A review of the effectiveness of Cimicifuga racemosa (black cohosh) for the symptoms of menopause

1. Environmental contact with cold air is a common cause of respiratory distress in obstructive lung disease, and direct and reflex changes in bronchial calibre are well documented with this stimulus when it is inhaled or contacts the exposed skin respectively. It is now known that skin chilling does not amplify the effects of breathing cold air, but it is not established if this lack of interaction is unique, or applies to other forms of airway constrictors. 2. To provide data on this issue, 10 subjects with atopic asthma underwent methacholine bronchoprovocations with and without chilling of the integument of their heads and thoraces for 30 min. Chilling was accomplished with a specially designed thermal garment. Spirometry as well as core and skin temperatures were serially monitored during all experiments. 3. In the control phase (no cooling), integumental temperatures rose slightly, the forced expiratory volume in 1.0 s (FEV1.0) did not change, and the mean provocative concentration of methacholine required to reduce the FEV1.0 by 20% (PC20 meth) was 0.47 +/- 0.17 mg/ml (2.4 +/- 0.87 mmol/l). In the cold trial, the temperature of the back fell 5.1 +/- 1.7 degrees C to 28.7 +/- 1.8 degrees C (P < 0.01), core temperatures did not change, and airway obstruction developed (delta FEV1.0 = -6.7 +/- 2.1%; P < 0.05). The PC20 meth, however, was unaltered [PC20 meth = 0.45 +/- 0.13 mg/ml (2.3 +/- 0.66 mmol/l); P = 0.85]. 4. These results demonstrate that although skin cooling produces mild airway obstruction in subjects with asthma, it does not change the response to non-specific bronchoconstrictors such as methacholine.     

Relationship between external resistances, lung function changes and maximal exercise capacity

In upper airway obstruction (UAO) the relationship between the degree of obstruction, exercise limitation and lung function indices is not well established. Therefore, we investigated in nine healthy subjects (age 36+/-9 yrs) the effects of two added resistances at the mouth (R1 = added resistance with 7.8 mm diameter; R2 = 5.7 mm) on forced expiratory volume in one second (FEV1), peak expiratory flow (PEF), airway resistance (Raw) and maximal breathing capacity (measured during 15 s = measured maximum breathing capacity (MBCm); calculated as FEV1x37.5 = calculated maximum breathing capacity (MBCc)) on the one hand, and maximum exercise capacity (W'max), minute ventilation (V'E) and CO2 elimination (V'CO2) on the other. We found that R1 had almost no influence on FEV1 but decreased PEF by approximately 35% and increased Raw by almost 300%; it decreased W'max by merely approximately 10% while maximal exercise ventilation (V'Emax) was only 65% of control and only reached approximately 40% MBCc and approximately 70% MBCm; yet V'E and V'CO2 were significantly reduced at high exercise levels indicating hypoventilation. With R2, FEV1 was reduced by 25% and PEF by 55%, and Raw was increased by 600%; W'max was approximately 60% of control, V'Emax was only 35% of control and reached approximately 30% MBCc and approximately 60% MBCm, V'E was already reduced at moderate exercise levels. We conclude that: 1) an upper airway obstruction of 6 mm diameter (but not of 8 mm) had a marked influence on maximum exercise capacity due to hypoventilation; 2) calculated maximum breathing capacity markedly overestimated measured maximum breathing capacity because the forced expiratory volume in one second is an insensitive index of upper airway obstruction and because it does not take inspiratory flow limitation into account; and 3) a 10% decrease in maximum exercise capacity was linearly related with a 7% decrease in the forced expiratory volume in one second and a 150% increase in airway resistance. A 10% decrease in maximal exercise ventilation was related to a 8.5% decrease in peak expiratory flow and 9% decrease in measured maximum breathing capacity.     

Differential effects of nasal continuous positive airway pressure on reversible or fixed upper and lower airway obstruction

Our study was to assess whether there were differential effects of nasal continuous positive airway pressure (nCPAP) on different kinds of obstruction in either upper or lower airways in patients with chronic obstructive pulmonary disease (COPD). nCPAP (6 cmH2O for ten minutes) was applied to 7 patients with reversible extrathoracic upper airway obstruction (RUAO) and 3 patients with fixed extrathoracic upper airway obstruction (FUAO). Eighteen stable asthmatics, receiving methacholine challenge to induce a more than 20% reduction in FEV1, were randomly investigated for the effect of nCPAP or sham pressure on reversible lower airway obstruction. Nine stable COPD patients were enrolled to study the effect on irreversible lower airway obstruction. Maximal expiratory and inspiratory flow volume curves and dyspnoea scores were obtained before and after immediate withdrawal of nCPAP. In the RUAO group, nCPAP significantly improved stridor and dyspnoea scores, decreased the ratio of FEF50/FIF50 from 2.05 +/- 0.25 to 1.42 +/- 0.16, and increased peak inspiratory flow (PIF) as well as forced inspiratory vital capacity by 26 +/- 8% and 9 +/- 4%, respectively. In expiratory phase, there was no significant change in pulmonary functions. In asthmatics, nCPAP significantly reversed methacholine-induced bronchoconstriction increasing forced vital capacity by 10 +/- 3%, FEV1 by 15 +/- 4% and PIF by 32 +/- 11%. nCPAP significantly increased the response to bronchodilators. The improvement in airflow rate persisted for at least 5 min after nCPAP withdrawal and was highly correlated with the response to bronchodilators. There was no significant effect of nCPAP on airflow rate in COPD patients. Subjective dyspnoea score changes paralleled the pulmonary function improvement. We conclude that there are differential effects of nCPAP on airflow rates in patients with different nature of airway obstruction. Patients with airway obstruction caused by structural changes may not benefit from the use of nCPAP in improving airflow rates.     

Bronchial obstruction and exhaled nitric oxide response during exercise in cold air

This study examines whether exhausting exercise in cold air induces bronchial obstruction and changes in exhaled [NO] and in exhaled NO output (V'NO). Thus, eight well-trained males performed two incremental exercise tests until exhaustion, followed by 5 min of recovery in temperate (22 degrees C) and cold (-10 degrees C) environments, at random. At -10 degrees C, they were dressed in warm clothes. Ventilation (V'E), oxygen consumption (V'O2), carbon dioxide production, cardiac frequency (fC), and [NO] and V'NO were measured continuously. Before and after each test, the subjects' maximal expiratory flow-volume curves and peak expiratory flow, forced expiratory volume in one second (FEV1) and forced expiratory flow at 25 (FEF25), 50 (FEF50) and 75% (FEF75) of forced vital capacity were determined. At -10 degrees C, significant decreases in FEV1 and FEF75 were observed after exercise. At rest and at the same submaximal intensity, V'O2, V'E and fC did not differ significantly. At rest and up to approximately 50% peak V'O2, [NO] and V'NO values were lower at -10 degrees C than at 22 degrees C. Thereafter, and during recovery, the V'NO response became similar at both -10 and 22 degrees C. This study confirms that considerable hyperpnoea in cold air causes a detectable airway obstruction. This airway cooling also induces an initial decrease in the exhaled NO response. Since endogenous NO-production is involved in bronchial dilation, it cannot be excluded that this lack of production may favour the appearance of airway obstruction.     

Malignant melanoma in Europe: changes in mortality rates (1970-90) in European Community countries

We measured metabolic rates (mL O2 h-1, converted to kcal d-1), deep body temperatures (degree C), and skin temperatures (degree C) and calculated whole-animal thermal conductances (mL O2 g-1 h-1 degree C-1) of five 3-yr-old harbor seals (Phoca vitulina concolor) at air temperatures between -20 degrees and 35 degrees C. The mean thermal neutral zone of these seals extended from a lower critical temperature of -12.9 degrees +/- 1.6 degrees C (SD) to an upper critical temperature of 28.6 degrees +/- 1.7 degrees C. Hyperthermia was observed at an ambient air temperature of 35 degrees C. Mean standard metabolic rate was 1,553.6 +/- 168.2 kcal d-1, about 1.2 times the value expected for adult animals of similar body mass (mean mass = 49.2 +/- 7.5 kg). Mean deep body temperature increased from 37.5 degrees +/- 0.30 degrees C at an ambient temperature of 30 degrees C and reached 39.3 degrees +/- 0.33 degrees C at an ambient temperature of 35 degrees C. Skin temperature decreased with decreasing ambient temperature but remained well above ambient temperature. Mean whole-animal thermal conductance decreased from an ambient temperature of 35 degrees C until it reached a minimum value of 0.007 mL O2 g-1 h-1 degree C-1 at -4.0 degrees C; it then increased with a further decrease in ambient temperature. In comparison to the thermal limits of the same seals during their first year of life, the results indicate a broadening of the thermal neutral zone with age: an 11 degrees C decrease in the lower critical temperature and a 3.5 degrees C increase in the upper critical temperature. These findings suggest that warm ambient air temperatures should not pose any particular thermoregulatory problems for larger and older harbor seals, even beyond the limits of their current annual distribution.     

The Yale Geriatric Care Program is not effective in a pilot study in The Netherlands

Brain temperature was measured at various depths beneath the pial surface in patients with hydrocephalus of varying aetiology. Temperature increased gradually with depth in all patients, with the highest temperature found in the ventricle. The difference between intraventricular and rectal temperatures (delta v-r) was greater in patients who underwent continuous ventricular drainage than in patients who underwent ventriculoperitoneal shunt (continuous ventricular drainage; 1.2 (SD 0.40) degrees C, mean (SD), n=5 v ventriculoperitoneal shunt; 0.4 (SD 0.45) degrees C, n=16; p< 0.05). The difference between intracerebral and rectal temperatures (delta b2-r) was also greater in patients with continuous ventricular drainage than in patients with ventriculoperitoneal shunt (continuous ventricular drainage; 0.1 (SD 0.86) degrees C, n=5 v ventriculoperitoneal shunt; -0.7 (0.86) degrees C, n=16; p< 0.05). Among patients with normal pressure hydrocephalus, these differences were greater in the patients with better outcomes after shunt surgery than in the less improved group (delta v-r; 0.7 (SD 0.27) degrees C, n=7 v 0.1 (SD 0.40) degrees C, n=5, p< 0.01, delta b2-r; -0.2 (SD 0.61) degrees C, n=7 v -1.4 (0.90) degrees C, n=5, p< 0.01).     

Indices from flow-volume curves in relation to cephalometric, ENT- and sleep-O2 saturation variables in snorers with and without obstructive sleep-apnoea

In a group of 37 heavy snorers with obstructive sleep apnoea (OSA, Group 1) and a group of 23 heavy snorers without OSA (Group 2) cephalometric indices, ENT indices related to upper airway collapsibility, and nocturnal O2 desaturation indices were related to variables from maximal expiratory and inspiratory flow-volume (MEFV and MIFV) curves. The cephalometric indices used were the length and diameter of the soft palate (spl and spd), the shortest distance between the mandibular plane and the hyoid bone (mph) and the posterior airway space (pas). Collapsibility of the upper airways was observed at the level of the tongue base and soft palate by fibroscopy during a Müller manoeuvre (mtb and msp) and ranked on a five point scale. Sleep indices measured were the mean number of oxygen desaturations of more than 3% per hour preceded by an apnoea or hypopnoea of more than 10 s (desaturation index), maximal sleep oxygen desaturation, baseline arterial oxygen saturation (Sa,O2) and, in the OSA group, percentage of sleep time with Sa,O2 < 90%. The variables obtained from the flow-volume curves were the forced vital capacity (FVC), forced expiratory and inspiratory volume in 1 s (FEV1 and FIV1), peak expiratory and peak inspiratory flows (PEF and PIF), and maximal flow after expiring 50% of the FVC (MEF50). The mean of the flow-volume variables, influenced by upper airway aperture (PEF, FIV1) was significantly greater than predicted.(ABSTRACT TRUNCATED AT 250 WORDS)     

Detection of nivalenol genotoxicity in cultured cells and multiple mouse organs by the alkaline single-cell gel electrophoresis assay

The effects of upper airway (UAW) flows and pressures on breathing pattern and respiratory muscle activities were studied in anesthetized rats breathing through a tracheostomy. A steady flow (approximately 1000 ml/kg/min) of cold dry air, or cold wet air, or warm wet air was passed through the UAW, in the expiratory direction for approximately 20 sec (20-40 sec). In other trials positive or negative pressure was applied to the isolated UAW for a similar duration. There was a marked prolongation of the expiratory duration and decreases in peak inspiratory flow, tidal volume, and peak diaphragm electromyogram (EMG) activity in response to cold dry airflow. The responses to cold wet air were reduced but still significant. Warm wet air had no effect on breathing. These responses show that UAW cooling and drying depress breathing in the rat and that cooling itself could cause the inhibition of breathing. Negative pressure induced substantial increases in genioglossus and laryngeal inspiratory activity while positive pressure caused a decrease in genioglossus activity. Positive pressure also increased expiratory time while negative pressure increased inspiratory time. These results confirm the functional role of the UAW dilating muscles in preventing UAW from collapse in rats.     

Differential respiratory muscle recruitment induced by clonidine in awake goats

The purpose of this study was to test the hypothesis that dysrhythmic breathing induced by the alpha2-agonist clonidine is accompanied by differential recruitment of respiratory muscles. In adult goats (n = 14) electromyographic (EMG) measurements were made from inspiratory muscles (diaphragm and parasternal intercostal) and expiratory muscles [triangularis sterni (TS) and transversus abdominis (Abd)]. EMG of the thyroarytenoid (TA) muscle was used as an index of upper airway (glottal) patency. Peak EMG activities of all spinal inspiratory and expiratory muscles were augmented by central and peripheral chemoreceptor stimuli. Phasic TA was apparent in the postinspiratory phase of the breathing cycle under normoxic conditions. During dysrhythmic breathing episodes induced by clonidine, TS and Abd activities were attenuated or abolished, whereas diaphragm and parasternal intercostal activities were unchanged. There was no tonic activation of TS or Abd EMG during apneas; however, TA activity became tonic throughout the apnea. We conclude that 1) alpha2-adrenoceptor stimulation results in differential recruitment of respiratory muscles during respiratory dysrhythmias and 2) apneas are accompanied by active glottic closure in the awake goat.     

Functional upper airway obstruction and chronic irritation of the larynx

Wheezing and dyspnoea are typical symptoms of asthma but can also be found in diseases of the extrathoracic airways. Functional upper airway obstruction may imitate, as well as complicate asthma. Functional upper airway obstruction was first described as a conversion disorder in young females with inspiratory stridor. Subsequently, it was found that functional upper airway obstruction was more often a secondary phenomenon in chronic asthma also involving the expiratory laryngeal airflow. During a period of 15 months, we diagnosed six cases of functional upper airway obstruction. Five patients were female and one male, and four were also asthmatics. Three cases showed chronic sinusitis with postnasal drip (PND) and/or gastro-oesophageal reflux. Both disorders may irritate the larynx. Treatment of sinusitis and gastro-oesophageal reflux led to a significant improvement of dyspnoea in all three of these patients. In asthma refractory to treatment and in the case of an asthmatic exacerbation without obvious cause, functional upper airway obstruction should be excluded to avoid unnecessary treatment with systemic steroids. Some of the possible causative factors of functional upper airway obstruction, such as postnasal drip and gastro-oesophageal reflux, are easily treatable.     

The influence of clinical factors on site of airway obstruction in asthma

The effect of breathing a gas mixture less dense than room air (80% helium, 20% 02) on the maximal expiratory flow-volume curve was used to determine the influence of clinical factors on the site and nature of the airway obstruction in asthmatics. If an asthmatic did not smoke or have chronic bronchitis or recurrent respiratory infections, the site of obstruction was in more central airways than it was in the presence of these factors, when the main site was more likely to be in more peripheral airways. Both the peripheral and the central airway obstruction were at least in part due to bronchoconstriction and could be reversed with bronchodilators. Comparison of maximal expiratory flow-volume curves when the subject was breathing air and when he or she was breathing a less dense gas mixture may indicate change in the mechanical properties of the lung after the use of bronchodilators that are not apparent breathing air alone. In some instances, bronchodilators produced no change in the maximal expiratory flow-volume curve when the subject was breathing air, but there were substantial changes when he or she was breathing a mixture of helium and O2.     

Influence of upper airway pressure oscillations on soft palate muscle electromyographic activity

Snoring is characterized by high-frequency (30-50 Hz) pressure oscillations (HFPO) in the upper airway (UA). The soft palate is a major oscillating structure during snoring, and soft palate muscle (SPM) activity is an important determinant of velopharyngeal patency. Consequently, we examined the effect of artificial HFPO applied to the UA on the integrated electromyographic (EMG) activity of the SPMs in 11 supine mouth-closed anesthetized (pentobarbital sodium/chloralose) dogs breathing spontaneously via a tracheostomy. The EMGs of the palatinus (Pal; n = 11), levator veli palatini (LP; n = 9), and tensor veli palatini (TP; n = 8) were monitored with intramuscular fine-wire electrodes. Peak inspiratory and peak expiratory EMG activity was measured in arbitrary units (au) as the mean of five consecutive breaths. HFPO [+/- 4.5 +/- 0.4 (SE) cmH2O; 30 Hz] applied at the laryngeal end of the isolated UA increased peak inspiratory EMG from 3.3 +/- 2.0 to 8.4 +/- 1.7 au (P < 0.05) for Pal and from 2.0 +/- 1.1 to 7.3 +/- 2.7 au (P < 0.05) for LP. For the TP, increases were evident in four dogs, but mean values for the group did not change (5.8 +/- 2.4 to 11.0 +/- 4.1 au, P = 0.5). The peak expiratory EMG did not change for any SPM (all P > 0.3). Thus HFPO applied to the UA augments inspiratory SPM activity. Reflex augmentation of SPM activity by HFPO may serve to dilate the retropalatal airway and/or stiffen the soft palate during inspiration in an attempt to stabilize UA geometry during snoring.     

Heavy snoring with upper airway resistance syndrome may induce intrinsic positive end-expiratory pressure

We studied eight heavy snorers with upper airway resistance syndrome to investigate potential effects of sleep on expiratory airway and lung resistance, intrinsic positive end-expiratory pressure, hyperinflation, and elastic inspiratory work of breathing (WOB). Wakefulness and non-rapid-eye-movement sleep with high- and with low-resistance inspiratory effort (H-RIE and L-RIE, respectively) were compared. No differences in breathing pattern were seen across the three conditions. In contrast, we found increases in expiratory airway and lung resistance during H-RIE compared with L-RIE and wakefulness (56 +/- 24, 16 +/- 4, and 11 +/- 4 cmH2O . 1(-1) . s, respectively), with attendant increases in intrinsic positive end-expiratory pressure (5.4 +/- 1.8, 1.4 +/- 0.5, and 1.3 +/- 1.3 cmH2O, respectively) and elastic WOB (6.1 +/- 2.2, 3.7 +/- 1.2, and 3.4 +/- 0.7 J/min, respectively). The increase in WOB during H-RIE is partly caused by the effects of dynamic pulmonary hyperinflation produced by the increased expiratory resistance. Contrary to the Starling model, a multiple-element compliance model that takes into account the heterogeneity of the pharynx may explain flow limitation during expiration.     

Effect of upper airway cooling and CO2 on diaphragm and geniohyoid muscle activity in the rat

Upper airway (UA) reflexes play an important role in regulating breathing and UA patency, but the effects of UA CO2 and cooling on ventilation and UA muscle activity are controversial. Diaphragm and geniohyoid electromyographic activities were recorded in anaesthetized rats, breathing spontaneously through a low-cervical tracheostomy. Warmed, humidified air containing 0 or 10% CO2 and cooled, room humidity air were applied at constant flow to the UA through a high- cervical tracheostomy. Spontaneous tracheal airflow, UA airflow and temperature, blood pressure, and rectal temperature were recorded. In all animals, the geniohyoid muscle had phasic inspiratory activity, which slightly preceded diaphragmatic activity. CO2 had no effect on mean peak integrated diaphragmatic activity and variable effects on geniohyoid activity. The coefficients of variation of these activities were unaffected by CO2. Similar results were obtained following bilateral mid-cervical vagotomy. Cool air decreased respiratory frequency (78+/-8%) (mean+/-SD % of control), peak inspiratory flow (78+/-5%) and diaphragmatic activity (77+/-4%), and increased geniohyoid activity (149+/-11%). Cutting the superior laryngeal nerves abolished these effects. In conclusion, whilst moderate upper airway cooling inhibits breathing and excites geniohyoid muscle activity, upper airway carbon dioxide has minimal effect.     

Kinetics of heat inactivation of Venezuelan equine encephalomyelitis virus

Thermal inactivation of Venezuelan Equine Encephalomyelitis Virus (VEEV) was studied at temperatures from 26 degrees to 55 degrees C. Inactivation of infectivity took place by two thermodynamically different reactions, one of which predominated at temperatures below 44 degrees C and the other at higher temperatures. The presence of 1 or 2 M NaCl stabilized the VEE virus at low temperatures but enhanced the inactivation at high temperatures. This latter effect at temperatures higher than 50 degrees C, is associated with the occurrence of two-component survival curves. The different effects of hypertonic NaCl concentrations at the two ranges of temperature, are related to different mechanisms of inactivation operating at each range (protein denaturation and nucleic acid-RNA breakdown). Different kinetics of thermal inactivation at 55 degrees C were observed between virus strains with different virulence. However, no significant correlations was found between the virulence of the eleven VEE virus strains studied and their thermostability at 37 degres and 55 degrees C.     

Airway resistance and work of breathing in tracheostomy tubes

Recommendations for sizing of tracheostomy tubes are generally based on anatomic considerations with the largest fitting tube most commonly placed. Once in the tracheostomy site, the tube assumes the new role of the upper airway. Consideration of the airway resistance of each tracheostomy tube and change in work of breathing are important in maintaining the respiratory system homeostasis. The airflow dynamics of neonatal, pediatric, and adult tracheostomy tubes were studied. Flow rates were plotted against change in pressure for inspiratory and expiratory flows and resistances for each tube were calculated. The expiratory resistances were larger for the neonatal tubes and pediatric tubes 0 and 00, while inspiratory resistances were the limiting factor in the adult tubes and the larger pediatric tubes. Comparison of calculated resistances of the tracheostomy tubes was made with known physiologic airway resistances. Adult tubes 8 and 10 most closely simulated the upper airway resistance of adults and neonatal tube 0 appeared most appropriate for the newborn. Work of breathing was determined for each tracheostomy tube. Increasing tube diameter as well as decreasing tidal volume and respiratory rate decreased the amount of work required to maintain a given flow.     

Isothermal titration microcalorimetric studies for the binding of octenoyl-CoA to medium chain acyl-CoA dehydrogenase

We investigated the binding of octenoyl-CoA to pig kidney medium chain acyl-CoA dehydrogenase (MCAD) by isothermal titration microcalorimetry under a variety of experimental conditions. At 25 degrees C in 50 mM phosphate buffer at pH 7.6 (ionic strength of 175 mM), the binding is characterized by the stoichiometry (n) of 0.89 mole of octenoyl-CoA/(mole of MCAD subunit), delta G = -8.75 kcal/mol, delta H = -10.3 kcal/mol, and delta S = -5.3 cal mol(-1) K(-1), suggesting that formation of MCAD-octenoyl-CoA is enthalpically driven. By employing buffers with various ionization enthalpies, we discerned that formation of the MCAD-octenoyl-CoA complex, at pH 7.6, accompanies abstraction (consumption) of 0.52 +/- 0.15 proton/(MCAD subunit) from the buffer media. We studied the effects of pH, ionic strength, and temperature on the thermodynamics of MCAD-octenoyl-CoA interaction. Whereas the ionic strength does not significantly influence the above interaction, the pH of the buffer media exhibits a pronounced effect. The pH dependence of the association constant of MCAD +octenoyl-CoA <==> MCAD-octenoyl-CoA yields a pKa for the free enzyme of 6.2. Among thermodynamic parameters, whereas delta G remains invariant as a function of temperature, delta H and deltaS(standard) both decrease with an increase in temperature. At temperatures of < 25 degrees C, delta G is dominated by favorable entropic contributions. As the temperature increases, the entropic contributions progressively decrease, attain a value of zero at 23.8 degrees C, and then becomes unfavorable. During this transition, the enthalpic contributions become progressively favorable, resulting in an enthalpy-entropy compensation. The temperature dependence of delta H yields the heat capacity change (delta Cp(0)) of -0.37 +/- 0.05 kcal mol(-1) K(-1), attesting to the fact that the binding of octenoyl-CoA to MCAD is primarily dominated by the hydrophobic forces. The thermodynamic data presented herein are rationalized in light of structural-functional relationships in MCAD catalysis.     

Physical properties of ceramides: effect of fatty acid hydroxylation

The structural and thermotropic properties of alpha-hydroxy fatty acid (HFA) and non-hydroxy fatty acid (NFA) ceramides (CER) have been studied using differential scanning calorimetry (DSC) and X-ray diffraction techniques. The DSC of anhydrous HFA-CER shows a single, sharp reversible transition at 95.6 degrees C (delta H = 15.3 kcal/mol). At intermediate hydrations HFA-CER exhibited more complex behavior but at maximum hydration only a single reversible transition is observed at 80.0 degrees C (delta H = 8.5 kcal/mol). X-ray diffraction of hydrated (74% water) HFA-CER at 20 degrees C shows a lamellar structure with a bilayer periodicity d = 60.7 Angstrum; a single wide angle reflection at 4.2 Angstrum is characteristic of hexagonal chain packing. Above the main transition temperature at 91 degrees C, a hexagonal (HII) phase is observed. In contrast, DSC of anhydrous NFA-CER demonstrates two thermal transitions at 81.3 degrees C (delta H = 6.8 kcal/mol) and 85.9 degrees C (delta H = 3.5 kcal/mol). With increasing hydration, both transitions shift towards lower temperatures; at maximum hydration, on heating, the endothermic transitions occur at 72.7 degrees C (delta H = 9.8 kcal/mol) and 81.1 degrees C (delta H = 4.0 kcal/mol). On cooling, there is hysteresis of both transitions. X-ray diffraction of NFA-CER (80% water) at 20 degrees C shows a well-ordered lamellar structure with a bilayer periodicity d = 58.6 Angstrum and three wide-angle reflections at 4.6 Angstrum, 4.2 Angstrum, and 3.8 Angstrum. At 77 degrees C (between the two transitions), again a lamellar structure exists with reduced bilayer periodicity d = 53.1 Angstrum and four wide-angle reflections at 4.6 Angstrum, 4.2 Angstrum, and 3.8 Angstrum are observed. Above the second transition, only a single low angle reflection at 30.0 Angstrum is observed; a diffuse reflection at 4.6 Angstrum is indicative of a melted chain phase. Thus, HFA-CER exhibits a simple phase behavior involving the reversible conversion of a gel phase to a hexagonal phase (L beta-->HII). However, NFA-CER shows a more complex polymorphic phase behavior involving two gel phases.     

Widespread short-latency stretch reflexes and their modulation during stumbling over obstacles

We investigated the extent to which measurements of maximal expiratory flow at FRC (V EmaxFRC) are influenced by the dynamic increase of FRC in young infants by superimposing partial forced expiratory flow-volume curves on those obtained after lung inflation to 2 kPa (20 cm H2O) in 12 infants during the first month of life. The elastic equilibrium volume (EEV) of the respiratory system was estimated by extrapolating the passive expiratory time constant (obtained after lung inflation but prior to forced deflation) to zero flow. There was a very strong relationship between V EmaxFRC (which ranged from 11 to 190 ml/s) and the extent to which FRC was dynamically increased above EEV (range: 0 to 5 ml/kg), r2 = 0.88. The results of this study suggest that, although V EmaxFRC remains a useful means of measuring peripheral airway function in infants, its values should be interpreted with caution during the neonatal period. In particular, the relatively high V EmaxFRC values reported in healthy newborn infants may reflect differences in breathing strategy rather than airway structure. More meaningful within- and between-infant comparisons of peripheral airway function may be obtained by calculating forced expiratory flows at a fixed interval (e.g., 3 ml/kg) above EEV, rather than at the FRC that is operational at the time of measurement.     

Sleep-induced breathing instability. University of Wisconsin-Madison Sleep and respiration Research Group

We present a view of the neuromechanical regulation of breathing and causes of breathing instability during sleep. First, we would expect transient increases in upper airway resistance to be a major cause of transient hypopnea. This occurs in sleep because a hypotonic upper airway is more susceptible to narrowing and because the immediate excitatory increase in respiratory motor output in response to increased loads is absent in non-REM sleep. Secondly, sleep predisposes to an increased occurrence of ventilatory "overshoots", in part because abruptly changing sleep states cause transient changes in upper airway resistance and in the gain of the respiratory controller. Following these ventilatory overshoots, breathing stability will be maintained if excitatory short-term potentiation is the prevailing influence. On the other hand, apnea and hypopnea will occur if inhibitory mechanisms dominate following the ventilatory overshoot. These inhibitory mechanisms include: a) hypocapnia-if transient, will inhibit carotid chemoreceptors and cause hypopnea, but if prolonged will inhibit medullary chemoreceptors and cause apnea; b) a persistent inhibitory effect from lung stretch; c) baroreceptor stimulation, from a transient rise in systemic blood pressure immediately following termination of apnea or hypopnea may partially suppress the accompanying hyperpnea; d) depression of central respiratory motor output via prolonged brain hypoxia. Once apneas are initiated, reinitiation of inspiration is delayed even though excitatory stimuli have risen well above their apneic thresholds, and these prolonged apneas are commonly accompanied by tonic EMG activation of expiratory muscles of the chest wall and upper airway.