Discovertebral (Andersson) lesions in severe ankylosing spondylitis: a study using MRI and conventional radiography

The objective of this study is to investigate the prevalence of Andersson lesions (AL) in ankylosing spondylitis (AS) patients who will start anti-tumor necrosis factor (TNF) treatment. Radiographs and magnetic resonance imaging (MRI) of the spine were performed before therapy with anti-TNF. ALs were defined as discovertebral endplate destructions on MRI, associated with bone marrow edema and fat replacement or sclerosis, a decreased signal on T1, enhancement after contrast administration (gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA)), and increased signal on T2 and short tau inversion recovery (STIR). Additionally, conventional radiography showed a fracture line, irregular endplates, and increased sclerosis of adjacent vertebral bodies. Fifty-six AS patients were included, 68% males, mean age of 43 years, and mean disease duration of 11 years. The mean bath ankylosing spondylitis disease activity index was 6.4, and 24% of all patients had ankylosis. Only one patient showed a discovertebral abnormality with bone marrow edema of more than 50% of the vertebral bodies adjacent to the intervertebral disk of T7/T8 and T9/T10, a hypodense signal area on T1, and a high signal on STIR. Irregular endplates were depicted, and T1 after Gd-DTPA demonstrated high signal intensity around the disk margins. However, no fracture line was visible on conventional radiology, and therefore, this case was not considered to be an AL. No AL was detected in our AS patients, who were candidates for anti-TNF treatment. One patient showed a discovertebral abnormality on MRI, without a fracture line on conventional radiology. The relative small proportion of patients with a long-established disease might explain this finding for, particularly, an ankylosed spine is prone to develop an AL

Effective Use of Empirical Data for Virtual Screening against APJR GPCR Receptor

Alzheimer’s disease is a neurodegenerative disorder incompatible with normal daily activity, affecting one in nine people. One of its potential targets is the apelin receptor (APJR), a G-protein coupled receptor, which presents considerably high expression levels in the central nervous system. In silico studies of APJR drug-like molecule binding are in small numbers while high throughput screenings (HTS) are already sufficiently many to devise efficient drug design strategies. This presents itself as an opportunity to optimize different steps in future large scale virtual screening endeavours. Here, we ran a first stage docking simulation against a library of 95 known binders and 3829 generated decoys in an effort to improve the rescoring stage. We then analyzed receptor binding site structure and ligands binding poses to describe their interactions. As a result, we devised a simple and straightforward virtual screening Stage II filtering score based on search space extension followed by a geometric estimation of the ligand—binding site fitness. Having this score, we used an ensemble of receptors generated by Hamiltonian Monte Carlo simulation and reported the results. The improvements shown herein prove that our ensemble docking protocol is suited for APJR and can be easily extrapolated to other GPCRs

Effects of L-phenylalanine on energy intake and glycaemia–impacts on appetite perceptions, gastrointestinal hormones and gastric emptying in healthy males

In humans, phenylalanine stimulates plasma cholecystokinin (CCK) and pyloric pressures, both of which are important in the regulation of energy intake and gastric emptying. Gastric emptying is a key determinant of postprandial blood glucose. We evaluated the effects of intragastric phenylalanine on appetite perceptions and subsequent energy intake, and the glycaemic response to, and gastric emptying of, a mixed-nutrient drink. The study consisted of two parts, each including 16 healthy, lean males (age: 23 ± 1 years). In each part, participants received on three separate occasions, in randomised, double-blind fashion, 5 g (Phe-5 g) or 10g ('Phe-10 g) L-phenylalanine, or control, intragastrically, 30 min before a standardised buffet-meal (part A), or a standardised mixed-nutrient drink (part B). In part A, plasma CCK and peptide-YY (PYY), and appetite perceptions, were measured at baseline, after phenylalanine alone, and following the buffet-meal, from which energy intake was assessed. In part B, plasma glucose, glucagon-like peptide-1 (GLP-1), insulin and glucagon were measured at baseline, after phenylalanine alone, and for 2 h following the drink. Gastric emptying of the drink was also measured by ¹³C-acetate breath-test. Phe-10 g, but not Phe-5 g, stimulated plasma CCK (p = 0.01) and suppressed energy intake (p = 0.012); energy intake was correlated with stimulation of CCK (r = -0.4, p = 0.027), and tended to be associated with stimulation of PYY (r = -0.31, p = 0.082). Both Phe-10 g and Phe-5 g stimulated insulin and glucagon (all p < 0.05), but not GLP-1. Phe-10 g, but not Phe-5 g, reduced overall plasma glucose (p = 0.043) and peak plasma glucose (p = 0.017) in response to the mixed-nutrient drink. Phenylalanine had no effect on gastric emptying of the drink. In conclusion, our observations indicate that the energy intake-suppressant effect of phenylalanine is related to the stimulation of CCK and PYY, while the glucoregulatory effect may be independent of stimulation of plasma GLP-1 or slowing of gastric emptying.Penelope C.E. Fitzgerald, Benoit Manoliu, Benjamin Herbillon, Robert E. Steinert, Michael Horowitz, and Christine Feinle-Bisse

Air in the carotid canal as a predictor of distal internal carotid artery laceration

The authors describe a 25-year old patient with blunt trauma-induced bilateral, distal segment internal carotid artery (ICA) lacerations, resulting in a left-sided direct carotid-cavernous sinus fistula (CCF) and presenting with massive oronasal bleeding. The combination of severe oronasal bleeding, with air in the carotid canal should alarm the treating physician to the presence of a distal internal carotid artery laceration

Efficacy of MRI and mammography for breast-cancer screening in women with a familial or genetic predisposition.

Contains fulltext : 58587.pdf (publisher's version ) (Open Access)BACKGROUND: The value of regular surveillance for breast cancer in women with a genetic or familial predisposition to breast cancer is currently unproven. We compared the efficacy of magnetic resonance imaging (MRI) with that of mammography for screening in this group of high-risk women. METHODS: Women who had a cumulative lifetime risk of breast cancer of 15 percent or more were screened every six months with a clinical breast examination and once a year by mammography and MRI, with independent readings. The characteristics of the cancers that were detected were compared with the characteristics of those in two different age-matched control groups. RESULTS: We screened 1909 eligible women, including 358 carriers of germ-line mutations. Within a median follow-up period of 2.9 years, 51 tumors (44 invasive cancers, 6 ductal carcinomas in situ, and 1 lymphoma) and 1 lobular carcinoma in situ were detected. The sensitivity of clinical breast examination, mammography, and MRI for detecting invasive breast cancer was 17.9 percent, 33.3 percent, and 79.5 percent, respectively, and the specificity was 98.1 percent, 95.0 percent, and 89.8 percent, respectively. The overall discriminating capacity of MRI was significantly better than that of mammography (P<0.05). The proportion of invasive tumors that were 10 mm or less in diameter was significantly greater in our surveillance group (43.2 percent) than in either control group (14.0 percent [P<0.001] and 12.5 percent [P=0.04], respectively). The combined incidence of positive axillary nodes and micrometastases in invasive cancers in our study was 21.4 percent, as compared with 52.4 percent (P<0.001) and 56.4 percent (P=0.001) in the two control groups. CONCLUSIONS: MRI appears to be more sensitive than mammography in detecting tumors in women with an inherited susceptibility to breast cancer