Pilot study of propranolol premedication to reduce FDG uptake in brown adipose tissue on PET scans of adolescent and young adult oncology patients.

OBJECTIVE: Physiologic uptake of 18F-fluorodeoxyglucose (FDG) in brown adipose tissue (adipose tissue) of cancer patients may confound interpretation of positron emission tomography (PET) scans. Uptake in adipose tissue occurs in up to half of pediatric oncology patients undergoing PET scans, and is especially common in adolescents. adipose tissue is innervated by the sympathetic nervous system, and beta blockers such as propranolol have shown efficacy in reducing adipose tissue uptake on PET scans done in older adult oncology patients. PARTICIPANTS: Because propranolol may cause hypoglycemia or other side effects in fasting patients, we prospectively assessed the safety of a single dose of 20 mg propranolol in adolescent and young adult oncology patients undergoing FDG-PET imaging. METHODS: Ten patients (median age 18 years, range 14-24) received propranolol premedication prior to FDG-PET. RESULTS: No adverse effects or clinically significant changes in serum glucose, heart rate, or blood pressure were observed. Five of the 10 patients had adipose tissue identified on previous PET scans. However, following propranolol administration only, one patient had persistent uptake in adipose tissue. CONCLUSIONS: Propranolol was convenient and safe in fasting adolescent and young adult oncology patients undergoing PET scans. Larger studies are warranted to better define the effectiveness of this approach.

A simple method for determining split renal function from dynamic (99m)Tc-MAG3 scintigraphic data.

PURPOSE: Commonly used methods for determining split renal function (SRF) from dynamic scintigraphic data require extrarenal background subtraction and additional correction for intrarenal vascular activity. The use of these additional regions of interest (ROIs) can produce inaccurate results and be challenging, e.g. if the heart is out of the camera field of view. The purpose of this study was to evaluate a new method for determining SRF called the blood pool compensation (BPC) technique, which is simple to implement, does not require extrarenal background correction and intrinsically corrects for intrarenal vascular activity. METHODS: In the BPC method SRF is derived from a parametric plot of the curves generated by one blood-pool and two renal ROIs. Data from 107 patients who underwent (99m)Tc-MAG3 scintigraphy were used to determine SRF values. Values calculated using the BPC method were compared to those obtained with the integral (IN) and Patlak-Rutland (PR) techniques using Bland-Altman plotting and Passing-Bablok regression. The interobserver variability of the BPC technique was also assessed for two observers. RESULTS: The SRF values obtained with the BPC method did not differ significantly from those obtained with the PR method and showed no consistent bias, while SRF values obtained with the IN method showed significant differences with some bias in comparison to those obtained with either the PR or BPC method. No significant interobserver variability was found between two observers calculating SRF using the BPC method. CONCLUSION: The BPC method requires only three ROIs to produce reliable estimates of SRF, was simple to implement, and in this study yielded statistically equivalent results to the PR method with appreciable interobserver agreement. As such, it adds a new reliable method for quality control of monitoring relative kidney function.

Effects of polysialic acid on sensory innervation of the cornea.

Sensory trigeminal growth cones innervate the cornea in a coordinated fashion during embryonic development. Polysialic acid (polySia) is known for its important roles during nerve development and regeneration. The purpose of this work is to determine whether polySia, present in developing eyefronts and on the surface of sensory nerves, may provide guidance cues to nerves during corneal innervation. Expression and localization of polySia in embryonic day (E)5-14 chick eyefronts and E9 trigeminal ganglia were identified using Western blotting and immunostaining. Effects of polySia removal on trigeminal nerve growth behavior were determined in vivo, using exogenous endoneuraminidase (endoN) treatments to remove polySia substrates during chick cornea development, and in vitro, using neuronal explant cultures. PolySia substrates, made by the physical adsorption of colominic acid to a surface coated with poly-d-lysine (PDL), were used as a model to investigate functions of the polySia expressed in axonal environments. PolySia was localized within developing eyefronts and on trigeminal sensory nerves. Distributions of PolySia in corneas and pericorneal regions are developmentally regulated. PolySia removal caused defasciculation of the limbal nerve trunk in vivo from E7 to E10. Removal of polySia on trigeminal neurites inhibited neurite outgrowth and caused axon defasciculation, but did not affect Neural Cell Adhesion Molecule (NCAM) expression or Schwann cell migration in vitro. PolySia substrates in vitro inhibited outgrowth of trigeminal neurites and promoted their fasciculation. In conclusion, polySia is localized on corneal nerves and in their targeting environment during early developing stages of chick embryos. PolySias promote fasciculation of trigeminal axons in vivo and in vitro, whereas, in contrast, their removal promotes defasciculation.

Is Ginkgo biloba and/or a Multivitamin-multimineral Supplement a Therapeutic Option for Parkinson's Disease? A Case Report.

For a number of years, there has been speculation about the potential benefit of Parkinson's disease by treatment with Ginkgo biloba. In this case report, my grandfather, who had a known history of Parkinson's, had dramatic improvement after supplementation with ginkgo and a multivitamin-multimineral supplement. Human studies are needed for confirmation.

Resistance of corneal RFUVA­cross-linked collagens and small leucine-rich proteoglycans to degradation by matrix metalloproteinases.

PURPOSE: Extracellular matrix metalloproteinases (MMPs) are thought to play a crucial role in corneal degradation associated with the pathological progression of keratoconus. Currently, corneal cross-linking by riboflavin and ultraviolet A (RFUVA) has received significant attention for treatment of keratoconus. However, the extent to which MMPs digest cross-linked collagen and small leucine-rich proteoglycans (SLRPs) remains unknown. In this study, the resistance of RFUVA-cross-linked collagens and SLRPs to MMPs has been investigated. METHODS: To investigate the ability of MMPs to digest cross-linked collagen and SLRPs, a model reaction system using purified collagen type I, type IV, and nonglycosylated, commercially available recombinant SLRPs, keratocan, lumican, mimecan, decorin, and biglycan in solution in vitro has been compared using reactions inside an intact bovine cornea, ex vivo. RESULTS: Our data demonstrate that corneal cross-linked collagen type I and type IV are resistant to cleavage by MMP-1, MMP-2, MMP-9, and MMP-13, whereas non-cross-linked collagen I, IV, and natively glycosylated SLRPs are susceptible to degradation by MMPs. In addition, both cross-linked SLRPs themselves and cross-linked polymers of SLRPs and collagen appear able to resist degradation. These results suggest that the interactions between SLRPs and collagen caused by RFUVA protect both SLRPs and collagen fibrils from cleavage by MMPs. CONCLUSIONS: A novel approach for understanding the biochemical mechanism whereby RFUVA cross-linking stops keratoconus progression has been achieved.

Risk for fatal pulmonary hemorrhage does not appear to be increased following dose escalation using stereotactic body radiotherapy (SBRT) in locally advanced non-small cell lung cancer (NSCLC).

PURPOSE: A prospective single institution study evaluating the feasibility of conventional chemoradiation (CRT) followed by SBRT as a means of dose escalation for patients with stage II-III NSCLC with residual disease recently completed accrual. Two patients enrolled developed unexpected fatal pulmonary hemorrhages. A post-hoc analysis was performed to evaluate for an association between protocol therapy and this grade 5 toxicity. METHODS AND MATERIALS: 17 patients enrolled on the protocol with medial tumors according to the RTOG 0813 definitions, were selected for analysis. Protocol therapy consisted of SBRT boost consisting of 10Gy times two or 6.5Gy times three fractions, after completing initial CRT. Chi-square and ANOVA associations were performed using patient-specific and dosimetric characteristics, particularly volume and point doses to mediastinal structures. RESULTS: After a median follow-up of 13 months, 2 patients developed a grade V pulmonary hemorrhage, in the setting of recurrent disease. Cumulative biological effective doses (BED3) were calculated using an α/ß 3.0 for the pulmonary vasculature and bronchial wall. No volumetric or point doses administered seemed to correlate with the risk for pulmonary hemorrhage, despite an average maximum pulmonary artery dose of 175 Gy BED3. The only significant association with fatal hemorrhage was local recurrence (p = 0.0441). CONCLUSION: SBRT boost does not appear to increase the risk for fatal pulmonary hemorrhage. A cumulative maximum BED3 to the pulmonary artery less than 175 Gy appears to be safe.

Early PET/CT scans for assessing treatment responses of non-small cell lung cancer for SBRT boost: what to do with scans from multiple scanners.

Chemoradiation remains the standard of care for the nonsurgical treatment of advanced non-small cell lung cancer (NSCLC) but local recurrence rates of 30-40% are documented. We examined the early PET/CT responses of NSCLC treated with standard chemoradiation in a prospective single institutional trial of early 18F-2-deoxy-D-glucose-PET/CT scans to help define patients appropriate for dose escalation with SBRT. 48 patients with stage IIA, IIB or IIIA-B NSCLC with no or non-bulky (

Stereotactic body radiation therapy can be used safely to boost residual disease in locally advanced non-small cell lung cancer: a prospective study.

PURPOSE: To report the results of a prospective, single-institution study evaluating the feasibility of conventional chemoradiation (CRT) followed by stereotactic body radiation therapy (SBRT) as a means of dose escalation for patients with stage II-III non-small cell lung cancer (NSCLC) with residual disease. METHODS AND MATERIALS: Patients without metastatic disease and with radiologic evidence of limited residual disease (≤5 cm) within the site of the primary tumor and good or complete nodal responses after standard CRT to a target dose of 60 Gy were considered eligible. The SBRT boost was done to achieve a total combined dose biological equivalent dose >100 Gy to the residual primary tumor, consisting of 10 Gy × 2 fractions (20 Gy total) for peripheral tumors, and 6.5 Gy × 3 fractions (19.5 Gy total) for medial tumors using the Radiation Therapy Oncology Group protocol 0813 definitions. The primary endpoint was the development of grade ≥3 radiation pneumonitis (RP). RESULTS: After a median follow-up of 13 months, 4 patients developed acute grade 3 RP, and 1 (2.9%) developed late and persistent grade 3 RP. No patients developed grade 4 or 5 RP. Mean lung dose, V2.5, V5, V10, and V20 values were calculated for the SBRT boost, and none were found to significantly predict for RP. Only advancing age (P=.0147), previous smoking status (P=.0505), and high CRT mean lung dose (P=.0295) were significantly associated with RP development. At the time of analysis, the actuarial local control rate at the primary tumor site was 82.9%, with only 6 patients demonstrating recurrence. CONCLUSIONS: Linear accelerator-based SBRT for dose escalation of limited residual NSCLC after definitive CRT was feasible and did not increase the risk for toxicity above that for standard radiation therapy.

Corneal sulfated glycosaminoglycans and their effects on trigeminal nerve growth cone behavior in vitro: roles for ECM in cornea innervation.

PURPOSE: Sensory trigeminal nerve growth cones innervate the cornea in a highly coordinated fashion. The purpose of this study was to determine if extracellular matrix glycosaminoglycans (ECM-GAGs), including keratan sulfate (KS), dermatan sulfate (DS), and chondroitin sulfate A (CSA) and C (CSC), polymerized in developing eyefronts, may provide guidance cues to nerves during cornea innervation. METHODS: Immunostaining using antineuron-specific-ß-tubulin and monoclonal antibodies for KS, DS, and CSA/C was performed on eyefronts from embryonic day (E) 9 to E14 and staining visualized by confocal microscopy. Effects of purified GAGs on trigeminal nerve growth cone behavior were tested using in vitro neuronal explant cultures. RESULTS: At E9 to E10, nerves exiting the pericorneal nerve ring grew as tight fascicles, advancing straight toward the corneal stroma. In contrast, upon entering the stroma, nerves bifurcated repeatedly as they extended anteriorly toward the epithelium. KS was localized in the path of trigeminal nerves, whereas DS and CSA/C-rich areas were avoided by growth cones. When E10 trigeminal neurons were cultured on different substrates comprised of purified GAG molecules, their neurite growth cone behavior varied depending on GAG type, concentration, and mode of presentation (immobilized versus soluble). High concentrations of immobilized KS, DS, and CSA/C inhibited neurite growth to varying degrees. Neurites traversing lower, permissive concentrations of immobilized DS and CSA/C displayed increased fasciculation and decreased branching, whereas KS caused decreased fasciculation and increased branching. Enzymatic digestion of sulfated GAGs canceled their effects on trigeminal neurons. CONCLUSIONS: Data herein suggest that GAGs may direct the movement of trigeminal nerve growth cones innervating the cornea.

Fibrinogen, riboflavin, and UVA to immobilize a corneal flap--molecular mechanisms.

PURPOSE: Tissue glue containing fibrinogen (FIB) and riboflavin (RF), upon exposure to long wavelength ultraviolet light (UVA, 365 nM) has been proposed potentially to solve long-standing problems presented by corneal wound and epithelial ingrowth side-effects from laser-assisted in situ keratomileuis (LASIK). Data presented in a previous study demonstrated an ability of FIB + RF + UVA to adhere two stromal surfaces; however, to our knowledge no molecular mechanisms have been proposed to account for interactions occurring between corneal extracellular matrix (ECM) and tissue glue molecules. Here, we document several covalent and noncovalent interactions between these classes of macromolecules. METHODS: SDS-PAGE and Western blot techniques were used to identify covalent interactions between tissue glue molecules and corneal ECM molecules in either the presence or absence of RF and UVA, in vitro and ex vivo. Surface plasmon resonance (SPR) was used to characterize noncovalent interactions, and obtain k(a), k(d), and K(D) binding affinity values. RESULTS: SDS-PAGE and Western blot analyses indicated that covalent interactions occurred between neighboring FIB molecules, as well as between FIB and collagen type I (Coll-I) proteins (in vitro and ex vivo). These interactions occurred only in the presence of RF and UVA. SPR data demonstrated the ability of FIB to bind noncovalently to corneal stroma molecules, Coll-I, decorin, dermatan sulfate, and corneal basement membrane molecules, laminin and heparan sulfate--only in the presence of Zn(2+). CONCLUSIONS: Covalent and (zinc-mediated) noncovalent mechanisms involving FIB and stromal ECM molecules contribute to the adhesion created by FIB + RF + UVA.

Fibrinogen, riboflavin, and UVA to immobilize a corneal flap--conditions for tissue adhesion.

PURPOSE: Laser-assisted in situ keratomileus (LASIK) creates a permanent flap that remains non-attached to the underlying laser-modified stroma. This lack of permanent adhesion is a liability. To immobilize a corneal flap, a protocol using fibrinogen (FIB), riboflavin (RF), and ultraviolet (UVA) light (FIB+RF+UVA) was devised to re-adhere the flap to the stroma. METHODS: A model flap was created using rabbit (Oryctolagus cuniculus) and shark (Squalus acanthias) corneas. Solutions containing FIB and RF were applied between corneal strips as glue. Experimental corneas were irradiated with long wavelength (365 nm) UVA. To quantify adhesive strength between corneal strips, the glue-tissue interface was subjected to a constant force while a digital force gauge recorded peak tension. RESULTS: In the presence of FIB, substantive non-covalent interactions occurred between rabbit corneal strips. Adhesiveness was augmented if RF and UVA also were applied, suggesting formation of covalent bonds. Additionally, exposing both sides of rabbit corneas to UVA generated more adhesion than exposure from one side, suggesting that RF in the FIB solution catalyzes formation of covalent bonds at only the interface between stromal molecules and FIB closest to the UVA. In contrast, in the presence of FIB, shark corneal strips interacted non-covalently more substantively than those of rabbits, and adhesion was not augmented by applying RF+UVA, from either or both sides. Residual RF could be rinsed away within 1 hour. CONCLUSIONS: Glue solution containing FIB and RF, together with UVA treatment, may aid immobilization of a corneal flap, potentially reducing risk of flap dislodgement.

Effect of the synthetic NC-1059 peptide on diffusion of riboflavin across an intact corneal epithelium.

PURPOSE: To investigate the effect of the peptide NC-1059 on riboflavin (RF) diffusion across an intact corneal epithelium into the stroma. METHODS: NC-1059 peptide was synthesized by solid-phase synthesis with 9-fluorenylmethoxycarbonyl chemistry, characterized by reversed-phase HPLC, and matrix-assisted laser desorption ionization time-of-flight mass spectroscopy. The diffusion of RF across embryonic day 18 chick corneal epithelium ex vivo was monitored using confocal microscopy. The depth distributions of RF in the corneal stroma were calculated using a group of linear equations based on the relationship between RF fluorescence intensity and concentration. RESULTS: Data presented in this study demonstrate that the NC-1059 peptide can transiently open the intact epithelial barrier to allow the permeation of RF into the stroma. The effect of NC-1059 peptide on RF diffusion across the corneal epithelium was concentration and time dependent. The amount of RF reaching a 50-µm depth of chick corneal stoma increased dramatically after exposure to NC-1059 for 10 minutes, reaching a plateau by 30 minutes. The concentrations of RF in the presence of NC-1059 at corneal stromal depths of 50, 100, and 150 µm were significantly higher than in the absence of the peptide, and almost as high as in corneas in which the epithelium first had been physically removed. In addition, a cell viability assay indicated that the NC-1059 peptide did not kill corneal epithelial cells. CONCLUSIONS: NC-1059 peptide significantly enhances the diffusion of RF across intact corneal epithelium into the stroma.

Development and mineralization of embryonic avian scleral ossicles.

PURPOSE: To investigate the development and mineralization of avian scleral ossicles using fluorescence microscopy in combination with field emission scanning electron microscopy (FESEM) and energy dispersive spectroscopy (EDS). METHODS: The anterior halves of whole eyeballs from chickens on embryonic (E) days E10 to E21 and Japanese quail on embryonic days E8 to E17 were fixed in 100% methanol for 1 min, stained with Giemsa solution for 5 min, destained with distilled water for 30 min, and then viewed by epifluorescence. Propidium iodide (PI) was used to detect the nuclei of osteocytes in scleral ossicles. FESEM and EDS were then used to show areas of mineralization and to identify differences in the elemental composition of different regions of the ossicles. RESULTS: Using Giemsa as a fluorescence stain, it was possible to observe the detailed morphology and development of both chicken and quail scleral ossicles. In chickens, bone microporosities first became visible at E15. Each microporosity contained a single nucleus, likely that of an osteocyte. The amount of carbon in ossicles steadily decreased during embryogenesis and post-hatching, while the concentration of oxygen showed a distinct increase over this time period. Calcium and phosphate levels in the ossicles increased gradually during embryonic and post-hatching stages. CONCLUSIONS: A novel approach to study the development and mineralization of avian scleral ossicles during embryogenesis is presented. This methodology was validated by studying two different species, both important models for avian developmental research.

Nerve repulsion by the lens and cornea during cornea innervation is dependent on Robo-Slit signaling and diminishes with neuron age.

The cornea, the most densely innervated tissue on the surface of the body, becomes innervated in a series of highly coordinated developmental events. During cornea development, chick trigeminal nerve growth cones reach the cornea margin at embryonic day (E)5, where they are initially repelled for days from E5 to E8, instead encircling the corneal periphery in a nerve ring prior to entering on E9. The molecular events coordinating growth cone guidance during cornea development are poorly understood. Here we evaluated a potential role for the Robo-Slit nerve guidance family. We found that Slits 1, 2 and 3 expression in the cornea and lens persisted during all stages of cornea innervation examined. Robo1 expression was developmentally regulated in trigeminal cell bodies, expressed robustly during nerve ring formation (E5-8), then later declining concurrent with projection of growth cones into the cornea. In this study we provide in vivo and in vitro evidence that Robo-Slit signaling guides trigeminal nerves during cornea innervation. Transient, localized inhibition of Robo-Slit signaling, by means of beads loaded with inhibitory Robo-Fc protein implanted into the developing eyefield in vivo, led to disorganized nerve ring formation and premature cornea innervation. Additionally, when trigeminal explants (source of neurons) were oriented adjacent to lens vesicles or corneas (source of repellant molecules) in organotypic tissue culture both lens and cornea tissues strongly repelled E7 trigeminal neurites, except in the presence of inhibitory Robo-Fc protein. In contrast, E10 trigeminal neurites were not as strongly repelled by cornea, and presence of Robo-Slit inhibitory protein had no effect. In full, these findings suggest that nerve repulsion from the lens and cornea during nerve ring formation is mediated by Robo-Slit signaling. Later, a shift in nerve guidance behavior occurs, in part due to molecular changes in trigeminal neurons, including Robo1 downregulation, thus allowing nerves to find the Slit-expressing cornea permissive for growth cones.

Expression and localization of neural cell adhesion molecule and polysialic acid during chick corneal development.

PURPOSE: To assay for expression and localization of neural cell adhesion molecule (NCAM) and polysialic acid (polySia) in the chick cornea during embryonic and postnatal development. METHODS: Real time quantitative PCR and Western blot analyses were used to determine NCAM expression and polysiaylation in embryonic, hatchling, and adult chick corneas. Immunofluorescence staining for NCAM and polySia was conducted on cryosections of embryonic and adult corneas, whole embryonic corneas, and trigeminal neurons. RESULTS: NCAM and ST8SiaII mRNA transcripts peaked by embryonic day (E)9, remained steady between E10 and E14 and slowly decreased thereafter during embryonic development. Both gene transcripts showed > 190-fold decline in the adult chick cornea compared with E9. In contrast, ST8SiaIV expression gradually decreased 26.5-fold from E6 to E19, increased thereafter, and rose to the early embryonic level in the adult cornea. Western blot analysis revealed NCAM was polysialylated and its expression developmentally changed. Other polysiaylated proteins aside from NCAM were also detected by Western blot analysis. Five NCAM isoforms including NCAM-120, NCAM-180 and three soluble NCAM isoforms with low molecular weights (87-96 kDa) were present in chick corneas, with NCAM-120 being the predominate isoform. NCAM was localized to the epithelium, stroma, and stromal extracellular matrix (ECM) of the embryonic cornea. In stroma, NCAM expression shifted from anterior to posterior stroma during embryonic development and eventually became undetectable in 20-week-old adult cornea. Additionally, both NCAM and polySia were detected on embryonic corneal and pericorneal nerves. CONCLUSIONS: NCAM and polySia are expressed and developmentally regulated in chick corneas. Both membrane-associated and soluble NCAM isoforms are expressed in chick corneas. The distributions of NCAM and polySia in cornea and on corneal nerves suggest their potential functions in corneal innervation.

Scintigraphic confirmation of brain death.

The concept of brain death has gained importance in the past few decades to prevent futile attempts to sustain ventilation and blood circulation when the brain has lost all function and to procure beneficial tissues or life-saving organs for transplantation. However, differences remain among professional societies and various study group recommendations, as well as among individual legal statutes, in how brain death is defined and the methodology for which the diagnosis is attained. Furthermore, reports have appeared both in the medical literature and the lay press concerning quality assurance measures in brain death documentation. Scintigraphy is a commonly used technique in the evaluation of brain death and can be performed with the use of either nonspecific tracers, such as Tc99m diethylene triamine pentaacetic acid, or brain-specific tracers, such as Tc99m hexamethylpropyleneamineoxime (HMPAO). Planar imaging, with or without radionuclide angiography, continues to be the mainstay for the scintigraphic confirmation of brain death. Flow with multiprojection static planar imaging with the use of Tc99m HMPAO can be used to evaluate the cerebral hemispheres, basal ganglia, thalamus, and cerebellum. Single-photon emission computed tomography (SPECT) can provide cross-sectional information but can be difficult to perform in the context of brain death. The current use of SPECT primarily is supplemental to help differentiate overlying scalp from intracerebral activity. The reliability of SPECT to exclude flow and metabolism in the brainstem remains to be scientifically validated.

Response of thyroglobulin to radioiodine therapy in thyroglobulin-elevated negative iodine scintigraphy (TENIS) syndrome.

BACKGROUND: While radioiodine (131-I) is widely used in the treatment of differentiated thyroid cancer, its role remains less certain when abnormal 131-I uptake cannot be demonstrated in a pre-therapy diagnostic scan. Documentation of abnormal 131-I uptake in a post-therapy scan in such cases helps to justify the radioiodine therapy, but the post-therapy scan can remain persistently negative. AIM: To evaluate (i) whether 131-I therapy had any measurable effect on thyroglobulin (Tg) levels in patients who were scan negative prior to radioiodine therapy and remained scan negative after therapy, and (ii) whether the magnitude of the effect on Tg depended on the pre-therapy Tg level. PATIENTS AND METHODS: Retrospective analysis of 78 patients. All patients had pre-therapy and post-therapy Tg levels measured under stimulation with thyroid stimulating hormone. Hospital data until date of last contact were analyzed to assess for recurrent disease. RESULTS: Tg levels decreased by 55% in those having Tg 10 µg/l or higher; and by 41% in those with less than 10 µg/l. In patients with detectable Tg antibodies, there were no statistically significant decreases demonstrated for either Tg or Tg antibody levels. CONCLUSION: Radioiodine therapy can reduce Tg levels, independently of the pre-therapy level, even when the pre-therapy level is low and the pre-therapy, as well as the post-therapy, radioiodine scan remains negative.

The role of nonenzymatic glycation and carbonyls in collagen cross-linking for the treatment of keratoconus.

PURPOSE: Corneal cross-linking (CXL) is a treatment for keratoconus that eliminates the need for keratoplasty in most patients. However, its molecular mechanisms remain under study. Advanced glycation end products (AGEs) have been suggested by many studies as the causative strengthening agent during CXL, though no studies to date have directly tested this hypothesis. METHODS: Corneas of young rabbits and sharks were pretreated with pyridoxal hydrochloride and copper ions before CXL. Two known inhibitors of AGE formation, aminoguanidine and rifampicin, were applied during CXL in the treatment solution. Tensile strength tests were conducted after these experiments to detect diminished or accentuated corneal stiffening after CXL. SDS-PAGE was performed on type I collagen cross-linked in the absence and presence of AGE inhibitors. RESULTS: Pretreatment with pyridoxal hydrochloride resulted in significantly higher corneal stiffening after CXL. AGE inhibitors significantly diminished cross-linking as detected by both tensile strength measurements using whole corneas and gel electrophoresis of in vitro cross-linking of type I collagen in solution, in the presence and absence of the inhibitors. Rifampicin inhibited CXL more significantly than aminoguanidine in gel electrophoresis and tensile strength tests, confirming recent findings on its efficacy as an AGE inhibitor. CONCLUSIONS: Data presented here suggest that CXL is carbonyl dependent and involves the formation of AGE cross-links. Six possible cross-linking mechanisms are discussed.

FDG PET/CT findings of a glomangiopericytoma.

Glomangiopericytoma (GPC) is a rare vascular neoplasm that arises almost exclusively from the nasal cavity or paranasal sinuses. GPC is also called sinonasal-type hemangiopericytoma, although current nomenclature, as well as classification in a group with myopericytomas, better emphasizes the relatively indolent behavior of this tumor. The authors present the FDG PET/CT findings of GPC in a 53-year-old with symptoms of nasal congestion and facial pressure. CT and MRI showed a nasal mass to extend along the sphenoid ridge from the posterior nasal cavity into the posterior nasopharynx. PET showed the mass to have uniformly low-grade FDG hypermetabolism. Pathologic examination of the surgical specimen showed classic features of GPC.