A Novel Nomogram to Identify Candidates for Extended Pelvic Lymph Node Dissection Among Patients with Clinically Localized Prostate Cancer Diagnosed with Magnetic Resonance Imaging-targeted and Systematic Biopsies

Background

Available models for predicting lymph node invasion (LNI) in prostate cancer (PCa) patients undergoing radical prostatectomy (RP) might not be applicable to men diagnosed via magnetic resonance imaging (MRI)-targeted biopsies.

Intravenous cidofovir treatment for recalcitrant warts in the setting of a patient with myelodysplastic syndrome

Cidofovir is an acyclic nucleoside phosphonate with broad-spectrum activity against DNA viruses, including human papilloma virus (HPV). However, data on the efficacy of cidofovir in an immunosuppressive setting remain contradictory. We report for the first time on the promotion of the healing of recalcitrant warts in a patient with myelodysplastic syndrome with intravenous cidofovir treatment.     

Dorsal fracture of the hamate: distinctive radiographic appearance

Six patients who injured their wrists had radiographs documenting a dorsal, 5- to 10-mm oblong fragment of bone immediately proximal to the base of the fourth and/or fifth metacarpal bones. The fragment was seen on the pronation oblique and/or lateral projections, but not on the posteroanterior projection. The radiographic appearance of the fragment was remarkably similar in all cases. In the one patient in which it was performed, pluridirectional tomography demonstrated that the fragment originated from the dorsal surface of the hamate. Five of the six patients also had associated posterior dislocation of the fourth and/or fifth metacarpals. We conclude that this fragment represents a coronal fracture through the body of the hamate resulting from posterior dislocation or subluxation of the fourth and/or fifth metacarpal.     

美托洛尔治疗老年冠心病慢性心力衰竭52例疗效观察

目的评价β-受体阻滞剂治疗老年冠心病慢性心力衰竭的疗效及安全性。方法105例老年冠心病慢性心力衰竭患者按就诊顺序随机分为两组，美托洛尔组52例在常规抗心力衰竭治疗基础上加用美托洛尔12．5～25mg，2／d；对照组53例采用常规抗心力衰竭治疗，未用美托洛尔。定期来诊随访，观察临床表现，监测治疗前后心率、血压、心功能参数变化。结果美托洛尔组显效率53．8％，总有效率88．5％；对照组显效率30．2％，总有效率67．9％，两者比较有显著性差异（P〈0．05）。美托洛尔组患者心率减慢、血压降低较对照组明显，超声心动图复查显示治疗6个月后左室舒张末期内径缩小，左室射血分数增高较对照组显著。结论美托洛尔为老年冠心病慢性心力衰竭提供一种较为安全有效的药物治疗手段。     

Glial cell line-derived neurotrophic factor-dependent recruitment of Ret into lipid rafts enhances signaling by partitioning Ret from proteasome-dependent degradation

The receptor tyrosine kinase (RTK) Ret is activated by the formation of a complex consisting of ligands such as glial cell line-derived neurotrophic factor (GDNF) and glycerophosphatidylinositol-anchored coreceptors termed GFRalphas. During activation, Ret translocates into lipid rafts, which is critical for functional responses to GDNF. We found that Ret was rapidly ubiquitinated and degraded in sympathetic neurons when activated with GDNF, but, unlike other RTKs that are trafficked to lysosomes for degradation, Ret was degraded predominantly by the proteasome. After GDNF stimulation, the majority of ubiquitinated Ret was located outside of lipid rafts and Ret was lost predominantly from nonraft membrane domains. Consistent with the predominance of Ret degradation outside of rafts, disruption of lipid rafts in neurons did not alter either the GDNF-dependent ubiquitination or degradation of Ret. GDNF-mediated survival of sympathetic neurons was inhibited by lipid raft depletion, and this inhibitory effect of raft disruption on GDNF-mediated survival was reversed if Ret degradation was blocked via proteasome inhibition. Therefore, lipid rafts sequester Ret away from the degradation machinery located in nonraft membrane domains, such as Cbl family E3 ligases, thereby sustaining Ret signaling.     

Plasma level studies in volunteers after intramuscular injection of various doses of etofenamate in an oily solution

Plasma level Studies on Volunteers after Intramuscular Application of Different Doses of Etofenamate in Oily Solution. After i.m. injections of etofenamate (active substance of Rheumon i.m.) in oily solution to 12 volunteers, courses of plasma levels of etofenamate, flufenamic acid and fenamate (sum of etofenamate and flufenamic acid) were measured by HPTLC. Maximum levels of etofenamate, flufenamic acid and fenamate, as well as areas under the plasma level time curve (AUC) after 250, 500 and 1000 mg etofenamate respectively are proportional to dose. Maxima of fenamate plasma levels are reached after 6.3, 6.2 and 5.4 h respectively, half maximal levels are present already after 2 h. The mean residence time is 21.8, 18.8 and 15.7 h. These values obtained from different doses are not statistically different from each other. Pharmacokinetics are therefore linear and dose independent. The courses of fenamate levels can be described by a two compartment model. The elimination half lives after 250, 500 and 1000 mg are 2.1, 2.3 and 1.9 h, the invasion half-lives (dominant half-life) 8.8, 7.8 and 6.8 h. Terminal half-lives are 50.3, 63.7 and 35.4 h. Since plasma levels have decreased to 2% of the maximum level after one terminal half-life, they have no practical importance for the duration of activity or for accumulation. No sex related differences are found for dose dependent and independent parameters. From the data it can be derived that after i.m. injection of etofenamate in oily solution a prolongation of the dominant half-life occurs by a factor of 4-5 (as compared to oral data) which is caused by prolonged liberation from the oily depot. This long lasting liberation of etofenamate leads to a prolonged residence time after a fast increase, at the same time avoiding unnecessary high peak levels. Therefore it is guaranteed that even after i.m. administration of 1000 mg etofenamate in oily solution plasma levels of fenamate do not exceed those after 300 mg given orally. According to pharmacokinetic data a fast onset of action, good tolerability and a therapeutic action over a period of 24 h can be expected.