临床健康促进与类风湿性关节炎病人生命质量

目的 :提高类风湿性关节炎病人的生命质量。方法 :以健康促进措施与传统临床治疗手段相结合方法 ,制定且实施了一套提高类风湿性关节炎病人生命质量的对策 ,并建立起相应的生命质量评价标准和方法。结果 :对 6 0例类风湿性病人的对照调查研究表明 ,在 2年期间干预组的生命质量上升6 0 .6 3% ,对照组下降 5 3.34%。结论 :上述对策可明显提高病人生命质量 ,能使病人保持良好的身体状况 ,恢复日常生活能力及改善心理状况而得到幸福感和满足感 ,以促进病人身心康复。     

Sleep patterns and blood pressure variability in patients with pure autonomic failure

Sleep patterns and 24-h blood pressure variability were studied in four female patients (age range: 56–82 years) with pure autonomic failure. All patients had severe symptomatic postural hypotension, without neurological deficits. In these patients the following patterns were observed: (i) a reversed diurnal blood pressure pattern, with the highest values observed at sleep onset; (ii) a prolonged sleep latency and increased amount of stage 3 sleep; (iii) difficulty with getting up after awakening in the morning, due to severe postural hypotension; (iv) an absence of prominent respiratory abnormalities during sleep; and (v) a dissociation between respiratory and haemodynamic findings. It is concluded that isolated deficiency of presumed postganglionic autonomic function influences sleep architecture, probably through absence of buffering of diurnal haemodynamic alterations, such as by postural hypotension and its consequences for body fluid volume regulation. This may be of relevance when sleep patterns are studied in other types of autonomic failure with postural hypotension involving central or preganglionic lesions, as in patients with the Shy—Drager syndrome or multiple system atrophy.     

Possible links between behavioral and physiological indices of tiredness, fatigue, and exhaustion in advanced cancer

Goals In this theoretical paper, we present the Edmonton Fatigue Framework (EFF), a new framework for the study of tiredness, fatigue, and exhaustion in advanced cancer. Materials and methods The Fatigue Adaptation Model (FAM), the starting point for the EFF, was drawn from a literature review pertaining to fatigue in depression, chronic fatigue syndrome, cancer, shift workers, and athletes published in the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Medical Literature Analysis and Retrieval System Online (MEDLINE), PubMed, PsychINFO, SPORTdiscus, and CancerLit between 1995 and 2004, and from seven qualitative studies conducted by our group. The EFF, an elaboration of the FAM, was constructed after an expansion of our literature review to 2006 and team discussion. The EFF provides new insights into possible links between behavioral and physiological indices of tiredness, fatigue, and exhaustion as they occur in both ill and non-ill states. In this paper, however, we consider only possible links in advanced cancer. Conclusions We propose that stressors associated with advanced cancer and its supportive treatment trigger declines in four systems—cognitive function, sleep quality, nutrition, and muscle endurance—and that these declines reduce one’s ability to adapt. While these systems each likely has its own effect on adaptation, we propose that the most important and serious effects arise from interactions among declines in cognitive function, sleep quality, nutrition, and muscle endurance. Conclusions Interventions for fatigue have been limited by a lack of understanding about its etiology. Hypotheses arising from the EFF` suggest a new direction for further study that focuses on interactions among cognitive function, sleep quality, nutrition, and muscle endurance.     

Single-dose pharmacokinetics and safety of a novel broad-spectrum cephalosporin (BAL5788) in healthy volunteers

BAL5788 is the water-soluble prodrug of BAL9141, a novel broad-spectrum cephalosporin with potent bactericidal activities against methicillin-resistant Staphylococcus aureus (MRSA) and penicillin-resistant Streptococcus pneumoniae. We investigated the safety and pharmacokinetics of BAL5788 in a double-blind, single-ascending-dose study with 40 healthy male subjects. The subjects were randomized to receive placebo (n = 2 subjects per dose) or BAL5788 (n = 6 subjects per dose) as a 200-ml intravenous infusion over 30 min. The BAL5788 doses used were 125, 250, 500, 750, and 1,000 mg (BAL9141 equivalents). All doses were well tolerated, with no severe or serious adverse events (AEs). The most frequent AE was taste disturbance. No electrocardiographic abnormalities and no trends or clinically significant changes in laboratory parameters or vital signs were observed. The maximum concentration of drug in serum and the area under the concentration-time curve for BAL9141 were dose proportional over the dosing range. The elimination half-life of BAL9141 was about 3 h. The volume of distribution at steady state was equal to the volume of the adult extracellular water compartment, and the rate of renal clearance of free drug corresponded to the normal glomerular filtration rate for adults. More than 70% of the administered dose was excreted as BAL9141 in the urine, and almost no prodrug was detected. After the infusion of 750 mg, the mean plasma BAL9141 concentrations exceeded the MIC at which 100% of MRSA isolates are inhibited (4 microg/ml) for approximately 7 h, or 58% of a 12-h dosing interval. These results indicate that infusions of 750 mg twice a day should be adequate for the treatment of infections caused by MRSA.     

Emerging Role of Ubiquitination in the Regulation of PD-1/PD-L1 in Cancer Immunotherapy

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急性脑出血患者血液中微粒促凝活性的变化

Objective To study the procoagulant activity of microparticles (MP) in patients with acute in-tracerebral hemorrhage (ICH) and to evaluate the correlation between procoagulant activity of MPs and disease out-come. Method From August 2006 through August 2008, 83 consecutive patients with history of hypertension ad-mitted for spontaneous basal ganglia hemorrhage including 54 male and 29 female, aged (60.9±9.7) years ranged from 41 to 79 years, were enrolled into this study. The control group was consisted of 30 age- and sex-matched (P= 0.429; P = 0.415) patients admitted for mild soft tissue injury. Patients with history of head trauma or previ-ous stroke, under the antiplatelet or anticoagulant medication, severe infection, or presence of previous cerebrovas-cttlar disease were excluded. Venous blood sample was kaken within the first 24 hours after disease onset. The MPs procoaulant potential was measured with a prothrombinase assay, and the levels of IL-6,TNF-α, D-dimer (DD)and thrombin-antithrombin Ⅲ complex (TAT) in plasma were measured with enzyme-linked immunosorbent assay. The multivariate analysis was made with forward stepwise logistic regression to determined the predictors of one. month mortality. The plasma levels of MPs were compared between ICH group and control group, between patients with intraventricular hemorrhage (IVH) and those without IVH,and between survivors and non-survivors with the Mann-Whitney U-test. The Spearman' s rank correlation coefficient was used to analyze the correlations between the plasma levels of MPs and ICH volume, Glasgow coma scale (GCS), and plasma levels of IL-6, TNF-α, DD and TAT. A receiver operating characteristic curve (ROC curve) identified the plasma MPs cutoff levels that predicted one-month mortality of patients. Under ROC curve, z statistic analysis was used to compare the area under curves (AUCs) between plasma IMPs and Glasgow coma scale, ICH volumes, and plasma levels of IL-6, TNF-α, DD and TAT for one-month mortality. Results Thirty-six patients (43.4%) died of ICH in a month. The multivariate analyses sorted out the GCS (odds ratio = 0.558, 95%CI:0.367-0.850, P = 0.007), Hematoma volume (odds ratio= 1.061, 95%C1:1.012- 1.113, P = 0.015) and IVH (odds ratio= 5.537, 95%CI:1.035-29.629, P = 0.045) as the independent pcedictors for one-week mortality. The MPs procoagulant activity in the ICH group (6.72±3.26 U/mL) was significantly higher than that in control group (1.84±0.82) U/mL (P = 0.000). The IMPs procoagulant activity in the non-survival group (8.51±3.45) U/mL was significantly higher than that in the survival group (5.35±2.33) U/mL (P = 0.000). The MPs procoagulant activity in the IVH group (7.66±3.39) U/mL was significantly higher than that in the non-lVH group (5.36±2.53) U/mL (P = 0.001). The MPs procoagulant activity was highly associated with GCS scores (r = -0.690, P = 0.000), ICH volumes (r =0.590, P = 0.000), and plasma IL-6 (r = 0.465, P = 0.015), TNF-α (r = 0.464, P = 0.016), DD(r= 0.567, P = 0.001) and TAT(r = 0.469, P = 0.014) in ICH. The ROC curve identified cutoff levels of MPs procoagulant activity to be 7.47 U/mL that predicted one-month mortality of patients with high sensitivity (77.8%) and specificity values (76.6%). Areas under curves (AUCs) of MPs procoagulant activity (AUC =0.825±0.048) were significantly larger than those of plasma IL-6 (AUC = 0.685±0.060, P = 0.042), TNF-α(AUC = 0.681±0.060, P =0.036) and TAT (AUC = 0.644±0.062, P =0.008).The AUCs ofMPs procoag-ulant activity were larger than those of plasma DD (AUC = 0.743±0.056), but this difference was not statistical significance (p = 0.226). Conclusions The procoagulant activity of MPs may contribute to the pathophysiology of ICH. The propcoagulant activity of MPs after spontaneous onset of ICH seems to correlate with clinical outcome in these patients. Its procoagulant activity can be used as an useful clinical marker for evaluating the prognosis of ICH.