Post-vitrectomy observation of Coat's disease associated with exudative retinal detachment, successfully treated with long-term silicone oil tamponade.

BACKGROUND: Treating Coat's disease with exudative retinal detachment remains a challenge, since vitreous surgery is frequently accompanied by serious complications such as secondary glaucoma. CASE: A 25-year-old woman with Coat's disease of the right eye had cystic exudative retinal detachment along the naso-inferior vessels at the peripheral retina, due to 5-o'clock telangiectasia. Right visual acuity was finger counting. This patient underwent vitrectomy simultaneously with cataract surgery, completed with silicone oil replacement, with thorough drainage of subretinal exudates through the artificial break. Although the complication of secondary glaucoma developed as a result of using silicone oil, approximately three years after the operation, this condition was ameliorated by removing the silicone oil. Thus, blindness was prevented in this patient. CONCLUSION: Long-term tamponade with silicone oil facilitates performing vitreous surgery in this patient suffering from Coat's disease associated from exudative retinal detachment.

[Analytical method of volatile substances in styrene polymers by head-space gas chromatography using o-dichlorobenzene].

A quantitative analytical method for 8 volatile substances (such as styrene) in styrene polymers that are not soluble in tetrahydrofuran (THF) and dimethylformamide was developed. The sample was chopped finely and a 0.1 g portion was weighed in a head-space vial. To this was added 2 mL of o-dichlorobenzene (DCB) including 50 µg/mL of internal standard. The vial was sealed and heated at 140℃ for 1 hour and then 1 mL of the head-space gas was injected into a gas chromatograph using an automatic sampler. Samples of syndiotactic polystyrene, styrene block copolymer and modified polyphenylenether were dissolved or dispersed in DCB. Separation and accuracy of the method were satisfactory. Recoveries were 95-113% at the spiked concentration of 300 µg/g. The method was confirmed to be suitable for general styrene polymers that are soluble in THF. Equivalent results were obtained with this method and the method in "Specifications and Standards for Food, Food Additives, etc. " for general purpose polystyrene, high impact polystyrene, styrene/acrylonitrile resin and acrylonitrile/butadiene/styrene resin.

Topical dorzolamide for macular edema in the early phase after vitrectomy and epiretinal membrane removal.

BACKGROUND: The purpose of this study was to evaluate prospectively the efficacy of a topical carbonic anhydrase inhibitor in macular edema after vitrectomy. METHODS: Forty patients were included, all of whom had undergone vitrectomy combined with phacoemulsification and intraocular lens implantation for epiretinal membrane. Twenty eyes from 40 patients received topical 2% dorzolamide three times a day. The patients were followed up for at least 3 months. In this study, we evaluated the effect of dorzolamide on visual acuity, intraocular pressure, central macular thickness, and aqueous flare. RESULTS: Mean logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity preoperatively and 2 weeks, 1 month, and 3 months after surgery was 0.48 ± 0.23, 0.60 ± 0.16, 0.40 ± 0.29, and 0.24 ± 0.32, respectively, in the treatment group, and 0.40 ± 0.09, 0.44 ± 0.12, 0.32 ± 0.10, and 0.16 ± 0.09, respectively, in the control group. No statistically significant difference was observed between the two groups. Mean central macular thickness preoperatively and at 2 weeks and 3 months after surgery was 572.6, 427.2, and 333.4 µm, respectively, in the treatment group, and 571.4, 485.2, and 388.4 µm, respectively, in the control group. Mean aqueous flare preoperatively, and 1 month and 3 months after surgery was 8.6, 34.2, and 23.5 photon counts per millisecond (pc/ms), respectively, in the treatment group, and 9.7, 24.7, and 23.4 pc/ms, respectively, in the control group. No statistically significant differences were observed between data from the two groups. However, statistically significant (P < 0.05) differences in mean central macular thickness at 1 month and mean aqueous flare at 2 weeks after surgery were found between the treatment group (358.8 µm, 36.8 pc/ms) and the control group (467.8 µm, 64.0 pc/ms). Differences in mean intraocular pressure preoperatively and at 2 weeks, 1 month, and 3 months after surgery were not statistically significant between the two groups. Intraocular pressure never exceeded 21 mmHg. CONCLUSION: Topical dorzolamide significantly reduced mean central macular thickness at 1 month and mean aqueous flare at 2 weeks after surgery for epiretinal membrane compared with controls. Although further investigation of more cases and longer follow-up are needed, this study suggests that topical dorzolamide can be efficacious in reducing macular edema in the early phase after vitrectomy via its anti-inflammatory effect.

The 23 gauge capsulorrhexis forceps having a cystotome function.

We evaluate the operational performance of the 23 gauge capsulorrhexis forceps with a cystotome function. The 23 gauge capsulorrhexis forceps were applied in 6 complex cases such as cataract surgery after closed-angle glaucoma with shallow anterior chamber, mal mydriasis, or lens subluxation. In all cases, we measured each patient's gonio angle level and degree of mydriasis. The forceps can be used in all cases even shallow anterior chamber glaucoma, because the forceps have both the functions of forceps and a cystotome with 55 degrees angulated needle. Although lens subluxation was found in 5 out of the 6 cases during continuous curvi-linear capsulorrhexis (CCC), implantation of the intraocular lens (IOL) in the capsular bag was successfully completed in these 5 cases. The 23 gauge forceps were effective particularly in cases for cataract surgery after glaucoma operation.

[Case of anterior ischemic optic neuropathy accompanied by Churg-Strauss syndrome].

BACKGROUND: Churg-Strauss syndrome (CSS) is a vasculitis which includes the three signs of bronchial asthma, hypereosinophilia, and vasculitis syndrome. We report a case in whom anterior ischemic optic neuropathy (AION) accompanied CSS. Such a case has not been reported previously in Japan. CASE: A 66-year-old woman with a history of bronchial asthma and eosinophilic pneumonia was hospitalized for fever, unusual feelings in both plantae and in a finger of her left hand, disturbance of visual acuity and visual field in the right eye, and skin rashes; a diagnosis of CSS was made. At the time of the first ophthalmological examination, AION was observed. Steroid therapy was started, but the treatment was not effective, despite an improvement in choroidal circulation confirmed by fluorescein angiography and indocyanine green angiography. In the unaffected eye, soft exudates appeared when the steroid dose was lowered and disappeared when the steroid dose was raised. CONCLUSION: Anterior ischemic optic neuropathy accompanied with Churg-Strauss syndrome resisted medical treatment and the prognosis was poor.

A case report of intraocular lens luxation with the capsular bag after vitrectomy.

We experienced a case of intraocular lens (IOL) luxation with the capsular bag after vitrectomy. The case was a 66-year-old female in whom an IOL was implanted one year after surgery for giant tear retinal detachment using silicone oil. Four years after the implantation surgery, the patient suffered subluxation of the IOL with the capsular bag. Examinations of the luxated IOL with the capsular bag using a stereoscopic microscope confirmed the presence of silicone oil droplets between the capsule and the IOL. Adhesion of vitreous body residues was observed in the capsule. Luxation of the IOL was thought to be connected with chronic inflammation resulting from the use of silicone oil and repeated vitrectomy. In addition to examining pathological findings of luxated IOL, it would also be important in the future to identify the pathology of the capsular bag.

Inhibition of granulation tissue cell apoptosis during the subacute stage of myocardial infarction improves cardiac remodeling and dysfunction at the chronic stage.

BACKGROUND: Granulation tissue cells at the subacute stage of myocardial infarction (MI) are eliminated by apoptosis to finally make a scar at the chronic stage. We hypothesized that postinfarct inhibition of apoptosis might preserve myofibroblasts and endothelial cells in granulation and modulate chronic left ventricular (LV) remodeling and heart failure. METHODS AND RESULTS: A pancaspase inhibitor, Boc-Asp-fmk (BAF, 10 micromol/kg per day), or vehicle (control) was given to rats with experimental large MI. The treatment was started on the third day after MI and continued until 4-week-old MI. Two weeks later, the apoptosis of granulation tissue cells was significantly reduced and conversely, the cell population was greater in BAF. Twelve weeks later, BAF showed significantly greater survival rates (84% versus 42%) with significantly smaller LV cavity, lower LV end-diastolic pressure and central venous pressure, and higher LV dP/dt, which indicated improvement of LV remodeling and dysfunction. A scar was established in old infarct of control subjects, but in BAF, the infarct wall was thicker because of greater old infarct area, which contained abundant myofibroblasts and vessels. Surprisingly, many of the alpha-smooth muscle actin-positive myofibroblast-like cells in BAF, making bundles and running parallel to the survived cardiomyocytes, were ultrastructurally mature smooth muscle cells with contractile phenotype. Cardiomyocyte apoptosis in the infarct area was equally rare in each group. CONCLUSIONS: The postinfarct treatment with BAF improved LV remodeling and dysfunction through inhibition of granulation tissue cell apoptosis. These findings imply a new therapeutic strategy against postinfarct heart failure.

Postinfarction treatment with an adenoviral vector expressing hepatocyte growth factor relieves chronic left ventricular remodeling and dysfunction in mice.

BACKGROUND: Hepatocyte growth factor (HGF) is implicated in tissue regeneration, angiogenesis, and antiapoptosis. However, its chronic effects are undetermined on postinfarction left ventricular (LV) remodeling and heart failure. METHODS AND RESULTS: In mice, on day 3 after myocardial infarction (MI), adenovirus encoding human HGF (Ad.CAG-HGF) was injected into the hindlimb muscles (n=13). As a control (n=15), LacZ gene was used. A persistent increase in plasma human HGF was confirmed in the treated mice: 1.0+/-0.2 ng/mL 4 weeks later. At 4 weeks after MI, the HGF-treated mice showed improved LV remodeling and dysfunction compared with controls, as indicated by the smaller LV cavity and heart/body weight ratio, greater % fractional shortening and LV +/-dP/dt, and lower LV end-diastolic pressure. The cardiomyocytes near MI, including the papillary muscles and trabeculae, were greatly hypertrophied in the treated mice. The old infarct size was similar between the groups, but the infarct wall was thicker in the treated mice, where the density of noncardiomyocyte cells, including vessels, was greater. Fibrosis of the ventricular wall was significantly reduced in them. Examination of 10-day-old MI revealed no proliferation or apoptosis but showed augmented expression of c-Met/HGF receptor in cardiomyocytes near MI, whereas a greater proliferating activity and smaller apoptotic rate of granulation tissue cells in the HGF-treated hearts was observed compared with controls. CONCLUSIONS: Postinfarction HGF gene therapy improved LV remodeling and dysfunction through hypertrophy of cardiomyocytes, infarct wall thickening, preservation of vessels, and antifibrosis. These findings imply a novel therapeutic approach against postinfarction heart failure.

Myocytes positive for in situ markers for DNA breaks in human hearts which are hypertrophic, but neither failed nor dilated: a manifestation of cardiac hypertrophy rather than failure.

The significance of DNA breaks reported in failing hearts is controversial, although they may suggest myocyte apoptosis and may thus be responsible for the progression of heart failure. This study attempted to check the validity of the in situ markers for DNA breaks for detecting myocyte death and to evaluate separately two factors, failure or hypertrophy, crucial for DNA breaks in pathological human hearts. In the autopsy study, myocytes showed positivity for in situ nick end-labelling (TUNEL) and of Taq and Pfu polymerase-based in situ ligation assays not only in dilated cardiomyopathy (DCM, n = 9) with failure, but also in hypertrophic cardiomyopathy (HCM, n = 8) and hypertensive heart disease (HHD, n = 4) without failure. There was a significant correlation between each in situ marker and heart weight. The incidence of TUNEL-positive myocytes always exceeded that seen in in situ ligation assays. In addition, there were significant correlations between the in situ markers and the expression of the proliferating cell nuclear antigen (PCNA) and of the spliceosome component of 35 kD (SC-35). Similarly, in the left ventricular biopsy study using 23 DCM, 21 HCM, 11 HHD, and 13 non-hypertrophic hearts, the incidence of the in situ markers showed significant correlations with the left ventricular mass index and myocyte size, but not with cardiac function and dilatation. Positivity of myocytes for in situ markers for DNA breaks, such as TUNEL and in situ ligation assays, may be an epiphenomenon accompanying cardiac hypertrophy, but not myocyte death in pathological human hearts.

Molecular mechanisms of non-apoptosis by Fas stimulation alone versus apoptosis with an additional actinomycin D in cultured cardiomyocytes.

OBJECTIVE: In cultured cardiomyocytes, apoptosis is induced not by Fas stimulation, a popular inducer of apoptosis, but by an additional treatment with actinomycin D (AD), a transcription inhibitor, although the mechanism is unknown. Our hypothesis is that Fas stimulation not only activates pro-apoptotic signals but also may inhibit some of them, and this inhibition is blocked by AD. METHODS: Cultured neonatal mouse cardiomyocytes were treated with agonistic anti-Fas antibody (FA), AD, or both (FA+AD). In this system, apoptotic signals related to Fas-induced apoptotic pathways were examined by RT-PCR and immunoblotting. In addition, antisense oligonucleotide (AS) studies were carried out. RESULTS: The treatment with FA+AD induced up-regulation of Fas, activation of c-Jun N-terminal kinase (JNK), which is one of the key molecules of the alternate pathway of Fas-induced apoptosis, up-regulation of Bax, up-regulation and activation of caspase-3, activation of caspase-3-dependent DNase (CAD), and final DNA fragmentation and apoptotic morphologies in cardiomyocytes. FA alone or AD alone did not affect any part of the above pathway. However, mRNA of mitogen-activated protein kinase phosphatase-1 (MKP-1), an inactivator of JNK, was up-regulated by FA alone, but not by FA+AD or AD alone. Pretreatment with AS against MKP-1 induced apoptosis in FA alone-treated cardiomyocytes, whereas AS against JNK1 prevented apoptosis induced by FA+AD. On the other hand, FA+AD did not result in the activation of either caspase-8, one of the key molecules of the classic pathway in Fas-induced apoptosis, p38 MAPK, or extracellular signal-regulated kinase (ERK). CONCLUSIONS: Cardiomyocyte apoptosis by FA+AD depends on the alternate pathway through the JNK, Bax and caspase-3, and CAD-dependent pathways including a positive feedback mechanism of Fas up-regulation. The molecular mechanism that prevents Fas stimulation alone from inducing apoptosis involves up-regulation of MKP-1, an inhibitor of JNK; this up-regulation is inhibited by AD.

Abundant apoptosis in nutmeg liver of cardiomyopathic hamsters. Apoptotic cell death as a possible mechanism of hepatic remodeling by congestion.

Chronic congestive heart failure (CHF) causes structural remodeling of the liver, generally leading to nutmeg liver. Male UM-X7.1 hamsters, a strain developing cardiomyopathy, had no CHF and decompensated CHF (n = 6 each) at the age of 10 and 30 weeks, respectively. We used age-matched, male Syrian hamsters without CHF (n = 6 each) as controls. All the 30-week-old UM-X7.1 hamsters had a typical nutmeg liver in which the population of hepatocytes was decreased. Positive in situ nick end labeling (TUNEL) was found in 2.2 +/- 0.74% of hepatocytes in congestive livers, being significantly higher compared with the other groups without CHF (< 0.5%). DNA ladder pattern was also evident in the congestive livers. Electron microscopy revealed a typical apoptotic ultrastructure in the hepatocytes of the 30-week-old UM-X7.1 hamsters. However, many showed secondary necrotic changes. Although hepatocytes undergoing oncosis (primary necrosis) are rare, they were also found. The level of soluble Fas ligand in the plasma was increased, and Fas receptor in the liver was overexpressed in the CHF animals. In addition, both the Bax/Bcl-2 ratio and the Bad/Bcl-xL ratio were increased, and caspase-3 was activated in them. Our findings suggest that hepatocyte apoptosis contributes to hepatic remodeling under conditions of CHF.

Sensitivity to apoptosis signal, clearance rate, and ultrastructure of fas ligand-induced apoptosis in in vivo adult cardiac cells.

BACKGROUND: Sensitivity to apoptotic signals, the clearance rate of apoptosis, and the apoptotic ultrastructure have not been studied in cells of the in vivo adult heart. METHODS AND RESULTS: To minimize the systemic influence, soluble Fas ligand was injected directly into in vivo rat hearts and livers (as the control) at concentrations of 0, 0.5, 2, and 5 microg/mL (groups C, F0.5, F2, and F5). Apoptotic cardiomyocytes and apoptotic noncardiomyocytes of the heart were identified with similar incidences only in F5. Their incidences peaked at 12 hours after injection (2.0+/-0.09% in cardiomyocytes) and diminished markedly 24 hours later. Caspase-3 was activated only in F5. Boc-Asp-fmk, a pancaspase inhibitor, inhibited apoptosis, suggesting that the apoptosis sensitivity was regulated upstream of caspase-3. Apoptotic noncardiomyocytes showed typical ultrastructure. In addition to the typical ultrastructure, such as cellular shrinkage, chromatin condensation, and apoptotic bodies, however, apoptotic cardiomyocytes showed unique features: doughnut-like, but not half-moon- or crescent-like, chromatin condensation; frequent plasma membrane rupture even during the early stage; condensed mitochondria with wrinkled cristae inside; the appearance of cytoplasmic lipid-like droplets; and myofibrillar derangement. In the livers, typical apoptosis was induced in hepatocytes and nonhepatocytes of the liver even in the F0.5 group, which were cleared 24 hours later. CONCLUSIONS: Compared with liver cells, cardiomyocytes as well as noncardiomyocytes of the heart are more resistant against the apoptotic signal, but the clearance is similarly rapid (within 24 hours). The ultrastructure of apoptotic cardiomyocytes is unique. These findings provide new insights into the dynamics of cell death in the heart.

In vivo quantitative tissue characterization of human coronary arterial plaques by use of integrated backscatter intravascular ultrasound and comparison with angioscopic findings.

BACKGROUND: The purpose of the present study was to define whether integrated backscatter (IB) combined with conventional intravascular ultrasound (IVUS) makes tissue characterization of coronary arterial plaques possible. METHODS AND RESULTS: IB-IVUS was performed in coronary arteries (total 18 segments) of 9 patients at autopsy, and the findings were compared with the histology. RF signals, which were digitized at 2 GHz in 8-bit resolution, were obtained with an IVUS system with a 40-MHz catheter. IB values of the RF signal from the region of interest (ROI) (100-microm depth, 1.4 degrees per line) were calculated by use of a personal computer. IB values on the ROIs were divided into 5 categories, compared with each of the plaque histologies: category 1 (thrombus), -88 < IB < or = -80; category 2 (intimal hyperplasia or lipid core), -73 < IB < or = -63; category 3 (fibrous tissue), -63 < IB < or = -55; category 4 (mixed lesions), -55 < IB < or = -30; and category 5 (calcification), -30 < IB < or = -23. On the basis of these categories, we analyzed 5120 ROIs per segment in each ring-like arterial specimen. Color-coded maps of plaques were constructed by use of these IB data and conventional IVUS data, which reflected the plaque histology of autopsied coronary arteries well. Then, the same method was undertaken in 24 segments with plaque from 12 patients in vivo with angina pectoris. Comparisons between coronary angioscopy and IB-IVUS revealed that the surface color of plaques in angioscopy reflected the thickness of the fibrous cap rather than the size of the lipid core. CONCLUSIONS: IB-IVUS represents a new and useful tool for evaluating the tissue structure of human coronary arterial plaques.