Fecal DNA testing compared with conventional colorectal cancer screening methods: a decision analysis

BACKGROUND & AIMS: Fecal DNA testing is an emerging tool to detect colorectal cancer (CRC). Our aims were to estimate the clinical and economic consequences of fecal DNA testing vs. conventional CRC screening. METHODS: Using a Markov model, we estimated CRC incidence, CRC mortality, and discounted cost/life-year gained for screening by fecal DNA testing (F-DNA), fecal occult blood testing (FOBT) and/or sigmoidoscopy, or colonoscopy (COLO) in persons at average CRC risk from age 50 to 80 years. RESULTS: Compared with no screening, F-DNA at a screening interval of 5 years decreased CRC incidence by 35% and CRC mortality by 54% and gained 4560 life-years per 100,000 persons at USD $47,700/life-year gained in the base case. However, F-DNA gained fewer life-years and was more costly than conventional screening. The average number of colonoscopies per person was 3.8 with COLO and 0.8 with F-DNA. In most 1-way sensitivity analyses and Monte Carlo simulation iterations, F-DNA remained reasonably cost-effective compared with no screening, but COLO and FOBT dominated F-DNA. Assuming fecal DNA testing sensitivities of 65% for CRC and 40% for large polyp, and 95% specificity, a screening interval of 2 years and a test cost of USD $195 would be required to make F-DNA comparable with COLO. CONCLUSIONS: Fecal DNA testing every 5 years appears effective and cost-effective compared with no screening, but inferior to other strategies such as FOBT and COLO. Fecal DNA testing could decrease the national CRC burden if it could improve adherence with screening, particularly where the capacity to perform screening colonoscopy is limited.     

A rapid flow cytometry assay for the assessment of calcium mobilization in human neutrophils in a small volume of lysed whole-blood

Flow cytometry-based methods have been developed to measure most neutrophil responses. The assessment of the mobilization of calcium, however, is routinely performed on neutrophils isolated from whole blood. This report describes a flow cytometry-based assay to measure the mobilization of calcium in neutrophils directly in whole blood. This method requires minimal sample manipulation, small volumes of blood and is performed in a short period of time. Both clinical and research laboratories will be able to assess neutrophil function and the quality of granulocyte preparations using a more time and cost effective calcium mobilization test.     

Anticonvulsant activities of the FS-1 subfraction isolated from roots of Delphinium denudatum

Delphinium denudatum Wall. (Ranunculaceae) is a medicinal herb used for the treatment of epilepsy in the subcontinent. The present study reports the anticonvulsant activities in the maximal electroshock test (MEST) and subcutaneous pentylenetetrazole (PTZ), bicuculline (BIC), picrotoxin (PIC)-induced seizures of the FS-1 subfraction (FS-1) that was obtained by purification of an aqueous fraction isolated from the roots of D. denudatum. In CF 1 mice, FS-1 (600 mg/kg i.p.) exhibited very potent anticonvulsant activity that was comparable to the effects of the well-known antiepileptic drug phenytoin (20 mg/kg) in MEST and protected 100% animals from hind limb tonic extension phase of this model. FS-1 also suppressed PTZ-induced threshold seizure and the loss of the righting reflex with tonic fore and hind limb extension by 100%, similar to the antiepileptic drug valproic acid (350 mg/kg). BIC-induced seizures were suppressed in 80% of the animals. FS-1 exhibited weak anticonvulsant effect on PIC-induced seizures, however, it significantly reduced mortality and delayed the onset of seizures. FS-1 had no effect on strychnine (STN)-induced extensor seizures. The results demonstrate the broad and potent anticonvulsant activity of the compounds in FS-1 of D. denudatum.     

术前左室射血分数及短缩分数对冠状动脉旁路术后恶性心律失常的预测价值

为了评价冠状动脉旁路术 (CABG)术前左室射血分数 (LVEF)及左室短缩分数 (LVFS)对术后室性心律失常 (VA)预测的准确性 ,采用术前及术后 2周心脏彩超EF、FS值 (面积长轴法 )、心室晚电位 (VLP)、心肌酶、持续心电监测的方法 ,对我院 1 5 0例行CABG术的患者进行分析。结果 :1 )术前心肌梗死 (MI)、室壁瘤、VA及VLP阳性患者EF、FS值明显减低 ;2 )术前左心功能不全 (LVD)患者术后EF、FS值明显改善 ;3 )术前LVD、VA、VLP阳性及室壁瘤患者术后VA发生率明显高于其他患者。提示 :1 )面积长轴法EF、FS值是反映左心功能的敏感指标 ;2 )术前LVD患者术后短期左心功能明显好转 ,获益最大 ;3 )非LVD患者术后因心肌顿抑导致近期心功能暂时下降 ;4 )EF≤ 4 0 %和(或 )FS≤ 2 4 %是预测术后VA的独立指标 ,FS较EF更能准确地反映心脏收缩功能 ;5 )LVD、VLP、室壁瘤等综合指标分析有助于提高对术后VA预期的敏感性、特异性和准确性     

Quantitative measurements of second harmonic Doppler using ultrasound contrast agents

Quantitative measurements of second harmonic and first harmonic Doppler were carried out using two ultrasound contrast agents, Albunex^® and FS069. The RMS amplitudes of the Doppler shift spectra were measured as a function of the concentration of the agents, frequency and transmitted acoustic pressure. The results showed that, for a given lot of contrast agent investigated, FS069 was able to produce higher levels of first and, especially, second harmonic signals compared to Albunex. Under the same experimental conditions, the RMS Doppler amplitude (RDA) of FS069 was 3.8 ± 0.8 dB higher than Albunex at first harmonic and 12.6 ± 0.8 dB higher at second harmonic. The ratio of the second harmonic to first harmonic RDA, which we called R₂/R₁, decreases at a rate of 7 dB/MHz for both agents with increasing frequency. The difference in the value of R₂/R₁ between FS069 and Albunex at any frequency was approximately 4.5 dB. R₂/R₁ was found to increase linearly as a function of the transmitted acoustic pressure for both agents. Simulations using the Rayleigh-Plesset equation show a decrease of R₂/R₁ at a rate of 5 dB/MHz. Comparison of experimental results with theory indicates that the shell elasticity parameter may be an increasing function of the mean diameter of the bubbles.     

In vitro and in vivo stability of diluted recombinant factor VIII for continuous infusion use in haemophilia A

Summary.  Factor VIII (FVIII) replacement by continuous infusion (CI) is used postoperatively or after significant bleeding. For young paediatric patients, CI may require FVIII dilution. Variable stabilities of diluted full-length recombinant FVIII Kogenate^® FS (KG-FS) have been reported under different storage conditions. We investigated the recovery and stability of diluted KG-FS in vitro and in vivo . Kogenate^® FS was diluted to 50–120 U mL⁻¹ and its recovery and stability in glass vials or polypropylene syringes was determined. Furthermore, stability of KG-FS diluted to 80 U mL⁻¹'administered' via single- and double-pump mock CI systems was tested. Finally, the in vivo stability of KG-FS diluted to ∼60 U mL⁻¹ and administered postsurgically by CI with the double-pump to a paediatric patient with severe haemophilia A undergoing implantable venous access device placement was investigated. Initial KG-FS dilution resulted in a 10–20% FVIII loss; a further 25–30% loss occurred over 72 h in vials or syringes. With the double-pump, 1 h recovery was 35%, increasing to 80% by 24 h; the initial losses were because of the Y-infusion of a 10-fold larger volume of saline concomitantly with the FVIII. In vivo , CI resulted in stable FVIII activity levels within the target range. These in vitro results are important for the generation of CI guidelines for diluted KG-FS in the paediatric haemophilic population. That FVIII losses occur upon dilution and with the double-pump does not preclude use of diluted KG-FS. Indeed, stable FVIII levels were maintained when diluted KG-FS was administered by CI with the double-pump to a paediatric patient postsurgically.     

Immunohistochemical Localization of the Water Channels AQP4 and AQP5 in the Rat Pituitary Gland

The pituitary gland is composed of the adenohypophysis and neurohypophysis. The adenohypophysis contains endocrine cells, folliculo-stellate (FS) cells, and marginal layer cells, whereas the neurohypophysis mainly comprises axons and pituicytes. To understand the molecular nature of water transfer in the pituitary gland, we examined the immunohistochemical localization of the membrane water channels aquaporin-4 (AQP4) and AQP5 in rat tissue. Double immunofluorescence analysis of AQP4 and S100 protein, a known marker for FS cells, marginal layer cells, and pituicytes, clearly revealed that FS cells and marginal layer cells in the adenohypophysis and the pituicytes in pars nervosa are positive for AQP4. AQP5 was found to be localized at the apical membrane in some marginal layer cells surrounding the Rathke's residual pouch, in which AQP4 was observed to be localized on the basolateral membranes. These results suggest the following possibilities: 1) FS cells especially require water for their functions and 2) transepithelial water transfer could occur between the lumen of Rathke's residual pouch and the interstitial fluid in the adenohypophysis through the AQP4 and AQP5 channels in the marginal layer cells.