Auditory brainstem responses after out-of-hospital cardiac arrest: Are they useful for outcome prediction?

We evaluated whether we could predict the neurologic outcome in 55 out-of-hospital cardiac arrest patients using auditory brainstem responses (ABR). ABR patterns were classified into one of 3 types by evaluation of 5 components: type 1, with all 5 components; type 2, lack of at least one response between the 2nd and 5th components; type 3, with only the first component or no response. The relation between the ABR patterns on the 3rd day following resuscitation and the neurologic outcome on hospital discharge was evaluated. The specificity that the 5 awake patients had type-1 ABR was 38%. The sensitivity that the 10 brain dead patients had type-3 ABR was 60%. In the type-1 ABR patients, the negative predictive value that the patients were awake was 100%. In the type-3 ABR patients, the negative predictive value that the patients became brain dead was 90.9%. These results suggest that ABR on the 3rd post-resuscitation day may not be useful for predicting if patients are awake or become brain dead, although the loss of components may be a sign of morbidity, and the presence of the 2nd or later components indicates possible future prevention of brain death.     

Immunological responses to pneumococcal vaccine in frail older people

Advanced age has been associated with a wide range of defects in both the innate and adaptive immune systems including diminished specific antibody responses that increase the risk of invasive pneumococcal disease (IPD) and limit the effectiveness of vaccines. However, the elderly are a heterogeneous group and measures of overall frailty may be a better indicator of disease susceptibility (or vaccine response) than chronological age alone.     

Fisher information matrix for nonlinear mixed effects multiple response models: Evaluation of the appropriateness of the first order linearization using a pharmacokinetic/pharmacodynamic model

We focus on the Fisher information matrix used for design evaluation and optimization in nonlinear mixed effects multiple response models. We evaluate the appropriateness of its expression computed by linearization as proposed for a single response model. Using a pharmacokinetic–pharmacodynamic (PKPD) example, we first compare the computation of the Fisher information matrix with approximation to one derived from the observed matrix on a large simulation using the stochastic approximation expectation–maximization algorithm (SAEM). The expression of the Fisher information matrix for multiple responses is also evaluated by comparison with the empirical information obtained through a replicated simulation study using the first‐order linearization estimation methods implemented in the NONMEM software (first‐order (FO), first‐order conditional estimate (FOCE)) and the SAEM algorithm in the MONOLIX software. The predicted errors given by the approximated information matrix are close to those given by the information matrix obtained without linearization using SAEM and to the empirical ones obtained with FOCE and SAEM. The simulation study also illustrates the accuracy of both FOCE and SAEM estimation algorithms when jointly modelling multiple responses and the major limitations of the FO method. This study highlights the appropriateness of the approximated Fisher information matrix for multiple responses, which is implemented in PFIM 3.0, an extension of the R function PFIM dedicated to design evaluation and optimization. It also emphasizes the use of this computing tool for designing population multiple response studies, as for instance in PKPD studies or in PK studies including the modelling of the PK of a drug and its active metabolite. Copyright © 2009 John Wiley & Sons, Ltd.     

Human recombinant erythropoietin directly stimulates B cell immunoglobulin production and proliferation in serum-free medium.

The effect of human recombinant erythropoietin (Epo) on B cell responses was studied in a serum-free medium. Epo enhanced IgM production and thymidine uptake by a human IgM-producing lymphoblastoid cell line, CBL. This effect was specific to Epo since enhancement was blocked by anti-Epo antibody but not by control antibody. Among the various cytokines, interleukin-4 (IL-4) enhanced IgM production and thymidine uptake while IL-6 enhanced IgM production without affecting thymidine uptake. In contrast, other cytokines including IL-1 beta, IL-2, IL-5, interferon-alpha (IFN-alpha), interferon-gamma (IFN-gamma), or granulocyte/macrophage colony-stimulating factor (GM-CSF) were without effect. However, the enhancing effect of Epo is different from that of IL-4 or IL-6, since Epo effect was not blocked by anti-IL-4 antibody or anti-IL-6 antibody. Moreover, specific binding of Epo was detected on CBL cells. Epo also enhanced immunoglobulin (IgG, IgM and IgA) production and thymidine uptake by purified tonsil small resting B cells stimulated by Staphylococcus aureus Cowan strain I (SAC) or by large activated B cells. In contrast, Epo had no effect on unstimulated small resting B cells. These results indicate that Epo could directly stimulate activated and differentiated B cells and could enhance B cell immunoglobulin production and proliferation.     

Monkey hippocampal neuron responses to complex sensory stimulation during object discrimination.

The purpose of this study was to investigate, during the performance of an object discrimination task, responses of neurons in the monkey hippocampal formation to the sight of several objects that have biological meaning, and compare these responses with those of amygdalar neurons studied previously using the same task. Neuronal activity in the hippocampal formation of conscious monkeys was recorded during performance of a task that led to presentation of familiar rewarding, familiar aversive, or unfamiliar objects. Of 864 neurons recorded in the hippocampal formation and adjacent cortices, 160 (18.5%) responded to the sight of a certain object(s). Responses to the sight of different kinds of objects were analyzed in detail. Nondifferential neurons (n = 73) responded to different objects with no significant difference in response magnitudes, and differential neurons (n = 87) responded to different objects with different response magnitudes. Of the differential neurons, 23 responded more strongly to rewarding objects than to other objects (rewarding-object-dominant neurons), but the magnitude of responses to objects did not necessarily correlates with the order of preferences to the objects as determined from observation of animal behavior. Aversive-object-dominant neurons (n = 13) responded more to aversive objects than to other objects. Unfamiliar-object-dominant neurons (n = 7) responded more to unfamiliar objects than to familiar objects. Selective neurons (n = 10) responded selectively to only one object or one category of objects. Fourteen of the rewarding- or averse-object-dominant neurons were tested in extinction or reversal trials. In 12 of 14 neurons, responses to a rewarding or aversive object did not change, or slightly weakened, in extinction or reversal trials. The results suggest the following. (1) Responses of rewarding- or aversive-object-dominant neurons may be involved in object-reward or object-aversion association. However, responses of many of these neurons might reflect past inputs to reinforcement rather than extant emotional processing. (2) Responses of unfamiliar-object-dominant neurons may be involved in recognition of objects based on their familiar or unfamiliar aspects. These results are further discussed and compared with responsiveness of amygdalar neurons.     

氟乙酰胺的极谱测定法

目的建立微量氟乙酰胺的极谱分析法。方法应用氟乙酰胺在高温强碱条件下的分解反应,利用极谱法对其分解产物形成的ALC-La-F-三元络合物在pH=4.90的含KNO3的六次甲基四胺缓冲液中的-0.67V处的络合物吸附波进行测定。结果在所选定的最佳条件下,氟乙酰胺的线性范围为5.0×10-8～1.2×10-6mol/L,回归方程y=3.49x+0.042,相关系数r=0.9996,方法的检测下限为2.0×10-8mol/L。结论该法可用于测定面粉中的氟乙酰胺。     

Trauma-Related Dissociative States and Long-Term Psychopathology in Posttraumatic Stress Disorder

Dissociative responses to trauma have been hypothesized to be associated with long-term increases in psychopathology. The purpose of this study was to examine dissociative responses to premilitary, combat-related and postmilitary traumatic events and long-term psychopathology in Vietnam combat veterans with (n = 34) and without (n = 28) posttraumatic stress disorder (PTSD). PTSD patients reported higher levels of dissociative states at the time of combat-related traumatic events than non-PTSD patients. Higher levels of dissociative states persisted in PTSD patients in the form of higher levels of dissociative states in response to postmilitary traumatic events. In addition, dissociative responses to combat trauma were associated with higher long-term general dissociative symptomatology as measured by scores on the Dissociative Experience Scale, as well as increases in the number of flashbacks since the time of the war. These findings are consistent with previous formulations that dissociation in the face of trauma is a marker of long-term psychopathology.     

Validity and ethics of penile circumference measures of sexual arousal: A reply to McConaghy

McConaghy (1989) argued that the validity of penile circumference responses (PCRs) is at best unestablished and that penile volume responses (PVRs) have been demonstrated to be clearly superior indices of sexual arousal and orientation. In his critique, McConaghy stated that (i) penile erection has been incorrectly identified with sexual arousal, (ii) that PCRs have not been shown to accurately discriminate between divergent patterns of sexual arousal (including paraphilias), (iii) that the methodologies used to compare the two types of transducers are inappropriate, and (iv) that PCRs should not be used for diagnostic and treatment decisions. In this paper, McConaghy's criticisms are reviewed in the context of the existing literature on the subject. Although PCRs and PVRs involve different methodologies, they generally yield results that bear more similarities than differences. Furthermore, there is an extensive and growing literature on the use of PCR measures with various paraphilias. Several of McConaghy's arguments should be considered tentative while others are clearly unsubstantiated. Most of McConaghy's concerns over the validity and uses of PCR measures are empirical questions. Suggestions for future research are offered.