Role of AS-OCT in Managing Corneal Disorders.

Optical coherence tomography (OCT) is analogous to ultrasound biometry in the cross sectional imaging of ocular tissues. Development of current devices with deeper penetration and higher resolution has made it popular tool in clinics for visualization of anterior segment structures. In this review, the authors discussed the application of AS-OCT for diagnosis and management of various corneal and ocular surface disorders. Further, recent developments in the application of the device for pediatric corneal disorders and extending the application of OCT angiography for anterior segment are introduced.

Sex ratio trajectory in mouse.

Skewing of the sex ratio towards males occurs in humans. The possible explanation for excess male births could be a preference for Y-bearing sperm at fertilization and/or selective elimination of female embryos during pregnancy. In this study, we have tested the sex ratio in the preimplantation embryo (2-3 cells stage/closest possible primary sex ratio), the post-implantation embryo (day E7.5), and at birth (secondary sex ratio) on a homogenous (genetic, environmental, and dietary) population of mice to ascertain the biological reason i.e., male preference at fertilization or female elimination during pregnancy or both. Primary sex ratio on early preimplantation embryos (2-3 cells stage) was studied on 598 embryos and secondary sex ratio (at birth) on 721 pups using PCR-based sexing (both X & Y chromosome-specific) besides sex ratio of 80 post-implantation embryos (day E7.5). We have also investigated whether the fat content (high & low) of the diet affects the sex ratio. We observed a skewed sex ratio (more female) in preimplantation embryos (0.436; 95 % CI 0.39, 0.48), and post-implantation embryos (0.462; 95 % CI 0.35, 0.57) but reverse skewing (more male) at birth (0.539; 95 % CI 0.5, 0.58). We also observed that high-fat diet promoted male sex ratio at birth (0.657; 95 % CI 0.57, 0.74) whereas a low-fat diet had the opposite effect (0.46; 95 % CI 0.36, 0.56) but no effect at fertilization (2-3 cells stage embryos). This indicates selective elimination of female embryo and fetus throughout pregnancy in mice, more so with a high-fat diet.

Eosinophilic pneumonia: a case of daptomycin induced lung injury.

Eosinophilic pneumonia is a category of lung diseases characterized by an increased number of eosinophils in alveolar spaces and interstitium. Acute cases are often caused by fungal infections, parasites, drugs or toxins and can present with respiratory failure. Daptomycin has been identified as one of the rare causes of acute eosinophilic pneumonia. We describe a case of an elderly man on daptomycin for MRSA endocarditis treatment who presented to the hospital with fevers and dyspnea within two weeks of daptomycin initiation. As an inpatient, he developed an increasing oxygen requirement necessitating intensive care unit management. Daptomycin cessation improved his symptoms and he was placed on a steroid taper. These findings suggested a diagnosis of daptomycin-induced eosinophilic pneumonia. However, the patient deteriorated and eventually passed away despite resuscitative efforts. This case highlights the importance of prompt identification of eosinophilic pneumonia, its potential severity and the need for more exploration regarding the timing of corticosteroid taper. This in turn will inform more effective approaches to this condition in the future.

Independent impact of plasma homocysteine levels on neurological outcome following head injury.

Homocysteine (tHcy) has been hardly studied among patients with head injury. This study was to evaluate whether there is any independent impact of tHcy levels on neurological outcome following head injury in a multivariate model. Patients admitted within 24 h of injury were included in the study, along with 20 age- and gender-matched controls. Plasma levels of tHcy were measured at admission using direct immunoassay. All the variables were analyzed with respect to tHcy levels and outcome according to Glasgow Outcome Score (GOS) at 3 months. Univariate and multivariate analyses were performed using SPSS 21. There were a total of 72 patients in the study. tHcy levels were significantly higher after head injury (mean 24.03[SD ± 16.0] µmol/L), compared to matched controls (mean 16.62 [SD ± 10.4] µmol/L) (p = 0.05). Patients with severe head injury, acute SDH, or diffuse higher radiological grades had greater levels of tHcy compared to others. There was a significant relationship between tHcy level and neurological outcome. tHcy levels were significantly higher in patients who had unfavorable GOS (mean 36.22[±25.3] µmol/L), compared to those with favorable GOS (mean 22.71[±14.3] µmol/L) (P = 0.03). In multivariate analysis, tHcy level (adj. odds ratio [OR] 1.17, P = 0.05) and Glasgow Coma Scale (adj. OR 5.17, P = 0.01) had significant association with neurological outcome at 3 months independent of age, dietary habit, radiological grading and of each other. tHcy level has significant independent impact on neurological outcome and may be useful as a prognostic marker following head injury.

Fluorescence in situ hybridization (FISH) using non-commercial probes in the diagnosis of clinically suspected microdeletion syndromes.

BACKGROUND & OBJECTIVES: Microdeletion syndromes are characterized by small (<5 Mb) chromosomal deletions in which one or more genes are involved. These are frequently associated with multiple congenital anomalies. The phenotype is the result of haploinsufficiency of genes in the critical interval. Fluorescence in situ hybridization (FISH) technique is commonly used for precise genetic diagnosis of microdeletion syndromes. This study was conducted to assess the role of FISH in the diagnosis of suspected microdeletion syndrome. METHODS: FISH was carried out on 301 clinically suspected microdeletion syndrome cases for the confirmation of clinical diagnosis using non-commercial probes. Of these, 177 cases were referred for 22q11.2 microdeletion, 42 cases were referred for William syndrome, 38 cases were referred for Prader Willi/Angelman and 44 cases were referred for other suspected microdeletion syndromes. RESULTS: FISH was confirmatory in 23 cases only (7.6%). There were 17 cases of 22q11.2 microdeletion, four cases of Prader Willi syndrome and two cases of William syndrome. INTERPRETATION & CONCLUSION: We conclude that FISH should not be the method of choice for clinically suspected microdeletion syndromes. We propose to follow strict clinical criteria for FISH testing or preferably to follow better methods (genotype first approach). Whole genome screening may be used as first line of test and FISH may be used for confirmation of screening result, screening of family members and prenatal diagnosis.

The Sertoli Cell Only Syndrome and Glaucoma in a Sex - Determining Region Y (SRY) Positive XX Infertile Male.

The XX male syndrome is a rare genetic disorder. The phenotype is variable; it ranges from a severe impairment of the external genitalia to a normal male phenotype with infertility. It generally results from an unequal crossing over between the short arms of the sex chromosomes (X and Y). We are reporting a case of a 38-year-old man who presented with infertility and the features of hypogonadism and glaucoma. The examinations revealed normal external male genitalia, soft small testes, gynaecomastia and glaucoma. The semen analysis showed azoospermia. The serum gonadotropins were high, with low Anti Mullerian Hormone (AMH) and Inhibin B levels. The chromosomal analysis demonstrated a 46, XX karyotype. Fluorescent In-Situ Hybridization (FISH) and Polymerase Chain Reaction (PCR) revealed the presence of a Sex-determining Region Y (SRY). Testicular Fine Needle Aspiration Cytology (FNAC) revealed the Sertoli Cell Only Syndrome (SCOS). The presence of only Sertoli Cells in the testes, with glaucoma in the XX male syndrome, to our knowledge, has not been reported in the literature.

Rapid detection of chromosome X, Y, 13, 18, and 21 aneuploidies by primed in situ labeling/synthesis technique.

AIMS AND OBJECTIVE: Primed in situ labeling/synthesis (PRINS) technique is an alternative to fluorescent in situ hybridization for chromosome analysis. This study was designed to evaluate the application of PRINS for rapid diagnosis of common chromosomal aneuploidy. MATERIALS AND METHODS: We have carried out PRINS using centromere specific oligonucleotide primers for chromosome X, Y, 13, 18 and 21 on lymphocyte metaphase and interphase cells spread. Specific primer was annealed in situ, followed by elongation of primer by Taq DNA polymerase in presence of labeled nucleotides. Finally, reaction was stopped and visualized directly under fluorescent microscope. RESULTS: Discrete centromere specific signals were observed with each primer. CONCLUSION: PRINS seems to be a rapid and reliable method to detect common chromosome aneuploidy in peripheral blood lymphocyte metaphase and interphase cells.

Chromosome 22q11.2 microdeletion in monozygotic twins with discordant phenotype and deletion size.

We report on a pair of male monozygotic twins with 22q11.2 microdeletion, discordant phenotype and discordant deletion size. The second twin had findings suggestive of DiGeorge syndrome, while the first twin had milder anomalies without any cardiac malformation. The second twin had presented with intractable convulsion, cyanosis and cardiovascular failure in the fourth week of life and expired on the sixth week of life, whereas the first twin had some characteristic facial appearance with developmental delay but no other signs of the 22q11.2 microdeletion syndrome including cardiovascular malformation. The fluorescence in situ hybridization (FISH) analysis had shown a microdeletion on the chromosome 22q11.2 in both twins. The interphase FISH did not find any evidence for the mosaicism. The genomic DNA microarray analysis, using HumanCytoSNP-12 BeadChip (Illumina), was identical between the twins except different size of deletion of 22q11.2. The zygosity using HumanCytoSNP-12 BeadChip (Illumina) microarray analysis suggested monozygosity. This observation indicates that altered size of the deletion may be the underlying etiology for the discordance in phenotype in monozygotic twins. We think early post zygotic events (mitotic non-allelic homologous recombination) could have been played a role in the alteration of 22q11.2 deletion size and, thus phenotypic variability in the monozygotic twins.

Prevalence of 22q11.2 microdeletion in 146 patients with cardiac malformation in a referral hospital of North India.

BACKGROUND: The 22q11.2 microdeletion syndrome is a common condition that is associated with cardiac as well as extra-cardiac manifestations. Its prevalence and manifestations from north India has not been reported. This study was designed to determine the prevalence and ability of clinical criteria to predict 22q11.2 microdeletion. METHODS: A total of 146 cases of cardiac malformation requiring tertiary care at a teaching hospital were prospectively screened for 22q11.2 microdeletion using fluorescence in situ hybridization test. Detailed clinical information was obtained as per guidelines of Tobias, et al (1999). RESULTS: Nine out of 146 patients (6.16%) was found to have 22q11.2 microdeletion. All the positive patients showed the presence of extra-cardiac features of 22q11.2 microdeletion syndrome. None of the cases with isolated cardiac defect were positive for microdeletion. CONCLUSIONS: It seems that 22q11.2 microdeletion syndrome is over-suspected in children with isolated congenital heart defects. Screening for 22q11.2 microdeletion should be considered in those cardiac malformation cases which have extra-cardiac manifestations in the form of facial dysmorphism and hypocalcaemia.