Effect of age of onset of temporal lobe epilepsy on the severity and the nature of preoperative memory deficits

The nature and severity of pre-operative memory deficits observed in unilateral temporal lobe epilepsy depend upon a number of variables. Among these variables, age of seizure onset seems to be important. The age at which the lesion is sustained could modify the normal functional organization of the brain. Many studies have examined the effect of age of onset on the severity of memory deficits but have seldom focused on the nature of such deficits (verbal/nonverbal) as a function of epileptic focus laterality. This study investigates the effect of age of onset on the nature and severity of memory impairments. Fifty-six epileptics with unilateral temporal lobe epilepsy and 20 normal subjects were administered a neuropsychological evaluation. Four groups of patients were constituted: left or right temporal lobe epilepsy with early (0-5 years) or late (10 years and over) age of seizure onset. The early group showed major verbal and nonverbal memory deficits. The late group presented minor specific deficits: essentially verbal deficits with left temporal lobe seizures and nonverbal deficits with right temporal lobe seizures. These results may be interpreted in the framework of ontogenesis theories of hemispheric specialization.     

Cannabis use correlates with schizotypal personality traits in healthy students

The literature suggests that cannabis use and schizotypal traits both constitute risk factors for the later development of schizophrenia. However, their interrelationships remain to be evaluated. The present study examined the association between cannabis use and schizotypal traits in 232 healthy students who ranged in age from 18 to 25 years. All the students had completed the Schizotypal Personality Questionnaire and four of the Chapman Psychosis Proneness Scales: the Magical Ideation Scale; the Perceptual Aberration Scale; the Revised Physical Anhedonia Scale; and the Revised Social Anhedonia Scale. Subjects were divided into three groups according to cannabis use typology: those who had never used cannabis, those who were past or occasional users, and those who were regular users. Higher scores on the Schizotypal Personality Questionnaire and the Magical Ideation Scale characterized the regular and past or occasional users compared with those who had never used cannabis. The co-occurrence of cannabis use and schizotypal traits appeared to be independent of anxiety and depression dimensions. These data suggest that cannabis use and schizotypal traits have to be jointly considered in further longitudinal studies of schizophrenia risk factors.     

Comparison between macaques' and humans' kinematics of prehension: the role of morphological differences and control mechanisms

Reaching and grasping has been widely studied in both macaques and humans, mainly with the aim of finding similar patterns of behavior in the two species. Little attention has yet been given to how morphological and behavioral differences between the two species might affect the kinematics of the movement. In this study, we present a careful analysis of the similarities and differences between humans' and macaques' prehension movements and discuss these with respect to both the control system and the biomechanics of the arm. Five humans and five macaques performed the same task, namely grasping small feeding objects using a precision grip. Macaques were observed in unconstrained conditions, free to adjust their body posture. The behavioral protocol for macaques revealed a postural preference for sitting and keeping the elbow slightly flexed when applying a precision grip. In agreement with the literature, kinematics revealed general features of movement common to both humans and macaques. However, within a similar timeframe, macaques produced steeper and wider excursion of the elbow and of the wrist, smaller abduction of the shoulder joint and larger displacement of the torso than humans did. The three-joint limb revealed stronger irregularities for the macaques. We hypothesize that the larger kinematic irregularities and the specific elbow--shoulder posture in macaques result in part from an effort of the control system to compensate for different biomechanical constraints, namely for limited shoulder-joint excursion, in order to achieve a similar range of comfort of motion. Finally, we briefly consider the influence of primitive neural circuits responsible for arm motion during locomotion and speculated on their influence on the control of reaching in macaques.     

Contribution of solid-state properties to the aqueous solubility of drugs.

This study investigates the influence of the solid-state properties melting point (T(m)), enthalpy of melting (DeltaH(m)) and entropy of melting (DeltaS(m)) of a drug on its intrinsic solubility (S(0)). For this purpose, 26 chemically and structurally diverse drugs covering the oral drug space were selected and the S(0), T(m), DeltaH(m) and DeltaS(m) were determined experimentally. The influence of T(m), DeltaH(m) and DeltaS(m) on S(0) was studied using regression analysis. The overall improvement of the predictions were 0.3 log units, however, five compounds (astemizole, glyburide, fenbufen, gliclazide and griseofulvin) were improved by more than one log unit. T(m) and DeltaH(m) had a larger effect than DeltaS(m) on the solubility predictions. The well-known general solubility equation (GSE) and the Dannenfelser semi-empirical equation for the calculation of DeltaS(m) were evaluated using our data set. While predictions of drug solubility obtained using the GSE were acceptable, the use of the experimental DeltaS(m) values instead of the constant 56.5 J mol(-1)K(-1) improved the accuracy of the prediction. The Dannenfelser equation underestimated the DeltaS(m) for most compounds with on average 15 J mol(-1)K(-1). Our results show that solid-state properties should be considered for improved performance of future models for prediction of drug solubility. In addition our study provides accurate experimental data on intrinsic solubility for 26 compounds, supplying a useful external data set for validation of drug solubility models.     

Structural investigations on lipid nanoparticles containing high amounts of lecithin.

Solid lipid nanoparticles (SLN), an alternative colloidal drug delivery system to polymer nanoparticles, emulsions and liposomes, possess inherent low incorporation rates resulting from the crystalline structure of the solid lipid. To increase the drug loading capacity of SLN, matrix modification by incorporation of the amphiphilic lipid lecithin within the lipid matrices has been proposed as a promising alternative. The objective of this work is to investigate the effects of the lecithin on the microstructure of matrix modified SLN. In addition, these systems were checked for the existence of aggregates like mixed micelles, liposomes, etc., which could possibly be formed by lecithin leakage into the aqueous phase during the preparation process. For this purpose, laser diffraction, photon correlation spectroscopy (PCS), small angle X-ray scattering (SAXS), nuclear magnetic resonance (NMR) and transmission electron microscopy (TEM) were performed to investigate the structure, mobility, and molecular environment of the compounds. Lecithin incorporation within the lipid matrices resulted in a concentration dependent decrease in particle size up to a critical concentration of 30%. Lecithin incorporation up to 50% was investigated but caused no further particle size decrease. TEM revealed anisometrical and crystalline platelets of ellipsoidal to disc-like shape. Furthermore, SAXS and TEM showed no signs of lecithin and nonionic emulsifier derived aggregates in the aqueous phase. This points in agreement with NMR measurements to a strong attachment of both substances to the SLN surfaces. The proposed structure of the particles after melt emulsification consists of two different layers: a crystalline triglyceride-rich core is covered in dependence of the lecithin content either by a monomolecular or multimolecular lecithin/Solutol HS15 (SOL) layer.     

Identity development, coping, and adjustment in emerging adults with a chronic illness: the sample case of type 1 diabetes

PURPOSE: The present study focused on identity development in emerging adults (aged 18-30 years) with type 1 diabetes. The three study aims were to examine the following: (1) whether identity development was affected by having diabetes, as compared with development in a nondiabetic sample; (2) how identity development was related to depressive symptoms, coping with diabetes, and diabetes-related problems in the diabetic sample; and (3) whether the pathways from identity development to problems with diabetes and depressive symptoms were mediated through coping strategies in the diabetic sample. METHODS: A total of 194 emerging adults with type 1 diabetes and 344 nondiabetic emerging adults participated. RESULTS: First, using analyses of variance, some mean identity differences between the diabetic and comparison samples were found, with emerging adults with diabetes scoring lower on proactive identity exploration. Using cluster analysis, we found that the same identity types or statuses emerged in both the diabetic and nondiabetic samples. Second, in emerging adults with diabetes, these identity statuses were differentially related to diabetes-related problems, depressive symptoms, and illness coping, with the identity statuses representing a strong sense of identity being accompanied by less diabetes-related problems and depressive symptoms and more adequate coping strategies. Third, using structural equation modeling, the pathways from a strong sense of identity to diabetes-related problems and depressive symptoms were mediated through adaptive and maladaptive coping. CONCLUSIONS: Clinicians should be sensitive to the normative task of identity development in emerging adults with diabetes because identity development can function as a resource in coping with and adjusting to diabetes.     

Maximum tolerated doses of methotrexate and 7-hydroxy-methotrexate in a model of acute toxicity in rats

Purpose: After more than 50 years of methotrexate (MTX) treatment of acute lymphoblastic leukaemia (ALL), it is currently believed that as long as dose escalations are followed by adequate leucovorin rescue guided by monitoring MTX serum concentrations, hydration and urinary alkalinization, high-dose MTX (HD-MTX) can be tolerated without life-threatening toxicity. However, our recent experimental animal studies of the major metabolite of MTX, 7-OH-MTX, indicate that this concept may have some limitations. Animals with levels of 7-OH-MTX of 1 mM, which is below the levels routinely found in patients on HD-MTX, demonstrate intolerable toxicity and some animals die within 8 h. Electron microscopy indicates that endothelial cell and platelet functions are perturbed. Since animal data are lacking, and interspecies differences not known, we wanted to investigate the maximum tolerated doses of MTX and 7-OH-MTX in a rat model of short-term effects. The maximum tolerated dose was chosen instead of LD₅₀ for reasons of animal welfare. Methods: We infused MTX and 7-OH-MTX into anaesthetized male Wistar rats and monitored the animals for 8 h. The drugs were given as a bolus plus continuous infusion. The dose-finding ranges were 1.8–11.3 g/kg MTX and 0.1–1.2 g/kg 7-OH-MTX. Results: The maximum tolerated dose was between 3 and 5 g/kg for MTX and lower than 0.1 g/kg for 7-OH-MTX. The mean serum concentrations of MTX and 7-OH-MTX in animals that did not survive the 8-h period were 21.9 and 1.6 mM, respectively. The animals that received the highest MTX or 7-OH-MTX doses and concentrations died after sudden reductions in heart rate and blood pressure. Conclusions: We demonstrated a lower maximum tolerated dose of 7-OH-MTX than of MTX in rats after 8 h. The 7-OH-MTX concentrations were in the therapeutic range after HD-MTX. If the rat/human interspecies differences are not large, our data may indicate that HD-MTX regimens should not be further dose intensified, due not so much to the effects of MTX as to those of 7-OH-MTX. Received: 28 July 1999 / Accepted: 25 January 2000     

Enhancement of the bacterial degradation of phenoxyalkanoate herbicides by the use of modified polyurethane foam as a support

The enhancement of the degradative behaviour of Flavobacterium sp. MH concerning the phenoxyalkanoate herbicides 2,4-D, 2,4-DP, 2,4-DB, MCPA, MCPP, and MCPB, respectively, was achieved by the use of an inert polyurethane (PU)-foam. In comparative batch-degradation experiments with and without the addition of the PU-carrier (1.25 % w/v), respectively, the advantages of the PU-supply were demonstrated. When 2,4-D, 2,4-DP, and MCPP, respectively, was used as a growth substrate by strain MH the PU-supply led to a reduced lag-phase. In the case of the stronger toxic phenoxyalkanoates 2,4-DB and MCPB, respectively, the inital substrate concentration (0.1 g/1) was significantly reduced to a minor toxic concentration due to a distinct adsorption to the PU-carrier, thus enabling the biodegradation. Finally, the total initially supplied amount of the phenoxyalkanoates was detoxified as verified by thechloride balance. After several steps of subcultivation, even a five-fold increased MCPB concentration (0.5 g/1) could be detoxified by strain MH in a PU-supplied bubble reactor within several days.     

Tibial tunnel enlargement after anterior cruciate ligament reconstruction by autogenous bone-patellar tendon-bone graft

This retrospective study was designed to evaluate changes in the diameter of the tibial tunnel over time following the reconstruction of the anterior cruciate ligament (ACL) with a bone-patellar tendon-bone autograft in 44 patients. The changes in the geometry of the bone tunnels were measured radiographically during the immediate postoperative period and at time intervals between 3 and 36 months after surgery. The dimensions at 1 year were correlated with the 1-year clinical results. The distance between the sclerotic margins of the tibial tunnel was measured at the distal tunnel exis on the medial tibial cortex, in the middle of the tunnel, and proximally at the level of the joint line. The dimensions were calculated by using a magnification factor determined by reference to the interference screw of known diameter located within the tunnel. The position of the centre of the tibial tunnel with regard to Blumensaat's line was also measured. The average tunnel diameter at the proximal tibial exit increased from 12±1.9 mm (mean ± standard deviation) postoperatively to 14±2.2 mm at 3 months. The average proximal tunnel diameter did not significantly change from 3 months to 2 years, and then decreased to 13±2.4 mm at 3 years. At 1 year, most of the patterns of osteolysis were of the cone type (57%), followed by the cavity type (40%) and line type (3%). The degree of osteolysis was not related to the tibial tunnel position with respect to Blumensaat's line. There was no correlation between the changes in tunnel diameter and either the IKDC score or the residual joint laxity measured by a KT-1000 arthrometer. The aetiology of tunnel enlargement is currently unknown. Possible factors responsible for bone resorption include micromotion of the graft relative to the tunnel wall, leading to an inflammatory response in the tunnel, or stress shielding of the tunnel wall proximal to the interference screw.