Investigation of critical factors for the resolution of SR695, a key impurity, from efavirenz in the reversed-phase assay of efavirenz dosage forms

An investigation of the critical factors effecting the resolution of SR695 from efavirenz in the assay of efavirenz by reversed-phase HPLC was performed. This study was implemented to address the inability of a subset of the Zorbax SB-CN columns used in this method to adequately perform this separation, which were otherwise indistinguishable from columns of this type that could. In this study, column temperature, detector time-constant, pre-gradient isocratic hold-time, pre-column mixing volume, column, and HPLC type were considered. Experimental Design methods were employed to find the relative importance of these factors and to find parameters that would optimize the resolution of SR695 and efavirenz on any HPLC, with any column of this type, for both efavirenz oral liquid and capsule samples. It was also desired that this method change be minimal, so that extensive revalidation would not be required. The most important factors were the column temperature, with lower temperatures giving better resolution, and pre-column mixing volume of sample with mobile phase, with higher mixing volumes giving better resolution up to an asymptote reached at around 150 microl. Added pre-gradient isocratic hold time was found to result in a small improvement in resolution, but was insignificant compared with the other factors mentioned above. A possible explanation is given for the mechanism by which temperature and pre-column mixing have this effect on the resolution obtained in this assay.     

Sleep disorders in Parkinson's disease: epidemiology and management

Sleep problems are an under-emphasised cause of disability in Parkinson's disease (PD) and may be seen independently of PD, associated with primary PD pathology, or as a result of antiparkinsonian medications. Common sleep disorders include excessive daytime sleepiness, rapid eye movement (REM) sleep behaviour disorder, night-time wakefulness and restless legs syndrome. A number of strategies may be used to improve sleep cycle disturbances, and often these interventions do not require pharmacological manipulation. Restoring traditional mealtimes and scheduling activities during predicted periods of sleepiness may help alleviate daytime somnolence; the use of controlled-release levodopa preparations or administration of a catechol-O-methyl transferase (COMT) inhibitor with levodopa at bedtime may reduce periods of night-time wakefulness. Administration of clonazepam at bedtime may assist with REM sleep behaviour disorder but, because this agent can result in daytime somnolence, experimentation with dosage times is recommended. Sleep attacks are described as a sudden, unavoidable transition from wakefulness to sleep and, although rare, have been described with pramipexole, ropinirole and other dopamine agonists. Although the condition has yet to be recognised by the International Association of Sleep Disorders, patients with PD who report rapid sleep onset should be evaluated for the possibility of sleep attacks. If sleep attacks are suspected, it is reasonable to strongly caution patients regarding potentially risk-associated activities such as driving, and to consider careful withdrawal of dopaminergic therapy.     

Progesterone attenuates the effect of the 5-HT1A receptor agonist, 8-OH-DPAT,and of mild restraint on lordosis behavior

Ovariectomized, hormone-primed rats were used to test the hypothesis that progesterone treatment attenuated the effects of the 5-HT(1A) receptor agonist, (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), on female rat lordosis behavior. Based upon prior evidence that prepriming with estradiol benzoate (EB) reduced the ability of 8-OH-DPAT to inhibit lordosis behavior, rats were preprimed with 10 microg EB 7 days before a second priming with 10 microg EB followed 48 h later with 500 microg progesterone or vehicle. Independent of the presence of progesterone, prepriming with EB attenuated the lordosis-inhibiting effects of systemic treatment with 8-OH-DPAT. However, progesterone also reduced the effects of 8-OH-DPAT and this effect was also seen in females primed only once with EB. In contrast, progesterone was relatively ineffective in attenuating the effects of bilateral infusion with 8-OH-DPAT into the ventromedial nucleus of the hypothalamus (VMN). The failure of progesterone to substantially reduce the effects of VMN infusion with 8-OH-DPAT contrasts with prior studies in which estrogen's protective action against the drug did include the VMN. Thus, while both estrogen and progesterone reduce the lordosis-inhibiting effect of 8-OH-DPAT, the mechanisms responsible for the effects of the two gonadal hormones may be different. Priming with progesterone also prevented the effects of 5 min of restraint. When rats were hormonally primed with EB and oil, rats showed a transient, but significant, decline in lordosis behavior 5 and 10 min after restraint. Rats primed with EB and progesterone were unaffected by the restraint. These results are discussed in terms of their implications for the role of progesterone in altering the 5-HT(1A) receptor modulation of lordosis behavior.     

Left ventricular assist device implantation via left thoracotomy: alternative to repeat sternotomy

Repeat sternotomy for left ventricular assist device insertion may result in injury to the right heart or patent coronary grafts, complicating intraoperative and postoperative management. In 4 critically ill patients, left thoracotomy was used as an alternative to repeat sternotomy. Anastomosis of the outflow conduit to the descending thoracic aorta provided satisfactory hemodynamic support.     

Aortic root replacement with anomalous origin of the coronary arteries

Coronary arteries with anomalous origin from the aorta can be at risk during aortic valve procedures. We report a case of origin of the circumflex and left coronary artery from the proximal right coronary artery in a patient with a bicuspid aortic valve and aortic root aneurysm. Attention to the anatomic relationship of the anomalous arteries to the aorta allowed safe aortic root replacement.     

Oat consumption does not affect resting casual and ambulatory 24-h arterial blood pressure in men with high-normal blood pressure to stage I hypertension

The results of epidemiologic studies suggest that increased intake of dietary fiber is associated with lower levels of arterial blood pressure (BP). However, there is little information available addressing the possibility that increased oat consumption may reduce arterial BP in individuals with elevated arterial BP. To test this hypothesis, middle-aged and older men (n = 36; body mass index, 25-35 kg/m(2); aged 50-75 y) with elevated BP (systolic BP 130-159 mmHg and/or diastolic BP 85-99 mmHg) were randomly assigned to consume an additional 14 g/d of dietary fiber in the form of oat (5.5 g beta-glucan, n = 18) or wheat cereals (no beta-glucan, n = 18) for 12 wk. Casual resting arterial BP was measured at baseline and after 4, 8 and 12 wk of intervention. The 24-h ambulatory arterial BP was measured at baseline and after 12 wk of intervention. There were no differences in casual resting or 24-h ambulatory BP at baseline in the two groups. Casual systolic BP (SBP) did not change as a result of the 12-wk intervention in the oat (138 plus minus 2 vs. 135 plus minus 3 mmHg) or wheat (142 plus minus 2 vs. 140 plus minus 3 mmHg) groups, respectively (all P > 0.05). Casual diastolic BP (DBP) also did not change in the oat (89 plus minus 2 vs. 88 plus minus 2 mmHg) or wheat (90 plus minus 2 vs. 91 plus minus 2 mmHg) group during this period (all P > 0.05). Further, 24-h, daytime and nighttime SBP and DBP did not decrease with the intervention. Therefore, the results of the present study suggest that any cardioprotective benefit of regular oat consumption may not be conferred via an arterial BP-lowering effect.     

Implicit and explicit alcohol-related cognitions

This article presents the proceedings of a symposium at the 2001 RSA Meeting in Montreal, Canada organized by Reinout W. Wiers and Alan W. Stacy. The purpose of the symposium was to present recent applications of implicit cognitive processing theory to alcohol research. Basic cognitive research has demonstrated that implicit cognition influences memory and behavior without explicit recall or introspection. The presentations from this symposium show that implicit cognition approaches yield new insights into understanding drinking motivation. The presentations were: (1) An introduction by Alan W. Stacy; (2) Implicit cognition and alcohol use. Involvement of other variables? (Susan L. Ames); (3) Alcohol expectancies and the art of implicit priming (Jane A. Noll); (4) Parental alcoholism and the effects of alcohol on semantic priming (Michael A. Sayette); (5) Implicit arousal and explicit liking of alcohol in heavy drinkers (Reinout W. Wiers); and (6) Negative affective cues and associative cognition in problem drinkers (Martin Zack). Comments were provided by the discussant Marvin Krank. The presented studies demonstrated that: (1) implicit memories of alcohol associations are powerful predictors and cross‐sectional correlates of alcohol use; (2) implicit retrieval processes influence alcohol outcome expectancies and alcohol consumption; (3) alcohol consumption influences implicit memory processing; (4) heavy drinkers reveal different affective responses in implicit and explicit tasks; and (5) negative affect exerts an implicit priming effect for alcohol associations in problem drinkers. These findings illustrate the importance of implicit cognition in understanding alcohol abuse and demonstrate the potential of the theoretical framework for more widespread application across a variety of areas of alcohol research, including diagnostics for the risk of alcohol abuse, treatment, and prevention.