Ventilatory dynamics during transient arousal from NREM sleep: implications for respiratory control stability

The polysomnographic and ventilatory patterns of nine normal adults were measured during non-rapid-eye-movement (NREM) stage 2 sleep before and after repeated administrations of a tone (40-72 dB) lasting 5 s. The ventilatory response to arousal (VRA) was determined in data sections showing electrocortical arousal following the start of the tone. Mean inspiratory flow and tidal volume increased significantly above control levels in the first seven breaths after the start of arousal, with peak increases (64.2% > control) occurring on the second breath. Breath-to-breath occlusion pressure 100 ms after the start of inspiration showed significant increases only on the second and third postarousal breaths, whereas upper airway resistance declined immediately and remained below control for > or = 7 consecutive breaths. These results suggest that the first breath and latter portion of the VRA are determined more by upper airway dynamics than by changes in the neural drive to breathe. Computer model simulations comparing different VRA time courses show that sustained periodic apnea is more likely to occur when the fall in the postarousal increase in ventilation is more abrupt.     

Randomized, double-blind placebo-controlled trial of coenzyme Q10 in patients with acute myocardial infarction

Adherence with inhaled beta-agonists and corticosteroids in 24 asthmatic children was tracked over 3 months utilizing the metered-dose inhaler chronolog (MDIC). Patients seldom took all of their medications as prescribed, and failed to take any inhaled corticosteroid doses on a median of 41.8% of days or inhaled beta-agonists on 28.1% of days despite prescribed daily use. Medication nonadherence was correlated with lower levels of asthma knowledge (Asthma Knowledge Questionnaire) and family dysfunction (Family Assessment Device), but not child behavior disorder (Child Behavior Checklist). Patients tended to dramatically over-report medication use. Improved identification of the markers of nonadherence can directly facilitate more efficient targeting of behavioral interventions, resulting in improved adherence, better illness control, and less requirement of urgent medication intervention.     

Relationship of the meniscofemoral ligaments of the knee to lateral meniscus tears: magnetic resonance imaging evaluation

This study sought to determine if the presence or absence of meniscofemoral ligaments exerts an influence on the prevalence of tears of the lateral meniscus. We reviewed the sagittal and coronal magnetic resonance images of 173 knees for lateral meniscus tears and the presence of the meniscofemoral ligaments. One or both meniscofemoral ligaments were present in 142 of 173 knees (82%). Fifty-four knees had lateral meniscus tears, 27 of which involved the posterior horn. Thirty-three percent of knees with meniscofemoral ligaments had a lateral meniscus tear, and 23% of knees without meniscofemoral ligaments had a lateral meniscus tear (no significant difference). We found no association between the presence of the meniscofemoral ligaments and tears of the lateral meniscus. Our study questions the importance of preserving or reconstructing these ligaments in instances of meniscal transplantation.     

Redistribution of NMDA receptors in the cochlear nucleus following cochleotomy

The major input to neurons of the cochlear nucleus comes from the glutamatergic cells of the spiral ganglion. We have studied the effect of unilateral destruction of the inner ear, including the spiral ganglion, with two antibodies against different types of NMDA receptor subunits, NMDAR1 and NMDAR2A/B, in the cochlear nucleus of the rat. Following cochleotomy, a dramatic redistribution of the receptor subunits was observed from a mostly perikaryal to a predominantly dendritic localization. Moreover, distinct changes in the composition of NMDA receptor complexes occurred. These effects were interpreted as compensatory responses to the massive loss of presynaptic release of the transmitter glutamate.     

CT angiography of the visceral vasculature

Gynecologic epithelial tumors can be grouped into two major categories depending on whether they are derived embryologically from squamous epithelium of the urogenital sinus or from müllerian ducts. Ovarian carcinomas appear morphologically similar to those arising in müllerian-derived organs, and molecular genetic defects present in tumors from these different sources appear to reflect more their histologic subtypes than their organ of origin. The possibility that ovarian epithelial tumors arise from remnants of müllerian ducts in the vicinity of the ovary therefore merits further investigation. Recent advances in our understanding of the state of clonality of various gynecologic tumors, of the influence of age and ovulatory activity on their genetic characteristics, and of their overall molecular genetic features, provide important clues about their initial underlying mechanisms. Novel strategies based on these advances are being tested for their potential utility in treating and monitoring gynecologic tumors.     

The use of E-mail by otolaryngologists

Electronic mail (e-mail) is an extremely powerful form of communication and the most frequently used application on the Internet. While e-mail is not the appropriate mode of communication for every situation, there are many instances where its use is invaluable.     

Syntheses of amino nitrones. Potential intramolecular traps for radical intermediates in monoamine oxidase-catalyzed reactions

Monoamine oxidase (MAO) is a flavin-dependent enzyme that catalyzes the oxidative deamination of a variety of amine neurotransmitters and toxic amines. Although there have been several studies that support the intermediacy of an amine radical cation and an alpha-radical during enzyme catalysis, there is no direct, i.e. EPR, evidence for these species as they are formed. Amino nitrones have been designed which, upon radical formation would produce an intermediate that is a resonance structure of the corresponding nitroxyl radical, which should be observable by EPR spectroscopy. Syntheses of seven different amino nitrones, three acyclic, and four cyclic analogues were attempted. The protected amino nitrones were stable, but all three of the acyclic amino nitrones were unstable. One of the cyclic analogues was very stable (39), one was stable only in organic solvents (40), one was stable only in aqueous medium below pH 6.5 (41), and the other (42) was stable for just a short time at room temperature, decomposing to a stable free radical. None of these analogues produced a MAO-catalyzed radical, yet 41 is a poor substrate (Km=0.2mM; k(cat) = 0.034 min-1) and 39 is a mixed inhibitor (Ki = 26.5 mM). Although this approach does not appear to be applicable to amino nitrones, it should be a valuable approach for other enzymes where radical intermediates are suspected and nonamine nitrones can be utilized.     

Modulation by dietary salt of verapamil disposition in humans

BACKGROUND: The intestine is an increasingly well-recognized site of first-pass drug metabolism. In this study, we determined the influence of dietary salt on the steady-state disposition of verapamil, a drug that undergoes extensive first-pass metabolism. METHODS AND RESULTS: Eight normal volunteers received 120 mg of racemic verapamil orally twice a day for 21 days. The disposition kinetics of verapamil enantiomers were determined after coadministration of intravenous deuterated verapamil with the morning oral dose on days 7, 14, and 21. Each study day was preceded by 7 days on a fixed-salt diet: in 5 subjects, the initial study was conducted during a low-salt (10 mEq/d) diet, the second study during a high-salt (400 mEq/d) diet, and the third during a low-salt diet, whereas in the other 3 subjects, the sequence of diets was reversed. Plasma concentrations of both unlabeled enantiomers (ie, from oral therapy) were significantly (P<0.05) lower during the high-salt phase (eg, mean area under the time-concentration curve [0 to 12 hours] for S-verapamil: 7765+/-2591 ng. min. mL-1 [high salt] versus 12 514+/-3527 ng. min. mL-1 [low salt], P<0.05). Peak plasma concentrations were significantly lower and the extent of PR interval prolongation significantly blunted with the high-salt diet. In contrast, data with labeled drug (ie, reflecting the intravenous route) were nearly identical for the 2 diets. CONCLUSIONS: These data indicate that a clinically important component of presystemic drug disposition occurs at the prehepatic (presumably intestinal) level and is sensitive to dietary salt.