Naltrexone modifies the palatability of basic tastes and alcohol in outbred male rats.

Naltrexone, an opioid antagonist, has been shown to reduce the palatability of 10% alcohol solutions in rats, as measured by taste reactivity. In the present study, the effect of acute naltrexone treatment on taste reactivity to a variety of taste solutions and concentrations was tested to determine whether naltrexone has generalized effects on taste responsiveness. Thirty minutes before a taste reactivity test, rats were injected with either naltrexone (3 mg/kg; n = 15) or saline (n = 15). On separate days, rats were tested with distilled water and three concentrations each of sucrose (0.1, 0.5, and 1.0 M), sodium chloride (0.06, 0.10, and 0.30 M), quinine hydrochloride (0.0005, 0.001, and 0.005 M), and alcohol [10%, 20%, and 40% (vol./vol.)]. In Experiment 1, naltrexone consistently reduced the palatability of alcohol and sodium chloride solutions (across concentrations), as reflected by a decrease in ingestive responding and an increase in aversive responding. Naltrexone increased aversive responding for sucrose but did not affect ingestive responding for these solutions. Finally, there was no significant effect of naltrexone on responding to quinine hydrochloride. A second experiment with naive rats and five concentrations of sucrose (0.01, 0.05, 0.1, 0.5, and 1.0 M) replicated the initial data: Across concentrations, naltrexone produced a significant increase in aversive responding but did not alter ingestive responding. In Experiment 3, naive rats were tested with five concentrations of quinine hydrochloride (0.00001, 0.00005, 0.0001, 0.0005, and 0.005 M). Results indicated that naltrexone significantly altered taste reactivity to the bitter solutions (less ingestive responding and more aversive responding), particularly at the lower concentrations. The results indicate that naltrexone treatment has significant effects on taste reactivity to some aqueous solutions (alcohol, sodium chloride), regardless of solution concentration. The effects of naltrexone on sucrose and quinine reactivity are more difficult to describe because the drug effects seemed to be dependent on the specific measure examined (ingestive vs. aversive responses) and the concentration of the solution. These results support the suggestion that naltrexone has a fairly generalized effect on taste reactivity to taste solutions; specifically, naltrexone seems to make solutions more aversive, as revealed by a decrease in ingestive responding and an increase in aversive responding.     

Minimum duration of light signals capable of producing the Aschoff effect

To further explore the validity of the non-parametric model of entrainment for predicting the phase-shifting effects of light pulses, we exposed rats to several intensities of continuous light (LL) and feedback lighting (LDFB). LDFB is a lighting condition that exposes the animal to light only during the interval of active locomotion; this interval is coincident with the photosensitive portion of the circadian cycle as defined by the phase-response-curve. This is achieved by linking lights on with locomotor activity. In addition to the comparison of LL with LDFB, the duration of the LDFB pulse was also varied in four rats. Whether rats were exposed to LL or LDFB, as light intensity increased, the free-running period (tau) of the locomotor activity rhythm also increased. This intensity-related increase in tau, which is known as the Aschoff effect, was similar for LL and LDFB 2 min at each light intensity (0.1, 1, and 100 lux). However, when the LDFB pulses were shortened from a duration of 2 min to a duration of approximately 1 sec, tau shortened significantly. These results demonstrate that the non-parametric model of entrainment adequately explains the major period-lengthening effects of LL. However, there are temporal limits to the light pulses that can be used to simulate the effects of LL (i.e., one second light pulses fail to produce the effects brought about by longer pulses).     

Brain gamma-aminobutyric acid abnormality in tardive dyskinesia. Reduction in cerebrospinal fluid GABA levels and therapeutic response to GABA agonist treatment

A double-blind, placebo-controlled trial of gamma-vinyl gamma-aminobutyric acid (GVG) and 4,5,6,7-tetrahydroisoxazolo-(5,4-c) pyridine-3-ol (THIP) was carried out in drug-free schizophrenic patients with tardive dyskinesia. A significant decrease in dyskinetic symptoms occurred with the administration of GVG, associated with a twofold increase in cerebrospinal fluid levels of GABA; THIP produced a more moderate, yet consistent decrease in the involuntary movements. A pathophysiologic role for gamma-aminobutyric acid (GABA)-mediated neuronal transmission in tardive dyskinesia was explored by analyzing cerebrospinal fluid GABA concentrations in drug-free schizophrenic patients with and without tardive dyskinesia. A significant reduction in cerebrospinal fluid levels of GABA was observed in the dyskinetic schizophrenics compared with the nondyskinetic controls. These data compliment a growing body of experimental evidence suggesting a critical role for GABA-ergic neurons in the pathophysiology of tardive dyskinesia.     

Cosegregation of hypertrophic cardiomyopathy and a fragile site on chromosome 16 in a large Italian family.

We studied the karyotypes of 10 members of a family in whom hypertrophic cardiomyopathy is segregating as an autosomal dominant trait. In all those affected by the disease, a fragile site on the long arm of chromosome 16 was found, expressed with different frequencies, but the unaffected family members did not show this trait.     

Developing a competency-based orientation program: the challenge of a multidisciplinary pediatric unit

In today's era of specialization, preparing novice nurses to assume care of infants, children, and adolescents in a multidisciplinary pediatric unit can be a formidable challenge, and until now, the nursing literature has lacked reference to a pediatric competency-based orientation program. This article discusses both the process and outcome of developing a pediatric competency-based orIEntation program for the Cleveland Clinic Foundation. Competency statements, documentation forms, sample learning tools, and recommendations for revision are provided to enhance reader utilization.     

Nigral influence on focal epilepsy

The substantia nigra (SN) has been proposed as a structure involved in epileptiform phenomena. Previous investigations demonstrated that SN is able to elicit hippocampal rhythmic slow activity (RSA) as well as to inhibit hippocampal interictal spikes induced by parenteral administration of penicillin. The present series of experiments was carried out in order to characterize the action of SN on a focal model of hippocampal epilepsy. Experiments were performed on encéphale isolé cats in which steady epileptiform activity was induced by locally applied penicillin. Electrical stimulation of SN pars reticulata (pr) caused a statistically significant decrease of hippocampal spike frequency and amplitude in 30% of the total number of stimulation sessions. Stimulation of SN pars compacta (pc) was even more effective. It induced inhibitory effects on hippocampal spikes in 91% of the cases. In 30% of the cats, RSA was noted on hippocampal recordings in correspondence to nigral activation. Experimental data support the hypothesis that the SNpc influences hippocampal excitability: a differential role may be played by SNpc and SNpr in the control of seizure processes.     

Comparative in-vitro activity of A-56268 (TE-031), a new macrolide antibiotic

The comparative in-vitro activity of A-56268 (TE-031), a new semisynthetic macrolide antibiotic, was assessed against approximately 400 bacterial isolates. The new drug demonstrated excellent activity against penicillin-susceptible streptococci (MIC90s less than or equal to 0.06 mg/l) and methicillin-susceptible staphylococci (MIC90 = 0.25 mg/l). Among other Gram-positive organisms tested, a significant number were resistant to A-56268 as well as to erythromycin and clindamycin. A-56268 was at least as active as erythromycin against Pasteurella multocida and Campylobacter jejuni, but was more active than erythromycin against Legionella spp. (MIC90 less than or equal to 0.06 mg/l), Bacteroides fragilis (MIC90 = 4 mg/l) and Bact. melaninogenicus (MIC90 less than or equal to 0.125 mg/l). Activity of A-56268 was pH dependent (more active at pH 7 than at pH 6) and was moderately affected by inoculum size. The drug was bactericidal against two strains of Streptococcus pyogenes tested, but exerted a bacteriostatic effect against Staphylococcus aureus and Str. faecalis.     

Lipoma causing a posterior interosseous nerve syndrome

. Posterior interosseous nerve syndrome is an entrapment neuropathy of the deep terminal branch of the radial nerve – the posterior interosseous nerve – at the radial tunnel. Radial neuropathy without prior injury or other obvious etiology occurs frequently. However, sometimes previous trauma, surgery, or tumors over the radial nerve contribute to chronic entrapment and can produce the classic syndrome. In this report we describe an unusual case of a 68-year-old-woman with a chronic posterior interosseous nerve syndrome due to a lipoma. The patient had poor recovery after surgery, despite splinting and rehabilitation physiotherapy, mainly because of the long duration (2 years) and severity of the compression neuropathy.     

Synergisms between different activation pathways in adult and aged human lymphocytes

The present report investigates the synergistic effects of different agents (phytohaemoagglutinin (PHA), anti-CD3, phorbol-12-myristate-13-acetate (PMA) and Ionomycin on T cell activation. Results indicate that in normal lymphocytes PMA causes a dose-dependent decrease of PHA-induced blastogenesis and a marked enhancement of anti-CD3-induced 3H-thymidine uptake. There is positive synergism when cells are costimulated with PMA and the calcium ionophore Ionomycin. These data show that phorbol esters can exert either positive or negative synergisms depending on the experimental conditions. We also studied the simultaneous stimulation with PHA and anti-CD3 which gives an addictive effect for the minimal doses of the two stimuli, and an appreciable negative synergism for their highest concentrations. In order to evaluate T lymphocyte functions in the age-associated immune defect, PHA plus anti-CD3 and PMA plus Ionomycin costimulation assays were applied to a population of healthy elderly subjects. An additive effect is found after costimulation with the highest doses of PHA and anti-CD3, at variance with the negative synergism found in younger adult controls. Following costimulation with PMA plus Ionomycin, elderly subjects also display an impaired response, as compared to adult controls. No correlation was found with PHA-, anti-CD3- and PMA plus Ionomycin-induced T cell proliferation. These results underline the complexity of age-associated immune defects and suggest that alterations in different mechanisms of lymphocyte activation are responsible for the immune deficiency of aging.