P.H. Robert

<i>Abstract</i>. In long-term peritoneal dialysis, functional deterioration of the peritoneal membrane is often associated with proliferative processes of the involved tissues leading to peritoneal fibrosis. In continuous ambulatory peritoneal dialysis (CAPD), failure to achieve target values for adequacy of dialysis is commonly corrected by increasing dwell volume; in case of ultrafiltration failure, osmolarity of the dialysate gets increased. In a prospective study, the impact of increasing dwell volume from 1500 ml to 2500 ml per dwell (volume trial) or changing the osmolarity of the dialysate from 1.36 to 3.86% glucose (hyperosmolarity trial) on the peritoneal endothelin-1 (ET-1) release was analyzed. ET-1 is known to exert significant proliferative activities on a variety of cell types leading to an accumulation of extracellular matrix. A highly significant difference in the cumulative peritoneal ET-1 synthesis was found between the low- and high-volume exchange, whereas differences in the hyperosmolarity setting were only moderate. Sixty minutes after initiating dialysis, the cumulative ET-1 synthesis was 2367 ± 1023 fmol for the 1500 ml <i>versus</i> 6062 ± 1419 fmol for the 2500 dwell (<i>P</i> &lt; 0.0001) and 4572 ± 969 fmol <i>versus</i> 6124 ± 1473 fmol for the 1.36 and 3.86% glucose dwell (<i>P</i> &lt; 0.05), respectively. In conclusion, increasing dwell volume leads to a strong activation of the peritoneal paracrine endothelin system. Because ET-1, apart from being a potent vasoactive peptide, contributes to fibrotic remodeling, this study indicates that volume stress-induced ET-1 release might contribute to structural alteration of the peritoneal membrane in long-term peritoneal dialysis.

Abstract Introduction Diagnostic relevance of plasma amyloid β (Aβ) for Alzheimer's disease (AD) process yields conflicting results. The objective of the study was to assess plasma levels of Aβ 42 and Aβ 40 in amnestic mild cognitive impairment (MCI), nonamnestic MCI, and AD patients and to investigate relationships between peripheral and central biomarkers. Methods One thousand forty participants (417 amnestic MCI, 122 nonamnestic MCI, and 501 AD) from the Biomarker of AmyLoïd pepTide and AlZheimer's diseAse Risk multicenter prospective study with cognition, plasma, cerebrospinal fluid (CSF), and magnetic resonance imaging assessments were included. Results Plasma Aβ 1–42 and Aβ 1–40 were lower in AD (36.9 [11.7] and 263 [80] pg/mL) than in amnestic MCI (38.2 [11.9] and 269 [68] pg/mL) than in nonamnestic MCI (39.7 [10.5] and 272 [52] pg/mL), respectively ( P = .01 for overall difference between groups for Aβ 1–42 and P = .04 for Aβ 1–40 ). Globally, plasma Aβ 1–42 correlated with age, Mini–Mental State Examination, and APOE ε4 allele. Plasma Aβ 1–42 correlated with all CSF biomarkers in MCI but only with CSF Aβ 42 in AD. Discussion Plasma Aβ was associated with cognitive status and CSF biomarkers, suggesting the interest of plasma amyloid biomarkers for diagnosis purpose.

AIM: Technetium-99m hexamethylpropylene amine oxime ((99m)Tc-HMPAO) and technetium-99m N,N-1,2-ethylene diylbis-Lcysteine diethyl ester dihydrochloride ((99m)Tc-ECD) SPECT are widely used in Dementia Clinics for early and differential diagnosis. They have been shown to perform differently in Alzheimer's disease (AD), but the impact of such differences on both research and clinical work is unknown. We investigated the differences between the 2 compounds in research work by assessing correlation between performance on a verbal memory task and cerebral perfusion in 2 matched groups of AD patients. METHODS: Nineteen pairs of patients with mild to moderate AD undergoing SPECT with either 99mTc-HMPAO or (99m)Tc-ECD were retrospectively selected in a Memory Clinic. Patients were matched for sex, age (+/-3 years) and the Mini-Mental State Examination score (+/-2 points) with a case-control procedure, thus obtaining 2 well-matched groups. The score on the Grober-Buschke selective reminding test (SRT) was correlated with SPECT in each group by means of statistical parametric mapping 99 (height threshold: P<0.01). RESULTS: (99m)Tc-HMPAO SPECT yielded 3 significant correlation clusters involving inferior and middle frontal gyri, para-hippocampal gyrus and putamen in the right hemisphere; the middle and superior temporal gyri, insula and claustrum in the left hemisphere. (99m)Tc-ECD gave a significant cluster of correlation in left postcentral gyrus and inferior parietal lobule. CONCLUSION: (99m)Tc-HMPAO SPECT correlation sites seem more consistent than (99m)Tc-ECD ones with the neurophysiological models of verbal memory, as designed both in normal individuals and in pathological conditions. The demonstration of such relevant differences introduces a source of variability among studies performed with either of the 2 compounds, which must be considered when interpreting results.