[Initial ophthalmic manifestation of a fatal underlying disease : Importance of perimetry in unspecific visual deterioration]. / Ophthalmologische Erstmanifestation einer letalen Grunderkrankung : Stellenwert der Perimetrie bei unspezifischer Sehverschlechterung.

A 55-year-old male patient presented with bilateral blurred vision. Chronic lymphocytic leukemia was generally known in the medical history, which was treated by immunochemotherapy with fludarabine, cyclophosphamide and rituximab. Static perimetry revealed a homonymous hemianopia to the left. The neurological examination was otherwise unremarkable. Progressive multifocal leukoencephalopathy (PML) was diagnosed by cranial magnetic resonance imaging and detection of JC virus DNA in the cerebrospinal fluid. The PML is a rare demyelinating disease of the central nervous system caused by reactivation of the JC virus. It affects patients with HIV, malignant hematological diseases and immunomodulatory therapy. A specific, antiviral treatment does not yet exist. The prognosis of PML is therefore poor. After a progressive course of the disease the patient died 4 months after the diagnosis.

[Dynamic Scheimpflug Analyzer (Corvis ST) for measurement of corneal biomechanical parameters : A praxis-related overview]. / Dynamischer Scheimpflug-Analyzer (Corvis ST) zur Bestimmung kornealer biomechanischer Parameter : Ein praxisbezogener Überblick.

BACKGROUND: Topographic and tomographic parameters alone are often not sufficient for early detection of corneal changes. Pathological alterations in the microstructure of the cornea occur before changes in topography and tomography can be detected. Biomechanical parameters show a strong correlation with microscopic structural changes. OBJECTIVE: The aim of the study was to gain information about the microscopic structure and consistency of the cornea by measuring biomechanical parameters. MATERIALS AND METHODS: The deformation behavior of the cornea was analyzed with the Dynamic Scheimpflug Analyzer (Corvis ST; OCULUS, Wetzlar, Germany). Deformation parameters and biomechanical indices were derived from the deformation response of the cornea. RESULTS: Deformation parameters and indices in keratoconus patients differ significantly from healthy subjects. Alterations of the cornea can be detected before topographic and tomographic changes occur. The repeatability and reproducibility of relevant deformation parameters is good to very good. In glaucoma patients a modified deformation behavior of the cornea can be observed, which might be related to structural changes. CONCLUSION: The Corvis ST allows a reliable characterization of the tissue structure and consistency of the cornea.

[Orbital cavity tumor with macular folds]. / Orbitale Raumforderung mit Makulafalten.

A 40-year-old patient presented with an orbital tumor of the right eye accompanied by visual impairment and macular folds. The diagnosis of mucocele was made through clinical and radiological investigations. The excision of the mucocele was performed immediately. As early as 8 weeks after the operation, an obvious increase in visual acuity was noticed. At this time, the macular folds were no longer detectable.

[Corneal Cross-Linking with Riboflavin and UVA in Keratoconus]. / Hornhautvernetzung mit Riboflavin und UV-A-Licht bei Keratokonus.

Changes in the biomechanical properties of the human cornea play an important role in the pathogenesis of corneal ectatic diseases. Many different pathological conditions in the cornea may reduce its biomechanical resistance. Corneal collagen cross-linking (CXL) has emerged as a promising technique to slow or even to stop the progression of ectasia. In this procedure, riboflavin (vitamin B2) is administered in conjunction with ultraviolet A light (UVA, 365 nm). This interaction causes the formation of reactive oxygen species, leading to additional covalent bonds between collagen molecules, with consequent biomechanical stiffening of the cornea. Although this method is not yet accepted as an evidence-based treatment of corneal ectasia, the results of prospective, randomised studies of CXL used in the treatment of this pathological entity show significant changes in the properties of corneal tissue. This procedure is currently the only aetiopathogenetic treatment of ectatic eyes that can delay or stop the process of cornea destabilisation, reducing the necessity for keratoplasty. Despite promising results, CXL is associated with issues that include long-term safety and duration of the stabilising effect.

[Ankyloblepharon filiforme adnatum]. / Ankyloblepharon filiforme adnatum.

The ankyloblepharon filiforme adnatum is a congenital eyelid anomaly in which the development of the eyelids is completed but the eyelids are not completely separated at birth. The abnormality can occur as an isolated anomaly, together with other eye diseases or in the context of systemic syndromes. In this case report the current classification and essential diagnostics of AFA will be reviewed.

[Therapy-resistant swelling of the upper eyelid in childhood]. / Therapieresistente Oberlidschwellung im Kindesalter.

HISTORY: Swelling of the upper eyelid in childhood is caused by a variety of diseases and is very often generated by inflammation but orbital tumors should always be considered in the differential diagnostics. METHODS: We report about a 4-year-old girl with a drug-resistant swelling of the upper eyelid and ptosis of the right eye. This case report demonstrates the route from initial clinical examination to diagnosis and additionally reviews the current status of therapeutic options. RESULTS: After magnetic resonance imaging (MRI) and diagnostic excision, Langerhans cell histiocytosis (LCH) could be histologically proven. Visual acuity and levator muscle function improved from 0.5 to 1.25 and from 2 mm to 12 mm, respectively, by amblyopic prophylaxis and immunosuppressive therapy. CONCLUSIONS: Persistent and drug-resistant swelling of the upper eyelid in childhood is also strongly suspicious for tumors. The suspicion of rare orbital tumors in children can be frequently substantiated by MRI. Biopsy and histological diagnosis are essential to plan adequate treatment and to estimate the prognosis. Particularly in Langerhans cell histiocytosis the methods of choice for over 10 years are specific immunochemical procedures (detection of protein s100 and CD1a).

[Bilateral visual loss in a young male patient]. / Bilaterale Visusminderung bei einem jungen Mann.

We present the case of a 36-year-old male patient who presented with an increasing bilateral loss of vision which had existed for several years. Slit-lamp examination revealed a conical anterior protusion of the lens and funduscopy showed a discreet perimacular dot and fleck retinopathy. In consideration of all clinical findings the patient was diagnosed with anterior lenticonus as an ocular manifestation of an Alport's syndrome which is a rare X-linked disease. Besides renal failure and hearing loss which occur early, ocular changes usually manifest later on. Patients with a anterior lenticonus can be effectively treated with phacoemulsification and intraocular lens implantation. The visual outcome after surgery is excellent.

[Maculopathy with subretinal yellow deposits]. / Makulopathie mit subretinalen, gelblichen Ablagerungen.

We present the case of a 52-year-old female patient who presented with bilateral loss of vision over the course of several years. Funduscopy revealed multiple drusen in a "honeycomb"-like configuration at the entire posterior pole and in the peripapillary region. Autofluorescence and fluorescence angiography (FLA) showed multiple hyperfluorescent defects which show no leakage due to staining of the drusen-like lesions. Optical coherence tomography (OCT) revealed a marked irregularity of the photoreceptor-retinal pigment epithelium complex. Electroretinography (ERG) was without pathological findings, while the electrooculography (EOG) was abnormal, reflecting a functional disturbance of the retinal pigment epithelium. In consideration of all clinical findings, our patient suffered from Doyne honeycomb retinal dystrophy (DHRD) which is a rare autosomal dominant inherited retinal disease with full penetrance. Patients with DHRD are usually asymptomatic until the age of 30-40 years. In the later stages of this disease, central vision deteriorates as a result of geographic atrophy or choroidal neovascularization.

[Siderosis bulbi after injury by an intraocular metal foreign body]. / Siderosis bulbi nach intraokularem Metallfremdkörper.

We report the case of a 42-year-old patient who presented with unilateral loss of vision in the left eye. The clinical examination revealed retinal detachment and a low intraocular pressure was found in the left eye. Except for an extinct electroretinogram (ERG) and a siderosis bulbi in the left eye no signs of an intraocular body were detectable, either in the ultrasound B-scan or in the clinical examination. Pars plana vitrectomy with silicon oil tamponade was performed and revealed an iron-containing body next to the fovea which was removed without any complications. Despite an initially easily visible retinal detachment, a newly acquired siderosis bulbi in combination with ocular trauma in the clinical history should raise the suspicion of a residual intraocular iron foreign body, until this can be disproven.

[Biomechanical condition of the cornea as a new indicator for pathological and structural changes]. / Biomechanische Zustand der Hornhaut als neuer Indikator für pathologische und strukturelle Veränderungen.

AIM: Several methods permit the measurement of geometric parameters of the cornea, but until now biomechanical conditions of the cornea have been ignored (e.g. in refractive corneal surgery). Besides the geometric condition, biomechanical properties of the cornea have been shown to influence applanation measurement of intra-ocular pressure (IOP) and epidemiological studies have identified corneal thickness as an independent risk factor for the development and progression of glaucoma. The aim of this investigation was to characterize the biomechanical properties of the cornea using the ocular response analyzer (ORA). METHODS: The ocular response analyzer (ORA) is a new method available for non-contact measurement of the biomechanical properties of the cornea. We evaluated the reproducibility of measurements, the difference between static and dynamic factors and the impact of independent factors (e.g. IOP, age, CCT, swelling of the cornea) on 2,500 measurements of corneal hysteresis (CH) and corneal resistance factor (CRF). RESULTS: In a large sample size we observed changes in CH and CRF after refractive surgery procedures (LASIK, UV-A cross-linking, keratoplasty) and in other corneal disorders (keratoconus, corneal dystrophies). CONCLUSIONS: CRF and CH changes may reflect structural changes of the cornea. Thus, the ORA provides valuable information for a better understanding and characterization of the biomechanical condition of the cornea, especially with regard to diseases such as keratoconus and glaucoma.

Effect of latanoprost and timolol on the histopathology of the human conjunctiva.

AIM: To investigate the effect of timolol and latanoprost on the extracellular matrix organisation, inflammatory infiltration, and expression of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) in the human conjunctiva. METHODS: Conjunctival biopsies were obtained from the inferior fornix during routine cataract surgery from 20 patients with primary open-angle glaucoma, who had received a monotherapy either with timolol or latanoprost, and from 10 non-glaucomatous patients. Specimens were investigated by light microscopy, immunohistochemistry using antibodies against MMP-1,-3, TIMP-2,-3 and CD 68 antibodies and by quantitative transmission electron microscopy. RESULTS: The number of collagen fibres was significantly decreased in latanoprost-treated conjunctival specimens compared with timolol-treated eyes (p<0.01) but showed no difference to controls. Amorphous material was increased in both treated groups compared with controls (p<0.001) but was less in latanoprost-treated specimens compared with timolol-treated eyes (p<0.001). Optically clear spaces, probably containing glycosaminoglycans, were significantly reduced in both treated groups-with less of a reduction in latanoprost-compared with timolol-treated eyes (p<0.001). A marked upregulation of MMP-1 and MMP-3 and moderately increased staining for TIMP-2 and TIMP-3 was found in epithelial cells and subepithelial stromal cells of latanoprost-treated eyes. A moderate infiltration with macrophages and inflammatory cells was observed in timolol-treated eyes. CONCLUSIONS: Latanoprost-treated conjunctival specimens showed a decreased stromal collagen density and a less pronounced inflammatory infiltration. The upregulation of MMP-1 and MMP-3 in latanoprost-treated eyes might explain the reduced extracellular matrix accumulation in the conjunctival stroma. Therefore, latanoprost therapy might have a more favourable effect on the outcome of glaucoma filtering surgery.

Nitroarene concentrations and direct-acting mutagenicity of diesel exhaust particulates fractionated by silica-gel column chromatography.

Diesel exhaust particulates were extracted with benzene-ethanol (3:1, v/v) and separated into five fractions by silica-gel column chromatography. Direct-acting mutagenic activity was assayed by the Ames test using the Salmonella typhimurium YG1024 strain. The total activity of five fractions was about four times greater than that of the crude extract, suggesting that the activities in the fractions were suppressed in the crude extract. Strong activity was observed in fraction 4 which was eluted with dichloromethane (61.5% of the total activity) and fraction 5 which was eluted with ethanol (35.3%). Nitropolycyclic aromatic hydrocarbons (NPAHs) were determined by high-performance liquid chromatography with chemiluminescence detection. They were found mainly in fraction 4, although one NPAH was in fraction 3 which was eluted with n-hexane-dichloromethane (3:1, v/v). Based on these results, 53.1% of the activity in fraction 4 was attributed to NPAHs. The contribution of 1-nitropyrene and 1,3-, 1,6- and 1,8-dinitropyrenes was great and that of the other NPAHs was small. The mutagenic compound in fraction 5 was not identified. Fractions 1 and 2, which were eluted with n-hexane, and fraction 3 suppressed the activity of fraction 4. Polycyclic aromatic hydrocarbons in fractions 2 and 3 were considered as possible suppressors of NPAHs.

An on-line reduction HPLC/chemiluminescence detection system for nitropolycyclic aromatic hydrocarbons and metabolites.

Various metal powders were batch screened as possible on-line reducers for nitropolycyclic aromatic hydrocarbons (NPAHs), in particular 1,3-dinitropyrene (1,3-DNP, 1,8-DNP and 1-nitropyrene (1-NP) and it metabolites. Zinc was found to be an excellent reducer in chemiluminescent compatible mobile phases without any associated disposal problems. Zinc reducer column parameters, namely pH, buffer concentration, packing composition (zinc:glass beads or zinc:silica gel) and column length were all optimized for the HPLC determination system with chemiluminescence detection, named NPAH analyser. The system consisted of three pumps, sample injector, reducer column packed with zinc:glass beads switching valve with a cutting loop, separation column (ODS), chemiluminescence detector and integrator. The mobile phase for the separation column and chemiluminescence reagent solution were respectively acetonitrile:imidazole-HClO44 and acetonitrile containing bis(2,4,6-trichlorophenyl)oxalate and H2O2. When the reducer column was introduced before the separation column, 1,3-, 1,6- 1,8-DNPs and 1-NP in benzene:ethanol extracts from airborne particulates were separately determined with detection limits of 2-50 fmol, respectively, in a 100 microL sample. When the reducer column was introduced just after the separation column, 1-NP, 1-nitrosopyrene and 1-aminopyrene in the incubation mixture of 1-NP and the Salmonella typhimurium YG1021 strain were separately determined with detection limits as low as sub fmol levels. 1,8-DNP and its metabolite were also separately determined in the incubation mixture of 1,8-DNP and the S. typhimurium TA98 strain.

[Interference of antibody reaction with porcine pancreatic amylase in enzymatic assay of total calcium].

Unreliable results were obtained in an enzymatic assay of total calcium (Ca) in a patient's serum using porcine pancreatic amylase (PPA). Besides, the result was different from that obtained by the atomic absorption analysis. Fractionation of the patient's serum by ultrafiltration and Sephadex G-200 gel filtration revealed the presence of an interference substance with a large molecular size of more than 200kDa. This interference substance was absorbed on a Protein A column. Furthermore, an immune precipitate was observed between the patient's serum and PPA by Ouchterlony double immunodiffusion. An antibody against PPA may exist in the patient's serum and interfere with the enzymatic assay of Ca using PPA.

Epstein-Barr virus (EBV)-carrying and -expressing T-cell lines established from severe chronic active EBV infection.

Four novel Epstein-Barr virus (EBV)-carrying T-cell lines, designated SIS, AIK-T8, AIK-T4, and SKN, were established from peripheral blood lymphocytes (PBL) of patients with severe chronic active EBV infection, in the presence of interleukin-2 and 4-deoxyphorbol ester. AIK-T8 and -T4 were derived from a single patient. Cell marker and genotype analyses showed that SIS, AIK-T8, and AIK-T4 had mature T-cell phenotypes with clonally rearranged T-cell receptor (TCR) genes, whereas SKN had an immature T-cell phenotype without TCR gene rearrangement. None of the cell lines expressed B, natural killer, or myeloid antigens or had Ig gene rearrangement. All lines carried EBV genomes in a single episomal form. SIS, AIK-T8, and SKN showed the same phenotype, TCR gene configuration, and/or EBV clonotype as their source or biopsied materials; therefore, they represented EBV-infected T cells proliferating in the patients. TCR gene and EBV episomal structures similar to those of AIK-T4 were not found in its source PBL, probably due to the few parental clones in vivo. All lines expressed EBV-encoded small RNA (EBER) 1, nuclear antigen (EBNA) 1, and latent membrane protein (LMP) 1, -2A, and -2B, but not other EBNAs that could be recognized by EBV-specific immune T cells. EBV replicative antigens were rarely expressed or induced. Such EBV latency reflects the in vivo situation, in which the T cells may evade immune surveillance and be insensitive to antiherpesvirus drugs. Collectively, the data suggest that EBV can target and latently infect T cells at any stage of differentiation in vivo, thus potentially causing uncontrolled T-cell proliferation. These cell lines will facilitate further analyses of possible EBV-induced oncogenicity in T cells.

Chromatographic determination method for 1-nitropyrene and its metabolites in biological samples with fluorescence detection after on-line reduction.

A high performance liquid chromatographic (HPLC) method with fluorescence detection after on-line reduction for the determination of 1-nitropyrene (NP), 1-nitrosopyrene (NSP), 1-aminopyrene (AP) and N-acetylaminopyrene (AAP) has been developed. The reduction efficiency of NP and NSP on a zinc column was found to be higher than that of an electrochemical reducer. Using a HPLC system equipped with a zinc column (4.0 mm i.d. x 10 mm) and an imidazole/HClO4 (pH 6.8): acetonitrile mobile phase, detection limits (S/N = 3) of 20-30 fmol for NP, NSP and AP and 350 fmol for AAP were obtained. NP, NSP and AP were determined in the incubation mixture of NP and Salmonella typhimurium, YG1021, by this method. Time course studies showed that a large ratio of NP was metabolized in the pre-incubation step of the Ames test.

[Relationship between biopsy and prognosis of breast cancer].

Clinical data from 131 patients who underwent primary radical operation for breast cancer at the Second Department of Surgery, Shinshu University Hospital during five-years from January 1976 to the end of December 1980 were analyzed to investigate for the relationship between biopsy and prognosis. The incisional biopsy group had a significant higher recurrence rate as compared with the no biopsy group, cytology group and the cancer negative group after excisional biopsy. Although the puncture aspiration cytology group did not show significant difference in recurrence rate, an any more than 3 weeks of interval between puncture aspiration cytology and radical surgery associated with a significant high recurrence rate. This suggests that the interval also exerts an unfavorable influence upon prognosis. Puncture aspiration cytology was recognized to be apt to result in distant metastasis than any other biopsy methods and also it is tended to have a higher recurrence rate in scirrhous and mucinous carcinoma of the breast.