Residual inhibition: From the putative mechanisms to potential tinnitus treatment.

Neurons in various sensory systems show some level of spontaneous firing in the absence of sensory stimuli. In the auditory system spontaneous firing has been shown at all levels of the auditory pathway from spiral ganglion neurons in the cochlea to neurons of the auditory cortex. This internal "noise" is normal for the system and it does not interfere with our ability to perceive silence or analyze sound. However, this internal noise can be elevated under pathological conditions, leading to the perception of a phantom sound known as tinnitus. The efforts of many research groups, including our own, led to the development of a mechanistic understanding of this process: After cochlear insult the input to the central auditory system becomes markedly reduced. As a result, the neural activity in the central auditory system is enhanced to compensate for this reduced input. Such hyperactivity is hypothesized to be interpreted by the brain as a presence of sound. This implies that suppression of hyperactivity should reduce/eliminate tinnitus. This review explores research from our laboratory devoted to identifying the mechanism underlying residual inhibition of tinnitus, a brief suppression of tinnitus following a sound stimulus. The key mechanisms that govern neural suppression of spontaneous activity in animals closely resemble clinical psychoacoustic findings of residual inhibition (RI) observed in tinnitus patients. This suppression is mediated by metabotropic glutamate receptors (mGluRs). Lastly, drugs targeting mGluRs suppress spontaneous activity in auditory neurons and reduce/eliminate behavioral signs of tinnitus in mice. Thus, these drugs are therapeutically relevant for tinnitus suppression in humans.

Use of solvents to enhance PAH biodegradation of coal tar-contaminated soils.

Bioremediation of coal tar-contaminated soils containing polycyclic aromatic hydrocarbons (PAHs) is highly challenging because of the low solubility and strong sorption properties of PAHs. Five coal tar-contaminated soils from former manufactured gas plant (MGP) sites were pretreated with two solvents, acetone and ethanol to enhance the bioavailability of the PAH compounds. The biodegradation of various PAHs in the pretreated soils was assessed using soil slurry reactors. The total PAH degradation rates for soils pretreated with solvents were estimated to be about two times faster than soils that were not pretreated with solvents. For example, the total PAH first order degradation rate constants were 0.165+/-0.032, 0.147+/-0.020, and 0.076+/-0.009 day(-1) for Vandalia (EXC) soil that were pretreated with acetone, ethanol, and with no solvent, respectively. A distinctive advantage for soils pretreated with solvents was the enhanced removal of 5-ring PAH compounds such as benzo(a)pyrene and to a limited extent 4-ring compounds such as chrysene. Even for soils with 3.5% or more organic carbon content (two soils out of five), the degradation rate constants of chrysene were found to be two times faster than soils that were not pretreated. The degradation rate constants of benzo(a)pyrene were enhanced by 2-6 times for all five contaminated soils that were pretreated with solvents. To further elucidate trends that control the solvent treatment, the percent improvement in degradation rate constants (100 x rate constants for pretreated soils/rate constants for non-treated soils) for 16 PAHs were found to correlate well with the PAH partition coefficients (K(oc)). Except for phenanthrene and the clay fraction of the soil, correlations between the percent improvement in degradation rates constants and several physical properties of the soils were poor and sporadic. This implies that the enhancement in PAH availability using solvent treatment was driven by the distribution of the PAHs between the solvent and the adsorbed PAHs.

Parent and nurse perceptions of parent stressors in the pediatric intensive care unit.

This study examined parent and nurse perceptions of parent stressors in a pediatric intensive care unit using the Parental Stressor Scale: Pediatric Intensive Care Unit (PSS:PICU) and standardized interviews of parents. A total of 41 parents and 34 nurses participated. Nurses expected parents to be more stressed by every dimension of the PSS:PICU than parents rated their own stress. Parents felt most stressed by the dimension relating to their child's behavioral and emotional responses, although nurses expected parents to be most concerned about staff communication and parental role alteration issues. Implications for clinical practice are discussed.

Regulatory aspects of fire toxicology.

Fire creates a complex toxic environment involving flame, heat, oxygen depletion, smoke, and toxic gases. The nature of that environment is dependent upon not only the materials present but on the fire event, that is, the fire scenario. Materials have different toxic gas profiles under different conditions; therefore, toxic fire gas generation is not intrinsic to any one material. Large fires in buildings constitute a severe toxic threat regardless of the materials being burned. In the past, building codes in the United States included the phrase, "no more toxic than wood," in reference to fire gases from building materials. Such phrases have recently been deleted, because of the lack of either an accepted definition or test methodology to assess toxicity. While several states have attempted regulatory activity, the most recent approach (taken by the state of New York) has been the establishment of a data bank on toxic potency of building and furnishing materials. The utility of such a data bank without available hazard analysis methodology is open to discussion, since toxic potency data are not directly applicable to toxic hazard assessment. A number of small-scale animal exposure tests have been developed to assess the potency of the toxic combustion products from combustible materials. Criticism of these tests relates to the relevance of the combustion module (a smoke generation apparatus) and the appropriateness of the animal model, particularly for irritant gases. Recent data from more than 2000 fire fatality cases and carbon monoxide exposure cases are discussed in this paper to help put small-scale laboratory test results into perspective. Toxicity is only one of the several fire properties related to materials. All fire parameters are interrelated, that is, they are not independent variables. Thus, predicting the toxicity of burning materials is a problem without a comprehensive solution. Measures have been taken, however, to reduce the number of fires and to reduce fire severity.

Coordinated treatment for long-term psychiatric inpatients.

Attempts to implement and maintain effective treatment of long-term psychiatric inpatients are difficult. In this article the authors describe a treatment program in which behavior modification, milieu therapy, and education strategies directed at teaching specific skills are combined in a coordinated system of steps.

Multiple-baseline analysis of a token economy for psychiatric inpatients.

Twelve behaviors selected for reinforcement among 16 chronic psychiatric inpatients were divided into four classes: (a) personal hygiene, (b) personal management, (c) ward work, and (d) social skills. A token economy program was introduced for each class in a sequential, cumulative, multiple-baseline format. Corrections were included for methodological deficiencies frequently enountered in past studies. Treatment variables were systematically monitored, and target behavior rates, levels of global individual functioning, general ward behavior, and off-ward behavior were assessed during baseline, implementation, and probe periods. Results indicated abrupt and substantial increases in performance of most target behaviors, significant improvements in global individual functioning (p less than .025), positive changes in general ward behavior, and increases in social interaction during off-ward activities. The findings provide strong evidence for the efficacy of a token economy and indicate that the multiple-baseline design can be a useful method for evaluating token economy programs.

Synthesis and antiarrhythmic activity of substituted (2-pyrimidinylthio)acetamidoximes.

A series of (2-pyrimidinylthiomethyl)carbonitriles and -carboxamidoximes was synthesized and the antiarrhythmic effects were evaluated against ventricular arrhythmias as measured by the electrical fibrillatory threshold in the anesthetized dog. Structure-activity studies indicated 2-[4-(p-chlorobenzylamino)-6-methyl-2-pyrimidinylthio]acetamidoxime dihydrochloride (6a) and 2-[4-(1,3-benzodioxol-5-ylmethylamino-6-propyl-2-pyrimidinylthio]acetamidoxime (6g) to be the most potent members of the series.

Training correct utensil use in retarded children: modeling vs. physical guidance.

Modeling and physical guidance were compared for teaching 24 retarded males (mean age = 13.5, mean IQ = 25.3) to use a knife, fork, and spoon. Initial premeal training methods resulted in no improvement over baseline. The methods were revised to extend throughout meals, and a third method (physical guidance with praise) replaced a former control procedure. Methods involving physical guidance produced significant improvement while modeling did not. All groups then received physical guidance with praise which resulted in their achieving similar levels of performance. Follow-up observations revealed that correct utensil use continued under maintenance conditions.