The prevalence of airways hyperresponsiveness in members of an exercise training facility.

Athletes have a high prevalence (11-50%) of exercise-induced asthma, which may be caused by the hyperventilation accompanying repetitive bouts of strenuous exercise. We hypothesized that recreational exercisers would display a similar trend. Eucapnic voluntary hyperventilation (EVH) bronchoprovocation (breathing 21% O2, 5% CO2, and 74% N2 at 60% of MVV for 5 minutes) was performed to determine the prevalence of airways hyperresponsiveness (AHR) in adults (n=212, 146 males, mean +/- standard deviation, age 32 +/- 10 years) who exercised regularly (10 +/- 10 years, 31 +/- 28% of their lives): none had a previous diagnosis of asthma. AHR was defined by at least a 10%, 20%, or 25% decline in FEV1, FEF(25-75), or PEFR, respectively, by spirometry at 1, 5, 10, and 15 minutes post-EVH. Forty-one of 212 (19%) tested positive for AHR: 20 of 41 (49%) were positive by FEV1, 28 of 41 (68%) by FEF(25-75), and 27 of 41 (66%) by PEFR. Comparing responders with nonresponders: pre-EVH lung function was equivalent, except for FEV1, which was reduced (p<0.05) in responders (96 +/- 13 vs. 102 +/- 12% predicted). Mean maximal negative deflections for responders were: for FEV1, -17 +/- 7%; FEF(25-75), -31 +/- 10%; PEFR, -38 +/- 11%. Ranges of decline for responders were: FEV1, -10 to -33%; FEF(25-75), -20 to -59%; PEFR, -25- to -70%. We conclude that in these regular exercisers, the prevalence of AHR is high and comparable with some athletic populations.     

Anxiety and hippocampus volume in the rat.

In depressed patients as well as healthy controls, a positive relationship between hippocampal volume and trait anxiety has been reported. This study sought to explore the possible inter-relation between hippocampal volume and trait anxiety further. Magnetic resonance imaging at 7 T was used to measure hippocampal volumes in a rat model of extremes in trait anxiety (experiment 1) and in a Wistar population with normal anxiety-related behavior (experiment 2). In addition to anxiety-related behavior, potentially confounding factors (depression-like, exploratory, and locomotor behavior) were assessed. Experiment 1 globally supported the hypothesis of a positive relationship between hippocampus volume and trait anxiety but did not allow for ruling out possible confounds arising from cosegregation of other behavioral traits. Experiment 2 yielded strong evidence for a negative relationship which was specific for trait anxiety. Thus, the relationship between hippocampal volume and anxiety may be more complex than expected. Interestingly, anxiety-related behavior in experiment 2 had a stronger influence on hippocampal volume than depression-like behavior. In the light of hippocampal volume loss in anxiety disorder and frequent comorbidity of anxiety and depression, this finding suggests that further research into the relationship between anxiety and hippocampal volume may be critical for understanding hippocampal contributions to normal and pathological behavior.     

Decrement of the skin conductance response to repeated volitional inspiration.

OBJECTIVE: To examine response decrement of the recently reported inspiratory skin conductance response (SCR) [Lim CL, Seto-Poon M, Clouston PD, Morris JG. Sudomotor nerve conduction velocity and central processing time of the skin conductance response. Clin Neurophysiol 2003;114:2172-80]. METHODS: Twelve healthy adult volunteers performed 3 tasks (A) a control task of maintaining tidal breathing and then two randomized tasks, (B) a deep inspiration to a target oral pressure and (C) tapping with a finger. Each task was performed 30 times on cue every 20s in 3 runs with 5 min of rest between runs. The SCR, oral pressure, airflow, inspired volume and cue signal were recorded continuously and analysed offline. SCR amplitude was logarithmically transformed and then statistically analysed, using a linear mixed effects model, as a function of run number, trial number and absolute error between target and actual oral pressures. RESULTS: Inspiratory efforts elicited exponentially decreasing SCR amplitude with increasing trial number during each run (P < 0.0001). After adjusting for trial number, the mean SCR amplitude of the second and the third run were, respectively, 24.2 (95% CI (0.175, 0.336), P < 0.001) and 14.4% (95% CI (0.104, 0.200), P < 0.001) of the first run amplitude. CONCLUSIONS: Volitional deep inspiration reliably activates an SCR that exhibits response decrement with repetition, which may be habituation. SIGNIFICANCE: The volitional inspiratory SCR may assist in the assessment of sympathetic autonomic status in patients with peripheral afferent neuropathy.     

Holmes-like tremor of the lower extremity following brainstem hemorrhage.

Holmes tremor is an arrhythmic, 2- to 5-Hz resting, postural, and kinetic upper extremity movement disorder that occurs weeks to months after acute mesencephalic pathology. We present a patient who developed tremor in three body parts postbrainstem hemorrhage with subsequent hypertrophic olivary degeneration and discuss the relevant clinical evolution. Our case is unique because in addition to expected upper extremity and cervical dystonic head tremors, the patient also developed a severe lower extremity movement disorder, which we believe to be a form of Holmes tremor. Tremor involving the lower extremity in this setting has not been previously reported.     

Indomethacin-Dipalmitoylphosphatidylcholine Interaction. A Calorimetric Study of Drug Release from Poly(Lactide-co-glycolide) Microspheres into Multilamellar Vesicles

A comparative study of indomethacin controlled release from poly(lactide-co-glycolide) (50:50, molecular weight 3000) (PLGA) microspheres loaded with two different amounts of drug (10.9 ± 1%, and 34.1 ± 1% w/w) and pure free indomethacin, considering the effects exerted by the drug on the thermotropic behavior of dipalmitoylphosphatidylcholine multilamellar vesicles, was carried out by differential scanning calorimetry (DSC). The release was monitored by comparing the effect exerted by the free indomethacin on lipid thermotropic behavior with that of the drug released by the microspheres and relating these effects to a lipid aqueous dispersion containing the molar ratio of drug able to cause it. By DSC measurements, the pure free indomethacin was found to be able to have a fluidifying effect on the model membrane, causing a shift toward lower values of the transitional temperature (T_m), characteristic of phospholipid liposomes, without variations in the enthalpic changes (ΔH). This shift was found to be modulated by the drug molar fraction with respect to the lipid concentration in the aqueous dispersion. Successively, calorimetric measurements were performed on suspensions of blank liposomes added to weighed amounts of unloaded and indometha-cin-loaded microspheres as well as free powdered indomethacin, and the T_m shifts of the lipid bilayer caused by the drug released from the polymeric system, as well as by the free drug, were compared with that caused by free drug increasing molar fractions dispersed directly on the membrane, employed as a calibration curve to obtain the fraction of drug released. This drug release model could be employed to determine the different kinetics involved in the drug transfer from the microspheres to a membrane. This in vitro study suggests that the kinetic process involved in drug release is influenced by the amount of drug loaded in the microspheres. This calorimetric study shows that the PLGA microspheres are a good delivery system able to sustain drug release. Moreover, the DSC technique applied to the drug interaction with biomembranes constitutes a good tool for determining the drug release representing an innovative alternative in vitro model.