Using amyloid PET imaging to diagnose Alzheimer’s disease in patients with multiple sclerosis

Journal of Neurology - Cognitive dysfunction affects 40–60% of individuals with multiple sclerosis (MS). The neuropsychological profile commonly consists of a subcortical pattern of deficits,...     

Methods to determine the minimum important difference for a sexual event diary used by postmenopausal women with hypoactive sexual desire disorder

IntroductionRecently, there has been much discussion in the literature about how to determine the meaningfulness of results generated from a patient-reported outcome measure. A number of reviews have shown that there are two main approaches: anchor- and distribution-based approaches for determining the minimum important difference (MID) for a new measure. There are issues with calculating an MID using each method: Will the two approaches give the same estimate? If the estimates differ, how do you decide on one estimate? Would asking patients directly be more beneficial?AimA case study was presented to address these issues based on a newly developed diary assessing number of satisfactory sexual events (SSEs) per week in women with hypoactive sexual desire disorder (HSDD).MethodsAnchor- and distribution-based estimates were generated from data gathered in two double-blind, placebo-controlled, parallel group trials for the treatment of HSDD (N = 788). A novel interview study was used to ask women directly about an MID for SSEs (N = 77).Main Outcome MeasuresDefining the MID for an SSE diary in women with HSDD.ResultsThe estimates varied, producing a range of mean MID estimates between 0.04 and 0.46 SSEs per week.ConclusionsWe recommend that rather than defining the MID, a range should be selected from the set of estimates formed by the limits of the 95% confidence intervals. Symonds T, Spino C, Sisson M, Soni P, Martin M, Gunter L, and Patrick DL. Methods to determine the minimum important difference for a sexual event diary used by postmenopausal women with hypoactive sexual desire disorder.     

Phase-Contrast Magnetic Resonance Angiography for the Determination of Cerebrovascular Reserve

Cerebrovascular reserve (CVR) is the potential for cerebral arteriolar dilatation to occur, in response to decreased cerebral perfusion pressure, in order to maintain constant cerebral blood flow. Diminution or absence of CVR is considered a risk factor for stroke. Current methods for determining CVR include singlephoton emission computed tomography, positron emission tomography and transcranial Doppler (TCD) ultrasonography. However, significant advantages could derive from the utilization of magnetic resonance angiography (MRA) based on the concurrent acquisition of hemodynamic information (CVR and collateral flow) with phase?contrast (PC) techniques and vascular morphology with three?dimensional, time?of?flight methods. With a 1.5?T scanner and acetazolamide (AZM), an arteriolar dilator, CVR was determined in 7 normal subjects. Mean flow velocity in the middle cerebral arteries was determined by PC MRA before and after AZM administration. For comparative purposes, mean flow velocities in the same middle cerebral arteries were determined by TCD before and after AZM administration. The mean flow velocities were as follows (mean ± standard deviation, n = 7): 40 ± 8 (PC MRA) versus 61 ±10 cm/sec (TCD) before AZM treatment and 58 ±11 (PC MRA) versus 85 ±15 cm/sec (TCD) after AZM administration. The increase in mean flow velocity (before vs after AZM), that is, the CVR, was 45 ±11 % as shown by PC MRA and 39 ± 14% as shown by TCD. Although significant differences were present between the mean flow velocities measured before and those after AZM administration, as determined by PC MRA and TCD, the CVR was not significantly different (45 vs 39%, respectively). These preliminary results suggest that PC MRA may be a method for determining CVR.     

Lipid hydroperoxide-induced tumor necrosis factor (TNF)-α, vascular endothelial growth factor and neovascularization in the rabbit cornea: effect of TNF inhibition

Lipid hydroperoxides (LHP) at high concentrations are cytotoxic, but at sublethal concentration, they induce synthesis of cytokine vascular growth factors. Intracorneal injections of 30 μg LHP placed 5 mm from the superior limbus stimulated early vasodilation of limbal vasculature and a rapidly developing, sustained neovascularization. Under these conditions, vessels grew at the rate of 0.3 mm/day to a total length of 7.5 mm, 25 days after injection. Cholesterol peroxides were less effective. Developing vessels were oriented towards the stimulus. Around the developing vessel there was dissolution of the stromal extracellular matrix. The most distal endothelial cells displayed prominent endoplasmic reticulum, a lack of basement membrane or tight junction complexes and leakage of fluorescein dye. Both the injection site and superior quadrant showed increased levels of tumor necrosis factor (TNF)-α and vascular endothelial growth factor after exposure to LHP. The neovascular response was inhibited by simultaneous administration of TNF-α antibody or pentoxifylline, an inhibitor of TNF-α synthesis. This corneal model of peroxide-induced neovascularization should prove useful for temporal studies of events in the initiation and propagation of signals leading to neovascularization, and for evaluating effects of treatment on neovascular growth.