[I]-TYR3-octreotide: clinical dosimetry and use for internal radiotherapy of metastatic paraganglioma and carcinoid tumors

Dosimetry and therapeutic application of [¹³¹I]-Tyr3-octreotide were evaluated in three patients with metastatic paraganglioma and carcinoid tumor. The in vitro stability of [¹³¹I]-Tyr3-octreotide was verified. Tumor uptake and residence time were between 0.02 and 0.1% and 0.5 to 9.8 h, respectively. The calculated tumor radiation doses were between 0.105 and 0.696 mGy·MBq⁻¹. No intolerance or adverse effects were observed after the therapeutic doses (3.3–6.6 GBq). A partial tumor response was obtained in one patient and no response occurred in two patients.     

Increased Dosage of DYRK1A and Brain Volumetric Alterations in a YAC Model of Partial Trisomy 21

A yeast artificial chromosome (YAC) transgenic murine model of partial trisomy 21 overexpressing five human genes—including DYRK1A, which encodes a serine threonine kinase involved in cell cycle control—has been shown to present an increase in brain weight. We analyzed this new phenotype by measuring total and regional brain volumes at different ages, using a 7 Tesla magnetic resonance imaging volumetric approach. Volumetric measurements showed a total volume increase of 13.6% in adult mice. Changes in brain morphogenesis were already visible at a very early postnatal stage (postnatal days 2–7). Region‐specific changes were characterized from postnatal day 15 to 5 months. These results, made it possible to define region‐specific effects of DYRK1A overexpression, with the strongest increase seen in the thalamus–hypothalamus area (24%). Anat Rec, 291:254–262, 2008. © 2008 Wiley‐Liss, Inc.     

Somatic markers and explicit knowledge are both involved in decision-making

In 1994, it was proposed that decision-making requires emotion-related signals, known as somatic markers. In contrast, some authors argued that conscious knowledge of contingencies is sufficient for advantageous decision-making. We aimed to investigate the respective roles of somatic markers and explicit knowledge in decision-making. Thirty healthy volunteers performed the Iowa Gambling Task (IGT). Conscious knowledge was assessed using a sensitive questionnaire and skin conductance responses (SCRs) were recorded. Most participants acquired a preference for advantageous choices during the task and generated larger anticipatory SCRs before disadvantageous relative to advantageous choices. Performance on the IGT and the autonomic response were positively correlated (r = 0.38, p = 0.045). Moreover, there was a statistically significant difference in performance according to conscious awareness (p = 0.009). There was no significant association between level of explicit knowledge and SCR (p = 0.1). Finally, we did not find any interaction between explicit knowledge and performance although a lack of statistical power is not to be excluded. Advantageous decision-making therefore seems to be associated with two distinct, namely implicit and explicit, systems.     

HIV prevention: What have we learned from community experiences in concentrated epidemics?

Drawing on lessons learned from community experiences in concentrated epidemics, this paper explores three imperatives in the effort to reduce the sexual transmission of HIV: combat prevention fatigue, diversify HIV testing and combat stigma and discrimination. The paper argues for a non‐judgmental harm reduction approach to the prevention of sexual transmission of HIV that takes into account the interpretation of risk by diverse individuals and communities in the era of antiretroviral therapy. This approach requires greater attention to increasing access to opportunities to know one's serostatus, especially among key populations at greater risk. Novel approaches to diversifying HIV testing approaches at community level are needed. Finally, the paper makes a plea for bold measures to combat stigma and discrimination, which continues to represent a formidable barrier for access to services for affected populations and may contribute to HIV‐related risk behaviours. A “triple therapy” approach to address stigma and discrimination is discussed, which includes greater acceptance of people living with HIV and AIDS (PLWHA), improving relevant laws and policies, and involving prevention users‐ working with people rather than for people‐. Note: this paper corresponds to the plenary talk of Bruno Spire at the XVIIth World AIDS Conference, August 8th, Mexico city: http://www.kaisernetwork.org/health_cast/player.cfm?id=4383     

Determination of total bilirubin in whole blood from neonates: results from a French multicenter study.

BACKGROUND: Jaundice is frequent in neonates and can cause severe complications, especially in premature neonates, particularly the risk of developing acute bilirubin encephalopathy. Our purpose was to verify if determination of total bilirubin (TBIL) in whole blood on an ABL 735 blood gas analyzer with a spectrophotometer module could provide an analytical alternative to chemical methods of TBIL measurement. METHODS: Our multicenter comparative study involved four hospital laboratories. We studied the repeatability and reproducibility of ABL 735 TBIL measurements in two control sera of medium (N1, 58.1 micromol/L) and high (N2, 275.3 micromol/L) TBIL levels. The same study was simultaneously conducted on four chemistry instruments (two LX 20, one Integra 800 and one Hitachi 917) using four Jendrassik-Grof derived methods. At one site, repeatability was performed with two adult whole-blood samples containing low and high TBIL levels (55.1 and 312.6 micromol/L). RESULTS: Repeatability tests provided coefficients of variation (CVs) between 0.67% and 1.86% on the ABL 735 system, vs. 0.35% and 1.96% for the chemistry instruments. Reproducibility tests for the same control sera resulted in CVs between 1.01% and 3.55% for the ABL 735 and between 0.52% and 3.65% for the chemistry instruments. Recovery for the N1 and N2 control sera was 102-120%. A correlation study of TBIL determination in whole blood vs. plasma was conducted on 473 neonatal blood samples. Correlation coefficients between whole blood and plasma TBIL ranged from 0.969 to 0.994. Passing-Bablok equations were y=1.17x+9.7 [site 1 (IP)], y=1.01x+5.6 [site 2 (JPB, MR)], and y=1.00x-20 [site 3 (AS)]. Only 10% of the results fell outside the 10% range in the bias-corrected Bland-Altman difference plot for the ABL 735 method compared to traditional laboratory methods. CONCLUSIONS: The ABL 735 instrument is reliable for measuring TBIL in 70-microL whole blood samples from neonates. Thus, this method might allow significant blood savings in preterm neonates. Correlation with the reference method for plasma or sera must be established to ensure good follow-up of patients.     

The pattern of expression of the voltage-gated sodium channels Na(v)1.8 and Na(v)1.9 does not change in uninjured primary sensory neurons in experimental neuropathic pain models

A spared nerve injury of the sciatic nerve (SNI) or a segmental lesion of the L5 and L6 spinal nerves (SNL) lead to behavioral signs of neuropathic pain in the territory innervated by adjacent uninjured nerve fibers, while a chronic constriction injury (CCI) results in pain sensitivity in the affected area. While alterations in voltage-gated sodium channels (VGSCs) have been shown to contribute to the generation of ectopic activity in the injured neurons, little is known about changes in VGSCs in the neighboring intact dorsal root ganglion (DRG) neurons, even though these cells begin to fire spontaneously. We have now investigated changes in the expression of the TTX-resistant VGSCs, Nav1.8 (SNS/PN3) and Nav1.9 (SNS2/NaN) by immunohistochemistry in rat models of neuropathic pain both with an intermingling of intact and degenerated axons in the nerve stump (SNL and CCI) and with a co-mingling in the same DRG of neurons with injured and uninjured axons (sciatic axotomy and SNI). The expression of Nav1.8 and Nav1.9 protein was abolished in all injured DRG neurons, in all models. In intact DRGs and in neighboring non-injured neurons, the expression and the distribution among the A- and C-fiber neuronal populations of Nav1.8 and Nav1.9 was, however, unchanged. While it is unlikely, therefore, that a change in the expression of TTX-resistant VGSCs in non-injured neurons contributes to neuropathic pain, it is essential that molecular alterations in both injured and non-injured neurons in neuropathic pain models are investigated.     

Towards ultrasound cardiac image segmentation based on the radiofrequency signal

In echocardiography, the radio-frequency (RF) image is a rich source of information about the investigated tissues. Nevertheless, very few works are dedicated to boundary detection based on the RF image, as opposed to envelope image. In this paper, we investigate the feasibility and limitations of boundary detection in echocardiographic images based on the RF signal. We introduce two types of RF-derived parameters: spectral autoregressive parameters and velocity-based parameters, and we propose a discontinuity adaptive framework to perform the detection task. In classical echographic cardiac acquisitions, we show that it is possible to use the spectral contents for boundary detection, and that improvement can be expected with respect to traditional methods. Using the system approach, we study on simulations how the spectral contents can be used for boundary detection. We subsequently perform boundary detection in high frame rate simulated and in vivo cardiac sequences using the variance of velocity, obtaining very promising results. Our work opens the perspective of a RF-based framework for ultrasound cardiac image segmentation and tracking.