Impact of mycophenolate mofetil loading on drug exposure in the early posttransplant period

Achieving adequate therapeutic levels of immunosuppressive medications is important in rejection prevention. This study examined exposure to mycophenolic acid (MPA) in kidney transplant patients within the first 5 days posttransplantation. Methods. This single-center, nonrandomized study of first solitary kidney allograft recipients receiving cyclosporine (n = 116) or tacrolimus (n = 50) included patients who received either 1 g or 1.5 g of mycophenolate mofetil twice daily starting postoperatively. Exposure to MPA was measured at days 3 and 5 posttransplant using published limited sampling time equations. Results. There were no significant differences in exposure in the cyclosporine-treated patients receiving 3-g (n = 22) compared to 2-g (n = 94) daily doses (AUC([0-12]) 33.8 +/- 10.0 mg*h/L versus 30.1 +/- 9.7 mg*h/L, P =.20, respectively). About half the patients in both groups had AUC([0-12]) < 30 mg*h/L on days 3 and 5 posttransplant. On the other hand, there was significantly greater exposure on day 3 in the tacrolimus-treated patients receiving 3 g (n = 21) compared to 2 g (n = 29) daily (AUC([0-12]) 43.1 +/- 9.0 mg*h/L versus 36.8 +/- 11.1 mg*h/L, P =.016, respectively). On day 3 one (4.8%) patient receiving 3 g had an AUC([0-12]) of < 30 mg*h/L; whereas, eight (27.5%) receiving 2 g were below this level (P =.068). The AUC([0-12]) levels were not different on day 5. Conclusions. Loading with higher doses of mycophenolate mofetil results in greater exposure and a trend toward more patients in the therapeutic window within the first week for tacrolimus- but not for cyclosporine-treated patients.

Effects of tensioning the lumbar fasciae on segmental stiffness during flexion and extension - Young investigator award winner

Study Design. Biomechanical study of unembalmed human lumbar segments. Objective. To investigate the effects of tensioning the lumbar fasciae ( transversus abdominis [TrA]) aponeurosis) on segment stiffness during flexion and extension. Summary of Background Data. Animal and human studies suggest that TrA may influence intersegmental movement via tension in the middle and posterior layers of lumbar fasciae ( MLF, PLF). Methods. Compressive flexion and extension moments were applied to 17 lumbar segments from 9 unembalmed cadavers with 20 N lateral tension of the TrA aponeurosis during: 1) static tests: load was compared when fascial tension was applied during static compressive loads into flexion-extension; 2) cyclic loading tests: load, axial displacement, and stiffness were compared during repeated compressive loading cycles into flexion-extension. After testing, the PLF was incised to determine the tension transmitted by each layer. Results. At all segments and loads (< 200 N), fascial tension increased resistance to flexion loads by similar to 9.5 N. In 15 of 17, fascial tension decreased resistance to extension by similar to 6.6 N. Fascial tension during cyclic flexion loading decreased axial displacement by 26% at the onset of loading (0 - 2 N) and 2% at 450 N ( 13 of 17). During extension loading, fascial tension increased displacement at the onset of loading ( 10 of 17) by similar to 23% and slightly (1%) decreased displacement at 450 N. Segment stiffness was increased by 6 N/mm in flexion (44% at 25 N) and decreased by 2 N/mm (8% at 25 N) in extension. More than 85% of tension was transmitted through the MLF. Conclusions. Tension on the lumbar fasciae simulating moderate contraction of TrA affects segmental stiffness, particularly toward the neutral zone.

The impact of peginterferon alfa-2a plus ribavirin combination therapy on health-related quality of life in chronic hepatitis C

Background/Aims: Peginterferon alfa-2a plus ribavirin improves sustained virological responses compared with interferon alfa-2b and ribavirin, or peginterferon alfa-2a alone in chronic hepatitis C. We examined the impact of these treatments on health related quality of life (HRQOL). Methods: Patients (n = 1121) were randomized to peginterferon alfa-2a weekly plus ribavirin or placebo, or interferon alfa-2b thrice weekly plus ribavirin. HRQOL was assessed with the SF-36 Health Survey and Fatigue Severity Scale (FSS). Results: Patients receiving peginterferon alfa-2a plus ribavirin reported better HRQOL than those receiving interferon alfa-2b plus ribavirin. These differences were statistically significant for three SF-36 domains and both FSS scores (p < = 0.05). Patients receiving peginterferon alfa-2a plus placebo had the least impairment; adding ribavirin significantly decreased five domains of the SF-36 and both FSS scores. Sustained virological response was associated with improvement at follow-up on all SF-36 and FSS scores. Conclusions: The effects of combination therapy on HRQOL and fatigue are less with peginterferon alfa-2a plus ribavirin than interferon alfa-2b plus ribavirin. Each medication in combination therapy with interferon and ribavirin, affects patients' quality of life differently. Understanding the relationship of specific therapeutic options to HRQOL may help physicians minimize the impact of therapy on HRQOL. (C) 2004 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Effects of potential models on the adsorption of ethane and ethylene on graphitized thermal carbon black. Study of two-dimensional critical temperature and isosteric heat versus loading

Adsorption of ethylene and ethane on graphitized thermal carbon black and in slit pores whose walls are composed of graphene layers is studied in detail to investigate the packing efficiency, the two-dimensional critical temperature, and the variation of the isosteric heat of adsorption with loading and temperature. Here we used a Monte Carlo simulation method with a grand canonical Monte Carlo ensemble. A number of two-center Lennard-Jones (LJ) potential models are investigated to study the impact of the choice of potential models in the description of adsorption behavior. We chose two 2C-LJ potential models in our investigation of the (i) UA-TraPPE-LJ model of Martin and Siepmann (J. Phys. Chem. B 1998,102, 25692577) for ethane and Wick et al. (J. Phys. Chem. B 2000,104, 8008-8016) for ethylene and (ii) AUA4-LJ model of Ungerer et al. (J. Chem. Phys. 2000,112, 5499-5510) for ethane and Bourasseau et al. (J. Chem. Phys. 2003, 118, 3020-3034) for ethylene. These models are used to study the adsorption of ethane and ethylene on graphitized thermal carbon black. It is found that the solid-fluid binary interaction parameter is a function of adsorbate and temperature, and the adsorption isotherms and heat of adsorption are well described by both the UA-TraPPE and AUA models, although the UA-TraPPE model performs slightly better. However, the local distributions predicted by these two models are slightly different. These two models are used to explore the two-dimensional condensation for the graphitized thermal carbon black, and these values are 110 K for ethylene and 120 K for ethane.

The impact of breast cancer on the lives of middle-aged women: Results from the Australian longitudinal study of women's health

This article investigated the impact of breast cancer (BC) in middle-aged Australian women (45-50 years). Two waves of data collected 2 years apart from a longitudinal survey of 12,177 women identified 3 groups: (a) 11,933 (98%) who reported never having had BC, (b) 181 (1.5%) who reported a diagnosis of BC at Time 1, and (c) 63 (0.5%) who reported onset of BC between Time I and Time 2. Repeated measures analysis of variance was used to compare the 3 groups. Women with recent onset of BC experienced significant changes across a range of functioning compared with the other 2 groups. Compared with women with no BC, women with longer established onset of BC had significantly worse health and social outcomes, but these were associated with small effect sizes. Both groups of women with BC reported less impact on mental and emotional health than on other areas of functioning.

The impact of neurodynamic testing on the perception of experimentally induced muscle pain

Neurodynamic tests such as the straight leg raising (SLR) and slump test are frequently used for assessment of mechanosensitivity of neural tissues. However, there is ongoing debate in the literature regarding the contributions of neural and non-neural tissues to the elicited symptoms because many structures are affected by these tests. Sensitizing manoeuvres are limb or spinal movements added to neurodynamic tests, which aim to identify the origin of the symptoms by preferentially loading or unloading neural structures. A prerequisite for the use of sensitizing manoeuvres to identify neural involvement is that the addition of sensitizing manoeuvres has no impact on pain perception when the origin of the pain is non-neural. In this study, experimental muscle pain was induced by injection of hypertonic saline in tibialis anterior or soleus in 25 asymptomatic, naive volunteers. A first experiment investigated the impact of hip adduction, abduction, medial and lateral rotation in the SLR position. In a second experiment, the different stages of the slump test were examined. The intensity and area of experimentally induced muscle pain did not increase when sensitizing manoeuvres were added to the SLR or throughout the successive stages of the slump test. The findings of this study lend support to the validity of the use of sensitizing manoeuvres during neurodynamic testing. (C) 2004 Elsevier Ltd. All rights reserved.

The impact of residential respite care on the behavior of older people

Background: The aim of this study was to examine the impact of residential respite care on disruptive behavior displayed by older people, particularly those with dementia. Methods: A quasi-experimental, repeated-measures, single-group design was used. The participants were a consecutive series of 100 older people with a mean age of 81.8 years (range 66-96 years) who had been booked for a respite admission to one of several residential aged care facilities in a provincial Australian city. A diagnosis of dementia was reported for 29% of the sample. Disruptive behaviors were rated before and after the period of respite by home caregivers (N = 100) and during the period of respite by nurses (N= 25) using the Dementia Behavior Disturbance Scale (DBDS). Results: Age, male gender and the presence of dementia were all significantly related to the frequency of reported disruptive behaviors. Residential respite care was associated with a significant reduction in the frequency of reported disruptive behaviors in older people (Wald chi(2) = 28.28, P < 0.0001). However, this improvement in behavior did not persist into the post-respite period. The deteriorating behavioral trajectory that was evident prior to respite care continued following the period of respite care. Conclusions: Residential respite care was associated with a temporary diminution in the frequency of reported disruptive behaviors in older people. This finding should be reassuring both for family carets considering placing a relative in residential respite care and for health workers considering whether to recommend such a course of action.

Apnea diving: Long-term neurocognitive sequelae of repeated hypoxemia

This article examines the neurocognitive sequelae of repeated exposure to hypoxemia in apnea (breath-hold) divers. A brief review of the literature on the physiological and neurological adaptations involved in the human diving reflex is presented. The results from a neuropsychological investigation of N = 21 elite apnea divers are evaluated. Standard neuropsychological tests, with known sensitivity to mild brain insults, included speed of visuo-motor responding, speed of language comprehension, response inhibition, and visual and verbal attention and recall tasks. Results indicated that the breath-hold divers performed tasks within the average range compared to norms on all tests, suggesting that 1-20 years of repeated exposure to hypoxemia including multiple adverse neurological events did not impact on performance on standard neuropsychological tasks. The results are discussed in relation to implications for clinical conditions such as sleep apnea, respiratory disorders, altitude sickness, and recreational apnea activities.

Dynamic assessment of articulation during lingual fatigue in myasthenia gravis

The present study aimed to investigate how induced lingual fatigue affected lingual strength, articulatory kinematics, and perceptual speech features in CS, a 51-year-old female with active myasthenia gravis (MG), and three age and gender matched control participants, Lingual fatigue was elicited via a series of endurance tasks using a tongue pressure bulb. Following each endurance task, the participants performed a speech task containing the phonemes /k/, /t/, and /j/ that was recorded with an electromagnetic articulograph, followed by a lingual strength assessment using a tongue pressure bulb. Participants repeated this schedule over five phases and kinematic and strength changes during each phase were compared to baseline measurements. All of CSs significant kinematic changes occurred during the final fatigue phase compared to 27.3% of the control group's kinematic changes occurring during this phase, suggesting the kinematic changes associated with fatigue were not accelerated in CS. The endurance tasks also elicited different kinematic effects for CSs anterior and posterior tongue segments. While CS exhibited mostly similar kinematic and perceptual changes to the control group, some of CS's perceptual transcriptions for /k/ and kinematic changes were not replicated, indicating that some different perceptual and physiological consequences to CS's speech were elicited by the endurance tasks.

Impact of two different body mass management strategies on repeat rowing performance

Purpose: The present study was conducted to examine the impact of acute weight loss on repeat 2000-m rowing ergometer performance during a simulated multiday regatta. and to compare two different body mass management strategies between races. Methods: Competitive rowers (N = 16) were assigned to either a control (CON), partial recovery (RECpartial), or complete recovery (RECcomplete) group. Volunteers completed four trials, each separated by 48 h. No weight restrictions were imposed for the first trial. Thereafter, athletes in RECpartial and RECcomplete were required to reduce their body mass by 4% in the 24 h before trial 2, again reaching this body mass before the final two trials. No weight restrictions were imposed on CON. Aggressive nutritional recovery strategies were used in the 2 h following weigh-in for all athletes. These strategies were maintained for the 12-16 h following racing for RECcomplete with the aim of restoring at least three quarters of the original 4% body mass loss. Postrace recovery strategies were less aggressive in RECpartial; volunteers were encouraged to restore no more than half of their initial 4% body mass loss. Results: Acute weight loss increased time to complete the first at-weight performance trial by a small margin (mean 3.0, 95% CI -0.3 to 6.3 s, P = 0.07) when compared with the CON response. This effect decreased when sustained for several day,. Aggressive postrace recovery strategies tended to eliminate the effect of acute Weight loss on subsequent performance. Conclusion: Acute weight loss resulted in a small performance compromise that was reduced or eliminated when repeated over several days. Athletes should be encouraged to maximize recovery in the 12-16 h following racing when attempting to optimize subsequent performance.