Congenital nasolacrimal duct obstruction update study (CUP study): paper I—role and outcomes of Crigler’s lacrimal sac compression

PurposeTo assess the exclusive role and outcomes of Crigler’s lacrimal sac compression in the management of congenital nasolacrimal duct obstruction (CNLDO).MethodsRetrospective interventional case-series was performed on patients diagnosed with CNLDO and who were advised Crigler’s lacrimal sac compression (CLSC) at a tertiary care Dacryology Institute from Jan 2016 to June 2019. CNLDO patients who were practicing incorrect techniques of lacrimal sac compression at presentation were separately assessed. All the patients were assigned to four groups (Gr 1: 0–3 months, Gr 2: >3 & <6 months, Gr 3: >6 & <9 months and Gr 4: >9 and <12 months) based on the age at which the CLSC was initiated and followed up quarterly or as needed till at least 1 year of age. The parameters studied include patient demographics, clinical presentation, age of initiation of CLSC, success rate with CLSC, and need for additional interventions. Success was defined as the subjective resolution of epiphora and discharge with objective measures of normal tear meniscus height and dye clearance on fluorescein dye disappearance test.ResultsA total number of 1240 patients with CNLDO were assessed. Of these, 1037 patients were advised correct techniques of CLSC from the beginning, and the remaining 203 patients were referred but performing it incorrectly at presentation. Of the 1037 patients, 236 were lost to follow-up; hence, a total of 1004 patients (801 + 203) were included for final analysis. CLSC was found to be an effective conservative strategy in the management of CNLDO. The rate of resolution of CNLDO in Gr 1 to Gr 4 was 87.3%, 78.9%, 77.9%, and 76.8%, respectively. There were no statistically significant differences in the outcomes based on the age of CLSC initiation. The referred patients whose techniques were rectified following the initial incorrect techniques showed a resolution of 61.2% (79/129). The correct techniques of CLSC appeared to influence the outcomes. However, the age of its initiation did not substantially impact the outcomes. Significantly high resolution was noted even beyond nine months of age and encouraging results beyond 12 months of age.ConclusionsIt is crucial to initiate the correct techniques of Crigler’s lacrimal sac compression to achieve favourable outcomes. Age of initiation of CLSC in infancy does not appear to influence the outcomes. The resolution rate continued to be significantly high up to 1 year of age. There is a need to assess the role of CLSC beyond 12 months of age.Subject terms: Lacrimal apparatus diseases, Respiratory tract diseases     

Sonographic features of breast carcinoma presenting as masses in BRCA gene mutation carriers.

OBJECTIVE: The purpose of this study was to review the sonographic features of breast cancer gene BRCA1- and BRCA2-associated breast carcinomas in comparison with "sporadic" breast carcinomas and benign breast masses. METHODS: Sonograms of 233 breast masses, including 33 BRCA-associated malignant masses (BRCA1, 15; BRCA2, 18), 148 sporadic malignant masses, and 52 benign masses, were reviewed by consensus by 2 radiologists according to American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) terminology. RESULTS: Most of the sporadic and BRCA1-and BRCA2-associated cancers displayed an irregular shape (91.2%, 93.3%, and 83.3%, respectively). BRCA1-associated cancers showed microlobulated margins in 53.3% versus 33.8% (sporadic) and 33.3% (BRCA2). A parallel orientation was most frequently encountered in BRCA1-associated lesions (46.7%) versus sporadic (33.8%) and BRCA2 (33.3%), whereas posterior acoustic shadowing was least frequently seen in BRCA1-associated lesions (13.3%) versus BRCA2 (16.7%) and sporadic (31.1%). Most (73.3%) of the BRCA1-associated lesions were classified as BI-RADS category 4, whereas most of the sporadic and BRCA2-associated lesions were classified as BI-RADS category 5 (66.2% and 72.2%). CONCLUSIONS: Sonographic features of BRCA-associated and sporadic breast carcinomas do not differ substantially. BRCA1-associated breast carcinomas trend toward less malignant sonographic characteristics, but strict application of the BI-RADS categorizations demands that they be classified as category 4 or 5.     

Efficacy of the potentized homeopathic drug, Carcinosin 200, fed alone and in combination with another drug, Chelidonium 200, in amelioration of p-dimethylaminoazobenzene-induced hepatocarcinogenesis in mice

OBJECTIVES: This study was conducted to examine whether the potentized homeopathic remedy Carcinosin 200, fed alone and in combination with Chelidonium 200, has differential protective effects against p-dimethylaminoazobenzene (p-DAB)-induced hepatocarcinogenesis in mice. DESIGN: Liver tumors were induced in mice through chronic feeding of p-DAB (initiator) and phenobarbital (PB, promoter). The mice were divided into two subgroups: (1) one was fed potentized Alcohol 200 and served as controls; and (2) the other was fed Carcinosin 200 alone or in combination with Chelidonium 200 and divided into several sets. The relative efficacy of the two potentized remedies, alone or in combination, in combating hepatocarcinogenesis was assessed through several cytogenetical endpoints such as chromosome aberrations, induction of micronuclei, sperm head anomaly, and mitotic index at several intervals of fixation (days 7, 15, 30, 60, 90, and 120). Several toxicity biomarkers such as acid and alkaline phosphatases, glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, and lipid peroxidation activity were also assayed in three organs of treated and control mice. In addition, recovery by the homeopathic drugs, if any, of tissue damage inflicted because of chronic feeding of p-DAB and PB was also assessed by optical, scanning, and transmission electron microscopies of liver done at days 60 and 120. RESULTS: Both Carcinosin 200 and Chelidonium 200 when administered alone show considerable ameliorative effect against p-DAB-induced hepatocarcinogenesis in mice; but the conjoint feeding of these two drugs appears to have had a slightly greater protective effect. CONCLUSIONS: These homeopathic remedies have the potential to be used as complementary and alternative medicine in liver cancer therapy, particularly as supporting palliative measures.     

Oral Exposure to Bisphenol A Increases Dimethylbenzanthracene-Induced Mammary Cancer in Rats

Background

Bisphenol A (BPA) is widely used in the manufacture of polycarbonate plastics, including infant formula bottles.

Objectives

Based on the reported endocrine disruptor activity of this polyphenol, we hypothesized that exposure to BPA early in life would elicit developmental changes in the mammary tissue and cause a predisposition for mammary cancer.

Methods

We exposed neonatal/prepubertal rats to BPA via lactation from nursing dams treated orally with 0, 25, and 250 μg BPA/kg body weight/day. For tumorigenesis studies, female offspring were exposed to 30 mg dimethylbenzanthracene (DMBA)/kg body weight at 50 days of age.

Results

The combination of DMBA treatment with lactational exposure to BPA demonstrated a dose-dependent increase in mammary tumor multiplicity and reduced tumor latency compared with controls. In the absence of DMBA treatment, lactational BPA exposure resulted in increased cell proliferation and decreased apoptosis at 50 but not 21 days postpartum (shortly after last BPA treatment). Using Western blot analysis, we determined that steroid receptor coactivators (SRCs) 1–3, Akt, phosphorylated Akt, progesterone receptor A (PR-A), and erbB3 proteins were significantly up-regulated at 50 days of age.

Conclusions

The data presented here provide the first evidence that maternal exposure to BPA during lactation increases mammary carcinogenesis in a DMBA-induced model of rodent mammary cancer. Changes in PR-A, SRC 1–3, erbB3, and Akt activity are consistent with increased cell proliferation and decreased apoptosis playing a role in mammary cancer susceptibility. These alterations provide an explanation of enhanced mammary carcinogenesis after lactational BPA exposure.     

Modeling conditional dependence between diagnostic tests: A multiple latent variable model

Applications of latent class analysis in diagnostic test studies have assumed that all tests are measuring a common binary latent variable, the true disease status. In this article we describe a new approach that recognizes that tests based on different biological phenomena measure different latent variables, which in turn measure the latent true disease status. This allows for adjustment of conditional dependence between tests within disease categories. The model further allows for the inclusion of measured covariates and unmeasured random effects affecting test performance within latent classes. We describe a Bayesian approach for model estimation and describe a new posterior predictive check for evaluating candidate models. The methods are motivated and illustrated by results from a study of diagnostic tests for Chlamydia trachomatis. Published in 2008 by John Wiley & Sons, Ltd.     

Protective effect of prion protein via the N-terminal region in mediating a protective effect on paraquat-induced oxidative injury in neuronal cells

Transmissible spongiform encephalopathies are a group of neurodegenerative disorders caused by a posttranslational, conformational change in the cellular isoform of the prion protein (PrP(C)) into an infectious, disease-associated form (PrP(Sc)). Increasing evidence supports a role for PrP(C) in the cellular response to oxidative stress. We investigated the effect of oxidative stress mediated by paraquat exposure on SH-SY5Y neuroblastoma cells. A loss of mitochondrial membrane potential and subsequent reduction in ATP production were demonstrated in untransfected SH-SY5Y cells, an effect that was ameliorated by the expression of PrP(C). Cells expressing either PrP-DeltaOct, which lacks the octapeptide repeats, or PrP-DA, in which the N-terminus is tethered to the membrane, showed increased sensitivity to paraquat compared with cells expressing wild-type PrP(C) as shown by reduced viability, loss of their membrane integrity, and reduced mitochondrial bioenergetic measurements. Exposure of prion-infected mouse SMB15S cells to paraquat resulted in a reduction in viability to levels similar to those seen in the untransfected SH-SY5Y cells. However, "curing" the cells with pentosan sulfate restored the viability to the level observed in the SH-SY5Y cells expressing PrP(C). These data would indicate that the molecular mechanism promoting cellular resistance to oxidative stress had been compromised in the infected SMB15S cells, which could be reinstated upon curing. Our study supports the hypothesis that PrP(C) expression protects cells against paraquat-induced oxidative injury, demonstrates the significance of the N-terminal region of the protein in mediating this protective effect, and also shows that the biochemical consequences of prion infection may be reversed with therapeutic intervention.     

Early structural and functional neurovascular changes in the retina in the prediabetic stage

PurposeThis study was undertaken to investigate the neurovascular changes in the retina of prediabetic subjects.MethodsSubjects enroled in a prospective study were separated into prediabetic and normal control groups based on their glycosylated haemoglobin (HbA1C) levels, fasting and postprandial blood sugar levels and glucose tolerance test. All the subjects underwent detailed ophthalmic evaluation, which included fundus examination, fundus photography, optical coherence tomography angiography (OCTA), and multifocal electroretinogram (mfERG). Comparisons were done between the groups using the Wilcoxon signed rank test.ResultsThe median age was 48 years for the normal controls (n = 40), and 49.5 years for prediabetic subjects (n = 45) (p = 0.306). There was no difference in the vision, contrast sensitivity, thickness of the ganglion cell complex or the foveal avascular zone parameters between the groups. But the central foveal thickness and subfoveal choroidal thickness were significantly reduced in prediabetics (p < 0.01). The mfERG showed significant differences in the amplitude. The average amplitude was 35 ± 12 nv/deg² in the normals and 29 ± 11 nv/deg² in the prediabetics (p = 0.003). A weak positive correlation was noted between the mfERG and vascular parameters in the prediabetic group.ConclusionsThe prediabetic stage reveals earliest functional neuronal changes in the retina. The neuronal function seems to be affected much earlier than clinically appreciable structural changes in the ganglion cell complex and precedes vascular changes in the retina.Subject terms: Predictive markers, Blood flow