Photoprotective effect of yellow-tinted intraocular lenses

Purpose  The aim of this study was to experimentally investigate changes in visible light-induced photo-oxidation and to evaluate the inhibitory effect of various acrylic tinted intraocular lenses (IOLs) on photooxidation. Methods  Three types of nontinted (VA-60BB, HOYA; SA60AT, Alcon; AU-6, Menicon) and tinted (YA-60BB, HOYA; SN60AT, Alcon; AN-6, Menicon) IOLs were used. In the first experiment, we investigated oxidation related to ultraviolet rays by using a mixed solution of reduced glutathione, nicotinamide adenine dinucleotide phosphate (NADPH), and glutathione reductase. The mixed glutathione solution was irradiated for 30, 60, or 90 min with direct artificial sunlight or artificial sunlight that had been passed through various IOLs. Oxidation was detected at 340 nm. In the second experiment, human retinal pigment epithelium (RPE) cells were prepared and cultured in a 96-well dish until confluent. After light exposure for 30 min or 48 h, lactate dehydrogenase (LDH) levels of the culture supernatant were measured to assess the amount of cell damage. Results  Visible light-induced glutathione oxidation progressed over time. Intraocular lenses inhibited photooxidation, with the inhibitory effect shown to increase when tinted IOLs were used. LDH levels in RPE cells increased as a result of exposure to visible light. There was a higher increase in LDH with nontinted than with tinted IOLs. Conclusion  Visible light causes photooxidation, which damages intraocular tissue in vitro. These results suggest that tinted IOLs effectively inhibit tissue damage from visible light. Presented in part at the Japanese Cataract Research Meeting, Ehime, Japan, 29 June 2007     

Characterization of childhood-onset complex partial seizures associated with autism spectrum disorder

Autism spectrum disorder (ASD) has a close relationship with epilepsy. A previous study showed complex partial seizures (CPS) to be the most frequent type of epileptic seizures in cases of ASD. Patients with childhood-onset CPS were retrospectively studied to investigate the prevalence of ASD and to characterize the association between CPS and ASD. The study cohort comprised 86 patients with CPS manifesting at 1 to 9 years of age. Symptomatic CPS and Panayiotopoulos syndrome were excluded. Patients with ASD (ASD group) were compared with those without ASD (non-ASD group). Of the 86 patients with childhood-onset CPS, 36 (42%) also had ASD. This ASD group was predominantly male (68.6%), with higher rates of intellectual disability (69%), and reported frequent seizures (60% had monthly or more frequent seizures). CPS without secondary generalization were more common in the ASD group (69%) than in the non-ASD group (36%), as were frontal paroxysms on EEG (54.5% vs 30%, respectively). In the non-ASD group, 82% of cases had been seizure free for 2 or more years, in comparison to 50% in the ASD group. ASD is frequently associated with childhood-onset CPS. Male gender, cognitive deficits, frequent seizures, and frontal paroxysms are risk factors for the association of ASD with CPS.     

Evaluation of crossing calibration of (123)I-MIBG H/M ration, with the IDW scatter correction method, on different gamma camera systems

(123)I-MIBG Heart-to-Mediastinum activity ratio (H/M) is commonly used as an indicator of relative myocardial (123)I-MIBG uptake. H/M ratios reflect myocardial sympathetic nerve function, therefore it is a useful parameter to assess regional myocardial sympathetic denervation in various cardiac diseases. However, H/M ratio values differ by site, gamma camera system, position and size of region of interest (ROI), and collimator. In addition to these factors, 529 keV scatter component may also affect (123)I-MIBG H/M ratio. In this study, we examined whether the H/M ratio shows correlation between two different gamma camera systems and that sought for H/M ratio calculation formula. Moreover, we assessed the feasibility of (123)I Dual Window (IDW) method, which is a scatter correction method, and compared H/M ratios with and without IDW method. H/M ratio displayed a good correlation between two gamma camera systems. Additionally, we were able to create a new H/M calculation formula. These results indicated that the IDW method is a useful scatter correction method for calculating (123)I-MIBG H/M ratios.     

Autoimmune Neutropenia of Infancy with Multiple Brain Abscesses during the Course of Human Herpesvirus-6 Infection

Autoimmune neutropenia of infancy is characterized by recurrent infections such as pneumonia, otitis media, impetigo, purulent skin regions, gastritis, and upper respiratory infection. However, severe bacterial infection is uncommon. This report documents a 9-month-old boy presenting with autoimmune neutropenia in association with multiple brain abscesses during the course of human herpesvirus (HHV)-6 infection. HHV-6 has a tendency of neurovirulence, which can destroy the blood-brain barrier and facilitate the easy invasion of agents inside the brain. Although autoimmune neutropenia of infancy is benign and self limiting, it must be emphasized that severe bacterial infection will be induced by concurrent viral infection in this specific disorder.     

Hypoxia induces gefitinib resistance in non‐small‐cell lung cancer with both mutant and wild‐type epidermal growth factor receptors

Somatic mutations in the epidermal growth factor receptor (EGFR) gene, such as exon 19 deletion mutations, are important factors in determining therapeutic responses to gefitinib in non‐small‐cell lung cancer (NSCLC). However, some patients have activating mutations in EGFR and show poor responses to gefitinib. In this study, we examined three NSCLC cell lines, HCC827, PC9, and HCC2935, that expressed an EGFR exon 19 deletion mutation. All cells expressed mutant EGFR, but the PC9 and HCC2935 cells also expressed wild‐type EGFR. The HCC827 cells were highly sensitive to gefitinib under both normoxia and hypoxia. However, the PC9 and HCC2935 cells were more resistant to gefitinib under hypoxic conditions compared to normoxia. Phosphorylation of EGFR and ERK was suppressed with gefitinib treatment to a lesser extent under hypoxia. The expression of transforming growth factor‐α (TGFα) was dramatically upregulated under hypoxia, and the knockdown of TGFα or hypoxia‐inducible factor‐1α (HIF1α) reversed the resistance to gefitinib in hypoxic PC9 and HCC2935 cells. Finally, introduction of the wild‐type EGFR gene into the HCC827 cells caused resistance to gefitinib under hypoxia. This phenomenon was also reversed by the knockdown of TGFα or HIF1α. Our results indicate that hypoxia causes gefitinib resistance in EGFR‐mutant NSCLC through the activation of wild‐type EGFR mediated by the upregulation of TGFα. The presence of wild‐type and mutant EGFR along with tumor hypoxia are important factors that should be considered when treating NSCLC patients with gefitinib.     

Pathogenesis of tendinous xanthoma: histopathological study of the extremities of Watanabe heritable hyperlipidemic rabbits

Background Tendinous xanthomas associated with heritable hyperlipidemia are clinically well known. Nevertheless, there have been few basic investigations of the pathogenesis of these xanthomas. To clarify the pathogenesis of these xanthomas, we examined the localization and histopathological features of xanthomatous tissues in the extremities of Watanabe heritable hyperlipidemic (WHHL) rabbits. Methods Twenty-six WHHL rabbits at 1–31 months of age were dissected to observe the localization of xanthomas. In the histopathological study, tendons and ligaments that included xanthomatous tissues were sectioned and stained with hematoxylin and eosin, Masson's trichrome, and toluidine blue. Immunohistochemical staining was performed with RAM-11, a monoclonal antibody specific for rabbit macrophages, and CD31, a monoclonal antibody specific for endothelial cells. Results At necropsy examination, spontaneous development of xanthomas was observed in the plantar side of the plantaris tendon, the flexor retinaculum of the carpus, and around the digital flexor tendons of each joint level. Xanthoma formation was observed from 10 months of age and progressed with advancing age. The histomorphological study revealed that xanthomas had developed in superficial paratenon of the tendons that wrap around bony or fibrous pulleys. Many fibrocartilage cells were observed in the deep side of affected tendons. A large number of blood vessels were seen in the xanthomatous tissues of these WHHL rabbits. Immunohistochemical evaluation revealed that the xanthoma plaques contained endothelial cells and macrophages. Conclusions It is likely that mechanical stress and extensive vascularization are essential factors for xanthoma formation. Moreover, endothelial cells and macrophages cells are principal contributors to the pathogenesis of tendinous xanthomas and to atherogenesis.     

Atrial Septal Aneurysm may Cause In-Hospital Recurrence of Cryptogenic Stroke

Aims: Awareness of potentially embologenic diseases is critical to determining the prognosis of cryptogenic stroke. The clinical significance of atrial septal aneurysm (ASA) in cryptogenic stroke has not been fully studied. Therefore, we explored clinical characteristics and in-hospital recurrence in patients with ASA in cryptogenic stroke. Methods: A multicenter observational registry of cryptogenic stroke patients was conducted. We obtained baseline characteristics, radiological and laboratory findings, and echocardiographic findings, especially of embolic sources on transesophageal echocardiography. The CHALLENGE ESUS/CS (Mechanisms of Embolic Stroke Clarified by Transesophageal Echocardiography for embolic stroke of undetermined source/cryptogenic stroke) registry was recorded at http://www.umin.ac.jp/ctr/ (UMIN000032957). Patients’ clinical characteristics were compared according to the presence of ASA, and factors associated with in-hospital stroke recurrence were assessed. Results: The study included 671 patients (age, 68.7±12.7 years; 450 males; median National Institutes of Health Stroke Scale score, 2). ASA was detected in 92 patients (14%), displaying higher age (72.4±11.0 vs. 68.1 ±12.9 years, p =0.004), reduced frequency of diabetes mellitus (16% vs. 27%, p =0.030), higher frequency of right-to-left shunt (66% vs. 45%, p ＜0.001), and in-hospital stroke recurrence (8% vs. 3%, p =0.034). ASA was relatively associated with in-hospital recurrence (odds ratio 2.497, 95% confidence interval 0.959–6.500, p = 0.061). Conclusions: The CHALLENGE ESUS/CS registry indicated that ASA was not rare in cryptogenic stroke, and ASA’s clinical characteristics included higher age, reduced frequency of diabetes mellitus, and increased frequency of concomitant right-to-left shunt. ASA may be related to in-hospital stroke recurrence in cryptogenic stroke.     

Validity of endoscopic resection for clinically diagnosed T1a-MM/T1b-SM1 N0 M0 esophageal squamous cell carcinoma

Background

Previous guidelines have not described clear recommendations for performing endoscopic resection (ER) of T1a-muscularis mucosa (MM)/T1b-submucosal (SM1) cancers that have invaded?≤?200 μm because these are considered to have a non-negligible risk of metastasis based on previous analyses of pathologically diagnosed (p)MM/SM1 cancers. Considering that the indication for ER is determined based on a clinical diagnosis, the applicability of ER should be investigated in clinical (c)MM/SM1 but not pMM/SM1 cancers. This study aimed to evaluate validity of ER for cMM/SM1 cancers.

Methods

In total, 175 cMM/SM1 esophageal squamous cell carcinoma cases that were endoscopically or surgically resected between January 2008 and December 2018 were identified from a prospectively maintained database. We histologically evaluated resected specimens and divided them into low- (n?=?92) and high-risk (n?=?83) cancers for metastasis.

Results

Univariate analysis showed that longer tumor length and larger circumferential extent were significantly correlated with high-risk cancer (P?<?0.001). Multivariate analysis showed that tumor circumference was an independent predictor of high-risk cancer (P?=?0.036). The proportion of low-risk cancers among cases with?≤?3/4,?>?3/4 and?<?1, and whole circumferential extent were 59, 17, and 14%, respectively, and the post-ER stricture rates of these groups were 12, 33, and 100%, respectively.

Conclusion

ER is the first-line treatment for cMM/SM1 cancers with?≤?3/4 circumferential extent considering that 59% of cMM/SM1 cancers were low-risk cancers for which ER is mostly curative. ER is not recommended for whole circumferential cMM/SM1 cancers given the low proportion of low-risk cancers and the high risk of stricture after ER.