Acute appendicitis in the developing world is a morbid disease

IntroductionAcute appendicitis in the developing world has a markedly different disease profile to that in the developed world.MethodsA retrospective study was undertaken over a four-year period at a university hospital in South Africa to review the disease spectrum and the clinical outcome of acute appendicitis.ResultsA total of 1,004 patients (54% male, median age: 18 years) with intraoperatively confirmed appendicitis were reviewed. Over half (56%) were from the urban district within the city of Pietermaritzburg and the remaining 44% were from the rural health district. The median duration of illness from onset to definitive care was 4 days. Sixty per cent of appendices were perforated and associated with intra-abdominal contamination. Forty per cent of patients required reoperation to control intra-abdominal sepsis. Ten per cent required admission to the intensive care unit. The median overall length of hospital stay was 5 days. The mortality rate was 1%.Rural patients had a longer median duration of illness (3 vs 5 days, p<0.001) as well as a more advanced disease profile associated with perforation and severe intra-abdominal sepsis (19% vs 71%, p<0.001). Female patients had a longer median duration of illness (3 vs 4 days, p<0.001), were more likely to present with severe intra-abdominal sepsis (31% vs 54%, p<0.001) and were more likely to require a laparotomy (50% vs 73%, p<0.001). The total cost of managing the entire cohort of 1,004 patients over the 4-year period was £2,060,972.ConclusionsAcute appendicitis in South Africa is a serious disease associated with significant morbidity. Late presentation is common. Female and rural patients have the worst clinical outcomes, with significant cost to the health system.     

Blood transfusion exposure does not influence survival in patients with carcinoma of the breast

There is abundant evidence of immune modulation induced by exposure to blood transfusions. Some studies have demonstrated a detrimental effect of transfusion on the recurrence of malignant disease and survival. We retrospectively studied the impact of blood transfusion exposure on 229 patients with breast cancer who were seen from July 1973 to September 1980, had at least 5 years' follow-up and had been randomized by therapy at the time of diagnosis. The patients were divided into four groups according to transfusion history: Group 1 (111 patients), no transfusion; Group 2 (34 patients), first transfusion after mastectomy; Group 3 (41 patients), first transfusion at mastectomy; and Group 4 (43 patients), first transfusion before mastectomy. All transfused patients received red cells or whole blood or both. At the time of analysis, 124 (54%) of the patients had died. Only Group 2 was statistically associated with decreased survival; recurrence of disease was 85 percent in this group, compared with 53 percent to 61 percent in the other three groups (p = 0.006, log-rank test). In general, Group 2 patients received transfusions because of recurrent disease. We conclude that transfusions before or at mastectomy are not associated with increased recurrence or reduced survival in patients with breast cancer.     

颈椎椎后肌肉组织中肌膜Na^＋-K^＋-ATP酶活性与颈椎病

目的:探讨颈椎椎后肌肉组织Na -K -ATP酶活性变化与颈椎病的关系。资料来源:应用计算机检索PubMed1988-01/2004-12相关骨骼肌损伤与肌组织Na -K -ATP酶关系的文献,检索词“Na -K pump,Na -K -ATPase,muscle”,限定文献语言种类为English。同时计算机检索CNKI1990-01/2005-12相关Na -K -ATP酶与骨骼肌损伤的关系及颈椎病发病病因的文献,检索词“Na -K -ATP酶,骨骼肌,颈椎病病因”,限定文献语言种类为中文。资料选择:对资料进行初审,选取包括Na -K -ATP酶与肌组织损伤关系的文献,开始查找全文。纳入标准:Na -K -ATP酶活性变化与骨骼肌损伤密切相关的文献研究。排除标准:重复研究,Meta分析类文章。资料提炼:共检索到939篇关于Na -K -ATP酶与骨骼肌损伤相关方面的文献,最终纳入20篇符合标准的文献。资料综合:众多研究表明,Na 、K 与骨骼肌的兴奋、收缩、疲劳有密切关系,而Na -K -ATP酶又是调节细胞内外Na 、K 浓度必不可少的高分子蛋白,也就是说,骨骼肌一系列活动均离不开Na -K -ATP酶,Na -K -ATP酶活性变化与骨骼肌损伤是相互影响的。而强迫屈颈体位作为颈椎病发病的危险因素之一,可使颈椎椎后肌肉Na -K -ATP酶活性降低,酶活性降低致使肌细胞损伤,并最终导致骨骼肌损伤而发病。结论:以颈椎椎后肌肉酶活性的变化来阐释中医药对颈椎病确切疗效的相关研究未见,这有待于进一步研究,以充分展示中医药在颈椎病等相关疾病中的治疗优势。     

肿瘤干细胞的研究与进展

目的:作为"种子细胞"的肿瘤干细胞对研究肿瘤发生及其临床治疗具有重要意义。总结近年来肿瘤干细胞的研究进展,对肿瘤干细胞的概念、特性及应用进行综述。资料来源:应用计算机检索Medline数据库1980-01/2006-12期间的相关文章,检索词为"cancer stem cells",限定文章语言种类为English。资料选择:对资料进行初审,并查看每篇文献后的引文。纳入标准:肿瘤干细胞的研究进展及临床价值。排除标准:重复研究。资料提炼:共收集到106篇相关文献,30篇文献符合纳入标准,排除的76篇文献为内容陈旧或重复。符合纳入标准的30篇文献中,分别涉及肿瘤干细胞的定义及来源、研究进展、临床治疗价值等内容。资料综合:肿瘤干细胞具有分裂增殖、自我更新以及分化成其他细胞的能力,目前已证实其存在于白血病、乳腺癌、脑癌、前列腺肿瘤等肿瘤组织中。目前的抗肿瘤治疗方法主要针对的是大多数已经分化的肿瘤细胞,而不能影响到肿瘤干细胞,即治标不治本。肿瘤的复发、转移以及耐药等特征都很可能与肿瘤干细胞有关,因此肿瘤治疗的关键应是针对肿瘤干细胞进行灭杀,又要保护正常干细胞,但此两种细胞表型极为相似,故应找到更为特异的靶点。结论:肿瘤干细胞不仅已经从血液系统的恶性肿瘤中成功分离出来,在大量实体瘤中也证实了肿瘤干细胞的存在,其耐药机制之一是表达一种或多种药物运载蛋白,对于肿瘤的发生及治疗提供了更多的思路和方向。     

颈动脉内中膜厚度与初诊2型糖尿病视网膜病变的关系

目的:研究发现,糖尿病视网膜病变和动脉粥样硬化终点事件相关。试验拟验证颈动脉内中膜厚度与初诊汉族2型糖尿病患者糖尿病视网膜病变相关危险因素的关系。方法:①试验对象:选择2006-06/2007-06本院住院的初诊2型糖尿病患者187例,男114例,女73例;平均年龄(51±14)岁;平均体质量指数(24.7±4.7)kg/m2。均符合1997年美国糖尿病协会的2型糖尿病诊断标准,排除既往已存在心血管疾病者。患者对治疗及试验均知情同意。根据眼底照相检查结果,将所有受检者分为糖尿病视网膜病变组及非糖尿病视网膜病变组进行统计分析。②试验方法及评估:所有患者询问一般情况,测量颈动脉内中膜厚度以及相关生化指标,对糖尿病视网膜病变相关因素进行单因素及多因素Logistic回归分析。结果:纳入2型糖尿病患者187例,均进入结果分析。单因素Logistic回归分析显示,高血压、糖尿病家族史、颈动脉内中膜厚度、尿白蛋白、低密度脂蛋白胆固醇与糖尿病视网膜病变发生呈显著正相关,多因素Logistic回归分析未见显效因素。结论:单因素回归分析中颈动脉内中膜厚度及其他4项指标与糖尿病视网膜病变相关,而多因素回归分析这些因素未进入主效基因模型。     

Preclinical to Clinical Translation of CNS Transporter Occupancy of TD-9855, a Novel Norepinephrine and Serotonin Reuptake Inhibitor

Background:

Monoamine reuptake inhibitors exhibit unique clinical profiles that reflect distinct engagement of the central nervous system (CNS) transporters.

Methods:

We used a translational strategy, including rodent pharmacokinetic/pharmacodynamic modeling and positron emission tomography (PET) imaging in humans, to establish the transporter profile of TD-9855, a novel norepinephrine and serotonin reuptake inhibitor.

Results:

TD-9855 was a potent inhibitor of norepinephrine (NE) and serotonin 5-HT uptake in vitro with an inhibitory selectivity of 4- to 10-fold for NE at human and rat transporters. TD-9855 engaged norepinephrine transporters (NET) and serotonin transporters (SERT) in rat spinal cord, with a plasma EC₅₀ of 11.7ng/mL and 50.8ng/mL, respectively, consistent with modest selectivity for NET in vivo.Accounting for species differences in protein binding, the projected human NET and SERT plasma EC₅₀ values were 5.5ng/mL and 23.9ng/mL, respectively. A single-dose, open-label PET study (4–20mg TD-9855, oral) was conducted in eight healthy males using the radiotracers [¹¹C]-3-amino-4- [2-[(di(methyl)amino)methyl]phenyl]sulfanylbenzonitrile for SERT and [¹¹C]-(S,S)-methylreboxetine for NET. The long pharmacokinetic half-life (30–40h) of TD-9855 allowed for sequential assessment of SERT and NET occupancy in the same subject. The plasma EC₅₀ for NET was estimated to be 1.21ng/mL, and at doses of greater than 4mg the projected steady-state NET occupancy is high (>75%). After a single oral dose of 20mg, SERT occupancy was 25 (±8)% at a plasma level of 6.35ng/mL.

Conclusions:

These data establish the CNS penetration and transporter profile of TD-9855 and inform the selection of potential doses for future clinical evaluation.     

Feasibility and effectiveness of a targeted diabetes prevention program for 18 to 60-year-old South Asian migrants: design and methods of the DH!AAN study

ABSTRACT: BACKGROUND: South Asian migrants are at particularly high risk of type 2 diabetes. Previous studies have shown that intensive lifestyle interventions may prevent the onset of diabetes. Such interventions have not been culturally adapted and evaluated among South Asians in industrialized countries. Therefore, we have set up a randomized controlled trial to study the effectiveness of a targeted lifestyle intervention for the risk of type 2 diabetes and cardiovascular risk factors among 18 to 60-year-old Hindustani Surinamese (South Asians) in The Hague, the Netherlands. Here we present the study design and describe the characteristics of those recruited. METHODS: Between May 18, 2009 and October 11, 2010, we screened 2307 Hindustani Surinamese (18-60 years old) living in The Hague. We sent invitations to participate to those who had an impaired fasting glucose of 5.6-6.9 mmol/l, an impaired glucose tolerance of 7.8-11.0 mmol/L, a glycated hemoglobin level of 6.0% or more and/or a value of 2.39 or more for the homeostasis model assessment of estimated insulin resistance. In total, 536 people (56.1% of those eligible) participated. People with a higher level of education and a family history of type 2 diabetes were more likely to participate. The control and intervention groups were similar with regard to important background characteristics. The intervention group will receive a culturally targeted intervention consisting of dietary counseling using motivational interviewing and a supervised physical activity program. The control group will receive generic lifestyle advice. To determine the effectiveness, a physical examination (anthropometrics, cardiorespiratory test, lipid profile, and measures of oral glucose tolerance, glycated hemoglobin, and insulin) and interview (physical activity, diet, quality of life, and intermediate outcomes) were carried out at baseline and will be repeated at 1 year and 2 years. The process and the costs will be evaluated. DISCUSSION: This trial will provide insight into the feasibility and effectiveness of a targeted, intensive, lifestyle intervention for the risk of type 2 diabetes and cardiovascular risk factors among 18 to 60-year-old South Asians. Trial registration: Dutch Trial Register: NTR1499.