IL-1beta, IL-12 and IL-1ra detected in our uveitis patients correlated with levels of MMP-2 (p < 0.07, p < 0.0004, p < 0.03) and MMP-9 (p < 0. 003, p < 0.0001, p < 0.002), and IL-12 (p < 0.004, p < 0.0001). Patients with moderately active uveitis presented with twice the level of MMP-2 as the control group; MMP-9 levels reached up to 92% of the amounts found in patients with active uveitis. Two patients in remission for almost one year still had detectable intraocular MMP-9 levels. CONCLUSION: Our data suggests that the high levels of MMPs found in patients with chronic uveitis might contribute to the damage often seen in these eyes. Since MMPs are capable of releasing proinflammatory cytokines bound to components of the extracellular matrix, and facilitate the secretion of active TNF-alpha by cleavage of the membrane bound form, it is conceivable that MMPs contribute to the chronicity of some uveitis cases.

Influence of intravenous immunoglobulin therapy on serum levels of anti-beta 4 antibodies in ocular cicatricial pemphigoid. A correlation with disease activity. A preliminary study.

PURPOSE: To determine any correlation between activity of ocular cicatricial pemphigoid and titer of anti-beta 4 antibodies, and any effect of intravenous immunoglobulin (IVIg) therapy on serum levels of anti-beta 4 antibodies followed over a 12 month period, using the specific immunoblot assay (IBA). PATIENTS AND METHODS: Eight patients diagnosed with OCP and treated with IVIg as monotherapy were included in the study. Each patient was treated with at least two immunosuppressive agents prior to the institution of IVIg. The presence of anti-beta 4 antibodies in the patients' sera was detected by IBA using bovine gingival lysate (BGL) or tumor cell line lysate (TCL) as substrates. The activity of OCP was graded based on the conjunctival injection using a scale of zero to four in increments of 0.5 at monthly intervals. To determine the correlation between serum levels of circulating autoantibody and the patients' conjunctival disease activity, the titer of anti-beta 4 antibodies was determined at monthly intervals during the course of IVIg therapy. Blood samples were drawn prior to administration of IVIg infusion. The titer was determined by IBA, using serial dilutions of the patients' sera. The highest dilution at which the binding was visible was considered the titer. The dose of IVIg administered was approximately 2-3 g/kg/cycle. The infusion cycles were initially given at monthly intervals, approximately 70 grams daily over four hours for three consecutive days. As clinical improvement was observed, the interval between the cycles was increased, but the dose of IVIg remained the same for each cycle. To study whether the IVIg has an effect on other antibodies, monthly serum levels of antibodies to tetanus toxoid were measured by ELISA. RESULTS: We observed a continuous decrease in mean monthly titer of circulating anti-beta 4 antibodies in the patients' sera during IVIg therapy. A decrease in conjunctival inflammation during the course of IVIg was documented by monthly examination in every patient and paralleled the decrease in titer of anti-beta 4 antibodies. Since the fifth month of IVIg therapy, the mean conjunctival inflammation remained less than 0.5, suggesting a clinical remission of OCP. Titers of antibodies to tetanus toxoid remained unchanged during the study period. CONCLUSIONS: This preliminary study demonstrates a correlation between serum titers of anti-beta 4 antibodies and clinical disease activity in patients with OCP. In addition, the study shows that the use of IVIg is associated with a decrease in the serum titer of anti-beta 4 antibodies.

Topical diclofenac sodium, dexamethasone and placebo compared in a model of immunogenic uveitis in rabbits.

Unacceptable side effects involved in topical steroid usage for uveitis have prompted the search for alternative antiinflammatory drugs for the treatment of ocular inflammation. Cyclooxygenase inhibitors have been widely used for systemic inflammatory conditions over the last two decades and are therefore natural candidates to be studied for uveitis therapy. Previous studies of cyclooxygenase inhibitors in uveitis models yielded inconclusive and sometimes contradicting results. The authors compared the clinical effect of topical dexamethasone, diclofenac and placebo in an immunogenic uveitis model produced in ovalbumin immunized NZW rabbits challenged with ovalbumin in the vitreous. Nine clinical parameters of inflammation were compared employing a double blind placebo controlled protocol. Three groups of 16 eyes each, were assigned for each preparation and were followed for nine days with biomicroscopic examinations. Diclofenac was superior or equal to dexamethasone for iris hyperemia (p=0.059) and conjunctival injection (p=0.02), equal for corneal haziness and AC fibrin, yet inferior for corneal endothelial debris, iris fibrin and AC cells and flare (p<0.05). Placebo was inferior (p<0.05) to the other groups for the above mentioned parameters excluding fibrin precipitation on the iris that was greater in diclofenac treated eyes. While some clinical criteria of inflammation responded better to steroids than to diclofenac, the results of this study show that others responded better or equal to diclofenac. The authors hypothesize that although diclofenac reduces prostaglandin levels it may induce high levels of leukotrienes that maintain cellular exudation.

Ultrasound-guided intrauterine removal of intrauterine contraceptive devices in pregnancy.

The risk to the embryo and to the mother when pregnancy results with an intrauterine device (IUD) in the uterus is well documented. Current advice in such cases is to remove the IUD if the string is visible; proper management when the string is not accessible is controversial. In four such cases, we were able to remove the IUDs from inside the uterine cavity using a small alligator forceps guided by high-resolution ultrasound. All four pregnancies progressed successfully to term. Based on the literature and our own experience, we recommend removal of IUDs or therapeutic abortion when pregnancy occurs with an IUD in situ.

Pulmonary pseudonodule.

A nodular density seen at the posterior lung base on lateral chest radiographs proved to be normal bone in the spine. This nodule results from slight thickening of the bone at the superior aspect of the area where the two laminae join to form the spinous process.

Improvement in the ultrasonic evaluation of the gall bladder by using the left lateral decubitus position.

The authors discuss the value of routinely using the left lateral decubitus position for ultrasound evaluation of the gall bladder. This technique often affords improved visualization, clarifies abnormalities suspected in the supine position, and in some cases demonstrates a gall bladder that cannot be seen in the supine position.

Lisfranc's tarsometatarsal fracture-dislocation.

Lisfranc's fracture-dislocation is an injury at the tarsometatarsal joints. Usually the metatarsals dislocate dorsally and laterally. These frectures can be subtle, and a knowledge of the normal relationships is essential. Review of foot radiographs indicated that the most constant normal relationship of the tarsometatarsal joints is the alignment of the second tarsometatarsal joint, which, fortunately, is involved in most Lisfranc's dislocations. There is more variation in normal alignment of the other tarsometatarsal joints, but gross abnormalities are detectable, and the presence of associated chip fractures and clinical correlation will usually clarify more subtle cases.