Clinical and genetic findings in Hungarian patients with X-linked juvenile retinoschisis.

PURPOSE: To determine clinical phenotypes, examine the age dependency of X-linked juvenile retinoschisis (XLRS), and identify mutations in the retinoschisis1 gene (RS1) in 13 Hungarian (Caucasian) families with this disease. METHODS: This study included 72 members in 13 families. Complete ophthalmological examinations, including optical coherence tomography (OCT) and full-field and multifocal electroretinography (ERG), were performed on 20 affected males, 13 female carriers, and 27 healthy controls. The patients were divided into two age groups (Group I <25 years and Group II >25 years), retrospectively, to assess the possible effects of age. Correlations among genotype, age, best corrected visual acuity (BCVA), OCT, and ERG results were analyzed. A modified classification scheme was done to identify the different phenotypes of the disease. In each of the 72 family members and 100 age-matched male controls, all exons and introns of RS1 were amplified by polymerase chain reaction (PCR) and directly sequenced. RESULTS: Foveal retinoschisis was detected in 25 eyes (62.5%) of patients by funduscopy, and in 29 eyes (72.5%) by OCT, while macular lamellar schisis was recognizable only by OCT in 30 eyes (75%) of patients. Foveal thickness (FT) and total macular volume were significantly increased in younger (Group I) patients only. For patients younger than 26 years, large inner nuclear central cysts were observable by OCT, while after 26 years, foveas were atrophic. White flecks and dots, which were like that seen in fundus albipunctatus, were detected in both eyes of one patient. In both patient groups, characteristically decreased b-waves of standard combined ERG were recorded without any significant difference between the patient groups. The BCVA and ERG parameters of all patients and the OCT of younger patients were significantly worse (p<0.05) than those of age-matched controls. A significant difference between the two age groups was found in case FT, total macular volume, and amplitudes of rod b-wave only. Moderate negative correlation (r=-0.54, p<0.001) was detected between age and FT, while only low negative correlation (r=-0.33, p<0.05) was detected between age and standard combined b-wave amplitudes of full-field ERG. BCVA LogMAR did not show any obvious correlation with age (r=-0.14, p=0.39) or with the type of mutation. Nine different mutations were identified in 25 male patients and 31 female carriers of 13 families: six known and one novel missense mutation (c.575C>T, p.Pro192Leu), one insertion mutation (c.579dupC, p.Ile194Hisfs29ext43), and one frameshift, causing splice site mutation (c.78+1G>C) were detected. These mutations were absent in the 100 age-matched male control samples. CONCLUSIONS: Foveal cystic schisis was found more often by OCT than by funduscopy (+10%), while flat macular lamellar schisis was recognizable only by OCT. Advancing age inversely influenced the size of cavities (FT), and standard combined b-wave amplitudes of full-field ERG, while BCVA, response density, and implicit times of multifocal electroretinography did not show any obvious correlation with age. The atrophic stage of the disease was observable after 26 years of age. The lesions that appeared to be indicative of fundus albipunctatus were proven to be palisades between the splitted retinal layers. Our modified classification scheme was helpful in assessing the prevalence of disease types. In these Hungarian patients, one novel and eight known mutations were detected. The distribution of mutations in RS1 was different to that reported in the literature, because the greatest number of different mutations was in exon 6 instead of exon 4. Two mutation hot spots were found: between c.418-422 in exon 5 and between c.574-579 in exon 6. Genotype-phenotype correlation was not demonstrable.

[Refraction and visual acuity after laser coagulation treatment for retinopathy of prematurity in stage 3+]. / Refraktion und Visus nach Laserbehandlung bei Retinopathia praematurorum (ROP) im Stadium 3+

PURPOSE: Correlations between myopia < or =-4.0 D, birth weight, gestation age at birth, extension of laser photocoagulation and mild posterior pole changes were assessed in eyes of 1-year-old children who underwent laser treatment for stage 3+ retinopathy of prematurity (ROP). In addition the relationship between best-corrected visual acuity (VA) and mild posterior pole alterations was evaluated at 3 years of age. PATIENTS AND METHODS: Patients who underwent argon or diode laser photocoagulation between 1996 and 2000 for ROP 3+ disease were analyzed in this retrospective study. Cycloplegic refraction was determined in 72 eyes of 1-year old patients ( n=39). At 3 years of age cycloplegic refraction was measured in 36 eyes of 19 patients, and visual acuity was determined in 25 eyes of 13 children. RESULTS: Myopia of < or =-4.0 D significantly correlated only with mild posterior pole changes (i.e. clinically significant dragging of the temporal vessels of the retina or macular heterotopia, p=0.001). The correlation was significant between a VA reduction to <0.8 and mild posterior pole alterations ( p=0.014). CONCLUSIONS: The prevalence of myopia < or =-4,0 D and visual acuity <0.8 appears to be increased even with mild posterior pole changes. Birth weight does not seem to be significant factor in the prevalence of myopia < or =-4.0 D following laser coagulation of stage 3 threshold ROP.

[Relapsing polychondritis associated with myelodysplasia and acute eosinophilic leukemia]. / Polychondritis recidivanshoz társuló myelodysplasiás syndroma és akut eosinophilsejtes leukaemia esete.

Authors report a case in which relapsing polychondritis had been diagnosed two years before myelodysplastic syndrome developed and terminated in eosinophilic leukemia. The observation that relapsing polychondritis may precede myelodysplasia is not in concordance with some of the previous reports regarding relapsing polychondritis as a paraneoplastic phenomenon of myelodysplastic syndrome. The terminally developed eosinophilic leukemia is not supposed to be a blastic phase of the underlying myelodysplasia, much rather a second malignant process. This opinion may be confirmed by the early presence of blast cells in the myelodysplastic process without eosinophilia. It seems interesting to note that both our patient and his daughter suffered from diseases of autoimmune origin: acquired vitiligo and subacute cutan lupus erythematodes, respectively.

Interaction of immunosuppressive agents and human adenovirus infection in mice.

It was examined whether sensitivity of mice to human adenovirus infections is affected by immunosuppressive agents. Mice treated with the lymphotropic cytostatic dianhydrodulcitol (DAD) or antilymphocytic serum (ALS) did not become susceptible to human adenovirus type 12 infection, as the virus did not replicate--not even in its component forms--in the animals. On the other hand, the effect of both DAD and ALS on the lymphoid organs of mice was intensified by human adenovirus infection. In tissue cultures the reproduction of adenovirus was facilitated by DAD.

The inhibition of retinal inducible nitric oxide synthase overexpression and the attenuation of experimental uveitis by anti-inflammatory drugs in rats.

OBJECTIVE AND DESIGN: The effect of a steroid and a non-steroid anti-inflammatory drug on the inducible nitric oxide synthase (NOS II) in rats suffering from lipopolysaccharide (LPS)-induced uveoretinitis was studied. TREATMENTS: Rats were injected with LPS to induce uveitis and divided into three groups: treated with LPS only, LPS + dexamethasone and LPS + indomethacin, respectively. METHODS: Retinal, peritoneal macrophages and white blood cells were isolated. The activity and the expression of NOS II were followed by citrulline formation and Western blotting, respectively. Phagocytosis of bacteria was also measured. RESULTS: The best induction of NOS II was achieved by the intravitreal administration of LPS. Dexamethasone and indomethacin significantly decreased the activity and the expression of inducible nitric oxide synthase in retinal tissue, peritoneal macrophages and white blood cells. LPS treatment also increased phagocytosis and neither dexamethasone nor indomethacin reversed this effect. CONCLUSIONS: The beneficial effects of these drugs in experimental uveitis are mediated, at least partly, by their inhibitory effect on NOS II induction.

Suppressed phagocytosis but promoted bacterial growth upon the effect of virus free supernatants of infected lymphocytes.

The pathomechanism of suppressed phagocytosis and bacterial superinfections which follow viral diseases is not completely understood. Both polymorphonuclear leukocytes (PMNL) and mononuclear phagocytes (MNPh) as well as bacterial growth are controlled by several cytokines produced by other immune cells. The effect of disturbed production of cytokines on phagocytes and microbes have not been studied yet. Peripheral T lymphocytes were infected with human adenoviruses (Ad) and herpes simplex virus type 1 (HSV-1) or were activated by phytohaemagglutinin (PHA), then culture supernatants containing no infectious virus were mixed to phagocytes swallowing viable Staphylococcus aureus. Influence of supernatants on eukaryotic and bacterial cell growth was compared to cytokine assays. Supernatant mediators, different from interferon (IFN) and tumour necrosis factor (TNF), induced by oncogenic Ad-12 or HSV-1 diminished phagocytosis of both PMNL and MNPh in a dose dependent manner, promoted bacterial growth free and inside MNPh, while those of latent Ad-5 and nononcogenic Ad-8 exerted moderate effects. Plating efficiency of HEp-2 cells was decreased by all of them. Supernatants of PHA treated lymphocytes containing IFN-gamma enhanced both phagocytosis and bacterial replication free and inside MNPh, while it suppressed HEp-2 plating. Neither viruses nor PHA affected phagocytic process directly. Staphylococci inside PMNL were not affected. Presumably, production of a single mediator by infected T lymphocytes is responsible for the multiple effects. Relationship with another soluble factors is discussed.