Evaluating Parkinson's disease patients at home: Utility of self‐videotaping for objective motor,dyskinesia, and ON–OFF assessments

The objective is to test feasibility and utility of home‐based videos for assessing Parkinson's disease (PD) patients. As part of a clinical trial, patients opted between coming to the study sites or learning to videotape assessments at home. Those opting for at‐home filming completed training on videotape techniques. Ten‐minute films were taken at 30‐minute intervals over 8.5 hours, 2 and 4 weeks after study entry using a protocol covering most items of the UDPRS motor examination and all Rush Dyskinesia Rating Scale items. After each filming, patients marked their ON/OFF status, based on prior training. We determined the number of patients who elected self‐taping and the quality of video segments obtained. To assess ON/OFF patient accuracy, we compared the rater's and patient's assessment of ON/OFF at each time point. Of 12 participants, 10 elected self‐videotaping and only 1 time point was missed (99.5% taping compliance). All self‐recorded video segments were clear with all protocol elements included. With the exception of one missed ON/OFF rating, patient‐based self‐ratings occurred on time. Rating ON/OFF, UPDRS, and RDRS assessments for 8.5 hours required 170 minutes by the blinded rater. In spite of patient training, mean ON/OFF concordance between rater and patients was only 64%. At home video‐based self‐recordings are feasible and allow accurate rater‐based ON/OFF assessments. In this group of patients with no or mild fluctuations, in spite of pretrial training, patients were inaccurate in separating ON vs. OFF status. © 2008 Movement Disorder Society     

Truly stentless molded autologous pericardial aortic valve prosthesis with single point attached commissures in a sheep model.

OBJECTIVE: Aortic valve cusp extension and free-hand aortic valve replacement with autologous pericardium has been described. The long-term results were shown to be comparable with commercially available aortic bioprostheses. Nevertheless the relatively demanding surgical technique could not find wide acceptance. We developed a new design of a molded aortic valve, fashioned from autologous pericardium, treated briefly with glutaraldehyde, and simplified the implantation technique using single point attached commissures (SPAC). METHODS: Molded autologous valve prostheses were implanted in the subcoronary aortic position in 10 sheep with the commissures connected to the aortic wall at three single commissural points (SPAC). The prosthesis mean size was 21.6+/-1.3 mm and the construction time (excluding 10 min glutaraldehyde treatment) was 6.2+/-1.2 min. Cardiopulmonary bypass and cross-clamp time was 111.1+/-12.4 min and 75.0+/-16.3 min, respectively. Six sheep were euthanized after 201.2+/-10.3 days (6 months) and four sheep were euthanized after 330.8+/-6.5 days (11 months) postoperatively. RESULTS: In all sheep, the valve was immediately competent. At sacrifice, SPAC has proven to be well anchored to the aortic wall and the pericardial valve to be pliable in all cases. The maximum transvalvular gradient after cardiopulmonary bypass and at sacrifice was 3.7+/-2.2 mmHg and 10.6+/-5.2 mmHg, respectively. CONCLUSIONS: This new truly stentless molded autologous aortic valve with simplified implantation technique (SPAC) makes a reliable implantation in a standard timeframe possible. The simplicity of construction, low cost and absent need for anticoagulation of this molded autologous aortic bioprosthesis offers an attractive alternative and not only for patients in the developing world.     

Potential improvement of tumor control probability by induction chemotherapy for advanced nasopharyngeal carcinoma

PURPOSE: To assess the reduction of tumor bulk and improvement of tumor control probability (TCP) by using induction chemotherapy for advanced nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: From February to December 2005, 20 patients with Stage III-IVB NPC were treated with induction-concurrent chemotherapy and intensity-modulated radiotherapy with accelerated fractionation. Combination of cisplatin and 5-fluorouracil was used in the induction phase and single agent Cisplatin in the concurrent phase. All patients were irradiated at 2Gy per fraction, 6 daily fractions per week, to a total dose of 70Gy. RESULTS: Nineteen (95%) patients completed all 3 cycles of induction chemotherapy and 90% had 2 cycles of concurrent chemotherapy. Induction chemotherapy achieved significant down-staging of T-category in 35% of patients (p=0.016) and reduction of gross tumor volume (GTV_P) from 55.6 to 22.9cc (mean 61.4%, p<0.001). Although the mean radiation dose did not show any substantial change, the volume within GTV_P that failed to reach 70Gy was reduced from 10.2% to 3.8% (p=0.017). The estimated local TCP increased from 0.83 to 0.89 (p=0.002). CONCLUSIONS: Induction chemotherapy using cisplatin-5-fluorouracil could significantly reduce tumor bulk leading to potential improvement in tumor control.     

Factorial design based optimization of the formulation of albumin microspheres containing adriamycin

The use of factorial design in the formulation of adriamycin-associated albumin microspheres, using the heat-stabilization technique, is illustrated. The effect of stabilization temperature, protein concentration and stabilization time on the entrapment and recovery of adriamycin in microspheres have been investigated using a 2 x 4 x 4 factorial design. The associated drug content in unwashed and four times washed microspheres was determined using HPLC. Maximum drug association and drug recovery were obtained from microspheres synthesised using 25 per cent w/v albumin solution and stabilized at 120 degrees C for 2.5 min. Under these conditions, the entrapped and total associated drug content of the microspheres was about 4 per cent and 12 per cent w/w respectively, and the drug recovery was about 75 per cent. The in vitro dissolution study carried out using dynamic dialysis revealed that the release of adriamycin from these particles follows a bi-phasic pattern. The results demonstrate that use of short stabilization time, low protein concentration and low stabilization temperature are required for the formulation of microspheres with high adriamycin content.     

The kallikrein-kininogen-kinin system in chronic inflammation

We examined bradykinin's effects on macrophages and fibroblasts, two cell types important in the pathogenesis of chronic inflammation. Bradykinin stimulated release of proteins of 18 kDa from macrophages. These proteins caused increased thymocyte proliferation (interleukin 1, IL-1) and completely inhibited lipoprotein lipase (tumor necrosis factor, TNF). When fibroblasts were incubated with bradykinin, PGE2 synthesis was stimulated. Pretreatment with IL-1 or TNF dramatically amplified bradykinin-stimulated PGE2 synthesis. Thus, bradykinin is involved in a positive feedback loop in which bradykinin activates macrophages to release potent inflammatory cytokines; these in turn amplify responsiveness of bradykinin target tissues.     

靛玉红肟衍生物及有关化合物的合成与抗肿瘤作用

靛玉红为治疗慢性粒细胞白血病新药。有效率为87.26％。为了进一步提高靛玉红的疗效,减少副作用,探索其构效关系,制备了十九种衛生物,经药理抗动物肿瘤筛选,N,N′—二甲基靛玉红、N—甲基靛玉红肟、N—甲基靛玉红、N—甲基靛玉红肟甲醚、N—乙酰靛玉红和靛玉红肟等有效.     

Assessing the risk of nasopharyngeal carcinoma on the basis of EBV antibody spectrum.

We have evaluated the performance of 3 new EBV ELISA for the diagnosis of nasopharyngeal carcinoma (NPC). The tests were specific for EBNA 1 IgA, EBNA 1 IgG and zta IgG, respectively. Their distinct antigenic specificity permits these assays to be used in concert in an approach that differentiates patients and apparently healthy subjects on the basis of their antibody spectrum. By so exploiting a distinguishing feature of NPC first described by Lloyd Olds and his group (Olds et al., Proc Nat Acad Sci 1966;56:1699-1704) [corrected] that the patients sustain high levels of a broad spectrum of serum EBV antibodies, this approach achieved a sensitivity of 92% and a specificity of 93%, surpassing the performance of each of these assays individually. The enhanced performance is especially useful in population screening. It was shown that relative risk of NPC sustained by apparently healthy subjects residing in a high incidence area for NPC in the Pearl River estuary in Southern China may vary according to EBV antibody spectrum. The risk of the cancer was markedly reduced with odds ratios of 0.009 for 59% of those who had low level of all 3 antibodies. The risk was increased as antibody spectrum broadens and the risk was the highest with an odds ratio of 138 for 0.4% of those who had high levels of all 3 antibodies. Thus, EBV antibody spectrum may serve to guide follow-up measures for early detection of the cancer and/or risk counseling according to level of the risk of the cancer sustained by the screened individuals.     

Clinical evaluation of glass ionomer-silver cermet restorations in primary molars: one year results

Using the half mouth technique, 33 silver amalgam (Dispersalloy) and 40 glass ionomer (Ketec silver) restorations were placed in the primary molars of children aged five to seven years. After one year, 73 restorations were evaluated. The amalgam restorations rated 90-100 per cent alpha for anatomic form and margins with no recurrent caries or fractures. The glass ionomer restorations rated 35 to 55 per cent alpha for anatomic form and margins with 40 per cent being replaced due to fracture of the material. Within the guidelines of this study, glass ionomer silver cermet was not a suitable material for the restoration of interproximal cavities in primary molars.     

Effect of hexasulfobutylated C(60) on the isolated aortic ring of guinea pig.

The effects of hexasulfobutylated C(60) (FC(4)S) and monomalonic acid C(60) (MMA C(60)), the fullerene C(60) derivatives, on isolated endothelium-containing or endothelium-denuded aorta of guinea pig were studied pharmacologically in vitro. In the endothelium-containing preparation of the aortic rings, phenylephrine (PHE) elicited contracture and acetylcholine (ACh) elicited a relaxing effect on the PHE-precontracted preparation. In the PHE-precontracted preparation, MMA C(60) (10 micromol/l) did not elicit a relaxing effect on the PHE-precontracted preparation. However, MMA C(60) (10 micromol/l) significantly reduced the maximum response of the relaxation elicited by ACh. FC(4)S itself significantly relaxed the PHE-precontracted aortic rings. ACh-induced relaxation in PHE-precontracted endothelium-containing strips of the aortic rings was significantly potentiated if pretreated with FC(4)S (10 micromol/l). In the denuded aortic rings, FC(4)S did not elicit the relaxing effect in the PHE-precontracted preparation. The relaxing effect of FC(4)S on the PHE-precontracted preparation was not altered when superoxide dismutase (250 units/ml) was pretreated. However, the relaxing effect was reduced when N(G)-nitro-L-arginine methyl ester (L-NAME, 1 mmol/l) or methylene blue (1 micromol/l) was pretreated. These results demonstrated that the vasorelaxation effect of FC(4)S on the PHE-precontracted aortic ring is partly dependent on the release of nitric oxide (NO) or an NO-derived substance from the vascular endothelium.