Low-coherence enhanced backscattering: review of principles and applications for colon cancer screening

The phenomenon of enhanced backscattering (EBS) of light, also known as coherent backscattering (CBS) of light, has been the object of intensive investigation in nonbiological media over the last two decades. However, there have been only a few attempts to explore EBS for tissue characterization and diagnosis. We have recently made progress in the EBS measurements in tissue by taking advantage of low spatial coherence illumination, which has led us to the development of low-coherence enhanced backscattering (LEBS) spectroscopy. In this work, we review the current state of research on LEBS. After a brief discussion of the basic principle of EBS and LEBS, we present an overview of the unique features of LEBS for tissue characterization, and show that LEBS enables depth-selective spectroscopic assessment of mucosal tissue. Then, we demonstrate the potential of LEBS spectroscopy for predicting the risk of colon carcinogenesis and colonoscopy-free screening for colorectal cancer (CRC).     

Focal myelomalacia and syrinx formation after accidental intramedullary lidocaine injection during lumbar anesthesia: a report of 3 cases

Three cases of focal myelomalacia and syrinx formation occurring as complications of lumbar spinal anesthesia are reported. In all three instances complication occurred due to accidental injection of lidocaine into the substance of the spinal cord. The primary complaint in all the three cases was severe sharp and shooting pain in both lower limbs, being more severe in certain dermatomes. Neurological deficits were noticed after the effect of the anesthetic agent had worn off. Sensory and motor deficits were asymmetrical and focal; these improved in 6-12 months time. Pain persisted for 1-3 years and then subsided gradually. Carbamazepine and gabapentin were effective in symptomatic relief of this pain. MRI of the dorsolumbar spine done 4-6 months after the spinal anesthetic procedure showed myelomalacic changes with focal syrinx formation in the conus and epiconus region of the spinal cord. The syrinx extended 1-2 vertebral segments in the vertical plane but was confined to a small area in the axial plane. Attempting to use higher lumbar intervertebral spaces for access to the subarachnoid space or epidural space may lead to inadvertent puncture of the lower dorsal spaces; this makes the procedure of spinal anesthesia at this level prone for spinal cord injury, with subsequent risk of development of myelomalacic syrinx in the conus and epiconus region of the spinal cord.     

Viral oncoproteins target the DNA methyltransferases

Small DNA tumour viruses have evolved a number of mechanisms to drive nondividing cells into S phase. Virally encoded oncoproteins such as adenovirus E1A and human papillomavirus (HPV) E7 can bind an array of cellular proteins to override proliferation arrest. The DNA methyltransferase Dnmt1 is the major mammalian enzyme responsible for maintaining CpG methylation patterns in the cell following replication. One of the hallmarks of tumour cells is disrupted DNA methylation patterns, highlighting the importance of the proper regulation of DNA methyltransferases in normal cell proliferation. Here, we show that adenovirus 5 E1A and HPV-16 E7 associate in vitro and in vivo with the DNA methyltransferase Dnmt1. Consistent with this interaction, we find that E1A and E7 can purify DNA methyltransferase activity from nuclear extracts. These associations are direct and mediated by the extreme N-terminus of E1A and the CR3 zinc-finger domain of E7. Furthermore, we find that a point mutant at leucine 20 of E1A, a residue known to be critical for its transformation functions, is unable to bind Dnmt1 and DNA methyltransferase activity. Finally, both E1A and E7 can stimulate the methyltransferase activity of Dnmt1 in vitro. Our results provide the first indication that viral oncoproteins bind and regulate Dnmt1 enzymatic activity. These observations open up the possibility that this association may be used to control cellular proliferation pathways and suggest a new mechanism by which small DNA tumour viruses can steer cells through the cell cycle.     

Blood and urine metal ion levels in young and active patients after Birmingham hip resurfacing arthroplasty: four-year results of a prospective longitudinal study

This is a longitudinal study of the daily urinary output and the concentrations in whole blood of cobalt and chromium in patients with metal-on-metal resurfacings over a period of four years. Twelve-hour urine collections and whole blood specimens were collected before and periodically after a Birmingham hip resurfacing in 26 patients. All ion analyses were carried out using a high-resolution inductively-coupled plasma mass spectrometer. Clinical and radiological assessment, hip function scoring and activity level assessment revealed excellent hip function. There was a significant early increase in urinary metal output, reaching a peak at six months for cobalt and one year for chromium post-operatively. There was thereafter a steady decrease in the median urinary output of cobalt over the following three years, although the differences are not statistically significant. The mean whole blood levels of cobalt and chromium also showed a significant increase between the pre-operative and one-year post-operative periods. The blood levels then decreased to a lower level at four years, compared with the one-year levels. This late reduction was statistically significant for chromium but not for cobalt. The effects of systemic metal ion exposure in patients with metal-on-metal resurfacing arthroplasties continue to be a matter of concern. The levels in this study provide a baseline against which the in vivo wear performance of newer bearings can be compared.     

Interrelationships between inflammation, C-reactive protein, and insulin resistance

The recognition that inflammation plays a fundamental role in atherothrombosis has led to the measurement of circulating inflammatory biomarkers such as high-sensitivity C-reactive protein (hs-CRP) as a means of improving cardiovascular disease detection and prevention. Clinically, levels of hs-CRP >3 mg/L indicate elevated risk for myocardial infarction and stroke, even among apparently healthy individuals with low-to-normal lipid levels. Emerging laboratory and epidemiologic data now link inflammation and hs-CRP to insulin resistance in that hs-CRP levels have been associated with impaired insulin sensitivity and the development of dysglycemic conditions, including the cardiometabolic syndrome and incident type 2 diabetes. hs-CRP has also been associated with each of the individual components of the cardiometabolic syndrome. Furthermore, in large prospective studies, hs-CRP adds prognostic information about cardiovascular risk beyond that provided by the cardiometabolic syndrome. These findings have led to discussion about the addition of hs-CRP measurement to the current definition of the cardiometabolic syndrome to improve detection of risk for both diabetes and cardiovascular events in patients. Multiple clinical studies are now underway that are evaluating whether agents traditionally used to improve glycemic control may also significantly reduce hs-CRP.