Bilateral optic disc pathologies as an accompanying feature of comitant strabismus in children

Purpose

To describe and report accompanying bilateral optic disc pathologies in children with comitant strabismus.

Methods

Twenty-eight patients (16 female, 12 male) aged between 1 and 12 years who had comitant strabismus and bilateral optic disc pathologies were included in the study. Visual acuity, refractive errors, amount of deviation and types of optic disc pathologies were all recorded. Each patient underwent complete neurological and ophthalmological examination.

Results

Of the 28 patients, 14 (50.0%) had esotropia and 14 (50.0%) had exotropia. The mean age was 4.18 ± 3.03 years. The mean deviation angle was 35.30 ± 13.26 prism diopters (PD) (20–70 PD). Optic atrophy as being the most common pathology was found in nine (32.1%) patients. Six (21.4%) patients had temporal disc pallor, six (21.4%) patients had optic nerve hypoplasia, and seven (25%) patients had other optic disc anomalies (tilted disc, megalodisc, disc coloboma, peripapillary staphyloma). Optic disc pathologies were found to be isolated in 12 patients. Nine of 13 patients with congenital optic disc pathologies had esotropia, whereas 10 of 15 patients with optic atrophy or optic disc pallor had exotropia.

Conclusion

Comitant strabismus in children can be associated with congenital or acquired optic disc pathologies. It is worthy of note that esotropia was more common in patients with congenital optic disc pathologies, whereas exotropia was more frequent in patients with optic atrophy or optic disc pallor. The findings of the present study show that complete ophthalmological examination including fundus evaluation should be carried out in all patients with strabismus even though the cause of ocular misalignment is obvious.

     

External validation and comparison of the scoring systems (S.T.O.N.E,GUY, CROES,S-ReSC) for predicting percutaneous nephrolithotomy outcomes for staghorn stones: A single center experience with 160 cases

The aim of this study was validation and comparison of stone scoring systems (S.T.O.N.E, GUY, CROES, S-ReSC) used to predict postoperative stone-free status and complications after percutaneous nephrolithotomy (PCNL) for staghorn stones. A total of 160 patients who had staghorn renal stones and underwent PCNL between January 2012 and August 2015 were included in the current retrospective study. Guy, S.T.O.N.E., S-ReSC (Seoul National University Renal Stone Complexity) and CROES (Clinical Research Office of the Endourological Society) nephrolithometry scores were calculated for each patient, and their potential association with stone-free status, operative and fluoroscopy time, and length of hospital stay (LOS) were evaluated. Postoperative complications were graded according to the modified Clavien classification, and the correlation of scoring systems with postoperative complications was also investigated. The mean CROES, S.T.O.N.E, Guy and S-ReSC scores were 143.5 ± 33.6, 9.7 ± 1.6, 3.5 ± 0.5 and 6.2 ± 2.0 respectively. The overall stone-free rate was 59%. All scoring systems were significantly correlated with stone-free status in univariate analysis. However, Guy and S-ReSC scores were the only significant independent predictor in multivariate analysis. And all four nomograms failed to predict complication rates. Current study demonstrated that Guy and S-ReSC scoring systems could effectively predict postoperative stone-free status for staghorn stones. However all four scoring systems failed to predict complication rates.     

Predictors of failure of the commonly used single-dose methotrexate protocol for treating tubal ectopic pregnancies

Objectives

This study identified patients who would benefit from an earlier additional medical intervention and/or continuing close surveillance even if commonly used parameters indicated sufficient medical treatment to determine markers of treatment failure.

Phosphorothioate 2′ Deoxyribose Oligomers as Microbicides That Inhibit Human Immunodeficiency Virus Type 1 (HIV-1) Infection and Block Toll-Like Receptor 7 (TLR7) and TLR9 Triggering by HIV-1

Topical microbicides may prove to be an important strategy for preventing human immunodeficiency virus type 1 (HIV-1) transmission. We examined the safety and efficacy of sequence-nonspecific phosphorothioate 2′ deoxyribose oligomers as potential novel microbicides. A short, 13-mer poly(T) phosphorothioate oligodeoxynucleotide (OPB-T) significantly inhibited infection of primary peripheral blood mononuclear cells (PBMC) by high-titer HIV-1_Ba-L and simian immunodeficiency virus mac251 (SIV_mac251). Continuous exposure of human vaginal and foreskin tissue explants to OPB-T showed no toxicity. An abasic 14-mer phosphorothioate 2′ deoxyribose backbone (PDB) demonstrated enhanced anti-HIV-1 activity relative to OPB-T and other homo-oligodeoxynucleotide analogs. When PDB was used to pretreat HIV-1, PDB was effective against R5 and X4 isolates at a half-maximal inhibitory concentration (IC₅₀) of <1 μM in both PBMC and P4-R5 MAGI cell infections. PDB also reduced HIV-1 infectivity following the binding of virus to target cells. This novel topical microbicide candidate exhibited an excellent in vitro safety profile in human PBMC and endocervical epithelial cells. PDB also retained activity in hydroxyethylcellulose gel at pH 4.4 and after transition to a neutral pH and was stable in this formulation for 30 days at room temperature. Furthermore, the compound displayed potent antiviral activity following incubation with a Lactobacillus strain derived from normal vaginal flora. Most importantly, PDB can inhibit HIV-1-induced alpha interferon production. Phosphorothioate 2′ deoxyribose oligomers may therefore be promising microbicide candidates that inhibit HIV-1 infection and also dampen the inflammation which is critical for the initial spread of the virus.The global spread of human immunodeficiency virus type 1 (HIV-1) is largely driven through sexual contact, particularly in sub-Saharan Africa, where 67% of the 33 million individuals who are currently infected with HIV-1 reside (23). In the absence of a vaccine that elicits sterilizing immunity and protects against HIV-1 infection (13, 21), significant effort is being directed to developing other prophylactic modalities that could potentially slow down or ultimately reverse the rate of propagation of the HIV/AIDS pandemic. One such alternative strategy for reducing the transmission of HIV-1 is the use of protective topical compounds that can be applied directly within the genital tract prior to sexual intercourse (10, 24). Candidate anti-HIV-1 microbicides that are under development for intravaginal application include surfactants that inactivate or disrupt the virus (20), inhibitors of viral binding, fusion, entry, or replication (3, 7, 22, 39, 46, 53), and agents that enhance the normal vaginal microflora (54). Investigations with the rhesus macaque animal model have revealed opportunities at the earliest stages of infection in which a microbicide may be protective by directly inhibiting intravaginal simian immunodeficiency virus (SIV) (50) or modulating the innate immune response to limit viral expansion from the portal of entry (18, 33).Previous studies have suggested that the local inflammation induced by HIV at the mucosal site of entry is an important amplification step for the spread of infection. The innate immune response to viral infection in the genital mucosa is initiated when Toll-like receptors (TLRs) expressed by epithelial cells, as well as antigen-presenting cells, bind virus-specific molecules (double-stranded RNA and single-stranded RNA) in the cytoplasm and endosomes (49). Plasmacytoid dendritic cells (pDC) produce the majority of alpha interferon (IFN-α) in response to TLR7 and TLR9 activation by HIV and SIV (30). Although the elaboration of IFN-α/β and antiviral chemokines by pDC may contribute to the initial suppression of viral replication, it also fulfills the more immediate requirement of HIV-1 for new target cells to establish local expansion upon which systemic infection depends (29). In support of this, it was reported that augmentation of antiviral innate immunity through the use of TLR7 and TLR9 agonists in a rhesus macaque challenge model enhanced vaginal transmission of SIV (49). The class A CpG oligodeoxynucleotide used in that study as a TLR9 agonist is a strong inducer of IFN-α but also elicits the production of low levels of proinflammatory cytokines in rhesus macaque peripheral blood mononuclear cells (PBMC) (1). When the type I interferon response was induced with class A CpG or the TLR7 agonist imiquimod at mucosal surfaces prior to intravaginal challenge with SIV, a marked increase in the level of plasma viral RNA was observed. Increased virus dissemination was attributed to a pronounced infiltrate of mononuclear cells consisting of dendritic cells (DC), beta-chemokine-producing cells, and activated CD4⁺ T lymphocytes present in the cervicovaginal mucosa of agonist-treated monkeys (49). Another report demonstrated that TLR9 activation enhances HIV-1 replication (12). Furthermore, Li and colleagues (29) recently established that inhibition of the innate response to SIV in the vaginal environment inhibits the influx of susceptible CD4⁺ T lymphocytes which is required for the systemic dissemination of the virus from a single small focus of infected cells. These studies strongly suggest that inhibition of TLR7/9-induced immunoinflammatory signaling may be a useful strategy for limiting the initial expansion of HIV/SIV from the mucosa to peripheral sites of infection, and such TLR antagonism may be a desirable property for microbicides to possess.In the context of modulating cervicovaginal innate immune responses against HIV/SIV infection, inhibition of TLR activation may need to be targeted to pattern recognition receptors that are specifically triggered by these viruses. Some polyanionic microbicides have been shown to inhibit the activation of multiple TLRs (TLR1, TLR2, TLR3, and TLR6) that recognize viral or bacterial components, and this inhibits innate immune responses by epithelial cells derived from the human female genital tract (48). Additionally, vaginal microflora abnormalities have been documented in clinical studies that evaluated the safety of the same class of polyanionic microbicide candidates (6, 43). Therefore, nonselective suppression of various TLRs that recognize different pathogen-associated molecular patterns can compromise host control of the vaginal microflora, as well as defense against pathogens, and thus enhance HIV/SIV transmission. In contrast, selective blocking of TLRs that are activated by HIV/SIV may inhibit the local inflammation that is required for viral expansion without impairing protective responses against other pathogens or the microflora of the cervicovaginal mucosa.The therapeutic potential of oligodeoxynucleotides containing specific immunosuppressive TTAGGG motifs has been described for different inflammatory diseases and other disorders that are characterized by persistent immune activation (25). Additionally, poly(T) oligodeoxynucleotides were reported to differentially modulate the activation of TLR7 and TLR8 by imidazoquinolines (15), and the phosphorothioate backbone can selectively inhibit TLR7/9 signaling (16). Thus, we investigated small molecules with phosphorothioate 2′ deoxyribose backbones as topical microbicides that may inhibit HIV-1-induced TLR triggering and discovered that they also possess antiviral properties. We report here that a 13-mer poly(T) phosphorothioate oligodeoxynucleotide, OPB-T, is effective at inhibiting HIV-1_Ba-L or SIV_mac251 infection in human or simian PBMC, respectively, and shows no toxicity against human vaginal and foreskin explants. A baseless 14-mer phosphorothioate 2′ deoxyribose backbone, PDB, possesses a higher level of inhibitory activity against HIV-1 than OPB-T. PDB exhibits efficacy against both CCR5-using (R5) and CXCR4-using (X4) HIV-1 isolates and exhibits no toxicity in a sensitive flow cytometric assay of cell death. Herein, we present data demonstrating that PDB is active when formulated in hydroxyethylcellulose (HEC) gel at pH 4.4, retains antiviral activity following transition to neutral pH, and is stable in gel at room temperature for more than a month. Furthermore, the compound was effective at inhibiting HIV-1 infection despite exposure to Lactobacillus jensenii, a predominant bacterial species of the normal vaginal microflora that produces hydrogen peroxide (H₂O₂), lactic acid, and other factors (42) that could potentially abrogate the function of microbicides. Notably, PDB is a TLR7/9 antagonist, and we show that it potently suppresses HIV-1-induced IFN-α production. Phosphorothioate oligomers may therefore be useful microbicides against HIV-1, as they not only directly inhibit viral infection but also block HIV-1-induced TLR7/9 activation. Such TLR activation drives the cytokine production required for the recruitment and establishment of HIV-1-infected founder cell populations at mucosal sites and promotes a self-propagating infection in secondary lymphoid organs.     

Choosing a model for laser speckle contrast imaging

Laser speckle contrast imaging (LSCI) is a real-time full-field non-invasive technique, which is broadly applied to visualize blood flow in biomedical applications. In its foundation is the link between the speckle contrast and dynamics of light scattering particles–erythrocytes. The mathematical form describing this relationship, which is critical for accurate blood flow estimation, depends on the sample’s light-scattering properties. However, in biological applications, these properties are often unknown, thus requiring assumptions to be made to perform LSCI analysis. Here, we review the most critical assumptions in the LSCI theory and simulate how they affect blood flow estimation accuracy. We show that the most commonly applied model can severely underestimate the flow change, particularly when imaging brain parenchyma or other capillary perfused tissue (e.g. skin) under ischemic conditions. Based on these observations and guided by the recent experimental results, we propose an alternative model that allows measuring blood flow changes with higher accuracy.     

Hypopharyngeal squamous cell carcinoma in a child

Squamous cell carcinoma of the hypopharynx is extremely rare in children. We present a 13-year-old girl with squamous cell carcinoma of the hypopharynx whose father was a coal-miner and a heavy smoker.     

Split sample comparison of ThinPrep and conventional smears in endoscopic retrograde cholangiopancreatography-guided pancreatic fine-needle aspirations

Fine-needle aspiration (FNA) of pancreatic lesions is a common procedure to establish a tissue diagnosis before chemotherapy or surgery. In this study, the authors attempt to compare the diagnostic value of the ThinPrep (TP) method with conventional smears (CSs) in samples obtained by endoscopic retrograde cholangiopancreatography (ERCP)-guided pancreatic FNAs. Material obtained, prospectively, from ERCP-guided pancreatic FNAs was split to prepare CSs (2-5 slides) first, the remainder being rinsed in PreservCyte, and in the laboratory, 1 TP slide was prepared. The diagnostic categories of unsatisfactory, benign, reactive, suspicious for malignancy, and malignant were compared. Fifty-one pancreatic FNAs prepared by split sample method yielded the following results: TP yielded unsatisfactory, 6 cases; benign, 3 cases; reactive, 5 cases; suspicious for malignancy, 11 cases; and malignant, 26 cases; in contrast, CS yielded unsatisfactory, 13 cases; benign, 4 cases; reactive, 3 cases; suspicious for malignancy, 13 cases; and malignant, 18 cases. Histological follow-up was available in 21 cases (reactive, 8 cases; suspicious for malignancy, 1 case, and malignant, 12 cases). The foregoing data indicate a higher sensitivity in detection of pancreatic adenocarcinoma by the TP method (TP, 91% vs. 58% CS) with equivalent specificity (100%). In addition, TP provides better preservation and cytological detail.     

What is behind smoking among pharmacy students: a quantitative and qualitative study from Turkey

This study, performed in two phases, compared the smoking status of first- and last-year pharmacy students and identified underlying factors of smoking using both "quantitative" and "qualitative" research techniques. The quantitative phase was a cross-sectional study with 207 students (of these, 102 were first-year and 105 were last-year students). The mean age at which first-year students tried tobacco/tobacco products was 14.1 +/- 3.2 and for last-year students, 16.0 +/- 2.4. The students completed an 18-item questionnaire at the end of the spring semester in May 2004. Chi-square and t-test analyses were used for statistical comparisons. Furthermore, focus group discussion techniques were used to find out the underlying factors of smoking in the second phase.     

Improvement in right ventricular systolic function after cardiac resynchronization therapy correlates with left ventricular reverse remodeling

Background: Cardiac resynchronization therapy (CRT) improves left ventricular (LV) systolic function in heart failure (HF). However, the effects of CRT on right ventricular (RV) systolic function are not fully understood. Objective: We aimed to determine echocardiographic correlates of improvement in RV systolic function after CRT. Methods: Fifty‐four patients (61.9 ± 10.5 years; 43 men; LV ejection fraction 24.6 ± 4.0%; QRS duration > 120 ms) with HF were enrolled. Standard echocardiography, strain rate (SR), and tissue Doppler imaging were performed in all patients before and 6 months after CRT. Pulsed‐wave TDI‐derived systolic indices of RV included systolic (RV_S) and isovolumic velocity (RV_IVV) and isovolumic acceleration (RV_IVA). Response to CRT was defined as decline in LV end‐systolic volume (LVESV) ≥ 10%. Results: When indices of RV systolic function were assessed between responders and nonresponders, in responders (38 patients, 70.4%) RV end‐diastolic diameters (RVD1–3), mid‐RV strain, and mid‐RV SR improved significantly (P < 0.01, for all). RV_S (10.77 ± 4.29 vs 12.62 ± 4.10 cm/sec, P = 0.005), RV_IVV (14.71 ± 5.88 vs 18.52 ± 6.62 cm/sec, P < 0.001), and RV_IVA (1.69 ± 0.70 vs 2.39 ± 0.77 m/sec², P < 0.001) significantly increased among responders. There was no significant change in these parameters among nonresponders. Pearson's analyses revealed moderate positive correlations between reduction of LVESV and ΔRV_IVV (r = 0.467, P = 0.001) and ΔRV_IVA (r = 0.473, P = 0.001), respectively. Conclusions: RV diameters and systolic indices after CRT improved only in the responder group. Improvement in RV systolic performance after CRT is correlated with the reduction of LVESV. (PACE 2011; 34:200–207)