Visual recovery after retinal detachment.

Visual recovery after successful surgery for the macula-off rhegmatogenous retinal detachment continues to be an important topic for ophthalmologists. Recent studies have shown that despite the intuitive notion regarding outcomes in macula-off detachment, there is no improvement in final visual acuity despite more expedient repair within the first week. Macula-off detachments can therefore be treated with less urgency and can wait for the next scheduled available operating room time. Surgeons involved in retinal detachment surgery should be aware that visual function based on acuity testing may continue to improve in the long term, most notably in those with the following patient characteristics: younger age, no or mild myopia (less than -5.00 D), and shorter duration of macular detachment (30 days or less).

Clinically suspected primary acquired nasolacrimal duct obstruction: clinicopathologic review of 150 patients.

PURPOSE: The incidence of lacrimal sac pathology in patients with clinically suspected primary acquired nasolacrimal duct obstruction is unknown. This is an important issue when considering the potential risk of either conservative nonsurgical management or laser dacryocystorhinostomy, neither of which permits direct visualization and biopsy of the lacrimal outflow apparatus. METHODS: A total of 162 lacrimal sac biopsy specimens were obtained in 150 consecutive patients undergoing external or endonasal dacryocystorhinostomy for clinical primary acquired nasolacrimal duct obstruction from January 1992 to October 1994. RESULTS: A total of 147 patients (98%) had histopathologic findings consistent with inflammation or fibrosis of the lacrimal sac or both. In the remaining three patients, abnormalities included sarcoid granuloma (one patient), oncocytoma (one patient), and lymphoma (one patient). CONCLUSIONS: The incidence of significant pathology of the lacrimal sac in clinically suspected primary acquired nasolacrimal duct obstruction is low. However, these cases can be identified correctly only by routine biopsy of the lacrimal sac during dacryocystorhinostomy.

Orbital granulocytic sarcoma.

AIM: Orbital granulocytic sarcoma is a localised tumour composed of cells of myeloid origin. Histological diagnosis can be difficult in patients with poorly differentiated orbital tumours and no evidence of systemic leukaemia. The naphthol AS-D chloracetate esterase (Leder stain) and immunohistochemical stains for lysozyme and MAC387 were used to determine the staining characteristics of these tumours. A case series of seven patients with orbital granulocytic sarcoma is presented. METHODS: Seven patients with orbital granulocytic sarcoma were studied. Haematoxylin and eosin, Leder, and lysozyme stained sections were available in seven cases. Unstained formalin fixed paraffin embedded sections of seven cases were available for immunohistochemical evaluation using the avidin-biotin-complex technique for MAC387. RESULTS: The mean age of presentation of the orbital tumour was 8.8 years. Four patients presented with an orbital tumour before any systemic manifestations of leukaemia. In two cases the diagnosis of the orbital tumour and systemic leukaemia was made simultaneously. There was one case of established systemic myeloid leukaemia in remission with the subsequent development of orbital granulocytic sarcoma. Six of seven cases (86%) were positive for the Leder stain. Five of seven cases (71%) showed positive immunoreactivity with lysozyme. The immunohistochemical stain for MAC387 was positive in all seven cases (100%) including one case that was negative for both lysozyme and Leder stains. CONCLUSIONS: Orbital granulocytic sarcoma is a tumour that affects children and can present with rapidly progressive proptosis. This tumour may develop before, during, or after the occurrence of systemic leukaemia. The combination of Leder and lysozyme stains is useful in the diagnosis of orbital granulocytic sarcoma. MAC387 may be a more reliable marker for orbital granulocytic sarcoma.

Thymic carcinoma metastatic to the orbit.

PURPOSE: To report a case of small cell carcinoma of the thymus metastatic to the orbit. METHODS: At age 37 years, a man who had been previously diagnosed and treated for small cell carcinoma of the thymus was initially examined for vertical diplopia and left proptosis. Computed tomographic scan disclosed a soft tissue mass in the superior aspect of the left orbit. A fine-needle aspiration biopsy of the mass was performed and submitted for cytopathologic examination. RESULT: The cytopathology and immunopathology disclosed malignant cells consistent with metastatic small cell thymic carcinoma. CONCLUSION: This is the first reported case of a primary thymus gland tumor metastatic to the orbit.

Antibodies to DNA, chromatin core particles and histones in mice with graft-versus-host disease and their involvement in glomerular injury.

Chronic graft-versus-host disease (GVHD) was induced in female (C57 B10S/DBA/2)F1 hybrid mice with two successive injections of lymphoid cells from parental DBA/2 strain. Serial bleedings of 27 GVHD mice were screened with a panel of antigens including the five histones H1, H2A, H2B, H3 and H4, 15 histone peptides, core particles, dsDNA, heat-shock proteins hsp70 and ubiquitin, a branched peptide of ubiquitinated H2A (U-H2A), poly(ADP-ribose) and SSB/La protein. The predominant IgG response to histone peptides was directed against regions 204-218 of H1, 1-25 of H2B and 1-29 of H4. GVHD mice also produced IgG antibodies to dsDNA and chromatin core particles as reported previously. IgG antibodies reacting with dsDNA appeared before antibodies to core particles and histones. Raised levels of antibodies to U-H2A, but not to monomeric ubiquitin, were also found. While the level of antibodies to dsDNA, histones and core particles decreased significantly before the appearance of proteinuria, suggesting their involvement in glomerular injury, the longitudinal pattern of anti-U-H2A peptide response was apparently not linked to the manifestation of lupus nephritis in GVHD mice.

A prospective study of the migration of two acetabular components. PCA versus RM cups.

Fifty-nine PCA cups and 61 hydroxyapatite-coated RM cups were included in a prospective randomised study with a mean follow up of 5.2 years. Clinical evaluation revealed better results with the RM cup. Radiological criteria of loosening could be applied only with considerable restrictions as different parameters were assessed: progressively loosened beads in PCA cups and faded contour in RM cups. Migration was measured by a computer assisted method (EBRA). PCA cups showed significantly more longitudinal migration 2 years after operation and subsequently. High migration values correlated with a limp. Loosening as defined by migration was of clinical relevance, could be measured early and predicted the survival rate.

A role for histones and ubiquitin in lupus nephritis?

Glomerulonephritis frequently develops in Systemic lupus erythematosus (SLE) but the pathogenesis is still poorly understood. Experimental evidence now suggests that histones can participate in immune complex formation in lupus nephritis. In a retrospective study, using samples from Northern and Southern Europe, Japan and South America, we searched for glomerular deposits of histones, both in native and ubiquitinated forms, in renal biopsy specimens from 48 patients with SLE and 70 cases of glomerulonephritis from patients without SLE. Positive glomerular immunofluorescent staining was revealed with rabbit antibodies to synthetic peptide 1-21 of histone H3, 22-45 of ubiquitin and to the branched region of ubiquitinated histone H2A (U-H2A) in 65% (31/48), 29% (14/48) and 54% (26/48) of the cases of SLE respectively. In total positive staining with at least one of the antibodies was seen in 36/48 (75%) cases. The staining was granular in nature and was present in capillary and mesangial areas. Only 3% (2/70) of non-SLE renal biopsies revealed positive staining with the above antibodies. None of the biopsy specimens from SLE patients were positive for ss- or ds-DNA, when tested with intercalating dyes. Serum samples were available from 15/48 SLE cases and were analysed with peptides and parent proteins by ELISA; epitopes in the N-terminal regions of core histones and in the C-terminus of histone H1 were often recognised by IgG antibodies in SLE sera, as was ubiquitin and the branched octapeptide of U-H2A. These results support the notion that the nuclear autoantigens histone and ubiquitin may be involved in the induction of glomerulonephritis in human SLE.

The role of cationic proteins in the pathogenesis of immune complex glomerulonephritis.

In spite of intensive endeavours, attempts to identify nephritogenic antigens in cases of immune complex glomerulonephritis have not yielded convincing results. Cationic antigens can have high affinity for the glomerular basement membrane and are prime candidates as nephritogens. They can be expected to play a role in post-infectious and in autoimmune glomerular disease. Histones show great promise in the latter case: we are able to demonstrate (1) a high affinity for the glomerular basement membrane and (2) their ability to promote glomerular deposition of anionic antigens as an additional target. Histones were detectable in glomerular deposits in two murine models of glomerulonephritis: the spontaneous lupus-like disease of NZB/W F1 mice and in graft-versus-host disease. We propose that histones may be responsible for the induction of glomerulonephritis in lupus-like syndromes, as well as other types of autoimmune renal disease. As an analogue, histone-like proteins from micro-organisms may also be responsible for glomerular disease in post-infectious nephritis.

Histones have high affinity for the glomerular basement membrane. Relevance for immune complex formation in lupus nephritis.

An effort has been made to integrate insights on charge-based interactions in immune complex glomerulonephritis with nuclear antigen involvement in lupus nephritis. Attention was focussed on the histones, a group of highly cationic nuclear constituents, which could be expected to bind to fixed anionic sites present in the glomerular basement membrane (GBM). We demonstrated that all histone subfractions, prepared according to Johns (4), have a high affinity for GBM and the basement membrane of peritubular capillaries. Tissue uptake of 125I-labeled histones was measured by injecting 200 micrograms of each fraction into the left kidney via the aorta and measuring organ uptake after 15 min. In glomeruli isolated from the left kidneys, the following quantities of histones were found: f1, 13 micrograms; f2a (f2al + f2a2), 17 micrograms; f2b, 17 micrograms; and f3, 32 micrograms. Kinetic studies of glomerular binding showed that f1 disappeared much more rapidly than f2a. The high affinity of histones (pI between 10.5 and 11.0; mol wt 10,000-22,000) for the GBM correlates well with their ability to form aggregates (mol wt greater than 100,000) for comparison lysozyme (pI 11, mol wt 14,000), which does not aggregate spontaneously bound poorly (0.4 micrograms in isolated glomeruli). The quantity of histones and lysozyme found in the isolated glomeruli paralleled their in vitro affinity for a Heparin-Sepharose column (gradient elution studies). This gel matrix contains the sulfated, highly anionic polysaccharide heparin, which is similar to the negatively charged heparan sulfate present in the GBM. Lysozyme eluted with 0.15 M NaCl, f1 with 1 M NaCl, and f2a, f2b, and f3 could not be fully desorbed even with 2 M NaCl; 6 M guanidine-HCl was necessary. Two further findings of great relevance for the concept of induction of immune complex glomerulonephritis by histones were: (a) glomerular-bound histone was accessible for specific antibody given intravenously; and (b) prior binding of histones promoted glomerular deposition of anionic antigens, as could be shown with ssDNA fragments. These data justify the proposal that glomerular deposition of histones can induce immune complex formation, start an inflammatory process, and produce tissue damage.

[Macromolecular basis of filtration and immune complex pathogenesis in the glomerulus]. / Makromolekulare Grundlagen der Filtration und der Immunkomplex-Pathogenese im Glomerulus.

Fractional clearance and ultrastructural studies produce results consistent with the idea that the glomerular filtration barrier is a heteroporous membrane. The majority of the pores being small, excluding molecules like serum albumin and larger moieties, while a low number of pores allow the passage of molecules as big as dimeric ferritin, in very restricted quantities. Cationic macromolecules, of a size which should effectively exclude them from the filtration process, readily gain access to all three layers of the GBM. Depending on charge (pI) and size they can in fact exhibit significant affinity for negatively charged structures in both laminae rarae. In addition, polycations can mediate the glomerular deposition of anionic macromolecules, for example DNA-fragments, by diminishing charge repulsion. A prerequisite for the local formation of glomerular immune complexes is that at least one of the reaction partners has an affinity for the GBM. Antigens bound to structures in the laminae rarae are accessible for circulating antibody. Immune complexes formed with cationic antigen in the lamina rara interna are transferred to the subepithelial region with time. Antigen and antibody molecules can penetrate the lamina densa only in dissociated form. The persistence of glomerular immune complexes can be explained by antigen-antibody lattice formation within the network of proteoglycan chains, followed by covalent binding between components of the complex and structures of the GBM.