The IL23 axis plays a key role in the pathogenesis of IBD

Exciting new results from a genetic study in humans and functional studies in mice have pinpointed interleukin 23 (IL23) and its receptor as a key pathway in the pathogenesis of inflammatory bowel disease (IBD). These findings reveal a hitherto unappreciated role for the IL23 axis in intestinal inflammation and may open new avenues for development of therapeutic strategies in IBD.     

Addition of monofluorophosphate to estrogen therapy in postmenopausal osteoporosis: a randomized controlled trial

INTRODUCTION: Treatment of osteoporosis with high-dose fluoride alone does not reduce fracture risk. We hypothesized that the antifracture efficacy of fluoride could be optimized by its use in low doses combined with an antiresorptive agent. EXPERIMENTAL SUBJECTS: Subjects included 80 women with postmenopausal osteoporosis who had been taking estrogen for at least 1 yr. METHODS: Subjects were randomized to receive monofluorophosphate (MFP) (fluoride content of 20 mg/d) or placebo over 4 yr in a double-blind trial. RESULTS AND DISCUSSION: There were progressive increases in lumbar spine bone density over the duration of the study (MFP, 22%; placebo, 6%; P < 0.0001). In the trabecular bone of L3, these increases were even greater (MFP, 49%; placebo, 2.5%; P < 0.0001). In the proximal femur, there were smaller but significant treatment effects (P = 0.015). Total body scans and their subregions also showed significantly greater increases in the MFP group. Bone formation markers increased significantly in the MFP group at yr 1. Hyperosteoidosis was present in biopsies from five of seven MFP subjects, with osteomalacia in two of seven. The hazards ratio for vertebral fractures was 0.20 (95% confidence interval, 0.05-1.30), and the incidence rate ratio was 0.12 (95% confidence interval, 0.06-0.23; P < 0.01). The hazards ratio for nonvertebral fractures was 3.3 (95% confidence interval, 0.8-12.0). CONCLUSIONS: We conclude that fluoride at 20 mg/d produces substantial increases in bone mineral density but still interferes with bone mineralization. This indicates that most previous studies with this ion have used toxic doses and that much lower doses should be assessed to find a safe dose window for the use of this powerful anabolic agent.     

Correlates of knee pain in younger subjects

The aim of this study was to describe clinical, structural and biochemical factors associated with knee pain in younger subjects. A cross-sectional convenience sample of 371 male and female subjects (mean age, 45 years, range 26–61) was studied. Knee pain was assessed by questionnaire. Chondral defects, cartilage volume, and bone area of the right knee were determined using T1-weighted fat saturation magnetic resonance imaging (MRI). X-ray was performed on the same knee for the assessment of radiographic features of osteoarthritis. The urinary C-terminal cross-linking telopeptide of type II collagen (CTX-II) was measured by enzyme-linked immunosorbent assay (ELISA). Height and weight were measured by standard protocols and body mass index (BMI) was calculated. The prevalence of knee pain was 35% in this sample. Chondral defect scores (particularly femoral and patellar but not tibial) were significantly associated with knee pain in a dose–response fashion (all p<0.01). Cartilage volume and bone area were not associated with knee pain in multivariate analysis in this sample. Urinary CTX-II was higher in subjects with knee pain (p=0.04), but this became nonsignificant after adjustment for BMI and osteophytes (both of which were significant) suggesting potential mechanisms of effect. In conclusion, knee pain is significantly associated with non-full thickness chondral defects (particularly femoral and patellar), osteophytes, CTX-II, and obesity but not other factors. MRI and biochemical measures can add to radiographs in defining unexplained knee pain in younger subjects. Sources of support. National Health and Medical Research Council of Australia, Masonic Centenary Medical Research Foundation.     

Long-term morphological changes in a cryopreserved pulmonary valve homograft

Pulmonary homografts (PHs) are frequently used to replace the native pulmonary valve in the Ross procedure, and in the reconstruction of the right ventricular outflow tract. The case of a 25-year-old man whose PH was replaced 12 years after undergoing the Ross procedure is reported. The clinical cause of the PH failure was stenosis. Morphological studies showed cusp tissue degeneration with tears and calcification, as well as pannus growth on the flow and nonflow surfaces of the cusps and the pulmonary artery graft. The durability of this PH was likely due to a combination of low pressure on the right side of the heart and the patient's age at surgery.     

Traumatic brain injury and prospective memory: influence of task complexity

A quantitative review indicated that prospective memory impairment is a consistent feature of traumatic brain injury (TBI). However, evidence also suggests that manipulations that increase demands on controlled attentional processes moderate the magnitude of observed deficits. A total of 16 TBI participants were compared with 15 matched controls on a task in which the number of prospective target events was manipulated. This manipulation was of interest because two competing models make different predictions as to its effect on controlled attentional processes. In the context of Smith and Bayen's (2004) preparatory attentional processes and memory processes (PAM) model increasing the number of target events should increase requirements for controlled attentional processing. In contrast, McDaniel and Einstein's (2000) multiprocess framework assumes that distinct target events presented in focal awareness of the processing activities required for the ongoing task are likely to depend on automatic processes. This latter model therefore leads to the prediction that increasing the number of target events should not increase demands upon controlled attentional processes. Consistent with McDaniel and Einstein's (2000) multiprocess framework, TBI patients were significantly and comparably impaired on the one- and the four-target-event conditions relative to controls. Further, TBI deficits could not be attributed to increased difficulty with the retrospective component of the prospective memory task. The practical and theoretical implications of these results are discussed.     

An investigation of factors associated with psychiatric hospital admission despite the presence of crisis resolution teams

Background

Evidence suggests that white matter integrity may play an underlying pathophysiological role in schizophrenia. N-acetylaspartate (NAA), as measured by Magnetic Resonance Spectroscopy (MRS), is a neuronal marker and is decreased in white matter lesions and regions of axonal loss. It has also been found to be reduced in the prefrontal and temporal regions in patients with schizophrenia. Diffusion Tensor Imaging (DTI) allows one to measure the orientations of axonal tracts as well as the coherence of axonal bundles. DTI is thus sensitive to demyelination and other structural abnormalities. DTI has also shown abnormalities in these regions.

Methods

MRS and DTI were obtained on 42 healthy subjects and 40 subjects with schizophrenia. The data was analyzed using regions of interests in the Dorso-Lateral Prefrontal white matter, Medial Temporal white matter and Occipital white matter using both imaging modalities.

Results

NAA was significantly reduced in the patient population in the Medial Temporal regions. DTI anisotropy indices were also reduced in the same Medial Temporal regions. NAA and DTI-anisotropy indices were also correlated in the left medial temporal region.

Conclusion

Our results implicate defects in the medial temporal white matter in patients with schizophrenia. Moreover, MRS and DTI are complementary modalities for the study of white matter disruptions in patients with schizophrenia.     

Metabolic adaptations to marathon training and racing

During the past 30 years, considerable progress has been made in our understanding of the cellular and molecular factors regulating fuel metabolism during exercise. In particular, advancements in the fields of exercise biochemistry and cell signalling have helped elucidate the mechanism(s) by which perturbations in energy status are monitored inside contracting muscle cells, and have helped identify target molecules that increase fuel supply to maintain adenosine triphosphate concentration. In this brief commentary, we summarise some of the major cellular and molecular adaptations in human skeletal muscle resulting from the intense endurance training required to run a marathon.     

Inflammatory myofibroblastic tumor of the nasal cavity

Inflammatory myofibroblastic tumor (IMT) is a rare tumor with a variable natural history and biologic behavior, ranging from completely benign to malignant with fatal outcome. We report a case of benign IMT in the left nasal cavity with radiologic features mimicking angiofibroma. We also demonstrate the hypervascular nature of this disease on angiography and the contribution of preoperative embolization in assisting surgical excision and minimizing the potential uncontrolled intraoperative bleeding.     

Respiratory biofeedback during CT-guided procedures

PURPOSE: Respiratory motion can be a complicating factor during image-guided interventions. The ability to reproduce breath-holds may facilitate safer needle-based procedures. The purpose of this study was to evaluate if respiratory biofeedback decreased variability among breath-holds and if the signals from the respiratory bellows belt can be used to measure target motion. MATERIALS AND METHODS: In phase 1 of the study, a respiratory bellows belt was applied to patients before image-guided interventional procedures. Belt stretch from respiratory motion was converted into voltage readings and displayed on a monitor as biofeedback. Patients were asked to perform inspiratory, expiratory, and midcycle breath-holds with and without the biofeedback. The variability in voltage readings between breath-holds with and without biofeedback was compared. In phase 2, the respiratory bellows belt was used during computed tomography (CT)-guided procedures with the patients blinded to the biofeedback. Voltage readings and CT series numbers were recorded as patients were asked to hold their breath during scans. The variability of CT z-axis targets was compared with the variability of voltage readings. RESULTS: A significant decrease in variability was found during expiratory breath-holds (P = .0083) with trends toward significance with midcycle and inspiratory breath-holds. A positive correlation (Kendall tau = 0.5; P = .024) was shown between CT z-axis and belt stretch variability in subjects who received smaller doses of moderate sedation compared with those who received larger doses or general anesthesia. CONCLUSIONS :Biofeedback may help the patient to have a more consistent breath-hold. The belt could decrease the error and unpredictability from craniocaudal motion of targets during image-guided interventions.     

Superparamagnetic iron oxides and low molecular weight gadolinium chelates are synergistic for direct visualization of advanced liver fibrosis

PURPOSE: To compare the contrast-to-noise ratio (CNR) of advanced liver fibrosis on nonenhanced (NE), gadolinium enhanced (Gd), superparamagnetic iron oxides enhanced (SPIO), and combined contrast-enhanced (CCE) spoiled gradient echoes (SGEs). MATERIALS AND METHODS: This retrospective study assessed 83 consecutive patients with cirrhosis and 10 consecutive patients without fibrosis. All patients had NE, Gd, SPIO, and CCE images at 1.5 T. A total of six breathhold SGE sequences with varying imaging parameters were assessed. MR images were evaluated qualitatively and, in 15 cirrhotics who underwent liver transplantation, compared to gross pathology. CNR of fibrosis to background liver was compared across sequences and contrast enhancement types. RESULTS: In cirrhotic patients, CCE images on all sequences showed fibrosis as a meshwork of high-signal 1-mm to 3-mm thick reticulations surrounding 2-mm to 5-mm low-signal regenerative nodules. Fibrosis was less visible on Gd and SPIO images and was barely visible on NE images. CNR was significantly higher for CCE than for NE, Gd, or SPIO images in eight of nine comparisons (P < 0.0001-0.05). The liver had a homogeneous appearance in subjects without fibrosis. CONCLUSION: CCE imaging depicts advanced liver fibrosis with higher CNR than NE, Gd, or SPIO SGEs.