Population Pharmacokinetics of High-dose Methotrexate After Intravenous Administration in Chinese Osteosarcoma Patients from a Single Institution

Background:High-dose methotrexate (HD-MTX) with folinic acid (leucovorin) rescue is the gold standard therapy in the treatment of osteosarcoma.The plasma concentration of MTX is closely related to effi...     

Macroscopic and Histological Evaluations of Meniscal Allograft Transplantation Using Gamma Irradiated Meniscus: A Comparative in Vivo Animal Study

Background:

Many studies suggest that the gamma irradiation decreases allograft strength in a dose-dependent manner. However, no study has demonstrated that this decrease in strength translates into higher failure rate in meniscal allograft transplantation (MAT). The aim of this study was to investigate the effects of gamma irradiation on macroscopic and histological alterations of transplanted meniscal tissue and joint cartilage after MAT.

Methods:

Medial total meniscectomies were performed on the right knees of 60 New Zealand white rabbits. All meniscal allografts were divided into three groups (20 in each group) and then sterilized with 0 Mrad, 1.5 Mrad, or 2.5 Mrad of gamma irradiation. For each group, 5 menisci were randomly chosen for scanning electron microscopic (SEM) analysis and the remaining 15 were prepared for MAT surgeries. Forty-five right knees received MAT surgeries (0 Mrad group, 1.5 Mrad group, 2.5 Mrad group, 15 in each group), whereas the remaining 15 only received medial meniscectomy (Meni group). The left knees of the Meni group were chosen as the Sham group (n = 15). All the rabbits were sacrificed at week 24 postoperatively. Cartilage of the medial compartment of each group was evaluated macroscopically using the International Cartilage Repair Society (ICRS) score and then histologically using the Mankin score based on the Masson Trichrome staining.

Results:

The SEM analysis confirmed that the meniscal collagen fibers would be significantly damaged as the dose of gamma irradiation increased. At week 24, the overall scores of macroscopic evaluations of the transplanted meniscal tissue showed no significant differences among the three groups receiving MAT surgeries, except for 2 in the 2.5 Mrad group presented partial radial tears at midbody. The ICRS scores and the Mankin scores showed the lowest in the Sham group and the highest in the Meni group (P < 0.05). For the three groups receiving MAT surgeries, the 2.5 Mrad group showed significant higher ICRS scores and Mankin scores than both the 0 Mrad group and the 1.5 Mrad group (P < 0.05). Whereas the 1.5 Mrad group presented similar results to the 0 Mrad group concerning both the ICRS scores and the Mankin scores.

Conclusions:

The current in vivo animal study proved that although the meniscal collagen fibers were damaged after gamma irradiation, the failure rate of MAT surgeries might not significantly increase if the irradiation dose was <1.5 Mrad for New Zealand white rabbits.     

北京、库尔勒地区胃食管反流病与幽门螺杆菌感染的临床观察

目的了解北京、新疆库尔勒(南疆)不同地区、性别、民族其成人胃食管反流病(GERD)、反流性食管炎(RE)的检出率及幽门螺杆菌(Hp)感染的情况,以期指导临床治疗。方法2000年7至12月,对北京、库尔勒两地有上消化道症状患者778例,进行胃镜、病理检查及快速尿素酶试验,部分患者还进行了24h食管pH动态监测和13C呼气试验。结果(1)北京地区汉族、库尔勒地区汉族和维族GERD检出率分别为6.4%、13.7%和25.5%(P<0.01);RE检出率分别为3.1%、6.6%和15.7%(P<0.01)。(2)北京地区汉族、库尔勒地区汉族和维族男性GERD检出率分别为6.5%、12.9%和25.0%(P<0.01),RE检出率分别为4.5%、9.7%和25.0%(P<0.01);女性GERD检出率分别为6.4%、14.4%和26.3%(P<0.05),RE检出率分别为1.3%、3.3%和0%(P>0.05)。(3)北京地区汉族、库尔勒地区汉族、维族GERD患者Hp感染率分别为20.0%、24.0%和23.1%(P>0.05);RE患者Hp感染率分别为23.5%、25.0%和25.0%(P>0.05)。结论北京和库尔勒地区不同民族、性别的GERD、RE的检出率均有差异,以后者为高,而其GERD、RE患者的Hp感染率差异无统计学意义。     

Search for clinical predictors of good glycemic control in patients starting or intensifying oral hypoglycemic pharmacological therapy: A multicenter prospective cohort study

AimsOur aim was to search for clinical predictors of good glycemic control in patients starting or intensifying oral hypoglycemic pharmacological therapy.MethodsA multicenter, prospective cohort of 499 diabetic subjects was enrolled in this study: patients with newly diagnosed diabetes (NDM group) or poor glycemic control with oral antidiabetic drugs (OADs) (PDM group). All subjects then started or intensified OADs therapy and followed up for 91 days. Glycemic control was determined according to HbA1c at day 91 with HbA1c <7% considered good.ResultsThe proportions of patients with good glycemic control after follow up for 91 days were 66.9% and 34.8% in NDM group and PDM group respectively. Logistic regression analysis showed that the change in GA at 28 days was the only predictor of good glycemic control in NDM patients (OR = 1.630, 95% CI 1.300–2.044, P < 0.001). In PDM patients, changes in GA at 28 days, CPI, baseline HbA1c, diabetic duration, and BMI were all independent predictors of good glycemic control (All P < 0.05).ConclusionsGA decline is a good predictor of future success in newly diagnosed patients. In patients intensifying therapy, beside GA decline, other individualized clinical characteristics should also be considered.     

富血小板血浆对兔骨关节炎软骨中基质金属蛋白酶-13表达的影响

目的 探讨富血小板血浆(platelet-rich plasm,PRP)抑制兔骨关节炎软骨表达基质金属蛋白酶-13(matrix metalloproteinase-13,MMP-13)的表达而发挥软骨保护作用。方法 选取30只成年清洁级新西兰大白兔,采用数字表法随机分为对照组、关节炎组、PRP组,每组各10只。关节炎组和PRP组按Hulth法制备后肢左膝关节炎模型,对照组行假手术。造模后第1周开始,各组抽取耳缘静脉血制备PRP 0.2 mL,仅PRP组给予关节腔注射。至第6周处死实验动物,获取各组左膝关节,分别行软骨组织HE染色测量软骨厚度,免疫组织化学染色计数MMP-13阳性细胞数,免疫荧光及Western blotting法检测MMP-13表达量。结果 对照组显示关节软骨形态接近正常,关节炎组软骨破坏明显,而PRP干预组较关节炎组,关节厚度得以保留,MMP-13阳性细胞及其表达量明显受到抑制。结论 PRP可减少MMP-13软骨细胞的数量和抑制MMP-13表达而发挥软骨保护作用。     

Complex regional pain syndrome of the upper limb: A review

In this paper, we present some impressions and thoughts about CRPS which we found useful in our proceedings with CRPS patients. The clinical sub-types of the CRPS are presented and differences in their characteristics are discussed. The current pathophysiological concepts for CRPS are outlined. Diagnostic criteria are presented and critically discussed. Both classification and diagnosing have translation on research and clinical practice. Treatment modalities are provided, addressing separately acute/early and chronic forms of the syndrome. The “Szczecin” protocol of management of early CRPS is presented in details. Some information about prevention of the syndrome is given. We believe that the information presented may support doctors in resolving their diagnostic dilemmas associated with CRPS.     

Aging might increase myocardial ischemia / reperfusion-induced apoptosis in humans and rats

Previous studies indicated aging results in the significant cardiac function decreasing and myocardial apoptosis increasing in normal humans or rats. Additionally, animal experiments demonstrated aging increased myocardial ischemia / reperfusion (MI/R)-induced apoptosis. However, whether more myocardial apoptosis happen in the old acute myocardial infarction (AMI) patients is unclear. Reperfusion injury-induced apoptosis is an important cause of heart failure. This study determined the effect of aging upon myocardial apoptosis and cardiac function in patients suffering AMI. All enrolled AMI patients received percutaneous coronary intervention therapy. Volunteers and AMI patients were assigned to four groups: adult (age <65, n = 24) volunteers, elderly (age ≥65, n = 21) volunteers, adult (age <65, n = 29) AMI patients, and elderly (age ≥65, n = 36) AMI patients. Blood samples were obtained from all study participants. Plasma apoptotic markers (soluble form of Fas, tumor necrosis factor alpha, and interleukin 6) levels were determined. Cardiac function was evaluated with echocardiogram and Killip class. Due to lack of a direct apoptotic assay method in live human subjects, an additional animal experiment was performed. Both young (2 months) and old (24 months) rats were subjected to 30-min myocardial ischemia and 3 (for TUNEL/caspase activity apoptotic assay) or 24-h (for cardiac function determination) reperfusion. Compared to adult patients, the elderly patients manifested decreased cardiac function and increased plasma apoptotic marker levels significantly. The animal experiment results (cardiac function and plasma apoptotic markers assays) were consistent with the human result data. Animal TUNEL staining and caspase activity measurement revealed a higher myocardial apoptotic ratio in the older rat group. Aging exacerbated MI/R injury in humans and rats. Differential myocardial apoptosis may play a vital role in mediating the observed effects.