Value of the multiple sleep latency test (MSLT) for the diagnosis of narcolepsy

Since its introduction, the multiple sleep latency test (MSLT) has played a major role in the diagnosis of narcolepsy. We assessed its diagnostic value in a series of 2,083 subjects of whom 170 (8.2%) were diagnosed with narcolepsy. The sensitivity of the combination of two or more sleep onset rapid eye movement (REM) periods (SOREMPs) with a mean sleep latency of < 5 minutes on an initial MSLT was 70% with a specificity of 97%, but 30% of all subjects with this combination of findings did not have narcolepsy. In some narcoleptics who had more than one MSLT, the proportion of naps with SOREMPs varied substantially from the initial MSLT to the follow-up test. The highest specificity (99.2%) and positive predictive value (PPV) (87%) for MSLT findings was obtained with the criteria of three or more SOREMPs combined with a mean sleep latency of < 5 minutes, but the sensitivity of this combination was only 46%. The combination of a SOREMP with a sleep latency < 10 minutes on polysomnography yielded a specificity (98.9%) and PPV (73%) almost equal to those obtained from combinations of MSLT findings, but the sensitivity was much lower. Our results suggest that the MSLT cannot be used in isolation to confirm or exclude narcolepsy, is indicated only in selected patients with excessive daytime sleepiness, and is most valuable when interpreted in conjunction with clinical findings.     

Carbohydrate drinks delay fatigue during intermittent, high-intensity cycling in active men and women

The effects of ingesting carbohydrate drinks on fatigue during intermittent, high-intensity cycling in men and women were determined. Physically active but untrained women (n = 7) and men (n = 9) completed one practice trial and two experimental sessions separated by 1 week. Sessions consisted of repeated 1-min cycling bouts on a bicycle ergometer at 120-130% VO2max separated by 3 min rest until fatigue. Carbohydrate (CHO) or placebo (P) beverages (4 ml.kg body weight-1) were ingested immediately before exercise (18% CHO) and every 20 min during exercise (6% CHO). Plasma glucose and insulin were higher, RPE for the legs was lower, and time to fatigue was longer in CHO than P. Men's and women's responses were not different for any variable measured. These data suggest a beneficial role of CHO drinks on performance of intermittent, high-intensity exercise in men and women.     

Chronic use of apraclonidine decreases its moderation of post-laser intraocular pressure spikes

OBJECTIVE: The purpose of the study is to investigate the efficacy of 1.0% apraclonidine in preventing intraocular pressure (IOP) spike after argon laser trabeculoplasty (ALT) in patients on chronic apraclonidine therapy compared with patients not on chronic apraclonidine use. DESIGN: The study design was a prospective study. PARTICIPANTS: This study consisted of 231 consecutive eyes of patients with primary open-angle glaucoma undergoing ALT: 70 eyes (30%) were started on a regimen including chronic apraclonidine 0.5% use (group A) and 161 eyes (70%) were started on a regimen without chronic apraclonidine 0.5% use (group B). INTERVENTION: Both groups received one drop of apraclonidine 1.0% 15 minutes before ALT to 180 degrees of previously untreated trabecular meshwork. Intraocular pressure was measured before the procedure and at 5 minutes, 1 hour, and 24 hours after the laser treatment. MAIN OUTCOME MEASURES: Incidences of an IOP spike and mean IOPs at 5 minutes, 1 hour, and 24 hours after the laser treatment were compared between the two groups. Multivariate logistic regression analysis also was carried out to identify the significant risk factors for post-ALT IOP spikes despite prophylactic apraclonidine 1.0% treatment. RESULTS: The incidences of IOP spikes greater than 0 mmHg, greater than 2 mmHg, and greater than 5 mmHg at 1 hour after ALT were 32.9%, 22.9%, and 12.9%, respectively, in group A versus 13.7%, 11%, and 3.1%, respectively, in group B (P = 0.0007, P = 0.009, and P = 0.004). Chronic apraclonidine 0.5% use was found to be the only significant risk factor for IOP spikes at 1 hour after ALT by multivariate logistic regression analysis. CONCLUSIONS: The incidences of IOP spikes in group A were significantly greater than in group B and approached the reported incidences of IOP spikes without perilaser apraclonidine prophylaxis. This indicates that peri-ALT apraclonidine is relatively ineffective in patients with chronic apraclonidine 0.5% use (group A) compared with patients without chronic apraclonidine use (group B), presumably because of saturation of the ocular alpha-2 receptors with apraclonidine in patients with chronic apraclonidine use. Therefore, in patients receiving chronic apraclonidine therapy, it is especially important to monitor their post-ALT IOPs and to be prepared to treat postlaser IOP spikes using agents other than apraclonidine.     

Pharmacological characterization of in vivo properties of putative mixed 5-HT1A agonist/5-HT2A/2C antagonist anxiolytics. I. Antipunishment effects in the pigeon

A conflict procedure in pigeons was used to characterize the antipunishment effects of the putative mixed 5-hydroxytryptamine (5-HT)1A agonist/5-HT2A/2C antagonists WY 50,324, CGS 18102A, LEK 8804 and FG 5974 and to further investigate interactions between the antipunishment effects of the 5-HT1A agonists buspirone and 8-OH-DPAT [8-hydroxy-2-(di-n-propylamino)tetralin] administered in combination with the mixed 5-HT2A/2C antagonist ritanserin and the alpha 1 antagonist prazosin. The 5-HT1A agonists, buspirone and 8-OH-DPAT, which lack affinity for 5-HT2A/2C receptors, produced dose-related increases in punished responding. Of the compounds with a mixed binding profile, only WY 50,324 showed effects that were comparable to those observed after 8-OH-DPAT, whereas FG 5974 and CGS 18102A exhibited limited effects on punished responding, and LEK 8804 was ineffective. Administration of a relatively low, behaviorally active dose of ritanserin (0.16 mg/kg) significantly enhanced the potency of 8-OH-DPAT and buspirone to increase punished responding from 8 to 50-fold without altering their effects on unpunished responding. Importantly, ritanserin failed to increase the number of doses of 8-OH-DPAT that significantly increased punished responding. In contrast, prazosin (2.5 mg/kg) significantly enhanced the potency and increased the number of doses of buspirone exerting significant effects on punished responding, but did not alter the effects of 8-OH-DPAT. Taken together, the results neither explain the suggested greater efficacy in producing anxiolytic effects of compounds with putative mixed 5-HT1A agonist and 5-HT2A/2C antagonist properties, nor confirm a proposed interaction between alpha1 adrenoreceptors and 5-HT1A agonists in preclinical tests of anxiolytic activity.     

Isolation of sucrose late-fermenting and nonfermenting variants of Vibrio cholerae O139 Bengal: implications for diagnosis of cholera

The sucrose-containing selective medium thiosulfate-citrate-bile salt-sucrose agar missed a sucrose nonfermenting and four sucrose late-fermenting variant strains of Vibrio cholerae O139 Bengal from diarrheal stools. These strains were, however, correctly identified as V. cholerae O139 on a sucrose-deficient selective medium, taurocholate-tellurite-gelatin agar.     

WIN 63480, a hydrophilic TCP-site ligand, has reduced agonist-independent NMDA ion channel access compared to MK-801 and phencyclidine

NMDA channel blockers are potentially advantageous therapeutic agents for the treatment of ischemia and head trauma, which greatly elevate extracellular glutamate, because they should most effectively inhibit high levels of receptor activation. A novel high affinity TCP site ligand, WIN 63480, does not produce MK-801- or PCP-like behavioral activation at anti-ischemic doses. While WIN 63480, MK-801 and PCP were all observed to be effective blockers of open NMDA channels, WIN 63480 had much less access to closed NMDA channels. This difference may be due to the fact that WIN 63480 is hydrophilic (logD = -4.1) while MK-801 and PCP are lipophilic (logD = +1.8). In vivo, closed channel access may result in a non-competitive profile of antagonism for MK-801 and PCP compared to a more uncompetitive profile for WIN 63480. Release of glutamate, and depolarization, are likely to produce a high level of NMDA receptor activation in ischemic areas compared to normal tissue. Consequently, at anti-ischemic doses, WIN 63480 may produce less inhibition of physiological NMDA-mediated processes in neural systems involved in behavioral regulation than MK-801 or PCP, leading to an improved side effect profile.     

Functional analysis of a rat sodium channel carrying a mutation for insect knock-down resistance (kdr) to pyrethroids

As a model for establishing an optimized medium for human in vitro fertilization (IVF), modified human tubal fluid (HTF) media containing amino acids at concentrations found in human serum and follicular fluid were prepared, and the effect of the media on development of random-bred (ICR) and F1 hybrid (CBF1) mice embryos was studied. The total concentrations of amino acids found in serum and follicular fluid were about one-third to one-half the concentrations present in two conventional media used in human IVF: Ham's F-10 and Eagle's minimal essential medium (MEM). When ICR mouse embryos were cultured in the HTF medium containing 21 amino acids at concentrations found in follicular fluid, the number of embryos developing to morulae at 72 h and to blastocysts at 96 h increased in comparison with those cultured in HTF medium. When HTF containing amino acids at concentrations found in serum was used, only induced morula formation at 72 h was enhanced. The number of hatching blastocysts at 96 h also increased when CBF1 mouse embryos were cultured with HTF supplemented with amino acids at concentrations found in follicular fluid. When ICR mouse embryos were cultured in modified HTF media containing concentrations of amino acids found in Ham's F-10 and MEM that contained higher concentrations of glutamine, embryo development was inhibited. The amount of ammonium produced during incubation for 3 days was significantly less when embryos were cultured in media containing concentrations of amino acids found in follicular fluid compared with when Ham's F-10 or MEM was the culture medium. Ammonium is produced by the breakdown of glutamine in the culture medium during incubation with or without embryos. These results suggest that the concentrations of amino acids found in follicular fluid are more effective and safer for embryo culture than those in other media currently in use.