The pharmacokinetics and safety of desvenlafaxine in subjects with chronic renal impairment.

BACKGROUND: Desvenlafaxine (administered as desvenlafaxine succinate), the major active metabolite of venlafaxine, is a new serotonin-norepinephrine reuptake inhibitor (SNRI) approved for the treatment of major depressive disorder (MDD). OBJECTIVE: To assess the pharmacokinetics, safety, and tolerability of desvenlafaxine in healthy volunteers vs. those with renal impairment. MATERIALS AND METHODS: A single, oral, 100 mg dose of desvenlafaxine was administered to healthy subjects (n = 8) and subjects with mild (n = 9), moderate (n = 9), or severe (n = 7) renal impairment (24-h creatinine clearance, ml/min: 50 - 80, 30 - 50, or < 30 ml/min, respectively) or end-stage renal disease (ESRD; on dialysis.

Cognitive visual perceptual deficits in patients with delirium.

BACKGROUND: Delirium is a neuropsychiatric disorder characterised by severe cognitive impairment, but the specific neuropsychological profile of this condition has not yet been clearly delineated. Psychiatric symptoms of perceptual disturbance--such as hallucinations, illusions and misperceptions--are common in delirium, suggesting that patients may have deficits in the cognitive systems underlying visual perception. METHODS: Five neuropsychological tests of visual perception were administered to 17 older patients with delirium, as well as to two control groups comprising 14 patients with Alzheimer's dementia and 18 cognitively normal patients. The Mini Mental State Examination and the Consortium to Establish a Registry for Alzheimer's Disease verbal memory test were also administered to assess the specificity of any perceptual impairments. RESULTS: Patients with delirium scored significantly lower than cognitively normal patients on all perceptual tasks and significantly lower than patients with dementia on three of these tasks. Mini Mental State Examination scores did not differ between the delirium and dementia groups, and patients with delirium showed significantly better verbal recognition performance than those with dementia. CONCLUSIONS: Patients with delirium have specific visual perceptual deficits that cannot be accounted for by general cognitive impairment. These novel findings provide insights into the neural mechanisms underling delirium and might help to improve clinical detection and management of the disorder. The results also support previous suggestions that cognitive perceptual deficits play a causal role in eliciting psychiatric symptoms of perceptual disturbance.

Cellular aspects of vascular remodeling in hypertension revealed by confocal microscopy.

Cellular aspects of remodeling in intact arteries have not been fully investigated, mainly due to the lack of an appropriate methodology that allows for simple measurements. The aim of this study was to develop a method based on laser scanning confocal microscopy (LSCM), compare it with previous methodology, and apply it to the study of remodeling in hypertension. The morphology of mesenteric resistance arteries from stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto rats (WKY) was determined with wire myography on one segment with a standardized diameter setting (0.9[d100]) and with perfusion myography on a second segment from the same artery at the calculated equivalent pressure. The second segments were stained with the nuclear dye Hoechst 33342 (live tissue) or propidium iodide (fixed tissue) and measured with LSCM and MetaMorph software. Compared with wire myography, perfusion myography showed similar differences from those previously reported. Compared with LSCM, perfusion myography showed a similar lumen but significantly smaller wall thickness in both live and fixed tissue, probably due to measurement underestimation. In the study with LSCM, arteries from SHRSP compared with those from WKY showed (1) reduced lumen, (2) altered cell density that was significantly increased in the adventitia, decreased in the media, and unchanged in the intima, (3) significantly increased medial volume, (4) significantly smaller endothelial cell nuclei, and (5) adventitial-like cells in the media. We conclude that (1) LSCM is a reliable and straightforward method to study morphology in intact vessels, (2) it provides new information on the cellular changes in remodeling, (3) adventitia might play an active role in the process of remodeling in hypertension, and (4) endothelium "remodels" in hypertension.

Intraoperative 5-fluorouracil for filtration surgery in the rabbit.

PURPOSE: Postoperative subconjunctival injections of 5-fluorouracil (5-FU) improve the success rate of filtration surgery, but there is still a 20% or greater failure rate at 1 year in pseudophakic and repeat trabeculectomy cases. The injections are inconvenient to give and may produce corneal epithelial toxicity and other side effects. An alternative method for administration of 5-FU is investigated. METHODS: A masked, randomized, prospective study was undertaken to compare bleb survival and complications in a rabbit model, after either a single intraoperative exposure to 5-FU (50 mg/ml concentration for 5 minutes) or five postoperative injections of 5-FU (5 mg injection on postoperative days 1, 3, 5, 7, and 9), or a combination of both, with controls that received only a 5-minute exposure to distilled water, intraoperatively. RESULTS: For the control eyes, all blebs were "flat" to masked grading, and intraocular pressure returned to preoperative levels by postoperative day 11. In the group receiving postoperative injections of 5-FU only, blebs were flat and the pressure normalized by postoperative day 14. Rabbits receiving intraoperative 5-FU only, or combined intraoperative and postoperative 5-FU, had consistently higher blebs than the former two groups, and some blebs survived until postoperative day 25. The mean intraocular pressure remained depressed in these groups until postoperative day 21 (P < 0.05 for days 5 through 18). A combination of intraoperative and postoperative 5-FU produced significantly higher blebs than intraoperative 5-FU alone on days 7 to 14. CONCLUSIONS: Intraoperative application of high-dose 5-FU to the filtration site either as a single 5-minute treatment, or in conjunction with postoperative injections of 5-FU greatly prolongs bleb function after filtration surgery in the rabbit.