Statin-fibrate combination: therapy for hyperlipidemia: a review.

Statins and fibrates are well-established treatments for hyperlipidaemias and the prevention of vascular events. However, fibrate + statin therapy has been restricted following early reports of rhabdomyolysis that mainly involved gemfibrozil, originally with bovastatin, and recently, with cerivastatin. Despite this limitation, several reports describing combination therapy have been published. This review considers these studies and the relevant indications and contraindications. Statin + fibrate therapy should be considered if monotherapy or adding other drugs (e.g. cholesterol absorption inhibitors, omega-3 fatty acids ornicotinic acid) did not achieve lipid targets or is impractical. Combination therapy should be hospital-based and reserved for high-risk patients with a mixed hyperlipidaemia characterised by low density lipoprotein cholesterol (LDL) >2.6 mmol/l(100 mg/dl, high density lipoprotein cholesterol (HDL) <1.0 mmol/l (40 mg/dl) and/or triglycerides> 5.6 mmol/l (500 mg/dl. These three 'goals' are individually mentioned in guidelines. Patients should have normal renal, liver and thyroid function tests and should not be receiving therapy with cyclosporine, protease inhibitors or drugs metabolised through cytochrome P450 (especially 3A4). Combination therapy is probably best conducted using drugs with short plasma half-lives; fibrates should be prescribed in the morning and statins at night to minimise peak dose interactions. Both drug classes should be progressively titated from low doses. Regular (3-monthly) monitoring of liver function and creatine kinase is required. In conclusion, fibrate + statin therapy remains an option in high-risk patents. However, long-term studies involving safety monitoring and vascular endpoints are required to demonstrate the efficacy of this regimen.

Neuropsychological effects of interferon beta-1a in relapsing multiple sclerosis. Multiple Sclerosis Collaborative Research Group.

Cognitive dysfunction is common in multiple sclerosis (MS), yet few studies have examined effects of treatment on neuropsychological (NP) performance. To evaluate the effects of interferon beta-1a (IFNbeta-1a, 30 microg administered intramuscularly once weekly [Avonex]) on cognitive function, a Comprehensive NP Battery was administered at baseline and week 104 to relapsing MS patients in the phase III study, 166 of whom completed both assessments. A Brief NP Battery was also administered at 6-month intervals. The primary NP outcome measure was 2-year change on the Comprehensive NP Battery, grouped into domains of information processing and learning/memory (set A), visuospatial abilities and problem solving (set B), and verbal abilities and attention span (set C). NP effects were most pronounced in cognitive domains vulnerable to MS: IFNbeta-1a had a significant beneficial effect on the set A composite, with a favorable trend evident on set B. Secondary outcome analyses revealed significant between-group differences in slopes for Brief NP Battery performance and time to sustained deterioration in a Paced Auditory Serial Addition Test processing rate, favoring the IFNbeta-1a group. These results support and extend previous observations of significant beneficial effects of IFNbeta-1a for relapsing MS.

The luteinizing hormone surge--the final stage in ovulation induction: modern aspects of ovulation triggering.

OBJECTIVE: To compile updated information regarding gonadotropin secretion, specifically the physiology of the midcycle LH surge, in natural cycles and under various ovulation induction protocols. DATA IDENTIFICATION AND SELECTION: Studies that deal with the clinical aspects of LH surge manipulation or substitution were identified through literature and Medline searches. RESULTS: Three major regulatory factors have been identified as participants in the induction of the midcycle gonadotropin surge. These are hypothalamic GnRH secretion, ovarian and adrenal steroids, and less well-characterized ovarian peptide hormones. Gonadotropin-releasing hormone pulsatility is regulated by a complex mechanism that integrates multiple neurotransmitters and sex steroids. Estradiol plays a central role in the pituitary secretion of LH, which also is influenced by P concentrations. Gonadotropin surge attenuating factor also has been implicated in the regulation of timing and amplitude of the LH surge. Human chorionic gonadotropin is used extensively as a LH surrogate, but its use is associated with a number of disadvantages. Induction of an endogenous LH surge through use of the flare effect of GnRH analogues has been examined more recently and has been found to have several advantages. Recombinant human LH is in the final stages of clinical testing. CONCLUSION: Although much is known about the physiology of the midcycle LH surge and its variations under different clinical conditions, new approaches to the induction or substitution of the LH surge currently are being examined and learned. The introduction of recombinant gonadotropins into clinical practice is likely to influence ovulation induction and IVF practice to a significant degree in the near future.