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To determine the frequency of multiple pathology [Alzheimer Disease (AD) plus Vascular Dementia and/or Dementia with Lewy Bodies] in patients enrolled in clinical trials of AD therapy, and to compare the cognitive and functional assessments between patients with pure AD and AD with multiple pathology.
We conducted a retrospective analysis of patients with a clinical diagnosis of AD who were enrolled in AD therapy clinical trials and subsequently received an autopsy for confirmation of their diagnosis from 2000 to 2009. Performance on cognitive screening tests, namely Modified Mini Mental state (3MS) exam, Mini Mental state Exam (MMSE) and Functional Rating Scale (FRS) were compared between patients with pure AD and multiple pathology.
Autopsy reports were available for 16/47 (34%) of deceased patients. Of these 16 patients, 5 (31%) had pure AD pathology, 10 (63%) had AD with other pathology, and 1 (6%) had non-AD pathology. Compared to patients with pure AD, patients with AD mixed with other pathology had poorer baseline FRS in problem-solving (p<0.01) and community affairs (p<0.02).
While the strict enrollment criteria for clinical trials identified the presence of AD pathology in the majority of cases (15/16), multiple pathology was more common than pure AD in our series of autopsied patients. Premortem biomarkers that can distinguish between pure AD and AD with multiple pathology will be beneficial in future clinical trials and dementia patient management.
A collagenous scar capsule forms around biomaterial implants and for deformable implants such as a breast prosthesis, this phenomenon of capsular scar contracture may lead to deformation and hardening of the implant. Relaxin, a peptide hormone of pregnancy which is known to affect collagen rich tissues, was given to mice in an attempt to eliminate or lessen this contracture. A short (8 day) study was performed to observe the effects of relaxin and estrogen on the mechanical properties of Skin and the interpubic ligament. A longer (27 day) study observed the effects of relaxin in estrogen primed mice containing implants. Changes in skin, interpubic ligament, scar capsule and contracture phenomenon were noted. Stress-strain characterization, dynamic mechanical spectroscopy and light microscopy were used to characterize the effects of relaxin and estradiol on the contracture phenomenon. Qualitatively, relaxin given to estrogen primed mice was shown to lessen implant contracture and deformability. Administration of relaxin produced the documented changes in the interpubic ligament, but differences were noted between the 8 and 27 day studies. Differences in the failure stress and strain and modulus for the long implant and short non-implant study were noted for the relaxin treated mice.
A study reported by Magowan et al. (2006) determined a large variation in growth rate, between herds of pigs in Northern Ireland reaching a live weight of 100 kg, equating to an average difference of 18 days. All pigs used in the study were of the Landrace x Large White breed. It was considered that the large variation in growth rate was mainly a result of different management or disease levels. It was therefore hypothesised that, if a representative sample of pigs from the various sources were housed in a common environment, performance of the pigs would be similar. The aim of this work was to investigate the variation in the performance of pigs sourced from herds with varying growth performance and housed in a common environment.
Previous studies from our group suggest that the synchronised onset of oestradiol secretion by preimplantation conceptuses from Meishan pigs may contribute to the enhanced prenatal survival characteristic of this breed (Ashworth and Pickard, 1998). We have recently reported that in vitro, the onset of oestradiol secretion by conceptuses can be regulated in a dose-dependent manner by an aromatase inhibitor (letrozole; Ashworth et al., 2005). Before commencing in vivo trials to assess the efficacy of letrozole to promote prenatal survival, it is important to determine whether exogenous letrozole reaches the uterine lumen and to establish the relationship between the dose administered and the impact on oestradiol secretion at the conceptus-uterine interface.
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