Sodium-glucose co-transporter 2 inhibitor therapy reduces the administration frequency of anti-vascular endothelial growth factor agents in patients with diabetic macular oedema with a history of anti-vascular endothelial growth factor agent use: A cohort study using the Japanese health insurance claims database.

AIM: We assessed the effectiveness of sodium-glucose co-transporter 2 inhibitors (SGLT2is) in reducing the administration frequency of anti-vascular endothelial growth factor (VEGF) agents in patients with diabetic macular oedema (DMO) using a health insurance claims database. MATERIALS AND METHODS: This retrospective cohort study analysed health insurance claims data covering 11 million Japanese patients between 2005 and 2019. We analysed the frequency and duration of intravitreal injection of anti-VEGF agents after initiating SGLT2is or other antidiabetic drugs. RESULTS: Among 2412 matched patients with DMO, the incidence rates of anti-VEGF agent injections were 230.1 per 1000 person-year in SGLT2i users and 228.4 times per 1000 person-year in non-users, respectively, and the risk ratio for events was unchanged in both groups. Sub-analysis of each baseline characteristic of the patients showed that SGLT2is were particularly effective in patients with a history of anti-VEGF agent use [p = .027, hazard ratio (HR): 0.44, 95% confidence interval (CI): 0.22-0.91]. SGLT2is reduced the risk for the first (p = .023, HR: 0.45, 95% CI: 0.22-0.91) and second (p = .021, HR: 0.39, 95% CI: 0.17-0.89) anti-VEGF agent injections. CONCLUSIONS: There was no difference in the risk ratio for the addition of anti-VEGF therapy between the two treatment groups. However, the use of SGLT2is reduced the frequency of anti-VEGF agent administration in patients with DMO requiring anti-VEGF therapy. Therefore, SGLT2i therapy may be a novel, non-invasive, low-cost adjunctive therapy for DMO requiring anti-VEGF therapy.

Integrated continuous downstream process of monoclonal antibody developed by converting the batch platform process based on the process characterization.

A continuous downstream process of monoclonal antibody was developed based on the process characterization. Periodic-counter current chromatography (PCCC) with two protein A columns was used for the capture step. For low pH virus inactivation (VI), a batch reactor was employed, which can work as a surge (buffer) tank. Flow-through chromatography (FTC) with two connected columns of different separation modes (anion-mixed mode and cation exchange) was designed as a polish step. After 24 h PCCC run, the collected pool was processed for VI. After adjusting pH and electric conductivity, the solution was fed to the two connected FTC columns for 24 h. Virus filter was also connected to the exit of the connected-column. PCCC and FTC were run in parallel. Six runs of different feed rates (0.5-10 L/day) and feed concentrations (1-3.2 g/L) were performed with protein A columns of 1-5 mL and FTC columns of 3-10 mL. The largest run (feed rate 10 L/day, feed concentration 2 g/L) was carried out at a GMP facility with 15 mL protein A columns and 100 mL FTC columns. Good recovery and purity values were obtained for all runs. The process was found to be flexible and stable for feed fluctuations. Only three surge or pool tanks were needed in addition to the final product pool tank.

Viral clearance in end-to-end integrated continuous process for mAb purification: Total flow-through integrated polishing on two columns connected to virus filtration.

There are few reports of the adoption of continuous processes in bioproduction, particularly the implementation of end-to-end continuous or integrated processes, due to difficulties such as feed adjustment and incorporating virus filtration. Here, we propose an end-to-end integrated continuous process for a monoclonal antibody (mAb) with three integrated process segments: upstream production processes with pool-less direct connection, pooled low pH virus inactivation with pH control and a total flow-through integrated polishing process in which two columns were directly connected with a virus filter. The pooled virus inactivation step defines the batch, and high impurities reduction and mAb recovery were achieved for batches conducted in succession. Viral clearance tests also confirmed robust virus reduction for the flow-through two-column chromatography and the virus filtration steps. Additionally, viral clearance tests with two different hollow fiber virus filters operated at flux ranging from 1.5 to 40 LMH (liters per effective surface area of filter in square meters per hour) confirmed robust virus reduction over these ranges. Complete clearance with virus logarithmic reduction value ≥4 was achieved even with a process pause at the lowest flux. The end-to-end integrated continuous process proposed in this study is amenable to production processes, and the investigated virus filters have excellent applicability to continuous processes conducted at constant flux.

A Pediatric Case of Extraneural Subcutaneous Metastasis of Ependymoma.

Ependymoma is the third most common brain tumor in children. Extracranial metastases of ependymomas are uncommon. A 21-month-old Japanese boy was diagnosed to be brain dead due to a posterior fossa (PF) brain tumor. Surgical resection of the tumor was not performed. Twenty-seven months later, he developed a truncal subcutaneous tumor, which was pathologically diagnosed as PF ependymoma group A. We observed the intracranial recurrence of the brain tumor, an invasion to the left orbit, and a neoplasm in his liver before he died. This case suggests that PF ependymoma group A can metastasize extracranially to various organs.

Genetic characterization of 1210 Japanese pedigrees with inherited retinal diseases by whole-exome sequencing.

Inherited retinal diseases (IRDs) comprise a phenotypically and genetically heterogeneous group of ocular disorders that cause visual loss via progressive retinal degeneration. Here, we report the genetic characterization of 1210 IRD pedigrees enrolled through the Japan Eye Genetic Consortium and analyzed by whole exome sequencing. The most common phenotype was retinitis pigmentosa (RP, 43%), followed by macular dystrophy/cone- or cone-rod dystrophy (MD/CORD, 13%). In total, 67 causal genes were identified in 37% (448/1210) of the pedigrees. The first and second most frequently mutated genes were EYS and RP1, associated primarily with autosomal recessive (ar) RP, and RP and arMD/CORD, respectively. Examinations of variant frequency in total and by phenotype showed high accountability of a frequent EYS missense variant (c.2528G>A). In addition to the two known EYS founder mutations (c.4957dupA and c.8805C>G) of arRP, we observed a frequent RP1 variant (c.5797C>T) in patients with arMD/CORD.

Long-term follow-up of retinal morphology and physiology after 2000 mg sildenafil overdose as a means of attempted suicide: a case report.

BACKGROUND: Few case reports have described sildenafil overdose, particularly ingestion of > 1000 mg, and overdose-induced changes in visual function remain unclear. We report retinal morphology, retinal sensitivity, and findings of electrophysiological evaluation over long-term follow-up in a case of sildenafil overdose (2000 mg). CASE PRESENTATION: Our patient developed visual abnormalities in the paracentral visual field accompanied by photophobia, decreased contrast sensitivity, and difficulty distinguishing colors in both eyes, 8 hours after the sildenafil overdose. These symptoms did not improve throughout the course, and although abnormalities of retinal morphology and sensitivity, as well as the electroretinogram findings showed slight improvement, the patient did not recover completely at 6-month follow-up. CONCLUSIONS: We observed that high-dose sildenafil ingestion leads to retinal toxicity; the ocular abnormalities may persist for at least 6 months. Optical coherence tomography, Humphrey perimetry, microperimetry, and multifocal electroretinography are useful to quantitatively monitor temporal changes.

Linear flow-velocity gradient chromatography-An efficient method for increasing the process efficiency of batch and continuous capture chromatography of proteins.

A new method was proposed for increasing the capture chromatography process efficiency, linear flow-velocity gradient (LFG). The method uses a linear decreasing flow-velocity gradient with time during the sample loading. The initial flow velocity, the final flow velocity and the gradient time are the parameters to be tuned. We have developed a method for determining these parameters by using the total column capacity and the total loaded amount as a function of time. The capacity can be calculated by using the relationships between dynamic binding capacity (DBC) and residence time. By leveraging the capacity, loading amount, and the required conditions, the optimum LFG can be designed. The method was verified by ion-exchange and protein A chromatography of monoclonal antibodies (mAbs). A two-fold increase in the productivity during the sample loading was possible by LFG compared with the constant flow-velocity (CF) operation. LFG was also applied to a 4-column continuous process. The simulation showed that the cost of resin per unit amount of processed mAbs can be reduced by 13% while 1.4 times enhancement in productivity was preserved after optimization by LFG compared to CF. The process efficiency improvement is more pronounced when the isotherm is highly favorable and the loading volume is large.

Comparisons of surgical outcomes after epiretinal membrane peeling in the myopic eyes with long to that with normal axial length.

PURPOSE: To compare the outcomes of vitrectomy with removal of an idiopathic epiretinal membrane (ERM) in the myopic eyes with long axial length (AL) to that in the eyes with normal AL. METHODS: This was a retrospective, observational, case-control study. Fifty-six eyes of 56 patients with an idiopathic ERM were studied. Twenty-eight of these eyes had an axial length longer than 26.0 mm (Group A), and the other 28 eyes had axial lengths < 26.0 mm (Group B). The age and visual acuity of the two groups were not significantly different. All subjects were treated by vitrectomy and peeling of the ERM with a 25- or 27-gauge system. The postoperative best-corrected visual acuity (BCVA) and optical coherence tomographic findings were determined at 3 and 6 months postoperatively. RESULTS: The mean BCVA improved from 0.35 ± 0.25 to 0.15 ± 0.25 logMAR units in the eyes with the long AL and from 0.35 ± 0.25 to 0.10 ± 0.21 logMAR units in the eyes with normal AL at 6 months postoperatively (both P < 0.001). The postoperative BCVA was not significantly different between the two groups at 6 months (P = 0.221). The central macula was thinner in the eyes of Group A than Group B (P < 0.001). The restorations of the ellipsoid zone and the external limiting membrane were observed in both groups, but the interdigitation zone was less frequently restored in Group A (P < 0.001). CONCLUSIONS: Vitrectomy with the removal of the epiretinal membrane is effective in attaining a good BCVA even in the myopic eyes with long AL.

Refractive errors after sutureless intrascleral fixation of intraocular lens.

PURPOSE: To determine the difference between the attempted and the achieved postoperative refractive error after sutureless intrascleral fixation of the haptics of an implanted intraocular lens (IOL). PATIENTS AND METHODS: This was a retrospective study of the medical charts of patients who had undergone sutureless intrascleral fixation of an IOL. The IOLs were fixed by inserting the haptics into scleral tunnels with or without flanges. The differences between the attempted and achieved postoperative refractive error (spherical equivalent) were determined. The relationships between the surgical options and the differences of the refractive error and degree of astigmatism were also determined. RESULTS: Two hundred and twenty-three eyes were studied. There was a myopic shift of - 0.38 ± 1.13 diopters (D). The mean of the differences between the achieved postoperative and the attempted refractive error was 0.89 ± 0.79 D. The achieved refractive error was significantly correlated with the attempted refractive error (P < 0.001, R2 = 0.631). The surgical procedures selected were not significantly associated with the differences between the attempted and achieved refractive error. The size of sclerocorneal incision and presence of sutures were significantly associated with the final degree of astigmatism (P = 0.006 and 0.008, respectively). CONCLUSIONS: The postoperative refractive error was significantly correlated with the attempted refractive error after intrascleral fixation of an IOL. The wound construction was associated with the postoperative degree of astigmatism.

Ten-year epidemiological study of ocular and orbital tumors in Chiba University Hospital.

BACKGROUND: The purpose of this study is to determine the epidemiology of tumors of the ocular adnexa and orbit in Japan. METHODS: We conducted a retrospective study on the histopathological reports in the medical records of the Chiba University Hospital from April 2009 to March 2019. Three hundred and seventy two records were examined. In addition, we examined the annual changes in the major types of tumors including malignant lymphomas and IgG4-related diseases (IgG4-RDs). RESULTS: There were 270 conjunctival or eyelid tumors with 166 benign and 104 malignant. There were 102 orbital tumors with 55 benign, 47 malignant tumors, and 21 cases of IgG4-RDs. Ten cases of adenoma (2.7%), another benign tumor, was also diagnosed. The major malignant tumors were malignant lymphoma in 74 cases, sebaceous gland carcinoma (SGC) in 28 cases, basal cell carcinoma in 15 cases, and squamous cell carcinoma in 8 cases. The SGCs were the most common malignant eyelid tumor at 54%. Among the malignant lymphomas, extranodal marginal zone lymphomas of the mucosa-associated lymphoid tissue type, MALT lymphomas, was the most common at 51 cases and the second most common was the diffuse large B-cell lymphoma at 11 cases. The ratio of MALT lymphomas to that of all malignant lymphomas increased significantly with years. The serum IgG4 values were measured more often in the last 5 years (70%) than in the former 5 years (33%). CONCLUSIONS: We conclude that malignant lymphoma is a major malignant tumor in Japan and pathological biopsies should be done proactively to prevent missing IgG4-positive MALT lymphomas.

Comparison of Internal Limiting Membrane Peeling and Flap Removal to Flap Insertion on Visual Outcomes in Highly Myopic Eyes with Macular-Hole Retinal Detachment.

INTRODUCTION: To compare the morphological and visual outcomes after pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling and flap removal to that with flap insertion in eyes with myopic macular-hole retinal detachment (MHRD). METHODS: Forty-six eyes of 45 patients with MHRD were studied. Eighteen eyes were treated by PPV with ILM peeling and flap removal and 28 eyes by flap insertion, respectively. The baseline characteristics and postoperative findings were compared between the 2 groups. RESULTS: The average age of the cases was 70.0 ± 8.5 years. The best-corrected visual acuity (BCVA) improved, from 1.51 ± 0.14 to 1.31 ± 0.20 logMAR units in the flap removal group, and from 1.20 ± 0.10 to 0.88 ± 0.10 logMAR units in the flap insertion group (p = 0.049). A significantly larger number of MHs were closed in the flap insertion group (96 vs. 50% in the removed group; p < 0.001). Restoration of the ellipsoid zone (EZ) and external limiting membrane (ELM) was also better in the flap insertion group than in the flap removal group (EZ 14 vs. 6%, p = 0.003; ELM 36 vs. 6%, p < 0.001). DISCUSSION: The technique of ILM peeling with flap insertion is more effective in closing the MH, and results in better BCVA and better restoration of the outer retinal microstructures than flap removal.

Improvements of Retinal Sensitivity after Intravitreal Injection of Aflibercept in Eyes with Neovascular Age-Related Macular Degeneration with or without Polypoidal Choroidal Vasculopathy.

PURPOSE: We aim to determine the effects of intravitreal aflibercept (IVA) on the mean sensitivity (MS) of the central retina, best-corrected visual acuity (BCVA), and central foveal thickness (CFT) in eyes with neovascular age-related macular degeneration (nAMD) with or without polypoidal choroidal vasculopathy (PCV). METHODS: This was a prospective, interventional study. All eyes were treatment-naive with nAMD with or without PCV. Each eye received 3 monthly IVA injections followed by an IVA injection every 2 months for 12 months. The primary outcome was the change in the MS within the central 2°. The secondary outcomes were the changes in BCVA, CFT, greatest linear dimension (GLD), and percentage of eyes with a dry macula. RESULTS: Thirty-seven eyes of 37 patients were studied. A significant improvement of the MS (dB) was observed +4.9 ± 4.6 dB (mean ± standard deviation) at 3 M (p < 0.001), +5.5 ± 4.9 dB at 6 (p < 0.001), and +7.0 ± 3.4 dB at 12 M (p < 0.001) compared to the baseline in all eyes. The MS of the eyes with non-PCV was not significantly different from that of eyes with PCV (p = 1.00, 1.00, 1.00, and 0.76 at baseline, 3, 6, and 12 M, respectively). The MS of 11 patients whose BCVA remained unchanged was significantly improved by +6.5 ± 2.8 dB at 3 M (p < 0.001), +6.1 ± 4.3 dB at 6 M (p < 0.001), and +6.4 ± 4.8 dB at 12 M (p = 0.003) compared to the baseline. The mean BCVA was significantly improved from the baseline to 3 M (p < 0.001), 6 M (p = 0.027), and 12 M (p = 0.003) in all eyes. The BCVA was improved or maintained in 97% of the patients at 12 M. The mean CFT and GLD were significantly reduced at 12 M (p < 0.001). Twenty-two eyes (71%) had a dry macula at 12 M. CONCLUSIONS: IVA administered by a fixed dosing regimen led to significant improvements of the central MS, BCVA, and macular morphology at 1 year in eyes with nAMD with or without PCV. These results were not significantly different between eyes with non-PCV and with PCV. The improvements of the MS of the retina of the central 2° in a subgroup whose BCVA remained unchanged through the 12-month experimental period was also significant. We conclude that the MS of the central 2° might be a better marker than the BCVA in determining the effectiveness of IVA treatments and might be helpful in determining early effects on the retina before BCVA changes can be detected.

Surgical outcomes of vitrectomy for breakthrough vitreous hemorrhage in eyes with exudative age-related macular degeneration.

PURPOSE: To report the outcomes of pars plana vitrectomy in cases with breakthrough vitreous hemorrhage (VH) secondary to exudative age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy. We also investigated the relationship between the preoperative b-mode ultrasonographic findings and the postoperative visual acuity to determine if the ultrasonographic findings can predict the surgical outcome after pars plana vitrectomy. METHODS: This was a retrospective, interventional, case series. Twenty eyes of 20 patients were studied. The associations between the pre- and intraoperative factors and the final best-corrected visual acuity (BCVA) were determined. Recombinant tissue-plasminogen activator (tPA) was used in cases with massive hemorrhagic retinal detachment. RESULTS: Ten eyes with polypoidal choroidal vasculopathy (PCV), two eyes with choroidal neovascularization (CNV), and eight eyes with an unknown type of AMD were studied. The mean BCVA was 0.73 ± 0.57 logarithm of the minimum angle of resolution (logMAR) units before developing the VH, 2.25 ± 0.45 logMAR units before the surgery, and 1.52 ± 0.87 logMAR units after the surgery. The BCVA improved significantly after the surgery (P = 0.004) but was significantly worse than that before developing the VH (P = 0.012). The cases of PCV had better final BCVA than cases of CNV (P = 0.043, Mann-Whitney test). The preoperative presence of a subretinal elevation at the macula detected by ultrasonography was significantly associated with a poorer final BCVA (P = 0.031). CONCLUSIONS: Vitrectomy significantly improved visual function in the eyes with VH associated with exudative AMD. The eyes with PCV and no macular subretinal elevation on ultrasonography had a better visual prognosis.

Microcalorimetric Analysis of the Adsorption of Lysozyme and Cytochrome c onto Cation-Exchange Chromatography Resins: Influence of Temperature on Retention.

We studied the adsorption mechanism of two basic proteins, equine cytochrome c (Cyt) and chicken egg-white lysozyme (Lys), adsorbing onto negatively charged chromatography surfaces. In liquid chromatography, the retention volume of Lys was larger than that of Cyt on negatively charged ion-exchange resins. When the temperature increased, the retention volume of Cyt increased, whereas that of Lys clearly decreased. Both Lys and Cyt share similar physical characteristics, so the opposite behavior with increasing temperatures was surprising, indicating a more complex mechanism of adsorption may be involved. We analyzed the adsorption of these proteins by using isothermal titration calorimetry (ITC). The change in adsorption enthalpy determined by ITC allowed the understanding of the reason for and underlying driving forces of protein adsorption that resulted in this opposite behavior. Large exothermic enthalpies of adsorption were observed for Lys (-43.95 kJ/mol), and Lys adsorption was found to be enthalpically driven. On the other hand, endothermic enthalpies were dominant for Cyt adsorption (32.41 kJ/mol), which was entropically driven. These results indicate that dehydration and release of counterions play a more important role in Cyt adsorption and ionic interaction and hydrogen bridges are more significant in Lys adsorption. Understanding of the adsorption mechanism of proteins onto chromatography resins is essential for modeling and developing new, efficient chromatographic processes.

REGIONAL DENSITIES OF RETINAL CAPILLARIES AND RETINAL SENSITIVITIES AFTER MACULAR HOLE SURGERY WITH INTERNAL LIMITING MEMBRANE PEELING.

PURPOSE: To measure the vascular density (VD) of the retinal capillary plexuses by optical coherence tomography angiography (OCTA) after surgery for an idiopathic macular hole. METHODS: Retrospective, observational case series.Sixteen eyes of 16 patients with an idiopathic macular hole underwent vitrectomy with internal limiting membrane peeling. The VDs of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) were determined by OCTA, and the retinal sensitivity (RS) and the inner retinal thickness (IRT) were measured before, and at 3, 6, and 12 months after the surgery. The VD, RS, and IRT were measured at the four parafoveal quadrants. RESULTS: The mean age was 68.9 years. The VDs of the SCP and DCP were significantly correlated with the RS and IRT at 12 months postoperatively (all P < 0.001 for both SCP and DCP). The VDs of the SCP and DCP were higher, the RS more sensitive, and the IRT thicker in the nasal than the temporal quadrant at 12 months (P < 0.001, <0.001, =0.009, <0.001, respectively). CONCLUSION: The significant correlation between the VDs of the SCP and DCP and the RS and IRT may be due to the nasal shift of the posterior retina.

Non-paraneoplastic autoimmune retinopathy that developed in fellow eye 10 years after onset in first eye: a case report.

BACKGROUND: Evidence-based criteria for the treatment of autoimmune retinopathy (AIR) have not been established. The pathology and clinical features of each antibody causing AIR, and its long-term course are still undetermined. We report our findings in a case of non-paraneoplastic AIR (npAIR) that developed in the fellow eye 10 years after the onset in the first eye. CASE PRESENTATION: Our patient had photophobia in both eyes and a rapidly progressing visual field defect in his right eye at the initial examination. He was diagnosed with non-paraneoplastic AIR based on the clinical findings and immunoblot analyses for anti-retinal antibodies, and he was treated with steroids. Ten years later, a visual field defect developed in the fellow eye, and a diagnosis of npAIR was made. Immunoblot analyses were positive for anti-α-enolase antibodies. He was treated with steroids, immunosuppressants, and plasma exchange. However, the response to the treatment was poor and both eyes eventually became blind. CONCLUSIONS: As best we know, this is the first case report of npAIR that developed in the fellow eye over 10 years after the development in the first eye. Long-term follow-up and a search for tumor lesions are necessary in cases of npAIR. Further understanding of the long-term course of AIR can contribute to an understanding of the pathology and treatment of npAIR.

CORRELATIONS BETWEEN CHOROIDAL STRUCTURES AND VISUAL FUNCTIONS IN EYES WITH RETINITIS PIGMENTOSA.

PURPOSE: To investigate the choroidal structures in the enhanced depth imaging optical coherence tomographic images in eyes with retinitis pigmentosa (RP) and to determine correlations between the choroidal structures and visual functions. METHODS: The enhanced depth imaging optical coherence tomographic images of 100 eyes with typical RP and 60 age-, sex-, and axial length-matched normal eyes were binarized using ImageJ. The cross-sectional luminal and stromal areas of the inner and outer subfoveal choroid of 1,500-µm width were measured. The inner choroid included the choriocapillaris and medium vessel layer, and the outer choroid included the larger vessel layer. RESULTS: In the inner choroid, the luminal area and the ratio of luminal/total choroidal area (L/C ratio) were significantly smaller in RP than in controls (P = 0.010, P < 0.001, respectively), whereas the stromal area was not significantly different (P = 0.114). The inner choroidal L/C ratio was significantly correlated with the best-corrected visual acuity, mean deviation, foveal sensitivity, width of the ellipsoid zone, and central foveal thickness in RP after adjusting for the axial length, age, and sex (all P < 0.005). CONCLUSION: The significant correlations between the inner choroidal structures and the visual functions and retinal structures indicate that the choroidal structures are altered in association with the progression of RP.

Comparison of the Efficacy of Sub-Tenon versus Intravitreal Triamcinolone Acetonide Injection during Cataract Surgery for Diabetic Macular Edema.

PURPOSE: We compared the efficacy of sub-Tenon triamcinolone acetonide (STTA) to intravitreal triamcinolone aceto-nide (IVTA) injections during cataract surgery (CS) for patients with diabetic macular edema (DME). METHODS: The medical records of 33 eyes (26 patients) with DME which had undergone CS with STTA were compared to those of 34 eyes (27 patients) with DME which had undergone CS with IVTA. Central foveal thickness and best-corrected visual acuity (BCVA) were measured at the baseline and 1, 3, and 6 months after the surgery. RESULTS: The BCVAs after STTA and IVTA were significantly improved at 3 and 6 months. Thirteen eyes in the IVTA group and 21 eyes in the STTA group required other therapies (p < 0.05). One case developed intraocular pressure elevation after IVTA and underwent selective la ser trabeculoplasty. CONCLUSIONS: Ophthalmologists should consider the merits and demerits of IVTA and STTA for DME treatment after CS.

Methyl Ether-Derivatized Sterols and Coprostanol Produced via Thermochemolysis Using Tetramethylammonium Hydroxide (TMAH).

Sterols are widely distributed in nature from lipids in organisms to sediments. As a conventional method, extraction and derivatization with TMS have been applied for sterol analysis, requiring a long preparation time for gas chromatography-mass spectrometry analysis. In this study, for sterol analysis, thermochemolysis using tetramethylammonium hydroxide (TMAH) was applied. This method performs hydrolysis and methylation simultaneously; thus, free and ether-bonding sterols can be analyzed as sterol methyl ethers in a relatively short time period. A sediment sample from a tideland (the Yatsu tideland, Japan) was analyzed using the TMAH method, and we detected more than 10 sterols, which include cholest-5-en-3ß-ol (cholesterol), 24-ethylcholest-5-en-3ß-ol (sitosterol), 24-methylcholesta-5,22E-3ß-ol (brassicasterol), 24-ethylcholesta-5,24(28)Z-dien-3ß-ol (isofucosterol), 4α,23,24-trimethyl-5α(H)-cholest-22E-en-3ß- ol (dinosterol), and 5ß(H)-cholestan-3ß-ol (coprostanol). The detection of the various sterols can be attributed to multiple natural and artificial sources around the Yatsu tideland. In this paper, the mass spectra of these sterols are provided together with an interpretation of their fragmentation patterns. Additionally, the fecal pollution in the Yatsu tideland is discussed in the context of the detection of coprostanol.

Case of convulsive seizure developing during electroretinographic recordings: a case report.

BACKGROUND: To present our findings in a case of convulsive seizures and loss of consciousness that developed during recording electroretinograms (ERG). CASE PRESENTATION: A 34-year-old man had reduced vision in his left eye for about 15 years, and night blindness for about two years. His visual acuity was 20/15 in the right eye and 20/50 in the left eye. The fundus was normal but the sensitivity in the macular region of the left eye was decreased. Optical coherence tomography (OCT) showed partial loss of the interdigitation zone. Upon completion of the flicker ERG recording, a paralysis developed in both upper limbs, then convulsions of the lower limbs followed by a loss of consciousness. The convulsions disappeared after an intravenous injection of diazepam. After that incident, he reported that he had had previous conscious-loss seizures. CONCLUSIONS: Photosensitive epileptic seizures can occur with the light stimuli used for conventional ERG recordings. We recommended that clinicians request information on any prior seizure episodes of the patients and their family members before ERG recordings.