The Rett syndrome: progress report on studies at the Kennedy Institute

Clinical, biochemical and pathological studies in patients with the Rett syndrome (RS) are presented. The neuropathological changes and alterations in neurotransmitter markers are particularly interesting and provide valuable information that may be helpful in understanding the behavior and neurological phenotype of RS.     

Palliative care development in South America: a focus on Argentina

Many Latin American and Caribbean national health systems mainly focus on disease prevention, prenatal assistance, undernourishment, etc. They still do not have the conditions for developing palliative care (PC). In general, quality of life during the dying process is poor, with fragmented assistance, uncontrolled suffering, poor communication between professionals, patients, and families, and a great burden on family caregivers. The development of PC in the region started around 1981, but it is still not available to an acceptable number of patients.     

The neural mechanisms underlying cholinergic celldeath within the basal FOREBRAIN

The basal forebrain region includes a large group of cholinergic neurons within themedial septal area and nucleus basalis magnocellularis (NBM) that project to the hippocampusand throughout the neocortex, respectively. This chapter will consider the mechanisms thatinfluence why cholinergic cells within the NBM die and discuss studies that have manipulated thefeatures of these cells that could make them differentially vulnerable to degeneration with agingand Alzheimer^fn3s Disease (AD). This chapter will focus upon the NBM cholinergic system because thisregions typically demonstrates a greater degree of cell loss with aging and AD.     

Population pharmacokinetics of tobramycin.

1. Population pharmacokinetic parameters of tobramycin were determined in a heterogenous group of 97 patients using serum samples drawn for the routine monitoring of tobramycin concentrations, following multiple dosing regimens. 2. To describe the accumulation kinetics of tobramycin a two-compartment pharmacokinetic model was required. The best fit to the data was obtained when drug clearance (1 h-1) was related linearly to creatinine clearance (proportionality constant: 0.059 +/- 0.002 x CLcr (ml min-1)) and initial volume of distribution (1) was related linearly to body weight (proportionality constant: 0.327 +/- 0.014 x body weight (kg)). The intersubject variability in these two parameters was 32% and 3%, respectively, whilst the residual or intrasubject variability amounted to 21% of the tobramycin concentration. The terminal half-life of tobramycin, 26.6 +/- 9.4 h, was appreciably shorter than previously reported. 3. The population pharmacokinetic model was validated against data obtained from 34 independent patients and the predicted and observed concentrations were found to be in good agreement. The population pharmacokinetic model was used to design a priori dosing recommendations for tobramycin.     

An anatomic study of the external laryngeal framework with surgical implications.

Precise knowledge of the level of the vocal fold as projected on the external thyroid cartilage is of critical importance for the performance of thyroplasty type I and supraglottic laryngectomy. Measurements of the external laryngeal framework were made on the larynges of 18 human cadavers in order to identify landmarks that will aid the surgeon in determining endolaryngeal anatomy. On the basis of our results, the following guidelines are recommended: (1) Thyroid cartilage incision for supraglottic laryngectomy should be made on a line joining the juncture of the upper one third and lower two thirds of the midline length and the juncture of the upper one third and lower two thirds of the oblique line. This will ensure a position above the level of the anterior commissure and the true vocal cord; (2) In thyroplasty type I, the superior border of the thyroid cartilage window should be made at a line joining the midpoint of the midline length and the juncture of the upper two thirds and lower one third of the oblique line. Formation of the cartilage window according to this guideline will ensure its placement lateral to the vocalis muscle.     

Effects of excitatory amino acid lesions upon neurokinin B and acetylcholine neurons in the nucleus basalis of the rat

The nucleus basalis magnocellularis (NBM) contains cholinergic neurons that project to the neocortex and is densely innervated by excitatory amino acid-containing terminals. A dysfunction in the balance of excitatory inputs or an alteration in the sensitivity of NBM cells to glutamate may underlie the selective vulnerability to aging. Some large NBM neurons contain neurokinin B (NKB) mRNA. The present study investigated whether α-2-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) orN-methyl-d-aspartate (NMDA) differentially destroy NKB-containing, NKB-receptive, or cholinergic NBM cells, and whether this vulnerability is altered by aging. Injections of AMPA or NMDA significantly decreased neocortical ChAT activity, as compared to control levels, across all three age groups, with no interaction between lesion and age group. The results of in situ hybridization histochemistry and NKB receptor studies suggest that NKB-containing neurons in the NBM, and the neurons they innervate, are not vulnerable to NMDA or AMPA in either young or old rats. While NKB mRNA-positive cells were diffusely distributed throughout the basal forebrain, only a small proportion of the large NBM cells contained NKB mRNA. The results suggest that NKB does not extensively colocalize with acetylcholine within the basal forebrain of rats and that NBM NKB neurons do not directly innervate cholinergic cells.     

Cadmium carcinogenesis in male Wistar [Crl:(WI)BR] rats: dose-response analysis of effects of zinc on tumor induction in the prostate, in the testes, and at the injection site

The ability of zinc acetate to modify the carcinogenic effects of CdCl2 in male Wistar [Crl:(WI)BR] rats was studied over a 2-year period. Groups of rats received a single s.c. injection of Cd (30.0 mumol/kg) in the dorsal thoracic midline or i.m. in the right thigh at time 0. Zinc was given in three separate s.c. doses of 0.1, 0.3, or 1.0 mmol/kg (at -6, 0, and +18 h relative to cadmium) in the lumbosacral area or p.o. at 100 ppm in the drinking water (-2 to +100 weeks). Cadmium treatments (s.c.) resulted in the appearance of tumors at the injection site and in the testes. The incidence of s.c. injection site tumors (mostly mixed sarcomas) was markedly reduced by high dose (1.0 mmol/kg) s.c. zinc (50% reduction) and was almost abolished by p.o. zinc (92% reduction). Testicular tumors (mostly Leydig cell adenomas) induced by s.c. cadmium were reduced in a dose-related fashion by zinc and were found to be highly dependent on the ability of zinc to prevent the chronic degenerative effects of cadmium in the testes. Oral zinc had no effect on s.c. cadmium-induced testicular tumors, while i.m. cadmium alone did not induce these tumors. In rats in which s.c. cadmium-induced testicular tumors and chronic degenerative effects were prevented by zinc (1.0 mmol/kg, s.c.), a marked elevation in prostatic tumors (exclusively adenomas) occurred (control, 9.6%; cadmium plus high zinc 29.6%). Cadmium given i.m., which did not result in testicular tumors or degeneration, also induced an elevated incidence (42.3%) of prostatic tumors, again indicating a dependence on testicular function. Prostatic tumor incidence was also significantly elevated (25.0%) in rats receiving 1.0 mmol/kg zinc, s.c., in combination with i.m. cadmium. These results indicate that zinc inhibition of cadmium carcinogenesis is a complex phenomenon, depending not only on dose and route but also on the target site in question.     

Basal forebrain lesions produce a dissociation of trial-dependent and trial-independent memory performance

The behavioral effects of lesions in the basal forebrain (BF) of rats were evaluated using two tasks. The BF lesions included both the nucleus basalis magnocellularis (NBM) and the medial septal area (MSA). The first task was a Stone maze, which has 14 consecutive choice points and is a task of complex, trial-independent memory. BF lesions did not impair choice accuracy in this task. The second task was a win-shift spatial discrimination in a radial arm maze, which requires trial-dependent memory. BF lesions produced a significant decrease in choice accuracy in this task. These results demonstrate that BF lesions impair trial-dependent (working) memory but not trial-independent reference memory, and that task difficulty is not the sole factor determining whether BF lesions produce behavioral impairments.