Kinetics of intraocular cytokines in the suppression of experimental autoimmune uveoretinitis by type I IFN

The systemic administration of IFN-alpha/beta was previously found to suppress inflammation in rats with experimental autoimmune uveoretinitis (EAU); however, an effect on the systemic immune response was not identified. In order to investigate an immunological basis for suppression at the intraocular level, rats immunized with interphotoreceptor retinoid-binding protein (IRBP) were administered daily intramuscular injections of 10(5) IU IFN-alpha/beta and cytokines were measured by ELISA in intraocular extracts prepared by ultrasonification at various timepoints throughout the course of EAU. In control EAU, intraocular concentrations of IFN-gamma were found to be non-detectable on day 8 before the onset of inflammation, significantly elevated on day 12 at peak inflammation (182+/-106 pg/ml), then non-detectable again on day 16 after inflammation had begun to subside. In contrast, intraocular IFN-gamma in IFN-alpha/beta- treated rats remained non-detectable or low at all timepoints. Measurement of intraocular IL-2 revealed no difference between the two groups of rats. Intraocular IL-4 concentrations were elevated in rats treated with IFN-alpha/beta, although this cytokine was also detected in the same range in controls as well as normal rats. Finally, intraocular IL-10 was non-detectable on day 8, significantly elevated at peak inflammation on day 12 (588+/-139 pg/ml), then decreased to low levels on day 16 in control EAU rats, while remaining non-detectable or low in IFN-alpha/beta-treated rats. These results suggest that acute inflammation in IRBP-induced EAU in rats involves both IFN-gamma and IL- 10 at the local intraocular level, and that systemic administration of IFN-alpha/beta inhibits EAU via a mechanism that involves suppression of both cytokines.      

Characterization of lymphocyte β-adrenoceptor activity and Gs-protein in patients with rheumatic heart valvular disease

Summary— In order to test whether the β-adrenoceptor activity in rheumatic heart valvular disease depends on the ventricular load conditions, we determined their density and binding affinity to [¹²⁵I]-iodocyanopindolol in lymphocytes, as well as plasma catecholamine and cAMP levels in 69 patients with regurgitant and stenotic lesions of the aortic and mitral valves. The patients were classified as having left ventricular pressure overload (LVP), left ventricular volume overload (LVV), mixed lesions (MOL) or right ventricular pressure overload (RVP). The β-adrenoceptor activity was determined by radioligand binding methods, catecholamines by high performance liquid chromatography using an electrochemical detector and cAMP by radioimmunoassay. The mean β-adrenoceptor density (B_max) of the control group was 60.1 ± 9.5 /mol ( n = 29) per 10⁶ lymphocytes. In the study population, the density was decreased by 83% in LVP, 78% in LVV, 87% in MOL and 86% in RVP. Plasma norepinephrine was elevated by 89% in LVP and 60% in MOL, epinephrine by 43% in LVP, 50% in VOL, 115% in MOL and 20% in RVP, while dopamine was not significantly changed, and cAMP was slightly elevated in all four groups. Screening for activating mutational changes in the G_sα-protein gave negative results, possibly dissociating the elevation in plasma cAMP from stimulatory effects of such abnormalities in the G_s-protein signaling. These results show a significant attenuation in lymphocyte β-adrenoceptor density of patients with rheumatic heart valvular disease, irrespective of the type of the prevailing ventricular load conditions. The reduction in receptor density is accompanied by a significant increase in plasma norepinephrine levels in patients with a left ventricular pressure overload and epinephrine in those with volume overload.     

Malignant Centroblastic-Histiocytic Lymphoma of the Skin

A mixed B-cell type centroblastic lymphoma with extraordinarily many histiocytes in a 68-year-old man is reported. Multiple skin tumours were the only clinical manifestation during the first 5 months. The disease then progressed to the lymph nodes, spleen, and parenchymal organs, but the bone marrow remained unaffected until death, 11 months after the onset of signs. C3d receptors were the only surface markers of the centroblasts. The histiocytes were normal with respect to morphology, muramidase staining, and Fc and C3b receptors. This highly unusual spread from skin to lymphoid and parenchymal organs is discussed in the light of lymphoid cell kinetics.     

Embolization of carotid cavernous fistulas via the superior ophthalmic vein

Background: Carotid cavernous fistulae are treatable by various means, one of which is embolization via the superior ophthalmic vein (SOV). The use of this technique over the past 12 years at the Royal Melbourne Hospital, Victoria, Australia, is reviewed.
Methods: Five patients with carotid cavernous fistulas were treated with embolization of the fistula via the surgically isolated SOV.
Results: Each patient had successful endovascular closure of the fistula using embolization via the SOV approach.
Conclusions: Treatment of certain types of carotid cavernous fistulas that cannot be closed by the conventional endovascular (arterial and venous) approaches can be successfully closed by using a transvenous approach through the SOV     

Superficial- and deep-tissue temperature increases in anesthetized dogs during exposure to high specific absorption rates in a 1.5-T MR imager

Superficial- and deep-tissue heating was measured in five dogs during high-specific-absorption-rate radiofrequency (RF) irradiation to see whether significant temperature changes could be produced by a 1.5-T clinical magnetic resonance imager. The RF power output employed was 6.3 times that required for routine imaging. Temperature probes were placed in both deep and superficial tissues, and temperatures were recorded before, during, and after exposure. In each dog, there was a linear temperature increase of several degrees during RF exposure; the maximal average change was 4.6 degrees C in the urinary bladder. The temperature increase was slightly greater in deep tissues than in superficial tissues. The calculated specific absorption rate, based on the temperature change, averaged 7.9 W/kg for all five dogs. These findings argue for continued caution in the design and operation of imagers capable of high specific absorption rates, particularly when they are used for imaging infants or patients with altered thermoregulatory capability.