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To enable rationale vaccine design, studies of molecular and cellular mechanisms of immune recognition need to be linked with clinical studies in humans. A major challenge in conducting such translational research studies lies in the management and integration of large amounts and various types of data collected from multiple sources. For this purpose, we have established 'IMMUNOCAT', an interactive data management system for the epitope discovery research projects conducted by our group. The system provides functions to store, query, and analyze clinical and experimental data, enabling efficient, systematic, and integrative data management. We demonstrate how IMMUNOCAT is utilized in a large-scale research contract that aims to identify epitopes in common allergens recognized by T cells from human donors, in order to facilitate the rational design of allergy vaccines. At clinical sites, demographic information and disease history of each enrolled donor are captured, followed by results of an allergen skin test and blood draw. At the laboratory site, T cells derived from blood samples are tested for reactivity against a panel of peptides derived from common human allergens. IMMUNOCAT stores results from these T cell assays along with MHC:peptide binding data, results from RAST tests for antibody titers in donor serum, and the respective donor HLA typing results. Through this system, we are able to perform queries and integrated analyses of the various types of data. This provides a case study for the use of bioinformatics and information management techniques to track and analyze data produced in a translational research study aimed at epitope identification. [ABSTRACT FROM AUTHOR]

Purpose: In the present study, we determined the prevalence of obstructive meibomian gland dysfunction (MGD), hyposecretory MGD, grossly normal MG, and hypersecretory MGD in patients with dry eye syndrome using lipid layer thickness (LLT) and MG dropout., Methods: Eighty-eight patients with dry eye syndrome were included in the study. Patients were categorized into four groups according to the LLT and weighted total meiboscore. The proportion of patients in each group was calculated. The age, sex, Ocular Surface Disease Index, LLT, Schirmer, tear film breakup time, cornea stain, weighted total meiboscore, expressibility, and quality of meibum were compared between the four groups., Results: Fifteen eyes (17.0%) had obstructive MGD, two eyes (2.3%) had hyposecretory MGD, 40 eyes (45.5%) had grossly normal MG, and 17 eyes (19.3%) had hypersecretory MGD. The obstructive MGD group was younger than the grossly normal MG group. In obstructive MGD, the ratio of men to women was higher than that of the other groups. However, Ocular Surface Disease Index, Schirmer, tear film breakup time, and corneal stain did not show statistically significant differences between the four groups. The meibum expressibility of the hyposecretoy MGD group was worse than those of the other groups. The meibum expressibility of the hyposecretoy MGD group was poor than those of the obstructive and hypersecretory MGD group., Conclusions: This categorization was expected to help determine the best treatment method for dry eye syndrome, according to the MG status.

Background: Corneal topography is a clinically validated examination method for keratoconus. However, there is no clear guideline regarding patient selection for corneal topography. We developed and validated a novel artificial intelligence (AI) model to identify patients who would benefit from corneal topography based on basic ophthalmologic examinations, including a survey of visual impairment, best-corrected visual acuity (BCVA) measurement, intraocular pressure (IOP) measurement, and autokeratometry., Methods: A total of five AI models (three individual models with fully connected neural network including the XGBoost, and the TabNet models, and two ensemble models with hard and soft voting methods) were trained and validated. We used three datasets collected from the records of 2,613 patients' basic ophthalmologic examinations from two institutions to train and validate the AI models. We trained the AI models using a dataset from a third medical institution to determine whether corneal topography was needed to detect keratoconus. Finally, prospective intra-validation dataset (internal test dataset) and extra-validation dataset from a different medical institution (external test dataset) were used to assess the performance of the AI models., Results: The ensemble model with soft voting method outperformed all other AI models in sensitivity when predicting which patients needed corneal topography (90.5% in internal test dataset and 96.4% in external test dataset). In the error analysis, most of the predicting error occurred within the range of the subclinical keratoconus and the suspicious D-score in the Belin-Ambrósio enhanced ectasia display. In the feature importance analysis, out of 18 features, IOP was the highest ranked feature when comparing the average value of the relative attributions of three individual AI models, followed by the difference in the value of mean corneal power., Conclusion: An AI model using the results of basic ophthalmologic examination has the potential to recommend corneal topography for keratoconus. In this AI algorithm, IOP and the difference between the two eyes, which may be undervalued clinical information, were important factors in the success of the AI model, and may be worth further reviewing in research and clinical practice for keratoconus screening., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ahn, Kim, Chung, Kim, Jun, Kim and Seo.)

Background: To investigate the correlation between the duration of Sjögren syndrome (SS) and ocular surface parameters in patients with SS-related dry eye., Methods: We analyzed 108 eyes of 108 female patients with primary SS-related dry eye. All patients underwent rheumatoid serologic tests and ocular surface assessments. The ocular surface assessment included the Standard Patient Evaluation of Eye Dryness (SPEED) score, meibomian gland (MG) atrophy, lipid layer thickness (LLT), partial and total blinking, partial blinking rate, Schirmer's I test, non-invasive tear break-up time, and ocular surface staining score. Correlations between the duration of SS and ocular surface assessments were calculated., Results: The average age and SS duration of the participants were 56.7 ± 10.2 (range 21-78) years and 54.15 ± 41.10 (range 1-134) months, respectively. There was a strong positive correlation between SS duration and MG atrophy (r = 0.766, p < 0.001). The correlation between SS duration and MG atrophy rate remained significant after controlling for age (r = 0.559, p < 0.001). Average, maximum, and minimum LLTs showed weak negative correlations with SS duration (r = - 0.310, - 0.211, and-0.304, respectively, p = 0.014, 0.028, and 0.022, respectively) and MG atrophy (r = - 0.191, - 0.326, and - 0.299, respectively, p = 0.049, 0.002, and 0.009, respectively). SPEED score showed a weak positive correlation to SS duration (r = 0.303, p = 0.042) and a moderate positive correlation to MG atrophy (r = 0.450, p = 0.029)., Conclusions: Longer duration of primary SS was related to more severe MG atrophy. Therefore, it is necessary to perform meibography in SS patients to verify MG atrophy status. A comparative study with non-SS dry eye patients is required to validate this study., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

We aimed to compare refractive outcomes between total keratometry using a swept-source optical biometer and conventional keratometry in cataract surgery with refractive multifocal intraocular lens (IOL) implantation. We included patients who underwent cataract surgery with refractive multifocal IOL implantation. The IOL power was calculated using conventional formulas (Haigis, SRK/T, Holladay 2, and Barrett Universal II) as well as a new formula (Barrett TK Universal II). The refractive mean error, mean absolute error, and median absolute error were compared, as were the proportions of eyes within ± 0.25 diopters (D), ± 0.50 D, and ± 1.00 D of prediction error. In total 543 eyes of 543 patients, the absolute prediction error of total keratometry was significantly higher than that of conventional keratometry using the SRK/T (P = 0.034) and Barrett Universal II (P = 0.003). The proportion of eyes within ± 0.50 D of the prediction error using the SRK/T and Barrett Universal II was also significantly higher when using conventional keratometry than total keratometry (P = 0.010 for SRK/T and P = 0.005 for Barrett Universal II). Prediction accuracy of conventional keratometry was higher than that of total keratometry in cataract surgery with refractive multifocal IOL implantation., (© 2021. The Author(s).)

We aimed to investigate the immunoglobulin E (IgE) detection rate and allergen patterns in patients with isolated allergic conjunctivitis using the multiple allergen simultaneous test (MAST)-immunoblot assay. A total of 120 patients with allergic conjunctivitis and no associated rhinitis, asthma, or dermatitis underwent the MAST-immunoblot assay to measure serum total IgE (TIgE) and serum specific IgE (SIgE) against 57 allergens. Patients were classified into subgroups based on the season when the eye symptoms were exacerbated, and TIgE and SIgE positivity. Differences between sex and age groups were also analyzed. Of the 120 patients, 57.5% (69 patients) and 69.2% (83 patients) were positive for TIgE (≥100 IU/mL) and SIgE (≥0.7 IU/mL), respectively. The allergens that most frequently triggered sensitization in the study population were Dermatophagoides farinae , Dermatophagoides pteronyssinus , Tyrophagus putrescentiae , Alternaria , and house dust. House dust mites, such as D. farinae and D. pteronyssinus , showed the highest detection rates regardless of the season. Men had a higher positive rate for TIgE than women, whereas a higher rate of sensitization, detected as SIgE positivity, was seen in younger patients. In conclusion, MAST-immunoblot assay can detect sensitizing allergens in patients with isolated allergic conjunctivitis.

We aimed to compare the refractive outcomes of cataract surgery with diffractive multifocal intraocular lenses (IOLs) using standard keratometry (K) and total keratometry (TK). In this retrospective observational case series study, a total of 302 patients who underwent cataract surgery with multifocal IOL implantation were included. Predicted refractive outcomes were calculated based on the current standard formulas and a new formula developed for TK using K and TK, which were obtained from a swept-source optical biometer. At 2-month postoperatively, median absolute prediction errors (MedAEs) and proportion of eyes within ± 0.50 diopters (D) of predicted postoperative spherical equivalent (SE) refraction were analyzed. There was no significant difference between MedAEs or proportion of eyes within ± 0.50D of predicted refraction from K and TK in each formula. In TFNT00 and 839MP IOL cases, there was no difference between MedAEs from K and TK using any formula. In 829MP IOL cases, MedAE from TK was significantly larger than that from K in Barrett Universal II/Barrett TK Universal II (P = 0.033). In 677MY IOL cases, MedAE from TK was significantly larger than that from K in Haigis (P = 0.020) and Holladay 2 (P = 0.006) formulas. In the subgroup analysis for IOL, there was no difference between the proportion of eyes within ± 0.50 D of predicted refraction from K and TK using any formula. TFNT00 and 839MP IOLs were favorable with TK, with 677MY IOL with K and 829MP IOL being in a neutral position, which necessitates the study that investigates the accuracy of the new TK technology.

Purpose: To investigate the efficacy of the combined phototherapeutic keratectomy (PTK) and peripheral anterior stromal puncture (ASP) compared with that of PTK alone in patients with recurrent corneal erosion syndrome (RCES)., Methods: The medical records of 25 patients (25 eyes) who underwent combined treatment of PTK and peripheral ASP for RCES from March 2016 to May 2017 were retrospectively reviewed. Twenty-three patients (23 eyes) treated with PTK alone from March 2015 to February 2016 served as a control group. All surgeries were performed by a single surgeon. This retrospective clinical study comprised 48 patients (48 eyes) who were followed up for more than 18 months. Clinical records of age, sex, laterality, etiology of RCES, and history of recurrence after treatment were evaluated., Results: Twenty-five eyes were treated with combined PTK and ASP, and 23 eyes were treated with PTK only. The mean follow-up period was 19.63 ± 2.97 and 19.75 ± 6.83 months, respectively. There were no differences in baseline parameters between the groups. In the combined treatment group, one patient experienced recurrence 6 months after the surgery. In the single treatment group, five patients showed recurrence at 4, 7, 8, 11, and 13 months after the surgery, respectively. Compared to the single treatment group, the combined treatment group showed significantly lower recurrence rate ( p < 0.05). All recurred patients required no additional treatment except temporary therapeutic contact lenses and topical lubricants., Conclusions: Our findings suggest that combined treatment of PTK and peripheral ASP is effective in alleviation of symptoms and prevention of recurrence in refractory RCES compared with treatment using PTK alone., Competing Interests: No potential conflict of interest relevant to this article was reported., (© 2020 The Korean Ophthalmological Society.)

Background: Traditional chemotherapy agents adversely affect wound healing and need to be held prior to or after surgery. Immune checkpoint inhibitors (ICIs) and targeted agents are now standard of care for the several treatment cancers. We hypothesize that ICI and targeted therapy do not have similar adverse effects on perioperative outcomes., Methods: We performed a review of melanoma patients undergoing surgery at an academic hospital between 2011 and 2019. All patients received ICI or targeted therapy ≤ 60 days prior to surgery, including palliative procedures. Preoperative performance status was assessed using Eastern Cooperative Oncology Group score and American Society of Anesthesiologists Classification System. Thirty-day complications were classified by Clavien-Dindo grade. No statistical comparisons were performed., Results: Of 63 patients included in the analysis, 29 (46%) patients received ICI and 34 (54%) received targeted therapy with median of 14 days (IQR 5-27 days) between the last preoperative dose and day of surgery (ICI, median 18 days [IQR 13-34.5]; targeted therapy, median 7 days [IQR 3-22.25]). There were no perioperative mortalities. Among patients treated with ICI, 22 patients (76%) had no complications. Four patients had wound infections (2 readmitted), 1 had reoperation (hematoma) and 2 readmitted for other reasons (fever; volvulus). Among patients treated with targeted therapy, 25 patients (74%) had no complications. Seven patients had wound infections (none readmitted), 1 had reoperation (flap failure) and 1 had dehiscence (not treated)., Conclusions: Patients undergoing treatment with ICI or targeted therapies can safely undergo surgery without substantially increased risk of serious intraoperative and postoperative complications.

Purpose: To evaluate changes in the tear meniscus area and tear meniscus height over time in patients with dry eye syndrome, using anterior segment spectral-domain optical coherence tomography after the instillation of 3% diquafosol ophthalmic solution., Methods: Sixty eyes from 30 patients with mild to moderate dry eye syndrome were included. Tear meniscus images acquired by anterior segment spectral-domain optical coherence tomography were analyzed using National Institutes of Health's image-analysis software (ImageJ 1.44p). Tear meniscus area and tear meniscus height were measured at baseline, 5 minutes, 10 minutes, and 30 minutes after instillation of a drop of diquafosol in one eye and normal saline in the other eye. Changes in ocular surface disease index score, tear film break-up time, corneal staining score by Oxford schema, and meibomian expressibility were also evaluated at baseline, and after 1 week and 1 month of a diquafosol daily regimen., Results: Sixty eyes from 30 subjects (mean age, 29.3 years; 8 men and 22 women) were included. In eyes receiving diquafosol, tear volume was increased at 5 and 10 minutes compared with baseline. It was also higher than saline instilled eyes at 5, 10, and 30 minutes. Changes in tear volume with respect to baseline were not statistically different after the use of diquafosol for 1 month. Ocular surface disease index score, tear film break-up time, and Oxford cornea stain score were significantly improved after 1 week and 1 month of daily diquafosol instillation, but meibomian expressibility did not change., Conclusions: Topical diquafosol ophthalmic solution effectively increased tear volume for up to 30 minutes, compared to normal saline in patients with dry eye syndrome., Competing Interests: No potential conflict of interest relevant to this article was reported., (© 2017 The Korean Ophthalmological Society)

Aim: To screen microRNAs (miRNAs) and set up target miRNAs in pterygium., Methods: Primary fibroblasts were isolated from pterygium and Tenon's capsule and cultured. Immunocytochemical analysis and Western blotting were performed to confirm the culture of fibroblasts. In all, 1733 miRNAs were screened in the first step by using GeneChip(®) miRNA3.0 Array. Specific miRNAs involved in the pathogenesis of pterygium were subsequently determined using the following criteria: 1) high reproducibility in a repetitive test; 2) base log value of >7.0 for both control and pterygial fibroblasts; and 3) log ratio of >1.0 between pterygial fibroblasts and control fibroblasts., Results: Primary screening showed that 887/1733 miRNAs were up-regulated and 846/1733 miRNAs were down-regulated in pterygial fibroblasts compared with those in control fibroblasts. Of the 1733 miRNAs screened, 4 miRNAs, namely, miRNA-143a-3p, miRNA-181a-2-3p, miRNA-377-5p and miRNA-411a-5p, met the above-mentioned criteria. Primary screening showed that these 4 miRNAs were up-regulated in pterygial fibroblasts compared with control fibroblasts and that miRNA-143a-3p had the highest mean ratio compared with the miRNAs in control fibroblasts., Conclusion: miRNA-143a-3p, miRNA-181a-2-3p, miRNA-377-5p and miRNA-411a-5p are up-regulated in pterygial fibroblasts compared with control fibroblasts, suggesting their involvement in the pathogenesis of pterygium.

Purpose: We investigated whether the tear interferometric pattern was able to identify differences in tear film kinetics among clinical subtypes of dry eye., Methods: A total of 138 eyes of 76 subjects (38 men and 38 women; mean age ± SD, 61.6 ± 16.2 years) with or without dry eye who visited Itoh Clinic from May to August 2015 were enrolled in a cross-sectional study. Clinical diagnosis of dry eye subtype was based on tear film parameters. The pattern of tear film kinetics determined by interferometry was classified as 0 (monotonous gray or multicolor interferometric fringe with a noninvasive breakup time [NIBUT] of ≥5 seconds), 1 (multicolor interferometric fringe with a NIBUT of <5 seconds), or 2 (grayish amorphous interferometric fringe with a NIBUT of <5 seconds), and reliability of classification was evaluated. Lipid layer thickness (LLT) for the tear film was also determined by interferometry., Results: Interrater κ values for evaluation of interferometric patterns ranged from 0.57 to 0.94 for both physicians and nonphysicians with reference to a dry eye expert, the latter of whom showed an intrarater reliability of 0.90. The distribution of eyes among interferometric patterns 0, 1, and 2 coincided well with the clinical subgroups of normal tear condition, non-Sjögren syndrome aqueous-deficient dry eye, and meibomian gland dysfunction, respectively. A multicolor interferometric fringe was essentially observed only at an LLT of >70 nm., Conclusions: Tear interferometry was able to reliably distinguish clinical subtypes of dry eye by reflecting the balance between the lipid and aqueous layers of the tear film.

Objective: To study electrical stimulation of the lacrimal gland and afferent nerves for enhanced tear secretion, as a potential treatment for dry eye disease. We investigate the response pathways and electrical parameters to safely maximize tear secretion., Approach: We evaluated the tear response to electrical stimulation of the lacrimal gland and afferent nerves in isofluorane-anesthetized rabbits. In acute studies, electrical stimulation was performed using bipolar platinum foil electrodes, implanted beneath the inferior lacrimal gland, and a monopolar electrode placed near the afferent ethmoid nerve. Wireless microstimulators with bipolar electrodes were implanted beneath the lacrimal gland for chronic studies. To identify the response pathways, we applied various pharmacological inhibitors. To optimize the stimulus, we measured tear secretion rate (Schirmer test) as a function of pulse amplitude (1.5-12 mA), duration (0.1-1 ms) and repetition rate (10-100 Hz)., Main Results: Stimulation of the lacrimal gland increased tear secretion by engaging efferent parasympathetic nerves. Tearing increased with stimulation amplitude, pulse duration and repetition rate, up to 70 Hz. Stimulation with 3 mA, 500 μs pulses at 70 Hz provided a 4.5 mm (125%) increase in Schirmer score. Modulating duty cycle further increased tearing up to 57%, compared to continuous stimulation in chronically implanted animals (36%). Ethmoid (afferent) nerve stimulation increased tearing similar to gland stimulation (3.6 mm) via a reflex pathway. In animals with chronically implanted stimulators, a nearly 6 mm increase (57%) was achieved with 12-fold less charge density per pulse (0.06-0.3 μC mm(-2) with 170-680 μs pulses) than the damage threshold (3.5 μC mm(-2) with 1 ms pulses)., Significance: Electrical stimulation of the lacrimal gland or afferent nerves may be used as a treatment for dry eye disease. Clinical trials should validate this approach in patients with aqueous tear deficiency, and further optimize electrical parameters for maximum clinical efficacy.

A recent study showed that 355-nm nanosecond lasers cut cornea with similar precision to infrared femtosecond lasers. However, use of ultraviolet wavelength requires precise assessment of ocular safety to determine the range of possible ophthalmic applications. In this study, the 355-nm nanosecond laser was evaluated for corneal and iris damage in rabbit, porcine, and human donor eyes as determined by minimum visible lesion (MVL) observation, live/dead staining of the endothelium, and apoptosis assay. Single-pulse damage to the iris was evaluated on porcine eyes using live/dead staining. In live rabbits, the cumulative median effective dose (ED50) for corneal damage was 231 J/cm2, as seen by lesion observation. Appearance of endothelial damage in live/dead staining or apoptosis occurred at higher radiant exposure of 287 J/cm2. On enucleated rabbit and porcine corneas, ED50 was 87 and 52 J/cm2, respectively, by MVL, and 241 and 160 J/cm2 for endothelial damage. In human eyes, ED50 for MVL was 110 J/cm2 and endothelial damage at 453 J/cm2. Single-pulse iris damage occurred at ED 50 of 208 mJ/cm2. These values determine the energy permitted for surgical patterns and can guide development of ophthalmic laser systems. Lower damage threshold in corneas of enucleated eyes versus live rabbits is noted for future safety evaluation.

Molecular dynamics simulations of lipid bilayer ribbons have been performed to investigate the structures and line tensions associated with free bilayer edges. Simulations carried out for dioleoyl phosphatidylcholine with three different force-field parameter sets yielded edge line tensions of 45 ± 2 pN, over 50% greater than the most recently reported experimentally determined value for this lipid. Edge tensions obtained from simulations of a series of phosphatidylcholine lipid bilayer ribbons with saturated acyl tails of length 12-16 carbons and with monounsaturated acyl tails of length 14-18 carbons could be correlated with the excess area associated with forming the edge, through a two-parameter fit. Saturated-tail lipids underwent local thickening near the edge, producing denser packing that correlated with lower line tensions, while unsaturated-tail lipids showed little or no local thickening. In a dipalmitoyl phosphatidylcholine ribbon initiated in a tilted gel-phase structure, lipid headgroups tended to tilt toward the nearer edge producing a herringbone pattern, an accommodation that may account for the reported edge-induced stabilization of an ordered structure at temperatures near a lipid gel-fluid phase transition.

Purpose: To compare the intraocular penetration of 4 fluoroquinolone eye drops after topical instillation into rabbit eyes., Methods: The tested drugs were levofloxacin 1.5% (LVFX), gatifloxacin 0.3%, moxifloxacin 0.5% (MFLX), and besifloxacin 0.6% (BFLX). Forty-eight New Zealand white rabbits were randomly assigned into 2 groups. For group 1 (40 rabbits, 80 eyes), single instillation was performed, and tissue samples were acquired after 0.5, 1, 2, 4, and 6 hours. For group 2 (8 rabbits, 16 eyes), repeated instillation was performed (4 times, every 15 minutes), and tissues were acquired 1 hour after the fourth instillation. The drug concentrations in ocular tissues (cornea, aqueous, conjunctiva, and trisected vitreous) were analyzed with high-performance liquid chromatography., Results: The AUC 0-6 h (area under the curve, in microgram.hour/gram) in group 1 and the mean concentration (in micrograms/gram) in group 2 for LVFX, gatifloxacin 0.3%, MFLX, and BFLX, respectively, were 22.97, 6.44, 13.54, and 3.29 and 22.60, 6.99, 13.69, and 1.91 in cornea; 5.66, 1.43, 3.38, and 0.42 and 5.52, 1.29, 2.47, and 0.19 in aqueous humor; 2.33, 0.91, 2.17, and 9.83 and 4.51, 0.78, 1.48, and 2.09 in bulbar conjunctiva; 0.243, 0.051, 0.134, and 0.018 and 0.182, 0.055, 0.122, and 0.015 in anterior vitreous; none of the drugs achieved enough concentration in equatorial and posterior vitreous. Repeated instillation resulted in approximately 2.1 times greater penetration than single instillation., Conclusions: LVFX and MFLX demonstrated good intraocular penetration particularly in cornea, aqueous humor, and anterior vitreous, and they may be considered the penetrative fluoroquinolones. BFLX showed high concentration in bulbar conjunctiva and may be considered the retentive fluoroquinolone.

Purpose: The corneal change induced by refractive procedures influence both the postoperative refractive status and the ocular spherical aberration (SA). We evaluated changes in corneal SA after three types of surface ablation: phototherapeutic keratectomy (PTK), myopic photorefractive keratectomy (PRK), and myopic wavefront-guided laser epithelial keratomileusis (LASEK)., Methods: Twenty-six eyes (25 patients) were subjected to PTK 26 eyes (14 patients) to PRK, and 34 eyes (17 patients) to wavefront-guided LASEK. Corneal SA was measured with the iTrace in all patients both preoperatively and 6 months postoperatively., Results: Six months after surgery, mean corneal SA was -0.173 ± 0.171 µm in the PTK group, 0.672 ± 0.200 µm in the PRK group, and 0.143 ± 0.136 µm in the wavefront-guided LASEK group. The mean difference between the preoperative and postoperative corneal SA (ΔSA) was -0.475 µm in the PTK group, 0.402 µm in the PRK group, and -0.143 µm in the wavefront-guided LASEK group., Conclusions: Surgically induced changes in corneal SA vary with procedure. The prediction of the pattern of SA change induced by various surface ablation procedures may be helpful for developing future surgical procedures.

Purpose: To compare the corneal astigmatism measurements from 6 instruments in preoperative assessment for toric intraocular lens (IOL) implantation., Setting: Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, South Korea., Design: Prospective comparative observational study., Methods: This study included patients with cataract and more than 1.00 diopter (D) of corneal astigmatism. For preoperative evaluation of toric IOL implantation, the net astigmatism was evaluated using manual keratometry, autokeratometry, partial coherence interferometry (PCI) (IOLMaster), corneal topography/ray-tracing aberrometry (iTrace), scanning-slit topography (Orbscan), and Scheimpflug imaging (Pentacam). All net astigmatisms were converted to polar values. Using the astigmatism measurements from manual keratometry as a standard, Bland-Altman analysis, linear mixed-model, and bivariate graphic analysis were performed., Results: The study group comprised 257 eyes of 141 patients. Bland-Altman plots showed good agreement between manual keratometry and each instrument for polar values. There was no significant between-instrument difference in KP(90) and KP(135) in the linear mixed model analysis or in bivariate polar values in bivariate confidence ellipses., Conclusion: The corneal astigmatism measurements from autokeratometry, PCI, corneal topography/ray-tracing aberrometry, scanning-slit topography, and Scheimpflug imaging were comparable to those from manual keratometry and can be used interchangeably with manual keratometry to measure corneal astigmatism., (Copyright © 2012 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Unlabelled: A 57-year-old woman had concomitant surgery of persistent pupillary membrane removal and uneventful phacoemulsification through the same temporal clear corneal incision in her left eye. Short axial lengths (right eye, 21.08 mm; left eye, 20.39 mm) with shallow angles were noted bilaterally, and other findings were not remarkable. The patient experienced angle-closure attacks 3 and 7 months postoperatively. At the second angle-closure attack, diffuse epithelial ingrowth was observed. The epithelial ingrowth covered the intraocular lens surface in the interpupillary area, the iris surface surrounding the pupil, and the temporal anterior chamber angle, but did not reach the corneal endothelial incision. After observation of iris blanching with laser photocoagulation, argon laser photocoagulation was applied to the epithelium covering the iris and angle 7 times during the following month. The epithelial ingrowth was completely removed and did not recur during the 36-month follow-up., Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned., (Copyright © 2012 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Purpose: Granular corneal dystrophy type 2 (GCD2) causes the formation of corneal deposits having 3 different morphological types. We used Fourier domain optical coherence tomography to assess the depths of each type according to the morphology., Methods: A prospective study was performed in 54 eyes of 54 heterozygous patients with GCD2. Corneal deposits of 54 patients with GCD2 were classified into 3 morphological types: type 1, diffuse haze; type 2, granular shape (2 subgroups: type 2a, round granulated and type 2b, round spiculated); and type 3, linear shape (2 subgroups: type 3a, short side branched and type 3b, long side branched). Using Fourier domain optical coherence tomography, we measured the distances from the Bowman layer to the upper surface of the deposits (USBL), to the lower surface of the deposits (LSBL), and the thickness of the deposits (TD). The deposits formed along the flap interface were also examined among 19 patients who had LASIK., Results: Types 1 and 2 deposits were always adjacent to the Bowman layer; thus the USBLs for each were 0.0 ± 0.0 μm, whereas that of type 3 deposits was 65.4 ± 48.0 μm (P < 0.0001). The LSBL and TD of linear deposits with long side branches (type 3) (313.3 ± 71.4 and 246.2 ± 71.9 μm) were greater than those of type 1 (47.7 ± 10.2 and 47.7 ± 10.2 μm) and type 2 (91.3 ± 39.5 and 91.3 ± 39.5 μm) (P < 0.0001). There were no differences in the measurements between the subgroups type 2a and type 2b or between types 3a and 3b. USBL of the laser in situ keratomileusis group was 54.5 ± 29.8 μm., Conclusions: The depths of corneal deposits in patients with GCD2 were associated with the morphology of the deposits. The linear deposits were located most deeply in the cornea, followed by granular deposits and diffuse haze moving anteriorly. Several deposits have distinct depths according to the morphological types.

We investigated the molecular determinants of allergen-derived T cell epitopes in humans utilizing the Phleum pratense (Timothy grass) allergens (Phl p). PBMCs from allergic individuals were tested in ELISPOT assays with overlapping peptides spanning known Phl p allergens. A total of 43 distinct antigenic regions were recognized, illustrating the large breadth of grass-specific T cell epitopes. Th2 cytokines (as represented by IL-5) were predominant, whereas IFN-gamma, IL-10, and IL-17 were detected less frequently. Responses from specific immunotherapy treatment individuals were weaker and less consistent, yet similar in epitope specificity and cytokine pattern to allergic donors, whereas nonallergic individuals were essentially nonreactive. Despite the large breadth of recognition, nine dominant antigenic regions were defined, each recognized by multiple donors, accounting for 51% of the total response. Multiple HLA molecules and loci restricted the dominant regions, and the immunodominant epitopes could be predicted using bioinformatic algorithms specific for 23 common HLA-DR, DP, and DQ molecules. Immunodominance was also apparent at the Phl p Ag level. It was found that 52, 19, and 14% of the total response was directed to Phl p 5, 1, and 3, respectively. Interestingly, little or no correlation between Phl p-specific IgE levels and T cell responses was found. Thus, certain intrinsic features of the allergen protein might influence immunogenicity at the level of T cell reactivity. Consistent with this notion, different Phl p Ags were associated with distinct patterns of IL-5, IFN-gamma, IL-10, and IL-17 production.

Background: Genomic tiling arrays have been described in the scientific literature since 2003, yet there is a shortage of user-friendly applications available for their analysis., Methodology/principal Findings: Tiling Array Analyzer (TiArA) is a software program that provides a user-friendly graphical interface for the background subtraction, normalization, and summarization of data acquired through the Affymetrix tiling array platform. The background signal is empirically measured using a group of nonspecific probes with varying levels of GC content and normalization is performed to enforce a common dynamic range., Conclusions/significance: TiArA is implemented as a standalone program for Linux systems and is available as a cross-platform virtual machine that will run under most modern operating systems using virtualization software such as Sun VirtualBox or VMware. The software is available as a Debian package or a virtual appliance at http://purl.org/NET/tiara.

Purpose: Vascular endothelial growth factor (VEGF) is essential for neovascularization, but the use of anti-VEGF therapies to inhibit neovascularization may influence epithelial wound healing. Here, the effects of bevacizumab on corneal epithelial wound healing time in rabbit models, cell proliferation, and expression of integrins in human corneal epithelial and fibroblast cells were evaluated., Methods: To compare epithelial wound healing times, epithelial defect sizes were measured after application of bevacizumab topical eye drops at 0, 0.5, 1.0, 1.5, 2.5, or 5 mg/mL, twice daily, to mechanically debrided epithelia of rabbit corneas. The cellular covering of wounded areas and expression of Ki67 were assessed after scrape injuries in cultures of human corneal epithelial and fibroblast cells. Expression of cell surface integrins and collagens was measured using plates coated with mouse monoclonal antibodies against human adhesion molecules, and relevant mRNA levels were assessed by reverse-transcription-polymerase chain reaction (RT-PCR)., Results: The application of bevacizumab topical eye drops at 1.0, 1.5, 2.5, or 5 mg/mL delayed rabbit corneal epithelial healing. Cell cultures growing under high concentrations of bevacizumab showed delay in the proliferation of corneal epithelial and fibroblast cells. Surface expression of mRNA encoding integrins and collagens were decreased by 1.5 mg/mL of bevacizumab., Conclusions: Bevacizumab delayed corneal epithelial wound healing and inhibited integrin expression. When bevacizumab is used to reduce the development of new corneal vessels, slight delays in epithelial wound healing are possible and cellular proliferation is to be expected.

Purpose: To determine the in vitro antibiotic susceptibility patterns of conjunctival bacterial flora isolated before surgery from patients undergoing refractive surgery., Design: In vitro laboratory investigation., Participants: One hundred five eyes from 105 patients scheduled for refractive surgery at Balgensesang Ophthalmology Clinic between September 2005 and January 2006 were studied. Among 105 patients, 71 (67.6%) underwent LASIK using a femtosecond laser, 24 (22.9%) underwent LASIK using an automated microkeratome, 8 (7.6%) underwent LASEK, and 2 (1.9%) patients underwent phakic intraocular lens implantation., Methods: Preoperative conjunctival swab samples were inoculated directly in culture media at the bedside before topical anesthetic or antibiotic application. Blood agar, chocolate agar, thioglycolate broth, Sabouraud dextrose agar, and Ogawa media were used for bacterial, fungal, and mycobacterial cultures., Main Outcome Measures: Minimum inhibitory concentrations (MICs) of ofloxacin (OFX), levofloxacin (LEV), gatifloxacin (GAT), moxifloxacin (MOX), gemifloxacin (GEM), and other commonly used antibiotics were determined using an E test., Results: From 105 patients, 73 (85%) coagulase-negative staphylococci (CNS), 2 (2.3%) Staphylococcus aureus, 1 (1.2%) Streptococcus pneumoniae, and 5 (4.8%) gram-negative bacilli were isolated. No fungi or mycobacteria were isolated. The MIC that would inhibit the growth of 90% of the tested bacterial isolates (MIC(90)) of OFX, LEV, GAT, MOX, and GEM for methicillin-susceptible CNS (n = 46) were 0.5 microg/ml, 0.19 microg/ml, 0.094 microg/ml, 0.047 microg/ml, and 0.023 microg/ml, respectively. The MIC(90) values for methicillin-resistant CNS (n = 27) were 32 microg/ml, 4 microg/ml, 1 microg/ml, 0.5 microg/ml, and 0.25 microg/ml, respectively (P<0.001)., Conclusions: The most effective against conjunctival bacteria isolated from refractive surgery patients were GEM, MOX, and GAT; however, resistance to earlier-generation fluoroquinolones (OFX and LEV) is increasing among methicillin-resistant CNS. It may be a therapeutic option to use newer fluoroquinolones in patients undergoing refractive eye surgery to reduce such infections as methicillin-resistant CNS., Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Background: To study the role played by eosinophil cationic protein (ECP) in patients with Mycoplasma pneumonia infection., Methods: Pediatric patients aged 4 to 14 years old were divided into 3 groups, each consisting of 30 patients. Group 1 comprised patients with known M. pneumoniae infection. Group 2 comprised patients with asthma who were in a stable condition with no infection, acute asthma exacerbation or steroid use in the last 2 months. Group 3 consisted of healthy children and was designated the control group. The level of ECP in patients' serum was measured by an ECP radioimmunoassay kit., Results: There were 90 children enrolled in this study; 59 (65.56%) were boys and 31 (34.44%) were girls. Mean serum ECP levels between males and females was not significantly different (p = 0.544). The variance of serum ECP levels decreased as patient age increased, but there was no relationship between serum ECP level and patient age (gamma = 0.118, p = 0.267). Serum ECP levels were similar in both the M. pneumoniae-infected and asthma groups; serum ECP levels in the control group were less than the levels seen in the other 2 groups. The difference in serum ECP levels among the 3 groups was statistically significant (p < 0.001)., Conclusion: Both the children who had M. pneumoniae infection and the children with asthma had significantly increased serum ECP levels compared to normal healthy children. The elevated ECP levels found in the serum of patients with M. pneumoniae infection may be associated with damage to the respiratory epithelium and accelerated hypersensitivity in the respiratory system. Decreasing the serum level of ECP may potentially be a method of relieving symptoms in patients with M. pneumoniae infection. Additional studies are warranted to further validate this conclusion.

Purpose: To present a case of Weill-Marchesani syndrome with corneal endothelial dysfunction due to anterior dislocation of a spherophakic lens and corneolenticular contact., Methods: A 17-year-old woman presented with high myopia and progressive visual disturbance. She was of short stature and had brachydactyly. Her initial Snellen best corrected visual acuity (BCVA) was 20/50 (-sph 20.50 -cyl 3.00 Ax 180) in her right eye and 20/40 (-sph 16.00 -cyl 6.00 Ax 30) in her left eye. Slit lamp examination revealed a dislocated spherophakic lens touching corenal endothelium. A microspherophakic lens, hypoplastic ciliary body, and elongated zonules were confirmed on rotating Scheimpflug camera (Pentacam) and on ultrasound biomicroscopy. Specular microscopy showed corneal endothealial dysfunction. Systemic evaluation was performed, and chromosomal study showed 46, XX, inv (15) (q13qter). The patient was diagnosed with Weill-Marchesani syndrome., Results: Due to impending corneal decompensation, phacoemulsification and suture fixation of the intraocular lens were performed. The operation and postoperative course were uneventful. Three months postoperatively, the visual acuity was 20/30 (OD) and 20/40 (OS) without correction, and BCVA was 20/20 (+sph 0.50 -cyl 2.00 Ax 160 : OD) and 20/25 (+sph 1.50 -cyl 3.00 Ax 30 : OS). During the follow-up period, increased corneal endothelial counts, hexagonality, and decreased corneal thickness were achieved., Conclusions: In Weill-Marchesani syndrome with a chromosomal anomaly, a dislocated spherophakic lens may cause severe corneal endothelial dysfunction due to corneolenticular contact, and prompt lensectomy is important to prevent such complications.

Unlabelled: Con-Struct Map is a graphical tool for the comparative study of protein structures. The tool detects potential conserved residue contacts shared by multiple protein structures by superimposing their contact maps according to a multiple structure alignment. In general, Con-Struct Map allows the study of structural changes resulting from, e.g. sequence substitutions, or alternatively, the study of conserved components of a structure framework across structurally aligned proteins. Specific applications include the study of sequence-structure relationship in distantly related proteins and the comparisons of wild type and mutant proteins., Availability: http://pdbrs3.sdsc.edu/ConStructMap/viewer&#95;argument&#95;generator/singleArguments., Supplementary Information: Supplementary data are available at Bioinformatics online.

Background: With the advent of increasing sequence and structural data, a number of methods have been proposed to locate putative protein binding sites from protein surfaces. Therefore, methods that are able to identify whether these binding sites interact are needed., Results: We have developed a new method using a machine learning approach to detect if protein binding sites, once identified, interact with each other. The method exploits information relating to sequence and structural complementary across protein interfaces and has been tested on a non-redundant data set consisting of 584 homo-dimers and 198 hetero-dimers extracted from the PDB. Results indicate 87.4% of the interacting binding sites and 68.6% non-interacting binding sites were correctly identified. Furthermore, we built a pipeline that links this method to a modified version of our previously developed method that predicts the location of binding sites., Conclusion: We have demonstrated that this high-throughput pipeline is capable of identifying binding sites for proteins, their interacting binding sites and, ultimately, their binding partners on a large scale.

A rapid increase in the number of experimentally derived three-dimensional structures provides an opportunity to better understand and subsequently predict protein-protein interactions. In this study, structurally conserved residues were derived from multiple structure alignments of the individual components of known complexes and the assigned conservation score was weighted based on the crystallographic B factor to account for the structural flexibility that will result in a poor alignment. Sequence profile and accessible surface area information was then combined with the conservation score to predict protein-protein binding sites using a Support Vector Machine (SVM). The incorporation of the conservation score significantly improved the performance of the SVM. About 52% of the binding sites were precisely predicted (greater than 70% of the residues in the site were identified); 77% of the binding sites were correctly predicted (greater than 50% of the residues in the site were identified), and 21% of the binding sites were partially covered by the predicted residues (some residues were identified). The results support the hypothesis that in many cases protein interfaces require some residues to provide rigidity to minimize the entropic cost upon complex formation.

A stimulation of the gigantocellular tegmental field (FTG) in the medulla oblongata often increases systemic arterial blood pressure (SAP) and decreases heart rate (HR). We investigated if the cardioinhibitory/depressor areas, including the nucleus ambiguus (NA), the dorsal motor nucleus of vagus (DMV) and the caudal ventrolateral medulla (CVLM), underlied the functional expression of FTG neurons in regulating cardiovascular responses. In 73 chloralose-urethane anesthetized cats, the HR, SAP and vertebral nerve activity (VNA) were recorded. Neurons in the FTG, NA, DMV and CVLM were stimulated by microinjection of sodium glutamate (25 mM Glu, 70 nl). To study if the NA, DMV, and CVLM relayed the cardioinhibitory messages from the FTG, 24 mM kainic acid (KA, 100 nl) was used as an excitotoxic agent to lesion neurons in the NA, DMV or CVLM. We found that the cardioinhibition induced by FTG stimulation was significantly reduced by KA lesioning of the ipsilateral NA or DMV. Subsequently, a bilateral KA lesion of NA or DMV abolished the cardioinhibitory responses of FTG. Compared to the consequence of KA lesion of the DMV, only a smaller bradycardia was induced by FTG stimulation after KA lesion of the NA. The pressor response induced by Glu stimulation of the FTG was reduced by the KA lesion of the CVLM. Such an effect was dominant ipsilaterally. Our findings suggested that both NA and DMV mediated the cardioinhibitory responses of FTG. The pressor message from the FTG neurons might be partly working via a disinhibitory mechanism through the depressor neurons located in the CVLM.

The aim of the present study was to examine the relationship between the lateral tegmental field (FTL), a cardioinhibitory area, with other cardioinhibitory areas, i.e., the ambiguus nucleus (NA) and the dorsal motor nucleus of vagus (DMV) and the caudal ventrolateral medulla (CVLM), a vasopressor inhibitory area. In 55 cats anesthetized with chloralose (40 mg/kg) and urethane (400 mg/kg), the cardiovascular responses of heart rate (HR), systemic arterial blood pressure (SAP) and vertebral nerve activity (VNA) were recorded. The FTL, NA, DMV and CVLM were identified first by stimulation (rectangular pulses in 80 Hz, 0.5 ms, 50-100 microA) and then confirmed by microinjection of sodium glutamate (Glu, 0.25M, 70 nl). In studying the influence of NA, DMV, or CVLM lesion on the Gluinduced responses in FTL, kainic acid (KA, 24 mM, 100 nl) was microinjected into the NA, DMV or CVLM. FTL stimulation produced an average decrease of HR by 55%. After KA lesioning of the ipsilateral NA or the DMV, the decreased HR induced by FTL was significantly diminished. After subsequent lesion of the contralateral DMV or NA, the bradycardia of FTL was abolished. The reduction of resting HR was more intense after lesioning the NA than DMV and with the left side more than that of the right side. These studies suggest that the cardioinhibitory responses of FTL are mediated through both NA and DMV with predominance of the former, while the hypotensive effect of FTL is mediated through CVLM. The precise pathway responsible for the FTL-induced bradycardia and hypotension is to be determined.

"13q-"syndrome is known to have widely variable manifestations, including retinoblastoma, mental & growth retardation, malformation of brain & heart, anal atresia, and anomalies of the face and limbs. Here we report a case of del(13)(q22) with multiple major congenital anomalies for the first time in Korea. The patient was born at 36(+4) weeks of pregnancy by caesarian section. Birth weight was 1490g. On examination the following features were noted: - imperforate anus, ambiguous genitalia (bifid scrotum, penoscrotal transposition, hypospadia), syndactyly of toes, absence of thumbs, abnormal facies (dolichocephaly, telecanthus, large low set ears, saddle nose, high arched palate, micrognathia). Neurocranial ultrasonography showed atrophy of the corpus callosum and multiple calcifications. He died at 14 days. Post-mortem autopsy findings showed cholestasis and fatty metamorphosis of liver, abnormal lobulation (Rt:2, Lt:1) and lymphangiectasis of the lung, VSD, ASD, PDA of heart, and acute tubular necrosis of kidney. Cytogenetic studies was confirmed to 46,XY,del(13) (q22) by Giemsa banded chromosomes from peripheral blood lymphocytes.

Hepatitis C virus infection is a global health problem; however, the interaction between pregnancy and chronic hepatitis C remains controversial. A Taiwanese woman with chronic hepatitis C had an uncomplicated pregnancy and gave birth to a female baby through spontaneous vaginal delivery. The serum levels of alanine aminotransferase and hepatitis C virus (HCV) RNA were measured before pregnancy, in the first and third trimesters, 1 and 3 months after delivery, respectively. During her pregnancy, the serum aminotransferase levels became normalized, while the serum HCV-RNA levels declined significantly and consecutively with the lowest viral load in the third trimester. One month after delivery, she had an abrupt elevation of serum HCV-RNA level, paralleling a hepatitis flare with serum aminotransferase level more than 20-fold the upper normal limit. The serum HCV-RNA levels declined thereafter, and serum aminotransferase levels became normalized 3 months postdelivery. She was infected with HCV genotype 1a throughout the entire follow-up period, and other causes of hepatitis flare were excluded. In conclusion, post-partum acute exacerbation of chronic hepatitis may occur in HCV-carrier mothers, and an abrupt elevation of serum HCV-RNA level may be associated with the acute exacerbation.

Unlabelled: The prevalence of hepatitis C virus (HCV) and a newly identified hepatitis G virus (HGV) and their clinical significance were studied in 42 polytransfused Taiwanese children. Serological assays for antibodies against HCV (anti-HCV) and polymerase chain reaction for serum HCV ribonucleic acid (RNA) and HGV RNA were performed. The prevalence of anti-HCV and HGV RNA was 17% and 14%, respectively in 42 polytransfused children. Anti-HCV seropositives had a significantly higher mean age, peak serum transaminase level, and longer transfusion duration than seronegatives, while children with HGV infection usually had no or only mild hepatitis activities. The prevalence of anti-HCV dropped sharply after implementation of anti-HCV screening, however the prevalence of HGV viraemia remained unchanged., Conclusions: HGV infection is not uncommon in polytransfused Taiwanese children and the virus does not cause significant hepatitis compared to HCV infection. Current blood donor screening for anti-HCV can effectively protect polytransfused children from HCV infection but the impact of additional screening for HGV markers awaits further studies.

Color Doppler ultrasonography was performed in 125 patients with 134 intussusceptions. Color flow was present in 121 cases of intussusception (group A) and was absent in 13 cases (group B). Young age and duration of symptoms greater than 48 hr were significantly related to the nonvisualization of blood flow detected by color Doppler sonography (P < 0.05). The successful rate of air reduction was significantly higher in group A than in group B (109 of 121 versus 4 of 13). Color Doppler ultrasonography is useful to predict the reducibility of an intussuscepted intestine. The nonvisualization of blood flow by this method is not a contraindication for air reduction.

Unlabelled: The diagnostic value of serum C-reactive protein (CRP) levels in children with perforated appendicitis was prospectively studied in 78 consecutive patients with histologically confirmed appendicitis. The patients were divided into two groups: group A included 56 patients with perforated appendicitis and group B consisted of 22 patients with simple appendicitis. Serum CRP level and leucocyte count were assayed in all and abdominal ultrasonography was performed in 75. The mean age group A patient was significantly lower than that of group B patients (7.5 vs. 10.4 years, P < 0.001). Group A patients had a significantly higher mean serum CRP levels than group B patients (92 vs. 31 mg/l, P < 0.001), while the mean leucocyte count was comparable in the two groups. Of 75 examined patients, 73 (97%) had a pre-operative sonographic diagnosis of appendicitis., Conclusion: Perforation is a common complication in children with appendicitis, especially in those of young age and with prolonged pain duration. Greatly increased serum CRP levels (> or = 50 mg/l) and abdominal ultrasonography are important diagnostic aids in such patients.

Over the past decade, pneumatic reduction has been increasingly accepted as the treatment of choice for pediatric intussusception. However the effectiveness of air compared with the more traditional barium reduction of intussusception continues to be a source of concern and debate. From August 1993 to November 1994, pneumatic reduction was used to treat 75 episodes in 73 patients with proven intussusception at Chang Gung Memorial Hospital, Taoyuan. Two patients underwent air reduction twice because of recurrence following an initial successful reduction. The recurrence rate was 3%. Successful reduction was achieved in 65/75 (87%) episodes. None of the patients experienced any complications following the procedure. In two of the 10 patients in whom reduction failed, one was subsequently found to have a Meckel's diverticulum and the other a duplication cyst as a leading point. This prospective study indicates that air enema is a safe and effective form of treatment for intussusception in infants and children. Pneumatic reduction should be the treatment of choice in the initial management of intussusception.

Intussusception is commonly the etiology of intestinal obstruction in infants and children. To investigate demographic data, clinicopathologic features and therapeutic prognosis of patients with intussusception, we reviewed 361 intussusceptions in 333 patients over an 11-year period. Most patients were below two years of age and there was a male preponderance of 1.6:1. There was no seasonal difference between the number of cases. The clinical triad of vomiting, abdominal colicky pain and bloody stools was manifested in only one-third of our patients. Secondary intussusception contributed to 6.6% of cases and Meckel's diverticulum was the most common pathologic cause. Positive findings were recorded in 82% of 67 patients undergoing sonographic examination. Intussusception of the ileo-colic type was most frequently encountered. Most patients (79%) were diagnosed within 48 hours and almost all cases underwent primary barium enema reduction. The success rate was 45%. Laparotomy was performed in 207 patients (57%) refractory to enema reduction or with critical illness, and intestinal resection was required in 28 (14%). Long-standing duration of illness (> 24 hours), positive clinical triad, positive pathologic lead point, and radiologic finding of bowel obstruction were identified as risk factors leading patients to surgical reduction (p < 0.001). Postoperative complications and recurrent intussusception developed in some patients, and the overall mortality was 0.6%. The clinical characteristics of intussusception in children generally remained unchanged as compared to previous reports. Early identification of patients with risk factors for surgical treatment is important to decrease the need for intestinal resection.

Extrapulmonary tuberculosis is not a rare infection of children in Taiwan. From 1985 to 1989, we studied 39 children with the diagnosis of extrapulmonary tuberculosis from a total of 43 sites. They were diagnosed by routine diagnostic tests including bacteriologic cultures in 11, pathological features in 25, and clinical presentations in 2 patients. Positive mycobacterial DNA probe method was obtained from a patient with tuberculous meningitis. The most common sites of involvement were lymph nodes in 9 (20.9%), meninges in 7 (16.3%), bone in 7 (16.3%), joint in 6 (14.0%) and miliary infection in 6 (14.0%). The median age of the 2 patients with renal tuberculosis was 14.5 years, which was older compared to the patients with other organ systems involvement. Tuberculin skin tests were significantly positive (> 10 mm) in 54% of the tested children. Among the treated patients, 76% were cured after 9 to 12 months of antituberculous chemotherapy without sequelae, while 24% had sequelae associated with tuberculous infection despite treatment. There was no death reported during the study period. We conclude that extrapulmonary tuberculosis remains an important health problem to the pediatric population of this island despite the overall decline in the incidence of tuberculosis. Early detection and thorough treatment for a suitable period are mandatory to improve the prognosis of this potentially curable infectious disease.

Triflavin, an Arg-Gly-Asp (RGD) containing peptide purified from Trimeresurus flavoviridis snake venom, inhibits human platelet aggregation by blocking fibrinogen binding to fibrinogen receptors associated with glycoprotein IIb/IIIa complex. In this study, we show that triflavin (1-30 micrograms/mouse) inhibits B16-F10 melanoma cell-induced lung colonization in C57BL/6 mice in a dose-dependent manner. In vitro, triflavin dose-dependently inhibits adhesion of B16-F10 melanoma cells to extracellular matrices (ECMs; i.e., fibronectin, fibrinogen, vitronectin, and collagen type I). Triflavin is approximately 600-800 times more potent than GRGDS at inhibiting cell adhesion. In addition, triflavin dose-dependently inhibits B16-F10 cell-induced platelet aggregation. These results imply that the inhibitory effect of triflavin on the adhesion of tumor cells to ECMs (e.g., fibronectin, vitronectin and collagen type I) and/or tumor cell-induced platelet aggregation may be partially responsible for its antimetastatic activity in C57BL/6 mice.

Triflavin, an Arg-Gly-Asp (RGD)-containing peptide, purified from snake venom of Trimeresurus flavoviridis, inhibits human platelet aggregation through the blockade of fibrinogen binding to fibrinogen receptors associated with glycoprotein IIb/IIIa complex. In this report, we examined the effect of triflavin on tumor cells (human hepatoma J-5)-induced platelet aggregation (TCIPA) of heparinized platelet-rich plasma (PRP). ADP-scavenger agents, apyrase (10 U/ml) and creatine phosphate (5 mM)/creatine phosphokinase (5 U/ml) did not inhibit TCIPA while hirudin (5 U/ml) completely inhibited it. J-5 cells initially induced platelet aggregation, then blood coagulation occurred. J-5 cells concentration-dependently shortened the recalcification time of normal as well as Factor VIII, IX-deficient human plasmas, while it was inactive at shortening the recalcification time of Factor VII-deficient plasma, suggesting J-5 cells induced platelet aggregation through activation of extrinsic pathway, leading to thrombin formation as evidenced by the amidolytic activity on s-2238 by expressing tissue factor-like activity. Triflavin inhibited TCIPA in a dose-dependent manner (IC50, 0.02 microM). When compared on molar ratio, triflavin was approximately 30,000 times more potent than GRGDS (IC50, 0.58 mM). On the other hand, GRGES showed no significant effect on TCIPA, even its concentration was raised to 4 mM. Additionally, the monoclonal antibodies, raised against glycoprotein IIb/IIIa complex (i.e., 7E3 and 10 E5) inhibited J-5 TCIPA. In conclusion, we suggest the inhibitory effect of triflavin on J-5 TCIPA may be chiefly mediated by the binding of triflavin to the fibrinogen receptor associated with glycoprotein IIb/IIIa complex on platelet surface membrane.

X-linked agammaglobulinemia (Bruton's disease) is a rare disease characterized by marked decrease in all classes of immunoglobulins and absence of circulating B cells and plasma cells. The affected boys frequently present with recurrent respiratory tract infections after 6 months to 2 years of age. A combination regimen of intravenous human immunoglobulins and strong parenteral antibiotics remains the stone of treatment. Herein we report a one year and ten months old boy with Bruton's disease. He has had repeated infections of upper and lower respiratory tract since 6 months of age. Immunological studies revealed panhypogammaglobulinemia, nearly total absence of circulating B cells, negative isohemagglutinins and reversed CD4/CD8 ratio. Pedigree analysis suggests a sex-linked recessive inheritance. Intravenous immunoglobulins as well as parenteral antibiotics were administered to overcome pneumonia and purulent otitis media. He is currently undergoing co-trimethoxazole prophylaxis and periodic intravenous immunoglobulins infusion.