Bone texture analysis is correlated with three-dimensional microarchitecture and mechanical properties of trabecular bone in osteoporotic femurs

Fracture of the proximal femur is a major public health problem in elderly persons. It has recently been suggested that combining texture analysis and bone mineral density measurement improves the failure load prediction in human femurs. In this study, we aimed to compare bone texture analysis with three-dimensional (3D) microarchitecture and mechanical properties of trabecular bone in osteoporotic femurs. Eight femoral heads from osteoporotic patients who fractured their femoral neck provided 31 bone cores. Bone samples were studied using a new high-resolution digital X-ray device (BMA?, D3A Medical Systems) allowing for texture analysis with fractal parameter H _mean, and were examined using micro-computed tomography (microCT) for 3D microarchitecture. Finally, uniaxial compression tests to failure were performed to estimate failure load and apparent modulus of bone samples. The fractal parameter H _mean was strongly correlated with bone volume fraction (BV/TV) (r = 0.84) and trabecular thickness (Tb.Th) (r = 0.91) (p < 0.01). H _mean was also markedly correlated with failure load (r = 0.84) and apparent modulus (r = 0.71) of core samples (p < 0.01). Bone volume fraction (BV/TV) and trabecular thickness (Tb.Th) demonstrated significant correlations with failure load (r = 0.85 and 0.72, respectively) and apparent modulus (r = 0.72 and 0.64, respectively) (p < 0.01). Overall, the best predictors of failure load were H _mean, bone volume fraction, and trabecular thickness, with r ² coefficients of 0.83, 0.76, and 0.80 respectively. This study shows that the fractal parameter H _mean is correlated with 3D microCT parameters and mechanical properties of femoral head bone samples, which suggests that radiographic texture analysis is a suitable approach for trabecular bone microarchitecture assessment in osteoporotic femurs.     

Tolerability of propofol in Wada testing

Objective:

To assess the tolerability of propofol (PF) in Wada test in an Arab population with temporal lobe epilepsy (TLE).

Methods:

This observational study with consecutive sampling took place in King Fahad Medical City, Riyadh, Saudi Arabia. Nine consecutive patients with mean (+SD) age of 26 (+5.8) years, 6 males and 3 females, underwent Wada test between January 2009 and December 2012. Six of them had left TLE, and 3 had right TLE. Each patient received 10 mg of PF in the internal carotid artery (ICA). Right hemispheric injection was followed by left hemisphere injection after 30 minutes. During the procedure, EEG monitoring showed changes within 5-18 seconds of injection as hemispheric delta slowing. Neuropsychological tests were carried out for localization of memory and language.

Results:

We were able to lateralize speech dominance in 8 patients and memory dominance in 6 patients. Peri-procedural complications included transient euphoria (n=1), transient spasm of ICA (n=1), eye pain (n=1), facial pain (n=1), and generalized tremulousness (n=2). None of the patients exhibited a symptomatic drop in blood pressure.

Conclusions:

We found that PF is well tolerable for the Wada test, with minimally significant complications, although blood pressure should be closely monitored.Wada test has been the gold standard for lateralization of speech and memory since 1960, when it was first introduced by Juhn Wada.1 The basic concept of the Wada procedure is to inject an anesthetic agent into the brain (through the carotid artery) to sedate one hemisphere transiently in order to localize the dominant hemisphere.1 Patients with temporal lobe epilepsy (TLE) who are candidates for temporal lobe resection are at risk of postsurgical language and/or memory impairment.2 The best agent used for the Wada test is sodium amytal (SA) due to its low toxicity, high efficacy, and adequate duration of action.3 However, SA is facing worldwide shortage, which necessitated the search for other alternatives.4 Propofol (PF) was proposed as a potential alternative.4 The objective of our study was to assess the tolerability of PF in the Wada test in an Arab population with TLE.     

Three-year changes of cortical 18F-FDG in amnestic vs. non-amnestic sporadic early-onset Alzheimer’s disease

European Journal of Nuclear Medicine and Molecular Imaging - To examine and compare longitudinal changes of cortical glucose metabolism in amnestic and non-amnestic sporadic forms of early-onset...     

Sorbitol-modified hyaluronic acid reduces oxidative stress,apoptosis and mediators of inflammation and catabolism in human osteoarthritic chondrocytes

Objective and design

Our study was designed to elucidate the precise molecular mechanisms by which sorbitol-modified hyaluronic acid (HA/sorbitol) exerts beneficial effects in osteoarthritis (OA).

Methods

Human OA chondrocytes were treated with increasing doses of HA/sorbitol ± anti-CD44 antibody or with sorbitol alone and thereafter with or without interleukin-1beta (IL-1β) or hydrogen peroxide (H₂O₂). Signal transduction pathways and parameters related to oxidative stress, apoptosis, inflammation, and catabolism were investigated.

Results

HA/sorbitol prevented IL-1β-induced oxidative stress, as measured by reactive oxygen species, p47-NADPH oxidase phosphorylation, 4-hydroxynonenal (HNE) production and HNE-metabolizing glutathione-S-transferase A4-4 expression. Moreover, HA/sorbitol stifled IL-1β-induced metalloproteinase-13, nitric oxide (NO) and prostaglandin E2 release as well as inducible NO synthase expression. Study of the apoptosis process revealed that this gel significantly attenuated cell death, caspase-3 activation and DNA fragmentation elicited by exposure to a cytotoxic H₂O₂ dose. Examination of signaling pathway components disclosed that HA/sorbitol prevented IL-1β-induced p38 mitogen-activated protein kinase and nuclear factor-kappa B activation, but not that of extracellular signal-regulated kinases 1 and 2. Interestingly, the antioxidant as well as the anti-inflammatory and anti-catabolic effects of HA/sorbitol were attributed to sorbitol and HA, respectively.

Conclusions

Altogether, our findings support a beneficial effect of HA/sorbitol in OA through the restoration of redox status and reduction of apoptosis, inflammation and catabolism involved in cartilage damage.     

Interleukin-28B Polymorphisms and Response of Chronic Hepatitis C Patients from Indonesia to Pegylated Interferon/Ribavirin Treatment

This study demonstrated that Indonesian patients with chronic hepatitis C (mostly ethnic Java people) mostly were infected with hepatitis C virus (HCV) genotype 1; however, they carried mainly the major genotypes of interleukin 28B (IL-28B) single nucleotide polymorphisms (SNPs) (rs12979860 CC, rs11881222 TT, rs8103142 AA, and rs8099917 TT), and they mostly achieved sustained virological responses to pegylated interferon/ribavirin treatment.     

A novel method using confocal laser scanning microscopy for sensitive measurement of P-glycoprotein-mediated transport activity in Caco-2 cells

Objectives The aim of this study was to use time‐lapse confocal laser scanning microscopy to establish a more sensitive and specific method for evaluating P‐glycoprotein activity in Caco‐2 cells. Methods The change in the fluorescence of residual rhodamine 123 at the apical and central regions of Caco‐2 cells was measured in the presence of digoxin or St John's wort by using time‐lapse confocal laser scanning microscopy. The data were compared with measurements made using conventional techniques, a fluorescence microplate reader and a fluorescence microscope. Key findings The percentage decrease of rhodamine 123 caused by 10 µm digoxin or 0.1 µg/ml St John's wort was significantly larger in the apical region of the Caco‐2 cell than in the central region or in the whole cell. The digoxin‐induced inhibition in the apical region as measured by time‐lapse confocal laser scanning microscopy was greater than that measured in the whole cell by a microplate reader or a fluorescence microscope. Conclusions The assay of residual rhodamine 123 in the apical region of Caco‐2 cells by confocal laser scanning microscopy was more sensitive than the conventional methods using a microplate reader or fluorescence microscopy. It will be a valuable screening tool for studying both the inhibition and induction of P‐glycoprotein activity.     

GC/MS determination of guanidinoacetate and creatine in urine: A routine method for creatine deficiency syndrome diagnosis

ObjectivesTo further facilitate the diagnosis of creatine deficiency syndromes (CDS) a modified method was developed for the quantification of urinary creatine and guanidinoacetoacetate using gas chromatography/mass spectrometry (GC/MS) and having the additional advantage of using the same derivatizing agents, column and equipment usually used for the diagnosis of the organic acidurias in the clinical biochemistry laboratories.Material and methodsGuanidinoacetic acid, creatine standard solutions and pooled urines and pathological samples were used to validate a new and simple GC/MS technique modified from reported methods; its accuracy was assessed by comparing with liquid chromatography–electrospray tandem mass spectrometry (HPLC-MS/MS) method.ResultsThe method is precise: intra assay and inter assay variability for low and high concentrations were 3%, 6.4%/1.4%, 6.9% for creatine and 1.4%, 6.4%/0.9%, 6.9% for guanidinoacetoacetate. Agreement with HPLC/MS-MS method is good.ConclusionThe GC/MS modified method is fast, reliable and practical for the diagnosis of CDS using the same means as those for organic acidurias diagnosis.     

Successful pregnancies after transvenous cardiac resynchronization therapy in a woman with congenitally corrected transposition of the great arteries

Congenitally corrected transposition of the great arteries is a rare heart defect that can be associated with systemic ventricular dysfunction and conduction disturbances. The use of cardiac resynchronization therapy in patients with congenital heart disease is not fully established, and achievement of successful pregnancies after implantation of transvenous, biventricular system has never been described, and which resulted in a significant clinical improvement.We describe a 33-year-old female with congenitally corrected transposition of the great arteries, who achieved six pregnancies and successful vaginal deliveries. The two last pregnancies were achieved after cardiac resynchronization therapy for systemic ventricular dysfunction and complete heart block. A congenital cardiac disease has been identified in only one offspring.     

Impact of energy deficit calculated by a predictive method on outcome in medical patients requiring prolonged acute mechanical ventilation

To assess energy balance in very sick medical patients requiring prolonged acute mechanical ventilation and its possible impact on outcome, we conducted an observational study of the first 14 d of intensive care unit (ICU) stay in thirty-eight consecutive adult patients intubated at least 7 d. Exclusive enteral nutrition (EN) was started within 24 h of ICU admission and progressively increased, in absence of gastrointestinal intolerance, to the recommended energy of 125.5 kJ/kg per d. Calculated energy balance was defined as energy delivered - resting energy expenditure estimated by a predictive method based on static and dynamic biometric parameters. Mean energy balance was - 5439 (sem 222) kJ per d. EN was interrupted 23 % of the time and situations limiting feeding administration reached 64 % of survey time. ICU mortality was 72 %. Non-survivors had higher mean energy deficit than ICU survivors (P = 0.004). Multivariate analysis identified mean energy deficit as independently associated with ICU death (P = 0.02). Higher ICU mortality was observed with higher energy deficit (P = 0.003 comparing quartiles). Using receiver operating characteristic curve analysis, the best deficit threshold for predicting ICU mortality was 5021 kJ per d. Kaplan-Meier analysis showed that patients with mean energy deficit > or =5021 kJ per d had a higher ICU mortality rate than patients with lower mean energy deficit after the 14th ICU day (P = 0.01). The study suggests that large negative energy balance seems to be an independent determinant of ICU mortality in a very sick medical population requiring prolonged acute mechanical ventilation, especially when energy deficit exceeds 5021 kJ per d.