Changes in the impulse activity of neurons of the human thalamic ventrolateral nucleus during voluntary movement

Functional differences were revealed in evoked activity of two types (A and B) of units of the human thalamic ventro-lateral nucleus (VL). Collective activities of these polyfunctional neurons were selectively related to triggering and execution phases of movement. Common character of dynamics of the responses seems to be due to similar polyfunctional nature as well as to the functional role of these two complementary elements in the motor signal transmission. The collective activities reflect in the VL the integrative processes related to processing and programming of generalised parameters of motor signals, but unrelated to performance of a concrete motor act.     

Long-term follow-up of an EORTC randomized prospective trial comparing intravesical bacille Calmette-Guérin-RIVM and mitomycin C in superficial bladder cancer. EORTC GU Group and the Dutch South East Cooperative Urological Group. European Organisation for Research and Treatment of Cancer Genito-Urinary Tract Cancer Collaborative Group

Posterior laryngeal clefts (PLCs) are described in the literature as rare laryngeal abnormalities. The authors believe type I clefts are much more common than previously reported. In two busy pediatric tertiary care centers, such clefts are the second most common congenital laryngeal finding at rigid endoscopy, second only to laryngomalacia. PLCs frequently present with symptomatology that can be attributed to other common disease processes and are often undiagnosed unless the surgeon maintains a high index of suspicion and specifically examines the posterior glottis by palpation during microlaryngoscopy. This report presents a series of 41 patients with type I PLCs, reviews their subtle and often confusing presenting signs and symptoms, and describes a simple yet reliable method of diagnosis.     

Pharmacokinetics of a single dose of teicoplanin in burn patients

Patients with severe burns are susceptible to infection with Gram-positive organisms including methicillin-resistant Staphylococcus aureus, and often require higher antibiotic dosages compared with other patients. This study examined the pharmacokinetics of a single iv dose of teicoplanin (12 mg/kg) in 15 adults and five children with severe burns. Adults were aged 21-82 years with a median total body surface area (TBSA) burn of 30% (range 15-60%). Children were aged 10 months-l0 years with median TBSA burn of 15% (10-30%). At 12 h, the median serum teicoplanin concentration was 12.8 mg/L (9.027.1 mg/L) in adults and 7.6 mg/L (6.6-l0.8 mg/L) in children, (P < 0.01); at 24 h, the corresponding values were 8.3 mg/L (4.6-l2.9 mg/L) and 5.2 mg/L (4.2-6.0 mg/L). Using a three-compartment model, the median terminal half life in adults was 114 h (47-278 h). Children fitted a two-compartment model with a terminal half-life of 38 h (2l-41 h). The median concentration of teicoplanin in fluid from the burn wound was 60% of the serum antibiotic concentration. A single iv dose of 12 mg/kg of teicoplanin was sufficient to produce therapeutic serum concentrations in burn patients for 24 h, but monitoring of antibiotic levels in serum may be advisable in those with high total clearance, especially children.     

The impact of an exocyclic cytosine adduct on DNA duplex properties: significant thermodynamic consequences despite modest lesion-induced structural alterations

The exocyclic base adduct 3,N4-deoxyethenocytosine (epsilonC) is a common DNA lesion that can arise from carcinogen exposure and/or as a biproduct of cellular processes. We have examined the thermal and thermodynamic impact of this lesion on DNA duplex properties, as well as the structural alterations imparted by the lesion. For these studies, we used calorimetric and spectroscopic techniques to investigate a family of 13-mer DNA duplexes of the form (5'CGCATGNGTACGC3')x(3'GCGTACNCATGCG5'), where the central NxN base pair represents the four standard Watson-Crick base pairs (corresponding to four control duplexes), and where either one of the N bases has been replaced by epsilonC, yielding eight test duplexes. Studies on these 12 duplexes permit us to assess the impact of the epsilonC lesion as a function of sequence context. Our spectroscopic and calorimetric data allow us to reach the following conclusions: (i) The epsilonC lesion imparts a large penalty on duplex stability, with sequence context only modestly modulating the extent of this lesion-induced destabilization. This result contrasts with our recent studies of duplexes with abasic sites, where sequence context was found to be the predominant determinant of thermodynamic damage. (ii) For the epsilonC-containing duplexes, sequence context effects are most often observed in the enthalpic contribution to lesion-induced duplex destabilization. However, due to compensating entropies, the free energy changes associated with this lesion-induced duplex destablization are nearly independent of sequence context. (iii) Despite significant lesion-induced changes in duplex energetics, our spectroscopic probes detect only modest lesion-induced changes in duplex structure. In fact, the overall duplex maintains a global B-form conformation, in agreement with NMR structural data. We discuss possible interpretations of the apparent disparity between the severe thermodynamic and relatively mild structural impacts of the epsilonC lesion on duplex properties. We also note and discuss the implications of empirical correlations between biophysical and biological properties of lesion-containing duplexes.     

Support of the talus: a biomechanical investigation of the contributions of the talonavicular and talocalcaneal joints, and the superomedial calcaneonavicular ligament

The goal of this study was to determine the magnitude of force transmission to the talus by its inferior articulations to provide insight into mechanisms involving acquired deformities of the hindfoot. Cadaver feet were mounted in a loading apparatus that applied axial force through the tibia and fibula as well as tensile loading of the tendons of extrinsic musculature. This also permitted positioning of the tibia in the sagittal plane. Eighteen specimens were tested in three selected positions of the gait cycle. In one series, pressure-sensitive film was inserted into the posterior and anteromedial facets of the talocalcaneal joint as well as into the talonavicular joint. In a second series, film was inserted between the talar head and the superomedial calcaneonavicular ligament. In stance position, the specimens were also tested without posterior tibial tendon (PTT) tension. Contact areas and force transmitted across the articulations were greatest in near toe-off position, in the posterior facet of the talocalcaneal joint. The talonavicular joint, the anteromedial facet of the talocalcaneal joint, and the calcaneonavicular ligament articulation showed sequentially decreasing amounts of contact area and force transmission. Mean pressures were similar across all articulations, except in the posterior facet in near toe-off position. From heel-strike to stance, to near toe-off, a trend to increasing contact area and force was noted. No difference in contact characteristics was found in the calcaneonavicular ligament articulation after PTT release. The contact force of the calcaneonavicular ligament against the talus was found to be much smaller than those of other talar articulations; however, its medially oriented direction must contribute to stabilization of the head of the talus against medial displacement. Loss of PTT tension was not found to alter the contact forces acting at the talar head in this model, which might indicate that it shares its talar stabilizing function with other structures.     

In vitro expansion and characterization of dendritic cells derived from human bone marrow CD34+ cells

Dendritic cells (DC), as professional antigen-presenting cells, play a major role in stimulating naive T cell responses in vivo and in vitro, and may exacerbate or modulate T lymphocyte-mediated reactions, such as interactions between a hematopoietic graft and the recipient, eg GVHD and graft-versus-leukemia. Here, we describe a two-stage cell culture system for expansion of functionally active human DC from CD34+ marrow precursors. Optimal outgrowth was achieved by initially culturing CD34+ cells for 5 days in medium containing GM-CSF, MGF and TNF-alpha. Substitution of CD40L and IL-4 for TNF-alpha during a subsequent 5-day subculture increased DC content, such that by 10 days the cultures contained approximately 40% DC as determined by immunophenotype and morphology. An increase in DC purity to 84% at 10 days was achieved by immunomagnetic separation for CD1a+ cells from 5-day cultures and subculturing these cells in medium with IL-4 and CD40L. Reversing the sequence of growth factors during culture and subculture decreased the yield and purity of DC. Expression of CD80 and CD86 was enhanced by adding CD40L and IL-4, and the DC showed stimulatory activity in MLC. In conclusion, we have described a simple two-stage culture system to generate functional DC from CD34+ marrow precursors.     

Arginine deficiency in bile duct-ligated rats after surgery: the role of plasma arginase and gut endotoxin restriction

BACKGROUND & AIMS: Arginine deficiency may underlie the cellular immune depression after surgery in obstructive jaundice, which is associated with gut-derived endotoxemia. The aim of this study was to study arginine metabolism in the bile duct-ligated rat (BDL) after laparotomy. METHODS: Treatment with cholestyramine, a known endotoxin binder, was used to evaluate the role of gut-derived endotoxemia. RESULTS: In BDL rats, arginine levels were lower compared with those in sham-operated controls (P < 0.005), despite a three-fold increase in renal arginine release (P < 0.01). Liver and gut arginine handling also could not explain the reduced arginine levels. Higher plasma arginase activity (P < 0.0001) was measured in BDL rats, explaining both the lower arginine levels (r = 0.73, P < 0.01) and the increase in arginase product levels: ornithine (P < 0.005 and r = 0.72; P < 0.01) and urea (P < 0.01). Cholestyramine treatment prevented the decrease in postoperative arginine deficiency by reducing plasma arginase activity by 43% (P < 0.005). In addition, it significantly lowered plasma levels of the other liver enzymes (aspartate transaminase, alanine transaminase, gamma-glutamyl transpeptidase, and alkaline phosphatase; P < 0.05) in BDL rats. CONCLUSIONS: The study concluded that arginine deficiency in BDL rats after surgery is caused by high plasma liver arginase activity. Cholestyramine prevented the arginine deficiency by reducing plasma arginase activity through the inhibition of additional endotoxin-mediated hepatocellular damage after surgery in BDL rats.