Icodextrin as salvage therapy in peritoneal dialysis patients with refractory fluid overload

Background Icodextrin is a high molecular weight, starch-derived glucose polymer, which is capable of inducing sustained ultrafiltration over prolonged (12–16 hour) peritoneal dialysis (PD) dwells. The aim of this study was to evaluate the ability of icodextrin to alleviate refractory, symptomatic fluid overload and prolong technique survival in PD patients. Methods A prospective, open-label, pre-test/post-test study was conducted in 17 PD patients (8 females/9 males, mean age 56.8 ± 2.9 years) who were on the verge of being transferred to haemodialysis because of symptomatic fluid retention that was refractory to fluid restriction, loop diuretic therapy, hypertonic glucose exchanges and dwell time optimisation. One icodextrin exchange (2.5 L 7.5%, 12-hour dwell) was substituted for a long-dwell glucose exchange each day. Results Icodextrin significantly increased peritoneal ultrafiltration (885 ± 210 ml to 1454 ± 215 ml, p < 0.05) and reduced mean arterial pressure (106 ± 4 to 96 ± 4 mmHg, p < 0.05), but did not affect weight, plasma albumin concentration, haemoglobin levels or dialysate:plasma creatinine ratio. Diabetic patients (n = 12) also experienced improved glycaemic control (haemoglobin Alc decreased from 8.9 ± 0.7% to 7.9 ± 0.7%, p < 0.05). Overall PD technique survival was prolonged by a mean of 11.6 months (95% CI 6.0–17.3 months). On multivariate Cox proportional hazards analysis, extension of technique survival by icodextrin was only significantly predicted by baseline net daily peritoneal ultrafiltration (adjusted HR 2.52, 95% CI 1.13–5.62, p < 0.05). Conclusions Icodextrin significantly improved peritoneal ultrafiltration and extended technique survival in PD patients with symptomatic fluid overload, especially those who had substantially impaired peritoneal ultrafiltration.

Role of LMP1 in immune control of EBV infection

The Epstein-Barr virus (EBV) encoded latent membrane protein (LMP1) plays a crucial role in the long-term persistence of this virus within the cells of the immune system. Not only is this protein critical for the transformation of resting B cells by EBV, it also displays pleiotropic effects on various cellular proteins expressed in the host cell. These include up-regulation of expression of B cell activation antigens, adhesion molecules and various components of the antigen processing pathway. Here we discuss how LMP1 acts like an expression 'switch' which, depending on the stage of EBV infection, manoeuvres various pathways that either modulate the immune system towards or against its survival.

Step size control for efficient discrete element simulation

The step size determines the accuracy of a discrete element simulation. The position and velocity updating calculation uses a pre-calculated table and hence the control of step size can not use the integration formulas for step size control. A step size control scheme for use with the table driven velocity and position calculation uses the difference between the calculation result from one big step and that from two small steps. This variable time step size method chooses the suitable time step size for each particle at each step automatically according to the conditions. Simulation using fixed time step method is compared with that of using variable time step method. The difference in computation time for the same accuracy using a variable step size (compared to the fixed step) depends on the particular problem. For a simple test case the times are roughly similar. However, the variable step size gives the required accuracy on the first run. A fixed step size may require several runs to check the simulation accuracy or a conservative step size that results in longer run times. (C) 2001 Elsevier Science Ltd. All rights reserved.

Postmenopausal Hormone Use, Screening, and Breast Cancer: Characterization and Control of a Bias

Previous investigators have suggested that screening-related biases may explain associations between postmenopausal hormone use and breast cancer. To investigate these biases, we studied postmenopausal women in the Nurses' Health Study from 1988 to 1994. Hormone use is associated with increased subsequent screening. Among women not screened in the previous 2 years, the probability difference, comparing current hormone users with others, for having mammography in the following 2 years is 19.5%; among women previously screened, the difference is 4.9%. These differences persist after control for other factors. If the increase in screening is causal, screening by mammogram could be intermediate in the causal pathway to breast cancer diagnosis. To deal with this problem, we restrict attention to a subset of the cohort in which the effect of postmenopausal hormone use on screening is small (women previously screened). In this subset, the rate ratio comparing breast cancer rates among current postmenopausal hormone users with others is 1.28. In a sensitivity analysis, the bias could not by itself plausibly account for the associations in our data. Our data provide evidence of an association between postmenopausal hormone use and breast cancer that is not solely the product of a detection bias.

Supervisory control of wastewater treatment plants by combining principal component analysis and fuzzy c-means clustering

In this paper a methodology for integrated multivariate monitoring and control of biological wastewater treatment plants during extreme events is presented. To monitor the process, on-line dynamic principal component analysis (PCA) is performed on the process data to extract the principal components that represent the underlying mechanisms of the process. Fuzzy c-means (FCM) clustering is used to classify the operational state. Performing clustering on scores from PCA solves computational problems as well as increases robustness due to noise attenuation. The class-membership information from FCM is used to derive adequate control set points for the local control loops. The methodology is illustrated by a simulation study of a biological wastewater treatment plant, on which disturbances of various types are imposed. The results show that the methodology can be used to determine and co-ordinate control actions in order to shift the control objective and improve the effluent quality.

Conversion of glucosamine to galactosamine and allosamine derivatives: Control of inversions of stereochemistry at C-3 and C-4

The reactions of sodium benzoate with a series of trimesylates derived from glucosamine have been examined in an attempt to gain facile access to galactosamine analogues. Trimesylate 17, in which the amino group was protected as a phthalimide, underwent double displacement at positions 4 and 6 to give the dibenzoate 18 with the desired galactosamine configuration. In contrast, trimesylates 21 and 27, in which the amino groups were protected as acetamides, unexpectedly underwent double displacement at positions 3 and 6, giving products 22 and 28, respectively, with allosamine configurations.

Manual asymmetries in the preparation and control of goal-directed movements

The primary purpose of this experiment was to determine if left hand reaction time advantages in manual aiming result from a right hemisphere attentional advantage or an early right hemisphere role in movement preparation. Right-handed participants were required to either make rapid goal-directed movements to small targets or simply lift their hand upon target illumination. The amount of advance information about the target for a particular trial was manipulated by precuing a subset of potential targets prior to the reaction time interval. When participants were required to make aiming movements to targets in left space, the left hand enjoyed a reaction advantage that was not present for aiming in right space: or simple finger lifts. This advantage was independent of the amount or type of advance information provided by the precue. This finding supports the movement planning hypothesis. With respect to movement execution, participants completed their aiming movements more quickly when aiming with their right hand, particularly in right space. This right hand advantage in right space was due to the time required to decelerate the movement and to make feedback-based adjustments late in the movement trajectory. (C) 2001 Academic Press.

Neural adaptations to resistance training - Implications for movement control

It has long been believed that resistance training is accompanied by changes within the nervous system that play an important role in the development of strength. Many elements of the nervous system exhibit the potential for adaptation in response to resistance training, including supraspinal centres, descending neural tracts, spinal circuitry and the motor end plate connections between motoneurons and muscle fibres. Yet the specific sites of adaptation along the neuraxis have seldom been identified experimentally, and much of the evidence for neural adaptations following resistance training remains indirect. As a consequence of this current lack of knowledge, there exists uncertainty regarding the manner in which resistance training impacts upon the control and execution of functional movements. We aim to demonstrate that resistance training is likely to cause adaptations to many neural elements that are involved in the control of movement, and is therefore likely to affect movement execution during a wide range of tasks. We review a small number of experiments that provide evidence that resistance training affects the way in which muscles that have been engaged during training are recruited during related movement tasks. The concepts addressed in this article represent an important new approach to research on the effects of resistance training. They are also of considerable practical importance, since most individuals perform resistance training in the expectation that it will enhance their performance in-related functional tasks.

Overexpression of a Slit homologue impairs convergent extension of the mesoderm and causes cyclopia in embryonic zebrafish

Slit is expressed in the midline of the central nervous system both in vertebrates and invertebrates. In Drosophila, it is the midline repellent acting as a ligand for the Roundabout (Robo) protein, the repulsive receptor which is expressed on the growth cones of the commissural neurons. We have isolated cDNA fragments of the zebrafish slit2 and slit3 homologues and found that both genes start to be expressed by the midgastrula stage well before the axonogenesis begins in the nervous system, both in the axial mesoderm, and slit2 in the anterior margin of the neural plate and slit3 in the polster at the anterior end of the prechordal mesoderm. Later, expression of slit2 mRNA is detected mainly in midline structures such as the floor plate cells and the hypochord, and in the anterior margins of the neural plates in the zebrafish embryo, while slit3 expression is observed in the anterior margin of the prechordal plate, the floorplate cells in the hindbrain, and the motor neurons both in the hindbrain and the spinal cord. To study the role of Slit in early embryos, we overexpressed Slit2 in the whole embryos either by injection of its mRNA into one-cell stage embryos or by heat-shock treatment of the transgenic embryos which carries the slit2 gene under control of the heat-shock promoter. Overexpression of Slit2 in such ways impaired the convergent extension movement of the mesoderm and the rostral migration of the cells in the dorsal diencephalon and resulted in cyclopia. Our results shed light on a novel aspect of Slit function as a regulatory factor of mesodermal cell movement during gastrulation. (C) 2001 Academic Press.

Urban birth and migrant status as risk factors for psychosis: An Australian case-control study

Background Urban birth and migrant status have been identified as risk factors for psychosis in North American and European studies. The aim of this study was to explore these variables in an Australian case-control study. Method Country of birth of subjects and their parents, and place of birth of Australian-born subjects, were examined in individuals with psychosis drawn from a prevalence study (n = 310) and well controls recruited from the same catchment area (n = 303). Results Migrant status was associated with a significantly decreased odds of having a psychotic disorder. For those born in Australia, neither migrant status of parents nor urban birth was associated with having a psychotic disorder. Conclusions The lack of effect for urban birth and second-generation migrant status may help generate candidate environmental risk factors that operate in Europe but not in Australia.

Articulatory dysfunction in multiple sclerosis: An electropalatographic study

Dysfunction of the articulatory subsystem (i.c.. the lips, tongue, and jaw) has bccn identified as a major contributor to the reduction in speech intelligibility experienced by a high proportion of people with multiple sclerosis (MS). In particular. consonant imprecision has been reported to be the articulatory deficit that contributes most to variations in overall intelligibility of MS speakers. Electropalatography(EPG) IS an instrurncntal technique that visually documents the location and timing of tongue-topalatc contacts during speech. Although such a technique would be valuablc in objectively assessing the articulatory disturbances exhibited by individuals with dysarthria ia motor speech disorder) associated with MS, to-date no such study ha< been reported. The aim of the present study was to use EPG to assess tongue-to-palate contact patterns and articulatory timing in patients with dysarthria associated with MS. A dysarthric participant with a diagnosis of definite MS was fitted with an acrylic EPG palate (Reading EPG.?) and asked to read aloud a list of single syllable words which contained lingual consonants in the word-initial position and in consonant clusters. Each mord was repeated five times. The EPG palate was specifically moulded to tit the participant's hard palate and contained 62 electrodes that detected the tongue contacts. A non-neurologically impaired participant matched for age and sex servcd as a control. The results of the study revealed that the tongue-to-palate contacts produced by the participant with MS varied from those produced by the control in a number of ways in regard to spatial configurations and timing characteristics exhibited. The rcsults arc discussed in relation to the neuropathophysiological effects of MS on speech production. The potcntial use of EPG in programs for treating speech disorders associated with MS will be highlightcd.

Long-distance signaling and the control of branching in the rms1 mutant of peal

The ramosus (rms) mutation (rms1) of pea (Pisum sativum) causes increased branching through modification of graft-transmissible signal(s) produced in rootstock and shoot. Additional grafting techniques have led us to propose that the novel signal regulated by Rms1 moves acropetally in shoots and acts as a branching inhibitor. Epicotyl interstock grafts showed that wild-type (WT) epicotyls grafted between rms1 scions and rootstocks can revert mutant scions to a WT non-branching phenotype. Mutant scions grafted together with mutant and WT rootstocks did not branch despite a contiguous mutant root-shoot system. The primary action of Rms1 is, therefore, unlikely to be to block transport of a branching stimulus from root to shoot. Rather, Rms1 may influence a long-distance signal that functions, directly or indirectly, as a branching inhibitor. It can be deduced that this signal moves acropetally in shoots because WT rootstocks inhibit branching in rms1 shoots, and although WT scions do not branch when grafted to mutant rootstocks, they do not inhibit branching in rms1 cotyledonary shoots growing from the same rootstocks. The acropetal direction of transport of the Rms1 signal supports previous evidence that the rms1 lesion is not in an auxin biosynthesis or transport pathway. The different branching phenotypes of WT and rms1 shoots growing from the same rms1 rootstock provides further evidence that the shoot has a major role in the regulation of branching and, moreover, that root-exported cytokinin is not the only graft-transmissible signal regulating branching in intact pea plants.

The calibre of the Foramen of Panizza in Crocodylus porosus is variable and under adrenergic control

The foramen of Panizza is located within the outflow tract of the crocodilian heart, between the left and right aortas. It has been suggested that the foremen of Panizza has a variable calibre, which could explain the profound changes in the distribution of flows and pressure profiles recorded in the right and left aortas. We investigated this possibility using a modified in-situ perfused heart preparation in combination with isolated strip preparations from the outflow tract. In the perfused heart preparation, bolus injections of adrenaline increased the resistance in the foramen of Panizza, indicating a decrease in its diameter. Isolated strip preparations from the outflow tract showed a concentration-dependent increase in tension in response to adrenaline, while vasoactive intestinal polypeptide caused a relaxation in adrenaline pre-contracted strip preparations. We propose that an increase in the diameter of the foremen of Panizza may be important during pulmonary to systemic shunts to allow blood to flow from the left to right aorta (reverse foramen flow) in order to supply the carotid and coronary arteries. During non-shunting conditions, a constricted foramen may prevent excess flow from the right to left aorta during diastole.