In vivo detection of the lumbar intraforaminal ligaments by MRI

Purpose

Intraforaminal ligaments (IFL) are of great interest to anatomists and clinicians to fully understand the detailed anatomy of the neuroforamina and to diagnose unclear radicular symptoms. Studies published until now have described radiological imaging of the IFLs using magnetic resonance imaging (MRI) on donor bodies. In the present study, we investigated the detectability of lumbar IFLs in vivo in adults using the high spatial resolution of the constructive interference in steady state (CISS) sequence.

Methods

A total of 14 patients were studied using a 1.5 T MRI scanner. The lumbar spine was imaged using the parasagittal CISS sequence, and the detectability of the IFLs was assessed for each lumbar level. All image datasets were analyzed by a radiologist, an orthopedic surgeon, and an anatomist. Interrater reliability was expressed as Fleiss’ Kappa. Using a single data set, a three-dimensional (3D) model was created to map the location of the IFLs within the intervertebral foramen (IF) and the immediate surrounding vessels.

Results

Overall, the radiologist was able to detect IFLs in 60% of all imaged IFs, the orthopedic surgeon in 62%, and the anatomist in 66%. Fleiss’ Kappa for the various segments varies from 0.71 for L4/5 up to 0.90 for L3/4.

Conclusion

Lumbar IFLs were successfully detected in vivo in every patient. The detection frequency varied from 42–86% per IF. We demonstrated reproducible imaging of the IFLs on MRI, with good interrater reliability. The present study was a launching point for further clinical studies investigating the potential impact of altered IFLs on radicular pain.

     

Cell surface engineering using glycosylphosphatidylinositol anchored tissue inhibitor of matrix metalloproteinase‐1 stimulates cutaneous wound healing

The balance between matrix metalloproteinases and their endogenous tissue inhibitors (TIMPs) is an important component in effective wound healing. The biologic action of these proteins is linked in part to the stoichiometry of TIMP/matrix metalloproteinases/surface protein interactions. We recently described the effect of a glycosylphosphatidylinositol (GPI) anchored version of TIMP‐1 on dermal fibroblast biology. Here, cell proliferation assays, in vitro wound healing, electrical wound, and impedance measurements were used to characterize effects of TIMP‐1‐GPI treatment on primary human epidermal keratinocytes. TIMP‐1‐GPI stimulated keratinocyte proliferation, as well as mobilization and migration. In parallel, it suppressed the migration and matrix secretion of dermal myofibroblasts, and reduced their secretion of active TGF‐β1. Topical application of TIMP‐1‐GPI in an in vivo excisional wound model increased the rate of wound healing. The agent positively influenced different aspects of wound healing depending on the cell type studied. TIMP‐1‐GPI counters potential negative effects of overactive myofibroblasts and enhances the mobilization and proliferation of keratinocytes essential for effective wound healing. The application of TIMP‐1‐GPI represents a novel and practical clinical solution for facilitating healing of difficult wounds.     

Catheter ablation of common-type atrial flutter guided by three-dimensional right atrial geometry reconstruction and catheter tracking using cutaneous patches: a randomized prospective study

INTRODUCTION: EnSite NavX (NavX) is a novel mapping and navigation system that allows visualization of conventional catheters for diagnostic and ablative purposes and uses them to create a three-dimensional (3D) geometry of the heart. NavX is particularly suitable for ablation procedures utilizing an anatomic approach, as in the setting of common-type atrial flutter (AFL). The aim of this study was to compare NavX-guided and conventional ablation procedures for AFL. METHODS AND RESULTS: Forty consecutive patients (32 male, 59 +/- 12 years) with documented AFL were randomized to undergo fluoroscopy-guided (group I, 20 patients) or NavX-guided (group II, 20 patients) ablation, including 3D isthmus reconstruction. The same catheter setup was used in both groups. The endpoint of bidirectional isthmus block was obtained in all patients. Compared to conventional approaches, NavX-guided procedures significantly reduced fluoroscopy time (5.1 +/- 1.4 min vs 20 +/- 11 min, P < 0.01) and total x-ray exposure (5.1 +/- 3.1 Gycm2 vs 24.9 +/- 1.6 Gycm2, P < 0.01). Isthmus geometry reconstruction could be performed in all patients of group II. In 4 patients (20%) of group II, anatomic isthmus variations were detected by NavX. No significant differences in radiofrequency current applications and procedural times were found between the two groups. CONCLUSION: NavX technology allows geometry reconstruction of the cavotricuspid isthmus. NavX-guided ablation of AFL reduces total x-ray exposure compared to the fluoroscopy-guided approach but does not prolong procedure time.     

Role of sphingosine-1-phosphate phosphohydrolase 1 in the regulation of resistance artery tone

Sphingosine-1-phosphate (S1P), which mediates pleiotropic actions within the vascular system, is a prominent regulator of microvascular tone. By virtue of its S1P-degrading function, we hypothesized that S1P-phosphohydrolase 1 (SPP1) is an important regulator of tone in resistance arteries. Hamster gracilis muscle resistance arteries express mRNA encoding SPP1. Overexpression of SPP1 (via transfection of a SPP1(wt)) reduced resting tone, Ca2+ sensitivity, and myogenic vasoconstriction, whereas reduced SPP1 expression (antisense oligonucleotides) yielded the opposite effects. Expression of a phosphatase-dead mutant of SPP1 (SPP1(H208A)) had no effect on any parameter tested, suggesting that catalytic activity of SPP1 is critical. The enhanced myogenic tone that follows overexpression of S1P-generating enzyme sphingosine kinase 1 (Sk1(wt)) was functionally antagonized by coexpression with SPP1(wt) but not SPP1(H208A). SPP1 modulated vasoconstriction in response to 1 to 100 nmol/L exogenous S1P, a concentration range that was characterized as S1P2-dependent, based on the effect of S1P(2) inhibition by antisense oligonucleotides and 1 mumol/L JTE013. Inhibition of the cystic fibrosis transmembrane regulator (CFTR) (1) restored S1P responses that were attenuated by SPP1(wt) overexpression; (2) enhanced myogenic vasoconstriction; but (3) had no effect on noradrenaline responses. We conclude that SPP1 is an endogenous regulator of resistance artery tone that functionally antagonizes the vascular effects of both Sk1(wt) and S1P2 receptor activation. SPP1 accesses extracellular S1P pools in a manner dependent on a functional CFTR transport protein. Our study assigns important roles to both SPP1 and CFTR in the physiological regulation of vascular tone, which influences both tissue perfusion and systemic blood pressure.     

Squamous cutaneous epithelial cell carcinoma in two CML patients with progressive disease under imatinib treatment

Imatinib (glivec), formerly known as STI571) effectively blocks the ATP-binding site of the bcr/abl fusion protein thereby inactivating selectively the tyrosine kinase activity of bcr/abl. Therefore, it is a promising drug in Philadelphia chromosome positive chronic myeloid leukemia showing high hematologic and cytogenetic response rates combined with a mild toxicity profile. Here we report two cases of squamous cell carcinoma of the skin, which appeared in the photo-exposed areas in two elderly patients treated for advanced chronic myeloid leukemia with imatinib. The role of chemotherapy, chronic sun exposure and of possible additional risk factors such as human papillomavirus infection is discussed.     

Some inconvenient truths about biosignatures involving two chemical species on Earth-like exoplanets

The detection of strong thermochemical disequilibrium in the atmosphere of an extrasolar planet is thought to be a potential biosignature. In this article we present a previously unidentified kind of false positive that can mimic a disequilibrium or any other biosignature that involves two chemical species. We consider a scenario where the exoplanet hosts a moon that has its own atmosphere and neither of the atmospheres is in chemical disequilibrium. Our results show that the integrated spectrum of the planet and the moon closely resembles that of a single object in strong chemical disequilibrium. We derive a firm limit on the maximum spectral resolution that can be obtained for both directly imaged and transiting planets. The spectral resolution of even idealized space-based spectrographs that might be achievable in the next several decades is in general insufficient to break the degeneracy. Both chemical species can only be definitively confirmed in the same object if absorption features of both chemicals can be unambiguously identified and their combined depth exceeds 100%.With almost a thousand confirmed exoplanets [Open Exoplanet Catalogue (1)], the prospects of detecting signs of a biosphere on a body outside our own solar system are more promising than ever before. However, there are still huge technological and theoretical challenges to overcome before one can hope to make a clear detection of life on an exoplanet. In this article, we discuss one of these complications, the possibility of false positives due to the presence of an exomoon orbiting the exoplanet.There are many ways that life on an exoplanet might affect the planet’s appearance, ranging from deliberate signals from intelligent civilizations (2) to subtler signs of simple life. To characterize an extrasolar world as fully as possible, we ideally would measure its spectrum as a function of time in both the optical and the infrared parts of the spectrum (e.g., refs. 3–6). For example, spectral evidence of water could suggest that a planet might be habitable. It has also been suggested that an intriguing indication of life might be an increase in the planet’s albedo toward the infrared part of the spectrum, which on Earth can be associated with vegetation (7). However, these features alone would not be smoking-gun proof of the presence of life. The terms “biomarker” and “biosignature” generally refer to chemicals or combinations of chemicals that could be produced by life and that could not be (or are unlikely to be) produced abiotically; hereafter, we use these terms interchangeably. If biosignature gases are detected in the spectrum of an exoplanet, the probability that they actually indicate life depends both on the prior probability of life (8) and on the probability that the observed spectroscopic feature could be produced abiotically. The latter possibility is the subject of this paper.Byproducts of metabolism are often thought of as the most promising biomarker (9–15). More specifically, an extreme thermodynamic disequilibrium of two molecules in the atmosphere is considered a biosignature (16–18). An example of two such species is the simultaneous presence of O₂ and a reduced gas such as CH₄. It is important to point out that a disequilibrium in a planet’s atmosphere should not be considered as clear evidence for life. [Also note that the Earth might have never had a phase of strong, observable O₂/CH₄ disequilibrium (19).] There is a long list of abiotic sources that could also create a disequilibrium such as impacts (20), photochemistry (21), and geochemistry (14).In this article, we describe a previously unidentified scenario for a possible false positive biosignature. If the exoplanet hosts a moon that has an atmosphere itself, the simultaneous observation of the planet and moon modifies the observed spectrum (see also refs. 22 and 23) and can produce a signal that looks like a disequilibrium in one atmosphere but is in fact created by two atmospheres blended together. It might be extremely difficult to discern that an exoplanet even has a moon, let alone that one component of a two-chemical biosignature comes from the moon instead of the planet.The outline of this article is as follows. We first describe our model atmospheres and present simulated spectra. Using those synthetic spectra, we show that the combined spectrum from an oxygen-rich atmosphere such as that of the Earth and a methane-rich atmosphere such as that of Titan indeed looks like it could have come from a single atmosphere with a strong disequilibrium. We then calculate a strong upper limit on the spectral resolution of such a system as observed from Earth under ideal conditions with a plausibly sized space telescope. Our estimate shows that the spectral resolution for such a system is unlikely to exceed ∼1,600 with foreseeable technology. Given this maximum possible resolution, discriminating between a single planet and a planet–moon system is in general unlikely to be possible.^† Nevertheless, we conclude with a summary and a positive outlook with two possibilities that can provide genuine biosignatures. The first possibility is to find a single chemical species that is sufficient to indicate life. The second one requires the unambiguous identification of both species’ absorption features and the combined depth of the features needs to exceed 100%.