Effect of mandibular position on upper airway collapsibility and resistance.

It has been proposed that advancement of the mandible is a useful method for decreasing upper airway collapsibility. We carried out this study to test the hypothesis that mandibular advancement induces changes in upper airway patency during midazolam sedation. To explore its effect, we examined upper airway pressure-flow relationships in each of 4 conditions of mouth position in normal, healthy subjects (n = 9). In the neutral position, Pcrit (i.e., critical closing pressure, an index of upper airway collapsibility) was -4.2 cm H(2)O, and upstream resistance (Rua) was 21.2 cm H(2)O/L/sec. In the centric occlusal position, Pcrit was -7.1 cm H(2)O, and Rua was 16.6 cm H(2)O/L/sec. In the incisor position, Pcrit was significantly reduced to -10.7 cm H(2)O, and Rua was significantly reduced to 14.0 cm H(2)O/L/sec. Mandibular advancement significantly decreased Pcrit to -13.3 cm H(2)O, but did not significantly influence Rua (22.1 cm H(2)O/L/sec). We conclude that the mandibular incisors' position improved airway patency and decreased resistance during midazolam sedation.

Mouth-opening increases upper-airway collapsibility without changing resistance during midazolam sedation.

Sedative doses of anesthetic agents affect upper-airway function. Oral-maxillofacial surgery is frequently performed on sedated patients whose mouths must be as open as possible if the procedures are to be accomplished successfully. We examined upper-airway pressure-flow relationships in closed mouths, mouths opened moderately, and mouths opened maximally to test the hypothesis that mouth-opening compromises upper-airway patency during midazolam sedation. From these relationships, upper-airway critical pressure (Pcrit) and upstream resistance (Rua) were derived. Maximal mouth-opening increased Pcrit to -3.6 +/- 2.9 cm H2O compared with -8.7 +/- 2.8 (p = 0.002) for closed mouths and -7.2 +/- 4.1 (p = 0.038) for mouths opened moderately. In contrast, Rua was similar in all three conditions (18.4 +/- 6.6 vs. 17.7 +/- 7.6 vs. 21.5 +/- 11.6 cm H2O/L/sec). Moreover, maximum mouth-opening produced an inspiratory airflow limitation at atmosphere that was eliminated when nasal pressure was adjusted to 4.3 +/- 2.7 cm H2O. We conclude that maximal mouth-opening increases upper-airway collapsibility, which contributes to upper-airway obstruction at atmosphere during midazolam sedation.

A pilot study of quantitative assessment of mandible advancement using pressure-flow relationship during midazolam sedation.

It has been proposed that a titration of the mandibular positioner would be a promising method for predicting the outcome of nasal continuous positive airway pressure (CPAP) therapy. This study was carried out to test the hypothesis that mandible advancement could be evaluated by analysis of inspiratory flow limitation using a titration procedure. To explore its effect, we examined upper airway pressure-flow relationships using a titrated mandible positioner during midazolam sedation. Non-flow limited inspiration occurred when the mandible was advanced 7.1 +/- 1.2 mm from centric occlusion position. In the centric occlusion position (0 mm advancement), Pcrit was -1.9 +/- 2.9 cmH2O and Rua was 23.3 +/- 4.5 cmH2O L(-1) s(-1). In the eMAP position, Pcrit was -7.3 +/- 1.9 cmH2O and Rua was 27.8 +/- 3.3 cmH2O L(-1) s(-1). Essentially no CPAP was required to overcome flow limitation in eMAP position, whereas 3.7 +/- 2.2 cmH2O CPAP was required in centric occlusion position. We conclude that assessing inspiratory flow limitation using a titrated mandible positioner was effective for estimating individual-matched mandible positions.

Neuronal expression in cleavage-arrested ascidian blastomeres requires gap junctional uncoupling from neighbouring cells.

1. When anterior-animal (a4-2) blastomeres isolated from 8-cell ascidian embryos were cultured under cleavage-arrested conditions in contact with anterior-vegetal (A4-1) blastomeres (a-A blastomere pairs), the a4-2 blastomeres differentiated into neuronal cells that expressed Na+ and delayed K+ channels at a time when normal sister embryos became tadpole larvae (after 40 developmental hours at 9 degrees C). When a4-2 blastomeres were cultured in contact with posterior-animal (b4-2) blastomeres (a-b blastomere pairs), the a4-2 blastomeres differentiated into epidermal cells expressing Ca2+ channels and tunic on their exterior surface. In these blastomere pairs, we analysed changes in gap junctional communication during neural and epidermal differentiation by using both dye transfer and double voltage clamp. 2. In both types of blastomere pairs, gap junctional communication was detectable at 5 h by double voltage clamp and at 7 h by dye transfer. Gap junctional communication in both types gradually increased until 25 h (equivalent to the neurula stage). However, during 25-35 h (late neurula or tailbud) in the a-A pair it decreased and finally disappeared, while it increased steeply in the a-A pair. When blastomere pairs were treated with a transcription inhibitor, actinomycin D, gap junctional communication also appeared at around 7 h but remained at a plateau level, showing neither a steep increase in a-b pairs nor a disappearance in a-A pairs. 3. In blastomere triplets in which an epidermally committed a4-2 was in contact with both blastomeres of an a-A pair, the epidermally committed a4-2 blastomere did, but the neurally committed a4-2 blastomere did not, communicate through gap junctions with the A4-1 blastomere, indicating that gap junctional communication is restricted when a4-2 blastomeres are neurally committed. 4. When a kinase inhibitor, K252a (0.5-1.0 microM), was applied at 20 h (prior to the disappearance of gap junctional communication), gap junctional communication was maintained in the a-A pair for more than 40 h. The persistence of gap junctional communication delayed the expression of Na+ and K+ channels in the a4-2 blastomere. However, channel expression followed an almost normal time sequence in single neuronally committed a4-2 blastomeres separated from A-a pairs and treated with K252a. 5. We conclude that the persistence of gap junctions causes a delay in expression of neuronal characteristics, and suggest that one of the functional roles of embryonic gap junctions is to time the expression of neuron-specific ion channels and other markers in preneuronal cells.

Basic fibroblast growth factor induction of neuronal ion channel expression in ascidian ectodermal blastomeres.

1. Cleavage-arrested anterior animal (a4-2) blastomeres isolated from eight-cell embryos of Halocynthia aurantium differentiated into neuronal type cells expressing neuron-specific ion channels when they were treated with basic fibroblast growth factor (bFGF). This induction process was very similar to that when a4-2 blastomeres were cultured in contact with anterior vegetal (A4-1) blastomeres from the same embryos or when treated with subtilisin, a serine protease. 2. Other growth factors, transforming growth factor (TGF) beta1, activin A, epidermal growth factor (EGF) and nerve growth factor (NGF), had no effect on the default epidermal differentiation of cleavage-arrested a4-2 blastomeres. 3. Messenger RNA of the ascidian neuronal Na+ channel, TuNa I, was detected using RT-PCR in a4-2-derived partial embryos of Halocynthia aurantium as well as in the cleavage-arrested a4-2 blastomeres treated with bFGF, confirming the neural inducer activity of bFGF during ascidian embryogenesis. 4. bFGF was effective at concentrations as low as 1 ng ml-1 in inducing neuronal ion channels in cleavage-arrested a4-2 blastomeres. EC50 for neuronal differentiation was estimated to be around 8 ng ml-1, and the maximum effect of 90 % neuronalization was obtained with above 100 ng ml-1. 5. For induction of neuronal differentiation, bFGF was required to be continuously present 8 to 14 h after fertilization. A similar time window was required for cell-contact induction, but it was considerably shorter for subtilisin induction. 6. We discuss whether activation of receptor tyrosine kinase is a common pathway for neural induction by bFGF, subtilisin, and cell-contact with A4-1 blastomeres.

Imaging of the parathyroid in chronic renal failure: diagnostic and therapeutic aspects.

On the basis of recent advances in our understanding of the pathogenesis of chronic renal failure, imaging of parathyroid hyperplasia in chronic dialysis patients has become a highly useful tool not only for identification, but also for evaluation of the nature of abnormal glands and for various intervention strategies. Rational imaging approaches, different from those used for primary hyperparathyroidism, should be established for secondary hyperparathyroidism.

Comparison of airway responsiveness to exercise and histamine inhalation in asthmatics.

In order to investigate the differences between EIA positive and negative subjects, pulmonary function data at rest, atopic tendency and bronchial sensitivity and reactivity were compared. Pulmonary function data revealed no significant difference between two groups except closing volume which was higher in EIA positive patients (p less than 0.01) and also Rrs which was higher in EIA positive patients only in female (p less than 0.05). Incidence of positive skin tests and higher levels of IgE were more frequent in EIA positive, however, IgE was not significantly different. Relationship between % fall of FEV1 after exercise and bronchial sensitivity was examined, however, no correlation was found in two parameters. Bronchial reactivity was not different in two groups. This suggests that EIA positive patients cannot be distinguished from EIA negative by pulmonary function data at rest or by atopic tendency, and also that different mechanisms play a role to produce airway constriction following exercise and inhalation challenge.

Glucocorticoid-regulated expression of exogenous human growth hormone gene in rats.

The aim of this study was to control in vitro and in vivo expression of the growth hormone (GH) gene using a glucocorticoid-sensitive promoter, the mouse mammary tumor virus long terminal repeat (MMTV LTR). We inserted the cDNA encoding the 20-kDa form of human GH (20K-GH) downstream of the MMTV LTR of plasmid pMSG, and used lipofection to transfer it to 3Y1 cells together with plasmid pMX, which contains a puromycin-resistant element. The secretion of GH from the selected transformants was dose-dependently augmented by the application of hydrocortisone, corticosterone, or dexamethasone, among which dexamethasone was the most potent. Analysis of the time course showed that 20K-GH secretion began to increase within 2 hours after the addition of glucocorticoid and reached a maximal level of about threefold over the unstimulated control at 3 hours; secretion then gradually declined and returned to near basal levels at 19 hours. Repeated glucocorticoid application led to repeated increases in GH secretion. When GH-producing cells were microcapsulated and transplanted into the abdominal cavities of rats, 20K-GH was detected in the plasma under control conditions and increased about 3.3-fold after administration of dexamethasone. We suggest that GH expression driven by the MMTV LTR promoter may be under the control of an endogenous glucocorticoid in vivo.