BACKGROUND & AIMS: :Outside the nasopharynx, undifferentiated carcinomas occur only rarely at other head and neck locations. Although the association between undifferentiated nasopharyngeal carcinoma and Epstein-Barr virus (EBV) is consistent, there is conflicting evidence as to the association of EBV with undifferentiated carcinomas outside the nasopharynx. Here, we report on a case of undifferentiated carcinoma of the tongue base. A 71-year-old male, who had been treated with irradiation for primary unknown right neck metastatic EBV-positive undifferentiated carcinoma 9 years previously, was referred to our clinic with masses at the tongue base and right neck. The lesion at the tongue base was revealed to be an EBV-positive undifferentiated carcinoma. He was treated with resection of tongue base tumor and bilateral-neck dissection, and the defect at the tongue base was reconstructed with a free rectus abdominis myocutaneous flap. Re-irradiation was added post-operatively because of a positive surgical margin at the tongue base. The patient is presently alive without recurrence or distant metastasis 20 months after treatment. Although it is unclear whether our case is recurrent or newly developed EBV-latently infected undifferentiated carcinoma, we propose that EBV-associated tumors should be carefully observed after treatment at least for more than 10 years.

背景与目标： ：在鼻咽以外，未分化癌仅在其他头颈部位置很少发生。尽管未分化的鼻咽癌和爱泼斯坦-巴尔病毒（EBV）之间的关联是一致的，但关于EBV与鼻咽外未分化癌的关联有相互矛盾的证据。在这里，我们报道一例未分化舌基癌。一位71岁的男性在9年前接受过放射治疗，原发性右颈部转移性EBV阳性原发性未分化癌已经接受过放射治疗，现被转诊至我们的诊所，舌根和右颈部有肿块。舌根处的病变显示为EBV阳性未分化癌。对他进行了舌根肿瘤切除术和双侧颈淋巴结清扫术，并用游离的腹直肌肌皮瓣修复了舌根缺损。由于舌根的手术切缘阳性，因此在术后增加了再次照射。治疗后20个月，该患者目前尚无复发或远处转移。尽管尚不清楚我们的病例是复发的还是新发的EBV潜伏感染的未分化癌，但我们建议治疗至少10年后应仔细观察与EBV相关的肿瘤。

BACKGROUND & AIMS: AIMS:Case reports suggest an interaction between rofecoxib and the CYP1A2 substrate tizanidine. Our objectives were to explore the extent and mechanism of this possible interaction and to determine the CYP1A2 inhibitory potency of rofecoxib. METHODS:In a randomized, double-blind, two-phase cross-over study, nine healthy subjects took 25 mg rofecoxib or placebo daily for 4 days and, on day 4, each ingested 4 mg tizanidine. Plasma concentrations and the urinary excretion of tizanidine, its metabolites (M) and rofecoxib, and pharmacodynamic variables were measured up to 24 h. On day 3, a caffeine test was performed to estimate CYP1A2 activity. RESULTS:Rofecoxib increased the area under the plasma concentration-time curve (AUC(0-infinity)) of tizanidine by 13.6-fold [95% confidence interval (CI) 8.0, 15.6; P < 0.001), peak plasma concentration (C(max)) by 6.1-fold (4.8, 7.3; P < 0.001) and elimination half-life (t(1/2)) from 1.6 to 3.0 h (P < 0.001). Consequently, rofecoxib markedly increased the blood pressure-lowering and sedative effects of tizanidine (P < 0.05). Rofecoxib increased several fold the tizanidine/M-3 and tizanidine/M-4 ratios in plasma and urine and the tizanidine/M-5, tizanidine/M-9 and tizanidine/M-10 ratios in urine (P < 0.05). In addition, it increased the plasma caffeine/paraxanthine ratio by 2.4-fold (95% CI 1.4, 3.4; P = 0.008) and this ratio correlated with the tizanidine/metabolite ratios. Finally, the AUC(0-25) of rofecoxib correlated with the placebo phase caffeine/paraxanthine ratio (r = 0.80, P = 0.01). CONCLUSIONS:Rofecoxib is a potent inhibitor of CYP1A2 and it greatly increases the plasma concentrations and adverse effects of tizanidine. The findings suggest that rofecoxib itself is also metabolized by CYP1A2, raising concerns about interactions between rofecoxib and other CYP1A2 substrate and inhibitor drugs.

背景与目标： 目的：病例报告表明罗非考昔与CYP1A2底物替扎尼定之间存在相互作用。我们的目标是探索这种可能的相互作用的程度和机制，并确定罗非昔布对CYP1A2的抑制作用。
方法：在一项随机，双盲，两阶段交叉研究中，九名健康受试者每天服用25毫克罗非考昔或安慰剂，持续4天，并在第4天，每人摄入4毫克替扎尼定。在长达24小时内测量替扎尼定，其代谢产物（M）和罗非考昔的血浆浓度和尿排泄，以及药效学变量。在第3天，进行了咖啡因测试以评估CYP1A2的活性。
结果：罗非昔布将替扎尼定的血浆浓度-时间曲线下面积（AUC（0-无穷大））增加了13.6倍[95％置信区间（CI）8.0、15.6； P <0.001），峰值血药浓度（C（max））从1.6到3.0 h的6.1倍（4.8，7.3; P <0.001）和消除半衰期（t（1/2））（P <0.001） 。因此，罗非昔布显着增强了替扎尼定的降压和镇静作用（P <0.05）。罗非昔布将血浆和尿液中替扎尼定/ M-3和替扎尼定/ M-4的比例提高了几倍，尿液中替扎尼定/ M-5，替扎尼定/ M-9和替扎尼定/ M-10的比例提高了几倍（P <0.05）。此外，它使血浆咖啡因/对黄嘌呤比率增加了2.4倍（95％CI 1.4、3.4； P = 0.008），并且该比率与替扎尼定/代谢产物比率相关。最后，罗非昔布的AUC（0-25）与安慰剂相咖啡因/对黄嘌呤的比​​例相关（r = 0.80，P = 0.01）。
结论：罗非昔布是一种有效的CYP1A2抑制剂，它大大提高了血浆浓度和替扎尼定的不良反应。研究结果表明罗非考昔本身也被CYP1A2代谢，引起对罗非考昔与其他CYP1A2底物和抑制剂药物之间相互作用的担忧。

BACKGROUND & AIMS: :The distributed genome hypothesis (DGH) states that each strain within a bacterial species receives a unique distribution of genes from a population-based supragenome that is many times larger than the genome of any given strain. The observations that natural infecting populations are often polyclonal and that most chronic bacterial pathogens have highly developed mechanisms for horizontal gene transfer suggested the DGH and provided the means and the mechanisms to explain how chronic infections persist in the face of a mammalian host's adaptive defense mechanisms. Having previously established the validity of the DGH for obligate pathogens, we wished to evaluate its applicability to an opportunistic bacterial pathogen. This was accomplished by construction and analysis of a highly redundant pooled genomic library containing approximately 216,000 functional clones that was constructed from 12 low-passage clinical isolates of Pseudomonas aeruginosa, 6 otorrheic isolates and 6 from other body sites. Sequence analysis of 3,214 randomly picked clones (mean insert size, approximately 1.4 kb) from this library demonstrated that 348 (10.8%) of the clones were unique with respect to all genomic sequences of the P. aeruginosa prototype strain, PAO1. Hypothetical translations of the open reading frames within these unique sequences demonstrated protein homologies to a number of bacterial virulence factors and other proteins not previously identified in P. aeruginosa. PCR and reverse transcription-PCR-based assays were performed to analyze the distribution and expression patterns of a 70-open reading frame subset of these sequences among 11 of the clinical strains. These sequences were unevenly distributed among the clinical isolates, with nearly half (34/70) of the novel sequences being present in only one or two of the individual strains. Expression profiling revealed that a vast majority of these sequences are expressed, strongly suggesting they encode functional proteins.

背景与目标： ：分布式基因组假设（DGH）指出，细菌物种中的每个菌株都从基于种群的超基因组中获得独特的基因分布，其比任何给定菌株的基因组都要大很多倍。自然感染种群通常是多克隆的，大多数慢性细菌病原体具有水平基因转移的高度发达的机制的观点提出了DGH，并提供了解释哺乳动物宿主面对适应性防御机制时慢性感染如何持续存在的手段和机制。先前已确定DGH对专性病原体的有效性，我们希望评估其对机会细菌病原体的适用性。这是通过构建和分析包含约216,000个功能性克隆的高度冗余的集合基因组文库实现的，该文库由铜绿假单胞菌的12种低通道临床分离株，6种耳泻分离株和6个其他身体部位构建而成。对来自该文库的3,214个随机挑选的克隆（平均插入片段大小，约1.4 kb）进行序列分析，结果表明，对于铜绿假单胞菌原型菌株PAO1的所有基因组序列，其中348个（10.8％）克隆是唯一的。在这些独特序列内的开放阅读框的假想翻译证明了与许多细菌毒力因子和以前在铜绿假单胞菌中未鉴定出的其他蛋白质的蛋白质同源性。进行了基于PCR和逆转录PCR的分析，以分析这些序列的70个开放阅读框子集在11种临床菌株中的分布和表达模式。这些序列在临床分离株中分布不均，只有一半或34个新序列出现在一个或两个单独的菌株中。表达谱分析表明这些序列中的绝大多数都被表达，强烈暗示它们编码功能蛋白。

BACKGROUND & AIMS: :Through an endoscopic transvesico-transurethral approach, we closed a vesicovaginal fistula that occurred after hysterectomy in a patient with uterine leiomyoma. The 3-mm fistula, located in the midportion of retrotrigone, was resected transurethrally and sutured in two layers through two 5-mm suprapubic trocars placed into the bladder and the urethral route under pneumobladder. The patient had no urine leakage from the vagina after surgery.

背景与目标： ：通过内窥镜经膀胱-经尿道入路，我们关闭了子宫平滑肌瘤患者子宫切除术后发生的膀胱阴道瘘。将3毫米的瘘管位于后三角骨的中部，经尿道切除，并通过两根5毫米的耻骨上耻骨套管针将其缝合在两层中，然后将其插入膀胱和在气囊下的尿道。病人术后没有尿液从阴道漏出。

BACKGROUND & AIMS: AIM:This paper reviews how the interpreter's role is described in empirically based, qualitative cross-cultural interview studies and how trustworthiness is determined. BACKGROUND:Increased immigration during the past decades has created a multiethnic society in many countries. This development poses a challenge to healthcare staff, in that they need to understand how people from different cultures experience health and illness. One way to assess immigrants' experiences is through cross-cultural interview studies, involving an interpreter. Thorough knowledge of the interpreter's role is needed in order to increase the trustworthiness of this kind of nursing research. METHOD:Literature searches were conducted from October to November 2004 using PubMed, CINAHL, Psycinfo, Sociological abstract, Your Journals@ovid, and Eric databases. Qualitative interview studies written in English and performed with an interpreter were included. The Matrix Method was used to review the literature. FINDINGS:In almost all of the 13 relevant papers found, the role of the interpreter(s) in the research process was only sparsely described. In addition, all studies except one employed different techniques to established trustworthiness. The most common techniques were prolonged engagement, member check or triangulation, the latter performed either on the data, investigators or methods. CONCLUSION:Methodological issues with respect to interpreters have received only limited attention in cross-cultural interview studies. Researchers in the field of nursing need to consider (1) the interpreter's role/involvement in the research process; (2) the interpreter's competence and the style of interpreting; (3) the interpreter's impact on the findings. This information is a prerequisite when trying to determine the trustworthiness of a cross-cultural study.

背景与目标： 目的：本文回顾了如何在基于经验的定性跨文化访谈研究中描述口译员的角色，以及如何确定信任度。
背景：过去几十年来移民的增加在许多国家创建了一个多种族的社会。这种发展对医护人员提出了挑战，因为他们需要了解来自不同文化背景的人们如何经历健康和疾病。评估移民经验的一种方法是通过跨文化访谈研究，其中包括一名口译员。为了增加这种护理研究的可信度，需要对口译员的作用有透彻的了解。
方法：从2004年10月至2004年11月使用PubMed，CINAHL，Psycinfo，Sociological abstract，Your Journals @ ovid和Eric数据库进行文献检索。包括用英语撰写并由口译员进行的定性访谈研究。矩阵法用于回顾文献。
结果：在发现的所有13篇相关论文中，几乎都很少描述口译员在研究过程中的作用。此外，除一项研究外，所有研究均采用不同的技术来建立可信度。最常见的技术是长时间的接触，成员检查或三角剖分，后者根据数据，研究人员或方法进行。
结论：关于口译员的方法论问题在跨文化访谈研究中仅受到了有限的关注。护理领域的研究人员需要考虑（1）口译员在研究过程中的角色/参与程度； （二）口译人员的能力和口译风格； （3）口译员对调查结果的影响。在尝试确定跨文化研究的可信赖性时，此信息是前提条件。

BACKGROUND & AIMS: :A case of Meibomian carcinoma of the left eyelid was observed in a 53-year-old-female patient. SHe had been previously treated for chronic unilateral blepharoconjunctivitis; an excisional biopsy disclosed a Meibomian carcinoma. First a total resection of both left eyelids was performed with plastic reconstructive surgery, three months later a recurrence required an orbital exenteration. This case underlines the interest of an early diagnosis which allows a more conservative treatment. The diagnosis must be kept in mind in any case of chronic unilateral blepharoconjunctivitis; histopathology has a key role in the diagnosis of Meibomian carcinoma.

背景与目标： ：在一名53岁的女性患者中观察到左眼睑睑肌癌的病例。他曾接受过慢性单侧睑结膜炎的治疗；切除活检揭示了睑板癌。首先用整形外科手术对两个左眼皮进行全切，三个月后复发，需要眼眶切除。该病例强调了允许更保守治疗的早期诊断的兴趣。在任何情况下，慢性单侧睑结膜炎都必须牢记诊断；组织病理学在睑板癌的诊断中具有关键作用。

BACKGROUND & AIMS: STUDY OBJECTIVE:To examine the prevalence, symptomatology, risk factors, and other infections associated with urogenital chlamydial infection in pregnant teenagers. DESIGN:Retrospective case-control study by medical record review. SETTING:Prenatal care clinic for adolescents at University of Tennessee Medical Center, Knoxville, Tennessee. PARTICIPANTS:Pregnant adolescents younger than 19 years of age who were diagnosed with chlamydial infection on the first prenatal visit from 1988 to 1994 were studied. Pregnant adolescents of similar age and socioeconomic background who came in the same day for the first prenatal visit, but were not infected, made up the control group. INTERVENTION:Routine prenatal questionnaires regarding personal and medical histories, and routine prenatal screening, including pelvic examination with Papanicolaou (PAP) smear and laboratory investigations for common genital infections and sexual transmitted disease (STDs), were obtained. MAIN OUTCOME MEASURES:Analyzed the prevalence of chlamydial infection and compared the infected group to the control group with regard to race, behavioral factors, symptoms, prenatal screening results, other concurrent genital infections, and histories of STDs. RESULTS:Of a total population of 596 pregnant teenagers, 67 (11.24%) were infected with Chlamydia trachomatis. In multivariate analysis, black race (odds ratio [OR] = 4.01; 95% confidence interval [CI] = 1.74-9.23; p = 0.001) and greater gestational age at first prenatal visit (OR = 1.11; 95% CI = 1.04-1.18; p = 0.001) were independently associated with chlamydial infection. Age, marital status, number of pregnancies, smoking, alcohol abuse, drug abuse, age at first intercourse, and multiple sex partners were not associated with the infection. Likewise, the symptom of vaginal discharge (a complaint of > 70% in each group), other genital co-infections (found > 50% in each group, mainly candidiasis and bacterial vaginosis), abnormal PAP smears (found > 60% in each group) and histories of STDs or previous chlamydial infection were not significantly different between case and control groups. Human papillomavirus infection, trichomonal infection, and dysplasia or atypia were found more often in patients infected with chlamydia, but were not statistically significant. CONCLUSION:Pregnant adolescents in east Tennessee were at risk for chlamydial infection as well as for other genital infections and abnormal PAP smears. Routine prenatal chlamydial screening is warranted because of a lack of specific symptoms.

背景与目标： 目的：研究孕妇青少年泌尿生殖道衣原体感染的患病率，症状，危险因素和其他感染情况。
设计：回顾性病例对照研究，病历审查。
地点：田纳西州诺克斯维尔市田纳西大学医学中心的青少年产前保健诊所。
研究对象：1988年至1994年第一次产前检查时被诊断患有衣原体感染的19岁以下的青少年。年龄相同，社会经济背景相似的怀孕青少年在同一天进行第一次产前检查，但未感染，组成了对照组。
干预措施：获得有关个人和医学史的常规产前问卷，以及常规的产前筛查，包括用帕潘尼古拉（PAP）涂片进行盆腔检查以及常见生殖器感染和性传播疾病（STD）的实验室检查。
主要观察指标：分析衣原体感染的发生率，并比较种族，行为因素，症状，产前筛查结果，其他并发生殖器感染和性病史，比较感染者与对照组。
结果：在596名怀孕的青少年总数中，有67名（11.24％）感染了沙眼衣原体。在多变量分析中，黑人种族（赔率[OR] = 4.01； 95％置信区间[CI] = 1.74-9.23； p = 0.001）和第一次产前检查时的胎龄较高（OR = 1.11； 95％CI = 1.04- 1.18； p = 0.001）与衣原体感染独立相关。年龄，婚姻状况，怀孕次数，吸烟，酗酒，药物滥用，初次性交年龄和多性伴侣均与感染无关。同样，白带的症状（每组投诉> 70％），其他生殖器合并感染（每组发现> 50％，主要是念珠菌病和细菌性阴道病），PAP涂片异常（每发现> 60％）病例组和对照组之间的性病史或以前的衣原体感染史无显着差异。感染衣原体的患者更常发现人乳头瘤病毒感染，滴虫感染和异型增生或异型性，但无统计学意义。
结论：田纳西州东部的怀孕青少年有衣原体感染以及其他生殖器感染和PAP涂片异常的危险。由于缺乏特定症状，需要常规的产前衣原体筛查。

BACKGROUND & AIMS: BACKGROUND:Current genomic research methods provide researchers with enormous amounts of data. Combining data from different high-throughput research technologies commonly available in biological databases can lead to novel findings and increase research efficiency. However, combining data from different heterogeneous sources is often a very arduous task. These sources can be different microarray technology platforms, genomic databases, or experiments performed on various species. Our aim was to develop a software program that could facilitate the combining of data from heterogeneous sources, and thus allow researchers to perform genomic cross-platform/cross-species studies and to use existing experimental data for compendium studies. RESULTS:We have developed a web-based software resource, called CROPPER that uses the latest genomic information concerning different data identifiers and orthologous genes from the Ensembl database. CROPPER can be used to combine genomic data from different heterogeneous sources, allowing researchers to perform cross-platform/cross-species compendium studies without the need for complex computational tools or the requirement of setting up one's own in-house database. We also present an example of a simple cross-platform/cross-species compendium study based on publicly available Parkinson's disease data derived from different sources. CONCLUSION:CROPPER is a user-friendly and freely available web-based software resource that can be successfully used for cross-species/cross-platform compendium studies.

背景与目标： 背景：目前的基因组研究方法为研究人员提供了大量数据。结合生物学数据库中常用的不同高通量研究技术的数据，可以得出新颖的发现并提高研究效率。但是，合并来自不同异构源的数据通常是一项艰巨的任务。这些来源可以是不同的微阵列技术平台，基因组数据库或对各种物种进行的实验。我们的目标是开发一个软件程序，以方便来自不同来源的数据的合并，从而使研究人员能够进行基因组跨平台/跨物种研究，并将现有的实验数据用于纲要研究。
结果：我们开发了一个基于Web的软件资源，称为CROPPER，该资源使用有关Ensembl数据库中不同数据标识符和直系同源基因的最新基因组信息。 CROPPER可用于组合来自不同异构来源的基因组数据，从而使研究人员无需复杂的计算工具或建立自己的内部数据库即可进行跨平台/跨物种纲要研究。我们还提供了一个简单的跨平台/跨物种纲要研究的例子，该研究基于从不同来源获得的公开可用的帕金森氏病数据。
结论：CROPPER是一种用户友好且免费提供的基于Web的软件资源，可以成功地用于跨物种/跨平台纲要研究。

BACKGROUND & AIMS: :A case of malignant ependymoma with extracranial metastases is reported. A 59-year-old male was admitted to our hospital with vomiting and ataxia. Following computed tomographic (CT) scanning indicating a ring-like enhanced mass in the cerebellum, the tumor was subtotally removed in December, 1985. Histological diagnosis was malignant ependymoma. A second operation was performed in February, 1987, due to recurrence of the tumor in the fourth ventricle. Postoperative radiation therapy at a total dose of 7780 rads was given over 2 years. Eleven months after radiation therapy was completed, he reported cough and multiple skin metastases. Chest x-rays showed metastases at the right hilus. Repeated CT scans revealed separate frontal cerebral metastatic tumors. He died of respiratory insufficiency. Extracranial metastases of infratentorial ependymoma to the skin and lung are rare pathological entities.

背景与目标： ：一例恶性室间隔膜瘤伴颅外转移的报道。一名59岁的男性因呕吐和共济失调入院。在计算机断层扫描（CT）扫描显示小脑环状肿块后，于1985年12月将肿瘤小块切除。组织学诊断为恶性室间隔膜瘤。由于第四脑室肿瘤的复发，于1987年2月进行了第二次手术。术后2年进行了总剂量为7780 rads的术后放射治疗。放疗结束11个月后，他报告出现了咳嗽和多处皮肤转移。胸部X光片显示右肺门有转移。重复的CT扫描显示单独的额叶脑转移瘤。他死于呼吸功能不全。颅下膜上室间隔瘤向皮肤和肺的颅外转移是罕见的病理学实体。

BACKGROUND & AIMS: BACKGROUND:Angiotensin-converting enzyme (ACE) inhibitors prevent the expansion and rupture of aortic aneurysms in animals. We investigated the association between ACE inhibitors and rupture in patients with abdominal aortic aneurysms. METHODS:We did a population-based case-control study of linked administrative databases in Ontario, Canada. The sample included consecutive patients older than 65 (n=15,326) admitted to hospital with a primary diagnosis of ruptured or intact abdominal aortic aneurysm between April 1, 1992, and April 1, 2002. FINDINGS:Patients who received ACE inhibitors before admission were significantly less likely to present with ruptured aneurysm (odds ratio [OR] 0.82, 95% CI 0.74-0.90) than those who did not receive ACE inhibitors. Adjustment for demographic characteristics, risk factors for rupture, comorbidities, contraindications to ACE inhibitors, measures of health-care use, and aneurysm screening yielded similar results (0.83, 0.73-0.95). Consistent findings were noted in subgroups at high risk of rupture, including patients older than 75 years and those with a history of hypertension. Conversely, such protective associations were not observed for beta blockers (1.02, 0.89-1.17), calcium channel blockers (1.01, 0.89-1.14), alpha blockers (1.15, 0.86-1.54), angiotensin receptor blockers (1.24, 0.71-2.18), or thiazide diuretics (0.91, 0.78-1.07). INTERPRETATION:ACE inhibitors are associated with a reduced risk of ruptured abdominal aortic aneurysm, unlike other antihypertensive agents. Randomised trials of ACE inhibitors for prevention of aortic rupture might be warranted.

背景与目标： 背景：血管紧张素转换酶（ACE）抑制剂可防止动物主动脉瘤的扩张和破裂。我们调查了腹主动脉瘤患者中ACE抑制剂与破裂之间的关系。
方法：我们在加拿大安大略省的相关行政数据库中进行了基于人群的病例对照研究。该样本包括1992年4月1日至2002年4月1日之间入院的65岁以上的连续患者（n = 15,326），其主要诊断为腹主动脉瘤破裂或完整。
结果：与未接受ACE抑制剂的患者相比，入院前接受ACE抑制剂的患者出现动脉瘤破裂的可能性显着降低（优势比[OR] 0.82，95％CI 0.74-0.90）。调整人口统计学特征，破裂危险因素，合并症，ACEI禁忌症，卫生保健措施和动脉瘤筛查得出相似的结果（0.83，0.73-0.95）。在高破裂风险的亚组中，包括在75岁以上的患者和有高血压病史的患者中，发现了一致的发现。相反，对于β受体阻滞剂（1.02，0.89-1.17），钙通道阻滞剂（1.01，0.89-1.14），α受体阻滞剂（1.15，0.86-1.54），血管紧张素受体阻滞剂（1.24，0.71-2.18）未观察到这种保护性关联。 ，或噻嗪类利尿剂（0.91、0.78-1.07）。
解释：与其他降压药不同，ACE抑制剂与降低腹主动脉瘤破裂的风险有关。 ACE抑制剂预防主动脉破裂的随机试验可能是必要的。

BACKGROUND & AIMS: :Cyclic and congenital neutropenia are caused by mutations in the human neutrophil elastase (HNE) gene (ELA2), leading to an immunodeficiency characterized by decreased or oscillating levels of neutrophils in the blood. The HNE mutations presumably cause loss of enzyme activity, consequently leading to compromised immune system function. To understand the structural basis for the disease, we implemented methods from bioinformatics to analyze all the known HNE missense mutations at both the sequence and structural level. Our results demonstrate that the 32 different mutations have diverse effects on HNE structure and function, affecting structural disorder and aggregation tendencies, stability maintaining contacts, and electrostatic properties. A large proportion of the mutations are located at conserved amino acids, which are usually essential in determining protein structure and function. The majority of the disease-causing HNE missense mutations lead to major structural changes and loss of stability in the protein. A few mutations also affect functional residues, leading into decreased catalytic activity or altered ligand binding. Our analysis reveals the putative effects of all known missense mutations in HNE, thus allowing the structural basis of cyclic and congenital neutropenia to be elucidated. We have employed and analyzed a set of some 30 different methods for predicting the effects of amino acid substitutions. We present results and experience from the analysis of the applicability of these methods in the analysis of numerous genes, proteins, and diseases to reveal protein structure-function relationships and disease genotype-phenotype correlations.

背景与目标： ：循环性和先天性中性粒细胞减少症是由人中性粒细胞弹性蛋白酶（HNE）基因（ELA2）突变引起的，导致免疫缺陷，其特征是血液中中性粒细胞水平降低或振荡。 HNE突变可能导致酶活性下降，因此导致免疫系统功能受损。为了了解该疾病的结构基础，我们采用了生物信息学的方法来分析序列和结构水平上所有已知的HNE错义突变。我们的结果表明，这32种不同的突变对HNE的结构和功能有多种影响，影响结构异常和聚集趋势，保持接触的稳定性以及静电性质。很大一部分突变位于保守氨基酸上，这通常是决定蛋白质结构和功能所必需的。大多数引起疾病的HNE错义突变会导致主要的结构变化和蛋白质稳定性的损失。一些突变也影响功能残基，导致催化活性降低或配体结合改变。我们的分析揭示了HNE中所有已知错义突变的推定作用，从而阐明了周期性和先天性中性粒细胞减少症的结构基础。我们已经采用并分析了一组约30种不同的方法来预测氨基酸取代的影响。我们通过分析这些方法在分析众多基因，蛋白质和疾病中的适用性来提供结果和经验，以揭示蛋白质结构与功能的关系以及疾病的基因型与表型的相关性。

BACKGROUND & AIMS: Previous mutagenesis studies with bacteriorhodopsin have shown that reprotonation of the Schiff's base is the rate-limiting step in the photocycle of the D96N mutant, whereas retinal re-isomerization and return of the protein to the initial state constitute the rate-limiting events in the photocycle of the L93A mutant. Thus, in the D96N mutant, decay of the M intermediate is slowed down by more than 100-fold at pH 7. In the L93A mutant, decay of the O intermediate is slowed down by 250-fold. We report here that in the L93A, D96N double mutant, decay of the M intermediate, as well as the formation and decay of the O intermediate, are slowed down dramatically. The photocycle is completed by the decay of a long-lived O intermediate, as in the L93A mutant. The decay of the M and O intermediates in the double mutant parallels the behavior seen in the single mutants over a wide temperature and pH range, arguing that the observed independence is an intrinsic property of the mutant. The slow decay of the M and O intermediates can be selectively and independently reversed under conditions identical to those used for the corresponding intermediates in the D96N and L93A single mutants. Because the effects of the two individual mutations are preserved in the double mutant and can be independently reversed, we conclude that residues Asp 96 and Leu 93 act independently and at different stages of the bacteriorhodopsin photocycle. These results also show that formation of the O intermediate only requires protonation of the Schiff's base and is independent of the protonation of Asp 96 from the aqueous medium.

背景与目标： 先前使用细菌视紫红质的诱变研究表明，席夫氏碱的质子化是D96N突变体光循环中的限速步骤，而视网膜重新异构化和蛋白质返回至初始状态构成了光循环中的限速事件L93A突变体的序列。因此，在D96N突变体中，pH值为7时，M中间体的衰减被减慢了100倍以上。在L93A突变体中，O中间体的衰减被减慢了250倍。我们在此报告，在L93A，D96N双重突变体中，M中间产物的衰减以及O中间产物的形成和衰减都大大减慢了。像L93A突变体一样，光循环是通过长寿命的O中间体的衰变完成的。双重突变体中M和O中间体的衰变与单个突变体在较宽的温度和pH范围内观察到的行为相似，认为观察到的独立性是突变体的固有特性。 M和O中间体的缓慢衰变可以在与D96N和L93A单突变体中相应中间体相同的条件下有选择地独立逆转。因为两个单独的突变的影响保留在双突变体中，并且可以独立逆转，所以我们得出结论，残基Asp 96和Leu 93分别在细菌视紫红质光循环的不同阶段起作用。这些结果还表明，O中间体的形成仅需要席夫碱的质子化，而与来自水性介质的Asp 96的质子化无关。

BACKGROUND & AIMS: PURPOSE:To determine the clinical importance and relative value of reinterpreting brain CT imaging studies by subspecialty experts regarding changes in clinical management. METHODS:Computerized records were queried at two institutions during the years 2002-2003 for both primary interpretation by board-certified nonneuroradiologists and secondary interpretation by three neuroradiologists. A total of 1,081 cases were reviewed. Each case was initially interpreted as an emergent or urgent study. The reinterpreted studies were scored as concordant or discordant by the subspecialty experts. The discordant studies were then categorized as a "major discordance" if there was a change in clinical management, or as a "minor discordance" if there was no impact or change in clinical management. RESULTS:Of the 1,081 studies reviewed, 14 studies were identified as discordant (1.3%). Of those discordant studies, four were categorized as major discrepancies necessitating a change in clinical management (0.4 %). Ten were categorized as minor discrepancies (0.9%). There were no permanent adverse outcomes with respect to morbidity and mortality as a result of any discrepancy. CONCLUSION:The vast majority of interpreted head CT cases read by board-certified general radiologists do not result in discordant interpretations as verified by subspecialty experts. Discordant interpretations did not result in changes in clinical management in most cases. Double reading of head CTs by subspecialty experts appears to be an inefficient method of substantially improving imaging health quality outcomes.

背景与目标： 目的：确定亚专业专家对临床管理变化进行重新解释脑CT成像研究的临床重要性和相对价值。
方法：在2002年至2003年期间，在两家机构中查询了计算机记录，以获取由董事会认证的非神经放射科医生进行的主要解释，以及由三位神经放射科医生进行的次要解释。总共审查了1,081例。最初，每个案例都被解释为紧急研究。重新解释的研究被专业专家评定为一致或不一致。如果临床管理发生变化，则将不一致的研究分类为“重大不一致”，如果临床管理没有影响或发生变化，则将其分类为“轻微不一致”。
结果：在所审查的1,081项研究中，有14项研究被确定为不一致（1.3％）。在这些不一致的研究中，有四项被归类为需要改变临床管理的主要差异（0.4％）。十个分类为轻微差异（0.9％）。任何差异都不会在发病率和死亡率方面带来永久性的不良后果。
结论：经董事会认证的一般放射科医生阅读的绝大多数解释性头部CT病例，经专科专家验证，并不会导致不一致的解释。在大多数情况下，不一致的解释并不会导致临床管理的改变。专科专家对头颅CT进行双重读取似乎是一种实质上改善影像健康质量结果的无效方法。

BACKGROUND & AIMS: BACKGROUND:Cholecystocolocutaneous fistula (CCCF) is a rare complication of gallstone disease resulting from spillage of gallstones from perforation of an empyema of the gallbladder, which can pose diagnostic dilemmas. We describe a patient, who presented initially with a swelling followed by discharging sinuses on her right flank where a diagnosis of CCCF was made and was treated surgically with satisfactory outcome. METHODS:A computed tomography (CT) scan showed an ill-defined soft tissue mass in the right subhepatic space and a fistulogram demonstrated passage of contrast into the gallbladder fossa and hepatic flexure of colon. At laparotomy, a cutaneous fistula containing two pigment stones led to the gallbladder fossa and hepatic flexure of colon. RESULTS:Debridement of infected granulation tissues which had replaced the gallbladder, closure of the cystic duct stump and colonic fistula followed by excision of the fistula tract led to complete resolution. CONCLUSIONS:CCCF is a rare complication of perforated gallbladder with spillage of calculi, and a fistulogram is helpful in establishing the diagnosis. This case highlights the importance of retrieving spilled stones following interventions in the gallbladder to prevent the complication.

背景与目标： 背景：胆囊管皮肤瘘（CCCF）是胆囊积脓性穿孔引起胆结石溢出引起胆结石疾病的罕见并发症，可引起诊断难题。我们描述了一名患者，该患者最初出现红肿，然后在其右牙侧排出鼻窦，在那里做出了CCCF的诊断，并接受了手术治疗，结果令人满意。
方法：计算机断层扫描（CT）扫描显示右肝下间隙有模糊不清的软组织肿块，而瘘管图显示造影剂进入胆囊窝和结肠肝弯曲。在剖腹手术中，包含两个色素结石的皮肤瘘导致胆囊窝和结肠的肝弯曲。
结果：清创的感染肉芽组织清创了胆囊，闭合了胆囊管残端和结肠瘘，然后切除了瘘管，从而彻底解决了问题。
结论：CCCF是胆囊穿孔伴结石溢出的罕见并发症，瘘管造影有助于诊断。该病例强调了在胆囊内进行干预以防止并发症后取出溢出的结石的重要性。