Atypical presentation of tuberous sclerosis and obsessive compulsive disorder in an adult male

Tuberous Sclerosis (TSC) is clinically marked by a triad of adenoma sebaceum, epilepsy and mental retardation. It can however manifest as various neuropsychiatric disorders. We report a patient who presented with TSC and co-morbid Obsessive Compulsive Disorder.     

Use of broadly neutralizing antibodies for HIV-1 prevention

Antibodies have a long history in antiviral therapy, but until recently, they have not been actively pursued for HIV-1 due to modest potency and breadth of early human monoclonal antibodies (MAbs) and perceived insurmountable technical, financial, and logistical hurdles. Recent advances in the identification and characterization of MAbs with the ability to potently neutralize diverse HIV-1 isolates have reinvigorated discussion and testing of these products in humans, since new broadly neutralizing MAbs (bnMAbs) are more likely to be effective against worldwide strains of HIV-1. In animal models, there is abundant evidence that bnMAbs can block infection in a dose-dependent manner, and the more potent bnMAbs will allow clinical testing at infusion doses that are practically achievable. Moreover, recent advances in antibody engineering are providing further improvements in MAb potency, breadth, and half-life. This review summarizes the current state of the field of bnMAb protection in animal models as well as a review of variables that are critical for antiviral activity. Several bnMAbs are currently in clinical testing, and we offer perspectives on their use as pre-exposure prophylaxis (PrEP), potential benefits beyond sterilizing immunity, and a discussion of future approaches to engineer novel molecules.     

Early events in Mycobacterium tuberculosis infection in cynomolgus macaques

Little is known regarding the early events of infection of humans with Mycobacterium tuberculosis. The cynomolgus macaque is a useful model of tuberculosis, with strong similarities to human tuberculosis. In this study, eight cynomolgus macaques were infected bronchoscopically with low-dose M. tuberculosis; clinical, immunologic, microbiologic, and pathologic events were assessed 3 to 6 weeks postinfection. Gross pathological abnormalities were observed as early as 3 weeks, including Ghon complex formation by 5 weeks postinfection. Caseous granulomas were observed in the lung as early as 4 weeks postinfection. Only caseous granulomas were observed in the lungs at these early time points, reflecting a rigorous initial response. T-cell activation (CD29 and CD69) and chemokine receptor (CXCR3 and CCR5) expression appeared localized to different anatomic sites. Activation markers were increased on cells from airways and only at modest levels on cells in peripheral blood. The priming of mycobacterium-specific T cells, characterized by the production of gamma interferon occurred slowly, with responses seen only after 4 weeks of infection. These responses were observed from T lymphocytes in blood, airways, and hilar lymph node, with responses predominantly localized to the site of infection. From these studies, we conclude that immune responses to M. tuberculosis are relatively slow in the local and peripheral compartments and that necrosis occurs surprisingly quickly during granuloma formation.     

Current profile of secondary glaucoma in a Northern India tertiary eye care hospital

Purpose: To study the current profile of secondary glaucoma in all age groups of patients presenting to a tertiary eye care hospital in Northern India

Materials and methods: In this retrospective study, files of 5725 patients who were newly diagnosed to have glaucoma in our tertiary eye care centre from January 2014 to December 2016 were reviewed. Detailed data were collected from patient’s records, including history, best-corrected visual acuity (BCVA), intraocular pressure (IOP), slit-lamp biomicroscopy findings, gonioscopy, and fundus findings. Demographic data, aetiology, and management in all these patients were also noted.

Results: Out of 5820 patients who visited glaucoma outpatient department (OPD) in a tertiary eye care hospital during 1 January 2014 to 31 December 2016, 5725 patients were diagnosed to have glaucoma by the glaucoma specialists. Five thousand three hundred and six patients (92.68%) were diagnosed to have primary glaucoma and 419 patients (7.32%) were diagnosed to have secondary glaucoma. The leading causes of secondary glaucoma were found to be neovascular glaucoma (17.42%), trauma (14.80%), post-keratoplasty (13.60%), post-cataract surgery (13.13%), and lens-induced glaucoma (12.41%). Secondary glaucoma was found to be an important cause of visual morbidity with 71.17% eyes presenting with BCVA < 6/60, IOP > 30 mm Hg in 62% eyes and 72% with cup-to-disc ratio of ≥0.7:1.

Conclusion: Secondary glaucoma is an important cause of visual morbidity. Timely diagnosis and prompt management are essential to prevent irreversible visual loss due to secondary glaucoma.     

Effect of dexmedetomidine on intraocular pressure as an additive in peribulbar block during glaucoma surgery

Purpose:The purpose of this study is to assess the effect of dexmedetomidine on intraocular pressure (IOP) as an additive in peribulbar injections in glaucoma surgeries.Methods:A prospective, randomized, double-blind, parallel assignment interventional study was conducted for patients undergoing glaucoma surgeries at a tertiary eye care hospital in North India. Patients were randomized to two groups, Dexmed group and Placebo group. In the Dexmed group, dexmedetomidine (0.4 μg/kg body weight) was given as an additive along with peribulbar block. The primary outcome was change in IOP pre- and postperibulbar injections (IOP before the block, and after 5 and 15 min of the block). Secondary outcome measures were onset of block, adverse effects (bradycardia, hypotension, respiratory depression, and level 4 sedation), and surgeon satisfaction.Results:A total of 104 patients were randomized, 52 each in the Dexmed group and Placebo group. The percentage decrease in IOP was significantly more in the Dexmed group than in the Placebo group both at 5 and 15 min'' post block (P < 0.05). At 5 min, the mean percent decrease in IOP in Dexmed group was -10.48, whereas it was 2.85 in the Placebo group. At 15 min, the mean percent decrease in IOP was -22.59 and -9.42 in the Dexmed and Placebo group, respectively. There was no significant difference between the two groups in the onset of block and adverse effects. Surgeon satisfaction was significantly greater in the Dexmed group than the Placebo group (P < 0.05).Conclusion:Dexmedetomidine lowers IOP significantly in patients undergoing glaucoma surgeries with safe hemodynamic changes and sedative effect.     

Concordance of immunological events between intrarectal and intravenous SHIVAD8-EO infection when assessed by Fiebig-equivalent staging

Primary HIV-1 infection can be classified into six Fiebig stages based on virological and serological laboratory testing, whereas simian-HIV (SHIV) infection in nonhuman primates (NHPs) is defined in time post-infection, making it difficult to extrapolate NHP experiments to the clinics. We identified and extensively characterized the Fiebig-equivalent stages in NHPs challenged intrarectally or intravenously with SHIV_AD8-EO. During the first month post-challenge, intrarectally challenged monkeys were up to 1 week delayed in progression through stages. However, regardless of the challenge route, stages I–II predominated before, and stages V–VI predominated after, peak viremia. Decrease in lymph node (LN) CD4⁺ T cell frequency and rise in CD8⁺ T cells occurred at stage V. LN virus-specific CD8⁺ T cell responses, dominated by degranulation and TNF, were first detected at stage V and increased at stage VI. A similar late elevation in follicular CXCR5⁺ CD8⁺ T cells occurred, consistent with higher plasma CXCL13 levels at these stages. LN SHIV_AD8-EO RNA⁺ cells were present at stage II, but appeared to decline at stage VI when virions accumulated in follicles. Fiebig-equivalent staging of SHIV_AD8-EO infection revealed concordance of immunological events between intrarectal and intravenous infection despite different infection progressions, and can inform comparisons of NHP studies with clinical data.     

Correlation between choroidal thickness and intraocular pressure control in primary angle-closure glaucoma

Purpose:To study the correlation between choroidal thickness (CT) and IOP control in primary angle-closure glaucoma (PACG).Methods:In total, 61 patients (102 eyes) with PACG underwent subfoveal CT (SFCT) scanning using enhanced depth imaging–optical coherence tomography. The subjects with PACG were further grouped as controlled IOP (≤21 mm Hg on maximal medical therapy) and uncontrolled IOP (>21 mm Hg on maximal medical therapy). The average CT of the PACG eyes was calculated and compared between both groups. A correlation analysis was done between CT and intereye difference in CT with the disease parameters.Results:The mean CT was 274.38 ± 42.10 μm in 102 PACG eyes. SFCT was significantly increased in the uncontrolled IOP group as compared with the controlled IOP group. The mean SFCT was 245.57 ± 62.10 μm in the controlled group and 294.46 ± 51.05 μm in the uncontrolled group (P < 0.01). Factors associated with a thicker choroid were younger age, high IOP, and higher optic nerve head cupping (P < 0.001). Neither the visual field-mean deviation (VF-MD) nor pattern standard deviation (PSD) was found to be associated with overall CT. The intereye asymmetry between CT was significantly associated with poor VF-MD and PSD.Conclusion:PACG eyes with thicker choroid may be a risk factor for poor IOP control on medical anti-glaucoma therapy. Thicker choroid as compared to the fellow eye is a poor prognostic sign and these eyes should be monitored closely.