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Background and Aims Screening for hepatopulmonary syndrome in cirrhotic patients is limited due to the need to perform contrast enhanced echocardiography (CEE) and arterial blood gas (ABG) analysis. We aimed to develop a simple and quick method to screen for the presence of intrapulmonary vascular dilation (IPVD) using noninvasive and easily available variables with machine learning (ML) algorithms. Methods Cirrhotic patients were enrolled from our hospital. All eligible patients underwent CEE, ABG analysis and physical examination. We developed a two-step model based on three ML algorithms, namely, adaptive boosting (termed AdaBoost), gradient boosting decision tree (termed GBDT) and eXtreme gradient boosting (termed Xgboost). Noninvasive variables were input in the first step (the NI model), and for the second step (the NIBG model), a combination of noninvasive variables and ABG results were used. Model performance was determined by the area under the curve of receiver operating characteristics (AUCROCs), precision, recall, F1-score and accuracy. Results A total of 193 cirrhotic patients were ultimately analyzed. The AUCROCs of the NI and NIBG models were 0.850 (0.738–0.962) and 0.867 (0.760–0.973), respectively, and both had an accuracy of 87.2%. For both negative and positive cases, the recall values of the NI and NIBG models were both 0.867 (0.760–0.973) and 0.875 (0.771–0.979), respectively, and the precisions were 0.813 (0.690–0.935) and 0.913 (0.825–1.000), respectively. Conclusions We developed a two-step model based on ML using noninvasive variables and ABG results to screen for the presence of IPVD in cirrhotic patients. This model may partly solve the problem of limited access to CEE and ABG by a large numbers of cirrhotic patients.

At present, there is no photographic evidence of splitting of the trapezius and sternocleidomastoid muscles (SCMs), which share a common anlage that extends caudally toward the limb bud in the embryo at a length of 9 mm. Therefore, the aim of the present study was to identify which structures divide the caudal end of the common anlage at the first sign of splitting into two muscles. In 11 mm-long specimens, the SCM and trapezius muscles were identified as a single mesenchymal condensation. In 15 and 18 mm-long specimens, the SCM and trapezius muscles were separated and extended posteriorly and lymphatic tissues appeared in a primitive lateral cervical space surrounded by the SCM (anterior). In 21 mm-long specimens, the lymphatic vessels were dilated and the accompanying afferents were forming connections with the subcutaneous tissue through a space between the SCM and trapezius muscles. In 27 mm-long specimens, cutaneous lymphatic vessels were evident and had entered the deep tissue between the SCM and trapezius muscles. Vascular dilation may be viewed as a result of less mechanical stress or pressure after muscle splitting.

Background In Pompe disease, glycogen deposition results in an augmentation of blood flow and abnormal remodeling, with resultant weakening of the arterial walls, which may result in pathologic dilatation of the cerebral arteries. This complication is rare in patients with late-onset Pompe disease, but it has not been well-described in infantile-onset Pompe disease. The effect of enzyme replacement therapy on this process is not known. Methods We examined clinical and imaging data on two patients who exhibit cerebrovascular arteriopathy: a 14-year-old boy with infantile-onset Pompe disease on enzyme replacement therapy and a 23-year-old woman with late-onset Pompe disease who was also receiving enzyme replacement therapy. Results Our 14-year-old patient exhibits cerebrovascular arteriopathy, primarily proximal and vertebrobasilar, while the 23-year-old patient has a more diffuse pattern. The 14-year-old patient is unique because cerebral dolichoectasias have not been described in infantile-onset Pompe disease. The 23-year-old patient is notable given the age and history of enzyme replacement therapy since age 15 years. Conclusions Dilative cerebral arteriopathy in infantile-onset Pompe disease is novel and similarly atypical is the diffuse vascular dilation seen in our young patient with late-onset Pompe disease, both receiving enzyme replacement therapy. We should be cognizant of the risk of cerebrovascular disease in Pompe disease regardless of the disease variant and enzyme replacement therapy status.

Background: Chronic subdural hematomas (CSDHs) mainly occur in elderly people and usually develop after minor head injuries. CSDH can be cured by a relatively simple burr hole surgery. Rarely reported, hemorrhagic postsurgical complications include subarachnoid, intracerebral, intraventricular, and remote cerebellar hemorrhages. The causes of such uncommon complications are difficult to explain and remain poorly understood. Case Description: We report the case study of an 89-year-old man with CSDH who presented with the right hemiparesis. He underwent burr hole surgery with a closed-drainage system. A computed tomography (CT) scan conducted the following day demonstrated an acute intraventricular hemorrhage and hyperperfusion of the ipsilateral hemisphere. Conclusion: This is a rare case of an acute hematoma in the ventricle following drainage of a CSDH. The likely mechanism of this intraventricular hemorrhage could be that the drainage of the hematoma produced a movement of the ventricle and hemisphere accompanied by hyperperfusion.

Subjectivity in the diagnosis of plus disease in retinopathy of prematurity has prompted the creation of computer programs to objectively measure vascular characteristics. ROPtool is a semiautomated computer program that analyzes retinal vascular dilation and tortuosity. To explore its ability to trace images taken with a FDA-approved, portable, handheld noncontact digital fundus camera (Pictor), we compared ROPtool analysis of Pictor still images acquired by nonophthalmologists to video indirect ophthalmoscopy (VIO) still images acquired by ophthalmologists. ROPtool could trace more Pictor versus VIO images. In addition, receiver operating characteristic curves showed that accuracy for diagnosing pre-plus or plus disease was higher using Pictor versus VIO images.

The objective of this study is to review the current state and role of computer-assisted analysis in diagnosis of plus disease in retinopathy of prematurity. Diagnosis and documentation of retinopathy of prematurity are increasingly being supplemented by digital imaging. The incorporation of computer-aided techniques has the potential to add valuable information and standardization regarding the presence of plus disease, an important criterion in deciding the necessity of treatment of vision-threatening retinopathy of prematurity. A review of literature found that several techniques have been published examining the process and role of computer aided analysis of plus disease in retinopathy of prematurity. These techniques use semiautomated image analysis techniques to evaluate retinal vascular dilation and tortuosity, using calculated parameters to evaluate presence or absence of plus disease. These values are then compared with expert consensus. The study concludes that computer-aided image analysis has the potential to use quantitative and objective criteria to act as a supplemental tool in evaluating for plus disease in the setting of retinopathy of prematurity.

Purpose: To evaluate the ultrawide field fundus fluorescein angiography (UWFA) characteristics of rhegmatogenous retinal detachments (RRDs) and compare the findings with an early treatment diabetic retinopathy study (ETDRS) 7 field (ETDRS7F) overlay. Methods: UWFA (Optos, PLC, Dunfermline, UK) was performed in 10 eyes with macula-off RRDs in 9 patients. The findings of UWFA were compared with that of an overlay of standard ETDRS7F. Results: Vascular dilation, tortuosity of vessels, and blockage of choroidal fluorescence were noted in all eyes in both UWFA and ETDRS7F overlay. Other findings in UWFA and ETDRS7F included peripheral perivascular staining (10 versus 4 eyes), peripheral capillary nonperfusion (CNP) (9 eyes compared to none), vascular loop formation (7 eyes versus none), optic disc hyperfluorescence (5 eyes in both), petaloid leak at macula (2 eyes in both), and neovascularization elsewhere (3 eyes versus none). Conclusions: Peripheral perivascular staining and leak, CNP, and vascular tortuosity are common UWFA features of RRDs. Standard ETDRS7F missed peripheral CNP, peripheral vascular loops, and peripheral retinal new vessels in all eyes compared to UWFA in the current study. Keywords: Capillary nonperfusion, Perivascular leak, Vascular loop, Arteriovenous shunt, Retinal neovascularization, Neovascularization of iris

Purpose: The aim of this study was to define a new pathogenetic classification of diabetic macular edema (DME) and to present the results of its application in common clinical practice. Methods: One hundred and seventy-seven consecutive patients with center-involving DME, central retinal thickness (CRT) ≥250 µm, were prospectively enrolled. A complete ophthalmological examination included best-corrected visual acuity (BCVA) assessment, fundus photography, and spectral-domain optical coherence tomography (OCT). The DME classification was broken down into 4 categories, combining the presence of retinal thickening with the presence/absence of visible vascular dilations and OCT-detectable macular traction. The OCT parameters included were as follows: CRT, subretinal fluid, intraretinal cysts, and hyper- reflective foci (HF). Results: Four subtypes of DME were identified: vasogenic (131 eyes, DME with vascular dilation), nonvasogenic (46 eyes, DME without vascular dilation), tractional (11 eyes), and mixed DME (13 eyes). Vasogenic DME was the pattern mainly represented in each subclass of CRT (< 300, 300–400, and > 400 µm), with tractional DME observed especially with CRT > 400 µm. Internal and external cysts and a greater presence of hard exudates were predominantly found in vasogenic DME, whereas HF was equally distributed in the 4 DME subgroups. Conclusion: The study offers a new pathogenetic classification able to detect significant differences among DME subtypes. A tailored therapeutic approach could take into consideration specific changes associated with the different DME subtypes.

Objectives: The aim of this study is to evaluate the effects of the herbal agent in the prevention and treatment of bacterial cystitis in a rat model. Material and Methods: A total of twenty-eight male Sprague- Dawley rats were divided into four groups. Group-1 constituted the control group (operated and normal saline injected into the bladder, received only drinking water for 7 days); Group-2 constituted the no-treatment group (operated, E.coli J96 strain injected into the bladder, received only drinking water for 7 days); Group-3 constituted the short-term treatment (operated, E.coli J96 strain injected into the bladder, received the herbal agent added into drinking water for 7 days) and Group-4 constituted the long-term treatment (operated, E. coli J96 strain injected into the bladder, received herbal agent added into drinking water for 14 days). At the end of the pre-defined treatment periods of duration, the rats were sacrificed, urine samples collected from the bladder for culture and bladders were harvested for histopathological evaluation. Urine culture results and histopathological findings were comparatively evaluated between the groups. Results: Urine cultures were positive for implanted E. coli strains in 0%, 85.7%, 42.8% and 0% of rats in Group 1, Group 2, Group 3 and Group 4, respectively (p = 0.001). Although histopathological evaluation revealed increased vascular dilation in the bladder specimens obtained from Group 2 and Group 3 (p = 0.028) no significant difference was noticed in level of inflammation (p = 0.610), edema (p = 0.754) and thickness of uroepithelium (p = 0.138). Conclusion: While long term (14 days) treatment with an herbal agent added into the drinking water resulted in complete clearance of urine from E. coli; shorter application of the agent revealed partial clearance. Further clinical studies are needed to support our results.

Purpose To study vascular features detected with spectral domain optical coherence tomography (SD-OCT) in subjects undergoing retinopathy of prematurity (ROP) screening. Design Cross-sectional study. Participants and Controls Fifty-seven premature neonates, 10 with plus disease in at least 1 eye and 47 without plus disease. Methods Bedside noncontact SD-OCT imaging was performed after obtaining parental consent on 97 consecutive infants between January 2009 and September 2012. Fifty-seven subjects (31–49 weeks' post-menstrual age) who had an SD-OCT scan in at least 1 eye showing the edge of the optic nerve and at least 1 major retinal vascular arcade were included. One eye per subject was randomly selected for analysis. Two masked graders evaluated scans for (1) retinal vessel elevation, (2) scalloped retinal layers, (3) hyporeflective vessels, and (4) retinal spaces. To coalesce the weight of these features, a Vascular Abnormality Score by OCT (VASO) was created. For quantitative assessment of vessel elevation, retinal surface maps were created. Main Outcome Measures Prevalence of SD-OCT vascular abnormalities, the VASO, intergrader agreement, and presence of elevation on surface maps. Results From among 67 SD-OCT characteristics that were recorded, the most common characteristics found were vessel elevation (44%), hyporeflective vessels (40%), scalloped layers (22%), and retinal spaces (11%). Features significantly associated with plus disease were vessel elevation ( P = 0.01), hyporeflective vessels ( P = 0.04), and scalloped retinal layers ( P = 0.006). Intragrader agreement was between 74% and 90% for all features. The VASO was significantly higher in subjects with plus disease ( P = 0.0013). On 3-dimensional SD-OCT volumes, eyes with plus disease had greater retinal surface elevation that more often matched en face retinal vascular patterns. Conclusions We present a novel 3-dimensional analysis of vascular and perivascular abnormalities identified in SD-OCT images of eyes with ROP. The SD-OCT characteristics that are more common in eyes with plus disease provide the first in vivo demonstration of the effects of vascular dilation and tortuosity on perivascular tissue. The VASO and surface maps also delineate the severity of vascular pathology in plus disease. Further studies evaluating these findings in eyes with pre-plus versus normal posterior pole vessels may determine the usefulness of SD-OCT in the early detection of vascular abnormalities in ROP.

355 We recently developed a prototype online program for training residents and fellows about retinopathy of prematurity (ROP). We were motivated by the lack of adequate training in this important area.[1‐5] Since ROP is a rapidly progressive disease that can result in blindness, adequate and efficient knowledge regarding ROP should be expected of retina and pediatric ophthalmology fellows and at least available to all ophthalmology residents.[1‐5] Although for teaching purposes it might be best for all training in ROP to take place in the NICU, this is not practical because of constraints in time and resources as well as the safety of affected infants. Fortunately, high quality wide‐angle images of the fundus can now be readily obtained for teaching and telemedicine. In the course of development of our program, it became clear that significant variability still exists among ROP practitioners in grading fundus photographs of infants with ROP. This has been previously discussed among experts.[6‐9] In addition, we realized that the most recent International Classification of ROP[10] does not fully reflect current thought, and that follow‐up schedules recommended in the latest consensus paper[11] do not fully take newly described features of the disease into account. Plus disease is defined as retinal vascular dilation and tortuosity. A standard photograph illustrating plus disease has been used for diagnosis since a consensus agreement for the CRYO‐ROP study in 1988.[12] Recognition of plus disease is critical because ROP diagnosis and treatment guidelines are now dependent on the presence or absence of this finding.[13] Thus, it has important implications for clinical care, development of computer‐based image analysis methods, and also telemedicine systems. Unfortunately, significant subjectivity in determination of plus disease remains a problem.[6,7,9,14,15] Using standard dilated ophthalmoscopy, disagreement was found in 12% of cases regarding a diagnosis of threshold disease in a report based on the CRYO‐ROP and LIGHT‐ROP studies.[14] Using image‐based diagnosis for identification Need for Refinement of International Retinopathy of Prematurity Guidelines and Classifications

Dicephalus, as one kind of congenital defect, is described as an abnormality of incomplete separation of heads, resulting from twinning in humans and animals. From a 4-year-old pregnant goat, a dicephalic malformed male newborn goat was born with cesarean operation. Externally, the dicephalic kid goat had a single body with duplicated heads that were of almost the same size and shape, four eyes, four ears, two mandibles, two maxillae, two forelimbs, and two hind limbs. The kid died 1 h after birth and was dissected for gross anatomical and histopathological studies. Necropsy revealed complete nasopharynx, oropharynx, laryngopharynx, and normal tongue in each head. The palates were grossly complete. It had two esophagi and two tracheas but esophagi became united before the esophageal hiatus and tracheas became united before connecting to the lung. Microscopic lesions including; vasogenic edema, status spongiosis, neuronal necrosis, vascular dilation, and hyperemia in the brains were seen. No gross or histopathological lesion was observed in the internal organs of the kid.

We investigated morphologic features of choroid in the choroidal thickening diseases, including central serous chorioretinopathy (CSC), polypoidal choroidal vasculopathy (PCV), and Vogt-Koyanagi-Harada disease (VKH), by a novel tomographic classification system of the choroid. This cross-sectional study involved 30 patients with active CSC, 30 patients with active PCV, and 27 patients with active VKH, and 30 normal controls. Utilizing enhanced depth imaging optical coherence tomography, we classified the morphology of the choroid into five categories: 1) Standard (S), 2) Dilated outer layer and Attenuated inner layer (DA), 3) Darkened (D), 4) Marbled (M), and 5) Pauci-Vascular (PV) types. Additional tomographic characteristics of the choroid such as choroidal vascular dilation, convolution, scleral invisibility, and choroidal hyper- or hypo-thickening were identified as well. The distribution of five choroidal tomographic morphology and additional tomographic characteristics in each group were analyzed. The DA type was observed in the CSC group more frequently than in the normal control group (53.3% vs 3.3%, P < 0.001). Additional tomographic characteristics, such as choroidal vascular dilation (76.7%), and choroidal hyper-thickening (36.7%), were more prevalent in the CSC group than in the control group. The PCV group showed higher prevalence of DA type (33.3% vs. 3.3%, P = 0.006) than the control group. The VKH group showed a significantly higher frequency of the D type (63.0%), convolution (40.7%), and scleral invisibility (70.4%) than controls (0% for all three findings). In conclusion, CSC and PCV shared common morphologic characteristics of choroid, including dilated outer vascular layer and focally attenuated innermost layer. Dense hypo-reflectivity and convolution of choroid were the specific tomographic markers for acute VKH. A new tomographic classification system of choroid may provide discrimination ability and insight into major pachychoroidopathies.

Aims/Introduction In order to characterize the impaired vascular function in type 2 diabetes (DM) patients, we evaluated the flow-mediated vascular dilation (FMD) with glyceryl trinitrate-mediated vascular dilation (NMD) using ultrasonography. Materials and Methods A total of 111 DM patients and 42 healthy control participants were studied. The maximal dilatation of FMD and NMD (%FMD and %NMD, respectively), the beginning time (T) of dilatation after stimulation and the velocity (V) of the vascular dilatation were also measured. Results Among DM patients, 49% had impaired %NMD, which affects the results of %FMD. In DM patients with normal %NMD, the %FMD was also significantly lower than that in control participants, although the T and the V were not impaired. In contrast, both the T and the V were disturbed in the DM patients with low %NMD. Multiple linear regression analysis showed that %NMD was independently correlated with albuminuria. Our results indicate that the impaired FMD in DM is be affected by low NMD, and impaired endothelial function already exists even in DM patients whose vascular smooth muscle function is still retained, and also albuminuria is the clinical feature of DM with low %NMD. Conclusions Examination of NMD, not only FMD, should be carried out as it offers the possibility of clarifying vascular function in DM patients.

Vascular function, as measured by flow mediated dilation (FMD) and nitroglycerin mediated dilation (NMD), is impaired in COPD. Increases in systemic inflammatory mediators during acute exacerbations of COPD (AECOPD) may further impair vascular function and may account for the increased prevalence of cardiovascular disease in COPD patients. Similarly it may account for the increased morbidity and mortality in COPD patients hospitalized with acute exacerbations. We hypothesized that FMD and NMD would be impaired during AECOPD requiring hospitalization and that vascular function would improve upon AECOPD resolution. We used FMD and NMD to evaluate vascular function in 19 patients hospitalized with AECOPD. FMD and NMD were repeated approximately three months later in 8 of these patients. In these eight patients significant improvements were observed in FMD (2.6 ± 1.5% vs 5.1 ± 2.4%, p = 0.04) and NMD (5.0 ± 2.6% vs 13.3 ± 4.5, p = 0.02) after resolution of their exacerbation. We conclude that endothelial and vascular smooth muscle function is markedly impaired during AECOPD requiring hospitalization and improves following resolution. The systemic vascular impairment that occurs during AECOPD may partially explain the observed increased in cardiac morbidity and mortality that occur in this population.

We report a 54-year-old patient with the association of hepatic dysfunction with cyanosis, severe hypoxemia, platypnea-orthodeoxia, diffuse cutaneous spider nevi, telangiectasia, palmar erythema, digital clubbing and findings of marked intrapulmonary vascular dilation and arterovenous shunt. The diagnosis of hepato-pulmonary-cutaneous syndrome, a term we think more appropriate and inclusive than that of hepato-pulmonary syndrome for this clinicopathological picture, is proposed. The putative underlying mechanism for these connected pulmonary and extrapulmonary syndromic features is discussed.

Plus disease is abnormal retinal vascular dilation and tortuosity, and it is now the primary indication for laser treatment in retinopathy of prematurity (ROP). ROPtool is a computer program that measures retinal arteriolar tortuosity. Our aim was to assess the accuracy of ROPtool's newly developed measurement of retinal vascular width (dilation).ROPtool was used to measure the width of 154 blood vessels in 20 high-quality RetCam images from 20 premature infants. ROPtool's accuracy was determined by comparing results with the mean grades of 2 authors who scored retinal vascular dilation using a 10-point scale.There was very good correlation (r = 0.80) between ROPtool's measurement of retinal vascular dilation and author judgment. Areas under receiver operating characteristics curves for identification of dilation sufficient for plus disease and for pre-plus disease were 0.93 and 0.90, respectively. At an optimal point on the receiver operating characteristics curve, ROPtool's sensitivity for diagnosing dilation sufficient for plus disease was 89% (24/27), and its specificity was 83% (106/127).In addition to measuring retinal vascular tortuosity, ROPtool now accurately measures retinal vascular width in high-quality RetCam images. Application of this technology has the potential to remove subjectivity from the assessment of plus disease.

Editor, W e read with great interest the article by Yang et al. (2013), reporting that central serous chorioretinopathy (CSCR) is significantly associated with the increased subfoveal choroidal thickness and the choroidal vascular dilation. In that article, the possible causes of choroidal vascular dilation, such as choroidal vascular innervation or endothelin-1 or inflammatory cytokines, have been discussed. As it was pointed out, however, the cause of choroidal vascular dilation has remained unclear. Some data in the literature may be helpful to clarify the cause of choroidal vascular dilation. It was shown that choroidal vessel diameter is mainly influenced by the temperature of the chorioretinal complex (Parver 1991); an increase in the temperature of the chorioretinal complex induces choroidal vascular dilation in both a passive (Parver et al. 1980) and a reflexive manner (Parver et al. 1983; Shih et al. 1999). The chorioretinal complex may be heated up by the light absorption in the melanosomes of the retinal pigment epithelium (RPE) and the choroid (Parver 1991). Therefore, an increase in the environmental light intensity increases the temperature of the macula which is at the focal point of the irradiating lights into the eye. If the focal heat is high enough to induce severe choroidal vasodilation but not to burn the tissue, and if the rate of the heat accumulation is higher than the rate of adaptation of choroidal circulation to bright lights, it may result in a focal serous leakage from the dilated choroidal vessels. In conclusion, CSCR may result from a response of choroidal vessels to an acute increase in the environmental light intensity. The increase in the light intensity may increase the choroidal temperature at the focal point of the irradiating lights into the eye. The resultant focal heat may induce local changes in the choroidal vessels leading to a focal leakage from the choroidal vessels and CSCR. However, this hypothesis should be experimentally tested. Future clinical researches should consider the history of acute increase in the intensity of lights to which patients with CSCR are exposed. Assessment of the relationship of increases in total time spent outdoors with prevalence of CSCR may be helpful. If the hypothesis is proved to be correct, it may be helpful to design more efficient strategies to prevent and manage CSCR.

Sparassis crispa is an edible mushroom recently cultivable in Japan. Polysaccharide fractions were prepared from the cultured S. crispa by repeated extraction with hot water (SCHWE), cold NaOH (SCCA), and then hot NaOH (SCHA). HWE was further separated by 1 volume (SCHWE1v) or 4 volumes (SCHWE4v) of ethanol-precipitable fractions. By chemical, enzymic, and NMR analyses, the primary structures of SCHWE1v, SCCA, and SCHA were 6-branched 1,3-beta-glucan, having one branch in approximately every third mainchain unit. All of these fractions showed antitumor activity to the solid form of Sarcoma 180 in ICR mice with strong vascular dilation and hemorrhage reaction. These fractions also showed enhanced hematopoietic response to cyclophosphamide induced leukopenic mice following intraperitoneal or peroral administration.

A case report of a 12-year-old spayed female Golden Retriever with a 4-month history of persistent diffuse erythema involving the right and left antebrachia is presented. Cutaneous biopsies revealed superficial dermal vascular dilation and proliferation with moderate epidermal acanthosis. Diagnostic tests failed to reveal an underlying aetiology. Telangiectasia is defined as a permanent dilation of pre-existing blood vessels creating small focal lesions. Generalized essential telangiectasia of humans is common in women of middle-age and can involve entire segments of the body. Lesions predominantly affect the extremities and can persist for years without any systemic effects. The cutaneous lesions in this case have remained static for 3 years with no manifestation of systemic signs. A diagnosis of idiopathic telangiectasia was made based on the clinical and histological findings in the dog of this report. The lesions described in this dog resemble generalized essential telangiectasia of humans.

It has been deduced (Lancaster, Proc. Natl. Acad. Sci. USA 91 (1994) 8137-8141), from a consideration of Fick's law of diffusion, that the very effective scavenging of nitric oxide (NO) by haemoglobin in red blood cells prevents any NO from endothelial cells migrating outwards into vascular smooth muscle. This conclusion has led some authors to suggest that endothelium-derived relaxing factor (EDRF) is not free NO. We have reconsidered the application of Fick's law to the migration of NO in the vasculature, making allowance for the reaction of NO with guanylate cyclase and for the layer of red blood-free plasma next to the endothelium. The source of NO is taken as an infinite cylinder. Calculations for vessels of various diameters indicate that a substantial amount of NO migrates outwards in spite of very effective scavenging by haemoglobin and that the relative amount of NO migrating outwards depends upon the radius of the vessel. The view that locally produced NO is not responsible for vascular dilation has not been sustained.

In autumn 1993, an outbreak of gill disease occurred in Atlantic salmon, Salmo salar L., smolts farmed in the Huon estuary in southern Tasmania, Australia. Histologically, the presumptive primary lesion appeared as focal, sometimes full thickness, gill necrosis, which showed no host reaction in the initial stages. Healing of these damaged areas gave rise to conspicuous expanded tips or clubbing of gill filaments. The term clubbing and necrosis gill (CNG) syndrome is suggested to include both these histological features. Fusion of lamellae proximally along the filament, often with vascular dilation, was also a feature of the condition. Similar lesions have been described previously in the literature, but the initial necrosis followed by the very prominent clubbing of filaments was sufficiently different from previous descriptions to warrant designation of this condition as a distinct entity.

To investigate whether parameters of retinal vascular dilation and/or tortuosity calculated by ROPtool software can help to predict, prior to diagnosis of plus disease, whether laser will be needed for treatment of retinopathy of prematurity (ROP).Video indirect ophthalmoscopy recordings were obtained during routine ROP examinations. One posterior pole still image of one eye was selected from each examination for each infant. ROPtool was used to calculate vessel dilation, tortuosity, and the sum of adjusted indices (SAI, combining dilation and tortuosity) for each image. The following values were calculated for each vessel characteristic: maximum value from any one vessel across all examinations, largest increase per week in maximum value, highest mean value of all vessels from any one examination, and largest increase per week in mean value. These parameters were compared between infants who eventually received laser and those who did not.Medians for maximum tortuosity indices were, for the eventual laser group (n = 28), 8.92 tortuosity units and, for the no laser group (n = 56), 6.87 (P0.001). Medians for highest mean tortuosity indices were 4.95 tortuosity units for the eventual laser group and 3.66 for the no laser group (P0.001). Parameters involving dilation and SAI did not differ significantly between groups. In multivariable analysis, highest mean tortuosity was associated with need for laser (P = 0.003).ROPtool analysis of tortuosity parameters from indirect ophthalmoscopy images can help predict need for laser in ROP.

A 38-year-old woman developed bilateral carotid cavernous fistulae (CCF) following a motor vehicle collision. Her initial ophthalmologic findings included periorbital edema, palsies of the left oculomotor and abducens nerves, and residual dilated pupils. She subsequently developed significant optic disc edema and retinal vascular dilation bilaterally. Patients with similar injuries typically require neurosurgical or vascular intervention. In this case, the patient’s signs resolved spontaneously by 21 months after onset, leaving no residual ocular deficits.

Ultra-wideband signals have a variety of applications. An upcoming medical application is the detection of the heart rate of patients. However, current UWB systems provide poor resolution and are only able to detect vessels with a large diameter, e.g. the aorta. The detection and quantification of vascular dilation of thinner vessels is essential to develop wearable ultra-wideband based devices for real-time detection of cardiovascular conditions of the extremities. The reflection and transmission processes of those signals within inhomogeneous bodies are complex and their prediction is challenging. In this paper, we present an experimental setup (UWB system; phantom) for the detection of vascular dilation within soft tissues. Furthermore, we suggest a theoretical simulation model for the prediction of the reflection of ultra-wideband pulses and compare these simulated predictions to results of measurements within the phantom. The results verify that we are able to identify vascular dilation within the simulation model and the experimental setup, depending on the depth of the vessel (20 mm, 40 mm, 60 mm).

To assess longitudinal changes and determine their angiographic risk factors in the fellow eyes of patients with unilateral polypoidal choroidal vasculopathy (PCV).We reviewed the medical records of 47 patients with unilateral PCV, all of whom had completed at least 12 months of follow-up. The angiographic features were evaluated including the development of active PCV over time, choroidal vessel dilation, choroidal vascular hyperpermeability, the branching vascular network (BVN) and late geographic hyperfluorescence (LGH), which was defined as a well-demarcated geographic hyperfluorescent lesion on late-phase on indocyanine green angiography (ICGA).The mean follow-up period was 30.3 ± 12.2 months. Among 47 fellow eyes, 24 (51.1%) had choroidal vascular dilation, 27 (57.4%) had choroidal vascular hyperpermeability, six (12.8%) had BVN and 23 (48.9%) had LGH. The development of active PCV was noted in nine fellow eyes (19.1%), all of which had exhibited LGH at baseline. However, PCV did not develop in eyes without features of LGH at baseline (p0.001). The development of PCV was noted in three eyes with notification of BVN at baseline; however, PCV also developed in six eyes without apparent features of BVN (p=0.08).The presence of LGH on ICGA in the fellow eye appears to be a significant risk factor for the development of active PCV and may constitute the diagnosis of preclinical PCV.

Background: Hypertension is associated with remodeling and mechanical alterations of resistance arteries. Numerous studies have investigated the mechanical and morphometric properties of small arteries obtained from hypertensive animals and humans. However, the functional properties of resistance arteries from normotensive and hypertensive subjects have only been examined under normotensive conditions. The objective of the present study was to evaluate the dilation responses of small mesenteric arteries (SMA) from spontaneously hypertensive rats (SHR) at various levels of intraluminal pressure. Methods and Results: SMA segments from Wistar Kyoto (WKY) rats and SHR were pressurized using pressure myography. Endothelium-dependent and -independent dilation responses of the SMA were examined under 3 different intravascular pressures (50, 80 and 120 mmHg). Endothelium-dependent dilation was evaluated by measuring vasodilator responses to increasing doses of acetylcholine or increases in intraluminal flow rate. Endothelium-independent vasodilator function was examined by using sodium nitroprusside. The results indicate that both endothelium-dependent and -independent dilation responses of SMA from WKY progressively decrease with increased intravascular pressure. In contrast, all dilatation responses of the SMA from SHR were enhanced at higher intraluminal pressures. Conclusions: These findings of differential sensitivity to luminal pressure should be considered during in vitro examination of vessels from normotensive and hypertensive subjects. (Circ J 2009; 73: 2091-2097)

The aim of this work is to analyze endothelium nitric oxide (NO) release in patients undergoing continu- ous or pulsatile flow cardiopulmonary bypass (CPB). Nine patients operated under continuous flow CPB, and nine patients on pulsatile flow CPB were enrolled. Plasma samples were withdrawn for the chemiluminescence detec- tion of nitrite and nitrate. Moreover the cellular component was withdrawn for the detection of nitric oxide synthase (NOS) activity in the erythrocytes, and an estimation of systemic inflammatory response was carried out. Significant reduction in the intraoperative concentration with respect to the preoperative was observed only under continuous flow CPB for both nitrite and NOx (nitrite + nitrate) con- centration (P = 0.010 and P = 0.016, respectively). Signifi- cant difference in intraoperative nitrite concentration was also observed between the groups (P = 0.012). Finally, erythrocytes showed a certain endothelial NOS activity, which did not differ between the groups, and no differences in the inflammatory response were pointed out. The signifi- cant reduction of NO2 - concentration under continuous perfusion revealed the strong connection among perfusion modality, endothelial NO release, and plasmatic nitrite concentration. The similar erythrocyte eNOS activity between the groups revealed that the differences in blood NO metabolites are mainly ascribable to the endothelium release. Key Words: Vascular dilation—Nitric oxide release—Cardiopulmonary bypass—Continuous flow— Pulsatile flow.

Background Alterations in intravascular pressure can affect vascular function and the morphological properties of arteries. Although it has been shown that a transient elevation of blood pressure impairs endothelium-dependent dilation in small arteries, the vascular dilation responses during high intravascular pressure have not yet been investigated. Methods and Results Using pressure myography, the endothelium-dependent and -independent dilation responses of small mesenteric arteries of rats were examined under 3 different intravascular pressure conditions (50, 80 and 120 mmHg). Endothelium-dependent dilation was evaluated by measuring vasodilator responses to increasing doses of acetylcholine (ACh, 10-9 to 10-4 mol/L) or increases in intraluminal flow (7-36 μl/min). Endothelium-independent vasodilator function was examined by using sodium nitroprusside (SNP, 10-9 to 10-4 mol/L). Flow-mediated dilation was significantly attenuated at 120 mmHg whereas ACh-induced dilation was progressively decreased with increases in intravascular pressure (at 80 and 120 mmHg). Significant attenuation in the vasodilator response to SNP was also observed at 80 and 120 mmHg. Conclusion Endothelium-dependent and-independent dilation responses are progressively attenuated with acute increases in intravascular pressure. (Circ J 2008; 72: 482 - 486)

To the Editor: Recently in this journal, a report by James et al1 was paired with an editorial by Gladwin and Schechter.2 However, the invited commentators did not discuss the novel finding of James et al that hemoglobin (Hb) glycosylation in diabetes impairs vasorelaxation by altering nitric oxide (NO) binding to Hb thiols. Instead, the guest editors focused on vascular dilation by red blood cells (RBCs) in the absence of disease, for which they now state that there are “two competing mechanisms.” This imposes an unnecessary dichotomy on our emerging understanding of how RBCs dilate blood vessels with NO, as in hypoxic dilation. If the two alternatives in a dichotomy are not the sole alternatives, or are not mutually exclusive, or if neither is true, the dichotomy is false and forces sincere dissenters into extreme points of view, allows the dichotomists to frame the debate improperly, and wastes intellectual resources. All this impedes scientific advance. This dialectic …

Previous studies suggest that hypnotizability represents a protective factor against the cardiac effects of cognitive stress and that hypnosis prevents vascular stress-induced modifications in highly hypnotizable individuals. The aim of the experiment was to investigate whether a similar effect at vascular level is present in awake subjects with a high (Highs) and a low (Lows) hypnotic susceptibility. Thus, brachial artery post-ischaemic flow-mediated vascular dilation (FMD) was evaluated non-invasively by ultrasound methodology during cognitive stress (mental computation) in Highs and Lows. Results showed that Highs, similarly to that previously observed in hypnotized Highs and in contrast with Lows, did not exhibit any stress-related endothelial dysfunction (FMD decrement). Thus, hypnotizability should be considered a protective factor against vascular disease.

El autor estudia las características del fondo del ojo en 50 sujetos aclimatados a 4,540 mts. sobre el nivel del mar, habiéndose encontrando cambios oftalmoscópicos notorios. Las modificaciones del fondo del ojo que dan la característica peculiar en los hombres aclimatados a las grandes alturas son principalmente de origen vascular: Hiperemia papilar, dilatación y tortuosidad vascular, gran ingurgitación venosa, retina oscura hiperémica y brillante, mácula con aspecto discoide, oscura y con reflejos aumentados y gran vascularización perimacular. Estos cambios se deben a la condición hipóxica climática constante en la que viven y se realizan en función del aumento de la capacidad de oxigenación y de la superficie de difusión de la sangre para mejorar la nutrición de la retina; interviniendo factores hematológicos como la hipervolemia. policitemia y aumento de la cifra de Hb. reducida y la vasodilatación, ya demostrada en otros órganos. La gran variabilidad de las modificaciones fundoscópicas hace difícil la determinación del tiempo requerido para su aparición en los sujetos que ascienden del llano, y su reversibilidad, en aquellos que descienden y permanecen a nivel del mar, no ha sido probada.

Purpose. Vascular endothelial growth factor (VEGF) causes widespread retinal vascular dilation, produces breakdown of the blood-retinal barrier, and is implicated in ocular neovascularization (NV). Basic fibroblast growth factor (bFGF) also has been implicated in the production of ocular NV. This study was performed to investigate the ability of simultaneous sustained intravitreal release of both VEGF and bFGF to induce robust retinal NV in the rabbit. Methods. Intravitreal implantation of sustained-release Hydron polymeric pellets containing both 20 μg of VEGF and 20 μg of bFGF was performed on adult male Dutch belted rabbits. In other animals either 20 μg or 50 μg bFGF-containing pellets was implanted intravitreally; also, either 20 μg VEGF or 50 μg VEGF-containing pellets was implanted. Control rabbits received either blank polymeric pellets or a pellet containing 30 μg bovine serum albumin. Eyes were examined by indirect ophthalmoscopy after surgery at 24 hrs, 48 hrs, 4 days, 7 days, 14 days, 21 days, and 28 days. Findings were documented by color fundus photography and fluorescein angiography (FA). Eyes were enucleated and prepared for histologic analysis at 28 days following intravitreal implantation of the VEGF/bFGF-containing pellets. Results. In all eyes implanted with VEGF/bFGF pellets, dilation and tortuosity of existing blood vessels were observed within 48 hrs after pellet implantation. The progression of retinal vascular changes was rapid and occurred over the entire optic disk and medullary rays between 4 and 7 days. Hemorrhage occurred as early as 14 days after VEGF/bFGF pellet implantation. In eyes with massive hemorrhage, total traction retinal detachment developed after the second week. The presence of abnormal tissues at the vitreo-retinal interface within 28 days was demonstrated by light microscopy while FA showed profuse leakage of dye from anomalous vessels within the first week. Neither bFGF-exposed eyes nor control eyes showed any vascular changes. Eyes that received only VEGF-containing pellets exhibited tortuosity of existing vessels, but neither hemorrhaging nor retinal detachment occurred. Conclusions. These results demonstrate that retinal vascular changes leading to hemorrhaging is produced rapidly in the rabbit by simultaneous intravitreal release of both VEGF and bFGF. Understanding how these growth factors induce retinal NV may suggest novel therapeutic treatment strategies.

Background: Plus disease, one of the most important prognostic indicators in retinopathy of prematurity (ROP), is designated as present or absent. A grading system based on comparison with standard, high-quality color photographs may be useful to more accurately describe the spectrum of vascular dilation and tortuosity preceding plus disease, but it is of practical value only if it has prognostic significance. We hypothesized that grading of "pre-plus" vascular changes can identify eyes at risk for progression to vision-threatening ROP. Methods: Video clips of posterior pole images captured at the examination closest to 33 weeks' postconceptional age of 32 infants screened during an 18-month period were randomized. Two masked examiners viewed and graded the images in comparison with standard photographs representative of 5 distinct grades of retinal vascular dilation and tortuosity. A case-control design was used to compare the incidence of progression to stage 3 ROP, development of plus disease, and requirement of laser treatment between infants with normal posterior poles and those judged to have early dilation and tortuosity insufficient for plus disease. Results: Of the 8 patients with mild vascular dilation and tortuosity insufficient for plus disease, 5 (63%) eventually required laser treatment, 4 (50%) later developed stage 3 ROP, and 5 (63%) progressed to plus disease. Of the 24 patients with normal posterior poles, none required laser treatment, 2 (8%) developed stage 3 ROP, and none progressed to plus disease. The group with mild vascular dilation and tortuosity had a significantly higher incidence of progression to laser treatment ( P =.0003), stage 3 ROP ( P =.027), and plus disease ( P =.0003). Conclusions: Early vascular dilation and tortuosity judged insufficient for plus disease have prognostic significance in the early course of ROP. A grading system that uses standard, high-quality color photographs representing the spectrum of "pre-plus" vascular changes has potential utility in both the clinical and research settings. (J AAPOS 2000;4:224–9)

Routine laparoscopic cholangiography and sonography have been recommended for identification of unsuspected bile duct stones in laparoscopic cholecystectomy. The increased prevalence of retained stones seems, however, to confirm that cholangiography has been used rather selectively. The aim of this study was to investigate the kind and extent of a possible correlation between inflammatory changes in the bile duct mucosa and the hepatoduodenal ligament in patients with and without unsuspected bile duct stones. Sixty-eight patients, without symptoms or signs of bile duct stones in their case histories, laboratory findings, and preoperative sonography results, underwent laparoscopic cholecystectomy for symptomatic gallstone disease and diagnostic transcystic cholangiography and cholangioscopy. The initial step at laparoscopy revealed edema of the periductal loose tissue, vascular dilation, and petechiae on the external surface of the distal portion of the extrahepatic bile duct in 47 of 68 patients. Cholangioscopy revealed inflammatory changes in the mucosa of the distal and sphincteric portions of the extrahepatic bile duct in 45 of 47 patients, and unsuspected ductal stones were identified in 41 of these 45 patients. Neither the external surface of the bile duct nor its mucosa exhibited any signs of inflammation in the 21 remaining patients (controls), all of whom showed stone-free bile ducts. Inflammatory changes in the bile duct mucosa, occurring along with unsuspected mobile ductal stones in this study, were reflected on the external surface of the bile duct with a specificity of 87%. The changes in the external surface of the bile duct can be recognized at the initial inspection in laparoscopic cholecystectomy, as in this study, and indicate that more accurate diagnostic procedures to identify unsuspected ductal stones should be used.

With the use of a laboratory model, arterial and intracranial pressure signals were obtained under conditions of varying depths of hypercapnia ranging from normocapnia to deep hypercapnia. Also, with the use of a closed cranial window, measures of cerebral arteriolar diameter and estimates of cerebral venous flow were obtained. The correlation of the intracranial and arterial pressure signals, arteriolar diameter, and estimates of venous flow exhibit a dose-dependent characteristic by increasing monotonically with increasing progressive states of increasing hypercapnia. These results indicate that the correlation between intracranial and arterial pressure signals provides an estimate of the gauge of the cerebral vasculature.