Safety of the long-term use of proton pump inhibitors

The proton pump inhibitors (PPIs) as a class are remarkably safe and effective for persons with peptic ulcer disorders. Serious adverse events are extremely rare for PPIs, with case reports of interstitial nephritis with omeprazole, hepatitis with omeprazole and lansoprazole, and disputed visual disturbances with pantoprazole and omeprazole. PPI use is associated with the development of fundic gland polyps (FGP); stopping PPIs is associated with regression of FGP. In the absence of Helicobacter pylori infec...     

Intravenous drug users' HIV-risk behaviors with primary/other partners

The objective of this study was to determine how injection drug users' (IDUs) HIV-risk behavior differs with primary and other sex partners. Interviews were conducted with injection drug users from a needle exchange program (n = 243). Those with one sexual partner were more likely to report never using condoms with primary partners than were those with more than one partner (74% vs. 54%, p < 0.001). Those with more than one partner differed, between primary and other sexual partners, in their disclosure of HIV and IDU status, condom use, and drug use in combination with sex. Primary sexual partners of IDUs are placed at risk from IDUs' risk behavior with other sexual partners. Those planning HIV-risk reduction interventions for IDUs should consider risk behavior with primary partners separately from behavior with other partners. Evaluation of intervention effects should use partner-specific assessments of risk behavior.     

Effect of blood donation on the establishment of normal ranges of lymphocyte subsets

BACKGROUND: Absolute counts of CD4+ T-lymphocytes are used in the management of patients with human immunodeficiency virus infection. Low absolute counts of CD3+CD4+ cells have also been observed in healthy people–a phenomenon called idiopathic CD4 lymphocytopenia. It is common practice for normal ranges for lymphocyte subsets to be derived from samples taken from blood donors. STUDY DESIGN AND METHODS: A sample of EDTA blood was taken through the donation line tubing, after donation from 565 blood donors in Sydney, Australia, who were selected from a range of age groups. An additional 12 donors provided a predonation sample as well as a postdonation sample. Hematologic assays were performed on two analyzers. Samples were stained for CD3, CD4, CD8, CD19, and CD56 and analyzed on a flow cytometer. RESULTS: Three donors were found to have absolute CD3+CD4+ counts < 300 cells per microL. The percentage of CD3+CD4+ cells was found to increase with age. Both the percentage and the absolute count of CD3+CD8+ cells decreased with age, which resulted in an increased CD4:CD8 ratio with age. Men had consistently higher absolute counts of CD3-CD56+ cells than women. The 12 additional donors all had greater percentages of CD3+CD4+ cells and lower absolute counts for CD3+, CD3+CD4+, CD3+CD8+, CD19+ and CD3-CD56+ cells after donation than they had before donation (p < 0.001). CONCLUSION: It is not satisfactory to base normal ranges for lymphocyte subsets on donor blood, from which the blood sample has been obtained after donation.     

Cigarette smoking and the risk of venous thromboembolism: The Tromsø Study

Summary. Background: Conflicting findings have been reported on the association between smoking and the risk of venous thromboembolism (VTE). Objectives: To conduct a prospective, population‐based cohort study to investigate the association between cigarette smoking and the risk of incident VTE. Patients/Methods: Information on smoking habits was assessed by self‐administered questionnaires in 24 576 subjects, aged 25–96 years, participating in the fourth Tromsø Study in 1994–1995. Incident cases of VTE were registered until the end of follow‐up at 1 September 2007. Results: A total of 389 incident VTE events (1.61 per 1000 person‐years) were registered during follow‐up (median of 12.5 years). Heavy smokers (> 20 pack‐years) had a hazard ratio (HR) of 1.46 (95% confidence interval [CI] 1.04–2.05) for total VTE, and and an HR of 1.75 (95% CI 1.14–2.69) for provoked VTE, as compared with never smokers. The risk of provoked VTE increased with more pack‐years of smoking (P = 0.02). Smoking was not associated with risk of unprovoked VTE. The number of pack‐years was associated with increased risk of cancer and myocardial infarction, whereas the association between pack‐years of smoking and VTE disappeared when failure times were censored at the occurrence of cancer or myocardial infarction. Conclusions: Heavy smoking was apparently a risk factor for provoked VTE in analyses with VTE events as the only outcome. The lack of association between smoking and risk of VTE in analyses censored at the occurrence of cancer or myocardial infarction may suggest that smoking‐attributable diseases or other predisposing factors are essential for smoking to convey a risk of VTE.     

中国病毒性乙型肝炎的研究

我国是病毒性乙型肝炎(HB)高发病国家,人群感染HBV约有6.5亿,而HBsAg慢性携带者则为1.2亿,每年死于HB及相关性疾病者在16万人以上,HB已成为我国危害最大的社会公共卫生问题。现就目前我国HB研究的状况,提出一些思考,希望能对HB的研究有所助益。 1 病毒性乙型肝炎的分类我国现行的病毒性肝炎分类方案(以下称分类方案)与国际上基本一致,将其分为急性、慢性和肝炎肝硬变三大类,又根据HB不同的临床体征及组织病理学表现,而分成若干亚型。     

Coblockade of the LFA1:ICAM and CD28/CTLA4:B7 pathways is a highly effective means of preventing acute lethal graft-versus-host disease induced by fully major histocompatibility complex-disparate donor grafts

We have developed an in vitro system in which C57BL/6 donor splenocytes are exposed to B10.BR host alloantigens in the context of deficient CD28:B7 signaling as a means of preventing graft-versus-host disease (GVHD). Although 54% to 82% of MLR alloresponse was inhibited by cytotoxic T-lymphocyte antigen 4 (CTLA4)-Ig treatment of host stimulator cells, treated splenocytes were still capable of causing GVHD when infused in vivo. By adding anti-leukocyte function antigen 1 (anti-LFA1) antibody to hCTLA4-Ig in vitro to coblock the LFA1:intercellular adhesion molecule (ICAM) signaling, splenic alloresponse was inhibited by > or = 89%, yet GVHD induction capabilities were retained. Because antigen-primed cells might be more susceptible to CD28:B7 blockade, we investigated whether hCTLA4-Ig alone, anti-LFA1 antibody alone, or the combination of both added to donor-antihost in vitro primed cells could reduce GVHD. To facilitate hyporesponsiveness induction and to block B7 and ICAM ligands that are upregulated during GVHD, these reagents were also administered to recipients post-BMT. We have shown that hCTLA4-Ig plus anti-LFA1 antibody is highly effective in preventing GVHD-induced lethality (88% to 100% of treated mice surviving versus 0% to 28% of controls surviving). For optimal prevention, both hCTLA4-Ig and anti-LFA1 must be used in vitro in the context of donor-antihost primed splenocytes and continued in vivo. This in vitro-in vivo combined approach was associated with donor engraftment, and recipients were not globally immunosuppressed. We conclude that blocking both the CD28/B7 and the LFA1:ICAM pathways are critical to effective GVHD prevention and may offer advantages to in vitro donor T-cell removal.     

Type 1 plasminogen activator inhibitor synthesis of endothelial cells is downregulated by smooth muscle cells

Plasminogen activator inhibitor type 1 (PAI-1), the physiologic inhibitor of both tissue-type plasminogen activator (tPA) and urokinase- type plasminogen activator (uPA), is a major biosynthetic product of endothelial cells in vitro; endothelial cells in vivo, in contrast, do not appear to produce significant amounts of PAI-1 as made evident by in situ-hybridization studies in normal mice. This suggests that the high rate of PAI-1 synthesis of endothelial cells in vitro might be a result of the culture conditions. When human umbilical vein endothelial cells (HUVEC) were grown on human amniotic membranes, resembling the natural growth support instead of coated plastic, their morphology was changed from the cobblestone-like appearance on plastic to an in vivo like flagstone pattern. However, this morphological change had no significant effect on the synthesis and secretion of PAI-1. When smooth muscle cell (SMC) conditioned media (CM) were added to HUVEC cultures, PAI-1 antigen secretion of HUVEC was reduced by 40% to 60% as measured by enzyme-linked immunosorbent assay (ELISA). Immunoprecipitation experiments using 36S-methionine metabolically labeled HUVEC and Northern blot analysis of HUVEC PAI-1 mRNA indicate that this reduction was attributable to decreased PAI-1 synthesis and reduced steady-state levels of both the 3.2 kb and 2.2 kb form of PAI-1 mRNA. This effect was dose-dependent and observed under serum-containing as well as serum- free conditions, in the absence or presence of endothelial cell growth supplement (ECGS, 0 to 100 micrograms/mL) and attributable to a nondialyzable factor. Our data suggest that the high level of PAI-1 biosynthesis of endothelial cells in vitro may be attributable to the lack of a soluble factor produced by SMC, which controls and suppresses PAI-1 biosynthesis of endothelial cells in vivo.     

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应用跨肾动脉支架人工血管腔内修复术治疗腹主动脉瘤,并探讨其手术适应证,操作要点及并发症的预防。方法对２例病人采用全麻,在动态数字减影血管造影监测下用跨肾动脉支架分叉型人工血管对腹主动脉瘤进行了腔内修复术,结果手术中ＤＳＡ提示动脉瘤消失,无内漏发生。术后１周及分别随访３和９个月,螺旋ＣＴ检查提示腔内人工血管无移位扭曲,血流通畅无内漏发生,结论腹主动脉瘤腔内修复术手术创伤小,病人恢复快,跨肾动支架人工     

Effect of renal and non‐renal ischemia/reperfusion on cell‐mediated immunity in organs and plasma

Brøchner AC, Dagnæs‐Hansen F, Toft P. Effect of renal and non‐renal ischemia/reperfusion on cell‐mediated immunity in organs and plasma. APMIS 2010; 118: 101–7. Acute renal failure (ARF) is a common morbidity factor among patients in the intensive care unit, reaching an incidence from 3% to 30% depending on the definition of ARF and the population. Although the majority of the patients with ARF are treated with continuous renal replacement therapy, the mortality rate still remains above 50%. The causes of death are primarily extra‐renal and include infection, shock, septicemia, and respiratory failure. We wanted to evaluate the cell‐mediated inflammatory response of renal ischemia–reperfusion (I/R) and non‐renal I/R, in blood and in distant organs. In our study, 80 mice were divided into four groups. The following surgeries were performed on the groups compared: bilateral renal I/R by clamping, unilateral renal ischemia, anesthesia only, and unilateral hind leg I/R. Half of the animals were killed after 2 h and the other half after 24 h. To assess the inflammatory response, we measured myeloperoxidase (MPO) in the organs, and CD 11b and major histocompatibility complex (MHC) II‐positive cells in the blood. Non‐renal I/R elicited the most elevated levels of MPO in extra‐renal tissue such as the lungs. There was a trend toward higher MPO levels in the kidney following renal I/R. All kinds of I/R induced an upregulation of the adhesion molecule CD 11b and a downregulation of MHC II. Renal and non‐renal I/R induced neutrophil infiltration in distant organs. Renal I/R does not induce a larger cell‐mediated inflammatory response in blood and organs than non‐renal I/R.