Immunoadsorption with tryptophan columns: A therapeutic option for the treatment of rheumatoid arthritis with septic complications

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease affecting multiple organs and tissues. Although there is a wide range of therapeutic applications, the coexistence of severe side effects and contraindications outlines the necessity of new therapeutic options in the treatment of severe RA. We report on the case of a 71‐year‐old patient with successful treatment of a complicated RA with tryptophan immunoadsorption combined with low‐dose steroids. Bacterial spondylitis developed in this patient during long‐term treatment with infliximab and methotrexate. Weekly immunoadsorption sessions with tryptophan columns resulted in continuous suppression of RA activity over a period of more than 5 months, as indicated by laboratory findings, the disease activity score, and the visual analog scale. This is the first report of successful treatment of a refractory and complicated RA using tryptophan immunoadsorption columns. In conclusion, immunoadsorption is a safe and effective therapeutic alternative, which should be considered to bridge infectious complications in patients with severe RA. J. Clin. Apheresis, 2009. © 2009 Wiley‐Liss, Inc.     

Inflammation of unknown origin versus fever of unknown origin: Two of a kind

ObjectivesA vast literature exists on fever of unknown origin (FUO), characterized by prolonged and perplexing fevers > 38.3 °C. In contrast, no studies are available to guide the approach to inflammation of unknown origin (IUO), defined as prolonged and perplexing inflammation with temperatures < 38.3 °C. We aimed to determine the diagnostic yield, the case-mix, and the outcome of patients with IUO, relative to patients with FUO.MethodsWe matched 57 patients with IUO to 57 patients with FUO of the same gender (54% male) and a similar age (median: 67 years).ResultsA diagnosis was established in 35 patients with IUO (61%) and in 33 patients with FUO (58%) (p = .70). The case-mix did not differ significantly (p = .43). Non-infectious inflammatory disorders were the dominant diagnostic category in the IUO group (16 patients), while in the FUO group, similar numbers of malignancies [10], infections [9], and non-infectious inflammatory diseases [9] were diagnosed. ¹⁸F-fluorodeoxyglucose-positron emission tomography (FDG-PET) scan contributed comparably to the diagnosis in both groups (in 18 of 50, 36%, patients with IUO and in 13 of 40, 33%, patients with FUO) (p = .83). In both groups, 7 patients (12%) died during an average follow-up of 1 year.ConclusionDiagnostic yield, case-mix, contribution of FDG-PET scan and vital outcome were similar in patients with IUO and FUO. These data suggest that the 38.3 °C boundary may be arbitrary and that the diagnostic approaches used in FUO can be applied to IUO.     

Age‐dependent normative values for differential luminance sensitivity in automated static perimetry using the Octopus 101

Purpose: To determine age‐dependent normative differential threshold values for the Octopus 101 instrument and to create a smooth mathematical model characterizing the age‐dependency and asymmetry of the hill of vision. Methods: Static automated perimetry within the central 30° visual field (VF) was conducted with the Octopus 101 (background luminance 10 cd/m²) in 81 eyes of 81 ophthalmologically healthy subjects (11–12 per decade of age) aged 10–79 years. A 4‐2‐2 staircase strategy with three reversals was run. The test point grid consisted of 68 concentrically arranged points with test point condensation towards the VF centre, representing the approximately rotation‐symmetrical 30° hill of vision. Thresholds of differential luminance sensitivity (DLS) were estimated by the maximum likelihood method. A smooth mathematical model was fitted to the normative data. Results: The model fit was satisfactory (r² = 0.74). Covariables were: age, eccentricity, angle and subject. Total random standard deviation (SD) was 1.75 dB. The residual SD exceeded 1.75 dB in the border region, was 1.5 dB within the centre and fell below 1.25 dB in a ring around the centre. Average thresholds of DLS varied with age quadratically. It is close to constant for the 10–40–year‐old age group and declines ever more steeply thereafter. The effect of age on DLS in the VF increased with eccentricity. The greatest drop was located in the peripheral superior hemifield: at 25° eccentricity the superior DLS was estimated to be 5.5 dB higher in 10‐year‐olds than in 75‐year‐olds. Conclusions: This new smooth model allows for the prediction of age‐related normal threshold values for any stimulus location within the 30° VF and thus for the calculation of global and local measures of defect such as mean defects or p‐values for any type of stimulus.     

Age dependent secretion of LH and ACTH in healthy men and patients with erectile dysfunction

OBJECTIVES: Age dependent secretion of testicular and adrenal androgens was examined in healthy men and patients with erectile dysfunction (ED). METHODS: In 95 healthy men (age 20-74 years) and 739 patients with ED, luteineizing hormone (LH, n = 739), adrenocorticotropic hormone (ACTH, n = 480) and the secretion products of testis and adrenal gland testosterone (T, n = 750), free testosterone (fT, n = 718), dehydroepiandrosteronesulfate (DHEAS, n = 598) and cortisol (n = 538) were measured. RESULTS: In healthy men, LH was measured from 0.75-8.58 mIU/ml and ACTH from 10.59-121.7 pg/ml. Statistically, age was not correlated to LH (P = 0.573) and ACTH (P = 0.833) in healthy men. The secretion products T (P < 0.05), fT (P < 0.001), DHEAS (P < 0.001) and cortisol (P < 0.05) declined significantly with age in healthy persons. In patients with ED, a significant age dependent increase of LH (P < 0.05, n = 739), but not ACTH (P = 0.469, n = 480) was found. T (P < 0.001, n = 736), fT (P < 0.001, n = 718) and DHEAS (P < 0.001, n = 598), but not cortisol (P = 0.307, n = 538) declined in age dependent patients with ED. Age matching revealed a statistical significant elevation (P < 0.05) only for LH (n = 659) in comparison to healthy men (n = 94), all other hormones were not different in both groups. CONCLUSION: An LH-increase in patients with erectile dysfunction underlines the importance of Leydig cell degeneration in this disease, but age dependent decline of T secretion was comparable to healthy men, demonstrating a working hypophyseal-testicular-axis. Indication of androgen replacement is therefore limited to selected cases.     

Effect of squalamine on iris neovascularization in monkeys

PURPOSE: To investigate the effect of squalamine, an antiangiogenic aminosterol, in an experimental model of iris neovascularization. METHODS: Iris neovascularization was created in cynomolgus monkeys by occluding retinal veins with an argon laser and inducing persistent hypotony with a central corneal suture. Twenty-four eyes were treated in three groups. In Group 1, four eyes were injected intravitreally with 3 microg/0.1 mL squalamine and four eyes with balanced saline solution (controls) immediately after vein occlusion (day 1); injections were repeated every 3 days for 3 weeks. In Group 2, 1 mg/kg squalamine was administered with intravenous infusion in dextrose 5% in four animals; four control animals received only dextrose. Infusions began on day 1 and were repeated every 3 days for 3 weeks. In Group 3, after development of iris neovascularization on day 7, 1 mg/kg squalamine was injected systemically in four animals; four control animals received dextrose 5%. Monkeys were examined by slit-lamp biomicroscopy and underwent color photography and fluorescein angiography. RESULTS: Group 1: All eyes, treated and control, developed intense and persistent rubeosis iridis. Group 2: Two of the four treated eyes in this group developed minimal iris neovascularization; the other two had no iris neovascularization. All four control eyes developed intense, persistent iris neovascularization. Group 3: All eyes developed extensive rubeosis iridis; iris neovascularization regressed in all four treated eyes after squalamine injections. Two of four treated eyes retained minimal iris neovascularization; two showed complete regression of rubeosis iridis. Rubeosis iridis completely regressed in two of the four control eyes; the remaining two control eyes had intense, persistent iris neovascularization. CONCLUSIONS: Intravitreally injected squalamine did not affect the development of iris neovascularization; however, systemic squalamine injection inhibited the development of iris neovascularization and caused partial regression of new vessels in a primate model.     

Ocular toxicity of intravitreal tacrolimus

BACKGROUND AND OBJECTIVE: To investigate the ocular toxicity of intravitreally administered tacrolimus, a drug with potent immunosuppressive activity. METHODS: To evaluate toxicity, tacrolimus was injected into the midvitreous cavity of 20 eyes of New Zealand pigmented rabbits at concentrations of 10, 50, 100, 250, 500, and 1000 microg. Control eyes received balanced salt solution. Eyes receiving 1000 microg were given injections of 0.2 mL solution; all others, including controls, received 0.1 mL. Rabbits were examined before the injections by slit-lamp biomicroscopy, indirect ophthalmoscopy, and an electroretinography test (ERG) was performed. The animals were followed up to 14 days postinjection by clinical examination and ERG. The animals were killed and the eyes were enucleated and processed for light microscopy. RESULTS: No evidence of a retinal toxic reaction was seen in the eyes receiving 10 or 50 microg of tacrolimus. One out of 4 eyes that received 100 microg of the drug developed a vitreous reaction. All eyes treated with 250 microg or more developed vitreous reaction. One eye injected with 1000 microg of the drug developed occlusion of the temporal retinal vessels. Electroretinography showed decreasing b-wave amplitude with both dark- and light-adapted stimulus in the 500 and 1000 microg groups, and it was normal in the other groups. Histopathologic sections showed mild disorganization of the retina only at the 500 and 1000 microg dosage. CONCLUSIONS: Doses of 10 and 50 microg of tacrolimus are nontoxic to rabbit eyes. Only transient vitreous opacities were observed in the groups that received 100 and 250 microg. Intravitreal doses of 500 and 1000 microg of tacrolimus proved to be toxic to the retina.