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The orbit houses and protects the ocular globe and the supporting structures, and occupies a strategic position below the anterior skull base and adjacent to the paranasal sinuses. Its embryologic origins are inextricably intertwined with those of the central nervous system, skull base, and face. Although the orbit contains important contributions from four germ cell layers (surface ectoderm, neuroectoderm, neural crest, and mesoderm), a significant majority originate from the neural crest cells. The bones of the orbit, face, and anterior cranial vault are mostly neural crest in origin. The majority of the bones of the skull base are formed through endochondral ossification, whereas the cranial vault is formed through intramembranous ossification. Familiarity with the embryology and fetal development of the orbit can aid in understanding its anatomy, as well as many developmental anomalies and pathologic conditions that affect the orbit.

BACKGROUND Numerous minimally invasive approaches to the skull base have been successively developed. Knowledge of the surgical nuances of a specific approach may facilitate approach selection. This study sought to compare the nuances of an extended version of the minipterional craniotomy (EMPT) with those of the transorbital endoscopic approach (TOEA) to the anterior and middle cranial fossae (ACF and MCF, respectively). OBJECTIVE To quantitatively analyze and compare the area of exposure and surgical freedom between EMPT and TOEA to the ACF and MCF. METHODS EMPT and TOEA were carried out in 5 latex-injected cadaveric heads, bilaterally (10 sides). For each approach, the area of exposure, surgical freedom, and angle of attack were obtained with neuronavigation and statistically compared. RESULTS No significant difference was found between the mean area of exposure of EMPT and TOEA at the ACF and MCF (P = .709 and .317, respectively). The mean exposure area at the ACF was of 13.4 ± 2.6 cm2 (mean ± standard deviation) and 13.0 ± 1.9 cm2 for EMPT and TOEA, respectively. Except for the crista galli, EMPT afforded a larger area of surgical freedom at all targets. EMPT also achieved significantly greater attack angles in vertical axis except to the crista galli. The horizontal attack angles to all targets were similar between approaches. CONCLUSION EMPT and TOEA offer a comparable area of exposure at the ACF and MCF in the cadaver; however, the instrument maneuverability afforded by EMPT is superior. Further studies are necessary to better define their precise surgical application.

Stereotactic body radiation therapy is a promising treatment modality for locally advanced pancreatic cancer. To determine the optimal radiation treatment, we compared the plan characteristics of volumetric-modulated arc therapy and intensity-modulated radiation therapy when administered with stereotactic body radiation therapy to treat pancreatic cancer.Fifteen patients with locally advanced pancreatic cancer were treated by stereotactic body radiation therapy at a dose of 24-32Gy in four fractions with marker-guided gated volumetric-modulated arc therapy. Four dimensional-computed tomography scans were used to assess the target and surrounding normal organs. The same images, contours, and dose constraints were used for dual-arc volumetric-modulated arc therapy and 9-field intensity-modulated radiation therapy planning. Plans were compared using dosimetric parameters and treatment performance.Volumetric-modulated arc therapy required significantly lower monitor units (1726 vs. 4188; P0.001) and shorter treatment delivery time in comparison with intensity-modulated radiation therapy (22.5min vs. 52.4min; P0.001). Regarding target volume coverage, both modalities demonstrated comparable results (VIn comparison with 9-field intensity-modulated radiation therapy, volumetric-modulated arc therapy significantly reduces the number of monitoring units and treatment delivery times while administering similar dosimetric quality. Based on these results, volumetric-modulated arc therapy might be an appropriate treatment for locally advanced pancreatic cancer when combined with stereotactic body radiation therapy.

Objectives This study sought to establish worldwide and regional diagnostic reference levels (DRLs) and achievable administered activities (AAAs) for single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). Background Reference levels serve as radiation dose benchmarks to compare individual laboratories against aggregated data, helping to identify sites in greatest need of dose reduction interventions. DRLs for SPECT MPI have previously been derived from national or regional registries. To date there have been no multiregional reports of DRLs for SPECT MPI from a single standardized dataset. Methods Data were submitted voluntarily to the INCAPS (International Atomic Energy Agency Nuclear Cardiology Protocols Study), a cross-sectional, multinational registry of MPI protocols. A total of 7,103 studies were included. DRLs and AAAs were calculated by protocol for each world region and for aggregated worldwide data. Results The aggregated worldwide DRLs for rest-stress or stress-rest studies employing technetium Tc 99m–labeled radiopharmaceuticals were 11.2 mCi (first dose) and 32.0 mCi (second dose) for 1-day protocols, and 23.0 mCi (first dose) and 24.0 mCi (second dose) for multiday protocols. Corresponding AAAs were 10.1 mCi (first dose) and 28.0 mCi (second dose) for 1-day protocols, and 17.8 mCi (first dose) and 18.7 mCi (second dose) for multiday protocols. For stress-only technetium Tc 99m studies, the worldwide DRL and AAA were 18.0 mCi and 12.5 mCi, respectively. Stress-first imaging was used in 26% to 92% of regional studies except in North America where it was used in just 7% of cases. Significant differences in DRLs and AAAs were observed between regions. Conclusions This study reports reference levels for SPECT MPI for each major world region from one of the largest international registries of clinical MPI studies. Regional DRLs may be useful in establishing or revising guidelines or simply comparing individual laboratory protocols to regional trends. Organizations should continue to focus on establishing standardized reporting methods to improve the validity and comparability of regional DRLs.

Background: Common carotid artery (CCA) and internal carotid artery (ICA) are aligned linearly, but their hemodynamic role in ischemic stroke has not been studied in depth. Objectives: We aimed to investigate whether CCA and ICA endothelial shear stress (ESS) could be associated with the ischemic stroke of large artery atherosclerosis (LAA). Methods: We enrolled consecutive patients with unilateral ischemic stroke of LAA and healthy controls aged >60 years in the stroke center of Jeonbuk National University Hospital. All patients and controls were examined with carotid artery time-of-flight magnetic resonance angiography, and their endothelial signal intensity gradients (SIGs) were determined, as a measure of ESS. The effect of right or left unilateral stroke on the association between carotid artery endothelial SIG and ischemic stroke of LAA was assessed. Results: In total, the results from 132 patients with ischemic stroke of LAA and 121 controls were analyzed. ICA endothelial SIG showed significant and independent associations with the same-sided unilateral ischemic stroke of LAA, even after adjusting for the potential confounders including carotid stenosis, whereas CCA endothelial SIG showed a significant association with the presence of the ischemic stroke of LAA. Conclusion: Although CCA and ICA are located with continuity, the hemodynamics and their roles in large artery ischemic stroke should be considered separately. Further studies are needed to delineate the pathophysiologic roles of ESS in CCA and ICA for large artery ischemic stroke.

Surgical management of thyroid eye disease (TED) has two general aims: (1) relieve symptoms of orbital congestion and fibrosis, including possibly compressive optic neuropathy, and (2) reconstruct the periocular region to reduce deformity and renormalize appearance. Surgical management follows a sequence that is tailored to individual patient needs. The signs and symptoms of TED that can be addressed surgically include proptosis, orbital pressure/pain, orbital inflammatory signs, diplopia secondary to restrictive strabismus, ocular surface exposure secondary to lagophthalmos, and eyelid retraction. Because orbital decompression surgery can improve lagophthalmos and eyelid retraction, and can affect strabismus (positively or negatively), these issues are traditionally addressed sequentially by orbital decompression first, followed by strabismus surgery, and finally eyelid retraction repair, as needed. In this chapter, we focus primarily on orbital decompression surgery and eyelid surgery, although key aspects of strabismus surgery are also discussed.

Objectives This study sought to describe worldwide variations in the use of myocardial perfusion imaging hardware, software, and imaging protocols and their impact on radiation effective dose (ED). Background Concerns about long-term effects of ionizing radiation have prompted efforts to identify strategies for dose optimization in myocardial perfusion scintigraphy. Studies have increasingly shown opportunities for dose reduction using newer technologies and optimized protocols. Methods Data were submitted voluntarily to the INCAPS (International Atomic Energy Agency Nuclear Cardiology Protocols Study) registry, a multinational, cross-sectional study comprising 7,911 imaging studies from 308 labs in 65 countries. The study compared regional use of camera technologies, advanced post-processing software, and protocol characteristics and analyzed the influence of each factor on ED. Results Cadmium-zinc-telluride and positron emission tomography (PET) cameras were used in 10% (regional range 0% to 26%) and 6% (regional range 0% to 17%) of studies worldwide. Attenuation correction was used in 26% of cases (range 10% to 57%), and advanced post-processing software was used in 38% of cases (range 26% to 64%). Stress-first single-photon emission computed tomography (SPECT) imaging comprised nearly 20% of cases from all world regions, except North America, where it was used in just 7% of cases. Factors associated with lower ED and odds ratio for achieving radiation dose ≤9 mSv included use of cadmium-zinc-telluride, PET, advanced post-processing software, and stress- or rest-only imaging. Overall, 39% of all studies (97% PET and 35% SPECT) were ≤9 mSv, while just 6% of all studies (32% PET and 4% SPECT) achieved a dose ≤3 mSv. Conclusions Newer-technology cameras, advanced software, and stress-only protocols were associated with reduced ED, but worldwide adoption of these practices was generally low and varied significantly between regions. The implementation of dose-optimizing technologies and protocols offers an opportunity to reduce patient radiation exposure across all world regions.

Chronic inflammatory demyelinating polyneuropathy is known to cause enlargement of the cranial nerves, particularly the trigeminal nerve. Several cases of orbital neuromas associated with this condition have been published, but surgical treatment has not been reported. The authors present a case of bilateral supraorbital neuromas associated with chronic inflammatory demyelinating polyneuropathy that underwent surgical excision and histopathologic examination.

Aims Critical limb ischemia (CLI) patients are characterized by intractable pain in spite of medication, non-healing ulcers, and gangrene. The objective of this study was to investigate whether or not isovolemic hemodilution treatment can reduce the rate of major amputations in CLI. Methods 28 patients were studied who had tissue loss on Rutherford Grade III, Category 5 or 6. The subjects were divided into two arms: standard-of-care, conventional therapy (CT) (n = 15) as a control group and hemodilution therapy (HT) (n = 13) as a study group. For the HT group, weekly isovolemic hemodilution was performed over 4 consecutive weeks, removing 250 ml of whole blood with the infusion of hydroxyl-ethyl starch solution. Blood viscosity, hematocrit, hemoglobin, ankle-brachial index, VA pain scale, time-to-amputation from admission, and survival time were measured. Results The mean Hct gradually decreased from 36.6 to 35.1, whereas the WBV at a shear rate of 1 s-1 significantly decreased from 18.2 to 10.5 during the same period. Subsequently, tissue oxygen delivery index, defined as the ratio of Hct to WBV at a shear rate of 1 s-1, increased from 24.4 to 37.0 by 51.7%, suggesting improvements in oxygen delivery in the patients. The average rate of lower limb major amputation in the control group was 93% (14/15), whereas that in the study group was 31% (4/13) (p = 0.001). Amputation-free median survival time and amputation-free 5-year survival rate in the control group were 1.2 months and 7%, while those in the study group were 30.2 months and 44% (p = 0.001). There were no adverse effects from repetitive hemodilution in the study group. Conclusions Isovolemic hemodilution treatment of CLI patients was found to be well-tolerated and reduced the rate of major amputation resulting from the deterioration of CLI.

Extraorbital approaches can be utilized to gain surgical access to the orbit in select cases. Endonasal approaches are useful for medial orbital decompression and optic canal decompression, and to address tumors or other processes in the medial orbit or orbital apex. Transcranial approaches can be utilized for orbital roof fractures or roof decompression, high-risk lesions of the orbital apex or superior orbit, and processes affecting both the orbit and anterior and/or middle cranial fossa. Commonly used approaches include frontotemporal, orbitozygomatic, and subfrontal (transbasal) craniotomies.

There are numerous indications for performing surgery in the orbit, including repair of orbital fractures, biopsy or excision of orbital tumors, drainage of orbital abscesses, and orbital decompression. Anterior orbitotomy can be performed through both transconjunctival and transcutaneous approaches. Commonly utilized approaches include the inferior conjunctival fornix incision, the transcaruncular incision, lateral canthotomy and cantholysis, and the upper eyelid crease incision.

Authors of this report describe a Fukushima Type D(b) or Kawase Type ME2 trigeminal schwannoma involving the right maxillary division in a 59-year-old woman who presented with intermittent right-sided facial numbness and pain. This tumor was successfully resected via a right lateral orbitotomy without the need for craniotomy. This novel approach to a lesion of this type has not yet been described in the scientific literature. The outcome in this case was good, and the patient's intra- and postoperative courses proceeded without complication. The epidemiology of trigeminal schwannomas and some technical aspects of lateral orbitotomy, including potential advantages of this approach over traditional transcranial as well as fully endoscopic dissections in appropriately selected cases, are also briefly discussed.

Objectives The aim of this study was to investigate gender-based differences in nuclear cardiology practice globally, with a particular focus on laboratory volume, radiation dose, protocols, and best practices. Background It is unclear whether gender-based differences exist in radiation exposure for nuclear cardiology procedures. Methods In a large, multicenter, observational, cross-sectional study encompassing 7,911 patients in 65 countries, radiation effective dose was estimated for each examination. Patient-level best practices relating to radiation exposure were compared between genders. Analysis of covariance was used to determine any difference in radiation exposure according to gender, region, and the interaction between gender and region. Linear, logistic, and hierarchical regression models were developed to evaluate gender-based differences in radiation exposure and laboratory adherence to best practices. The study also included the United Nations Gender Inequality Index and Human Development Index as covariates in multivariable models. Results The proportion of myocardial perfusion imaging studies performed in women varied among countries; however, there was no significant correlation with the Gender Inequality Index. Globally, mean effective dose for nuclear cardiology procedures was only slightly lower in women (9.6 ± 4.5 mSv) than in men (10.3 ± 4.5 mSv; p Conclusions Despite significant worldwide variation in best practice use and radiation doses from nuclear cardiology procedures, only small differences were observed between genders worldwide. Regional variations noted in myocardial perfusion imaging use and radiation dose offer potential opportunities to address gender-related differences in delivery of nuclear cardiology care.

Purpose To describe a novel technique to correct cicatricial lower lid entropion and retraction using a transverse lower lid tarsotomy with an interposed tarsoconjunctival flap posterior lamellar spacer. Methods Technique description and retrospective interventional case series. Results Four patients underwent the procedure-two with complications following treatment of sinonasal carcinoma and two with complications following orbital fracture repair. All patients had failed prior posterior lamellar spacer grafts, including donor sclera, dermis-fat graft, and hard palate mucosa. Average time to flap takedown was 20 (11-28) days, with an average follow-up interval of 8.4 (6.2-11.5) months. All patients had resolution of lower lid entropion and significant improvement of lower lid retraction with an average of 2.8 mm (2.0-4.3) of elevation. There were no serious complications, and all patients reported significant improvement in ocular surface symptoms. Conclusions Transverse tarsotomy combined with a tarsoconjunctival flap is effective for the correction of cicatricial lower lid retraction and entropion in eyelids that have failed surgery with traditional posterior lamellar spacer grafts.

Undifferentiated pleomorphic sarcoma is a malignancy of mesenchymal origin, which was previously known as malignant fibrous histiocytoma. It is known to occur on rare occasion as a primary orbital tumor, but no known cases of metastatic orbital involvement have been reported since 2002, when the reclassification of these tumors took place. The authors report a patient who presented with a metastasis to the left orbit 2 years after undergoing treatment of a high-grade undifferentiated pleomorphic sarcoma of the right thigh. Histopathology of the orbital mass was similar to the primary tumor biopsy prior to neoadjuvant chemotherapy and radiation. The appearance was markedly altered in the subsequent excisional tissue, which showed treatment changes. Immunohistochemistry and genetic testing also supported the metastatic nature of the orbital lesion. The patient's tumor progressed rapidly despite systemic targeted therapy and orbital exenteration was performed. At 2 years follow up, the patient remained without evidence of tumor recurrence in the socket.

Blood flow simulations can identify arterial regions that are vulnerable to atherosclerotic or thrombotic evolution. To accurately define vulnerable arterial regions, hemodynamic parameters such as arterial geometry, blood flow velocity and blood viscosity (BV) must be measured individually. However, previous numerical studies have largely employed either a single representative value or simply used a nonspecific curve of non-Newtonian characteristics of BV. This study aimed to evaluate whether various BV models could produce similar arterial wall shear stress (WSS) results. We performed a blood flow simulation in carotid arteries obtained from time-of-flight magnetic resonance (TOF MR) angiography using the hemodynamic characteristics of subjects via carotid duplex ultrasonography. The BV models were categorized into the following five types: patient-specific non-Newtonian BV (model 1), representative non-Newtonian BV based on the Carreau model (BV model 2), Newtonian BV measured at a specific shear rate of 300[Formula: see text][Formula: see text] (BV model 3), Newtonian BV obtained from a hematocrit-based equation (BV model 4) and a representative Newtonian BV of 4[Formula: see text]cP (BV model 5). In total, 20 carotid arteries from 20 healthy volunteers (mean age [Formula: see text] SD of [Formula: see text] years; 50% women) were examined. Compared with the mean values of carotid WSS in BV model 1 as the reference model, the other four models showed significant differences in both genders for all carotid segments. To obtain reliable physiological WSS results, patient-specific non-Newtonian BV should be carefully employed.

Background Nitric oxide (NO) is tonically synthesized by the vascular endothelium and known as a marker of vasodilatation and blood flow. As NO has a critical role in hemodynamics, NO may be associated with other hemodynamics-related factors including atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP) and whole blood viscosity (WBV). It has been reported that serum NO level increased in patients undergoing hemodialysis. However, there are few reports about the relationship between NO and hemodynamic parameters in hemodialysis patients. Objective We investigated the associations between serum levels of NO and other hemodynamics-related factors such as ANP, BNP and WBV in patients with hemodialysis. Methods NO, ANP, and BNP levels before hemodialysis were measured using ELISA method. We measured WBV in pre- and post-dialysis. Results Mean serum levels of NO, ANP, and BNP were 13.97 ± 10.34 μg/mL, 198.85 ± 61.56 pg/mL, and 1233.32 ± 280.81 pg/mL, respectively in patients with hemodialysis. The mean WBV values at shear rates of 1, 5, and 300 s−1 for pre-dialyses were 168.5 ± 62.5, 76.9 ± 20.6, and 33.3 ± 3.8 mP, respectively. Serum NO level was positively correlated with WBV at shear rates of 1, 5, and 300 s−1 at pre- and post-hemodialysis. There is a correlation between serum nitrite levels and the change of SBV during hemodialysis. Serum nitrite levels correlated with the serum BNP levels. ANP levels have a negative correlation with pre-dialytic WBV. However, BNP levels did not correlate with WBV during hemodialysis. Conclusions WBV is linked to an imbalance in serum vasoactive substances in hemodialysis patients and can cause significant hemodynamic disturbance.

The aim of the study was to calculate the arterial wall signal intensity gradient (SIG) from time-of-flight MR angiography (TOF-MRA) and represent arterial wall shear stress. We developed a new algorithm that uses signal intensity (SI) of a TOF-MRA to directly calculate the signal intensity gradient (SIG). The results from our phantom study showed that the TOF-MRA SIG could be used to distinguish the magnitude of blood flow rate as high (mean SIG ± SD, 2.2 ± 0.4 SI/mm for 12.5 ± 2.3 L/min) and low (0.9 ± 0.3 SI/mm for 8.5 ± 2.6 L/min) in vessels (p<0.001). Additionally, we found that the TOF-MRA SIG values were highly correlated with various flow rates (β=0.96, p<0.001). Remarkably, the correlation coefficient between the WSS obtained from the computational fluid dynamics (CFD) analysis and the TOF-MRA SIG was greater than 0.8 in each section at the carotid artery (p<0.001 for all β values). This new technique using TOF-MRA could enable the rapid calculation of the TOF-MRA SIG and thereby the WSS. Thus, the TOF-MRA SIG can provide clinicians with an accurate and efficient screening method for making rapid decisions on the risk of vascular disease for a patient in clinical practice.

Hematocrit (HCT), the volume fraction of cells in whole blood, is one of the most important variables that affect the viscosity of whole blood. Matrai's HCT-correction model (Matrai model) provides a method of HCT-correction so that the blood viscosity can be compared at a standard HCT of 45%. Since the Matrai model requires the plasma viscosity, there is a need to have another method for HCT correction of the blood viscosity in cases when the plasma viscosity is not available. The present study introduced a new method of HCT correction using the whole blood viscosity measured over a range of shear rates without plasma viscosity. For validation of the new method, three different human blood samples were used. Each blood sample was reconstituted to eight different HCT levels (from 25 to 60%) and the blood viscosity at each HCT level was measured over a range of shear rates, including the blood viscosity at HCT 45%. HCT-correction results from the Matrai model and the present model were compared with the blood viscosity measured at HCT 45%. The present model gave significantly better HCT corrections (i.e., about 3 times less error) than the Matrai model.

The present study investigated the residual effect of gliding arc discharge (GAD) treatment on the inactivation of bacteria in a large volume of water (i.e., 20 L). Pure water and air were introduced to GAD separately, and then both the gas and water treated by plasma were sent to bacteria-containing water. Water contaminated by Escherichia coli (E. coli) was first treated by GAD for 10, 13 and 16, and 25 min and then stored for the next 4 h, during which time the E. coli concentration and pH were measured. In general, GAD produced the strong anti-microbial properties, a phenomenon which increased with plasma treatment time. More specifically, E. coli was partially inactivated (i.e., approximately 2.7-log reduction) with 16-min plasma treatment. However, E. coli was almost completely inactivated (over 99.9% with 5-log reduction) during the subsequent 4-h storage period, a phenomenon that was attributed to the residual effect of the plasma treatment. The optimum plasma energy cost of the GAD treatment to inactivate E. coli in 20-L water in the present study was found to be approximately 0.57 kJ/L per 1-log reduction.

The inward rectifier Kir2.1 current (IKir2.1) was reported to be facilitated by fluid flow. However, the mechanism underlying this facilitation remains uncertain. We hypothesized that during K+ influx or efflux, [K+] adjacent to the outer mouth of the Kir2.1 channel might decrease or increase, respectively, compared with the average [K+] of the bulk extracellular solution, and that fluid flow could restore the original [K+] and result in the apparent facilitation of IKir2.1. We recorded the IKir2.1 in RBL-2H3 cells and HEK293T cells that were ectopically over-expressed with Kir2.1 channels by using the whole-cell patch-clamp technique. Fluid-flow application immediately increased the IKir2.1, which was not prevented by either the pretreatment with inhibitors of various protein kinases or the modulation of the cytoskeleton and caveolae. The magnitudes of the increases of IKir2.1 by fluid flow were driving force-dependent. Simulations performed using the Nernst-Planck mass equation indicated that [K+] near the membrane surface fell markedly below the average [K+] of the bulk extracellular solution during K+ influx, and, notably, that fluid flow restored the decreased [K+] at the cell surface in a flow rate-dependent manner. These results support the “convection-regulation hypothesis” and define a novel interpretation of fluid flow-induced modulation of ion channels.

The objective of the present study was to investigate the feasibility of using a gliding arc (GA) discharge to inactivate microorganisms in water. Microbubble generators were utilized to uniformly disperse gas bubbles that contain H 2 O 2 in water. In addition, the residual effect of H 2 O 2 in plasma-treated water was assessed by continuous quantitative measurement of microbiological colony forming units (cfu) in water after the completion of GA discharge. Application of the GA plasma discharge to water decreased pH from 6.15 to 3.55 after 25-min treatment, and the lowered pH was maintained for 4 h after treatment ceased. The present study showed a total 6-log reduction in the cfu counts of Escherichia Coli with plasma treatment of 25 min duration: 4-log reduction from 10 6 to 10 2 during treatment and an additional 2-log reduction from 10 2 to 10 0 during the 2 h after treatment. The use of microbubble generators significantly enhanced the benefit of H 2 O 2 in acidic water, increasing the bacterial inactivation ability of the plasma treatment with GA discharge.

Summary Purpose: Kikuchi disease (KD) is a benign and self-limited syndrome characterized by cervical lymphadenopathy. This study evaluated 18F-fluorodeoxyglucose positron emission tomography/ computed tomography (FDG PET/ CT) findings in patients with KD and analyzed their imaging features. Patients, material, methods: We evaluated the FDG PET/CT findings of 22 patients (14 men, 8 women) with KD, ranging in age from 9 to 73 years. All patients had been diagnosed based on the pathological findings of biopsy. We examined the locations, metabolic activity and size of hypermetabolic lymph nodes (LNs) on FDG PET/CT imaging with medical history including laboratory results. Results: Among the 22 patients, we identified 619 hypermetabolic LNs which had maximum standard uptake value (SUVmax) above 3.0. The 16 patients were studied with FDG PET/CT to identify the cause of fever, another 5 patients for their neck masses, and the remaining patient for his left inguinal mass. Hypermetabolic LNs were noted in neck (18 bilaterally, 2 right, 1 left) of 21 patients, axilla of 10, mediastinum of 9, abdomen of 17, pelvis of 6, and inguinal area of 3. The SUVmax of FDG uptake in affected LNs by patient base analysis were 6.2–29.4. Of the 619 hypermetabolic LNs identified, 440 LNs (71.1%) were less than 10 mm in their short axis determined by CT, and were occasionally aggregated. No patient showed solid organ hypermetabolic lesion in FDG PET/CT. Conclusion: Kikuchi disease could present multiple hypermetabolic LNs in body on FDG PET/CT. Based on the physical findings, consideration of the generalized distribution of the relatively small-sized hypermetabolic LNs, FDG PET/CT may be useful as a diagnostic tool in cases of Kikuchi disease.

Whole blood viscosity (WBV) plays a role in hemorheology and is determined by many factors such as red blood cell factors, plasma protein and blood volume. As WBV changes during hemodialysis, mortality may be due to changes in WBV in patients on hemodialysis. However, there are few prospective data on the relationship between changes in WBV and overall mortality in dialysis patients. We tried to investigate the correlations between values of WBV at variable shear rates before and after hemodialysis and overall or atherosclerosis-related mortality in patients with end-stage kidney disease.Forty-three patients receiving hemodialysis were enrolled in this study. In this 5.8-year prospective observational study, analyses of the effects of WBV at shear rates of 300 s-1 (systolic WBV; SBV), 5 s-1 (diastolic WBV5; DBV5), and 1 s-1 (diastolic WBV1; DBV1) during dialysis on all-cause and atherosclerotic mortality was performed.Among a total of 43 patients, 27 (62.7%) died over the course of the study. Thirteen deaths were caused by atherosclerotic events. A high degree of change in WBV at shear rates of 300 s-1 and 5 s-1 during hemodialysis (ΔSBV, ΔDBV5) was positively correlated with overall mortality (HR = 4.688, 95% confidence interval [CI], 1.269-17.319, p = 0.020; HR = 3.941, 95% CI, 1.057-14.701, p = 0.041, respectively). A high degree of change in diastolic blood pressure (ΔDBP) during hemodialysis was also positively correlated with overall mortality (HR = 3.035, 95% CI, 1.039-8.867, p = 0.042). However, comparative analysis between WBV at shear rates of 300 s-1, 5 s-1, and 1 s-1 and overall mortality did not reveal any significant relationships. Kaplan-Meier analysis revealed that the all-cause mortality was significantly higher in patients from a high degree of change of WBV at shear rates of 300 s-1, compared to those from the moderate or low degree of changes of WBV at shear rates of 300 s-1 (p = 0.020, log-rank test). Survival rate in high ΔDBP was lower than that of moderate or low ΔDBP group in Kaplan-Meier survival analysis (p = 0.004, log-rank test).Our data showed that a high degree of change in WBV at variable shear rates during hemodialysis might impact overall survival in patients with end-stage kidney disease. However, large-scale studies to evaluate the relationship of WBV with overall mortality and atherosclerotic mortality will be needed.

Since liver function is changed by chronic liver diseases, chronic liver disease can lead to different hemorheological alterations during the course of the progression. This study aims to compare alterations in whole blood viscosity in patients with chronic liver disease, focusing on the gender effect. Chronic liver diseases were classified into three categories by patient’s history, serologic markers, and radiologic findings: nonalcoholic fatty liver disease (NAFLD) (n = 63), chronic viral hepatitis B and C (n = 50), and liver cirrhosis (LC) (n = 35). Whole blood viscosity was measured by automated scanning capillary tube viscometer, while liver stiffness was measured by transient elastography using FibroScan®. Both systolic and diastolic whole blood viscosities were significantly lower in patients with LC than NAFLD and chronic viral hepatitis (P < 0.001) in male patients, but not in female patients. In correlation analysis, there were inverse relationships between both systolic and diastolic whole blood viscosity and liver stiffness (systolic: r = −0.25, diastolic: r = −0.22). Whole blood viscosity was significantly lower in male patients with LC than NAFLD or chronic viral hepatitis. Our data suggest that whole blood viscosity test can become a useful tool for classifying chronic liver disease and determining the prognosis for different types of chronic liver diseases., Graphical Abstract

Male vulnerability in health and growth outcomes has often been reported in very low birth weight (VLBW) preterm neonates. On the basis of gender-difference theories, possible associations were explored between the levels of postnatal salivary testosterone/cortisol and the outcomes of neonatal health/growth.This study used an exploratory and comparative research design. One-hundred-one mother-VLBW preterm neonate pairs were recruited from the neonatal intensive care unit (NICU) of a tertiary medical center in the Southeastern, US. Demographic information, health and growth variables of neonates, and pregnancy and labor variables of mothers were obtained from the medical record reviews and interviews of mothers. Saliva samples from each pair were collected between 9 and 60 days of age. The levels of testosterone and cortisol were determined by using an enzyme immunoassay methodology.Linear regression analysis showed that neonatal health problems were positively associated with the levels of postnatal salivary testosterone and cortisol, while growth delays were positively associated with the levels of postnatal salivary testosterone after adjusting for the characteristics of neonates and mothers and day of saliva sampling. The salivary levels of testosterone and cortisol were higher in neonates than in mothers. A positive correlation between the levels of testosterone and cortisol was found in neonates and in mothers.The level of postnatal salivary testosterone is a more reliable marker in assessing neonatal health and growth outcomes compared to salivary cortisol. Further research on both testosterone and cortisol measurements at various stages during the neonatal period may elucidate further these associations.

Hematocrit has been considered as an important marker of oxygen carrying capacity of the blood associated with whole blood viscosity to assess the mortality risk of both cardiovascular, cerebral, and kidney diseases. The present study developed a new on-line conductivity cell to measure the hematocrit of whole blood using a bipolar square-wave voltage signal at a frequency of 5 kHz. By applying such a voltage signal to a blood flowing in a range of 1.2–3.0 mL/min, the electrolyte effect of blood plasma, the conductive and capacitive effects of blood cells, and the sedimentation effect of erythrocytes on the conductivity of whole blood could be minimized for an accurate hematocrit measurement. The coefficient of correlation between the present method and conventional microcentrifuge method showed an excellent linear relationship. A new equation between the specific conductance and Hct of whole blood was obtained: C = 12.561 − 0.1527 Hct (P

The whole blood viscosity (WBV) is one of the major independent indicators for the risk of cardiovascular disease, stroke, and peripheral arterial diseases. Furthermore, oxidized LDL molecules are known to cause atherosclerotic plaques in arteries, and it is one of the key components that increase WBV. The present study attempted to reduce WBV by coagulating plasma proteins and lipid molecules from blood plasma using non-thermal dielectric barrier discharge (DBD) and removing them through filtration. The DBD treatment was found to produce coagulated particles in blood plasma. After filtration of the coagulated particles, WBV decreased by 9.1 and 17.7% for both systolic and diastolic blood viscosities, respectively. The present results suggest that the removal of excess plasma proteins and lipid molecules might be feasible using DBD treatment.

On radionuclide scanning, acute tubular necrosis (ATN) commonly manifests as adequate perfusion represented by persistently diffuse radiotracer activity throughout the parenchyma of renal allograft transplanted with a single artery with no or poor excretion of radiotracer. Following transplantation, the abnormal “wedge-shaped” finding of radiotracer retention in an isolated arterial segment of the graft kidney on Tc-99 m mercaptoacetyltriglycine (MAG3) scan with significant clearance on sequential study demonstrates vascular etiology of tubular dysfunction and represents segmental ATN rather urinary extravasation or artifact. Dial. Transplant. © 2011 Wiley Periodicals, Inc.

Purpose: To compare the efficacy of lateral orbital decompression with medial orbital decompression for the treatment of compressive optic neuropathy (CON) caused by thyroid eye disease (TED). Methods: A retrospective review of all patients undergoing orbital decompression for TED-associated CON between 2003 and 2008 was conducted. Clinical outcome measures included visual acuity, mean deviation on Humphrey visual field, Ishihara color plate testing, afferent pupillary defect, and Hertel exophthalmometry. A composite CON score was also calculated for each patient based on the 3 visual outcome measures, with a higher CON score reflecting greater disease severity. Results: Twenty-eight eyes of 17 patients were included in the study. Ten orbits underwent lateral wall decompression, and 18 orbits underwent medial decompression. Both groups showed a significant postoperative improvement in visual acuity, Humphrey visual field testing, and color testing at 3 months following the initial surgery. The composite CON score improved 9.04 ± 9.97 points after lateral decompression (p = 0.02) and 9.03 ± 10.84 points after medial decompression (p = 0.003). There was no significant difference in the degree of improvement in any of the visual outcome measures between the lateral and medial groups. There was a statistically significant difference in the amount of proptosis reduction resulting from lateral decompression compared with medial decompression (6.3 versus 3.1 mm, respectively, p Conclusions: Lateral orbital decompression and medial orbital decompression are both efficacious for the treatment of TED-associated CON. Lateral decompression also results in a greater proptosis reduction than medial decompression.

The efficacy of gliding arc (GA) discharge for the generation of hydrogen peroxide (H2O2) and water with a low pH was studied because H2O2 combined with low-pH environment is known as a strong oxidizer that can be used for the bacterial inactivation. The ability of the GA discharge to inactivate Escherichia coli in water was tested experimentally, and the inactivation was found to increase with the plasma treatment time and rate of water injection flow to the GA discharge system. The best result showed a 2-log reduction of the number of colony-forming units of E. coli from 104 to 102 at a water injection flow rate of 180 mL/min. Furthermore, pH in the plasma-treated water was decreased from 6.0 to 3.55 after 25

Purpose: To evaluate the efficacy of ultrasonic bone removal during lateral orbital decompression for thyroid eye disease. Methods: Retrospective, comparative, interventional case series of lateral orbital decompressions performed by the senior author for thyroid eye disease between July 2005 and July 2008. Patients were excluded if they had other coexisting orbital conditions or concurrent decompression of other orbital walls. Primary outcome measures included visual acuity, proptosis, lagophthalmos, eyelid retraction, and exposure keratopathy. Results: Thirty-six consecutive lateral orbital decompressions performed by the senior author were reviewed. The Sonopet Omni ultrasonic surgical aspirator was used to remove the lateral wall in 18 cases, and a high-speed drill with a cutting burr was used in the other 18 cases. There was no significant difference between the groups in postoperative visual acuity, proptosis reduction, lagophthalmos, eyelid retraction, exposure keratopathy, or surgical complications. The average reduction in proptosis was 3.9 mm (range, 1–6.5 mm) in the Sonopet group and 4.0 mm (range, 1–6 mm) in the drill group (p = 0.86). In our series, the average surgical case time was slightly shorter in the Sonopet group than in the drill group (104 vs. 118 minutes, p = 0.032). Conclusions: Ultrasonic bone removal is a safe and effective alternative to high-speed burring during lateral orbital decompression for thyroid eye disease.

Aim: Nutritional parameters, such as B-vitamins, have not been studied for an association with low-density lipoprotein (LDL) particle size. The present study explored whether serum vitamin levels, including folate and vitamin B-12, could be associated with LDL particle size.Methods: Using a randomly selected population of 255 hospital workers, we collected detailed lipid profiles, including triglyceride (TG), high-density lipoprotein (HDL) cholesterol, and LDL particle sizes. The peak particle size of LDL was measured by density gradient ultracentrifugation and a pore gradient lipoprotein system. Serum folate and vitamin B-12 levels were measured about 1 year later and analyzed. Carotid intima-media thickness (IMT) and hepatic steatosis were diagnosed ultrasonographically, and metabolic syndrome was diagnosed using ATP III criteria.Results: LDL peak particle size was significantly correlated with carotid mean IMT (r=-0.16, p=0.010). Serum folate levels were significantly and positively correlated with HDL cholesterol and negatively with TG, although the latter showed borderline significance. With increasing serum folate levels, the LDL peak particle size showed a gradual independent increase, even when adjusted for age, sex, hepatic steatosis, metabolic syndrome, and the TG/HDL cholesterol ratio.Conclusion: Folate may act to enhance LDL particle size. Future clinical and research work should include a study of the safe application and manipulation of folate levels in order to control LDL particle size.

Background The aim of the present study was to evaluate the therapeutic efficacy of dendritic cell (DC)–tumor fusion hybrids with Toll-like receptor (TLR) agonists. Methods DC–tumor fusion hybrids were generated by electrofusion and injected into the inguinal lymph nodes of C57BL/6 mice with 3-day established pulmonary metastases. Paired TLR agonists polyinosine:polycytadilic acid [poly(I:C)] and cytosine–phosphate–guanine (CpG) were then injected intraperitoneally. Enzyme-linked immunosorbent assay (ELISA) was used to evaluate interleukin (IL)-12 production from the DC–tumor fusion hybrids in vitro. Results Fusion + TLR agonists (60 metastases) had significantly fewer metastases than did the untreated control (262 metastases, p = .0001) and fusion alone (150 metastases, p = .02). ELISA showed that the DC–tumor fusion hybrids yielded 90 pg of IL-12 after TLR stimulation compared with 1610 pg from dendritic cells alone. Conclusions CpG and poly(I:C) administered as a third signal with fusion hybrids as described significantly reduce melanoma metastasis compared with fusion hybrids alone. Fusion hybrids do not appear to be a significant source for IL-12 secretion. © 2009 Wiley Periodicals, Inc. Head Neck, 2010

Background and Purpose— A pulsatility index (PI) represents vascular resistance distal to an examined artery. The purpose of the present study was to evaluate an association between plasma total homocysteine (tHcy) and PIs of the cerebral arteries in patients with ischemic stroke. Methods— Consecutive patients with ischemic stroke referred to a neurovascular ultrasound laboratory were evaluated from March 2007 to February 2008. PI was defined as (peak systolic velocity−end-diastolic velocity)/mean flow velocity as recommended. Transcranial Doppler was examined in both middle cerebral arteries and vertebral arteries, and basilar arteries. All patients with ischemic stroke were subdivided according to the presence of proximal internal carotid arterial steno-occlusion (ICS). Results— The numbers of patients enrolled for the present analysis as ischemic stroke without and with ICS were 272 and 92, respectively. PIs measured in the cerebral arteries did not show a significant difference in the two groups, in spite of the fact that mean flow velocities of both basilar arteries and vertebral arteries were significantly elevated in the patients with ICS. Plasma tHcy was found to be independently associated with graded increases of PIs in all cerebral arteries in the patients without ICS, even adjusted for the potential confounders. However, there was no association between tHcy and PI in the patients with ICS. Conclusion— Plasma tHcy was directly associated with increased cerebral arterial resistance. But in clinical situations when the cerebral arterial hemodynamics were altered as in the patients with ICS, the effect of tHcy on arterial remodeling could be obscured.

Doxorubicin was chemically conjugated to acrylated chitosan in order to obtain sustained-release profiles of doxorubicin from thermo-responsive and photo-crosslinkable hydrogels. Chitooligosaccharide was acrylated with glycidyl methacrylate and subsequently conjugated to doxorubicin via an amide linkage. A mixture of doxorubicin-chitosan conjugates, acrylated Pluronic, and doxorubicin formed physical gels at 37 degrees C. Photo-irradiation was subsequently performed to chemically crosslink the physical hydrogel at 37 degrees C. Chitooligosaccharide-doxorubicin conjugates in the doxorubicin hydrogels significantly reduced burst release of free doxorubicin from doxorubicin hydrogels compared hydrogels without the conjugates. Upon incubating doxorubicin hydrogels at 37 degrees C, chitosan-doxorubicin conjugates were confirmed to be degraded into more hydrophilic oligomers by reversed-phase chromatography. In vitro cytotoxicity assay using released media from doxorubicin hydrogels showed that degraded chitosan-doxorubicin had cytotoxicity comparable to free doxorubicin. Athymic nude mice bearing human lung adenocarcinoma were subjected to intra-tumoral injections of physical hydrogels. After photo-crosslinking injected hydrogels using surgical catheters, tumor sizes, body weights, and survivals were measured for 1 month. Released media from doxorubicin hydrogels exerted similar cytotoxicities to free doxorubicin, and the tumor volume was significantly reduced for 1 month compared to other samples. Thus, doxorubicin hydrogels containing doxorubicin conjugates can be employed as a novel injectable anti-cancer drug aiming to achieve sustained release of doxorubicin for several weeks against solid tumors.

The objective of the present study is to review hemorheological disorders in diabetes mellitus. Several key hemorheological parameters, such as whole blood viscosity, erythrocyte deformability, and aggregation, are examined in the context of elevated blood glucose level in diabetes. The erythrocyte deformability is reduced, whereas its aggregation increases, both of which make whole blood more viscous compared to healthy individuals. The present paper explains how the increased blood viscosity adversely affects the microcirculation in diabetes, leading to microangiopathy.

We tracked smoking outcomes – quitting, stage of readiness, action, motivation, self-efficacy, and confidence – over time among 943 low-SES women smokers accrued in an earlier smoking cessation intervention trial conducted in public health clinics. We assessed outcomes at 2, 6, 12 and 18 months post-initial clinic visit. Controlling for baseline characteristics and earlier program participation, we used hierarchical linear modeling to assess how intervening life events – pregnancy and exposure to subsequent clinic smoking interventions – affected smoking outcomes directly and indirectly, through the mediators, perceived stress and health concerns. Results: All longitudinal smoking outcomes were positively related to health concerns and negatively related to perceived stress. Pregnancy favorably influenced all smoking outcomes but confidence, but exposure to additional interventions affected only motivation. Health concerns and stress partially mediated the positive impact of pregnancy. Conclusion: Public health efforts targeted to low-SES women smokers should continue to emphasize the benefits of quitting smoking for health maintenance and incorporate more effective stress-coping mechanisms. Pregnancy increases abstinence, but preventing post-delivery relapse may require stress management and re-focusing of health concerns.

The role of human papilloma virus (HPV) infection in the development of cervical carcinoma is well established, however, the prevalence of HPV DNA in cervical adenocarcinoma varies from study to study. It appears to be caused by a number of factors, one of which is that cervical adenocarcinomas comprise a heterogeneous group of multiple subtypes. To clarify the impact of HPV infection on the development of cervical adenocarcinoma with diverse histological subtypes, we performed a population-based study in Korean women from 15 different institutes for the status of HPV infection in adenocarcinoma of uterine cervix. A total of 432 cervical adenocarcinomas from 1997 to 2001 were reviewed and classified according to the modified WHO classification. For 135 cases, HPV typing was performed with HPV DNA chip (82 cases) and PCR HPV typing (53 cases), using formalin-fixed, paraffin-embedded archival tissue. The overall prevalence of HPV infection in cervical adenocarcinoma was 90%. The infection of HPV 16 and/or HPV 18 accounted for 78% of HPV-positive adenocarcinomas. Multiple HPV types were found in 13% of the cases. The HPV DNA was rarely detected in minimal deviation adenocarcinoma. Interestingly, HPV 16 was a predominant type in endometrioid and villoglandular types, whereas HPV 16 and HPV 18 were detected with equal prevalence in other subtypes. In conclusion, HPV infection, mostly HPV 16 and HPV 18, is highly associated with most of the cervical adenocarcinomas, whereas endometrioid and villoglandular type have a different pattern of HPV infection status. Minimal deviation adenocarcinoma does not seem to be related with HPV infection.

Objective: The purpose of this analysis is to determine whether a significant correlation exists between cyclooxygenase-2 (COX-2) expression and local relapse in a large cohort of patients with T1 to 2N0 laryngeal cancer treated with primary radiation therapy. Methods and Materials: Clinical and molecular analyses were conducted on 123 patients with biopsy-proven T1 to 2N0 laryngeal cancer. Clinical prognostic factors included pretreatment hemoglobin, age, sex, race, T stage, tumor subsite, beam energy, biologically equivalent dose, therapy duration, and treatment date. Molecular prognostic factors included COX-2, p53, and Ki-67 expression. Expression levels were determined by immunohistochemistry on paraffin-embedded tissues arrayed on tissue microarrays. Multivariate analysis was done with the Cox proportional hazards model. Results: Thirty-two patients have locally relapsed, for an actuarial 5-year local relapse-free rate of 70.4%. On multivariate analysis, positive COX-2 expression predicted local relapse after radiation therapy. The relative risk (RR) for local relapse with COX-2 positivity was 2.57 (95% CI, 1.21–5.47; P = .01). Other prognostic factors for local relapse included negative Ki-67 expression (RR = 5.72; 95% CI, 2.04–16.1; P < .001), T2 stage (RR = 2.98; 95% CI, 1.39–6.38; P = .005), and therapy duration greater than 43 days (RR = 6.04; 95% CI, 1.37–26.7; P = .02). Conclusions: Positive COX-2 expression predicts for local relapse in T1 to 2N0 larynx cancer in a multivariate model. This relationship may have potential therapeutic implications regarding the use of COX-2 inhibitors during radiation therapy for optimal outcome.

Purpose To elucidate a relationship between pretreatment hemoglobin and local control in patients with T1-T2N0 larynx cancer treated with radiotherapy. Methods and materials A total of 246 patients with T1-T2N0 cancer of the larynx were included in this analysis. Patients were treated using a median daily fraction of 200 cGy to a total median dose of 66 Gy within 47 days. Prognostic factors included pretreatment hemoglobin, age, gender, race, T stage, tumor subsite, beam energy, biologically equivalent dose, and therapy duration. Results Fifty patients developed local relapse, for an actuarial 5-year relapse-free rate of 77.3%. The actuarial 5-year survival rate was 69.8%. The pretreatment hemoglobin levels were assessed using the following hemoglobin quartiles: 10.1–13.3, 13.4–14.1, 14.2–14.9, and 15.0–18.3 g/dL. On Cox multivariate analysis, the pretreatment hemoglobin level predicted for local failure and poorer overall survival. The relative risk for 5-year local relapse by hemoglobin quartile was 2.70, 2.33, 1.91, and 1.00 ( p = 0.034). The relative risk for poorer 5-year overall survival by hemoglobin quartile was 2.23 1.30, 0.80, and 1.00 ( p Conclusion Pretreatment hemoglobin levels predicted for local control and overall survival for larynx cancer in a multivariate model. This relationship has potential therapeutic implications regarding correcting anemia before the initiation of radiotherapy for optimal outcome.

To determine the effect of orbital decompression surgery on lid retraction as a function of proptosis reduction in the setting of thyroid eye disease.Retrospective interventional case series of all consecutive medial and lateral orbital decompressions performed by the authors for thyroid eye disease from 1999 to 2008. Primary outcome measures included postoperative proptosis and lid retraction.One hundred sixty-five eyes of 89 patients were included. The average amount of proptosis reduction at final follow up (average 30 months) was 4.6 mm. The average improvement in upper lid retraction was 0.9 mm, and the average improvement in lower lid retraction was 0.8 mm. There was a statistically significant correlation (0.12, p = 0.005) between the amount of proptosis reduction and lower lid elevation. No such correlation (-0.010, p = 0.90) was seen for upper lid position. In cases where inferior rectus recession was performed subsequent to decompression surgery (n = 20), the effect of proptosis reduction on lower lid position was negated (correlation -0.01, p = 0.980).A statistically significant correlation exists between the amount of proptosis reduction from orbital decompression surgery and improvement in lower lid retraction. No such correlation exists between proptosis reduction and upper lid retraction. Inferior rectus recession negates the positive effect of orbital decompression on lower lid position.

The present research investigated the role of blood viscosity on flow within a microvascular network to identify the conditions of blood flow stagnation. When the yield stress of blood was less than 0.005 Pa, there were no stagnant regions in the microvasculature. However, when the yield stress increased to 0.05 Pa, stagnant or reduced flow areas began to appear, which grew and expanded rapidly with further increase in the yield stress. Thus, the yield stress determined from blood viscosity profile of a patient can be utilized to evaluate the risk of circulatory impairment.

SummaryAim The peripheral artery questionnaire (PAQ) is a disease-specific health status measure of patients with peripheral artery disease (PAD). Whether the PAQ scores are associated with a PAD diagnosis among patients with symptoms suspicious for PAD is unknown and could help increase the pretest probability of ankle brachial index (ABI) screening among patients with suspicious symptoms. Methods The PAQ was completed by 567 patients evaluated for potential intermittent claudication at six tertiary centres. Demographics, medical history, physical examination findings and the PAQ domain scores were compared with ABI. A diagnostic threshold < 0.90 for a PAD diagnosis was assessed with a ROC of PAQ scores. The correlation between the PAQ Summary Score and ABI was also calculated. Results The PAQ Summary Score was significantly lower in patients with low ABI as compared with those having a normal ABI (37.6 ± 19.0 vs. 70.1 ± 22.7, p