Paricalcitol reduces oxidative stress and inflammation in hemodialysis patients

Background

Treatment with selective vitamin D receptor activators such as paricalcitol have been shown to exert an anti-inflammatory effect in patients on hemodialysis, in addition to their action on mineral metabolism and independently of parathyroid hormone (PTH) levels. The objective of this study was to evaluate the additional antioxidant capacity of paricalcitol in a clinical setting.

Methods

The study included 19 patients with renal disease on hemodialysis, of whom peripheral blood was obtained for analysis at baseline and three months after starting intravenous paricalcitol treatment. The following oxidizing and inflammatory markers were quantified: malondialdehyde (MDA), nitrites and carbonyl groups, indoleamine 2,3-dioxygenase (IDO), tumor necrosis factor alfa (TNF-α), interleukin-6 (IL-6), interleukin-18 (IL-18) and C-reactive protein (CRP). Of the antioxidants and anti-inflammatory markers, superoxide dismutase (SOD), catalase, reduced glutathione (GSH), thioredoxin, and interleukin-10 (IL-10) levels were obtained.

Results

Baseline levels of oxidation markers MDA, nitric oxide and protein carbonyl groups significantly decreased after three months on paricalcitol treatment, while levels of GSH, thioredoxin, catalase and SOD activity significantly increased. After paricalcitol treatment, levels of the inflammatory markers CRP, TNF-α, IL-6 and IL-18 were significantly reduced in serum and the level of anti-inflammatory cytokine IL-10 was increased.

Conclusions

In renal patients undergoing hemodialysis, paricalcitol treatment significantly reduces oxidative stress and inflammation, two well known factors leading to cardiovascular damage.

     

Pre-B acute lymphoblastic leukemia cells may induce T-cell anergy to alloantigen

Even if neoplastic cells express tumor associated antigens they still may fail to function as antigen presenting cells (APC) if they lack expression of one or more molecules critical for the induction of productive immunity. These cellular defects can be repaired by physiologic activation, transfection, or fusion of tumor cells with professional APC. Although such defects can be repaired, antitumor specific T cells may still fail to respond in vivo if they may have been tolerized. Here, human pre-B cell acute lymphoblastic leukemia (pre-B ALL) was used as a model to determine if primary human tumor cells can function as alloantigen presenting cells (alloAPC) or alternatively whether they induce anergy. In the present report, we show that pre-B cell ALL express alloantigen and adhesion molecules but uniformly lack B7-1 (CD80) and only a subset express B7-2 (CD86). Pre-B ALL cells are inefficient or ineffective alloAPC and those cases that lack expression of B7-1 and B7-2 also induce alloantigen specific T- cell unresponsiveness. Under these circumstances, T-cell unresponsiveness could be prevented by physiologic activation of tumor cells via CD40, cross-linking CD28, or signaling through the common gamma chain of the interleukin-2 receptor on T cells. Taken together, these results suggest that pre-B ALL may be incapable of inducing clinically significant T-cell-mediated antileukemia responses. This defect may be not only due to their inability to function as APC, but also due to their potential to induce tolerance. Attempts to induce clinically significant antitumor immune responses may then require not only mechanisms to repair the antigen presenting capacity of the tumor cells, but also reversal of tolerance.     

A heavy metal baseline score predicts outcome in acute myeloid leukemia

Despite abundant epidemiological data linking metals to leukemia and other cancers, baseline values of toxic and essential metals in patients with leukemia and the clinical impact of these metals remain unknown. Thus, we sought to quantify metal values in untreated patients with acute myeloid leukemia (AML) and controls and determine the impact of metal values on AML patients' survival. Serum samples from patients with untreated AML and controls at Hospices Civils de Lyon were analyzed and compared for trace metals and copper isotopic abundance ratios with inductively coupled plasma mass spectrometry. Survival analysis was performed as a function of metal values, and a multi-metal score was developed for patients with AML. Serum samples were collected from 67 patients with untreated AML and 94 controls. Most patients had intermediate-risk cytogenetics (63.1%) without FLT3 internal tandem duplication mutations (75.6%) or NPM1 mutations (68.1%). Most metal values differed significantly between AML and control groups. Patients with lower magnesium and higher cadmium values had the worst survival rates, with only 36% surviving at 6 months (P = .001). The adverse prognostic effect of this combination was maintained on multivariate analysis. Based on this, we developed a novel metal score, which accounts for multiple relative abnormalities in the values of five toxic and five essential metals. Patients with a higher metal score had significantly worse survival, which was maintained on multivariate analysis (P = .03). This baseline metal scoring system was also prognostic when we applied it to a separate population of front-line AML patients.     

Coincidental diagnosis of tuberculous lymphadenitis: a case report

The aim of this case report was to present a case of multiple calcified tuberculous lymph nodes found on a panoramic radiograph coincidently diagnosed in an endodontic clinic. A detailed discussion on the differential diagnosis of similar such calcification found in the same region is also presented. A 14‐year‐old girl was referred to our department with the complaint of painless swelling in the left side of the lower jaw. Clinical and radiographical examinations were performed, leading to the initial diagnosis of chronic periapical abscess. The patient's medical history was re‐evaluated. Advanced imaging and excisional biopsy were performed in order to confirm the final diagnosis. Regarding the presenting signs and symptoms of bilateral carious mandibular molars, a periapical inflammatory process was considered in the provisional diagnosis. A thorough examination and investigations were suggestive of cervical tuberculous lymphadenitis (scrofula), and the patient underwent excision of the same. The clinician should consider the possibility of chronic granulomatous inflammatory lesions in the differential diagnosis of radiopaque lesions.     

综合性ICU患者监护记录单临床应用的前瞻性研究

目的研究新时期综合ICU患者的临床监护记录单,以保证患者及护士使用过程的便利及安全。方法将我院ICU自2002年使用的“图标式ICU监护记录单”,在原表格的基础上根据综合ICU患者需要多系统监测的特点进行修订,主要以数字和符号表示形式形成新的护理记录表格,并采取对比的方法考证新旧两种表格的效用。结果两种表格各项指标比较：相同人数的护士分别填写两种不同表格所使用的时间分别是新表格平均（66±11）min,旧表格平均（97±10）min,每份表格的分数设为100分,护理质量检查小组检查的结果,新表格平均（97±2）分,旧表格平均（94±2）分,两组时间及分数比较差异有统计学意义（t=10．6263,4．0307;P〈0．01）;新旧表格使用合格率比较差异有统计学意义（90．12％比82．62％,x2=67．49,P〈0．01）。结论新的监护记录单更科学、更全面、简洁、更适合综合ICU不同种类的患者的记录要求,减轻护士工作量,减少记录时间,提高工作效率。     

Immunologically reactive <Emphasis Type="Italic">M. leprae</Emphasis> antigens with relevance to diagnosis and vaccine development

Background  

Leprosy is a chronic infectious disease caused by Mycobacterium leprae that can manifest a wide variety of immunological and clinical outcomes ranging from potent humoral responses among borderline lepromatous (BL) and lepromatous (LL) patients to strong cellular responses among tuberculoid (TT) and borderline tuberculoid (BT) patients. Until recently, relatively little has been known about the immune responses to individual proteins of M. leprae recognized during leprosy.     

Postoperative complications associated with 25-gauge pars plana vitrectomy.

BACKGROUND AND OBJECTIVE: To report postoperative complications in eyes undergoing 25-gauge pars plana vitrectomy (PPV). PATIENTS AND METHODS: Seventy consecutive eyes that underwent 25-gauge PPV for various indications, including epiretinal membrane, non-clearing vitreous hemorrhage, and idiopathic macular hole, and had a minimum follow-up of 12 weeks were reviewed retrospectively. Main outcome measures included best-corrected Snellen visual acuity, intraocular pressure (IOP), intraoperative complications, and postoperative complications. RESULTS: The mean visual acuity improved from 20/368 preoperatively to 20/105 postoperatively (P < .00005). Intraoperative complications included retinal tears in 2 eyes (2.9%). Postoperative complications included cataract progression in 17 eyes (42.5%), cystoid macular edema exacerbation in 5 eyes (7.1%), and retinal detachment in 1 eye (1.4%). Postoperative day 1 IOP was statistically lower than preoperative IOP in fluid-filled eyes (P = .031) but not in eyes filled with intravitreal air (P = .30) or gas (P = .52). Sclerotomy sutures were required intraoperatively in 5 eyes (7.1%) and postoperative day 1 hypotony was noted in 4 eyes (5.7%). All of these complications were noted in fluid-filled eyes except for one case of postoperative day 1 hypotony with gas tamponade. CONCLUSIONS: Intraoperative and postoperative complications were rare in this series of 25-gauge PPV. Postoperative cataract progression and hypotony were the most common complications. Fluid-filled eyes appear to have a higher risk of wound leakage and postoperative hypotony after 25-gauge PPV than eyes with air or gas tamponade.