BACKGROUND & AIMS: Levodopa-induced psychosis can complicate the treatment of Parkinson's disease (PD). In this retrospective, uncontrolled report, we describe our experience treating PD-related psychosis with clozapine, emphasizing those patients treated for longer than 1 year. Twenty-seven patients were treated, 14 for longer than 1 year. Most patients showed a rapid improvement from baseline within 1 month using the Clinical Global Impression and Global Psychosis Rating Scores. Five patients discontinued the drug due to side effects, but only two patients reported side effects after 6 months of treatment. Clozapine appears to be effective in treating PD related psychotic symptoms while not interfering with motor function.

背景与目标： 左旋多巴引起的精神病会使帕金森氏病 (PD) 的治疗复杂化。在这份回顾性，不受控制的报告中，我们描述了我们用氯氮平治疗PD相关精神病的经验，强调了那些治疗时间超过1年的患者。27例患者接受了治疗，其中14例超过1年。使用临床总体印象和总体精神病评分，大多数患者在1个月内从基线显示出快速改善。五名患者因副作用而停药，但只有两名患者在治疗6个月后报告副作用。氯氮平似乎可有效治疗PD相关的精神病性症状，同时不干扰运动功能。

BACKGROUND & AIMS: :The transcription factor signal transducer and activator of transcription-1 (STAT1) plays a key role in immunity against mycobacterial and viral infections. Here, we characterize three human STAT1 germline alleles from otherwise healthy patients with mycobacterial disease. The previously reported L706S, like the novel Q463H and E320Q alleles, are intrinsically deleterious for both interferon gamma (IFNG)-induced gamma-activating factor-mediated immunity and interferon alpha (IFNA)-induced interferon-stimulated genes factor 3-mediated immunity, as shown in STAT1-deficient cells transfected with the corresponding alleles. Their phenotypic effects are however mediated by different molecular mechanisms, L706S affecting STAT1 phosphorylation and Q463H and E320Q affecting STAT1 DNA-binding activity. Heterozygous patients display specifically impaired IFNG-induced gamma-activating factor-mediated immunity, resulting in susceptibility to mycobacteria. Indeed, IFNA-induced interferon-stimulated genes factor 3-mediated immunity is not affected, and these patients are not particularly susceptible to viral disease, unlike patients homozygous for other, equally deleterious STAT1 mutations recessive for both phenotypes. The three STAT1 alleles are therefore dominant for IFNG-mediated antimycobacterial immunity but recessive for IFNA-mediated antiviral immunity at the cellular and clinical levels. These STAT1 alleles define two forms of dominant STAT1 deficiency, depending on whether the mutations impair STAT1 phosphorylation or DNA binding.

背景与目标： 转录因子信号转导和转录激活因子-1 (STAT1) 在抵抗分枝杆菌和病毒感染的免疫中起关键作用。在这里，我们描述了来自其他健康的分枝杆菌疾病患者的三个人类STAT1种系等位基因。先前报道的L706S，如新型Q463H和E320Q等位基因，对干扰素 γ (IFNG) 诱导的 γ 激活因子介导的免疫和干扰素 α (IFNA) 诱导的干扰素刺激基因因子3介导的免疫具有内在的有害作用，如用相应等位基因转染的STAT1-deficient细胞所示。然而，它们的表型效应是由不同的分子机制介导的，L706S影响STAT1磷酸化，Q463H和E320Q影响STAT1 DNA结合活性。杂合子患者表现出特异性受损的IFNG诱导的 γ 激活因子介导的免疫力，导致对分枝杆菌的敏感性。实际上，IFNA诱导的干扰素刺激基因因子3介导的免疫不受影响，并且这些患者对病毒性疾病并不特别敏感，这与其他纯合的患者不同，同样有害的STAT1突变对两种表型均隐性。因此，三个STAT1等位基因在IFNG介导的抗分枝杆菌免疫中占主导地位，但在细胞和临床水平上对IFNA介导的抗病毒免疫具有隐性。这些STAT1等位基因定义了两种形式的显性STAT1缺陷，具体取决于突变是否损害STAT1磷酸化或DNA结合。

BACKGROUND & AIMS: :Hepatic steatosis is defined by an increased content of hepatocellular lipids (HCLs) and is frequently observed in insulin-resistant states including type 2 diabetes mellitus. A dietary excess of saturated fat contributes significantly to HCL accumulation. Elevated HCL levels mainly account for hepatic insulin resistance, which is probably mediated by partitioning of free fatty acids to the liver (fat overflow) and by an imbalance of adipocytokines (decreased adiponectin and/or increased proinflammatory cytokines). Both free fatty acids and adipocytokines activate inflammatory pathways that include protein kinase C, the transcription factor nuclear factor kappaB, and c-Jun N-terminal kinase 1 and can thereby accelerate the progression of hepatic steatosis to nonalcoholic steatohepatitis and cirrhosis. Proton magnetic resonance spectroscopy has made it possible to quantify HCL concentrations and to detect even small changes in these concentrations in clinical settings. Moderately hypocaloric, fat-reduced diets can decrease HCL levels by approximately 40-80% in parallel with loss of up to 8% of body weight. Treatment with thiazolidinediones (e.g. pioglitazone and rosiglitazone) reduces HCL levels by 30-50% by modulating insulin sensitivity and endocrine function of adipose tissue in type 2 diabetes. Metformin improves hepatic insulin action without affecting HCL levels, whereas insulin infusion for 67 h increases HCL levels by approximately 18%; furthermore, HCL levels positively correlate with the insulin dosage in insulin-treated type 2 diabetes. In conclusion, liver fat is a critical determinant of metabolic fluxes and inflammatory processes, thereby representing an important therapeutic target in insulin resistance and type 2 diabetes mellitus.

背景与目标： : 肝脂肪变性是由肝细胞脂质 (HCLs) 含量增加定义的，在胰岛素抵抗状态 (包括2型糖尿病) 中经常观察到。饮食中过量的饱和脂肪会显着促进HCL的积累。HCL水平升高主要是导致肝胰岛素抵抗的原因，这可能是由游离脂肪酸分配到肝脏 (脂肪溢出) 和脂肪细胞因子失衡 (脂联素减少和/或促炎细胞因子增加) 介导的。游离脂肪酸和脂肪细胞因子都激活炎症途径，包括蛋白激酶C，转录因子核因子kappaB和c 6月N端激酶1，从而可以加速肝脂肪变性向非酒精性脂肪性肝炎和肝硬化的进展。质子磁共振波谱已使量化HCL浓度并在临床环境中检测到这些浓度的微小变化成为可能。中度低热量，减脂饮食可使HCL水平降低约40-80%，同时减少多达8% 的体重。噻唑烷二酮类药物 (例如吡格列酮和罗格列酮) 的治疗通过调节2型糖尿病中脂肪组织的胰岛素敏感性和内分泌功能，将HCL水平降低30-50%。二甲双胍改善肝胰岛素作用而不影响HCL水平，而胰岛素输注67小时可使HCL水平增加约18%; 此外，在胰岛素治疗的2型糖尿病中，HCL水平与胰岛素剂量呈正相关。总之，肝脏脂肪是代谢通量和炎症过程的关键决定因素，因此是胰岛素抵抗和2型糖尿病的重要治疗目标。

BACKGROUND & AIMS: Activated neutrophils take a long time to pass through a narrow lumen like a micropore, and are supposed to play a deteriorating effect on microcirculation. Although the activation of neutrophils has been demonstrated in Behçet's disease, nobody analyzes the clinical activity of the disease by means of the rheological measure of neutrophils activity. Using a micropore (pore diameter 5 microns) filtration technique, we measured the filtration time of peripheral blood neutrophils, as a rheological measure of their activity, in order to determine the clinical activity of Behçet's disease. Twenty-one patients with Behçet's disease and 14 healthy control individuals were enrolled in the study. Symptoms and signs exhibited in the patients led us to distinguish the Behçet's disease into inactive and active cases. The latter were further differentiated into cases with absent symptoms and with present symptoms. Neutrophil filtration times were 11.5 +/- 4.8 s in the active cases with present symptoms, which were significantly (P < 0.05) larger than those (7.4 +/- 1.9 s) in the active cases with absent symptoms. The latter filtration times were further significantly (P < 0.001) larger than values (3.7 +/- 1.3 s) in the inactive cases and also those (4.8 +/- 1.2 s) in control subjects. Furthermore, increases in the filtration time obtained immediately after the exposure of cells to the chemotactic peptide formyl-methionyl-leucyl-phenylalanine (FMLP10 nM) were significantly (P < 0.01) larger in the active cases with present symptoms than those in the active cases with absent symptoms. The latter were also larger, but not significantly, than those in the inactive cases, and were significantly (P < 0.01) larger than those in control subjects. The present results demonstrate that the micropore filtration method reflects well the rheological activity of neutrophils as well as the clinical status of Behçet's disease. This method is much better than the measurement of O2 production to differentiate between active cases with absent symptoms and inactive patients or even control individuals. Furthermore, it is more sensitive and useful than laboratory data like the CRP value or the number of peripheral blood neutrophils.

背景与目标： 活化的中性粒细胞需要很长时间才能通过像微孔一样的狭窄管腔，并且应该对微循环起到恶化的作用。尽管在beh ç et病中已经证明了中性粒细胞的激活，但没有人通过中性粒细胞活性的流变学测量来分析该疾病的临床活性。使用微孔 (孔径5微米) 过滤技术，我们测量了外周血中性粒细胞的过滤时间，作为其活性的流变学指标，以确定白塞氏病的临床活性。21名beh ç et病患者和14名健康对照者参加了这项研究。患者表现出的症状和体征使我们将白塞氏病区分为不活跃和活跃的病例。后者进一步分为无症状和现有症状的病例。有症状的活动病例的中性粒细胞过滤时间为11.5 +/- 4.8 s，显著 (P < 0.05) 大于无症状的活动病例的中性粒细胞过滤时间 (7.4 +/- 1.9 s)。后者的过滤时间进一步显著 (P < 0.001) 大于非活性情况下的值 (3.7 +/- 1.3 s)，也大于对照受试者中的值 (4.8 +/- 1.2 s)。此外，在细胞暴露于趋化肽甲酰基-甲硫酰基-亮氨酸-苯丙氨酸 (fmlp10nm) 后立即获得的过滤时间的增加在存在症状的活动病例中比在不存在症状的活动病例中显着 (P < 0.01) 大。后者也比不活跃的情况更大，但不显著，并且显著 (P < 0.01) 大于对照组。目前的结果表明，微孔过滤方法很好地反映了嗜中性粒细胞的流变活性以及白塞病的临床状况。此方法比O2产生的测量要好得多，可以区分无症状的活跃病例和不活跃的患者甚至对照组。此外，它比CRP值或外周血中性粒细胞数量等实验室数据更敏感和有用。

BACKGROUND & AIMS: OBJECTIVE:This study was directed at identifying clinical features of chronic rhinosinusitis with asthma, and examining the differences of the postoperative outcomes in asthmatics and nonasthmatics. STUDY DESIGN AND SETTING:Twenty-one asthmatic and 77 nonasthmatic patients who underwent functional endoscopic sinus surgery (FESS) were entered into the study. The following six parameters were determined in asthmatic and nonasthmatic groups; the presence of allergy, previous sinus surgery, severity of preoperative rhinosinusitis symptoms, improvements in postoperative rhinosinusitis symptoms, preoperative disease extent, and postoperative endoscopic outcomes. RESULTS:Symptom scores improved significantly in both asthmatics and nonasthmatics postoperatively, and asthmatics exhibited significantly worse postoperative endoscopic outcomes compared with nonasthmatics. No difference was found in other parameters between two groups. Multivariate analysis revealed asthma continues to be an independent predictor of success. CONCLUSIONS:The present study found that chronic rhinosinusitis in asthmatics showed worse postoperative outcomes than in nonasthmatics, and every attempt should be made for the improvement of surgical results in these patients.

背景与目标：

BACKGROUND & AIMS: AIMS:Allergic eye disease affects up to 20% of the population with varying severity. The conjunctival epithelium plays a key role in allergic eye disease. The purpose of this study was to determine whether the conjunctival epithelium is abnormal in allergic eye disease. METHODS:Conjunctival biopsy samples were taken from patients with seasonal allergic conjunctivitis (SAC) 'in' and 'out of season' and nonatopic control subjects. Specimens were fixed in glycol methacrylate, 2 microm serial sections cut and Image-J used to assess the sites and areas of immuno-staining. RESULTS:E-cadherin, CD44, keratins K5/6, K8, K13, K14, K18 and pan-keratin immuno-staining were all significantly lower in patients 'out of season' compared with normal controls. No structural differences in the epithelium were observed between the two groups. The epithelium of patients 'in season' was thicker and immuno-staining of the above markers similar to controls. CONCLUSIONS:The expression of a wide spectrum of epithelial cell adhesion proteins and cytoskeletal elements is downregulated in the conjunctiva of SAC patients 'out of season' compared with normal controls. We suggest that this could have an important impact on the ability of the epithelium to protect itself against allergen penetration, potentially influencing the development and course of allergic eye disease and offering a novel area for therapeutic control.

背景与目标：

BACKGROUND & AIMS: The dose, efficacy, and side effects of continuous intravenous infusion (CIVI) of morphine were compared with continuous subcutaneous infusion (CSCI) of morphine in patients with chronic cancer pain. Eligible patients were referred to the Palliative Care Program and were receiving a stable dose of CIVI of morphine. The design was a within-patient, one-way crossover; in which each patient provided data before and after a switch from CIVI to CSCI of morphine. "Rescue" doses were 50% of the hourly dose given every 2 hours as needed. Morphine was infused intravenously (i.v.) and subcutaneously (s.c.) via a McGaw/AccuPro Volumetric Infusion Pump. After baseline data, including side effects and pain assessment, were obtained, patients were evaluated twice daily for toxicity and analgesic efficacy. Those who had a stable CIVI dose for 48 consecutive hr were crossed over to the CSCI at the same dose as the intravenous (i.v.) phase. A stable dose was defined as no dose change, four or less rescue doses in the previous 24 hr, and a pain rating of none or mild. CIVI was considered equal to CSCI if these criteria were maintained for 96 consecutive hr. Fifty-seven patients were entered, and 40 were evaluable (15 women and 25 men). The median age was 67 (range 30-83 years). All 40 participants, after maintaining a stable dose throughout the i.v. phase, crossed to the s.c. phase and remained on s.c. for at least 48 hr. Thirty-two patients maintained a stable dose throughout the i.v. and s.c. phases. The mean stable i.v. dose (day 2) was 5.05 mg/hr, and the mean stable s.c. dose (day 4) was 5.7 mg/hr (P = 0.01). The mean number of rescue doses on day 2 was 0.83 per 24 hr versus 0.80 per 24 hours on day 4 (P = 0.6). The mean categorical pain score on day 2 was 0.83, and on day 4, 0.85 (P = 0.7). The mean visual analogue scale (VAS) on day 2 was 22.9 mm versus 17.6 mm on day 4 (P = 0.1). The mean incidence of side effects on day 2 was 1.7, and on day 4, 2.0 (P = 0.2). No patient was withdrawn or had a dose reduction due to unacceptable toxicity. There were two reports of local toxicity (mild erythema) at the SC needle insertion point, which required a site change. All of our 40 patients had adequate pain control with CIVI and CSCI morphine. Of the eight participants who were not maintained on the same i.v. and s.c. dose, all had adequate pain control and a similar side-effect profile on a higher s.c. morphine dose. These data suggest that the i.v. and s.c. routes are equianalgesic for most patients when administered as a continuous infusion. Pain control and side-effect profiles are quite similar and acceptable. s.c. morphine is an excellent alternative to i.v. morphine in both inpatients and outpatients requiring parenteral morphine for pain.

背景与目标： 比较了慢性癌痛患者持续静脉输注 (CIVI) 吗啡与持续皮下输注 (CSCI) 吗啡的剂量，疗效和副作用。符合条件的患者被转诊到姑息治疗计划，并正在接受稳定剂量的CIVI吗啡。该设计是患者内部的单向交叉; 其中每个患者在吗啡从CIVI切换到CSCI之前和之后提供数据。“抢救” 剂量是根据需要每2小时给予的每小时剂量的50%。通过McGaw/AccuPro容积输液泵静脉内 (i.v.) 和皮下 (s.c.) 注入吗啡。获得包括副作用和疼痛评估在内的基线数据后，每天两次评估患者的毒性和镇痛效果。那些连续48小时稳定的CIVI剂量的人以与静脉 (i.v.) 阶段相同的剂量交叉到CSCI。稳定剂量定义为无剂量变化，在之前的24小时内有四个或更少的抢救剂量，并且疼痛等级为无或轻度。如果连续96个小时保持这些标准，CIVI被认为等于CSCI。进入了57名患者，其中40名可评估 (15名女性和25名男性)。中位年龄为67岁 (范围30-83岁)。所有40名参与者在整个静脉内保持稳定剂量后。阶段，越过s.C.阶段并保留在s.c.至少48小时。32名患者在整个静脉内保持稳定剂量。和南卡罗来纳州阶段。平均稳定的静脉注射。剂量 (第2天) 为5.05 mg/hr，平均稳定s.c.剂量 (第4天) 为5.7 mg/hr (P = 0.01)。第2天的平均抢救剂量为每24小时0.83次，而第4天的平均抢救剂量为每24小时0.80次 (P = 0.6)。第2天和第4天的平均分类疼痛评分为0.83，0.85 (P = 0.7)。第2天的平均视觉模拟量表 (VAS) 为22.9毫米，第4天为17.6毫米 (P = 0.1)。第2天和第4天的平均副作用发生率为1.7，2.0 (P = 0.2)。没有患者因不可接受的毒性而退出或剂量减少。有两份关于SC针插入点局部毒性 (轻度红斑) 的报告，需要改变部位。我们的40名患者均使用CIVI和CSCI吗啡进行了足够的疼痛控制。在没有保持相同i.v.的八名参与者中。和南卡罗来纳州剂量，都有足够的疼痛控制，并且在较高的s.C.上有相似的副作用。吗啡剂量。这些数据表明，静脉注射和南卡罗来纳州当作为连续输注给药时，大多数患者的途径是等镇痛。疼痛控制和副作用特征非常相似且可以接受。吗啡是静脉注射的绝佳替代品需要胃肠外吗啡治疗疼痛的住院患者和门诊患者的吗啡。

BACKGROUND & AIMS: -2

背景与目标： -2

BACKGROUND & AIMS: OBJECTIVE:The 24-hour creatinine clearance is the standard clinical technique for measuring kidney function; however, this measurement is cumbersome and inconvenient for patients. We hypothesized that a camera-based technetium-99m mercaptoacetyltriglycine (MAG3) clearance obtained simultaneously with a standard MAG3 scan would correlate well with the 24-hour creatinine clearance and could serve as a simple marker of kidney function. MATERIALS AND METHODS:Data were obtained from a retrospective analysis of 28 patients with varying degrees of kidney dysfunction and 85 subjects evaluated for kidney donation. The MAG3 clearance was calculated using a camera-based technique without blood or urine sampling. The creatinine clearance was measured using the plasma creatinine and a 24-hour urine collection. The MAG3 and creatinine clearances were corrected for body surface area, and clearance values in healthy subjects and patients were compared using the paired Student's t test. The linear association between the MAG3 and creatinine clearances was expressed by Pearson's correlation coefficient. RESULTS:The mean MAG3 clearance in the potential kidney donors was 321 +/- 95 mL/min/1.73 m2 (95% CI, 171-546 mL/min/1.73 m2), significantly higher than the mean creatinine clearance of 152 +/- 51 mL/min/1.73 m2 (79-278 mL/min/1.73 m2, p < 0.001). The mean MAG3 clearance in patients was 153 +/- 70 mL/min/1.73 m2 (32-316 mL/min/1.73 m2) and was also significantly higher than the mean creatinine clearance of 74 +/- 36 mL/min/1.73 m2 (21-138 mL/min/1.73 m2, p < 0.001). The ratio of the mean creatinine clearance to the mean MAG3 clearance was essentially the same for volunteers and patients, 0.47 and 0.48, respectively. The Pearson's correlation between the MAG3 and creatinine clearances was 0.80 (0.72-0.86). CONCLUSION:The camera-based 99mTc-MAG3 clearance correlates well with the 24-hour creatinine clearance and can provide a simple and convenient index of kidney function.

背景与目标：

BACKGROUND & AIMS: OBJECTIVE:Evaluate in patients with celiac disease the tolerance of prolonged consumption of small amounts of gliadin contained in products containing wheat starch.

DESIGN:Open 1-year trial of the addition of wheat starch to a gluten-free diet in a cohort of adult patients with biopsy-proven celiac disease who had never consumed wheat starch. The control group consisted of patients with celiac disease who tolerated wheat starch.

SUBJECTS:Seventeen patients with celiac disease and 14 control patients, all diagnosed according to criteria of the European Society of Pediatric Gastroenterology and Nutrition, were recruited from the Canadian Celiac Association and the Quebec Celiac Foundation.

SETTING:The study was conducted in the outpatient clinic of the Gastroenterology and Nutrition Service of Ste Justine Hospital, Montreal, Quebec, Canada.

INTERVENTIONS:Patients were asked to consume four to six portions daily of a wheat starch-containing product, mainly bread, for up to 1 year.

MAIN OUTCOME MEASURES:The gliadin content of the wheat starch product used in this trial was quantified by enzyme-linked immunosorbent assay. Patient outcome measures included symptoms, nutritional parameters (anthropometric data, complete blood count, serum folate and iron levels), and immunologic parameters (antigliadin antibody and antiendomysium antibody titers).

RESULTS:A quantifiable amount of immunoreactive gliadin (0.75 mg/100 g) was found in the wheat starch. The majority of the patients with celiac disease (11 of 17) who had never consumed wheat starch previously developed symptoms, which resolved within weeks of discontinuing the product. Relapse of skin lesions was seen in two of three patients with coexisting dermatitis herpetiformis. No weight loss or biochemical changes were observed. Despite the presence of symptoms, antigliadin antibody and antiendomysium antibody determinations were not useful to detect the clinical intolerance.

APPLICATIONS:The innocuousness of the long-term ingestion of "gluten-free" products containing wheat starch is still unproven, and prolonged use of such products by patients with celiac disease cannot be recommended.

背景与目标： 目标 : 评估乳糜泻患者对含有小麦淀粉的产品中含有的少量麦醇溶蛋白的长期食用的耐受性。
设计 : 在从未食用过小麦淀粉的活检证实的乳糜泻成年患者队列中，将小麦淀粉添加到无麸质饮食中进行了为期1年的开放试验。对照组由耐受小麦淀粉的乳糜泻患者组成。
受试者 : 17例乳糜泻患者和14例对照患者，均根据欧洲儿科胃肠病与营养学会的标准进行诊断，是从加拿大乳糜泻协会和魁北克乳糜泻基金会招募的。
设置 : 该研究是在魁北克蒙特利尔Ste Justine医院胃肠病学和营养服务门诊进行的，加拿大。
干预措施 : 要求患者每天食用四到六份含小麦淀粉的产品，主要是面包，长达1年。
主要结果指标 : 通过酶联免疫吸附测定法对该试验中使用的小麦淀粉产品的麦醇溶蛋白含量进行了定量。患者结局指标包括症状，营养参数 (人体测量数据，全血细胞计数，血清叶酸和铁水平) 和免疫学参数 (抗麦醇溶蛋白抗体和抗肌内膜抗体滴度)。
结果 : 在小麦淀粉中发现可定量的免疫反应性麦醇溶蛋白 (0.75 mg/100g)。以前从未食用过小麦淀粉的大多数乳糜泻患者 (17人中有11人) 出现症状，这些症状在停用该产品后的几周内得到缓解。在三名并存的疱疹样皮炎患者中，有两名发现了皮肤病变的复发。未观察到体重减轻或生化变化。尽管存在症状，但抗麦醇溶蛋白抗体和抗肌内膜抗体的测定对检测临床不耐受没有用。
应用 : 长期摄入含有小麦淀粉的 “无麸质” 产品的无伤害性仍未得到证实，并且不建议乳糜泻患者长期使用此类产品。

BACKGROUND & AIMS: :Group B streptococcal (GBS) infections are the leading cause of bacterial disease and death among newborns in the United States and an important cause of morbidity among peripartum women and nonpregnant adults with chronic medical conditions. Disease in infants usually presents as sepsis, pneumonia or meningitis but also may include cellulitis or osteomyelitis. In 1990, GBS infections caused an estimated 7600 serious illnesses and 310 deaths among U.S. infants aged < or = 90 days; infections among infants aged < 7 days (i.e., early-onset disease) accounted for approximately 80% of these illnesses. To determine the incidence of GBS disease during 1993-1995, CDC conducted surveillance for this disease in an aggregate population of 12.5 million persons with 190,000 annual live-born infants. This report summarizes the findings of surveillance in this population, which indicate that a statistically significant decline in the incidence of early-onset GBS disease occurred in some surveillance areas.

背景与目标： : B组链球菌 (GBS) 感染是美国新生儿细菌性疾病和死亡的主要原因，也是围产期妇女和患有慢性疾病的未怀孕成年人发病的重要原因。婴儿的疾病通常表现为败血症，肺炎或脑膜炎，但也可能包括蜂窝织炎或骨髓炎。1990年，GBS感染在 <或 = 90天的美国婴儿中导致估计7600种严重疾病和310例死亡; <7天的婴儿 (即早发疾病) 感染约占这些疾病的80%。为了确定1993-1995年期间GBS疾病的发生率，CDC对1250万名每年有190,000名活产婴儿的人群进行了该疾病的监测。该报告总结了该人群的监测结果，这表明在某些监测地区，早发性GBS疾病的发病率在统计学上显着下降。

BACKGROUND & AIMS: OBJECTIVE:To investigate renal preservation by a novel method of perfusion using an oxygenated perfluorocarbon (PFC) emulsion via retrograde access to the kidney, as preserving renal function during urological surgery has been elusive, and the recognized technique of nephron-sparing surgery has increased its application and practice in modern urology. MATERIALS AND METHODS:After institutional review and approval, 30 New Zealand White rabbits were studied. In a solitary kidney model, each rabbit had the ureter catheterized before 40 min of renal artery occlusion. Each rabbit was randomized to one retrograde perfusion group, i.e. sham, normothermic PFC, chilled PFC, normothermic saline, and chilled saline. The rabbits were maintained for 2 weeks, during which renal function, urine output, systemic blood gases, weight and serum creatinine level were measured. After death, the kidneys were individually examined and graded by one renal pathologist unaware of the treatment. RESULTS:The rabbits treated with retrograde PFC perfusion (normothermic and chilled) had less change in their creatinine clearance, at 3.6 and 4.0 mL/min per kg, than the sham group, at 7.8 mL/min per kg, while also having significantly higher systemic venous oxygenation, at 26.3 and 10.0 mmHg, than the sham group, at 0.2 mmHg. Normothermic and chilled perfusion with PFC was also associated with less histological evidence of ischaemic damage, with mean (sd) scores of 13.0 (13.5) and 8.7 (4.5), respectively, than in the sham group, at 33.3 (16.8), while favourably matching the contralateral control kidney group, at 5.5 (2.3). The rabbits treated with saline retrograde perfusion also had better outcomes than the sham cohort. There were no adverse effects in any of the study arms or with the use of PFC. CONCLUSION:Retrograde oxygen delivery to the kidney through the urinary collecting system was successful in this pilot study. Renal function, laboratory and histological data indicate a trend towards renal preservation and even systemic oxygenation in the experimental groups compared with the sham rabbits, with no adverse effects attributed to this technique.

背景与目标：

BACKGROUND & AIMS: :Darier disease is an uncommon genodermatosis reflecting defective desmosomal structure and function. The present report details the oral features of a patient with well-characterized Darier disease and reviews current knowledge of the genetic basis of this genodermatosis that can often affect the craniofacial tissues.

背景与目标： : Darier病是一种罕见的遗传皮肤病，反映了桥粒体结构和功能缺陷。本报告详细介绍了患有特征性Darier疾病的患者的口腔特征，并回顾了有关这种通常会影响颅面组织的遗传皮肤病的遗传基础的最新知识。

BACKGROUND & AIMS: :Fludarabine and alemtuzumab are routinely used for treatment of B-cell chronic lymphocytic leukemia (B-CLL). The present study aimed to compare the expression of signaling molecules and cytokine production by T cells of B-CLL patients in long-term unmaintained remission/plateau phase following fludarabine or alemtuzumab treatment with that of indolent/untreated B-CLL patients and healthy donors. The frequency and intensity of TCR-CD3zeta chain, p56lck, p59fyn, ZAP-70, PI3-kinase and interferon (IFN)-gamma/interleukin (IL)-4 production in CD4 and CD8 T cells was examined by flow cytometry. T-cell function was assessed by stimulation with purified protein derivative (PPD) and phytohemagglutinin (PHA). Despite a reduction in number, the expression of IFN-gamma/IL-4 in T-cells in patients was significantly higher than in healthy donors. The intensity of most signaling molecules in treated patients was relatively unaffected vs. healthy donors but lower than untreated-indolent patients. However, the total number of T cells which expressed each of the signaling molecules was decreased in patients, with no difference between fludarabine- and alemtuzumab-treated patients. The T-cell response to PHA but not PPD was reduced in treated patients. The results suggest that, despite some alterations in signaling molecules and a reduction in T-cell number, overall T-cell functions may be relatively well preserved long-term after treatment with fludarabine and alemtuzumab.

背景与目标： : 氟达拉滨和阿仑单抗通常用于治疗b细胞慢性淋巴细胞白血病 (b-cll)。本研究旨在比较在氟达拉滨或阿仑单抗治疗后长期未维持缓解/平台期的b-cll患者的T细胞与惰性/未治疗的b-cll患者和健康的T细胞的信号分子表达和细胞因子产生供体。通过流式细胞术检查CD4和CD8 T细胞中TCR-CD3zeta链，p56lck，p59fyn，ZAP-70，PI3-kinase和干扰素 (IFN)-γ/白细胞介素 (IL)-4产生的频率和强度。通过纯化蛋白衍生物 (PPD) 和植物血凝素 (PHA) 刺激来评估T细胞功能。尽管数量减少，但患者T细胞中IFN-γ/IL-4的表达显着高于健康供体。与健康供体相比，接受治疗的患者中大多数信号分子的强度相对不受影响，但低于未经治疗的惰性患者。然而，在患者中表达每种信号分子的T细胞总数减少，而氟达拉滨和阿仑单抗治疗的患者之间没有差异。在治疗的患者中，T细胞对PHA的反应降低，但对PPD的反应降低。结果表明，尽管信号分子发生了一些变化，T细胞数量减少，但在用氟达拉滨和阿仑单抗治疗后，总体T细胞功能可能长期保持良好。

BACKGROUND & AIMS: :Acute kidney injury is followed by regeneration of damaged renal tubular epithelial cells. The purpose of this study was to test the hypothesis that renal stem cells exist in the adult kidney and participate in the repair process. A unique population of cells that behave in a manner that is consistent with a renal stem cell were isolated from rat kidneys and were termed multipotent renal progenitor cells (MRPC). Features of these cells include spindle-shaped morphology; self-renewal for >200 population doublings without evidence for senescence; normal karyotype and DNA analysis; and expression of vimentin, CD90 (thy1.1), Pax-2, and Oct4 but not cytokeratin, MHC class I or II, or other markers of more differentiated cells. MRPC exhibit plasticity that is demonstrated by the ability of the cells to be induced to express endothelial, hepatocyte, and neural markers by reverse transcriptase-PCR and immunohistochemistry. The cells can differentiate into renal tubules when injected under the capsule of an uninjured kidney or intra-arterially after renal ischemia-reperfusion injury. Oct4 expression was seen in some tubular cells in the adult kidney, suggesting these cells may be candidate renal stem cells. It is proposed that MRPC participate in the regenerative response of the kidney to acute injury.

背景与目标： : 急性肾损伤后，受损的肾小管上皮细胞再生。目的检验肾干细胞存在于成人肾脏并参与修复过程的假说。从大鼠肾脏中分离出一种独特的细胞群，其行为方式与肾干细胞一致，被称为多能肾祖细胞 (MRPC)。这些细胞的特征包括梭形形态;> 200种群倍增的自我更新，没有衰老的证据; 正常的核型和DNA分析; 波形蛋白，CD90 (thy1.1)，Pax-2和10月4的表达，而不是细胞角蛋白，MHC I或II类，或更多分化细胞的其他标记。MRPC表现出可塑性，通过逆转录酶PCR和免疫组织化学诱导细胞表达内皮，肝细胞和神经标志物的能力证明了这种可塑性。当在未受伤的肾脏的胶囊下注射或在肾缺血再灌注损伤后动脉内注射时，细胞可以分化为肾小管。在成人肾脏的某些肾小管细胞中观察到10月4的表达，表明这些细胞可能是候选的肾干细胞。建议MRPC参与肾脏对急性损伤的再生反应。