Palliative care and the hospitalist: an opportunity for cross-fertilization

Most US citizens die in acute care hospitals, often in physical pain, without attention to emotional and spiritual suffering. This represents an ethical failure of our current health-care system. The field of palliative medicine aims to address the physical, emotional, and spiritual needs of patients with advanced disease. At the same time, a new specialty of hospitalists is emerging, providing care for acutely ill hospitalized patients, many of whom will die. Thus, the hospitalist may become the primary deliverer of palliative care. This presents many potential opportunities for dying patients and their families, including increased time and attention from a physician; enhanced knowledge and skills around the physical symptoms, and emotional and spiritual distress; perhaps more detached and therefore more accurate prognostication; and increased efficiency, leading to a more rapid discharge to home. Hospitalists could enhance the quality of care for the dying by emphasizing interdisciplinary communication and involvement of hospital-based health professionals to address emotional and spiritual distress and bereavement issues, as well as through specific quality-improvement efforts. Finally, hospitalists can provide strong role modeling of optimal care for dying patients and their families. When hospitalists are not selected and trained effectively around palliative care issues, the risks are great. Discontinuity of physicians can lead to miscommunication and misunderstanding (by professionals, patient, and family); disagreement about treatment focus (especially as it relates to a shift from curative to palliative); inappropriate deferring of advance care planning to the hospital setting; and, most worrisome, a lack of expertise in symptom control, communication skills, and attention to patient and family distress and the provision of emotional and spiritual support. This article evaluates the convergence of the 2 fields of palliative medicine and hospitalist medicine and reviews the opportunities for mutual education and improved patient care.     

Use of concurrent pupil dilation assessment to inform interpretation and analysis of fMRI data

Potential contributions of concurrently acquired pupil dilation data to functional magnetic resonance imaging (fMRI) experiments were examined. Sixteen healthy participants completed a working memory task (digit sorting) during measurement of pupil dilation outside the fMRI environment and during concurrent 3T fMRI assessment. Pupil dilation increased parametrically with task difficulty inside and outside the scanner, on a similar time course, suggesting that task demand was similar in both environments. The time course of pupil dilation during digit sorting was similar to the time course of the fMRI signal in the middle frontal gyrus, suggesting that middle-frontal gyrus activity indexed the engagement working memory processes. Incorporating individual differences in pupil dilation improved the sensitivity and specificity of general linear modeling analyses of activity in the middle frontal gyrus, above and beyond standard analytic techniques. Results suggest concurrent pupil dilation during fMRI assessment can help to (1) specify whether task demand is the same inside and outside the fMRI environment, (2) resolve the extent to which fMRI signals reflect different aspects of event-related designs, and (3) explain variation in fMRI data due to individual differences in information processing.     

The use of pre-cannulation local anaesthetic and factors affecting pain perception in the emergency department setting

Study objective—To determine whether the use of subcutaneous local anaesthetic (lignocaine) is associated with a reduction in cannulation pain in the emergency department setting.

Methods—Patients over 18 with a Glasgow Coma Score (GCS) of 15 and conversational English were allocated into one of three groups: Group 1 were cannulated after routine skin preparation; Group 2 received 1% lignocaine 0.1 ml via a 27 gauge needle and diabetic syringe before cannulation; Group 3 were injected as for Group 2 but saline was substituted for lignocaine. The cannulator and subject were blinded to the ampoule. The pain was measured using a 100 mm visual analogue scale.

Setting—A large urban university hospital emergency department.

Results—366 patients were recruited and the data on 322 analysed. Those receiving lignocaine before cannulation reported lower pain scores (1.9 cm) than the saline (4.1 cm) or immediate cannulation (3.6 cm) groups, p<0.0001. Other factors such as the experience of cannulator, patient characteristics, the presence of a painful underlying condition and cannula size did not effect pain scores.

Conclusion—The use of lignocaine before cannulation reduced cannulation pain in the emergency department setting. Other factors examined did not influence pain perception.

     

The separated enantiomers of 2''-deoxy-3''-thiacytidine (BCH 189) both inhibit human immunodeficiency virus replication in vitro.

Racemic 2'-deoxy-3'-thiacytidine (BCH 189) is a dideoxycytidine analog having a sulfur atom in place of the 3' carbon. The enantiomers of BCH 189 have been resolved and found to be equipotent in antiviral activity against human immunodeficiency virus types 1 and 2. However, the (-)-enantiomer (3TC) is considerably less cytotoxic than the (+)-enantiomer.     

中国人胚胎肝组织来源纤溶酶原kringle5基因的克隆与序列分析

目的：分离、克隆和测定中国人纤溶酶原Kringle5功能区基因，为进一步研究其功能奠定基础。方法：实验于2002—06／2003-05在广州医学院金域医学检验中心完成。①实验材料：国人胚肝组织取自广州医学院第一附属医院的流产胚胎（取得家属同意，并经广州医学院第一附属医院伦理委员会批准）。pET21a（＋）载体购自Novagen公司，大肠杆菌BL21（DE3）为医学检验中心保存。引物均由上海生工合成。②实验方法：从国人胚肝组织中提取mRNA，用反转录-聚合酶链反应方法将人纤溶酶原Kringle5的cDNA扩增出来，克隆到pET21a（＋）载体中测序。（D实验评估：采用紫外分光光度仪和琼脂糖凝胶电泳分析胚肝组织总RNA的抽提结果；经琼脂糖凝胶电泳鉴定Kringle5的反转录-聚合酶链反应扩增结果；pET-Kringle5重组质粒的酶切鉴定；序列测定。结果：①胚肝组织提取总RNA结果：提取的总RNA经紫外分光光度仪测得A260nm/A80nm〉1．8，A60nm，A270nm〉1.2，表明无蛋白残留；电泳结果显示提取的总RNA有明显的28S、18S两条带，说明RNA基本完整。②Kringle5的反转录-聚合酶链反应扩增结果：人Kringle5 cDNA片段长为240bp，加上引物设计的2个酶切位点，总长度为258bp，聚合酶链反应产物长度与该长度一致，符合预期结果。③）pET-Kringle5重组质粒的构建和酶切鉴定结果：用引物所带的限制性内切酶BamH Ⅰ、NdeⅠ双酶切，结果有250bp左右条带出现。④序列测定结果：证实国人纤溶酶原Kringle5功能区基因被成功克隆，序列分析证实为该基因，未发现有基因突变或多态性现象，但第153位核苷酸与文献比较存在碱基替代现象，其组成的密码子由于遗传的简并性，所编码的氨基酸相同，并未造成氨基酸组成的改变。结论：中国人纤溶酶原Kringle5功能区cDNA基因编码序列与国外文献报道的相应序列可能存在碱基替代现象。     

骨髓干细胞移植对心肌梗死大鼠血流动力学指标和心脏功能的影响

目的:心肌梗死所致的细胞缺失和瘢痕形成是心力衰竭乃至死亡的病理基础,目前药物治疗、介入治疗和外科手术均不能替代坏死心肌和彻底改善心脏功能。观察骨髓干细胞移植对心肌梗死大鼠血流动力学指标和心功能的影响。方法:实验于2005-03/2006-10在哈尔滨医科大学附属第一医院细胞移植中心完成。①实验动物:SD雄性大鼠60只作为细胞移植的受体,随机数字表法分成假手术组、心肌梗死组、细胞移植组,20只/组。另取SD雄性幼鼠10只作为骨髓干细胞的供体。实验过程中对动物的处置符合动物伦理学标准。②实验方法:取幼鼠股骨骨髓,Percoll分离后收取细胞层,加入含体积分数为0.1的胎牛血清、100IU/mL青霉素、100g/mL链霉素的DMEM营养液,差速贴壁法分离骨髓干细胞,达80%～90%融合时采用胰酶 乙二胺四乙酸消化传代。向含有第3代骨髓干细胞的培养液中加入5-氮杂胞嘧啶核苷进行诱导,3周后行BrdU标记,离心后配制成1×1012L-1的细胞悬液用于移植。心肌梗死组、细胞移植组大鼠建立心肌梗死模型,假手术组未结扎冠状动脉。细胞移植组吸取0.2mL骨髓干细胞悬液注射到瘢痕组织中,心肌梗死组注入等量干细胞培养液基质,假手术组不予任何移植处理。③实验评估:术后4周,利用导管和心动超声技术检测各组大鼠左室舒张末期内压、左室收缩末期内压、左室压力最大变化值、左室压力最小变化值、等容时间常数和心率。结果:术后4周,与假手术组比较,心肌梗死组左室收缩末期内压、左室压力最大变化值、左室压力最小变化值均明显降低(P<0.01),左室舒张末期内压、等容时间常数均明显增高(P<0.01);与心肌梗死组比较,细胞移植组以上各项指标均明显好转(P<0.01)。结论:骨髓干细胞移植到瘢痕心肌组织中,能改善心肌梗死后大鼠的血流动力学参数和心脏功能。     

Factors affecting Yersinia enterocolitica (serotype O:8) viability in deliberately inoculated blood

Interpretation of in vitro experiments using Yersinia enterocolitica in blood components requires information on factors affecting the organism's survival. Several factors were found to influence the survival of Y. enterocolitica (serotype O:8) in blood components. A 20- minute room-temperature incubation with plasma-containing components resulted in approximately 2 log10 inactivation. Inactivation could be prevented by preincubation treatment of the plasma at 55 degrees C for 1 hour, which suggests the involvement of heat-labile plasma factors. No antibacterial activity was observed in washed red cells during the 20-minute room-temperature incubation. However, Y. enterocolitica colony-forming units declined by up to 2 log10 in washed red cells during the first days of 4 degrees C storage. Use of a white cell- reduction filter on freshly inoculated samples removed approximately 1 log10 of the organism regardless of whether bacteria were suspended in saline or washed red cells. Thus, bacterial levels may be affected by plasma, cellular components, and white cell-reduction filters. However, caution should be exercised in interpreting in vitro spiking studies designed to investigate the potential benefits of white cell reduction to eliminate the growth of Y. enterocolitica because of potential differences between naturally infected and experimentally inoculated blood.     

Late onset systemic lupus erythematosus and lupus-like disease in patients with apparent idiopathic glomerulonephritis

We report 17 patients who presented with either apparent idiopathic glomerulonephritis (16 patients) or post-streptococcal glomerulonephritis (one patient). Doubts arose about the nature of these patients' disease, either because their initial renal histology was suggestive of systemic lupus erythematosus (SLE) in the absence of its clinical or serological features, or because they developed with time the clinical or serological features of SLE. Three patients had a positive antinuclear antibody (ANA) test at the onset of their illness, but normal levels of serum binding of double-stranded DNA (dsDNAB). In another four patients the dsDNAB was slightly raised but with a negative ANA. On renal biopsy the predominant appearance was membranous glomerulonephritis (GN) in 10, subendothelial mesangiocapillary GN (MCGN) in three, and focal segmental glomerulosclerosis in two; one patient each had a focal proliferative GN and a diffuse endocapillary GN. On 1 micron renal sections stained with toluidine blue, 10 patients had immune deposits at multiple sites within the glomeruli. Over a period of one to 14 years, six patients developed extrarenal features suggestive of SLE, nine a positive ANA, and 12 increased serum levels of dsDNAB. Five patients became hypocomplementaemic. Cryoglobulins were isolated from the sera of 10 out of 12 patients; seven contained DNA. Separated cryoglobulin IgG from eight patients showed antibody activity directed against both ss and dsDNA in four, and against dsDNA only in three. On the basis of the clinical, histological and serological observation during follow-up five patients were reclassified as definite SLE, four as probable SLE and two as possible SLE. Rarely, SLE may present with nephritis as the sole disease manifestation, antedating other clinical features and even immunological markers of the disease by years. In addition, some patients with a glomerulonephritis may show clinical and immunological, or histological features of SLE, but do not fit accepted definitions of the disease.     

Memory B cells at successive stages of differentiation. Affinity maturation and the role of IgD receptors

The following evidence, mainly presented here, suggests that IgD receptors play a crucial role in determining the potential for affinity maturation in memory B cell populations. IgD receptors are present on the first memory B cells to appear after priming. These memory cells give rise to more-mature memory cells that have lost their IgD receptors. The proportions of early (IgD(+)) and mature (IgD(-)) memory cells found in individual donors vary with time, priming conditions, and the availability of T cell help, and both populations frequently coexist for long periods of time. IgD(+) and IgD(-) memory cells carry IgG receptors and give rise to IgG responses with identical isotype representation in adoptive recipients. IgD(+) memory cells, however, always give rise to predominantly low-affinity antibody responses, whereas IgD(-) memory cells consistently generate responses of substantially higher average affinity. This affinity differential is maintained between early and mature memory populations in the same donor and does not appear to be a result of selective differentiation of higher-affinity IgD(+) memory cells into the IgD(-) memory pool. Thus, the selective forces responsible for affinity maturation appear to operate mainly in mature memory cell populations that have already lost IgD receptors; or, stated conversely, little or no selection towards high-affinity memory appears to occur among memory cells that retain IgD receptors. In discussing these findings, we suggest that the IgD receptors themselves are responsible for maintaining early memory populations at a lower average affinity than IgD(-) populations in the same animal. The IgD receptors, we argue, serve to increase the antigen-binding capacity of lower-affinity memory cells so that these cells can survive, expand, and differentiate (to IgD(-)) at antigen concentrations that select against expansion of low- affinity memory cells no longer carrying IgD receptors. Thus, when antigen is limiting, IgD(-) memory populations will be selectively expanded to higher average affinities, whereas coexisting IgD(+) populations will retain their initial affinity profile. This hypothesis suggests that mechanisms that regulate expression and loss of IgD receptors are central to the adaptability of the immune system in its response to invading pathogens. Two related roles can be envisioned for the IgD receptors in this regard. First, they extend the lower boundary of the affinity range of early memory cell populations induced by a given antigenic stimulus and therefore broaden the diversity of responses obtainable from these populations. Secondly, they support the persistence of low-affinity memory populations under conditions where antigen becomes limiting and eventually disappears. These persisting populations then serve as a diversely reactive reservoir from which mature memory populations can be drawn with higher affinities either for the original antigen or, more importantly, for related antigens that the animal may subsequently encounter. Thus the existence of IgD receptors on early memory cells maintains the full range of response diversity despite ongoing selective expansion of (mature) memory populations to produce antibodies with high combining affinities for individual antigens. The flexibility inherent in such an organizational system, we believe, could be expected to account for the evolutionary development of IgD receptors and the regulatory capabilities that support operation of the system.     

Augmentation of spontaneous macrophage-mediated cytolysis by eosinophil peroxidase

Eosinophil peroxidase (EPO), a cationic protein purified from horse blood, adhered to four different types of tumor cells, markedly potentiating their lysis by preformed or enzymatically generated H(2)0(2) (up to 76-fold, as assayed in serum-containing tissue culture medium without supplemental halide). Similarly, compared with uncoated tumor cells, EPO-coated tumor cells were up to 32 times more sensitive to lysis when incubated with macrophages or granulocytes whose respiratory burst was triggered by PMA. However, EPO-coated tumor cells were also readily lysed by bacillus Calmette- Guerin-activated macrophages in the absence of exogenous triggering agents. This spontaneous cytolysis was rapid (50 percent at 2 h) and potent (50 percent lysis at macrophage/tumor cell ratios of 1.5 to 4.6), and was observed with both a peroxide-sensitive tumor (TLX9) and a peroxide-resistant tumor (NK lymphoma). Under the conditions used, neither EPO alone nor macrophages alone were spontaneously cytolytic. Neither EPO nor EPO-coated tumor cells triggered a detectable increment in H(2)0(2) release from macrophages. Nonetheless, spontaneous macrophage-mediated cytolysis of EPO- coated tumor cells was completely inhibitable by catalase (50 percent inhibition, 23 U/ml), although not by heated catalase, indicating a requirement for H(2)0(2). Cytolysis was also completely inhibitable by azide (50 percent inhibition, 2.6 X 10 -5 M), indicating a requirement for enzymatic activity of EPO. Thus, a cytophilic peroxidase from eosinophils and H(2)0(2) spontaneously released from activated macrophages interacted synergistically in a physiologic medium to destroy tumor cells.