Feasibility and efficacy of gonadotropin-releasing hormone agonists for the prevention of chemotherapy-induced ovarian insufficiency in patients with malignant ovarian germ cell tumours (KGOG 3048R).

BACKGROUND: This study assessed the effects of gonadotropin-releasing hormone agonists (GnRHa) on the prevention of chemotherapy-induced ovarian insufficiency among young patients with malignant ovarian germ cell tumour (MOGCT) receiving chemotherapy. METHODS: This multicentre, retrospective study was conducted at 15 sites affiliated with the Korean Gynecologic Oncology Group and enrolled 354 patients between January 1995 and September 2018. Among them, 227 patients were included in this study and divided into two groups according to the use of GnRHa during chemotherapy (GnRHa versus no GnRHa groups). The primary objective was to compare the rates of menstrual resumption between the two groups. We also assessed the clinical determinants affecting menstrual resumption among the study groups. RESULTS: There were no significant differences between the GnRHa (n = 63) and no GnRHa (n = 164) groups regarding age at diagnosis, parity, ethnicity, age at menarche, body mass index, International Federation of Gynecology and Obstetrics stage, mode of surgery and surgery type. The rate of menstrual resumption after chemotherapy was 100% (63 of 63) in the GnRHa group and 90.9% (149 of 164) in the no GnRHa group (p = 0.013). The mean periods from last chemotherapy to menstrual resumption were 7.4 and 7.3 months in the GnRHa and no GnRHa groups, respectively. GnRHa co-administration during chemotherapy reduced the likelihood of amenorrhoea after chemotherapy, although statistical significance was not confirmed in the univariate analysis (odds ratio: 0.276; 95% confidence interval, 0.004-1.317; p = 0.077). CONCLUSION: Temporary ovarian suppression with GnRHa during chemotherapy does not significantly increase the chances of menstrual resumption in young patients with MOGCT.

Patterns of peritraumatic threat perceptions in patients evaluated for suspected acute coronary syndrome according to prior and current posttraumatic stress symptoms.

OBJECTIVE: Prior posttraumatic stress disorder (PTSD) and elevated threat perceptions predict posttraumatic psychopathology after evaluation for acute coronary syndrome (ACS), but most research has measured threat retrospectively. We investigated how threat perceptions during ACS evaluation in the emergency department (ED) and upon recall were associated with posttraumatic psychopathology burden due to prior trauma and the suspected ACS. METHODS: Perceived threat was assessed in the ED, and ED threat recall was assessed upon inpatient transfer/discharge, along with acute stress disorder (ASD) symptoms due to suspected ACS and PTSD symptoms due to prior trauma. The sample comprised 894 participants (mean age = 60.7 ±â€¯13.1 years; 46.8% female; 56.3% Hispanic; 20.5% Black). One-way ANOVAs examined how those with consistent posttraumatic psychopathology (prior PTSD/ASD; 14.8%), prior posttraumatic psychopathology (prior PTSD/no ASD; 6.8%), new-onset posttraumatic psychopathology (no PTSD/ASD; 15.7%), or no posttraumatic psychopathology (no PTSD/no ASD; 62.8%) differed in threat perception, threat recall, and their discrepancy. RESULTS: Threat perception scores ranged from 6 to 24. Participants with consistent posttraumatic psychopathology had higher threat perceptions (M = 14.01) than those with prior posttraumatic psychopathology (M = 12.02) and new-onset posttraumatic psychopathology (M = 12.21) (ps ≤ 0.001); the latter two did not differ significantly but had higher threat perceptions than those with no posttraumatic psychopathology (M = 9.84) (p < .001). Similar results were observed for threat recall (p < .001). The new-onset posttraumatic psychopathology group also had a greater increase in perceived threat versus the no posttraumatic psychopathology group (p = .06). Results were similar adjusting for potential confounders. CONCLUSIONS: Assessing threat perceptions during ACS evaluation and hospitalization may help identify those at risk for emotional difficulties post-ACS.

Oriental Medicine Samhwangsasim-tang Alleviates Experimental Autoimmune Encephalomyelitis by Suppressing Th1 Cell Responses and Upregulating Treg Cell Responses.

Oriental medicine Samhwangsasim-tang (SHSST) has traditionally been used in East Asia to treat hypertension and its complications. However, little is known about its potential value regarding the treatment of chronic inflammatory diseases such as multiple sclerosis (MS). In this study, we investigated whether SHSST has a beneficial effect in treating myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (EAE). Onset-treatment with SHSST was found to alleviate neurological symptoms as well as demyelination and glial activation in the spinal cords from the EAE mice. The SHSST also attenuated the mRNA or protein expression of pro-inflammatory cytokines (interleukin-1beta and tumor necrotic factor-alpha); chemokines (RANTES, monocyte chemotactic protein-1, and macrophage inflammatory protein-1alpha); inducible nitric oxide synthase; and cyclooxygenase-2 in correspondence with the down-regulation of the nuclear factor-kappa B and mitogen-activated protein kinases signal pathways in the spinal cords from EAE mice. Interestingly, the protective effect of the SHSST was related to a decreased number of Th1 cells and an increased number of Treg cells in spinal cords from EAE mice. Taken together, our finding firstly suggested that SHSST could delay or mitigate EAE with a wide therapeutic time-window by suppressing Th1 cell responses and upregulating Treg cell responses. Also, our findings are strong enough to warrant further investigation of SHSST as a treatment for chronic autoimmune diseases including MS.

Long-term surgical outcomes after vitrectomy for symptomatic lamellar macular holes.

PURPOSE: To determine long-term surgical findings and outcomes after vitrectomy for symptomatic lamellar macular holes. METHODS: This is a retrospective, consecutive, interventional case series. Sixteen patients (31 eyes) with lamellar macular holes and central visual loss participated in the study. All patients underwent 3-port pars plana vitrectomy with membranectomy and/or internal limiting membrane peeling and gas tamponade under the care of one author. Best-corrected visual acuity and optical coherence tomography appearance were determined preoperatively and postoperatively. RESULTS: Final visual acuity improved more than 2 lines postoperatively in 18 eyes (58.1%) and decreased in 2 eyes (6.5%) leading to a mean gain of 0.18 logarithm of the minimum angle of resolution visual acuity during the mean follow-up period of 39 ± 24 months (12-85 months). Twenty-eight eyes (90.3%) improved or normalized in foveal appearance on postoperative optical coherence tomography images of the macula, 1 eye remained unchanged, and 1 eye (3.2%) had chronic cystoid macular edema, 1 eye was unchanged, and 1 eye showed recurrence of lamellar macular hole. CONCLUSION: In patients with central visual loss from lamellar macular holes, vitrectomy, membranectomy, and/or internal limiting membrane peeling and gas tamponade appear to have a beneficial effect for a mean of 3 years.

High-strain-rate brain injury model using submerged acute rat brain tissue slices.

Blast-induced traumatic brain injury (bTBI) has received increasing attention in recent years due to ongoing military operations in Iraq and Afghanistan. Sudden impacts or explosive blasts generate stress and pressure waves that propagate at high velocities and affect sensitive neurological tissues. The immediate soft tissue response to these stress waves is difficult to assess using current in vivo imaging technologies. However, these stress waves and resultant stretching and shearing of tissue within the nano- to microsecond time scale of blast and impact are likely to cause initial injury. To visualize the effects of stress wave loading, we have developed a new ex vivo model in which living tissue slices from rat brain, attached to a ballistic gelatin substrate, were subjected to high-strain-rate loads using a polymer split Hopkinson pressure bar (PSHPB) with real-time high-speed imaging. In this study, average peak fluid pressure within the test chamber reached a value of 1584±63.3 psi. Cavitation due to a trailing underpressure wave was also observed. Time-resolved images of tissue deformation were collected and large maximum eigenstrains (0.03-0.42), minimum eigenstrains (-0.33 to -0.03), maximum shear strains (0.09-0.45), and strain rates (8.4×10³/sec) were estimated using digital image correlation (DIC). Injury at 4 and 6 h was quantified using Fluoro-Jade C. Neuronal injury due to PSHPB testing was found to be significantly greater than injury associated with the tissue slice paradigm alone. While large pressures and strains were encountered for these tests, this system provides a controllable test environment to study injury to submerged brain slices over a range of strain rate, pressure, and strain loads.

MR elastography of the ex vivo bovine globe.

PURPOSE: To evaluate the feasibility of using MR elastography (MRE) to assess the mechanical properties of the eye. MATERIALS AND METHODS: The elastic properties of the corneoscleral shell of an intact, enucleated bovine globe specimen were estimated using MRE and finite element modeling (FEM), assuming linear, isotropic behavior. The two-dimensional (2D), axisymetric model geometry was derived from a segmented 2D MR image, and estimations of the Young's modulus in both the cornea and sclera were made at various intraocular pressures using an iterative flexural wave speed matching algorithm. RESULTS: Estimated values of the Young's moduli of the cornea and sclera varied from 40 to 185 kPa and 1 to 7 MPa, respectively, over an intraocular pressure range of 0.85 to 9.05 mmHg (1.2 to 12.3 cmH(2)O). They also varied exponentially as functions of both wave speed and intraocular dP/dV, an empirical measure of "ocular rigidity." CONCLUSION: These results show that it is possible to estimate the intrinsic elastic properties of the corneoscleral shell in an ex vivo bovine globe, suggesting that MRE may provide a useful means to assess the mechanical properties of the eye and its anatomy. Further development of the technique and modeling process will enhance its potential, and further investigations are needed to determine its clinical potential.

Density of common complex ocular traits in the aging eye: analysis of secondary traits in genome-wide association studies.

Genetic association studies are identifying genetic risks for common complex ocular traits such as age-related macular degeneration (AMD). The subjects used for discovery of these loci have been largely from clinic-based, case-control studies. Typically, only the primary phenotype (e.g., AMD) being studied is systematically documented and other complex traits (e.g., affecting the eye) are largely ignored. The purpose of this study was to characterize these other or secondary complex ocular traits present in the cases and controls of clinic-based studies being used for genetic study of AMD. The records of 100 consecutive new patients (of any diagnosis) age 60 or older for which all traits affecting the eye had been recorded systematically were reviewed. The average patient had 3.5 distinct diagnoses. A subset of 10 complex traits was selected for further study because they were common and could be reliably diagnosed. The density of these 10 complex ocular traits increased by 0.017 log-traits/year (P = 0.03), ranging from a predicted 2.74 at age 60 to 4.45 at age 90. Trait-trait association was observed only between AMD and primary vitreomacular traction (P = 0.0009). Only 1% of subjects age 60 or older had no common complex traits affecting the eye. Extrapolations suggested that a study of 2000 similar subjects would have sufficient power to detect genetic association with an odds ratio of 2.0 or less for 4 of these 10 traits. In conclusion, the high prevalence of complex traits affecting the aging eye and the inherent biases in referral patterns leads to the potential for confounding by undocumented secondary traits within case-control studies. In addition to the primary trait, other common ocular phenotypes should be systematically documented in genetic association studies so that adjustments for potential trait-trait associations and other bias can be made and genetic risk variants identified in secondary analyses.

Expression of the Na+-HCO3- cotransporter and its role in pHi regulation in guinea pig salivary glands.

Patterns of salivary HCO(3)(-) secretion vary and depend on species and gland types. However, the identities of the transporters involved in HCO(3)(-) transport and the underlying mechanism of intracellular pH (pH(i)) regulation in salivary glands still remain unclear. In this study, we examined the expression of the Na(+)-HCO(3)(-) cotransporter (NBC) and its role in pH(i) regulation in guinea pig salivary glands, which can serve as an experimental model to study HCO(3)(-) transport in human salivary glands. RT-PCR, immunohistochemistry, and pH(i) measurements from BCECF-AM-loaded cells were performed. The amiloride-sensitive Na(+)/H(+) exchanger (NHE) played a putative role in pH(i) regulation in salivary acinar cells and also appeared to be involved in regulation in salivary ducts. In addition to NHE, NBC also played a role in pH(i) regulation in both acini and ducts. In the parotid gland, NBC1 was functionally expressed in the basolateral membrane (BLM) of acinar cells and the luminal membrane (LM) of ducts. In the submandibular gland, NBC1 was expressed only in the BLM of ducts. NBC1 expressed in these two types of salivary glands takes up HCO(3)(-) and is involved in pH(i) regulation. Although NBC3 immunoreactivity was also detected in submandibular gland acinar cells and in the ducts of both glands, it is unlikely that NBC3 plays any role in pH(i) regulation. We conclude that NBC1 is functionally expressed and plays a role in pH(i) regulation in guinea pig salivary glands but that its localization and role are different depending on the type of salivary glands.

Inhibitory effects of autoantibodies on the muscarinic receptors in Sjögren's syndrome.

Sjogren's syndrome (SS) is a systemic autoimmune disease that involves reduced salivary secretions. Recently, circulating autoantibodies from SS patients against the type 3 muscarinic cholinergic receptor (M3R) has been reported in the sera of SS patients. However, the role of these autoantibodies in the development of SS has not been elucidated. In this study, purified IgG was obtained from the sera of 11 SS patients, and its inhibitory effect on the M3R of the salivary glands was evaluated using RT-PCR, microspectrofluorimetry, immunohistochemistry, and Western blot analysis. Stimulation with carbachol (CCh) evoked a [Ca2+]i transient in the fura-2 loaded HSG cells. However, pretreatment of the cells with SS IgG (0.5 mg/ml) for 12 or 24 h significantly reduced the magnitude of the CCh-induced [Ca2+]i transient (CICT). We found that the magnitude of CICT was decreased by 62-45% when cells were pretreated with the SS IgG. However, the [Ca2+]i response to ATP was not altered by the pretreatment of SS IgG. The effect of SS IgG on CICT was abrogated by the inclusion of excessive competitive peptides that encode the amino-acid sequence of M3R, which was not recapitulated by nonspecific peptides. The inhibitory effect of SS IgG on the aquaporin (AQP)-5 expression was also examined. After confirming the apical localization of AQP-5 along with its increase by pilocarpine (10(-5) M), we examined whether SS IgG had an effect on pilocarpine-induced AQP-5 trafficking to the apical membrane (APM) using rat parotid acinar cells. After incubating the cells with SS IgG for 12 h, the amount of pilocarpine-induced AQP-5 significantly decreased compared to the control groups. In conclusion, autoantibodies from the SS patients inhibit the function of the human M3R that is mediated by Ca2+ mobilization and AQP-5 trafficking. Our results could partly explain the underlying mechanisms of glandular dysfunction and associated features of impaired autonomic function in SS patients.

Opacification of a hydrophilic acrylic intraocular lens with exacerbation of Behçet's uveitis.

Behçet's disease is 1 of the most common causes of uveitis in the Eastern world. Its common ocular complications are uveitis, cataract, and obliteration of retinal vessels. Phacoemulsification with intraocular lens (IOL) implantation in patients with Behçet's disease is known to be a safe procedure. We managed a patient with Behçet's disease who had aggravated uveitis and opacification of a hydrophilic acrylic IOL (ACRL-C160, Ophthalmed) 4 months after cataract surgery. Recalcitrant uveitis despite maximum tolerable medication and IOL opacification with vitreous opacity necessitated an IOL exchange and trans pars plana vitrectomy. After the procedure, the eye became quiescent. However, the visual acuity was 20/200 because of the obliteration of retinal vessels.

Visual field defect caused by nerve fiber layer damage associated with an internal limiting lamina defect after uneventful epiretinal membrane surgery.

PURPOSE: To report a case of visual field defect caused by damage of the nerve fiber layer associated with an internal limiting lamina defect after uneventful epiretinal membrane peeling. DESIGN: Interventional case report. METHODS: In the right eye, a 43-year-old male patient developed a nasal step and mild inferior arcuate scotoma after uneventful epiretinal membrane surgery without any associated glaucoma. Transmission electron microscopy was performed on the epiretinal membrane specimens. RESULTS: An epiretinal membrane specimen showed adhesion between epiretinal membrane and axons of nerve fiber layer in the area of the internal limiting lamina defect. CONCLUSION: Adhesion between epiretinal membrane and retinal tissue in the area of the internal limiting lamina defect may cause damage of the nerve fiber layer and visual field defect after epiretinal membrane peeling.