Lauflumide (NLS-4) Is a New Potent Wake-Promoting Compound.

Psychostimulants are used for the treatment of excessive daytime sleepiness in a wide range of sleep disorders as well as in attention deficit hyperactivity disorder or cognitive impairment in neuropsychiatric disorders. Here, we tested in mice the wake-promoting properties of NLS-4 and its effects on the following sleep as compared with those of modafinil and vehicle. C57BL/6J mice were intraperitoneally injected with vehicle, NLS-4 (64 mg/kg), or modafinil (150 mg/kg) at light onset. EEG and EMG were recorded continuously for 24 h after injections and vigilance states as well as EEG power densities were analyzed. NLS-4 at 64 mg/kg induced significantly longer wakefulness duration than modafinil at 150 mg/kg. Although no significant sleep rebound was observed after sleep onset for both treatments as compared with their vehicles, modafinil-treated mice showed significantly more NREM sleep when compared to NLS-4. Spectral analysis of the NREM EEG after NLS-4 treatment indicated an increased power density in delta activity (0.75-3.5 Hz) and a decreased power in theta frequency range (6.25-7.25 Hz), while there was no differences after modafinil treatment. Also, time course analysis of the delta activity showed a significant increase only during the first 2 time intervals of sleep after NLS-4 treatment, while delta power was increased during the first 9 time intervals after modafinil. Our results indicate that NLS-4 is a highly potent wake-promoting drug with no sign of hypersomnia rebound. As opposed to modafinil, recovery sleep after NLS-4 treatment is characterized by less NREM amount and delta activity, suggesting a lower need for recovery despite longer drug-induced wakefulness

Safety and tolerability of flexible dosages of prolonged-release OROS methylphenidate in adults with attention-deficit/hyperactivity disorder

The osmotic release oral system (OROS) methylphenidate formulation is a prolonged-release medication for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children, adolescents, and adults. We conducted a seven-week open-label extension of a double-blind study to assess the safety and tolerability of OROS methylphenidate in a flexible dose regimen (18–90 mg daily) for the treatment of adults diagnosed with ADHD (N =370). Medication was adjusted to optimize efficacy and tolerability for each patient. Adverse events, vital signs, and laboratory parameters were assessed. Most patients (337; 91%) completed the seven-week treatment and the final dispensed dose was 18 mg (8%), 36 mg (29%), 54 mg (34%), 72 mg (20%), or 90 mg (9%). Adverse events were reported in 253 (68%) patients and most were mild or moderate in severity; most frequently reported included headache (17%), decreased appetite (13%), and insomnia (11%). Adverse events were rarely serious (<1%; 2/370). Small mean increases in systolic and diastolic blood pressure (both 2.4 mmHg) and pulse (3.2 bpm) were observed. Body weight decreased slightly (−1.5 kg). The results provide additional support for the safety and tolerability of prolonged-release OROS methylphenidate in a flexible dose regimen (18–90 mg/day) for the treatment of adults with ADHD

Lauflumide (NLS-4) Is a New Potent Wake-Promoting Compound

Psychostimulants are used for the treatment of excessive daytime sleepiness in a wide range of sleep disorders as well as in attention deficit hyperactivity disorder or cognitive impairment in neuropsychiatric disorders. Here, we tested in mice the wake-promoting properties of NLS-4 and its effects on the following sleep as compared with those of modafinil and vehicle. C57BL/6J mice were intraperitoneally injected with vehicle, NLS-4 (64 mg/kg), or modafinil (150 mg/kg) at light onset. EEG and EMG were recorded continuously for 24 h after injections and vigilance states as well as EEG power densities were analyzed. NLS-4 at 64 mg/kg induced significantly longer wakefulness duration than modafinil at 150 mg/kg. Although no significant sleep rebound was observed after sleep onset for both treatments as compared with their vehicles, modafinil-treated mice showed significantly more NREM sleep when compared to NLS-4. Spectral analysis of the NREM EEG after NLS-4 treatment indicated an increased power density in delta activity (0.75–3.5 Hz) and a decreased power in theta frequency range (6.25–7.25 Hz), while there was no differences after modafinil treatment. Also, time course analysis of the delta activity showed a significant increase only during the first 2 time intervals of sleep after NLS-4 treatment, while delta power was increased during the first 9 time intervals after modafinil. Our results indicate that NLS-4 is a highly potent wake-promoting drug with no sign of hypersomnia rebound. As opposed to modafinil, recovery sleep after NLS-4 treatment is characterized by less NREM amount and delta activity, suggesting a lower need for recovery despite longer drug-induced wakefulness

The influence of air attenuation in characteristic curve for mammographic screen-film system

マンモグラフィ専用装置を使用して，距離法で低エネルギー領域のX線におけるマンモグラフィ用増感紙／フィルムシステムの特性曲線を得るためには，空気滅弱の影響を考慮する必要がある。その影響について，実効エネルギーから空気減弱分を補正，照射線量測定による補正，Bednarek法を応用した新距離法の3種類の方法を使って検討した。さらに，一般撮影装置でも，マンモ用システムに対して距離法で特性曲線を作成し，エネルギ ーの変化による影響についても検討した。その結果，3方法の特性曲線およびグラディエント曲線は，新距離法が高濃度域でわずかにずれるもののほぼ一致した。新距離法に対する平均階調度，最大階調度の最大誤差は，2.7％，0.2％であり，一般撮影用装置の距離法と3方法との間では，一般撮影用装置の距離法に対して最大誤差は2.7％，1.5％であった。以上のことから，エネルギーの変化による特性曲線への影響はほとんどなく，低エネルギー領域での特性曲線は空気特配の補正を行うことのみで得られると考えられる。It is necessary to take air attenuation into account when we use inverse square sensitometry to obtain characteristic curve for the mammographic screen-film system at low x-ray energies as used with the dedicated unit. Three kinds of the inverse square sensitometry approach of correcting by air attenuation obtained from effective energy, of correcting by exposure dosimetry and of using modified the technique of Bednarek were employed to investigated the influence of x-ray energy in the characteristic curves for the mammographic screen-film system. In addition, the inverse square sensitometry with the general radiographic unit was employed and the influence of x-ray high energy in the characteristic curves was also investigated for the same screeri-film system. Though characteristic curves and gradient curves of the new inverse square sensitometry were a little lower than the others in high-density region, the curves with three kinds of methods almost coincided. Maximum relative errors of average gradient and maximum gradient for modified the technique of Bednarek were found to be 2.7% and 0.2% among the others respectively. Moreover, maximum relative errors of gradient and maximum gradient for the inverse square sensitometry with the general radiographic unit were 2.7% and 1.5% among three kinds of methods with the dedicated unit respectively. It was considered that the characteristic curves for the mammographic screen-film　system were little influenced by x-ray energy and could be obtained only by correcting　air attenuation from above results

Parental rating of sleep in children with attention deficit/hyperactivity disorder

Objective: Sleep problems have often been associated with attention deficit/hyperactivity disorder (ADHD). Parents of those with ADHD and children with ADHD report sleep difficulties more frequently than healthy children and their parents. The primary objective of this paper is to describe sleep patterns and problems of 5 to 11-year-old children suffering from ADHD as described by parental reports and sleep questionnaires. Method: The study included 321 children aged 5–11 years (average age 8.4 years); 45 were diagnosed with ADHD, 64 had other psychiatric diagnoses, and 212 were healthy. One hundred and ninety-six of the test subjects were boys and 125 were girls. A semi-structured interview (Kiddie-SADS-PL) was used to DSM-IV diagnose ADHD and comorbidity in the clinical group. Sleep difficulties were rated using a structured sleep questionnaire (Children Sleep Behaviour Scale). Results: Children diagnosed with ADHD had a significantly increased occurrence of sleep problems. Difficulties relating to bedtime and unsettled sleep were significantly more frequent in the ADHD group than in the other groups. Children with ADHD showed prolonged sleep onset latency, but no difference was shown regarding numbers of awakenings per night and total sleep time per night. Comorbid oppositional defiant disorder appeared not to have an added effect on problematic behaviour around bedtime. Conclusion: Parents of children with ADHD report that their children do not sleep properly more often than other parents. The ADHD group report problems with bedtime resistance, problems with sleep onset latency, unsettled sleep and nightmares more often than the control groups. It may therefore be relevant for clinicians to initiate a closer examination of those cases reporting sleep difficulties