Ultrasensitive analysis of the intestinal absorption and compartmentalization of aluminium in uraemic rats: a 26Al tracer study employing accelerator mass spectrometry

BACKGROUND: Developments in accelerator mass spectrometry (AMS) now permit the determination of femtogram amounts of 26Al in blood and in various tissues with good precision and free of external contamination. METHODS: In the present study we used trace quantities of 26Al to investigate the intestinal absorption and compartmentalization of aluminium in rats with renal failure (Nx, 5/6 nephrectomy) and in pair- fed controls (C). Single oral doses of 20 ng 26Al were administered to six animals in each group and, subsequently, 24-h post-load 26Al was analysed in serum, urine, bone, liver, and spleen by means of AMS. RESULTS: Serum concentrations of 26Al were significantly lower in uraemic rats compared to controls, whereas urinary excretion was comparable (Nx, 7.11 +/- 5.78 pg/day vs C, 9.46 +/- 6.10 pg/day), suggesting a higher fraction of ultrafiltrable serum 26Al in uraemia. The target tissues of cellular transferrin-mediated 26Al uptake, liver and spleen, tended to show a larger degree of aluminium accumulation in controls (0.26 +/- 0.31 pg/g vs Nx, 0.14 +/- 0.10 pg/g and 0.37 +/- 0.27 pg/g vs Nx, 0.25 +/- 0.27 pg/g respectively). In contrast, in bone, a site of extracellular aluminium deposition, 26Al concentrations were more elevated in uraemia (1.22 +/- 0.59 pg/g vs C: 0.68 +/- 0.30 pg/g). Estimated total 26Al accumulation in all measured target tissues was significantly higher in uraemic rats (28.15 +/- 9.90 pg vs C: 17.03 +/- 7.03 pg) and total recovery of 26Al from tissue and urine was 26.58 +/- 6.74 pg in controls and 35.75 +/- 7.03 pg in uraemic animals, suggesting a fractional absorption of 0.133% and 0.175% respectively. CONCLUSIONS: Our data suggest that fractional absorption from a dietary level dose of 26Al is about 0.13%. Compartmentalization occurs in transferrin-dependent target tissues such as liver and spleen; however, in quantitative terms extracellular deposition in bone is more important. Uraemia has a significant effect on the intestinal absorption and compartmentalization of aluminium. It enhances fractional absorption and increases subsequent extracellular deposition of aluminium in bone. However, at the same time uraemia does not increase transferrin-dependent cellular accumulation of aluminium in liver and spleen.      

Emotional Numbness Modifies the Effect of End-of-Life Discussions on End-of-Life Care

ContextOverall, end-of-life (EOL) discussions are unrelated to psychological distress and associated with lower rates of aggressive care near death. Nevertheless, patients who report that they feel emotionally numb about their illness might encounter difficulties cognitively processing an EOL discussion.ObjectivesWe hypothesized that emotional numbness would modify the effect of EOL discussions on the receipt of less aggressive EOL care.MethodsData were derived from structured interviews with 290 participants in the federally-funded Coping with Cancer Study, a multisite, prospective cohort study of patients with advanced cancer followed-up till their death. Patients' reports of EOL discussions with their physician and emotional numbness were assessed at a median of 4.6 months before their death. Information about aggressive EOL care (i.e., ventilation, resuscitation in the last week of life, death in the intensive care unit) was obtained from postmortem caregiver interviews and medical charts. Main and interactive effects of EOL discussions and emotional numbness on aggressive EOL care, adjusting for potential confounds, were evaluated using multiple logistic regression.ResultsThe likelihood of aggressive EOL care associated with having EOL discussions increased by a factor of nine (adjusted odds ratio = 9.02, 95% CI 1.37, 59.6, P = 0.022) for every unit increase in a patient's emotional numbness score.ConclusionEmotional numbness diminishes a patient's capacity to benefit from EOL discussions. The EOL decision making may be more effective if clinical communications with emotionally numb patients are avoided.     

Interrelationship between TP53 gene deletion, protein expression and chromosome 17 aneusomy in gastric adenocarcinoma

Background  

This study evaluates the existence of numerical alterations of chromosome 17 and TP53 gene deletion in gastric adenocarcinoma. The p53 protein expression was also evaluated, as well as, possible associations with clinicopathological characteristics.     

Pharmacological pain management in chronic pancreatitis

Intense abdominal pain is a prominent feature of chronic pancreatitis and its treatment remains a major clinical challenge.Basic studies of pancreatic nerves and experimental human pain research have provided evidence that pain processing is abnormal in these patients and in many cases resembles that seen in neuropathic and chronic pain disorders.An important ultimate outcome of such aberrant pain processing is that once the disease has advanced and the pathophysiological processes are firmly established,the generation of pain can become self-perpetuating and independent of the initial peripheral nociceptive drive.Consequently,the management of pain by traditional methods based on nociceptive deafferentation(e.g.,surgery and visceral nerve blockade)becomes difficult and often ineffective.This novel and improved understanding of pain aetiology requires a paradigm shift in pain management of chronic pancreatitis.Modern mechanism based pain treatments taking into account altered pain processing are likely to increasingly replace invasive therapies targeting the nociceptive source,which should be reserved for special and carefully selected cases.In this review,we offer an overview of the current available pharmacological options for pain management in chronic pancreatitis.In addition,future options for pain management are discussed with special emphasis on personalized pain medicine and multidisciplinarity.     

Resident approaches to advance care planning on the day of hospital admission

BACKGROUND: Advance care planning is the process of establishing a patient's goals and preferences for future care. Previous research has demonstrated a need to improve patient-physician communication around advance care planning. A critical time for advance care planning conversations is the day of admission to the hospital. METHODS: A survey of internal medicine residents was administered at Duke University Medical Center and the Brigham and Women's Hospital, 2 major academic teaching centers. Residents were questioned about their approaches to advance care planning on their last on-call admitting day. RESULTS: Of 347 residents solicited, 292 (84.1%) participated in the survey. Residents reported that they established preferences for cardiopulmonary resuscitation (CPR) with 70.5% of patients, established a health care proxy with 33.7% of patients, discussed goals and values concerning end-of-life care with 32.0% of patients, and asked 35.6% of patients if they had an advance directive. Although 89.0% of residents had observed an advance care planning discussion model, only 66.4% had received teaching and 36.6% had received feedback about advance care planning conversations. In multivariable analysis, having received feedback about advance care planning conversations was associated with a higher percentage of conversations about health care proxy and goals and values related to the end of life. CONCLUSIONS: Residents discuss patient preferences for CPR on the day of admission with most patients. Preparing residents, particularly through feedback, may improve communication around other elements of advance care planning.     

理科大学生网络成瘾与人格特质的关系

目的:分析理科大学生网络成瘾与其人格特质的关系。方法:于2005-09/11在上海某高校以班级为单位,对4个理科专业的220名学生进行问卷调查,4个专业分别是数学教育、计算机教育、物理师范和应用心理学。采用大学生因特网成瘾量表、交往焦虑量表、UCLA孤独量表和YG性格测验等4份问卷进行调查。大学生上网情况调查表共有52个题目,5级计分,成瘾诊断标准有耐受性、脱瘾综合症、计划性、控制性、行为特征、危害性、主观认识和行为等7个维度。按1,2,3,4,5记分,即每题填什么数记什么分,然后将各题得分相加得到维度分。判断标准:每题得1～3分转化为0分,4分转化为1分,5分转化为2分。测验每一部分导出分相加。若测验7部分中有3部分以上得分超过4分,则可基本诊断该大学生为因特网成瘾障碍患者。交往焦虑量表包含15个自陈条目,5级计分,总分从15(社交焦虑程度最低)到75(社交焦虑程度最高)。UCLA孤独量表(第3版)包含20个自陈条目,4级计分,总分从20(孤独程度最低)到80(孤独程度最高)。需要补充说明的是,交往焦虑量表是测量独立于行为的社交焦虑,UCLA孤独量表也主要是特质量表,因此这两个量表所测量的都是焦虑和孤独的人格特质而不是状态。YG性格测验问卷包含12个分量表,每个分量表有10个题目,测量一种特质。结果:共发出220份问卷,收回有效问卷211份。①成瘾者和非成瘾者在焦虑和孤独量表上的得分差异没有显著性意义。②成瘾者和非成瘾者在YG性格测验中的抑郁性、循环性、神经质、非合作性和攻击性等特质得分上,差异十分显著[(9.81±4.97),(5.95±5.10)分;(10.81±4.56),(6.78±4.46)分;(9.63±4.72),(6.51±4.67)分;(11.15±4.19),(7.28±4.43)分;(12.41±4.05),(8.69±3.69)分,均P<0.001],自卑感、主观性和细致性等特质得分上差异显著[(9.15±4.51),(6.83±4.49)分;(10.04±3.50),(7.63±4.09)分;(12.67±3.45),(10.26±4.23)分,P<0.01或P<0.05],在一般活动性、思维外向性、支配性和社会外向性等特质得分上两者没有差异。结论:理科大学生的部分人格特质和网络成瘾密切相关。     

缺血预处理程序中心肌环磷酸腺苷含量及环磷酸腺苷依赖蛋白激酶活性的变化

目的:制备大鼠在体缺血再灌注模型,观察缺血预处理程序中心肌环磷酸腺苷含量及环磷酸腺苷依赖蛋白激酶活性的变化。方法:实验于2005-03/2006-10在解放军沈阳军区总医院医学实验动物中心和全军心血管研究所实验室完成。实验分组:选用健康雌性SD大鼠36只,根据预适应程序分为第1,2,3次缺血,第1,2,3次再灌注,每一时间点6只大鼠。实验过程:用手术套管法造成左冠状动脉主干缺血及再灌注。所有实验动物在实验程序结束后,取出心脏迅速置液氮保存备用。实验评估:用放射免疫法测环磷酸腺苷水平,生化法测环磷酸腺苷依赖蛋白激酶活性变化。结果:36只大鼠均进入结果分析。①环磷酸腺苷含量:第1次再灌注组低于第1次缺血组[(0.325±0.015),(0.395±0.024)pmol/g,t=6.06,P<0.001],第2次再灌注组低于第2次缺血组[(0.523±0.017),(0.708±0.067)pmol/g,t=6.56,P<0.001],第3次再灌注组低于第3次缺血组[(0.567±0.031),(0.712±0.038)pmol/g,t=7.24,P<0.001]。②环磷酸腺苷依赖蛋白激酶活性:第1次再灌注组低于第1次缺血组[(10.115±1.000),(16.351±0.849)pkat/g,t=11.12,P<0.001],第2次再灌注组低于第2次缺血组[(11.877±2.213),(14.869±0.619)pkat/g,t=3.31,P<0.01],第3次再灌注组低于第3次缺血组[(11.745±0.987),(14.766±0.329)pkat/g,t=7.09,P<0.001]。③缺血预处理程序中心肌环磷酸腺苷含量及环磷酸腺苷依赖蛋白激酶活性随缺血及再灌注呈周期性波动。在5min缺血预处理时表现为明显增高,而在间隔的再灌注程序中恰呈相反改变,有明显下降的趋势。结论:环磷酸腺苷及环磷酸腺苷依赖蛋白激酶的周期性波动变化可能是激发心肌缺血预处理的机制之一,环磷酸腺苷可能在预处理保护作用中起一些作用。     

Effect of amphotericin B and fluconazole on platelet membrane glycoproteins

BACKGROUND : Fever, chills, and reduced platelet recovery may result when platelets are transfused simultaneously with amphotericin B. Amphotericin B reportedly increases the pitting of membranes in stored platelets. STUDY DESIGN AND METHODS : The effects of amphotericin B and another antifungal agent, fluconazole, on platelet membrane glycoproteins (GP) were examined by the incubation of split aliquots of fresh and stored platelet concentrates (PCs) with these drugs for 3 days in storage bags. To determine the effect of storage, PCs were stored for 5 days, and aliquots removed on Days 1 through 5 were placed in platelet storage bags with 4 micrograms per mL of amphotericin B for 2 to 6 hours. Membrane glycoprotein expression was assessed by flow cytometry with fluorescein isothiocyanate-labeled monoclonal antibodies (MoAbs) directed against the following antigens: GPIb (CD42b), CD63 (an activation protein), P-selectin (CD62), and GPIIb/IIIa (CD41a). RESULTS : Amphotericin B produced a concentration-dependent decrease in the surface binding of CD42b MoAb with no consistent changes in the binding of CD41a, CD63, or CD62 MoAbs after a 3-day exposure. Stored but not fresh PCs showed decreased binding of MoAb CD42b after a 6-hour exposure to amphotericin B (4 micrograms/mL). Fluconazole produced no changes. When the binding of MoAb CD42b to permeabilized platelets was used to measure total platelet content, amphotericin B (4 micrograms/mL) decreased MoAb CD42b binding to a similar degree in fresh and stored platelets. Inhibition of aggregation to ADP and collagen and ADP and epinephrine was seen in stored but not fresh PCs. CONCLUSION : Therapeutic levels of amphotericin B resulted in partial loss of total platelet GPIb in fresh and stored PCs, but decreased surface expression of platelet membrane GPIb only in stored platelets. This difference between fresh and stored platelets may be related to the limited reservoir of GPIb available for redistribution to the membrane in the previously stored PCs and may account for the decreased recovery of transfused platelets observed in some patients receiving amphotericin B.