Optical coherence tomography.

Optical coherence tomography (OCT) is a non-contact method for imaging the topological and internal microstructure of samples in three dimensions. OCT can be configured as a conventional microscope, as an ophthalmic scanner, or using endoscopes and small diameter catheters for accessing internal biological organs. In this Primer, we describe the principles underpinning the different instrument configurations that are tailored to distinct imaging applications and explain the origin of signal, based on light scattering and propagation. Although OCT has been used for imaging inanimate objects, we focus our discussion on biological and medical imaging. We examine the signal processing methods and algorithms that make OCT exquisitely sensitive to reflections as weak as just a few photons and that reveal functional information in addition to structure. Image processing, display and interpretation, which are all critical for effective biomedical imaging, are discussed in the context of specific applications. Finally, we consider image artifacts and limitations that commonly arise and reflect on future advances and opportunities.

Experimental verification of principal losses in a regulatory particulate matter emissions sampling system for aircraft turbine engines.

A sampling system for measuring emissions of nonvolatile particulate matter (nvPM) from aircraft gas turbine engines has been developed to replace the use of smoke number and is used for international regulatory purposes. This sampling system can be up to 35 m in length. The sampling system length in addition to the volatile particle remover (VPR) and other sampling system components lead to substantial particle losses, which are a function of the particle size distribution, ranging from 50 to 90% for particle number concentrations and 10-50% for particle mass concentrations. The particle size distribution is dependent on engine technology, operating point, and fuel composition. Any nvPM emissions measurement bias caused by the sampling system will lead to unrepresentative emissions measurements which limit the method as a universal metric. Hence, a method to estimate size dependent sampling system losses using the system parameters and the measured mass and number concentrations was also developed (SAE 2017; SAE 2019). An assessment of the particle losses in two principal components used in ARP6481 (SAE 2019) was conducted during the VAriable Response In Aircraft nvPM Testing (VARIAnT) 2 campaign. Measurements were made on the 25-meter sample line portion of the system using multiple, well characterized particle sizing instruments to obtain the penetration efficiencies. An agreement of ± 15% was obtained between the measured and the ARP6481 method penetrations for the 25-meter sample line portion of the system. Measurements of VPR penetration efficiency were also made to verify its performance for aviation nvPM number. The research also demonstrated the difficulty of making system loss measurements and substantiates the E-31 decision to predict rather than measure system losses.

Multicenter study on the diagnostic performance of multiframe volumetric laser endomicroscopy targets for Barrett's esophagus neoplasia with histopathology correlation.

Volumetric laser endomicroscopy (VLE) has been shown to improve detection of early neoplasia in Barrett's esophagus (BE). However, diagnostic performance using histopathology-correlated VLE regions of interest (ROIs) has not been adequately studied. We evaluated the diagnostic accuracy of VLE assessors for identification of early BE neoplasia in histopathology-correlated VLE ROIs. In total, 191 ROIs (120 nondysplastic and 71 neoplastic) from 50 BE patients were evaluated in a random order using a web-based module. All ROIs contained histopathology correlations enabled by VLE laser marking. Assessors were blinded to endoscopic BE images and histology. ROIs were first scored as nondysplastic or neoplastic. Level of confidence was assigned to the predicted diagnosis. Outcome measures were: (i) diagnostic performance of VLE assessors for identification of BE neoplasia in all VLE ROIs, defined as accuracy, sensitivity, and specificity; (ii) diagnostic performance of VLE assessors for only high level of confidence predictions; and (iii) interobserver agreement. Accuracy, sensitivity, and specificity for BE neoplasia identification were 79% (confidence interval [CI], 75-83), 75% (CI, 71-79), and 81% (CI, 76-86), respectively. When neoplasia was identified with a high level of confidence, accuracy, sensitivity, and specificity were 88%, 83%, and 90%, respectively. The overall strength of interobserver agreement was fair (k = 0.29). VLE assessors can identify BE neoplasia with reasonable diagnostic accuracy in histopathology-correlated VLE ROIs, and accuracy is enhanced when BE neoplasia is identified with high level of confidence. Future work should focus on renewed VLE image reviewing criteria and real-time automatic assessment of VLE scans.

Interpretation of volumetric laser endomicroscopy in Barrett's esophagus using image enhancement software.

Image interpretation of Barrett's esophagus (BE) with volumetric laser endomicroscopy (VLE) can be enhanced by image processing software that highlights established features using a color-graded scale (intelligent real-time image segmentation, IRIS). This study aims to provide a description of IRIS features of various gastroesophageal tissue types using histologic correlation. A database of 80 VLE laser-marked targets with histologic correlation was reviewed for various tissue types. IRIS was applied off-line to the VLE scans, laser-marked targets were identified, and feature review was performed. Squamous epithelium targets (N = 7) showed IRIS layered architecture with lack of surface hyper-reflectivity and epithelial glands. Gastric cardia targets (N = 10) showed absent layering (100%) and surface hyper-reflectivity with epithelial glands (40%). Nondysplastic BE targets (N = 39) showed surface hyper-reflectivity (64%), epithelial glands (51%), and lack of layering (74%). Targets of BE with early neoplasia (N = 24), showed surface hyper-reflectivity (96%), epithelial glands (67%), and lack of layering (96%). IRIS features that characterize each tissue type appear to mirror the nonenhanced VLE counterparts that define them.

Food impaction: etiology over 35 years and association with eosinophilic esophagitis.

With the emergence of eosinophilic esophagitis (EoE) as a common cause of food impaction (FI) and a presumed increase in incidence of EoE in the population, the effect on the incidence of FI has not been well described. The aim of this study is to describe the incidence of FI and endoscopic findings in these patients and the association with EoE. A population-based retrospective chart review of the Rochester Epidemiology Project database was performed to identify all patients within Olmsted County that presented with FI from 1976 to 2012. A review of all endoscopic findings, biopsy results, and demographic data was performed. 497 patients were identified with FI from 1976 to 2012. The overall incidence of FI has changed from 1976 to 2012 (Fig. 1) (P < 0.001). The peak incidence of 17.12 per 100,000 people occurred in the time period 1995 to 2000. Both the incidence of comorbid gastroesophageal reflux disease (GERD) and proton pump inhibitor (PPI) use increased over the time period of the study (P < 0.001 for both). Of these patients, 188 (46.7%) had no abnormalities on their endoscopy. The most common endoscopic finding was stricture in 71 (17.6%) patients followed closely by Schatzki's ring in 68 (16.9%) patients. 139 patients had biopsies performed within 2 years of FI and 50 (36.0%) of those were diagnosed with EoE. We present for the first time the changing incidence of FI over the last 35 years in a population-based setting. We also demonstrate the rise of EoE as an important clinical consideration in patients with FI.

Clutch cutter is a safe device for performing endoscopic submucosal dissection of superficial esophageal neoplasms: a western experience.

Although the endoscopic submucosal dissection (ESD) has been established to be more efficacious in the treatment of superficial gastrointestinal neoplasia than the piecemeal resection, its use is still limited due to the concern about serious adverse events particularly in the west. Newer ESD knives have been developed that have been said to be safer than the first-generation devices. We aimed to report a Western single center experience regarding the initial safety and performance of ESD for superficial esophageal neoplasia treated with the Clutch Cutter (DP2618DT; Fujifilm Corporation, Tokyo, Japan). Our main outcome was safety in terms of bleeding or perforation. Secondary outcomes included en bloc resection and the R0 resection. Fourteen patients with superficial esophageal neoplasia underwent 15 ESDs using the Clutch Cutter. The mean age was 65 ± 16.7 years and 10 (71.4%) males. Eight (57%) patients had esophageal adenocarcinoma, 3 (21.4%) had high-grade dysplasia, 1 (7%) had nodular low-grade dysplasia, and 2 (14.3%) had squamous cell carcinoma. Mild anticipated intraprocedural bleeding was present with most procedures. However, no significant postoperative bleeding or perforation was encountered. One patient had mild chest pain postprocedure. En bloc resection was achieved in all lesions 100%. Histological R0 was achieved in 5/12 lesions (41.6%). The mean length of the resected area was 24.8 ± 13 mm (IQR: 17-30 mm). All patients were safely discharged home after overnight observation. In conclusion, this is the largest series of esophageal ESD using the multimodal Clutch Cutter in the United States; we found that the device effectively achieved en bloc resection of superficial esophageal neoplasia without significant adverse events. The use of the Clutch Cutter should be considered as one option to minimize adverse events during ESD in the Western population.

Structural and spectroscopic studies of a rare non-oxido V(v) complex crystallized from aqueous solution.

A non-oxido V(v) complex with glutaroimide-dioxime (H3L), a ligand for recovering uranium from seawater, was synthesized from aqueous solution as Na[V(L)2]·2H2O, and the structure determined by X-ray diffraction. It is the first non-oxido V(v) complex that has been directly synthesized in and crystallized from aqueous solution. The distorted octahedral structure contains two fully deprotonated ligands (L3-) coordinating to V5+, each in a tridentate mode via the imide N (R V-N = 1.96 Å) and oxime O atoms (R V-O = 1.87-1.90 Å). Using 17O-labelled vanadate as the starting material, concurrent 17O/51V/1H/13C NMR, in conjunction with ESI-MS, unprecedentedly demonstrated the stepwise displacement of the oxido V[double bond, length as m-dash]O bonds by glutaroimide-dioxime and verified the existence of the "bare" V5+/glutaroimide-dioxime complex, [V(L)2]-, in aqueous solution. In addition, the crystal structure of an intermediate 1 : 1 V(v)/glutaroimide-dioxime complex, [VO2(HL)]-, in which the oxido bonds of vanadate are only partially displaced, corroborates the observations by NMR and ESI-MS. Results from this work provide important insights into the strong sorption of vanadium on poly(amidoxime) sorbents in the recovery of uranium from seawater. Also, because vanadium plays important roles in biological systems, the syntheses of the oxido and non-oxido V5+ complexes and the unprecedented demonstration of the displacement of the oxido V[double bond, length as m-dash]O bonds help with the on-going efforts to develop new vanadium compounds that could be of importance in biological applications.

Predictive biomarkers for Barrett's esophagus: so near and yet so far.

Barrett's esophagus (BE) is the strongest risk factor for the development of esophageal adenocarcinoma. However, the risk of cancer progression is difficult to ascertain in individuals, as a significant number of patients with BE do not necessarily progress to esophageal adenocarcinoma. There are several issues with the current strategy of using dysplasia as a marker of disease progression. It is subject to sampling error during biopsy acquisition and interobserver variability among gastrointestinal pathologists. Ideal biomarkers with high sensitivity and specificity are needed to accurately detect high-risk BE patients for early intervention and appropriate cost-effective surveillance. To date, there are no available molecular tests in routine clinical practice despite known genetic and epigenetic aberrations in the Barrett's epithelium. In this review, we present potential biomarkers for the prediction of malignant progression in BE. These include markers of genomic instability, tumor suppressor loci abnormalities, epigenetic changes, proliferation markers, cell cycle predictors, and immunohistochemical markers. Further work in translating biomarkers for routine clinical use may eventually lead to accurate risk stratification.

Galactorrhoea. Report of a case in a male patient.

Galactorrhoea is the secretion of milk from the breast in non-physiological circumstances. It is rare in males of any age. We report the case of an adult male who presented with enlarged breasts and tenderness of the left breast, with milky discharge. Bilateral subcutaneous mastectomies were performed.

Metastases from carcinoma of the breast involving the central nervous system.

A general discussion is made of the incidence, biological behaviour, diagnosis and management of metastatic disease involving the central nervous system secondary to malignant disease of the breast. Illustrative case histories selected from patients treated for carcinoma of the breast in the period 1978-88 are included.

Role of prostaglandins in controlling plasma fibronectin levels.

Fibronectin is a normal glycoprotein component of plasma, interstitial fluid, and extracellular matrix which has binding sites for collagen, gelatin, actin, glycosaminoglycans, fibrin, Staphylococcus aureus, and some cells. Since it is a dimer, it can crosslink these substances to each other or to extracellular components of basement membrane, thereby affecting many physiological processes. The level of circulating fibronectin is markedly reduced following even moderate blunt or operative trauma, thermal injury, starvation, advanced cancers, hemorrhage, etc. Replacement therapy has been tried with some success in patients who become septic following multiple injuries. The reduction in plasma fibronectin has been attributed to several causes including consumption by binding to cell debris at the site of injury, binding to circulating cell debris and its subsequent removal by elements of the phagocytic system, and degradation by proteolytic cleavage. However, the amount of fibronectin removed from circulation raises some question about this. In this paper, we used indomethacin, ibuprofen, imidazole, and essential fatty acid deprivation to inhibit the synthesis of prostaglandins in young adult rats. Thirty minutes after ip administration of one of the inhibitors, the rats were subjected to a midline laparotomy and mild intestinal manipulation. Blood samples were taken at intervals following closure of the incision and analyzed for fibronectin. In all cases, the normal decline in plasma fibronectin seen in untreated rats was abrogated by inhibiting prostaglandin synthesis. Since imidazole specifically inhibits thromboxane A synthesis, this strongly suggests that thromboxanes directly or indirectly control the trauma-induced reduction in circulating fibronectin. This was confirmed by ip injection of thromboxane into the rats which resulted in a decline in plasma fibronectin levels.

Fibronectin enhances healing of excised wounds in rats.

Fibronectin (Fn) is a normal plasma and extracellular matrix glycoprotein that is involved in each phase of wound healing. For example, it is incorporated into both fibrin and collagen fibers; it opsonizes circulating tissue debris for removal by the reticuloendothelial system; it is used by macrophages, fibroblasts, and epithelial cells to move into the wound; and fragments of Fn are chemotactic for fibroblasts. In this study, experiments with rats showed that excised lesions treated with Fn healed more rapidly than paired control lesions treated with the carrier alone. Applications of Fn once a day for two days were as effective in speeding healing as twice-daily applications of Fn for 12 days. A single treatment with Fn soon after the initial injury was nearly as effective as more prolonged treatment regimens.

Iontophoresis of vidarabine monophosphate for herpes orolabialis.

The cutaneous application of antiviral agents was studied by iontophoresis, a process that increases penetration of most drugs 20- to 60-fold. Twenty-seven subjects with vesicular orolabial herpes were treated one time in a double-blind, placebo-controlled clinical study: nine received vidarabine monophosphate (ara-AMP), nine received acyclovir (ACV), and nine received NaCl. Ara-AMP-treated lesions yielded lower titers of virus after 24 hr compared with lesions treated with NaCl or ACV (P less than .05). Ara-AMP significantly decreased the duration of shedding of virus (P less than .05) and time to dry crust (P less than .05) compared with the other two agents. There was a trend toward decreased healing time after ara-AMP treatment.

Local recurrence of carcinoma of the breast.

The following consideration of the forms and significance of local recurrence after mastectomy is based on the experience gained during the follow-up study of approximately one thousand cases of carcinoma of the breast treated in the private service of the author. Detailed description of locally recurrent disease is rare and appears to justify the recording of the following observations.

The management of pelvic abscess.

Pelvic abscess is a relatively uncommon condition in current surgical practice. However, candidates for higher surgical degrees have shown an inadequate knowledge of the management of the various types of pelvic abscess. This observation includes candidates confining their activities to the surgical aspects of gynaecology. It is considered, therefore, that a contribution on the subject of the management of pelvic abscess is justifiable.