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Tion in 1999 and will be edited by Julian E. Bailes, MD and Author L. Day, MD. The 20-chapter book will include chapters covering new forms of concussion classification, neurosurgical treatment of athletes, and controversial issues. It is expected to advance our understanding of neurological and neurosurgical athletic injuries and the role of the neurosurgeon in delivering their care. I continue to encourage neurosurgeons to become more involved in the care of the injured athlete. We feel that progress has been made and that we are gaining both recognition and representation on a national level with our other sports medicine colleagues concerning the necessity and advantage of having active neurosurgical involvement.
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Background: Increasing evidence indicates differential protease inhibitor pharmacokinetics PK ; between males and females. This has been underscored by recent studies in which significantly higher saquinavir plasma concentrations were observed in females. However, there are also clear data indicating higher hepatic CYP3A4 activity in females and therefore higher saquinavir clearance i.e. lower concentrations ; would be expected. Physiological differences between genders may account, in part, for the disparity in PK but host factors, such as transporter expression may also contribute. We have evaluated the impact of gender on saquinavir hard-gel ritonavir SQV RTV ; PK in HIVinfected patients. In a separate study, expression of drug transporters in PBMCs was explored in an attempt to elucidate an underlying mechanism. Materials & Methods: A retrospective analysis of four SQV RTV 1000 100mg bid ; PK studies included 34 patients [6 females; median range ; CD4 count at screening: 362cells m3 99-970 ; ]. SQV RTV was quantified by HPLC-MS MS and PK parameters calculated. Transporter expression was evaluated in PBMCs isolated from 93 HIV-infected individuals [30 females; median range ; CD4 count: 343cells mm3 8-1318 ; ]. P-glycoprotein and MRP expression was determined by flow cytometry and expressed as relative fluorescence units RFU ; . Differences in PK and transporter expression were assessed Mann-Whitney ; Results: A higher median SQV AUC0-12h 13804 vs. 24775ng.h ml; p 0.05 ; , Ctrough 271 vs. 786ng ml; p 0.05 ; and Cmax 2343 vs. 4373ng ml; p 0.05 ; was observed in females. Median RTV AUC0-12h 7587 and 15412ng.h ml ; , Ctrough 192 and 558ng ml ; and Cmax 1052 and 2818ng ml ; were significantly higher in females p 0.0001, and 0.001, respectively ; . SQV and RTV half-life were similar between genders p 0.55 and 0.36, respectively ; . Median p-glycoprotein expression was 0.66RFU in females compared to 0.89RFU in males p 0.0016 ; . Median expression of MRP in females was 0.14RFU compared to 0.35RFU in males p 0.018 ; . Conclusions: Higher SQV RTV plasma concentrations demonstrated in females is in agreement with other recent studies. However, a mechanism for this effect is not yet known. Differential expression of p-glycoprotein and MRP in PBMCs between genders was observed. Although recent data have shown no difference in duodenal p-glycoprotein, differential expression of transporters at other sites could limit access to CYP3A4 and reduce clearance. Gender differences in gut and hepatic transporters are controversial and require clarification.
Compared to direct ophthalmoscopy the technique is less affected by corneal clouding, cataracts, or vitreous hemorrhage. Other advantages include a relatively large field of view, high resolution and an ability to visualize the peripheral retina. Disadvantages include low magnification and a projected aerial image that is inverted and laterally reversed. A valuable skill for forensic pathologists, the technique of postmortem monocular indirect ophthalmoscopy can be challenging for pathology residents and forensic pathology fellows to master. Indirect ophthalmoscopy is not routinely taught in most medical schools so with the exception of ophthalmologists-in-training most residents and fellows have a limited exposure to the technique. Because the projected aerial image is inverted and laterally reversed precise descriptions or recording of fundal abnormalities can be challenging. Since the image cannot be viewed simultaneously by the instructor and student, learning PMIO can be intimidating because the more experienced forensic pathologist must teach the technique and describe the orientation of any fundal abnormalities observed. To facilitate skill acquisition in PMIO, a simple and inexpensive teaching model can be constructed from hinged, cylindrical plastic containers having an internal diameter of 35 mm and a depth of 30 mm. A 9-mm hole drilled in the center of the hinged lid from a 1-oz cylindrical plastic canister creates an artificial pupil. Fundal images depicting hemorrhagic retinopathy printed on 8 x10-inch matte photographic paper are cropped into 3.5 mm circles with available imaging software. Trimmed images from the photographic paper are fitted into the canister's base. The lid of the canister marked as to the appropriate eye and correct orientation completes the model. Using a procedural headlight and an aspherical indirect condensing lens, the resident or fellow can practice viewing the simulated fundal image. Multiple funduscopic abnormalities with retinal hemorrhages can be created for teaching with variations in the number, location preretinal, intra-retinal, subretinal ; , distribution and orientation relative to the optic disc. Using this simple teaching model, the pathology resident or fellow can be assessed as to his her ability to accurately identify and describe the number, location, distribution and orientation of retinal hemorrhages and various other fundal abnormalities of pathological significance. Postmortem Monocular Indirect Ophthalmoscopy, Ocular Fundus, Retinal Hemorrhage.
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