CLINICAL SIGNIFICANCE OF THE DETECTION OF MINIMAL RESIDUAL DISEASE IN CHILDHOOD B-ALL BY FLOW CYTOMETRY

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Decrement of the skin conductance response to repeated volitional inspiration.

OBJECTIVE: To examine response decrement of the recently reported inspiratory skin conductance response (SCR) [Lim CL, Seto-Poon M, Clouston PD, Morris JG. Sudomotor nerve conduction velocity and central processing time of the skin conductance response. Clin Neurophysiol 2003;114:2172-80]. METHODS: Twelve healthy adult volunteers performed 3 tasks (A) a control task of maintaining tidal breathing and then two randomized tasks, (B) a deep inspiration to a target oral pressure and (C) tapping with a finger. Each task was performed 30 times on cue every 20s in 3 runs with 5 min of rest between runs. The SCR, oral pressure, airflow, inspired volume and cue signal were recorded continuously and analysed offline. SCR amplitude was logarithmically transformed and then statistically analysed, using a linear mixed effects model, as a function of run number, trial number and absolute error between target and actual oral pressures. RESULTS: Inspiratory efforts elicited exponentially decreasing SCR amplitude with increasing trial number during each run (P < 0.0001). After adjusting for trial number, the mean SCR amplitude of the second and the third run were, respectively, 24.2 (95% CI (0.175, 0.336), P < 0.001) and 14.4% (95% CI (0.104, 0.200), P < 0.001) of the first run amplitude. CONCLUSIONS: Volitional deep inspiration reliably activates an SCR that exhibits response decrement with repetition, which may be habituation. SIGNIFICANCE: The volitional inspiratory SCR may assist in the assessment of sympathetic autonomic status in patients with peripheral afferent neuropathy.     

Interaction of epidermal growth factor, Ca2+, and matrix metalloproteinase-9 in primary keratinocyte migration

Elevations of epidermal growth factor (EGF) and Ca²⁺ concentrations in the wound site are associated with reepithelialization during wound healing. In addition, Ca²⁺ and EGF can both induce increases in matrix metalloproteinase‐9 (MMP‐9) synthesis. However, little is known about the interplay of these events in regulating the migration properties of primary keratinocytes on collagen I, the most abundant extracellular matrix component in the skin. We found that EGF stimulated both chemokinetic and chemotactic migration of primary keratinocytes on collagen I; however, MMP‐9 was required for EGF‐stimulated chemotaxis but not EGF‐stimulated chemokinesis. Calcium at 0.5 mM stimulated chemokinetic migration of keratinocytes. Together, Ca²⁺ and EGF stimulated higher levels of chemokinesis than either stimulus alone. Furthermore, Ca²⁺ could restore the ability of keratinocytes from MMP‐9 null mice to undergo EGF‐stimulated chemotaxis. The phosphatidylinositol‐3 kinase inhibitor LY294002 inhibited both EGF‐ and Ca²⁺‐stimulated chemokinetic migration. In contrast, the MEK inhibitor PD98059 blocked Ca²⁺‐ but not EGF‐stimulated chemokinetic migration of keratinocytes. A combination of PD98059 and LY294002 was required to inhibit Ca²⁺ enhancement of EGF‐stimulated migration completely. Calcium‐stimulated chemokinesis was completely blocked by either the protein kinase C‐α inhibitor Gö6976 or the src/fyn inhibitor PP2. Using primary keratinocytes, our results showed how the combined action of Ca²⁺, EGF, and MMP‐9 regulated the contributions of extracellular‐regulated kinase and phosphatidylinositol‐3 kinase toward chemokinetic and chemotactic migration of keratinocytes.     

Automated three-dimensional analysis of histological and autoradiographic rat brain sections: application to an activation study.

Besides the newly developed positron emission tomography scanners (microPET) dedicated to the in vivo functional study of small animals, autoradiography remains the reference technique widely used for functional brain imaging and the gold standard for the validation of in vivo results. The analysis of autoradiographic data is classically achieved in two dimensions (2D) using a section-by-section approach, is often limited to few sections and the delineation of the regions of interest to be analysed is directly performed on autoradiographic sections. In addition, such approach of analysis does not accommodate the possible anatomical shifts linked to dissymmetry associated with the sectioning process. This classic analysis is time-consuming, operator-dependent and can therefore lead to non-objective and non-reproducible results. In this paper, we have developed an automated and generic toolbox for processing of autoradiographic and corresponding histological rat brain sections based on a three-step approach, which involves: (1) an optimized digitization dealing with hundreds of autoradiographic and histological sections; (2) a robust reconstruction of the volumes based on a reliable registration method; and (3) an original 3D-geometry-based approach to analysis of anatomical and functional post-mortem data. The integration of the toolbox under a unified environment (in-house software BrainVISA, http://brainvisa.info) with a graphic interface enabled a robust and operator-independent exploitation of the overall anatomical and functional information. We illustrated the substantial qualitative and quantitative benefits obtained by applying our methodology to an activation study (rats, n=5, under unilateral visual stimulation).     

感染性休克早期目标指导性治疗方案的应用体会

目的 为加强外科围手术期处理，观察应用早期目标指导性治疗方案（early goal directed therapy，EGDT）对感染性休克患者的救治效果。方法 运用EGDT使入ICU8h内的感染性休克患者的中心静脉压（CVP）、平均动脉压（MAP）和上腔静脉血氧饱和度（ScvO2）达标。结果 本组20例感染性休克患者，在8h内CVP达标20例，MAP达标20例，ScvO2达标16例。结论 应用EDGT治疗感染性休克有较好的理论基础和实用性，在限定的时间内使所有的目标值达标存在一定的困难。     

膀胱出口梗阻后逼尿肌收缩蛋白表达和膀胱重量的改变

目的探讨膀胱出口梗阻(BOO)后逼尿肌收缩蛋白表达和膀胱重量的改变及意义。方法BOO组病人16例,筛选条件为入院诊断良性前列腺增生症(BPH)并经尿动力学压力-流率检查证实为高压低流型;对照组5例,为外伤等情况入院并排除有下尿路梗阻病史者。BOO组所有病例均行耻骨上经膀胱前列腺摘除术,术前B超检查测定膀胱重量和前列腺内外径比值,术中切取膀胱上壁组织2cm×1cm×1cm大小,标本行RT-PCR反应,检测膀胱逼尿肌中肌动蛋白和肌球蛋白mRNA的表达,并比较其与膀胱重量间的线性相关性。结果BOO组与对照组膀胱重量分别为(92.15±34.89)g和(56.08±20.35)g,(P<0.05);前列腺内外径比值分别为(0.57±0.16)和(0.18±0.06),(P<0.01);与对照组相比,BOO组肌动蛋白和肌球蛋白mRNA的表达量均有显著增加,分别为(40.32±59.67)×106和(6.59±5.62)×106,(P值均<0.01);且两者表达量与膀胱重量之间均有明显线性正相关性(P<0.05)。结论逼尿肌中肌动蛋白和肌球蛋白的表达与膀胱逼尿肌的功能状态密切相关。     

Multifocal calcifying epithelial odontogenic tumor.

The calcifying epithelial odontogenic tumor (CEOT), or Pindborg tumor, is a rare and benign odontogenic neoplasm that affects the jaw. The most common manifestation of CEOT is a unifocal or localized lesion of the involved jaw, which may appear clinically as a hard tissue swelling and radiographically as a mixed radiolucent-radiopaque mass. In this article, we present a unique case of CEOT affecting multiple sites in the maxilla and mandible of a 51-year-old white man. Though biopsy samples from all involved sites revealed similar histopathologic features consistent with CEOT, the fact that there was a multifocal presentation is an unusual phenomenon for CEOT and has never been reported. Multifocal odontogenic lesions are not typical but have been observed in conditions associated with known genetic mutations. For example, multiple odontogenic keratocysts are the most common feature of the inherited condition known as nevoid basal cell carcinoma syndrome. This case, however, is the first one to demonstrate that there may be a multifocal variant of CEOT that has not been previously recognized.     

Evaluation of BioCorkscrew and Bioknotless RC suture anchor rotator cuff repair fixation: an in vitro biomechanical study

This in vitro biomechanical study used cadaveric specimens to compare the rotator cuff repair fixation provided by BioCorkscrew and Bioknotless RC suture anchors. Three cm wide by 1-cm long full-thickness supraspinatus defects were repaired using either two BioCorkscrew suture anchors with combined vertical and horizontal mattress sutures (n = 7) or three Bioknotless RC suture anchors with simple sutures (n = 7). Therefore, the BioCorkscrew suture anchor group had two sutures per anchor (four total sutures), while the Bioknotless RC suture anchor group had one suture per anchor (three total sutures). Two-phase cyclic (5–100 N, 1,000 cycles and 5–180 N, 2,000 cycles) and load to failure tests (31 mm/s) were performed. Non-parametric statistics were used to compare group differences (P < 0.05). All of the BioCorkscrew group specimens (seven of seven) completed the two phase cyclic test regimen without failure or gapping ≥ 5 mm, compared to only three of seven of the Bioknotless RC group (Fisher’s Exact test = 0.03). Groups did not differ for repair site gapping during the 5–100 N cyclic test phase (Fisher’s Exact test = 0.77), however more of the Bioknotless RC group displayed gapping ≥ 5 mm during the 5–180 N cyclic test phase than the BioCorkscrew group (P = 0.02). The BioCorkscrew group also displayed greater yield load during load to failure testing (492.2 ± 204 N vs. 296.4 ± 155 N, P = 0.03). In this in vitro biomechanical study, the BioCorkscrew group with combined vertical and horizontal mattress sutures displayed greater cyclic test survival, less repair site gapping, and superior yield load compared to the Bioknotless RC group with simple sutures. These results in human cadaveric rotator cuff-humerus specimens suggest better immediate post-operative repair site strength and a reduced need for post-operative restrictions. Clinical studies are needed to determine how these rotator cuff repair modes withstand the forces of early rehabilitation and activities of daily living that potentially influence patient outcomes.     

Pravastatin therapy is associated with reduction in coronary allograft vasculopathy in pediatric heart transplantation.

BACKGROUND: Hydroxymethylglutaryl CoA reductase inhibitors (statins) have been demonstrated to reduce the risk of developing coronary allograft vasculopathy (CAV) following heart transplantation in adults and are used routinely in many centers. CAV and lipid abnormalities have been reported to be less prevalent in pediatric heart transplant recipients. It is not known whether statins reduce the risk of CAV in this population METHODS: A retrospective review was performed to analyze the risk factors for developing CAV following pediatric heart transplantation with particular attention to the impact of pravastatin therapy. The study population was comprised of 129 pediatric patients who underwent 142 heart transplants at our institution from 1988 to 2003. The outcome variable was freedom from CAV, CAV being determined by coronary angiography or autopsy. RESULTS: CAV was identified in 25 recipients at a median of 3.7 years after transplantation. There were 331 patient-years of pravastatin therapy. Pravastatin therapy resulted in a reduction in total cholesterol levels, 162 +/- 29 to 137 +/- 20 mg/dl, p = 0.01. In multivariate analysis the use of pravastatin was associated with a lower incidence of CAV (p = 0.03), whereas an increased frequency of late rejection (p = 0.003) and earlier year of transplantation (p = 0.04) were associated with increased risk of CAV. CONCLUSIONS: The routine use of pravastatin was associated with a lower risk following pediatric heart transplantation. Further studies into the relationship between lipid abnormalities, inflammation and rejection, and the development of CAV in children are warranted.