Nutrition support affects the distribution and organ uptake of cachectin/tumor necrosis factor in rats

BACKGROUND: We have previously observed a potentiation of the metabolic response to cachectin/tumor necrosis factor (TNF) by total parenteral nutrition (TPN) but not in anorexic orally fed animals. We hypothesized that nutritional status might affect TNF clearance kinetics. METHODS: We compared the clearance of a bolus of labeled TNF in TPN-fed animals given sufficient nutrients to grow called weight-gaining rats (WGR) with those given 50% of the WGR called weight-losing rats (WLR) and with orally fed rats (OFR). Data were analyzed using a two-compartment open system model and by linear systems analysis. RESULTS: The data from both types of analysis indicator that although metabolic clearance was similar, WGR had a slower fractional TNF clearance rate (FCR) as well as a larger volume of distribution than WLR or OFR. Further analysis showed that an increased proportion of the total mass of TNF resided in a plasma-associated compartment in WGR compared with WLR and OFR. In addition, WGR had reduced uptake of labeled TNF by the kidney. CONCLUSION: The data suggest that nutrition support influences either the distribution of TNF or the FCR, resulting in a greater retention in the plasma-associated compartment with intact absolute removal rates. This study has important implications concerning the type of nutrition support provided to the critically ill patient because our data suggest that clinical states with increased circulating TNF levels may be adversely affected by currently available nutritional practices.     

Bovine IgG2a antibodies to Haemophilus somnus and allotype expression

AIMS/BACKGROUND: To characterise clinically a large kindred segregating retinitis pigmentosa and sensorineural hearing impairment in an autosomal dominant pattern and perform genetic linkage studies in this family. Extensive linkage analysis in this family had previously excluded the majority of loci shown to be involved in the aetiologies of RP, some other forms of inherited retinal degeneration, and inherited deafness. METHODS: Members of the family were subjected to detailed ophthalmic and audiological assessment. In addition, some family members underwent skeletal muscle biopsy, electromyography, and electrocardiography. Linkage analysis using anonymous microsatellite markers was performed on DNA samples from all living members of the pedigree. RESULTS: Patients in this kindred have a retinopathy typical of retinitis pigmentosa in addition to a hearing impairment. Those members of the pedigree examined demonstrated a subclinical myopathy, as evidence by abnormal skeletal muscle histology, electromyography, and electrocardiography. LOD scores of Zmax = 3.75 (theta = 0.10), Zmax = 3.41 (theta = 0.10), and Zmax = 3.25 (theta = 0.15) respectively were obtained with the markers D9S118, D9S121, and ASS, located on chromosome 9q34-qter, suggesting that the causative gene in this family may lie on the long arm (q) of chromosome 9. CONCLUSIONS: These data indicate that the gene responsible for the phenotype in this kindred is located on chromosome 9 q. These data, together with evidence that a murine deafness gene is located in a syntenic area of the mouse genome, should direct the research community to consider this area as a candidate region for retinopathy and/or deafness genes.     

QoS enhancement for adaptive streaming services over WCDMA

This paper presents a new method to adapt the quality-of-service (QoS) in a wideband code-division multiple-access (WCDMA) system, called radio network feedback (RNF). The concept of RNF is in general applicable to all the services requiring a minimum quality (i.e., non best effort) and in this paper, the focus is on streaming. In this context, RNF makes it possible for a streaming server to adapt its source bit rate to a WCDMA radio link, whose bandwidth may vary in time due, for example, to decongestion/congestion situations over the air interface or to handover. This is very beneficial for the end user as it allows to increase the bandwidth (i.e., the quality) when possible and to decrease it (instead of just dropping the service) when needed. RNF was compared with Client-based adaptation solutions. Simulation results show that RNF is fast and accurate and performs better than Client-based adaptation. For example, rebuffering occurs only with Client-based method. Moreover, with RNF the up-switch is performed only when needed, whereas the up-switch performed by means of the Client-based method is often erroneous and may annoy the end user.     

Gait function in spastic hemiparetic patients walking barefoot, with firm shoes, and with ankle-foot orthosis

Cortical spreading depression is a wave of electrical and biochemical changes that spreads across the cerebral cortex. It has been hypothesized to be an important underlying cause of the visual disturbances occurring during the migraine aura, but this is difficult to test in animals or humans. We created a computational model of cortical spreading depression and found that during the wave of biochemical changes the spatial pattern of neural activity broke up into irregular patterns of lines and small patches of highly activated elements. The corresponding visual disturbances that would be produced by these patterns of neural activity resemble the hallucinations reported during the migraine aura, providing strong support for the cortical spreading depression hypothesis of migraine. The model also makes the testable prediction that these hallucinations move at an exponentially increasing speed across the visual field.     

Disturbance of continuous, pump administration of cardiovascular drugs by hydrostatic pressure

Administration of highly concentrated, highly potent, and therefore highly dangerous drugs with syringe pumps is common in modern anaesthesia as well as in intensive care and emergency medicine. Because of their exact flow rates down to < 1 ml/h, these pumps are predestined for delivery of drugs with short half-lives, such as catecholamines and vasodilators. But intravenous application of drugs with syringe pumps is not without problems. While it is well known that syringes not fixed correctly into the pump can empty themselves by the influence of gravity, it seems not to be known that hydrostatic pressure can influence the flow rate of a correctly connected system even during continuous infusion. In this situation a change of height of the syringe pump in relation to the patient's position can have tremendous effects on hemodynamics due to unintended acceleration or deceleration of the flow rate. This case report demonstrates that the elevation of a connected epinephrine pump while moving a cardiac surgery patient after ACB operation from the operation table into his bed led to critical increases of heart rate, blood pressure and left atrial pressure. In order to quantify the problem we repeated the situation experimentally. It could be demonstrated that the elevation of the syringe pump by 80-100 cm delivers an additional bolus of 4-5 drops as the central venous catheter outlet. Lowering the pump consecutively leads to the opposite effect. In the case reported, the accidentally administered bolus of epinephrine was 12-15 micrograms (we use a concentration of 60 micrograms/ml epinephrine for continuous infusion with syringe pumps). From this accidental observation the following conclusion can be drawn: The change of height, in relation to the patient's position, of a running syringe pump during continuous infusion of highly concentrated cardiovascular drugs may cause considerable, even life-threatening hemodynamic disorders. Even in a closed infusion system (syringe-extension-central venous catheter), hydrostatic pressure influences infusion rate. Elevation of the pump leads to unintended bolus administration, and lowering of the pump is followed by an interruption of the infusion. In the knowledge of this phenomenon, unexpected hemodynamic reactions during transport of critically ill patients cannot always be interpreted as a result of inadequate anesthesia or volume load, but may be a consequence of incorrect handling of the syringe pumps as described in this report.     

Global folds of highly deuterated, methyl-protonated proteins by multidimensional NMR

The development of 15N, 13C, 2H multidimensional NMR spectroscopy has facilitated the assignment of backbone and side chain resonances of proteins and protein complexes with molecular masses of over 30 kDa. The success of these methods has been achieved through the production of highly deuterated proteins; replacing carbon-bound protons with deuterons significantly improves the sensitivity of many of the experiments used in chemical shift assignment. Unfortunately, uniform deuteration also radically depletes the number of interproton distance restraints available for structure determination, degrading the quality of the resulting structures. Here we describe an approach for improving the precision and accuracy of global folds determined from highly deuterated proteins through the use of deuterated, selectively methyl-protonated samples. This labeling profile maintains the efficiency of triple-resonance NMR experiments while retaining a sufficient number of protons at locations where they can be used to establish NOE-based contacts between different elements of secondary structure. We evaluate how this deuteration scheme affects the sensitivity and resolution of experiments used to assign 15N, 13C, and 1H chemical shifts and interproton NOEs. This approach is tested experimentally on a 14 kDa SH2/phosphopeptide complex, and a global protein fold is obtained from a set of methyl-methyl, methyl-NH, and NH-NH distance restraints. We demonstrate that the inclusion of methyl-NH and methyl-methyl distance restraints greatly improves the precision and accuracy of structures relative to those generated with only NH-NH distance restraints. Finally, we examine the general applicability of this approach by determining the structures of several proteins with molecular masses of up to 40 kDa from simulated distance and dihedral angle restraint tables.     

Dyspnea resulting from phrenic nerve paralysis after interscalene brachial plexus block in an obese male--a case report

While current psychiatric taxonomies recognise a classification of amphetamine dependence, derived from the notion of an alcohol dependence syndrome, little research has validated that such a condition exists for this drug. Current amphetamine users (N = 331), were interviewed using the World Health Organization operationalisation of DSM-III-R substance dependence criteria, and a measure of the psychological components of dependence. Structural analyses indicated that a unidimensional dependence syndrome as assessed by DSM-III-R and DSM-IV criteria exists for amphetamine, and that physiological, psychological and behavioural indicators were all important in accounting for the variance in responses. It was demonstrated that the concept of a dependence syndrome is applicable to amphetamine, and that the inclusion of the amphetamine dependence syndrome in DSM-III-R and DSM-IV is valid.