Frailty and Somatic Comorbidity in Older Patients With Medically Unexplained Symptoms

ObjectivesTo examine the level of frailty and somatic comorbidity in older patients with medically unexplained symptoms (MUS) and compare this to patients with medically explained symptoms (MES).DesignCross-sectional, comparative study.SettingCommunity, primary care, and secondary healthcare to recruit patients with MUS in various developmental and severity stages and primary care to recruit patients with MES.ParticipantsIn total, 118 patients with MUS and 154 patients with MES, all aged ≥60 years.MethodsFrailty was assessed according to the Fried criteria (gait speed, handgrip strength, unintentional weight loss, exhaustion, and low physical activity), somatic comorbidity according to the self-report Charlson comorbidity index, and the number of prescribed medications.ResultsAlthough patients with MUS had less physical comorbidity compared with patients with MES, they were prescribed the same number of medications. Moreover, patients with MUS were more often frail compared with patients with MES. Among patients with MUS, physical frailty was associated with the severity of unexplained symptoms, the level of hypochondriacal beliefs, and the level of somatisation.Conclusions and implicationsDespite a lower prevalence of overt somatic diseases, patients with MUS are more frail compared with older patients with MES. These results suggest that at least in some patients age-related phenomena might be erroneously classified as MUS, which may affect treatment strategy.     

Peptidoglycan increases firm adhesion of monocytes under flow conditions and primes monocyte chemotaxis

The Toll-like receptor (TLR) 2/nucleotide-binding oligomerization domain ligand peptidoglycan (PG) has been shown to be present in macrophage-rich regions within atherosclerotic lesions, and stimulation of TLR2 promotes atherosclerotic plaque and intima formation in in vivo mouse models. We determined the effect of a PG preparation and Pam(3)Cys-SK(4), a synthetic TLR2 activator, on (1) adhesion molecule expression by flow cytometry; (2) monocyte adhesion under flow conditions, and (3) monocyte migration. The total adhesion (rolling and firm adhesion) of the PG-preparation-stimulated monocytes to L cells, constitutively expressing ICAM-1 (intercellular adhesion molecule-1) and E-selectin, was decreased. This was most likely due to the L-selectin shedding, since monocyte incubation with a blocking L-selectin antibody resulted in a comparable number of adherent monocytes as PG-stimulated cells. The PG preparation induced an increased percentage of firmly adherent, polarized cells and a beta(2)-integrin-dependent binding to ICAM-1-coated beads. Interestingly, the PG preparation induced a priming of the monocytes for increased migration towards the chemoattractant C5a which was TLR2 and beta(2)-integrin dependent. Pam(3)Cys-SK(4) gave comparable results to the PG preparation in all assays tested. This study demonstrates that PG activation of monocytes results in an increase in adhesive and migratory capacities of these cells. This might be a mechanism by which PG promotes atherosclerotic disease in vivo.     

Intestinal bile salt absorption in Atp8b1 deficient mice

BACKGROUND/AIMS: Mutations in the ATP8B1 gene can cause Progressive Familial Intrahepatic Cholestasis type 1. We have previously reported that Atp8b1(G308V/G308V) mice, a model for PFIC1, have slightly, but significantly, higher baseline serum bile salt (BS) concentrations compared to wt mice. Upon BS feeding, serum BS concentrations strongly increased in Atp8b1-deficient mice. Despite these findings, we observed only mildly impaired canalicular BS transport. In the present report we tested the hypothesis that Atp8b1(G308V/G308V) mice hyperabsorb BS in the intestine during BS feeding. METHODS: Intestinal BS absorption was measured in intestinal perfusion and in intestinal explants. In addition, we measured BS concentrations in portal blood. Ileal expression of the Fxr-targets Asbt, Ilbp and Shp was assessed. RESULTS: In wt and Atp8b1(G308V/G308V) mice, intestinal taurocholate absorption is primarily mediated by the ileal bile salt transporter Asbt. Neither of the experimental systems revealed enhanced absorption of BS in Atp8b1(G308V/G308V) mice compared to wt mice. In line with these observations, we found no difference in the ileal protein expression of Asbt. Induction of Shp expression during BS feeding also demonstrated that Fxr signalling is intact in Atp8b1(G308V/G308V) mice. CONCLUSIONS: The accumulation of BS in plasma of Atp8b1(G308V/G308V) mice during BS feeding is not caused by increased intestinal BS absorption.     

Genetics in liver diseases

In recent years, few fields in medicine have witnessed discoveries as momentous as those pertaining to the liver. Dramatic advances have been made, particularly in the areas of molecular biology and genetics. A joint EASL/AASLD Monothematic Conference was held on June 23rd-24th, 2006, in Modena, Italy, to bring the latest breakthroughs in different fields of genetics to hepatologists. This article reports the highlights of the conference and summarizes the main conclusions and implications for clinical and experimental hepatology.