Factors associated with intrachoroidal cavitation and sinkhole formation in eyes with glaucomatous visual-field defects.

PURPOSE: To investigate factors associated with intrachoroidal cavitation (ICC) and sinkhole formation in eyes with glaucomatous visual-field defects. METHODS: This retrospective, cross-sectional study enrolled a total of 2808 eyes of 1482 patients who were diagnosed/treated for glaucoma and underwent swept-source optical coherence tomography (OCT). We first determined the prevalence of ICCs and sinkholes and their locations. Next, we selected one eye from each patient and compared the clinical characteristics of eyes with and without ICCs. Finally, in eyes with ICCs, we compared the clinical characteristics of eyes with and without sinkholes. Blood flow (BF), represented by laser speckle flowgraphy-measured tissue-area mean blur rate (MBR), was measured in the temporal optic nerve head (ONH), temporal peripapillary chorioretinal atrophy (PPA) zone, and in the ICC zone. ICC area and angle were analyzed in OCT en-face images. Mean deviation and total deviation in the central area (TD-central) were measured with Humphrey visual-field testing. RESULTS: A total of 86 eyes (3.1%) had ICCs and 52 eyes (1.9%) had sinkholes. ICC eyes had a lower spherical equivalent and longer axial length (AL) than non-ICC eyes (P < 0.05). Patients with eyes with sinkholes were more elderly and had worse best-corrected visual acuity, worse TD-central, a larger ICC, and lower tissue-area MBR in the temporal ONH, temporal PPA zone, and ICC zone (P < 0.05). CONCLUSION: In eyes with glaucoma, AL elongation might be linked to ICC formation. Sinkhole formation might be associated with ICC enlargement, impaired ocular BF, and impaired retinal structure and function involving the central area.

Predictive potential of optical coherence tomography parameters for the prognosis of decreased visual acuity after trabeculectomy in open-angle glaucoma patients with good vision.

BACKGROUND: Trabeculectomy (trab) is the most effective surgical procedure for lowering IOP and preventing glaucoma progression. However, decline in best-corrected visual acuity (BCVA) is one of the most serious postoperative complications of trab. Here, we investigated methods to predict decreased BCVA after trab in glaucoma patients with good preoperative BCVA. METHODS: This study included 35 eyes of 35 open-angle glaucoma (OAG) patients (male / female: 21 / 14, age: 64.0 ± 9.7 years old, preoperative intraocular pressure: 15.9 ± 5.4 mmHg, mean deviation: -18.1 ± 5.6 dB) with preoperative BCVA of 0.7 or better who underwent trab and were observed for more than 12 months. As a preoperative analysis, we measured temporal quadrant circumpapillary retinal nerve fiber layer thickness (cpRNFLT) and ganglion cell complex thickness in a central strip between the disc and fovea (csGCCT), an area that corresponds to the location of the papillomacular bundle (PMB) in swept-source optical coherence tomography (OCT). We defined BCVA decline as a loss of more than 3 lines of BCVA after 12 months. Measurement parameters were compared between the BCVA-decline group and the non-BCVA-decline group. RESULTS: BCVA decline was detected in 11 cases (31.4%) 12 months after trab. There was a statistically significant difference in axial length (P = 0.049). A single logistic analysis showed that the BCVA-decline group had significantly lower cpRNFLT than the non-BCVA-decline group (27.7 ± 8.0 µm vs. 45.1 ± 5.3 µm, P < 0.001, cut-off value: 33.4 µm), as well as lower csGCCT (72.4 ± 7.7 µm vs. 87.5 ± 5.1 µm, P = 0.002, cut-off value: 82.3 µm). Multivariable logistic analysis showed that the BCVA-decline group had significantly lower temporal quadrant cpRNFLT (P < 0.001) and lower middle csGCCT (P < 0.001) compared to the non-BCVA-decline group. CONCLUSIONS: Lower temporal quadrant cpRNFLT and middle csGCCT, OCT scan areas that correspond to the location of the PMB, might be biomarkers that predict BCVA decline after trab in OAG patients with good vision.

Blood coagulation dynamics during adrenocorticotropic hormone therapy in pediatric patients with infantile spasms.

INTRODUCTION: Adrenocorticotropic hormone (ACTH) therapy is a first-line treatment for infantile spasms, which may rarely cause intracranial hemorrhage. However, the changes in blood coagulation during ACTH therapy are poorly understood, with little description in the management guidelines. OBJECTIVE: To assess the changes in blood coagulation during ACTH therapy. PATIENTS/METHODS: This retrospective study reviewed the medical records of 10 patients diagnosed with infantile spasms and treated with ACTH therapy, between January 2015 and March 2021. The underlying diseases included intracranial hemorrhage, hypoxic-ischemic encephalopathy, tuberous sclerosis, and cerebral infarction. Antiepileptic drugs administered were valproic acid (VPA), vitamin B6, zonisamide, topiramate, clobazam, clonazepam, and phenobarbital. RESULTS: The 10 patients had a median age of 8 months (4-17 months) and included eight males. The median fibrinogen (Fbg) level before ACTH therapy was 202 mg/dL (125-392 mg/dL); however, this significantly decreased to 108.5 mg/dL (65-135 mg/dL) during treatment at a median of 12 days after (days 8-17) (p < 0.01). Decreased Fbg levels were observed with and without VPA. This suggests the possible influence of ACTH therapy on Fbg levels, irrespective of the VPA combination. Additionally, prothrombin time and activated partial thromboplastin time were significantly shortened when compared to those before ACTH therapy and at the lowest of Fbg levels. CONCLUSIONS: Careful coagulation monitoring, especially during the second week of treatment, is necessary for the safe completion of ACTH therapy, with or without concomitant VPA.

Carnitine in severely disabled patients: relation to anthropometric, biochemical variables, and nutritional intake.

BACKGROUND: Carnitine plays a pivotal role in a variety of cellular functions. Carnitine deficiency often occurs in severely disabled patients, especially under valproic acid administration. However, the possible causative factors underlying carnitine deficiency have not been fully identified. The present study aimed at clarifying the association of various anthropometric and biochemical variables, including dietary intake of carnitine, with carnitine levels in severely disabled patients. METHODS: Twenty-six severely disabled patients (mean age: 14.1 years; s.d. 7.8) were enrolled. Plasma carnitine levels were evaluated by an enzyme cycling assay. Estimation of the dietary intake of carnitine was made based on dietary records over a 3-day period. RESULTS: Plasma total and free carnitine levels in patients were significantly lower than those in controls obtained from the previous report. However, the ratios of free carnitine to total carnitine did not change significantly. Free carnitine levels were well correlated with a nutritional intake of carnitine. Administration of not only valproic acid but also other anti-epileptic drugs was found to cause a significant decrease of free carnitine levels after adjusting the nutritional intake of carnitine. Among various anthropometric or biochemical variables, albumin and uric acid showed a significant correlation with free carnitine levels. CONCLUSIONS: Physicians should be aware of the fact that severely disabled patients are at risk for carnitine deficiency even in the absence of valproic acid administration, and pay more attention to the nutritional intake of carnitine.

A rare congenital extrahepatic portosystemic shunt affecting the inferior mesenteric vein, inferior vena cava, and left ovarian vein.

PURPOSE: To observe a case of congenital extrahepatic portosystemic shunt and discuss it from the embryological and clinical viewpoints. METHODS: An 85-year-old female cadaver was employed for a dissection course at Aichi Medical University in 2009. RESULTS: There was no evidence of liver cirrhosis macroscopically or microscopically. A portosystemic shunt was observed that involved communication between the inferior mesenteric vein, inferior vena cava (IVC), and left ovarian vein by a single Y-shaped shunt vessel. CONCLUSIONS: To the best of our knowledge, this is the first reported case of the above-mentioned three veins being connected by a single Y-shaped shunt vessel. Considering the other venous diameters, the shunt appeared to flow into the splenic vein and IVC. It cannot be denied that this shunt may have led to hepatic encephalopathy, although the shunt effect may have been minimal. Embryological development of IVC appears to occur close to the plexus of anastomosing vitelline veins, forming the portal vein.

Effect of intravenous saccharated ferric oxide on serum FGF23 and mineral metabolism in hemodialysis patients.

BACKGROUND/AIMS: Fibroblast growth factor-23 (FGF23) plays a central role in the development of hypophosphatemia and inappropriately low 1,25-dihydroxyvitamin D induced by iron therapy for iron-deficiency anemia. The aim of this study was to examine the effect of intravenous saccharated ferric oxide on serum FGF23 levels and mineral metabolism in hemodialysis patients. METHODS: This prospective study enrolled 27 hemodialysis patients who had iron-deficiency anemia defined by a hemoglobin concentration < 10.5 g/dl and serum ferritin < 100 ng/ml. Intravenous saccharated ferric oxide at a dose of 40 mg was administered three times weekly over 3 weeks. The dose of active vitamin D and phosphate binders was kept unchanged. Serum FGF23, intact parathyroid hormone (PTH) and other parameters were prospectively monitored for 5 weeks. RESULTS: Serum FGF23 levels were markedly elevated [3,453 (338-6,383) pg/ml] at baseline. After 3 weeks of intravenous saccharated ferric oxide treatment, serum FGF23 further increased to 4,701 (1,251-14,396) pg/ml, and returned to the baseline values after 2 weeks of observation. There was also a significant decrease in intact PTH but no changes in serum calcium and phosphorus. CONCLUSIONS: Intravenous saccharated ferric oxide induces further increase in elevated FGF23 levels in hemodialysis patients. This increase does not induce hypophosphatemia and inappropriately low 1,25-dihydroxyvitamin D in the absence of functioning kidney, but may result in transient PTH suppression - possibly by directly acting on the parathyroid.

Involvement of OCTN2 in the transport of acetyl-L-carnitine across the inner blood-retinal barrier.

PURPOSE: To elucidate the mechanisms of acetyl-L-carnitine transport across the inner blood-retinal barrier (inner BRB). METHODS: In vivo integration plot and retinal uptake index (RUI) analyses were used to examine acetyl-L-[(3)H]carnitine transport in the retina across the inner BRB in rats. RUI was determined from the ratio of acetyl-L-[(3)H]carnitine and [(14)C]n-butanol, a freely diffusible internal reference, in the retina divided by the same ratio in the solution injected in the carotid artery. The transport mechanism was characterized in a conditionally immortalized rat retinal capillary endothelial cell line (TR-iBRB2 cells), as an in vitro inner BRB model. RESULTS: The apparent influx permeability clearance (K(in)) per gram retina of acetyl-L-[(3)H]carnitine was found to be 2.31 microL/(minute . g retina). The K(in) of acetyl-L-[(3)H]carnitine was 3.7-fold greater than that of [(3)H]D-mannitol, a nonpermeable paracellular marker. Acetyl-L-[(3)H]carnitine uptake by the retina was found to be significantly inhibited by L-carnitine and acetyl-L-carnitine, supporting a carrier-mediated influx transport of acetyl-L-carnitine at the inner BRB. L-[(3)H]carnitine and acetyl-L-[(3)H]carnitine uptake by TR-iBRB2 cells was Na(+)- and concentration-dependent, with a K(m) of 29 and 26 microM, respectively. These forms of transport were significantly inhibited by organic cation/carnitine transporter (OCTN) substrates and inhibitors such as L-carnitine and acetyl-L-carnitine, tetraethylammonium, quinidine, and betaine. These transport properties are consistent with those of carnitine transport by OCTN2. OCTN2 was predominantly expressed in TR-iBRB2 cells and isolated rat retinal vascular endothelial cells. CONCLUSIONS: The findings suggest that OCTN2 is involved in the transport of acetyl-L-carnitine from the circulating blood to the retina across the inner BRB.

[Case of goodpasture syndrome associated with minimal change nephrotic syndrome (MCNS) in a patient with rheumatoid arthritis (RA)].

In early June 2004, a 50-year-old female was admitted to the hospital for slight fever, general fatigue, hemoptysis, dyspnea, and renal dysfunction (serum creatinine[Cr] : 6.05 mg/dL). She had been treated with prednisolone (PSL : 10-20 mg/day) for RA. She was diagnosed with Goodpasture syndrome based on a high titer of anti-glomerular basement membrane antibody (87 EU), and pulmonary hemorrhage. The renal and pulmonary impairments were markedly improved by the pulse therapy, plasma exchange and temporary hemodialysis. However, the Cr level remained at 2.0 mg/dL, indicating nephrotic syndrome. Light microscopy with Periodic acid-Shiff(PAS) staining demonstrated global sclerosis in three of ten glomeruli. Five glomeruli showed the formation of cellular, and fibrocellular crescents, and the formation of fibrous crescents. Tubular damage and interstitial fibrosis were severe. Immunofluorescence microscopy disclosed major depositions of IgG in a linear pattern along the glomerular basement membrane(GBM). Electron microscopy revealed foot process effacement (>50%)and no electron-dense deposits. Therefore, we diagnosed Goodpasture syndrome associated with minimal change nephrotic syndrome (MCNS). Some reports have dealt with the association of RA and Goodpasture syndrome with D-penicillamine, and of RA and antineutrophil cytoplasmic antibodies (ANCA)-related vasculitis with pulmonary hemorrhage, but none has dealt with cases complicated with RA and Goodpasture syndrome associated with MCNS. Accordingly, whether or not there is a causal relationship between RA and Goodpasture syndrome remains obscure, but since the number of reported cases is small, experience with more cases is necessary to clarify this matter.

Reversed whole PTH/intact PTH ratio as an indicator of marked parathyroid enlargement: five case studies and a literature review.

Parathyroid hormone (PTH) levels detected by intact PTH assays are generally higher than those detected by the whole PTH assay because the latter does not detect non-(1-84) PTH fragments, mainly PTH (7-84). Rare exceptions to this rule have been reported in patients with severe primary or secondary hyperparathyroidism and parathyroid carcinoma. Overproduction of an N-form of PTH other than PTH (1-84) has been observed in the sera of these patients. We report five additional cases with the reversed whole PTH/intact PTH ratio associated with severe hyperparathyroidism in haemodialysis patients. Three patients demonstrated enlargement of a single hypervascular gland, whereas the other two had undergone surgical parathyroidectomy and later showed recurrent hyperparathyroidism due to progressive autograft hyperplasia. In the case of a single enlarged gland, the pathological pattern and heterogeneous expression of parathyroid adenomatosis 1/cyclin D1 suggested it to be a single nodule of uraemic hyperparathyroidism rather than sporadic primary adenoma. These cases suggested that the reversed whole PTH/intact PTH ratio could be an indicator of marked parathyroid enlargement. Further studies are required to elucidate the clinical significance of the reversed whole PTH/intact PTH ratio in haemodialysis patients.

Characterization of teleost phagocyte NADPH oxidase: molecular cloning and expression analysis of carp (Cyprinus carpio) phagocyte NADPH oxidase.

We previously demonstrated that some fish have unique response in the form of reactive oxygen species (ROS) production. In the present study, we cloned and sequenced the full-length cDNAs for carp (Cyprinus carpio) phagocyte NADPH oxidase components: gp91phox, p22phox, p47phox, p67phox and p40phox. These amino acid sequences were compared with other teleost and mammalian homologues, to elucidate the features of ROS production of fish neutrophils. The phylogeny analysis clearly demonstrates that the radiation of phagocyte oxidase components took place in the common ancestor of teleosts and mammals. Thereafter, the overall structure and expression pattern of phagocyte oxidase have been highly conserved in two different strains. However the amino acid identity of p67phox and p47phox was relatively lower than the amino acid identities of other components. Moreover, a synteny analysis supports the hypothesis that there was strong selective pressure in the p67phox and p47phox genes. Thus, it is likely that the higher divergence of p67phox and p47phox are responsible for the difference of ROS responses between different species of teleosts.

Association and dissociation of the cell puncturing complex of bacteriophage T4 is controlled by both pH and temperature.

The tail lysozyme, gp5, of bacteriophage T4 is a trimeric protein and all the subunits are nicked between Ser351 and Ala352 during assembly through processing. When subsequently heated, the resulting (gp5*)(3) (gp5C)(3) (the asterisk "*" denotes that the intact pre-gp5 trimer has been nicked) dissociates into three gp5* (three independent N-terminal monomeric peptides, that carry lysozyme moieties at the C-termini of gp5*), and a C-terminal trimeric beta-helical structure (gp5C)(3). The interaction between gp27 and gp5* during infection is sundered by reducing pH. This dissociation would be physiologically relevant because the lysozyme moieties should be free in the periplasm (where the pH is low) and would digest the peptidoglycan layer, thereby enabling the tail tube to contact the inner membrane, and probably help to form a pore for DNA injection.

Inhibition of cell spreading in CHO cells transfected with cDNA of a glycosylphosphatidyl inositol-anchored protein, GPI-80.

We have previously cloned a glycosylphosphatidyl inositol (GPI)-anchored protein, designated GPI-80 that associated with integrin and may modulate leukocyte adherence and migration. Recent studies have shown that GPI-80 belongs to a Vanin family that is related to pantetheinase, but the regulatory function of GPI-80 in cell adherence is still unclear. To clarify the possible functions of GPI-80, we transfected GPI-80 cDNA into Chinese hamster ovary (CHO) cells and observed adherence and morphological changes. Adherence of GPI-80 transfectants was significantly decreased when signal strength for the cell adhesion is weak, and the cell spreading of the transfectants was strongly inhibited. This inhibitory effect of GPI-80 expression was largely canceled by GPI-80 shedding with phosphatidy-linositol-specific phospholipase C. Interestingly, spreading of GPI-80 transfectants was temporarily recovered from the round shape but not maintained by stimulation with known activators of beta1 integrins, phorbol myristate acetate and manganese ions. Taken together, these results suggest that the expression of GPI-80 on CHO cells can influence cell spreading in weak adhesive signal conditions via extracellular matrix molecules.