TREATMENT OF INSOMNIA WITH ZALEPLON,A NOVEL SLEEP MEDICATION

Insomnia is a highly prevalent sleep problem that often results in poor daily functioning of the affected patient. Unfortunately, sedative hypnotic agents prescribed in the past often resulted in residual sedation, as well as impairment of cognitive and psychomotor performance, throughout the day after use. Newer agents with relatively rapid elimination require administration regularly each night before bedtime if symptoms of insomnia are to be prevented and next-day sedation is to be avoided. The availability of zaleplon challenges these standards of practice. The rapid elimination of zaleplon, combined with its unique receptor binding affinity, permits 10 mg of zaleplon to be taken at bedtime or later in the night with minimal concern for next-day residual effects. Clinical studies of zaleplon also identified the low risk of withdrawal syndrome or rebound insomnia after the discontinuation of nightly use. If used only on the nights when symptoms actually occur, the occurrence of such problems with zaleplon will be minimal.     

Differential impact of pavlovian drug conditioned stimuli on in vivo dopamine transmission in the rat accumbens shell and core and in the prefrontal cortex

Rationale Conditioned stimuli (CSs) by pavlovian association with reinforcing drugs (US) are thought to play an important role in the acquisition, maintenance and relapse of drug dependence. Objective The aim of this study was to investigate by microdialysis the impact of pavlovian drug CSs on behaviour and on basal and drug-stimulated dopamine (DA) in three terminal DA areas: nucleus accumbens shell, core and prefrontal cortex (PFCX). Methods Conditioned rats were trained once a day for 3 days by presentation of Fonzies filled box (FFB, CS) for 10 min followed by administration of morphine (1 mg/kg), nicotine (0.4 mg/kg) or saline, respectively. Pseudo-conditioned rats were presented with the FFB 10 h after drug or saline administration. Rats were implanted with microdialysis probes in the shell, core and PFCX. The effect of stimuli conditioned with morphine and nicotine on DA and on DA response to drugs was studied. Results Drug CSs elicited incentive reactions and released DA in the shell and PFCX but not in the core. Pre-exposure to morphine CS potentiated DA release to morphine challenge in the shell but not in the core and PFCX. This effect was related to the challenge dose of morphine and was stimulus-specific since a food CS did not potentiate the shell DA response to morphine. Pre-exposure to nicotine CS potentiated DA release in the shell and PFCX. Conclusion The results show that drug CSs stimulate DA release in the shell and medial PFCX and specifically potentiate the primary stimulant drug effects on DA transmission.     

Follicular flushing at oocyte retrieval: a reappraisal

A survey of Australian assisted reproduction technique (ART) units revealed many (> 50%) use flushing of the follicle in addition to direct aspiration of the fluid during oocyte retrieval. The rationale is that flushing offers an advantage to the patient, with a larger number of oocytes being collected and thus a higher potential for pregnancy Following a complication in a patient, the medical staff determined that flushing might have been implicated. While this was later shown to be unfounded, the unit changed the method of oocyte collection, thus providing an opportunity historically to evaluate the differences between aspiration of follicular fluid alone or with additional flushing of each follicle. Thus the aim of this analysis was to test the hypothesis that aspiration alone does not effect the outcomes of ART with respect to oocyte numbers collected, their quality and subsequent fertilisation, or ultimate pregnancy rate in a large patient group (n = 2378). During the review period (1991-1993) the manufacturer of the aspiration needles; the pump and pressure used for aspiration; the staff involved in all procedures; and the premises, equipment and media used for oocyte collection and culture remained constant. Similarly the two patient groups did not differ in their demographics and physical characteristics. There was no difference (p > 0.5) in the number of oocytes collected, the number of embryos created or the pregnancy rate for that treatment cycle. There was also no significant difference between the two groups in fertilisation rates, irrespective of the type of treatment being used in vitro fertilisation (IVF), gamete intrafallopian transfer (GIFT) or intracytoplasmic sperm injection (ICSI)). The data presented in this paper are not prospective. They use historical comparison and are confounded by minor changes in ovarian stimulation protocols, but the conclusions are still valid. These data suggest there is no difference in the outcome of ART (from oocyte collection through to pregnancy rate) whether or not aspiration of follicles is accompanied by flushing. First principles of surgery advocate the shortest possible operating time, the simplest procedure and minimum amount of tissue handling as maxims for reducing complication. Therefore, as a routine, flushing would seem superfluous in ART.     

Headache in systemic lupus erythematosus: a controlled study

Intractable headaches, the so-called 'lupus headaches', have been long thought of as a common and characteristic manifestation of systemic lupus erythematosus (SLE). Seventy-eight patients with SLE, including 10 patients with definite central nervous system (CNS) involvement, and 89 healthy individuals matched for age, sex and socioeconomic status, were studied by a specific questionnaire addressing the characteristics and type of headache. Clinical features of SLE, neurological manifestations and treatment, disease severity and autoantibody profiles were correlated to the presence of headache. One year prevalence of headache was similar between patients (32%) and otherwise healthy individuals (30%). No significant differences regarding frequency, family history of headache and need for analgesic medication were observed. Headache refractory to analgesic treatment, but responsive to corticosteroid regimen, was recorded in only one patient. Clinical and serological features of SLE, including Raynaud's phenomenon and the presence of anticardiolipin antibodies, were not significantly different between headache sufferers and non-sufferers. In the majority of patients reporting headache, anxiety and/or depression co-existed. Episodic tension headache was the most frequent type, while migraine was traced in a quarter of headache sufferers. Neither the presence nor the clinical type of headache was related to, or predictive of, the development of seizures or psychosis. These results indicate that headache is not specifically related to SLE expression or severity, and suggest that accepting the presence even of a severe headache as a neurological manifestation of SLE in the absence of seizures or overt psychosis may result in overestimation of the disease status.      

Prostacyclin production by perturbed bovine aortic endothelial cells in culture

This study reports that endotoxin (Escherichia coli serotype 026:B6) and 12-O-tetradecanoyl-phorbol-13-acetate stimulate cultured bovine aortic endothelial cells to generate prostacyclin. The prostacyclin concentration of the culture medium was measured indirectly by radioimmunoassay for 6-keto-PGF1 alpha. The amount of prostacyclin generated depended on the concentration of endotoxin or phorbol diester. Prostacyclin generation was not immediate, but occurred slowly after a six-hour lag period. The perturbed cells contracted and showed marked shape changes that correlated temporally with the start of enhanced prostacyclin production. Cytochalasins B and D, vinblastine, and colchicine inhibited prostacyclin production, indicating involvement of the cytoskeleton in the cellular response to endotoxin and phorbol diester. The increase in prostacyclin production was prevented by trifluoperazine, an inhibitor of the Ca++-calmodulin system, which is known to be involved in cytoskeletal function. Generation of prostacyclin was inhibited by cycloheximide and actinomycin D, indicating dependence on protein and ribonucleic acid synthesis. It is postulated that exposure to endotoxin or phorbol diester leads, via a series of reactions that involve RNA and protein synthesis and require intact cytoskeletal function, to the generation of toxic active intermediate(s) that stimulate the enzymes necessary for prostacyclin production.     

An anionic material at the advancing front of blood cells entering the bone marrow circulation

The selective entry of mature blood cells into the peripheral circulation of the bone marrow is a transcellular process. The mature blood cells penetrate the cytoplasm of the endothelial cells lining the myeloid sinuses and form a migration pore in the cell body of the lining cell, which closes after the blood cell reaches the intravascular space. The changes at the surfaces of the cells involved in this selective transcellular process were studied by means of the cationic cell surface markers colloidal iron (CI) and polycationic (high isoelectric point) ferritin (PCF). The anionic cell surface charges resulting from the presence of sialated glycoproteins remain, as shown by the application of these markers at low pH (1.8), evenly distributed at the cell surfaces of both the blood cell and the sinus lining cell. However, there is at the advancing margin of the diapedesing blood cells a marked accumulation of a nonsialated anionic material binding PCF at high pH (7.2). This material first accumulates extravascularly beneath the endothelium at an area of the blood cell surface near the site of the migration pore formation, remains at the cell surface during the initial phases of transcellular passage and disappears, either through shedding in the vascular lumen or through redistribution on the cell surface, when the cell reaches the intravascular space. This anionic material, which is neuraminidase resistant and has a pKa higher than sialic acid, is a characteristic concommitant in the selective transcellular blood cell passage in bone marrow.     

Prospective randomized controlled trial comparing partially absorbable lightweight mesh and multifilament polyester anatomical mesh in laparoscopic inguinal hernia repair

Introduction

Tension‐free mesh repair is currently the gold standard treatment for inguinal hernia. Recent evidence has shown that both open and laparoscopic approaches to inguinal hernia repair can achieve good results. Lots of meshes with different properties are available on the market, but direct comparisons between them are scare. We conducted a prospective randomized controlled trial comparing a partially absorbable lightweight mesh (ULTRAPRO?) and a multifilament polyester anatomical mesh (Parietex?) in laparoscopic total extraperitoneal inguinal hernia repair.

Methods

This study was a single‐center, prospective randomized controlled trial to compare the surgical handling and clinical outcomes between two different types of meshes. All operations were performed using a standardized operative protocol. This study was approved by the Institutional Review Board of the Hong Kong East Cluster Health Service in 2009 (reference number: 2009‐087). The study was registered in the Australian New Zealand Clinical Trial Registry (ACTRN12610000031066).

Results

From October 2009 to August 2011, 85 laparoscopic total extraperitoneal inguinal hernia repairs were performed. The mean mesh handling time was 152 s for the ULTRAPRO group and 206 s for the Parietex group (P = 0.001). There were three cases of seroma formation in the ULTRAPRO group and nine in the Parietex group (P = 0.02). The overall recurrence rate was 2.5%.

Conclusion

It took less time to manipulate the flat mesh (ULTRAPRO) than the anatomical mesh (Parietex) in laparoscopic total extraperitoneal inguinal hernia repair, but the time difference was small. Lightweight mesh and heavyweight mesh offered similar clinical outcomes in terms of discomfort sensation and foreign body sensation during long‐term follow‐up.