Experimental studies on imaging of infected site with 99mTc-Iabeled ciprofloxacin in mice

Background Bacterial infection can pose a substantial diagnostic dilemma.99mTc-labeled ciprofloxacin (CPF) was developed as a biologically active radiopharmaceutical to diagnose infection.In the present research,we studied the biodistribution and imaging properties of infection tracer 99mTc-CPF in a mouse model of infection.Methods CPF was labeled with 99mTc and the radiochemical purity and labeling rate were measured.A mouse model of infection was established.We then determined the biodistribution of 99mTC-CPF and conducted the whole body scintigraphy of the animal model.Results 99mTc-Ciprotech was stable for at least 6 hours at room temperature.The labeling rate of CPF by 99mTc was over 90%.Clearance of radioactivity mainly occurred in the liver and kidney,and the clearance from blood was rapid.Both biodistribution and imaging results showed higher uptake of 99mTc-CPF at sites of infection.The infectious tissue/normal tissue ratio peak was 4.30 at 4 hours after injection.Conclusions 99mTc-CPF is a sensitive radiopharmaceutical for scintigraphy of infectious lesions and it is easy to prepare.     

Pre-clinical evaluation of a new indirectly labeled 99mTc-6-hydrazinopyridine-3-carboxylic acid (HYNIC)-depreotide with HYNIC as bifunctional chelator

Background  Technetium-99m or ^99mTc is widely used for labeling peptide in nuclear medicine. Somatostatin and its analog can inhibit tumor cell growth after binding with its receptor. This research was to study the preclinical effect of a new ^99mTc-6-hydrazinopyridine-3-carboxylic acid (HYNIC)-depreotide, indirect ^99mTc labeling of depreotide using HYNIC as a bifunctional chelator.

Methods  The cyclopeptide, cyclo-[(N-Me) Phe-Tyr-D-Trp-Lys-Val-Hcy], the linear peptide, and [ClCH₂-CO×b-Dap-Lys- Cys-Lys×amide] were synthesized by Fmoc solid-phase synthesis. The cyclopeptide and the linear peptide were linked by liquid-phase synthesis. The product depreotide was isolated and purified by high performance liquid chromatography and was confirmed by mass spectrography. Depreotide was labeled with ^99mTc through a direct labeling method, using HYNIC as a bifunctional chelator. Paper chromatography method was used to calculate the labeling rate, and through the comparative analysis selected the best mark conditions. The new ^99mTc-HYNIC-depreotide was tested by high-performance liquid chromatography (HPLC). The internalization and externalization rates of the new ^99mTc-HYNIC-depreotide were studied in A549 cells. Furthermore, biodistribution of the radiopeptide was studied in nude mice, bearing tumors from human lung carcinoma cells SPC-A1.

Results  The molecular of synthesize depreotide was 1358, and the purity of it was 95.29%. The labeling efficiency of ^99mTc-HYNIC-depreotide was highest at pH 6.0 and 15°C, about (70.95±0.84)%. The labeling rate of the new ^99mTc-HYNIC-depreotide rose to a peak of (20.75±0.48)% at 60 minutes in A549 cells at 37°C and decreased slightly later, while it elevated gradually during the time course at 4°C and 25°C. The internalization rate of the new ^99mTc-HYNIC-depreotide at 37°C increased gradually and reached the peak of 84.4% in 120 minutes, while the externalization rate of the new ^99mTc-HYNIC-depreotide was always less than 20%. In mice bearing the experimental SPC-A1 tumor, the new ^99mTc-HYNIC-depreotide demonstrated a high tumor uptake of (4.05±0.04)% ID/g at 1.5 hpi and remained high ((2.51±0.06)% ID/g) at 4 hpi. The tumor-to-lung activity concentration ratio (T/Lu) was very high for the new ^99mTc-HYNIC-depreotide at all time points. So did the tumor-to-muscle activity (T/Mu) and tumor-to-blood activity concentration ratios (T/Bl).

Conclusion  The findings suggested that the new ^99mTc-HYNIC-depreotide might be a promising candidate radiopharmaceutical for imaging somatostatin receptor positive lung cancer.     

全自动合成3-~(18)F-2-羟基丙烷-2-硝基咪唑及临床前研究

目的研究一种全自动合成肿瘤乏氧显像剂3-18F-2-羟基丙烷-2-硝基咪唑(18F-FMISO)的方法。方法采用改良的FDG(氟代脱氧葡萄糖)模块,在密闭体系下4～6mg前体与F-18离子在110℃反应300s,1mol/LHCl120℃下水解180s,经柱色层纯化得18F-FMISO。检测正常小鼠、荷瘤鼠的生物学分布及PET显像。结果采用FDG模块自动化合成18F-FMISO,合成效率为67%,时间为25min,放化纯度>99%,体外稳定性良好。生物学分布及PET显像表明,肿瘤明显摄取18F-FMISO,120min时瘤/肌比为2.99,但肝、肾、肠的放射性较高。结论改良的FDG模块可高效、快速合成18F-FMISO,其产品质量符合临床要求。18F-FMISO适于胸、颈部肿瘤的乏氧评价。     

Early changes of CD4+CD25+Foxp3+ regulatory T cells and Th1/Th2, Tc1/Tc2 profiles in the peripheral blood of rats with controlled hemorrhagic shock and no fluid resuscitation

Background  Hemorrhagic shock induces immune dysfunction. Regulatory T cells (Tregs), T-helper (Th) cells, and cytotoxic T-lymphocytes (CTLs) can execute many crucial actions in immune and inflammatory responses. This study was conducted to investigate the early pathophysiological changes of CD4⁺CD25⁺Foxp3⁺ Treg and Th1/Th2, Tc1/Tc2 profiles in the peripheral blood of rats with controlled hemorrhagic shock and no fluid resuscitation.

Methods  A rat model of controlled hemorrhagic shock with no fluid resuscitation was established. Peripheral blood samples were taken before and four hours after hemorrhagic shock with no fluid resuscitation. Three color flow cytometry was used to detect Tregs, Th1, Th2, Tc1 and Tc2 cells in the samples.

Results  In the peripheral blood of rats, the percentage of Tregs four hours after hemorrhagic shock was significantly lower than before hemorrhagic shock (P=0.001). The ratios of Th1/Th2 and Tc1/Tc2 were changed from (23.08±8.98)% to (23.91±15.36)%, and from (40.40±21.56)% to (65.48±23.88)%, respectively.

Conclusions  At an early stage, the advent of hemorrhagic shock is related to an early decrease of Tregs, and a mild shift in the Th1/Th2, Tc1/Tc2 balance toward Th1 and Tc1 dominance. These changes are part of a hyper-inflammatory state of the host, and will deteriorate the maintenance of immune balance. Further influences and detailed mechanisms need to be investigated.     

High extracellular potassium ion concentration attenuates the blockade action of ketanserin on Kv1.3 channels expressed in xenopus oocytes

Background Ketanserin （KT）, a selective serotonin （5-HT） 2-receptor antagonist, reduces peripheral blood pressure by blocking the activation of peripheral 5-HT receptors. In this study electrophysiological method was used to investigate the effect of KT and potassium ion on Kv1.3 potassium channels and explore the role of blocker KT in the alteration of channel kinetics contributing to the potassium ion imbalances. Methods Kv1.3 channels were expressed in xenopus oocytes, and currents were measured using the two-microelectrode voltage-clamp technique. Results KCI made a left shift of activation and an inactivation curve of Kv1.3 current and accelerated the activation and inactivation time constant. High extracellular [K^＋] attenuated the blockade effect of KT on Kv1.3 channels. In the presence of KT and KCI the activation and inactivation time constants were not influenced significantly no matter what was administered first. KT did not significantly inhibit Kv1.3 current induced by tetraethylammonium （TEA）. Conclusions KT is a weak blocker of Kv1.3 channels at different concentrations of extracellular potassium and binds to the intracellular side of the channel pore. The inhibitor KT of ion channels is not fully effective in clinical use because of high [K^＋]. and other electrolyte disorders.     

Novel side branch ostial stent （BIGUARD^TM）： first-in-man study

Background Stenting a bifurcation lesion is technically challenging. No study has reported the clinical outcome of a dedicated bifurcation stent in China. We aimed to analyze the safety and clinical outcome of a novel side branch ostial stent （BIGUARDTM） stent in treating coronary bifurcation lesions. Methods Forty-seven patients were enrolled in this first-in-man study, with 61.7% true bifurcation lesions （0,1,1 and 1,1,1） and 26.7% diabetes. A two-stent technique was used in 27.6% of the patients, and 64.7% of patients crossed from the one-stent technique to the two-stent arm. Clinical and angiographic follow-up data at 12 months were available in all the 47 patients and in 43 patients （91.9%）, respectively. The study endpoint was the occurrence of major adverse cardiac events （MACE） at 12 months. Results Only one patient had a non-ST segment elevation myocardial infarction, which led to 2% of the in-hospital composite MACE. Notably, the target lesion revascularization at 12 months was 8.6%, with a 10.6% composite MACE at 12 months. Neither cardiac death nor stent thrombosis was seen during the follow-up. By quantitative coronary analysis, the restenosis rate at the main vessel and ostium of the side branch was 9.4% and 2.1%, respectively. Four of 12 patients （33.3%） treated with one-stent and kissing balloon inflation had restenosis in the main vessel. Conclusion BIGUARDTM stent was safe and feasible in treatment of bifurcation lesions.     

食蟹猴上肢取食执行时间的随龄变化及其与~(99m)Tc-TRODAT-1摄取率的相关关系研究

目的研究食蟹猴随年龄增长伴随的用上肢取食执行时间的变化及其与纹状体99mTc-TRODAT-1〔锝99-2β-[N,N'-双(2-巯乙基)乙撑二胺基]甲基,3β-(4-氯苯基)托烷〕摄取率之间的相关关系。方法选取4、10和15岁3个年龄组的健康食蟹猴共30只,利用改良的运动活动平板定量测定上肢取食执行时间,各年龄组分别选取4只动物用多巴胺转运体(dopamine transporter,DAT)配体99mTc-TRODAT-1结合的单光子发射体层摄影术(single-photon emission computed tomography,SPECT)显像观察脑内纹状体多巴胺转运体放射性摄取率(99mTc-TRODAT-1摄取率)的变化。结果随着年龄的增长,食蟹猴用上肢取食执行时间逐渐延长,纹状体99mTc-TRODAT-1放射性摄取率呈逐渐减低的趋势,直线回归分析结果显示食蟹猴上肢取食执行时间与年龄呈统计学相关关系,且与纹状体99mTc-TRODAT-1放射性摄取率亦呈统计学的相关关系。进一步的独立于年龄的部分相关分析表明年龄增长驱动2者的相关。结论正常食蟹猴随年龄增长脑内99mTc-TRODAT-1摄取率的减少是造成食蟹猴上肢取食执行时间延长的关键因素之一。     

Hepatitis C virus infections from a contaminated radiopharmaceutical used in myocardial perfusion studies

Context  Nuclear pharmacies prepare radiopharmaceutical products for use in common diagnostic procedures, including myocardial perfusion studies. Hepatitis C virus (HCV) transmission has not been reported previously in the setting of nuclear imaging studies. Objective  To investigate an outbreak of acute HCV infection identified among patients who underwent myocardial perfusion studies on October 15, 2004, using an injected radiopharmaceutical. Design, Setting, and Patients  Outbreak investigation including molecular epidemiology and pharmacy site investigation at outpatient cardiology clinics and a nuclear pharmacy in Maryland. Ninety patients who received injections drawn from select radiopharmaceutical vials prepared on October 14-15, 2004, at a single nuclear pharmacy were offered testing for bloodborne pathogens. Pharmacy procedures were reviewed and HCV quasi species analysis was performed. Main Outcome Measures  Hepatitis C virus infection and quasispecies sequence similarity. Results  Sixteen patients with acute HCV infection were identified from 3 separate clinics. All patients received radiopharmaceutical injections drawn from a single pharmacy vial (vial 1). None of the 59 tested patients who received doses from 6 other vials had acute HCV infection. Blood from a potential source patient with HCV and human immunodeficiency virus (HIV) infection was processed for a radiolabeled white blood cell study in the pharmacy 12 hours before vial 1 was prepared. The HCV quasispecies sequences from this potential source patient were nearly identical to those from cases (97.8%-98.5% similarity). No acute HIV infections were identified. Pharmacy practices that could have led to blood cross-contamination included reuse of needles and syringes during dilutions and use of common flow hoods for some steps in the preparation of sterile and blood-derived products. Conclusions  Sixteen persons acquired HCV infection from a blood-contaminated radiopharmaceutical. The source and practices that could have facilitated breaks in aseptic technique were identified at the pharmacy. Nuclear pharmacies that handle biological products should follow appropriate aseptic technique to prevent contamination of sterile radiopharmaceuticals.      

Effects of arotinoid acid on induction of apoptosis and differentiation and telomerase activity and cell cycle in the HL-60 cell line

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Mechanical reperfusion in patients with acute myocardial infarction presenting more than 12 hours from symptom onset: a randomized controlled trial

Context  No specifically designed studies have addressed the role of primary percutaneous coronary intervention in patients with acute ST-segment elevation myocardial infarction (STEMI) presenting more than 12 hours after symptom onset. Current guidelines do not recommend reperfusion treatment in these patients. Objective  To assess whether an immediate invasive treatment strategy is associated with a reduction of infarct size in patients with acute STEMI, presenting between 12 and 48 hours after symptom onset, vs a conventional conservative strategy. Design, Setting, and Patients  International, multicenter, open-label, randomized controlled trial conducted from May 23, 2001, to December 15, 2004, of 365 patients aged 18 to 80 years without persistent symptoms admitted with the diagnosis of acute STEMI between 12 and 48 hours after symptom onset. Interventions  Random assignment to either an invasive strategy (n=182) based predominantly on coronary stenting with abciximab or a conventional conservative treatment strategy (n=183). Main Outcome Measures  The primary end point was final left ventricular infarct size according to single-photon emission computed tomography study with technetium Tc 99m sestamibi performed between 5 and 10 days after randomization in 347 patients (95.1%). Secondary end points included composite of death, recurrent MI, or stroke at 30 days. Results  The final left ventricular infarct size was significantly smaller in patients assigned to the invasive group (median, 8.0%; interquartile range [IQR], 2.0%-15.8%) vs those assigned to the conservative group (median, 13.0%; IQR, 3.0%-27.0%; P<.001). The mean difference in final left ventricular infarct size between the invasive and conservative groups was –6.8% (95% confidence interval [CI], –10.2% to –3.5%). The secondary end points of death, recurrent MI, or stroke at 30 days occurred in 8 patients in the invasive group (4.4%) and 12 patients in the conservative group (6.6%) (relative risk, 0.67; 95% CI, 0.27-1.62; P = .37). Conclusion  An invasive strategy based on coronary stenting with adjunctive use of abciximab reduces infarct size in patients with acute STEMI without persistent symptoms presenting 12 to 48 hours after symptom onset.      

Childhood vaccination and nontargeted infectious disease hospitalization

Context  It has been hypothesized that multiple-antigen vaccines, such as measles-mumps-rubella vaccine, or aggregated vaccine exposure could lead to immune dysfunction, resulting in nontargeted infectious diseases as a result of an "overload" mechanism. Objective  To evaluate the relationship between routinely administered childhood vaccines (Haemophilus influenzae type b; diphtheria-tetanus-inactivated poliovirus; diphtheria-tetanus-acellular pertussis-inactivated poliovirus; whole-cell pertussis; measles-mumps-rubella; oral poliovirus) and hospitalization for nontargeted infectious diseases. Design, Setting, and Participants  Population-based cohort comprising all children born in Denmark from 1990 through 2001 (N = 805 206). Longitudinal information was collected on type and number of vaccine doses received and hospitalization with infectious diseases, specifically acute upper respiratory tract infection, viral and bacterial pneumonia, septicemia, viral central nervous system infection, bacterial meningitis, and diarrhea. Main Outcome Measures  Rate ratios for each type of infectious disease according to vaccination status. Results  During 2 900 463 person-years of follow-up, 84 317 cases of infectious disease hospitalization were identified. Out of 42 possible associations (6 vaccines and 7 infectious disease categories), the only adverse association was for Haemophilus influenzae type b vaccine and acute upper respiratory tract infection (rate ratio, 1.05; 95% confidence interval, 1.01-1.08 comparing vaccinated participants with unvaccinated participants). This one adverse association of 42 possible outcomes was within the limits of what would be expected by chance alone and the effect was not temporal or dose-response. When considering aggregated vaccine exposure, we found no adverse associations between an increasing number of vaccinations and infectious diseases. Conclusion  These results do not support the hypotheses that multiple-antigen vaccines or aggregated vaccine exposure increase the risk of nontargeted infectious disease hospitalization.      

99mTcO4-甲状腺显像对甲状腺摄碘-131 率测定的影响

目的 观察Na^99mTcO^-₄甲状腺显像对甲状腺¹³¹I放射性计数的影响及其随时间变化的规律。方法 以2013年3月至5月在北京协和医院核医学科就诊并已行甲状腺摄碘率(RAIU)测定的40例Graves病甲状腺功能亢进患者为研究对象,静脉注射Na^99mTcO^-₄(185MBq)行甲状腺显像以测定甲状腺面积,采用甲状腺功能仪分别测定患者注射Na^99mTcO^-₄后1、25、49、73、169 h甲状腺内放射性计数,并利用半衰期公式推算25、49、73 h时甲状腺内来自于¹³¹I及^99mTc的放射性计数,以^99mTc/室本底计数(1200)相对值为参考,观察^99mTc放射性计数随时间的变化规律及其对RAIU的影响,同时计算出⁹⁹Tc^m在甲状腺内的有效半衰期(Teff ^99mTc),观察其与游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)、¹³¹I有效半衰期(Teff ¹³¹I)间的相关性。结果 静脉注射Na^99mTcO^-₄后第1、25、49、73h,通过甲状腺功能仪测定出来自^99mTc的放射性计数分别为(440.16±247.35)×10⁴、(11.37±10.67)×10⁴、(0.13±0.36)×10⁴、(-0.10±0.19)×10⁴,其与室本底比值分别为3668.00、94.75、1.08、NA。Teff ^99mTc为(4.41±0.49)h,与FT3、FT4和Teff ¹³¹I均无明显相关;Teff ¹³¹I与FT3(r=-0.503,P=0.003)、FT4(r=-0.516,P=0.002)则呈负相关。结论 甲状腺功能亢进患者甲状腺内Teff ^99mTc为4.41 h。注射Na^99mTcO^-₄ 3 d后,Na^99mTcO^-₄甲状腺显像对RAIU测定已无影响。^99mTc的有效半衰期与患者甲状腺激素水平和摄碘功能无明显相关性。     

Stem cell mobilization by granulocyte colony-stimulating factor in patients with acute myocardial infarction: a randomized controlled trial

Context  Experimental studies and early phase clinical trials suggest that transplantation of blood-derived or bone marrow–derived stem cells may improve cardiac regeneration and neovascularization after acute myocardial infarction. Granulocyte colony-stimulating factor (G-CSF) induces mobilization of bone marrow stem cells. Objective  To assess the value of stem cell mobilization by G-CSF therapy in patients with acute myocardial infarction. Design, Setting, and Patients  Randomized, double-blind, placebo-controlled trial of patients diagnosed with ST-segment elevation acute myocardial infarction who had successful reperfusion by percutaneous coronary intervention within 12 hours after onset of symptoms in Germany between February 24, 2004, and February 2, 2005. Interventions  Patients were randomly assigned to receive subcutaneously either a daily dose of 10 µg/kg of G-CSF or placebo for 5 days. Main Outcome Measures  The primary end point was reduction of left ventricular infarct size according to technetium Tc 99m sestamibi scintigraphy performed at baseline and at 4 to 6 months after randomization. Secondary end points included improvement of left ventricular ejection fraction measured by magnetic resonance imaging and the incidence of angiographic restenosis. Results  Of the 114 patients, 56 were assigned to receive treatment with G-CSF and 58 were assigned to receive placebo. Treatment with G-CSF produced a significant mobilization of stem cells. Between baseline and follow-up, left ventricular infarct size according to scintigraphy was reduced by a mean (SD) of 6.2% (9.1%) in the G-CSF group and 4.9% (8.9%) in the placebo group (P = .56) and left ventricular ejection fraction was improved by 0.5% (3.8%) in the G-CSF group and 2.0% (4.9%) in the placebo group (P = .14). Angiographic restenosis occurred in 19 (35.2%) of 54 patients in the G-CSF group and in 17 (30.9%) of 55 patients in the placebo group (P = .79). The most common adverse event among patients assigned to G-CSF was mild to moderate bone pain and muscle discomfort. Conclusion  Stem cell mobilization by G-CSF therapy in patients with acute myocardial infarction and successful mechanical reperfusion has no influence on infarct size, left ventricular function, or coronary restenosis. Clinical Trial Registration  ClinicalTrials.gov Identifier: NCT00126100      

小剂量多巴酚丁胺门控心肌显像预测左心室功能受损的冠心病患者CABG术后早期疗效

目的用小剂量多巴酚丁胺结合99mTc-甲氧基异丁基异腈(MIBI)门控心肌显像(SPECT)检测结果预测存活心肌在接受冠状动脉旁路移植术(CABG)的左心室功能受损的冠心病患者的疗效。方法对38例接受CABG的患者手术前行静息与小剂量多巴酚丁胺结合99mTc-MIBISPECT显像,术后3个月行静息SPECT随访。根据术后左心室射血分数(LVEF)与基线的变化,患者被分为2组:A组19人,术后LVEF值提高≥5%;B组19人,术后LVEF值提高<5%。结果A组术后LVEF值较基线提高(P<0.001),左心室舒张末期容积(EDV)、左心室收缩末期容积(ESV)明显缩小(P<0.05);B组术后LVEF、EDV、ESV值均无明显改善(P>0.05)。临床随访过程中B组有3位患者因心力衰竭再次住院治疗。以术后LVEF较基线提高≥5%作为标准,用ROC曲线得出多巴酚丁胺负荷试验过程中LVEF提高≥4.5%为预测值。多巴酚丁胺负荷试验过程中LVEF提高≥4.5%在A组中有10人,在B组中有3人。以多巴酚丁胺负荷试验过程中LVEF提高≥4.5%作为术后LVEF提高的标准,敏感度为76.9%,特异性为64%,准确性为68.4%。多巴酚丁胺负荷试验过程中LVEF与术后LVEF有明显相关性(r=0.83,P=0.000);多巴酚丁胺负荷试验过程中EDV、ESV与术后EDV、ESV有明显相关性(r=0.79,P=0.000,r=0.88,P=0.000)。结论小剂量多巴酚丁胺结合99mTc-MIBISPECT显像中LVEF提高≥4.5%可作为术后LVEF提高的预测指标。     

Complications of femoral and subclavian venous catheterization in critically ill patients: a randomized controlled trial

Jacques Merrer, MD; Bernard De Jonghe, MD; Franck Golliot, MS; Jean-Yves Lefrant, MD; Brigitte Raffy, MD; Eric Barre, MD; Jean-Philippe Rigaud, MD; Dominique Casciani, MD; Benoît Misset, MD; Christophe Bosquet, MD; Hervé Outin, MD; Christian Brun-Buisson, MD; Gérard Nitenberg, MD; for the French Catheter Study Group in Intensive Care

JAMA. 2001;286:700-707.

Context  Whether venous catheterization at the femoral site is associated with an increased risk of complications compared with that at the subclavian site is debated.

Objective  To compare mechanical, infectious, and thrombotic complications of femoral and subclavian venous catheterization.

Design and Setting  Concealed, randomized controlled clinical trial conducted between December 1997 and July 2000 at 8 intensive care units (ICUs) in France.

Patients  Two hundred eighty-nine adult patients receiving a first central venous catheter.

Interventions  Patients were randomly assigned to undergo central venous catheterization at the femoral site (n = 145) or subclavian site (n = 144).

Main Outcome Measures  Rate and severity of mechanical, infectious, and thrombotic complications, compared by catheterization site in 289, 270, and 223 patients, respectively.

Results  Femoral catheterization was associated with a higher incidence rate of overall infectious complications (19.8% vs 4.5%; P<.001; incidence density of 20 vs 3.7 per 1000 catheter-days) and of major infectious complications (clinical sepsis with or without bloodstream infection, 4.4% vs 1.5%; P = .07; incidence density of 4.5 vs 1.2 per 1000 catheter-days), as well as of overall thrombotic complications (21.5% vs 1.9%; P<.001) and complete thrombosis of the vessel (6% vs 0%; P = .01); rates of overall and major mechanical complications were similar between the 2 groups (17.3% vs 18.8 %; P = .74 and 1.4% vs 2.8%; P = .44, respectively). Risk factors for mechanical complications were duration of insertion (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.03-1.08 per additional minute; P<.001); insertion in 2 of the centers (OR, 4.52; 95% CI, 1.81-11.23; P = .001); and insertion during the night (OR, 2.06; 95% CI, 1.04-4.08; P = .03). The only factor associated with infectious complications was femoral catheterization (hazard ratio [HR], 4.83; 95% CI, 1.96-11.93; P<.001); antibiotic administration via the catheter decreased risk of infectious complications (HR, 0.41; 95% CI, 0.18-0.93; P = .03). Femoral catheterization was the only risk factor for thrombotic complications (OR, 14.42; 95% CI, 3.33-62.57; P<.001).

Conclusion  Femoral venous catheterization is associated with a greater risk of infectious and thrombotic complications than subclavian catheterization in ICU patients.

     

Role of Rifampin for Treatment of Orthopedic Implant-Related Staphylococcal Infections: A Randomized Controlled Trial

Context.— Rifampin-containing regimens are able to cure staphylococcal implant-related infections based on in vitro and in vivo observations. However, this evidence has not been proven by a controlled clinical trial. Objective.— To evaluate the clinical efficacy of a rifampin combination in staphylococcal infections associated with stable orthopedic devices. Design.— A randomized, placebo-controlled, double-blind trial conducted from 1992 through 1997. Setting.— Two infectious disease services in tertiary care centers in collaboration with 5 orthopedic surgeons in Switzerland. Patients.— A total of 33 patients with culture-proven staphylococcal infection associated with stable orthopedic implants and with a short duration of symptoms of infection (exclusion limit <1 year; actual experience 0-21 days). Intervention.— Initial debridement and 2-week intravenous course of flucloxacillin or vancomycin with rifampin or placebo, followed by either ciprofloxacin-rifampin or ciprofloxacin-placebo long-term therapy. Main Outcome Measures.— Cure was defined as (1) lack of clinical signs and symptoms of infection, (2) C-reactive protein level less than 5 mg/L, and (3) absence of radiological signs of loosening or infection at the final follow-up visit at 24 months. Failure was defined as (1) persisting clinical and/or laboratory signs of infection or (2) persisting or new isolation of the initial microorganism. Results.— A total of 18 patients were allocated to ciprofloxacin-rifampin and 15 patients to the ciprofloxacin-placebo combination. Twenty-four patients fully completed the trial with a follow-up of 35 and 33 months. The cure rate was 12 (100%) of 12 in the ciprofloxacin-rifampin group compared with 7 (58%) of 12 in the ciprofloxacin-placebo group (P=.02). Nine of 33 patients dropped out due to adverse events (n=6), noncompliance (n=1), or protocol violation (n=2). Seven of the 9 patients who dropped out were subsequently treated with rifampin combinations, and 5 of them were cured without removal of the device. Conclusion.— Among patients with stable implants, short duration of infection, and initial debridement, patients able to tolerate long-term (3-6 months) therapy with rifampin-ciprofloxacin experienced cure of the infection without removal of the implant.      

Expression of chemokine receptors CCR3, CCR5 and CXCR3 on CD4^＋ T cells in CBA/J×DBA/2 mouse model,selectively induced by IL-4 and IL-10, regulates the embryo resorption rate

Background Chemokines and their receptors have been a research focus in transplantation immunology. Chemokines and their receptors play a role in lymphocyte recruitment and differentiation process. This study aimed to observe whether IL-4 and IL-10 may regulate the expression of chemokine receptors CCR3, CCR5 and CXCR3 on CD4^＋ T cells in CBA/J×DBA/2 mouse model and to explore the role of CCR3, CCR5, CXCR3 in immune tolerance in pregnancy. Methods The mouse model of spontaneous abortion （CBA/J×DBA/2） and the normal pregnant mouse model （CBA/J×BALB/c） were used. CBA/J×DBA/2 mice were injected with IL-4 （CBA/J×DBA/2-IL-4）, IL-4 and IL-10 （CBA/J×DBA/2-IL-4＋IL-10）, or normal saline （CBA/J×DBA/2-NS） as a control. The expression of CCR3, CCR5 and CXCR3 on CD4^＋ T cells from mouse peripheral blood was measured by the double-labelled FCM method, and the embryo resorption rate was also examined. Results The embryo resorption rate in the CBA/J×DBA/2 group without any treatment was significantly higher than that in the CBA/J×BALB/c group （17.9% vs 3.7%, P 〈0.01）. The embryo resorption rate in the CBA/J×DBA/2 group immunized with IL-4 or IL-4 together with IL-10 was significantly decreased, compared with that in the control and NS groups respectively. CCR3 expression on CD4^＋ T cells in the CBA/J×DBA/2 group without any treatment was significantly lower than that in the CBA/J×BALB/c group （0.3738±0.3575 vs 1.2190±0.2772, P 〈0.01）; both CCR5 （3.0900±1.5603 vs 1.2390±0.6361, P〈0.01） and CXCR3 （2.4715±0.9074 vs 0.9200±0.5585, P 〈0.01） expressions on CD4^＋ T cells of the CBA/J×DBA/2 group without any treatment were significantly higher than those of the CBA/J×BALB/c group. Significant up-regulation of CCR3 and down-regulation of CXCR3 were found in the CBA/J×DBA/2 group treated with IL-4 （CCR3： 2.0360±0.6944, CXCR3： 1.3510±0.5263, P〈0.01） or IL-4 and IL-10 （CCR3： 1.8160±1.0947, CXCR3：1.0940±0.7168, P〈0.01）. Because of the CCR5, IL-4 and IL-10 （1.9400±0.8504 vs 3.0900±1.5603, P 〈0.05）, but IL-4 alone （2.5310±1.3595 vs 3.0900±1.5603, P 〉0.05） treatment significantly decreased the expression of CCR5 in CBA/J×DBA/2. Conclusions The abnormal expression of CCR3, CCR5 and CXCR3 on CD4^＋ T cells may play an important role in the pathogenesis of spontaneous abortion. The pregnancy immune tolerance may be induced through selective induction of CCR3, CCR5 and CXCR3 expressions by IL-4 together with IL-10.     

Protective effect of low potassium dextran solution on acute kidney injury following acute lung injury induced by oleic acid in piglets

Background  Low potassium dextran (LPD) solution can attenuate acute lung injury (ALI). However, LPD solution for treating acute kidney injury secondary to ALI has not been reported. The present study was performed to examine the renoprotective effect of LPD solution in ALI induced by oleic acid (OA) in piglets.

Methods  Twelve animals that suffered an ALI induced by administration of OA into the right atrium were divided into two groups: the placebo group (n=6) pretreated with normal saline and the LPD group (n=6), pretreated with LPD solution. LPD solution was injected intravenously at a dose of 12.5 ml/kg via the auricular vein 1 hour before OA injection.

Results  All animals survived the experiments with mild histopathological injury to the kidney. There were no significant differences in mean arterial pressure (MAP), creatinin and renal damage scores between the two groups. Compared with the placebo group, the LPD group had better gas exchange parameters at most of the observation points ((347.0±12.6) mmHg vs. (284.3±11.3) mmHg at 6 hours after ALI, P <0.01). After 6 hours of treatment with OA, the plasma concentrations of NGAL and interleukin (IL)-6 in both groups increased dramatically compared to baseline ((6.0±0.6) and (2.50±0.08) folds in placebo group; and (2.5±0.5) and (1.40±0.05) folds in LPD group), but the change of both parameters in the LPD group was significantly lower (P <0.01) than in the placebo group. And 6 hours after ALI the kidney tissue concentration of IL-6 in the LPD group ((165.7 ± 22.5) pg∙ml^-1∙g^-1 protein) was significantly lower (P <0.01) than that in placebo group ((67.2± 25.3) pg∙ml^-1∙g^-1 protein).

Conclusion  These findings suggest that pretreatment with LPD solution via systemic administration might attenuate acute kidney injury and the cytokine response of IL-6 in the ALI piglet model induced by OA injection.

     

肺栓塞动物模型(猪)V/Q SPECT显像与平面显像的对比

目的应用201Tl标记栓子制作肺栓塞动物模型(猪),比较肺V/QSPECT显像和平面显像的灵敏度、特异性和准确性,探讨肺通气显像在肺栓塞诊断中的意义及V/Q显像在亚肺段肺动脉栓塞(PE)诊断中的作用。方法16头试验用小型猪,栓塞前应用不同技术参数行99Tcm窗肺灌注平面及断层显像,每头猪分别置入0～3个栓子,栓塞后行99Tcm窗及201Tl窗双窗肺通气平面、断层显像及99Tcm窗肺灌注平面、断层显像。最后行X线平片或CT显像并进行肺脏解剖确定栓子位置。结果共可见栓子28个,其中17个位于左肺,11个位于右肺。平面显像的敏感性、特异性和准确性分别为75%、75%和75%,而断层显像的敏感性、特异性、准确性分别为100%、75%和96.9%。结论肺通气/灌注断层显像的灵敏度及准确性均较平面显像高,而特异性两者相同。同时行V/Q显像可提高肺栓塞的诊断率。V/QSPECT断层显像可提高亚肺段性PE的诊断率。选用低能通用准直器、平面显像矩阵128×128、断层影像Zoom1.46可较好的满足临床诊断需要。