Sildenafil Citrate Increases Fetal Weight in a Mouse Model of Fetal Growth Restriction with a Normal Vascular Phenotype

Fetal growth restriction (FGR) is defined as the inability of a fetus to achieve its genetic growth potential and is associated with a significantly increased risk of morbidity and mortality. Clinically, FGR is diagnosed as a fetus falling below the 5(th) centile of customised growth charts. Sildenafil citrate (SC, Viagra™), a potent and selective phosphodiesterase-5 inhibitor, corrects ex vivo placental vascular dysfunction in FGR, demonstrating potential as a therapy for this condition. However, many FGR cases present without an abnormal vascular phenotype, as assessed by Doppler measures of uterine/umbilical artery blood flow velocity. Thus, we hypothesized that SC would not increase fetal growth in a mouse model of FGR, the placental-specific Igf2 knockout mouse, which has altered placental exchange capacity but normal placental blood flow. Fetal weights were increased (by 8%) in P0 mice following maternal SC treatment (0.4 mg/ml) via drinking water. There was also a trend towards increased placental weight in treated P0 mice (P = 0.056). Additionally, 75% of the P0 fetal weights were below the 5(th) centile, the criterion used to define human FGR, of the non-treated WT fetal weights; this was reduced to 51% when dams were treated with SC. Umbilical artery and vein blood flow velocity measures confirmed the lack of an abnormal vascular phenotype in the P0 mouse; and were unaffected by SC treatment. (14)C-methylaminoisobutyric acid transfer (measured to assess effects on placental nutrient transporter activity) per g placenta was unaffected by SC, versus untreated, though total transfer was increased, commensurate with the trend towards larger placentas in this group. These data suggest that SC may improve fetal growth even in the absence of an abnormal placental blood flow, potentially affording use in multiple sub-populations of individuals presenting with FGR

Asking Family About Memory Loss: Is It Helpful?

OBJECTIVE: To compare a family informant's report of memory loss in an older family member to standardized clinical diagnoses of cognitive impairment. SETTING: Duke Established Populations for Epidemiologic Studies of the Elderly (EPESE), a 10-year longitudinal study of community dwellers aged 65 and greater in five counties of North Carolina. PARTICIPANTS: A stratified random sample of potentially demented participants was selected from the second wave of the Duke EPESE using responses to a brief cognitive screen. A neuropsychological battery was administered to these participants, and their family informants were asked whether they recognized memory loss in the participant. One hundred fifty-seven participants completed the full evaluation and also had an available family informant. MAIN OUTCOME MEASURES: Family informant's report of memory loss (yes, no, sometimes) compared to expert consensus diagnosis of cognitive impairment or dementia. RESULTS: There was poor concordance between the clinical diagnoses of cognitive impairment or dementia and the family informant's recognition of memory loss (κ=−0.05; P =.74). When informants reported memory loss, 30% of participants were found not to have a cognitive loss. Among participants in whom family informants reported no memory loss, 75% were diagnosed with dementia or cognitive impairment (sensitivity, 0.70, 95% confidence interval [CI], 0.61 to 0.78; specificity, 0.24, 95% CI, 0.13 to 0.40; positive predictive value, 70%; negative predictive value, 25%). CONCLUSIONS: Asking family members about memory loss in a patient may be an unreliable strategy to detect dementia