Grading of Atrophic Gastritis is Useful for Risk Stratification in Endoscopic Screening for Gastric Cancer.

OBJECTIVES: In order to screen for gastric cancer effectively, its interval should be set according to the risk. This study aimed to determine whether risk stratification is possible using the data obtained from medical examination or endoscopic findings. METHODS: First, subjects who underwent both cancer screening and medical examination from 2009 to 2015 and underwent cancer screening once more by 2016 were studied. Data such as the lipid profile and history of smoking obtained during the medical examination, and the grade of atrophy and presence of peptic ulcers were studied using multivariate analysis. Next, subjects who underwent cancer screening twice or more between 2009 and 2015 with or without medical examinations were studied to analyze any correlation between the grade of atrophy and cancer occurrence using univariate analysis. In both studies, the status of Helicobacter pylori (HP) infection was determined. RESULTS: In the multivariate analysis, 9378 subjects were included. Aging, advanced atrophy, presence of ulcers, and uric acid levels were identified as risk factors. Among subjects who underwent successful HP eradication therapy, advanced atrophy and aging were observed to be crucial risk factors. In the univariate analysis, there were 12,941 subjects. Gastric cancer occurred more frequently in the more severe atrophy group (P < 0.001). The annual rate of cancer occurrence in the most severe atrophy group was 0.31%, which was approximately thrice as that in the less atrophy group. CONCLUSIONS: Risk stratification was possible based on endoscopic examination alone. The interval should be set depending on each case.

[A case of button battery-induced corneal and conjunctive burn injury and experimental findings of local damage].

PURPOSE: To report a case of button battery-induced alkaline burn injury of the cornea and conjunctiva, with experimental findings of local damage. CASE: A three-year-old girl had a hard and polished white opacity on the nasal lower cornea and conjunctival injection, caused by a button battery remaining in the conjunctival sac for several hours. The ocular surface was washed carefully with distilled water. The opacity improved gradually over several months and scarring was replaced by secondary pterygium. EXPERIMENT: A button battery was placed on an eyeball of a pig, with the cathode directed toward the cornea. Corneal opacity developed in five minutes and increased thereafter. Another battery was sanded with saline-soaked gauze and the gauze near the cathode turned dark brown. This change intensified when the gauze was in contact with the side of the battery. CONCLUSIONS: The cornea and conjunctiva of the patient were damaged by continuous exposure to alkaline solution (concentrated NaOH) after the button battery had entered the lacrimal sac causing fixation by chemosis. The recent development of smaller batteries increases the risk of similar accidents. Button battery-induced burn injuries may be severe and require immediate correct diagnosis and treatment, especially in small children who may be difficult to examine.

[Curatively resected case of non-functioning pancreatic neuroendocrine carcinoma with multiple liver metastases after downstaging with S-1 monotherapy].

A 73-year-old man diagnosed as having pancreatic body cancer with multiple liver metastases was referred to our hospital. Since the patient preferred oral agents, S-1 monotherapy (4-week administration followed by 2-week interval) was started. The initial dose of S-1 was 80 mg, and gradually increased to 150 mg/day. There were no significant adverse events. The liver metastases disappeared and the pancreatic tumor was markedly reduced in size at the completion of 4 courses. Distal pancreatectomy was carried out at 7 months since his first visit. Pathological diagnosis was non-functioning well-differentiated neuroendocrine carcinoma (pT4, pN0, pM0, Stage IVa). He is alive without relapse 6 months after operation. S-1 might be a candidate for chemotherapy for this neuroendocrine tumor.

Evaluation of optical function using a new point spread function analysis system in cataractous and pseudophakic eyes: preliminary results.

PURPOSE: To evaluate optical function in cataractous and pseudophakic eyes using the new point spread function (PSF) analysis system in a clinical setting. METHODS: We applied this new analysis system in the study of two cataractous eyes and one pseudophakic eye of two patients. Using a PSF analyzer, double-pass PSF was measured directly for each subject, and the single-pass modulation transfer function (MTF) and single-pass PSF were calculated. The simulated retinal images of various sizes of Landolt's rings and their contrast characteristics were also calculated by the PSF analyzer. RESULTS: The MTF and the contrast of the simulated retinal images degraded in cataractous eyes were compared with data for normal eyes; the degradation pattern depended on the opacification pattern. The MTF and the contrast of the simulated retinal images in the pseudophakic eye improved significantly compared with the cataractous eyes, although both values were lower in the pseudophakic eye than in young normal eyes. CONCLUSIONS: Our data showed degradation of optical function in cataractous and pseudophakic eyes in comparison with optical function in young normal eyes. If further accumulations of PSF data are made, it may be possible to establish an objective standard by which to measure the progression of cataract, as well as an objective indication for treatment in the future.

Referred pain distribution of the cervical zygapophyseal joints and cervical dorsal rami.

The purpose of this study was to determine the distribution of referred pain from the cervical zygapophyseal joints (C0/1 to C7/Th1) and the cervical dorsal rami (C3 to C7). The subjects were 61 patients who had occipital, neck, and shoulder pain of suspected zygapophyseal origin in whom pain was reproduced by injection of contrast medium into the joints or by electrical stimulation of the dorsal rami. Under fluoroscopic control, the zygapophyseal joints from C0/1 to C7/Th1 were stimulated by the injection of contrast medium and while electrical stimulation of the cervical zygapophyseal dorsal rami at segments C3 to C7 was performed during facet denervation. If injection or electrical stimulation reproduced the patient's usual pain, the distribution of referred pain was determined and the sites of referred pain were divided into 10 areas. A total of 181 joints and 62 segments were studied. Each joint and dorsal ramus produced referred pain with a characteristic distribution. The main distribution of referred pain was as follows. Pain in the occipital region was referred from C2/3 and C3, while pain in the upper posterolateral cervical region was referred from C0/1, C1/2, and C2/3. Pain in the upper posterior cervical region was referred from C2/3, C3/4, and C3, that in the middle posterior cervical region from C3/4, C4/5, and C4, and that in the lower posterior cervical region from C4/5, C5/6, C4, and C5. In addition, pain in the suprascapular region was referred from C4/5, C5/6, and C4, that in the superior angle of the scapula from C6/7, C6, and C7, and that in the mid-scapular region from C7/Th1 and C7.

Keratocyte activation and apoptosis in transplanted human corneas in a xenograft model.

PURPOSE: To study keratocyte activation and cellular apoptosis in transplanted human corneas during the early postoperative period. METHODS: Ten human donor corneas preserved for 6 days at 4 degrees C were transplanted into the eyes of 10 adult cats. After confocal and specular microscopy in vivo 1 week after keratoplasty, the cats were killed, and the fixed corneas were examined by TUNEL assay and by scanning (SEM) and transmission electron microscopy (TEM). RESULTS: Abnormal keratocytes, in which portions of cell bodies and processes as well as nuclei were visible, were present in all corneas and occupied the anterior 16 to 562 microm of the stroma. By TEM in the same corneas, these abnormalities represented keratocytes that were activated to a repair phenotype. Only 0% to 1% of all corneal cells were apoptotic by TUNEL assay, except for the donor keratocytes near the wound, where 7% were apoptotic. The midstromal keratocyte density was decreased at 13,936 +/- 5,910 cells/mm(3) (mean +/- SD), and the endothelial cell density was 2,298 +/- 688 cells/mm(2), representing an endothelial cell loss of 7% +/- 16%. CONCLUSIONS: Substantial keratocyte activation and low levels of cellular apoptosis occur 1 week after human corneal transplantation. The human-to-cat xenograft model of corneal transplantation demonstrated endothelial cell loss and other clinical findings similar to human allografts. The model will be useful for preclinical testing of new methods of long-term corneal preservation and of donor endothelial cell augmentation, as well as the study of human corneal wound healing and keratocyte replacement during the early postoperative period.

Calculation of ocular single-pass modulation transfer function and retinal image simulation from measurements of the polarized double-pass ocular point spread function.

The single-pass modulation transfer function (MTF(sgl)) is an important numerical parameter that can help elucidate the performance and some processes of the human visual system. In previous studies, the MTF(sgl) was calculated from double-pass point spread function (PSF) measurements. These measurements include a depolarized reflection component from the retina that introduces a measurement artifact, and they require long acquisition times to allow averaging to reduce speckle. To solve these problems, we developed a new ocular PSF analysis system (PSFAS) that uses polarization optics to eliminate the depolarized retinal reflection component, and a rotating prism to increase measurement speed. Validation experiments on one patient showed that the MTF(sgl) measured by PSFAS agrees closely with the MTF calculated from contrast sensitivity measurements. A simulated retinal image was calculated by convolution of Landolt rings with the calculated single-pass PSF provided by the PSFAS. The contrast characteristic then was calculated from the simulated retinal images. These results indicate that the MTF(sgl) obtained using the PSFAS may be a reliable measure of visual performance of the optics of the eye, including the optical effects of the retina. The simulated retinal images and contrast characteristics are useful for evaluating visual performance.

Da-Chaihu-Tang alters the pharmacokinetics of nifedipine in rats and a treatment regimen to avoid this.

OBJECTIVES: To investigate the influence of co-administrated Da-Chaihu-Tang (DCT; a traditional Chinese formulation) on the pharmacokinetics of nifedipine, as well as the safe optimal dosing interval to avoid the adverse interactions. METHODS: A single dose of DCT was administered with nifedipine simultaneously, 2 h before, 30 min before or 30 min after nifedipine administration. Pharmacokinetics of nifedipine with or without DCT were compared. The influences of DCT on nifedipine intestinal mucosal and hepatic metabolism were studied by using rat in-vitro everted jejunal sac model and hepatic microsomes. KEY FINDINGS: A simultaneous co-administration of DCT significantly increased the area under concentration-time curve from time zero to infinity (AUC0-inf ) of nifedipine. In-vitro mechanism investigations revealed that DCT inhibited both the intestinal and the hepatic metabolism of nifedipine. Further study on the optimal dosing interval for nifedipine and DCT revealed that administration of DCT 30 min before or after nifedipine did not significantly change the AUC of nifedipine. CONCLUSIONS: The bioavailability of nifedipine is significantly increased by a simultaneous oral co-administration of DCT. This increase is caused by the inhibitory effect of DCT on both the intestinal mucosal and the hepatic metabolism of nifedipine. The dose interval between DCT and nifedipine needs to be set for over 30 min to avoid such drug-drug interactions.

KRT12 mutations and in vivo confocal microscopy in two Japanese families with Meesmann corneal dystrophy.

PURPOSE: To identify genetic mutations and study the corneal epithelium in Japanese patients with Meesmann corneal dystrophy. DESIGN: Laboratory investigation and prospective observational case series. METHODS: Slit-lamp biomicroscopy with fluorescein vital staining and in vivo confocal microscopy were performed. Mutation screening of the KRT3 and KRT12 genes was performed via polymerase chain reaction and direct sequencing for 5 patients in 2 families. RESULTS: Slit-lamp biomicroscopy revealed multiple corneal intraepithelial microcysts in all patients. A clear zone was seen in the younger generation, whereas mild subepithelial opacity was seen in the older generation. In the in vivo confocal microscopy, numerous corneal intraepithelial microcysts and hyperreflective materials, which were believed to be degenerative cells, were detected closer to the basal layer of the corneal epithelium in older patients. The superficial layer contained more enlarged microcysts, and the hyperreflective materials showed atrophic changes, as compared to the basal layer. The demarcation line between the microcysts and normal epithelial cells was clearly visualized by in vivo confocal microscopy and corresponded to the demarcation line of the clear zone observed by the slit-lamp examination. Two heterozygous mutations (Q130P, L140Q) in the KRT12 gene, one of which (L140Q) was novel, were identified only in the affected patients of the families. CONCLUSIONS: We identified a novel missense mutation of the KRT12 gene in Meesmann corneal dystrophy. The in vivo confocal microscopy examinations revealed previously unreported depth-dependent ultrastructural changes in the living cornea of Meesmann corneal dystrophy patients.

Customized photorefractive keratectomy for the correction of regular and irregular astigmatism after penetrating keratoplasty.

PURPOSE: To report visual, wavefront, and topographic outcomes in 5 post-penetrating keratoplasty patients who underwent customized aspheric topography-guided photorefractive keratectomy for high astigmatism or severe higher-order aberrations. METHODS: A chart review was performed for data collection. The custom aspheric transition zone ablation algorithm (CATz) with the CX III excimer was used for all treatments. Ablations were calculated based on corneal elevation data. Phototherapeutic keratectomy was the first step of the procedure. Visual acuity, corneal higher-order wavefront aberrations (Zernike sixth order and 4-mm diameter), corneal topography, and patient satisfaction were evaluated preoperatively and at the last visit postoperatively (range, 3 months to 4.5 years). The paired t test was used for statistical comparison of higher-order aberrations, with P < 0.05 indicating statistical significance. RESULTS: The mean spherical equivalent was -4.50 diopters (D) (range, -9.50 to +3.25 D) preoperatively and -1.00 D (range, -3.25 to +0.25 D) at the final visit. The mean cylinder was -7.00 D (range, -4.75 to -9.00 D) preoperatively and -1.25 D (range, -0.50 to -2.50 D) postoperatively. Postoperative uncorrected distance visual acuity increased in all eyes. No eyes lost corrected distance visual acuity postoperatively. There was a statistically significant decrease in higher-order corneal spherical aberration postoperatively (P = 0.02). Four patients were "very satisfied" or "satisfied" with the postoperative outcome, and 1 patient was "somewhat satisfied". All patients reported reduced symptoms postoperatively. CONCLUSIONS: Phototherapeutic keratectomy with CATz was effective as a single-step treatment for severe higher-order aberrations or moderate astigmatism after penetrating keratoplasty.

Signaling pathways activated by epidermal growth factor receptor or fibroblast growth factor receptor differentially regulate branching morphogenesis in fetal mouse submandibular glands.

Although growth factor signaling is required for embryonic development of organs, individual signaling mechanisms regulating these organotypic processes are just beginning to be defined. We compared signaling activated in fetal mouse submandibular glands (SMGs) by three growth factors, epidermal growth factor (EGF), fibroblast growth factor (FGF) 7, or FGF10, and correlated it with specific events of branching morphogenesis. Immunoblotting showed that EGF strongly stimulated phosphorylation of extracellular signal-regulated kinase-1/2 (ERK-1/2) and weakly stimulated phosphorylation of phospholipase Cgamma1 (PLCgamma1) and phosphatidylinositol-3 kinase (PI3K) in cultured E14 SMG. However, FGF7 and FGF10 stimulated phosphorylation of both PLCgamma1 and PI3K, but elicited only minimal phosphorylation of ERK-1/2. Morphological study of mesenchyme-free SMG epithelium cultured in Matrigel revealed that EGF induced cleft formation of endpieces, that FGF7 stimulated both cleft formation and stalk elongation, but that FGF10 induced only stalk elongation. In mesenchyme-free SMG epithelium cultured with EGF, FGF7 and FGF10, U0126 (MEK inhibitor) completely blocked cleft formation, whereas U73122 (PLCgamma1 inhibitor) suppressed stalk elongation. These finding suggest that EGF stimulates cleft formation and drives branch formation via ERK-1/2, and that FGF7 stimulates both cleft formation and stalk elongation via PLCgamma1 and partly via ERK-1/2, but that FGF10 stimulates stalk elongation mainly via PLCgamma1.

Bofutsushosan, a traditional Chinese formulation, prevents intimal thickening and vascular smooth muscle cell proliferation induced by balloon endothelial denudation in rats.

Bofutsushosan (BOF), a traditional Chinese formulation (Kampo formulation in Japanese), is widely used for patients with obesity and hyperlipidemia resulting from long-term inappropriate lifestyles. Since atherosclerosis, a lifestyle-related disease, is accompanied by an abnormal accumulation of vascular smooth muscle cells (VSMCs) in the intimal area of the artery, we investigated the preventive effect of BOF on intimal thickening. Oral administration of BOF extracts 3 d before and 7 d after balloon endothelial denudation dose dependently suppressed the intimal thickening and proliferation of VSMCs in the intimal area in rat carotid arteries. This model has a similar pathologic process to atherosclerosis and is considered to be an "accelerated atherosclerosis" model. BOF extract also dose dependently inhibited the migration of cultured VSMCs. BOF extract suppressed serum lipid levels, which are a major risk factor for atherosclerosis. These findings clarified the usefulness of BOF in cardiovascular risk-reduction therapy.

Transplantation of cryopreserved human corneas in a xenograft model.

An ideal model to test methods of corneal storage for transplantation would simulate the environment of the grafted human cornea and predict the success of clinical corneal transplants (human to human). In this study, we tested such a model, the corneal xenograft (human to cat). Nine pairs of human corneas were transplanted into both eyes of nine recipient cats. One cornea of each pair was cryopreserved at -196 degrees C in 2.5 M dimethyl sulfoxide while the other was stored in preservative medium at 4 degrees C (control) for 6 +/- 2 (mean +/- SD) days before transplantation. One week after transplantation, the cats were euthanized and the eyes were examined. Three of the grafts (all cryopreserved) were clinical failures and showed no survival of donor corneal endothelial cells on scanning electron microscopy. The remaining six pairs of grafts were examined with a specular microscope and showed endothelial cell losses of 48 +/- 16% in cryopreserved and 8 +/- 16% in control corneas (p < 0.05). This survival is similar to survival in an earlier corneal perfusion model. The nine cryopreserved grafts were thicker than the control grafts, had fewer surviving keratocytes in the central stroma, and had more apoptotic central keratocytes (TUNEL assay). This failure rate in cryopreserved corneas clearly shows that this technique of cryopreservation was not adequate for clinical use. The corneal xenograft model can be used to study cellular survival and apoptosis in vivo after preservation as well as to test new methods of corneal preservation before initiating clinical trials.