A randomized phase II trial of interferon-α2b versus 5-fluorouracil after trabeculectomy*

Purpose: The aim of the present study was to investigate the safety and potential efficacy of subconjunctival interferon-α2b (IFN-α), either alone or in combination with 5-fluorouracil (5-FU), in reducing the risk of failure of glaucoma surgery. Methods: A prospective, masked randomized phase II study was undertaken in which patients received three subconjunctival injections per week for 3–4 weeks postoperatively. Three treatments were compared: (i) IFN-α (1 × 10 ⁶ IU per dose); (ii) 5-FU (5 mg per dose); and (iii) alternating IFN-α and 5-FU (BOTH). The primary outcome measures were: (i) rate of successful control of intra-ocular pressure without further surgery; and (ii) the incidence of side effects. Results: Fifty-seven patients undergoing glaucoma surgery with an increased risk of failure were evaluated, including 23 patients (40%) undergoing trabeculectomy combined with extracapsular cataract extraction as well as other conventional high-risk groups. With 53 patients (93%) completing 2 years follow up, there was no significant difference in success rates among the three groups. Intra-ocular pressure was controlled without further surgery in 79% of patients (95% confidence interval (CI): 61, 97%) receiving IFN-α, in 89% of patients (76, 100%) receiving 5-FU and in 89% of patients (76, 100%) receiving BOTH. Side effects were similar among the three groups. Conclusions: These results are consistent with a beneficial effect of IFN-α2b given either alone or in combination with 5-FU after glaucoma filtering surgery. However, the lack of a clear and substantial benefit over conventional anti-fibrotic therapy does not support the further clinical evaluation of these treatments.     

Effects of intracameral Na2EDTA and EGTA on aqueous outflow routes in the monkey eye

Intracameral perfusion with 4 to 6 mM Na2EDTA or 4 mM EGTA for 40 to 80 min caused a very large increase in gross outflow facility. This effect was partly reversible when followed by perfusion with mock aqueous humor. Eyes perfused with Na2EDTA were studied morphologically. In the trabecular meshwork the cells separated due to a splitting of the cell junctions. A distention of the cribriform meshwork, a wash-out of extracellular material , and a disintegration of the denuded trabecular cores were also noticed. The inner wall of Schlemm's canal protruded in a "balloonlike" manner into the lumen of the canal and showed frank ruptures, especially after prolonged perfusion times. The conventional outflow pathways beyond Schlemm's canal showed no abnormalities. In the uveoscleral outflow routes the anterior and middle part of the ciliary muscle demonstrated very wide intermuscular clefts and many degenerated muscle fibers. The posterior third of the muscle was normal. So were the ciliary epithelium, the choroid, and the retina. The pupillary sphincter also showed degeneration. The corneal endothelial cells separated, starting at the apical junctional complex.     

Effects of Sex,Handedness, Stimulus and Visual Field on “Mental Rotation”

Shepard's mental rotation paradigm (e.g. Shepard and Metzler, 1971) was modified to allow tachistoscopic presentation of stimuli at varying angles of orientation (0° to 180°) in the right and left visual fields. Thirty male and thirty female subjects divided into three handedness groups (right-handers, non-familial and familial left-handers) judged whether a stimulus was a standard form or its mirror image. In general response times for correct judgements (RT_c) increased monotonically as a function of angle of orientation though the curves tended to be negatively accelerated rather than linear. Right-handers showed a slower rate of increase in RT_c as a function of angle than either left-handed group. Mean RT_c and the rate of increase in RT_c were equivalent for the two sexes and for the two visual fields. Both mean RT_cs and on the rate of increase in RT_c varied as a function of the stimulus.Error rates also increased monotonically as a function of angle of orientation. No sex or handedness differences in error rates were found. However, errors increased significantly less rapidly when stimuli were presented in the left visual field. It is argued that right hemisphere specialization for spatial processing minimizes the rate of increase in errors.The present failure to find sex differences may be of interest and it is argued that rapid presentation of stimuli results in subjects setting maximum and minimun response times. Within this relatively restricted “bandwith” of response times males and females may perform spatial tasks equally efficiently. Some confirmation for this hypothesis vs. an alternative based upon differences in hemispheric organization was found in a second experiment.     

Klinische und molekulargenetische Befunde bei Familien mit Cherubismus über 3 Generationen

Hintergrund  

Cherubismus ist eine seltene genetisch bedingte Erkrankung der Knochen, die fast ausschlie?lich den Ober- und Unterkiefer betrifft.     

Bladder Cancer and Arsenic Exposure： Differences in the Two Populations Enrolled in A Study in Southwest Taiwan

Objective Analyses of bladder cancer mortality in the Black Foot Disease (BFD) endemic area of southwest Taiwan conducted by Morales et al. showed a discontinuity in risk at 400 μg/L arsenic in the drinking water in a stratified analysis and no discontinuity in a continuous analysis.     

Porous hydroxyapatite granules for alloplastic enhancement of the facial region

Hydroxyapatite is a biocompatible alloplast with the same chemical composition as bone. It is readily incorporated into host bone, does not undergo appreciable resorption, does not incite a clinically significant foreign body reaction, and resists infection. This article describes forms of hydroxyapatite, procedures for use, and clinical examples.     

Apoptotic-regulatory and complement-protecting protein expression in chronic lymphocytic leukemia: relationship to in vivo rituximab resistance.

PURPOSE: Rituximab has clinical activity in patients with chronic lymphocytic leukemia (CLL) and has a variety of proposed mechanisms, including apoptosis, complement-dependent cell lysis (CDC), and antibody-dependent cellular cytotoxicity (ADCC). Here we examine pretreatment biologic features that promote resistance to apoptosis and CDC in CLL patients and correlate it with clinical outcome to rituximab-based therapy. PATIENTS AND METHODS: Pretreatment samples from 21 CLL patients treated on a prospective, single-agent rituximab trial were examined for quantitative expression of apoptotic and CDC regulatory proteins, and the level of expression of these proteins was correlated with clinical outcome. RESULTS: Of the 21 patents for whom samples were available, 10 attained a partial response and 11 failed to respond to rituximab therapy. The mean pretreatment expression of Bcl-2, Mcl-1, XIAP, and the ratio of Bcl-2/Bax were higher but not statistically increased in nonresponding patients versus those responding to treatment. In contrast, the pretreatment Mcl-1/Bax ratio was significantly elevated (0.82 +/- 0.28 v 0.39 +/- 0.29, P <.016) in nonresponding patients compared with patients responding to rituximab therapy. Although pretreatment expression of CD55 and CD59 was not associated with response to rituximab therapy, significantly higher levels of CD59 were observed in the CLL cells that were not cleared from the blood at completion of therapy than the level observed at baseline levels (P =.02). CONCLUSION: These data indicate that baseline expression of the Mcl-1/Bax ratio, but not CD55 and CD59, predict for clinical response to rituximab therapy in CLL patients. Further study of disrupted apoptosis in CLL as a potential mechanism of resistance to rituximab appears warranted.     

Recombinant human complement C5a receptor antagonist reduces infarct size after surgical revascularization

OBJECTIVES: This study tested the hypothesis that a recombinant human C5a antagonist, CGS 32359, attenuates neutrophil activation and reduces infarct size in a porcine model of surgical revascularization. METHODS: CGS 32359 (0.16-16 micromol/L) dose-dependently inhibited superoxide production by human C5a-activated porcine neutrophils (18 +/- 3.7 vs 1.6 +/- 0.5 nmol/5 min/5 x 10(6) neutrophils; P <.05) and reduced neutrophil adherence to coronary endothelium from 194 +/- 9 to 43 +/- 6 neutrophils/mm(2) (P <.05). The left anterior descending coronary artery was occluded for 50 minutes, after which saline solution (n = 8), mannitol-buffer vehicle (n = 9, 102 mg/kg bolus, 102 mg. kg(-1). h(-1)), or CGS 32359 (CGS, n = 7, 60 mg/kg bolus, 60 mg. kg(-1). h(-1)) was infused. After ischemia, 1-hour arrest was achieved by means of multidose hypothermic (4 degrees C) blood cardioplegia, followed by 2.5 hours of off-bypass reperfusion. The ligature on the left anterior descending artery was released before the second infusion of cardioplegic solution. RESULTS: Area at risk was similar in all groups (saline solution, 27% +/- 2%; mannitol-buffer vehicle, 26% +/- 2%; CGS, 26% +/- 2% left ventricular mass). Infarct size (area necrosis/area at risk) was significantly reduced by CGS (18% +/- 6%, P <.05) versus saline solution (52% +/- 3%) and mannitol-buffer vehicle (60% +/- 4%). Postischemic systolic shortening (sonomicrometry) in the area at risk was significantly improved with CGS (0.8% +/- 0.9%) compared with saline solution (-3.7% +/- 1.1%) and mannitol-buffer vehicle (-6.4% +/- 1.0%). Myeloperoxidase activity from accumulated neutrophils was less in the ischemic zone of CGS (0.014 +/- 0.002 U/100 mg tissue; P <.05) than mannitol-buffer vehicle (0.133 +/- 0.012 U/100 mg tissue). CONCLUSIONS: We conclude that the recombinant human C5a receptor antagonist CGS 32359 inhibits surgical ischemia-reperfusion injury after coronary occlusion.