Animal models and treatment of prostate cancer

Model systems for prostate cancer in rats have been developed and used for investigations on tumor biology and therapy. The "Pollard tumors" provide a combination of in vitro and in vivo attributes by which investigations can be directed at local tumor development and spontaneous metastasis. The evolution and early applications of this model system are reviewed, and the therapeutic benefits of delayed release of cyclophosphamide are presented.     

Flexor Tenosynovectomy for Recurrent Carpal Tunnel Syndrome: A Retrospective Case Series of 108 Hands

Background: The etiology of recurrent carpal tunnel syndrome (CTS) is unclear, and outcomes following secondary surgery in this demographic have been poorer than primary surgery. Fibrosis and hypertrophy have been identified in the flexor tenosynovium in these patients. The authors use flexor tenosynovectomy (FTS) for recurrent CTS after primary carpal tunnel release and present a review of these patients. Methods: A retrospective chart review was performed of 108 cases of FTS for recurrent CTS from 1995 to 2015 by 4 attending surgeons at one institution. Demographic information, symptoms, and outcomes were among the data recorded. A phone survey was conducted on available patients where the shortened version of the Disabilities of the Arm, Shoulder and Hand Questionnaire (QuickDASH) and satisfaction were assessed. Results: Average office follow-up was 12 months. Average age was 57.5 years. A total of 104 (96%) reported symptom improvement and 48 (44%) reported complete symptom resolution. Forty patients were available for long-term follow-up at an average 6.75 years postoperatively via phone interview. Average QuickDASH score was 31.2 in these patients. Thirty-six (90%) of 40 patients were initially satisfied at last office visit, and 31 (78%) of 40 were satisfied at average 6.9 years, a maintenance of satisfaction of 86%. Satisfied patients were older (58 years) than unsatisfied patients (51 years). Conclusion: Both long-term satisfaction and QuickDASH scores in our cohort are consistent with or better than published results from nerve-shielding procedures. The authors believe a decrease in both carpal tunnel volume and potential adhesions of fibrotic or inflammatory synovium contributes to the benefits of this procedure. This remains our procedure of choice for recurrent CTS.     

Implications of the 2018 Canadian Cannabis Act: Should regulation differ for medicinal and non-medicinal cannabis use?⋆

The regulatory framework for access to medical cannabis has been established in Canada since 2001, with the number of patients seeking access growing substantially over the years. With the novel enactment of the Cannabis Act in October 2018, Canada now maintains two distinct mechanisms for accessing cannabis - one for medical cannabis and the other for non-medical cannabis. With two regulatory access mechanisms in place, questions have arisen in the country as to the necessity of maintaining regulatory separation and the integrity of the medical access framework. A single framework would remove the gate-keeping function that the medical profession currently holds, streamlining processes and simplifying the current regulatory landscape. This approach has been advocated for by the Canadian Medical Association, despite objections from multiple stakeholders. Critical questions arise should the medical access framework be dissolved into a single, non medical-based regulatory framework. Insurance coverage, control mechanisms, market incentives, and patient obligations represent some examples of these issues. This paper will expand upon these considerations and highlight why maintaining two separate access mechanismss best serves the Canadian public. As medicinal cannabis continues to be liberated in international jurisdictions, this paper can help to illuminate the current status of medical cannabis in Canada, and provide insights to those from other countries on our current approach and domestic challenges.     

支气管动脉灌注化疗治疗晚期原发性肺癌近期疗效影响因素分析

目的探讨经支气管动脉灌注化疗(BAI)治疗晚期肺癌近期疗效的影响因素。方法回顾性分析1990年3月至2006年6月间胸部X线片复查资料相对完整的82例经BAI治疗的原发性晚期肺癌的近期疗效。结果完全有效(CR)10例(12.2%)、部分有效(PR)32例(39.0%)、轻微有效(MR)23例(28.0%)、稳定(SD)15例(18.3%)、进展(PD)2例(2.4%)。单因素方差分析结果显示,半月时肿瘤缩小率(TDR1/2month)(χ2=25.92,P<0.01)、BAI次数(TBAI)(χ2=17.70,P<0.01)、肿瘤大小(Tsize)(χ2=14.21,P<0.01)和肿瘤血供丰富程度(χ2=6.59,P<0.01)对近期疗效的影响具有统计学意义。对年龄、病理类型等12项协变量进行二项分类Logistic回归分析,采用向后删除法经10步二次迭代,得到Logistic回归方程:P(1)=1/[1 e-(-8.953 2.656TDR1/2month 1.382TBAI 1.230Tsize)],方程对BAI近期疗效有效与无效的预测正确率分别为85.7%和70.0%。结论第1次BAI后半月时的肿瘤缩小率、BAI治疗次数和肿瘤的大小是影响BAI近期疗效的因素。     

A Theoretical Model for the Margination of Particles within Blood Vessels

The margination of a particle circulating in the blood stream has been analyzed. The contribution of buoyancy, hemodynamic forces, van der Waals, electrostatic and steric interactions between the circulating particle and the endothelium lining the vasculature has been considered. For practical applications, the contribution of buoyancy, hemodynamic forces and van der Waals interactions should be only taken into account, whilst the effect of electrostatic and steric repulsion becomes important only at very short distances from the endothelium (1–10 nm). The margination speed and the time for margination t_s have been estimated as a function of the density of the particle relative to blood , the Hamaker constant A and radius R of the particle. A critical radius R_c exists for which the margination time t_s has a maximum, which is influenced by both and A: the critical radius decreases as the relative density increases and the Hamaker constant decreases. Therefore, particles used for drug delivery should have a radius smaller than the critical value (in the range of 100 nm) to facilitate margination and interaction with the endothelium. While particles used as nanoharvesting agents in proteomics or genomics analysis should have a radius close to the critical value to minimize margination and increase their circulation time.     

Behandlung mit Mexiletin

Summary Pharmacokinetics of the antiarrhythmic agent mexiletine were found to be highly variable. Ineffective or toxic doses can be avoided by monitoring mexiletine concentrations in patients plasma. However, the success of antiarrhythmic therapy is mainly determined by the severety of the underlying disease. Therefore, the efficacy of treatment with mexiletine should be controlled by Holter monitoring.

Herrn Prof. Dr. G. Schütterle zum 60. Geburtstag gewidmet     

Pentobarbital-induced drinking does not rely on a renal dipsogen

Injections of pentobarbital have been shown to produce drinking in both deprived and nondeprived rats and a number of other studies have shown that pentobarbital is a potent renin releasor. Since renin has been shown to be involved in thirst regulatory mechanisms and since the dipsogenic actions of other renin-releasing agents have been blocked by nephrectomy, we sought to determine whether or not pentobarbital-induced drinking relies on a renal dipsogen. Rats were either "sham" operated or nephrectomized under ether anesthesia. Five to six hours later, animals in each group were injected with either 9.5 mg/kg pentobarbital sodium or vehicle, and intakes were measured 60 minutes later. Statistical analysis of water intakes indicated that pentobarbital produced significant drinking in both control operated and in nephrectomized rats, and that the intakes in these two groups did not differ. These results indicate that pentobarbital-induced drinking is not secondary to increased plasma renin activity and may suggest the involvement of central mechanisms in the drinking response.