SPECT—CT显像估算甲状腺体积的探讨

目的探讨SPECT和CT估算甲状腺体积的准确性,为甲亢131I治疗剂量计算提供依据。方法用SPECT／CT仪对实测体积为8．5、12、17、20、24、33、42及66cm^3的8个仿真甲状腺模型行断层显像及图像融合处理,观察甲状腺模型SPECT和CT断层图像的对应关系以及SPECT最高计数阈值法估算体积的变化,并与CT估算体积及模型实测体积作配对资料t检验和相关关系分析。结果SPECT最高计数阈值法估算的模型体积随阈值增大而逐渐减小,反之,阈值减小,则体积增大,变化趋于线性,最佳阈值为49％;配对资料t检验,甲状腺模型实测体积、SPECT最高计数（49％）阈值法估算体积及CT估算体积相互无统计学差异（t=-0．6605,0．6088,0．2780;P=-0．5619,0．5301;0．7890）且高度正相关（r=-0．996,0．998,0．998）。结论SPECT最高计数（49％）阈值法和CT均可较准确地估算甲状腺体积,而前者为功能显像,有利于更好的指导甲亢131I治疗剂量的计算。     

A dose-response curve for the negative bias pressure of an intrathoracic pressure regulator during CPR

An intrathoracic pressure regulator (ITPR) is a device that can be added to the external end of a tracheal tube to create controlled negative airway pressure between positive pressure ventilations. The resulting downward bias of the airway pressure baseline promotes increased venous return and enhanced circulation during CPR and also during hypovolemic shock. In the present study, we exercised a mathematical model of the human cardiopulmonary system, including airways, lungs, a four chambered heart, great vessels, peripheral vascular beds, and the biomechanics of chest compression and recoil, to determine the relationship between systemic perfusion pressure during CPR and the value of baseline negative airway pressure in an ITPR. Perfusion pressure increases approximately 50% as baseline airway pressure falls from zero to -10 cm H2O. Thereafter perfusion pressure plateaus. Negative bias pressures exceeding -10 cm H2O are not needed in ITPR-CPR.     

Fear of pain, not pain catastrophizing, predicts acute pain intensity, but neither factor predicts tolerance or blood pressure reactivity: an experimental investigation in pain-free individuals.

Previous studies of the Fear-Avoidance Model of Exaggerated Pain Perception have commonly included patients with chronic low back pain, making it difficult to determine which psychological factors led to the development of an "exaggerated pain perception". This study investigated the validity of the Fear-Avoidance Model of Exaggerated Pain Perception by considering the influence of fear of pain and pain catastrophizing on acute pain perception, after considering sex and anxiety. Thirty-two males and 34 females completed the State-Trait Anxiety Inventory, the Fear of Pain Questionnaire, and the Coping Strategies Questionnaire. Subjects underwent a cold pressor procedure and tolerance, pain intensity, and blood pressure reactivity were measured. Sex, anxiety, fear of pain, and pain catastrophizing were simultaneously entered into separate multiple regression models to predict different components of pain perception. Tolerance was not predicted by fear of pain, pain catastrophizing, or anxiety. Pain intensity at threshold and tolerance were significantly predicted by fear of pain, only. Blood pressure reactivity to pain was significantly predicted by anxiety, only. These results suggest that fear of pain may have a stronger influence on acute pain intensity when compared to pain catastrophizing, while neither of the factors predicted tolerance or blood pressure reactivity.     

TTC-based risk assessment of tetrachlorobutadienes and pentachlorobutadienes – The in vitro genotoxic contaminants in ground and drinking water

Tetrachlorinated butadienes (TetraCBDs), pentachlorinated butadienes (PentaCBDs) and hexachlorobutadiene (HexaCBD) were detected in groundwater wells of drinking water supplier near Basel up to maximally 157 ng/L (sum value), 15 ng/L (sum value), and <50 ng/L, in 2006. HexaCBD is toxicologically well characterized and the WHO has derived a TDI of 0.2 μg/kg body weight (bw)/day and a drinking-water guideline value of 600 ng/L. However, due to insufficient toxicity data, neither health-based guideline values nor maximum contaminant levels have been established for the TetraCBDs and PentaCBDs yet. Since TetraCBDs and PentaCBDs show structural alerts for potential genotoxicity, the genotoxicity of TetraCBDs and PentaCBDs was examined in vitro. All the TetraCBDs and PentaCBDs as well as HexaCBD were clastogenic in the chromosome aberration test. In addition, 1,1,3,4-TetraCBD and 1,2,3,4-TetraCBD were positive in the Ames test while the other polychlorinated butadienes including HexaCBD were negative. Using the threshold of toxicological concern (TTC) concept, the target value for TetraCBDs and PentaCBDs in drinking water was set at 75 ng/L (sum value of both substance groups). For the main component 1,1,4,4-TetraCBD, which is negative in the Ames, it is recommended to perform a third in vitro genotoxicity test, the HPRT test, before it can be decided whether to refer to the guideline value of HexaCBD at 600 ng/L or still to use the conservative TTC-based target value of 75 ng/L.     

Potentially mutagenic impurities: Analysis of structural classes and carcinogenic potencies of chemical intermediates in pharmaceutical syntheses supports alternative methods to the default TTC for calculating safe levels of impurities

Potentially mutagenic impurities in new pharmaceuticals are controlled to levels with negligible risk, the TTC (threshold of toxicological concern, 1.5 μg/day for a lifetime). The TTC was based on the more potent rodent carcinogens, excluding the highly potent “cohort of concern” (COC; for mutagenic carcinogens these are N-nitroso, Aflatoxin-like, and azoxy structures). We compared molecules with DEREK “structural alerts” for mutagenicity used in drug syntheses with the mutagenic carcinogens in the Gold Carcinogenicity Potency Database. Data from 108 diverse synthetic routes from 13 companies confirm that many “alerting” or mutagenic chemicals are in structural classes with lower carcinogenic potency than those used to derive the TTC. Acceptable daily intakes can be established that are higher than the default TTC for many structural classes (e.g., mono-functional alkyl halides and certain aromatic amines). Examples of ADIs for lifetime and shorter-term exposure are given for chemicals of various potencies. The percentage of chemicals with DEREK alerts that proved mutagenic in the Ames test ranged from 36% to 83%, depending on structural class, demonstrating that such SAR analysis to “flag” potential mutagens is conservative. We also note that aromatic azoxy compounds need not be classed as COC, which was based on alkyl azoxy chemicals.     

A Threshold Regression Mixture Model for Assessing Treatment Efficacy in a Multiple Myeloma Clinical Trial

A first-hitting-time (FHT) survival model postulates a health status process for a patient that gradually declines until the patient dies when the level first reaches a critical threshold. Threshold regression (TR) is a new regression methodology that incorporates the effects of covariates on the threshold and process parameters of this FHT model. In this study, we use TR to analyze data from a randomized clinical trial of treatment for multiple myeloma. The trial compares VELCADE and high-dose Dexamethasone, the former a new therapy and the latter an established therapy for this disease. Patients are switched between the two drugs based on patient response. The novel contribution of this work is the modeling of this clinical trial design using a mixture of TR models. Specifically, we propose a mixture FHT model to fit the survival distribution. The model includes a composite time scale that differentiates the rate of disease progression before and after switching. The analysis shows significant benefit from initial treatment by VELCADE. A comparison is made with a Cox proportional hazards regression analysis of the same data.     

Treating acetaminophen overdose: thresholds,costs and uncertainties

The United Kingdom's Medicines and Healthcare Products Regulatory Agency (MHRA) modified the indications for N-acetylcysteine therapy of acetaminophen (paracetamol) overdose in September 2012. The new treatment threshold line was lowered to 100 mg/L (662 μmol/L) for a 4 hours acetaminophen concentration from the previous 200 mg/L (1325 μmol/L). This decision has the potential to substantially increase overall costs associated with acetaminophen overdose with unclear benefits from a marginal increase in patients protected from hepatotoxicity, fulminant hepatic failure, death, or transplant. Changing the treatment threshold for acetaminophen overdose also implies that ingestion amounts previously thought not to require acetaminophen concentration measurements would need to be revised. As a result, more individuals will be sent to hospitals in order that everyone with a predicted 4 hours concentration above the 100 mg/L line will have concentrations measured and potentially be treated with N-acetylcysteine. Before others consider adopting this new treatment guideline, formal cost-effectiveness analyses need to be performed to define the appropriate thresholds for referral and treatment.     

Partial nerve injury induces electrophysiological changes in conducting (uninjured) nociceptive and nonnociceptive DRG neurons: Possible relationships to aspects of peripheral neuropathic pain and paresthesias

Partial nerve injury leads to peripheral neuropathic pain. This injury results in conducting/uninterrupted (also called uninjured) sensory fibres, conducting through the damaged nerve alongside axotomised/degenerating fibres. In rats seven days after L5 spinal nerve axotomy (SNA) or modified-SNA (added loose-ligation of L4 spinal nerve with neuroinflammation-inducing chromic-gut), we investigated a) neuropathic pain behaviours and b) electrophysiological changes in conducting/uninterrupted L4 dorsal root ganglion (DRG) neurons with receptive fields (called: L4-receptive-field-neurons). Compared to pretreatment, modified-SNA rats showed highly significant increases in spontaneous-foot-lifting duration, mechanical-hypersensitivity/allodynia, and heat-hypersensitivity/hyperalgesia, that were significantly greater than after SNA, especially spontaneous-foot-lifting. We recorded intracellularly in vivo from normal L4/L5 DRG neurons and ipsilateral L4-receptive-field-neurons. After SNA or modified-SNA, L4-receptive-field-neurons showed the following: a) increased percentages of C-, Ad-, and Ab-nociceptors and cutaneous Aa/b-low-threshold mechanoreceptors with ongoing/spontaneous firing; b) spontaneous firing in C-nociceptors that originated peripherally; this was at a faster rate in modified-SNA than SNA; c) decreased electrical thresholds in A-nociceptors after SNA; d) hyperpolarised membrane potentials in A-nociceptors and Aa/b-low-threshold-mechanoreceptors after SNA, but not C-nociceptors; e) decreased somatic action potential rise times in C- and A-nociceptors, not Aa/b-low-threshold-mechanoreceptors. We suggest that these changes in subtypes of conducting/uninterrupted neurons after partial nerve injury contribute to the different aspects of neuropathic pain as follows: spontaneous firing in nociceptors to ongoing/spontaneous pain; spontaneous firing in Aa/b-low-threshold-mechanoreceptors to dysesthesias/paresthesias; and lowered A-nociceptor electrical thresholds to A-nociceptor sensitization, and greater evoked pain.     

Comparison between a new multiplex electrochemiluminescence assay and the WHO reference enzyme-linked immunosorbent assay to measure serum antibodies against pneumococcal serotype-specific polysaccharides

Background

Two electrochemiluminescence (ECL) assays were developed which, together, can simultaneously measure serum antibodies against pneumococcal capsular polysaccharides (PnPS) for 17 serotypes. The assays were validated for the 13 PnPS included in the 13-valent pneumococcal conjugate vaccine (PCV13). As recommended by the World Health Organization (WHO), we compared the ECL assays with the WHO reference enzyme-linked immunosorbent assay (ELISA) and derived a threshold corresponding to the 0.35?µg/mL threshold established for the WHO reference ELISA for the non-inferiority comparison and licensure of new PCVs against invasive pneumococcal disease.

Linear Versus Non-Linear Dose-Response Relationship Between Prenatal Alcohol Exposure and Meconium Concentration of Nine Different Fatty Acid Ethyl Esters

Presence of individual fatty acid ethyl esters (FAEEs) in meconium is considered to be a reliable biomarker of prenatal alcohol exposure, and their concentration has been found to be linearly associated with poor postnatal development, supporting the widely extended idea that ethanol is a non-threshold teratogen. However, a growing number of epidemiological studies have consistently found a lack of adverse short- and long-term fetal outcomes at low exposure levels. We therefore aimed to investigate the relationship between the concentration of individual FAEEs and prenatal alcohol exposure in meconium samples collected within the first 6 to 12?h after birth from 182 babies born to abstainer mothers and from 54 babies born to women who self-reported either light or moderate alcohol ingestion in the second or third trimester of pregnancy. In most cases, the individual FAEE concentrations were negligible and not significantly different (P >0.05) between exposed and control babies. The concentrations appeared to increase linearly with the dose only in the few babies born to mothers who reported >3 drinks/week. These results provide evidence that the correlation between prenatal alcohol exposure and individual FAEE concentrations in meconium is non-linear shape, with a threshold probably at 3 drinks/week.