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The incidence, morbidity, and mortality of group B streptococcal disease in the UK and Republic of Ireland are largely unknown. Between Feb 1, 2000, and Feb 28, 2001, we identified cases of invasive group B streptococcal disease in infants younger than 90 days through surveillance involving paediatricians, microbiologists, and parents. 568 cases were identified, equivalent to a total incidence of 0.72 per 1000 live-births (95% CI 0.66-0.78); the incidence for early-onset disease (n=377) was 0.48 per 1000 (0.43-0.53), and for late-onset disease (n=191) was 0.24 per 1000 (0.21-0.28). Risk factors were identifiable for 218 (58%) cases of early-onset disease. 53 infants died (overall 9.7%). We have established the minimum current burden of group B streptococcal disease in UK and Irish infants. This information will assist in the formulation of guidelines for prevention of this disease. [ABSTRACT FROM AUTHOR]

Aims: To study ocular pathology and systemic correlations in a series of 73 postmortem eyes from British patients who died from AIDS before the introduction of a HAART regimen., Methods: The eyes were studied with conventional histology, special histochemical stainings, and immunohistochemistry., Results: 72.6% of the cases showed chronic uveal inflammation, caused by opportunistic agents in 37.7% of them (cytomegalovirus (CMV) in 30.1%, C neoformans in 5.6%, and Gram positive bacteria in 1.8%). Cytoid bodies were noted in 10/73 eyes, three linked to CMV retinitis. Six retinal haemorrhages, four of which were secondary to CMV, were found. 14 specimens (19. 1%) showed foci of calcification, and a further 11 (15%) calcium oxalate deposits. In no cases were the calcific deposits suspected clinically. Six eyes (8.2%) did not show any abnormality., Conclusions: CMV retinitis is the most common (28.7%, 21/73) ocular infection in this series and may occur either during or in the absence of systemic dissemination. Conversely, ocular cryptococcosis appears to be an epiphenomenon of systemic and CNS disease. No other opportunistic ocular infections were present in this series. Interesting findings were the presence of intraocular precipitates of calcium oxalate and calcium phosphate or carbonate in a significant number of cases (15% and 19%, respectively), and the high prevalence of idiopathic uveal inflammation (43.8%).

Objectives: The relative contributions of reactivation of latent infection and clusters of new infections to the overall incidence of tuberculosis in the U.K. is unknown. A study was carried out in North-West London to determine the feasibility of IS6110 RFLP strain typing as a tool to investigate the relative contributions of these two sources., Methods: All available isolates of M. tuberculosis from specimens collected over a calendar year at three participating hospitals were typed by RFLP using an IS6110 probe. Isolates exhibiting a single band pattern were subject to further typing using an oligonucleotide direct repeat probe. Demographic and clinical information on cases was obtained from the National Survey of Tuberculosis Notifications in England and Wales and further information sought on clustered cases as identified by RFLP typing., Results: Twenty-seven (23%) of the 118 cases had shared IS6110 RFLP patterns. Strains from nine cases had single band patterns, but these were all distinguishable from each other when subjected to further typing by direct repeat probe. The remaining 18 cases belonged to eight clusters. Epidemiological links were established between all the patients in each cluster. The likelihood of being in a cluster was increased in cases with pulmonary smear-positive disease. It was lower in cases of Indian Sub-continent ethnic origin. For 10 of the 18 clustered cases epidemiological links had not been established by conventional contact tracing., Conclusions: Investigation of the relative contributions of reactivation of latent infection and new infection is feasible in a UJK population, using IS6110 RFLP typing of M. tuberculosis isolates and epidemiological enquiries. This study in London identified clustered, presumably new cases, the majority of whom had not been linked epidemiologically. Comprehensive IS6110 RFLP typing of UK isolates would probably identify many clusters of incident tubercular infection.

Changes in integrin expression have been shown to be important for the growth and metastatic capacity of melanoma cells. In this study, we have examined the expression of alphav integrins by three uveal and four cutaneous malanoma lines. No lines expressed alphavbeta6 and only TXM13, a cutaneous line, expressed alphavbeta8. All lines expressed alphavbeta5 and alphavbeta3 (four out of four cutaneous, two out of three uveal) or avpl (OM431, an uveal line). Thus, OM431 is the second uveal melanoma we have described that expresses alphavbeta1 and this, we report again, functions as an alternative vitronectin/fibronectin receptor. Subcutaneous growth of cell lines in athymic mice correlated with an alphavbeta3-positive, alphavbeta1 -negative phenotype. Analysis of clinical material from cutaneous melanoma showed that although alphav expression was increased in 88% of metastases, this could not all be explained by up-regulation of alphavbeta3, with only 2 out of eight skin metastases expressing this heterodimer. Using antibody SZ.21, which as we report here works in archival material, only 1 out of 15 uveal metastases expressed detectable beta3. Thus, acquisition of alphavbeta3 expression, which has been implicated in cutaneous melanoma progression, may not be required for development of metastases from uveal melanoma or indeed for skin, as distinct from lymph node, metastases of cutaneous melanoma.

Biopsy of fetal tissues is a relatively new procedure for the diagnosis of congenital malformations. The authors report the first case in which this technique has been applied to an orbital mass, in which heterotopic brain tissue was diagnosed by prenatal biopsy and excised in infancy. The wider implications of such intrauterine procedures are discussed.

We report an unusual case of posterior polymorphous dystrophy in which corneal failure began within a few weeks of birth. Histopathologic findings included the presence of abnormal corneal endothelial cells with many microvilli on the surface. Descemet membrane was severely attenuated, and there was a thick posterior collagenous layer consisting of numerous fibroblast-like cells in a fibrillar extracellular matrix; ultrastructural immunocytochemistry showed this to contain tenascin, fibronectin, and collagen type I. Few histopathologic data on this disease at such an early age have been available, and to our knowledge, the composition of Descemet membrane has not been examined before. The microvilli-covered cells are shown to be present from the outset of the disease, not just in long-standing cases as in previous reports; changes in Descemet membrane may influence disease evolution.

We report the presence of peculiar nonbanded calcification of the cornea in three patients with acquired immunodeficiency syndrome, discovered on postmortem histological examination of the globes. In one patient, multiple calcium salt precipitates also affected other ocular and orbital structures. Calcium deposits were present in the corneal stroma but spared Bowman's layer, as is usually seen in primary and secondary corneal calcification. The calcified areas were positive to von Kossa, alizarin red, alcian blue, and colloidal iron stains. Electron probe analysis of the three cases showed the presence of calcium and phosphorus in a ratio characteristic for hydroxyapatite. No predisposing factors could be found. The possible role of associated alterations in the mucopolysaccharide content or composition in the calcified areas is unclear.

The iridocorneal-endothelial (ICE) syndrome is characterised clinically by a "hammered-silver" appearance of the corneal endothelium, corneal failure, glaucoma, and iris destruction. Specular photomicroscopic studies of the corneal endothelium have demonstrated a population of abnormal cells termed "ICE cells." The purpose of this study was to define the histological appearances typical of this disease and in particular the ultrastructural morphology of the ICE cell. Thirty-five corneas, 11 trabeculectomy specimens, and 3 failed corneal grafts taken from patients with the ICE syndrome were examined by transmission and scanning electron microscopy. Comparison was made with seven normal corneas. Ten corneas and two trabeculectomy specimens demonstrated a population of well-differentiated cells with epithelial features such as desmosomes, tonofilaments, and microvilli. Other cell types identified were cells that resembled those of normal corneal endothelium, inflammatory cells, and cells with a fibroblast-like morphology. It seems likely that the epithelial cells of our specimens are the histological equivalent of the ICE cell seen by specular photomicroscopy. The other cell types may be either residual normal endothelial cells or else arise from secondary phenomena of various kinds.

Descemet's membrane, the specialised basement membrane of the corneal endothelium, contains a form of extracellular matrix described as wide-spaced collagen. In healthy human Descemet's membrane, wide-spaced collagen forms a highly ordered array in a region called the anterior banded zone. However, in corneal endotheliopathies such as Fuchs' endothelial dystrophy and the iridocorneal-endothelial syndrome large amounts of wide-spaced collagen are deposited posterior to Descemet's membrane in a grotesque parody of the anterior banded zone termed a posterior collagenous layer. The purpose of this study was to identify the composition of the wide-spaced collagen found in the Descemet's membrane of normal and diseased human corneas. Tissue from three normal human corneas, three from patients with Fuchs' endothelial dystrophy and five from patients with the iridocorneal-endothelial syndrome was prepared for immuno-electron microscopy by freezing or embedding in Lowicryl K4M resin. Immunocytochemistry on ultrathin sections was performed with antibodies to collagen Types I, III, V, VI and VIII, fibronectin, laminin, P component and tenascin. Ultrastructural labelling of the wide-spaced collagen in the anterior banded zone of normal and diseased corneas and also of the wide-spaced collagen in the posterior collagenous layer of all the diseased corneas was demonstrated with antibody to collagen Type VIII. Wide-spaced collagen was not labelled by any of the other antibodies used. Large amounts of Type VIII collagen are present in discrete regions of healthy and diseased Descemet's membrane. The deposition of Type VIII collagen may significantly influence the pathobiology of the corneal endotheliopathies.

Purpose: The iridocorneal-endothelial (ICE) syndrome is characterized by glaucoma, corneal failure, and iris destruction. Specular photomicroscopy of the corneal endothelium in this disease shows a population of abnormal cells named ICE-cells. Comparison between ultrastructural examination and specular photomicroscopy demonstrates that the histologic equivalent of ICE-cells are cells with an epithelial phenotype. The authors have studied the differentiation markers expressed by ICE-cells using an ultrastructural immunocytochemical technique., Methods: Seven keratoplasty specimens from patients with the ICE syndrome were examined by scanning and transmission electron microscopy and light and electron microscopic immunocytochemistry. Comparison was made with three normal corneas. Immunocytochemical studies were performed with monoclonal antibodies to broad-spectrum cytokeratins, cytokeratins 3, 5/8, 8/18 and 19, vimentin, and epithelial membrane antigen., Results: ICE-cells were morphologically similar to epithelial cells and expressed the same profile of differentiation markers as did normal limbal epithelial cells., Conclusions: ICE-cells may arise from an embryologic ectopia of ocular surface epithelium. Alternatively, these findings are consistent with a metaplastic stimulus resulting in a profound change in the phenotype of normal corneal endothelial cells.

Review of a series of 98 eyes removed at autopsy from 86 AIDS patients identified 12 cases (14%) showing varying degrees of microscopic calcium oxalate deposition. The oxalate crystals were birefringent using polarisation microscopy and were stained histochemically by the silver nitrate-rubeanic acid method (Yasue), a stain considered to be specific for calcium oxalate. In two cases, the deposition was extensive and involved the surface of the ciliary processes, ciliary body and pars plana of the retina, the retinal and optic nerve blood vessel wall, a few retinal pigment cells, and the anterior inner sclera. A lesser degree of intraocular involvement was observed in the remaining 10 cases. In all but two eyes, where a peripheral active area of cytomegalovirus retinitis was present, no other significant microscopical abnormality was found. Clinically, these patients were asymptomatic. At autopsy, oxalate deposits were found in the kidney and/or thyroid in seven of the patients.

Descemet's membrane consists of two zones, the 'anterior banded zone' which contains wide-spaced collagen and the amorphous 'posterior non-banded zone'. It is attached anteriorly to the corneal stroma by a narrow transitional zone termed the 'interfacial matrix'. The distribution of fibronectin and P component within the different layers of Descemet's membrane was investigated using an ultrastructural immunogold technique. Seven normal human corneas from an eye bank and one specimen from an orbital exenteration were examined. Fibronectin was predominantly present in the posterior part of the posterior non-banded zone and in the anterior banded zone. The anterior part of the posterior non-banded zone contained less fibronectin. P component was present throughout the anterior banded and posterior non-banded zones. There was a sharp demarcation at the interfacial matrix since neither substance was observed in the corneal stroma. The differences shown in the distribution of fibronectin and P component within Descemet's membrane may have resulted from their binding to other substances or alternatively from differences in the quantities laid down during the evolution of this basement membrane.

The iridocorneal-endothelial syndrome is a disease of the ocular anterior segment characterized by corneal failure, glaucoma and iris destruction. Specular photomicroscopical and histological studies suggest the disorder is caused by a population of abnormal corneal endothelial cells. In other corneal endotheliopathies Descemet's membrane, the basement membrane underlying the endothelial cells, is disfigured by the presence of an abnormal region of extracellular matrix termed a posterior collagenous layer, which is laid down by the diseased endothelial cells. In this study we sought to establish the typical morphology and composition of Descemet's membrane in the iridocorneal-endothelial syndrome. Ultrastructural examination of Descemet's membrane in 27 keratoplasty specimens identified three morphologic patterns. In the majority there was a posterior collagenous layer which in all cases consisted of an anterior layer of wide-spaced collagen and a posterior layer of microfibrils embedded in an amorphous matrix. In four specimens which did not possess a posterior collagenous layer the anterior banded zone of Descemet's membrane was absent. In five corneas Descemet's membrane was normal. The composition of the posterior collagenous layer was examined by immunoelectron microscopy (five corneas) and histochemistry (six corneas). Collagen Types I, III, V, VI and VIII, fibronectin, tenascin and oxytalan were microfibrillar components, collagen Type VIII formed wide-spaced collagen whilst laminin was present in the amorphous matrix. The stereotyped derangements of structure and composition identified in the endothelial basement membrane may significantly influence the pathobiology of this disorder.

A 19 week female fetus is described with a de novo X;1 reciprocal balanced translocation, with the breakpoint on the X chromosome at Xp11.4, and eye pathology consistent with the early stages of Norrie disease. The fetus seems to be an example of a female manifesting an X linked recessive disease, and it was shown that the normal X chromosome was completely inactivated in all cells examined. Norrie disease has been mapped to Xp11.3, and fluorescence in situ hybridisation studies showed that the Norrie disease gene had not obviously been disrupted. Mutation screening by SSCP analysis showed no aberrant fragments of the coding region of the gene. Several eye disease genes map to the same region of the X chromosome, but are excluded on grounds of pathology. One possibility is that this fetus has a Norrie-like eye disease caused by the mutation of another gene located at Xp11.4. If this is so, there are implications for prenatal diagnosis.

Primary ocular melanomas usually arise in the uvea, in the choroid and ciliary body. They metastasize primarily and initially exclusively, to the liver. Metastasis and survival is determined by the maximum tumour dimension, the number of epithelioid cells present within the tumour, vascular patterns within the tumour and nucleolar size and activity. Ganglioside and integrin profiles differ from cutaneous melanomas. Iris melanocytic lesions tend not to metastasize, most being naevi of varying degrees of aggressiveness which may cause glaucoma and corneal decompensation. Conjunctival melanoma is a rare unilateral tumour arising either in primary acquired melanosis or de novo rather than within a naevus. Survival of the patient depends on the location of the tumour and the histological subtype. Tumours not arising in the bulbar or limbal conjunctiva have a much poorer prognosis as do eyelid (cutaneous) melanomas if they involve the lid margin.

We have shown previously that VUP was the only line out of ten human melanoma lines that failed to express the vitronectin receptor alpha v beta 3, but instead expressed alpha v beta 1. Levels of alpha v beta 1 expression were low on parental VUP cells so that iterative sorting by FACS, using an anti-alpha v antibody (13C2), was utilised to derive sublines with 8- to 10-fold higher amounts of cell surface alpha v beta 1. There was little difference between low (V-) and high (V+) alpha v beta 1-expressing sublines with regard to adherence to collagen type I, collagen type IV or laminin substrata. However, adherence to vitronectin and fibrinogen correlated closely with alpha v beta 1 expression (35-42% adhesion for V(+) lines versus 6-8% adhesion for V- lines on vitronectin, for example). Utilising a high alpha v beta 1-expressing subline (V + B2) we have shown that binding to vitronectin and fibrinogen was inhibited specifically by function-blocking antibodies to alpha v (17E6 and 14D9) and beta 1 (A11B2). V(+) sublines spread more compared with V(-) sublines on both vitronectin and fibronectin. However, neither alpha 5- nor alpha v-blocking antibodies had any effect on attachment or spreading of V + B2 on fibronectin whereas the combination of alpha 5 (PID6)- and alpha v(17E6)-blocking antibodies abrogated binding to fibronectin almost completely. This is the first report of an alpha v beta 1 integrin able to recognize vitronectin and fibrinogen, and also cooperate with alpha 5 beta 1 to mediate attachment to and spreading on fibronectin.

Background: It has been suggested that pregnancy may promote metastases in melanoma and that the contraceptive pill may be an etiologic factor. The purpose of this study is to determine if uveal or conjunctival melanomas express estrogen or progesterone receptors., Methods: Twenty-seven choroidal and five conjunctival melanomas were investigated. Immunohistochemistry was performed using the antibodies ER-D5, which recognizes heat-shock protein 27 (formerly called the estrogen receptor-associated cytoplasmic antigen); ER-1D5, which recognizes the estrogen receptor; and PgR, which recognizes the progesterone receptor., Results: Most of the conjunctival and uveal melanomas stained strongly for heat-shock protein 27 but none of the tumors showed positive nuclear staining for either the estrogen or the progesterone receptor., Conclusions: No evidence was found for either estrogen receptor or progesterone receptor expression in choroidal or conjunctival melanomas. Based on the literature, there is little evidence for these hormones having a role in the development or progression of these tumors.

The iridocorneal-endothelial syndrome (ICE syndrome) is characterised by corneal failure, glaucoma and iris destruction. Specular photomicroscopical and histological studies of the corneal endothelium in this disease show a population of abnormal cells named 'ICE-cells'. In many patients some areas of the endothelium are occupied by ICE-cells and others by normal cells, an appearance described as 'subtotal-ICE'. Specular photomicroscopical observations suggest that ICE-cells and normal endothelial cells may actively interact at the boundary zone where they meet. The purpose of this study was to examine the ultrastructural appearances of the boundary zone to gain insight into the cellular pathology of this region. Thirty-five corneas taken from patients with the ICE syndrome were examined by light, transmission and scanning electron microscopy. The subtotal-ICE appearance was demonstrated in four specimens. The morphology of ICE-cells at the boundary zone suggests that they are non-motile but also implies a general state of high metabolic activity. Many of the normal endothelial cells in this region are damaged, an appearance which may result from a toxic effect from the nearby ICE-cells.

Background: Granular corneal dystrophy is a rare indication for corneal transplantation. Both penetrating and lamellar keratoplasty have been recommended, but because granular corneal dystrophy is known to recur within the donor material and multiple grafts may be necessary, the best surgical option has not been clearly established. The cellular cause of the dystrophy is unknown and the authors hypothesized that the rate and pattern of recurrence within lamellar and penetrating grafts might give clues to its etiology., Methods: The authors compared the visual outcome, rate, and pattern of recurrence after 20 penetrating keratoplasties and 11 lamellar keratoplasties for granular corneal dystrophy., Results: Penetrating keratoplasty and lamellar keratoplasty have a good visual outcome in granular corneal dystrophy. Visual acuities after both procedures were not statistically different. Recurrence of the dystrophy within the graft material was almost universal within 4 years. It first appeared centrally and superficially, occasionally adopting a vortex pattern suggesting epithelial involvement. The recurrence-free interval was independent of size and type of graft performed., Conclusion: The authors recommend lamellar keratoplasty as a primary procedure in managing visually disabling granular corneal dystrophy if the deposits are limited to the superficial cornea. This is particularly applicable in younger patients in whom multiple procedures may be necessary over a lifetime due to recurrence of the dystrophy, and the lower morbidity rate associated with lamellar keratoplasty becomes appreciable. Although granular corneal dystrophy generally is classified as a stromal dystrophy, the pattern of recurrence is more consistent with an epithelial or tear-borne abnormality than a disease of the stromal keratocyte.

Purpose: To quantify the variation in the blood supply of the retrolaminar optic nerve in humans. The retrolaminar anterior optic nerve is supplied by an elliptical arterial "circle" of Haller and Zinn formed by anastomoses around the optic nerve between medial and lateral paraoptic short posterior ciliary arteries (PO-SPCAs). The frequency with which complete perioptic nerve arteriolar anastomoses (PONAA) occur is unknown, yet they form the basis for many postulated pathophysiological mechanisms., Methods: Scanning electron microscopy was performed on 25 orbital and ocular microvascular corrosion casts (methyl methacrylate) from 20 human cadavers of subjects 21 to 97 years of age without known ocular disease., Results: Eighteen casts were examined in detail after microdissection (the analysis of seven casts was limited because of their fragility). In 15/18 (83%) casts, the PONAA were supplied by branches of a medial and lateral PO-SPCA; in 2/18, they were supplied by one (lateral) PO-SPCA; and in 1/18, they were supplied by a superior PO-SPCA and two horizontal PO-SPCAs. The PONAA had intact superior and inferior anastomoses in 8/18 (44%) casts, anastomoses with narrowed portions in 6/18 (33%), and incomplete in 4/18 (23%). Narrowed portions were not preferentially distributed to either superior or inferior anastomoses., Conclusions: Complete PONAA was found in more than 75% of casts, including anastomoses with narrow portions in 33% of casts.

Mycobacteria are unusual causes of keratitis and other ocular infections but the outcome of infection is often serious. We report a case of keratitis due to Mycobacterium chelonae, a rapidly growing environmental mycobacterium, in a soft contact-lens wearer, and discuss the difficulty and delay in identifying the organism, twice erroneously identified as Nocardia asteroides on morphological grounds. Despite in vitro susceptibility, the response to anti-bacterial agents was negligible and a second keratoplasty was required after a recurrence of disease at the donor-host junction. We review the role of mycobacteria as the cause of keratitis and other forms of ocular disease.

The role of orbital exenteration in the management of malignant melanoma of the conjunctiva has been underexplored. The outcome in 95 patients with this condition, who underwent exenteration as a primary treatment (n = 36) or after failure of other treatment (n = 59) for early to advanced stages of the disease, was evaluated. The majority of treated cases had multicentric melanomas sited at prognostically unfavourable locations. In the group of tumours with a maximum thickness of 1.0 mm no melanoma related mortality was noted. Melanomas thicker than 1.0 mm were associated with a mortality varying between 33% and 50%, independent of whether exenteration was performed as primary or secondary treatment. An especially poor outcome was noted for the group of caruncular melanomas despite exenteration. These findings indicate that total eradication of tumour should be performed at an early stage. For this purpose, a combination of debulking surgery and adjunctive cryotherapy or beta radiotherapy is more appropriate than orbital exenteration which causes disfigurement and blindness. Exenteration of the orbit should be reserved as a palliative procedure for advanced stages of neoplastic disease.

A series of 256 consecutive cases of invasive primary conjunctival malignant melanomas was examined to identify clinical and histopathological prognostic factors. The follow up period varied between 0.3 and 45.9 years (mean 9 years, median 6.3 years). The 5 year survival rate was estimated at 82.9%, the 10 year survival rate at 69.3%. Multiple regression analysis with the Cox proportional hazards model was used to assess sex, age, and a number of baseline features of conjunctival malignant melanoma as possible prognostic factors influencing melanoma related mortality. In assessing each potential prognostic factor, the effects of all other factors were taken into account in the modelling process. Tumours in unfavourable locations--that is, those involving the palpebral conjunctiva, fornices, plica, caruncle, and lid margins, were associated with 2.2 times higher mortality compared with (epi)bulbar melanomas. Patients with mixed cell type tumours had about three times higher mortality compared with those with pure spindle cell melanomas, and histological evidence of lymphatic invasion by tumour cells was also a prognostic feature, carrying a fourfold increase in the death rate. Multifocal tumours were associated with a fivefold increase in mortality among those with tumours in favourable (epi)bulbar locations, but were not prognostic in patients with melanomas in unfavourable sites. The death rate was significantly higher in those with initial tumour thickness of more than 4 mm, but only among patients with unfavourably located melanomas. Sex, age, and clinical origin of the tumour (primary acquired melanosis, pre-existing naevus, or de novo) were not useful prognostic indicators in this study.

In 1905, Parsons first described a family with a history of four generations with uveal melanoma associated with breast cancer. The family history has now been brought up to date using genealogical sources to determine the origin of this family which was traced to the East End of London in the early 19th century. In addition, immunohistochemical investigations have showed mutant p53, a tumor suppressor gene, in museum specimens of uveal melanoma after 150 years. This family probably represents the earliest example of the Li-Fraumeni syndrome on record.

A 28 year old West Indian patient is described who had a relapsing and remitting steroid-sensitive illness for 3 years. The clinical features included uveitis and widespread CNS involvement. The patient was treated as though he had neurosarcoidosis. Post mortem examination revealed histological changes compatible with a diagnosis of Behçet's disease, but at no time did he suffer from oral or genital ulceration or arthritis. The authors suggest a new term to encompass such an entity: the "Behçet's MINUS" syndrome (multifocal intermittent neurological and uveitic syndrome).

Electron microscopy was performed on the irides of a man with a history of a long standing Horner's syndrome which resulted in iris heterochromia. Comparison of his normal brown iris with the depigmented blue iris showed depletion of anterior border cells and absence of sympathetic nerve fibres. Stromal melanocyte numbers were also diminished but melanosome numbers within the residual cells were not significantly different. Postnatal maintenance of stromal and anterior border zone pigmentation, derived from the neural crest, would appear to be dependent on an intact sympathetic nerve supply in contrast to the iris pigment epithelium which remains normally unaffected in Horner's syndrome.

Using a silver staining technique, argyrophilic nucleolar organiser region-associated proteins (AgNORs) have been studied in routinely processed paraffin sections of 46 invasive malignant melanomas (MM) of the conjunctiva. The aim of this retrospective study was to assess the value of the AgNOR method as a prognostic indicator for this neoplasm. The 46 cases were divided into two groups: (A) 14 cases of MM that metastasised and caused death of the patient within 5 years of (histological) diagnosis, and (B) 32 cases of MM that did not metastasise and in which patients survived beyond 5 years. The mean of the AgNOR counts per nucleus was 7.03 (95% CI: 5.81-8.24) in group A, and 7.15 (95% CI: 6.53-7.77) in group B. A comparison using a multifactor analysis of variance (ANOVA) model, which corrected for possible confounding effect of tumour thickness, site, and cell type showed no significant difference in AgNOR counts between groups A and B (p = 0.8). Analysis by the Cox proportional hazards regression model showed that survival was not influenced significantly by the mean AgNOR number (hazard ratio: 0.92). Whereas the AgNOR technique may be used to distinguish benign from malignant melanocytic lesions of the conjunctiva, we conclude it has no value in predicting the outcome for patients with conjunctival MM.

Intravenous drug abuse is an increasing problem. Septic complications occur frequently at the injection site, especially in the groin where large abscesses around the femoral vessels can threaten life or limb. We report four patients with extensive or complex groin abscesses following attempted self-injection into the femoral vein. Streptococcus milleri was cultured from all of these abscesses and prompted a review of the isolation of this organism in this hospital.

In our experience 5% of invasive malignant melanomas of the conjunctiva arising from areas of primary acquired melanosis with atypia spread to the ipsilateral nasal cavity and paranasal sinuses. Twenty one years after orbital exenteration for multicentric conjunctival melanoma an 82-year-old man was seen with an orbital recurrence, which had extended to the nasal cavity and paranasal sinuses through the nasolacrimal duct without invading the mucosa. This previously undescribed way of spread after the longest symptom-free interval following exenteration ever reported is illustrated.

Impression cytology using cellulose acetate paper has been used in various ocular surface disorders as a simple non-invasive diagnostic test. To assess its value in differentiating melanocytic tumours, 24 patients with a range of pigmented lesions of the conjunctiva were examined using this technique. Cytological and histological diagnoses were compared in 23 cases. In 73% of cases impression cytology predicted the histological diagnosis by detection of superficial atypical melanocytes and their proportion relative to benign epithelial cells. This pilot study shows impression cytology to be a useful diagnostic aid in the differentiation of pigmented tumours of the bulbar conjunctiva.

Clinical and histopathological features of four cases of multifocal amelanotic malignant melanoma of the conjunctiva in association with 'acquired melanosis sine pigmento' are reported. The absence of conjunctival pigmentation in this extremely rare combination of lesions prevented early diagnosis and clinical monitoring. As a result orbital exenteration was required in three cases. This multicentric non-pigmented variety of conjunctival malignant melanoma tends to present later than pigmented forms and may require exenteration of the orbit as a primary procedure.

Xeroderma pigmentosum is a rare autosomal recessive dermatosis. The neoplastic changes in sunlight-exposed areas of the skin and eyes may be related to the impaired replication of ultraviolet radiation-damaged DNA. A 38-year-old Greek woman is reported with a mild form of xeroderma pigmentosum and primary acquired melanosis with atypia of her right limbal conjunctiva and cornea. The development of this precursor of conjunctival malignant melanoma in a xeroderma pigmentosum patient may support the putative role of sunlight exposure in malignant transformation of conjunctival melanocytes.

Despite extensive study, the pathogenic mechanisms of Behçet's disease remain uncertain. The ocular inflammation caused by this disease is severe, often causing significant visual loss and, although the nature of the cellular infiltrate has been examined in many of the involved organs, the infiltrating cells in inflamed eyes have not. To investigate the mechanisms involved in perpetuating the ocular inflammation, five enucleated eyes from patients with Behçet's disease were examined by immunohistochemical staining using a panel of monoclonal and polyclonal antibodies. Control eyes from patients with chronic intraocular inflammation from other causes were also examined. Cellular infiltrates were a consistent finding in choroid and periretinal scar tissue, formed almost entirely by mononuclear cells. T lymphocytes were found to predominate (largely the CD4+ subset). B lymphocytes and NK cells were infrequent findings but macrophages were present in significant numbers. No complement or immunoglobulin deposits were found. Infiltrating lymphocytes and macrophages were HLA DR positive. Retinal vascular and retinal pigment epithelium were only occasionally positive. Our findings suggest that cell mediated immunity, rather than immune complex deposition is responsible for the perpetuation of the ocular inflammation in Behçet's disease and that CD4+ T lymphocytes play a central role in this.

Aims: To evaluate the Uristat test, an indirect enzyme linked immunosorbent assay for the qualitative detection of antibodies in urine, as a screening, and in the diagnosis of urinary tract infection in the elderly., Methods: Semiquantitative culture was compared with conventional microscopy, dipstick analysis and the ELISA. In the ELISA, 371 urine samples were examined for antibodies to an antigen mixture of six common urinary pathogens., Results: The sensitivity was 91% and the specificity 25% for the ELISA. The negative predictive value was 81% and the positive predictive value was 43%., Conclusions: In its present form the Uristat test has no clear advantages over conventional bacteriological techniques for screening urine samples for infection in an elderly population.

Histopathological and immunohistochemical findings in 11 patients with spontaneous congenital non-pigmented epithelial cysts of the iris stroma were studied. The cysts were lined by stratified squamous to unilayered cuboidal non-pigmented epithelium. Goblet cells were present in nine cysts, indicating a similarity to conjunctival epithelium. The demonstration of higher-molecular-weight keratins and absence of S-100 protein, by monoclonal and polyclonal antibodies, argues for surface ectodermal rather than neuroectodermal origin of the cysts. Theories of embryogenesis have been conflicting, but our results support the theory that they arise from surface ectoderm, displaced probably at the time of lens vesicle formation. The finding of normally sited subepithelial S-100 positive melanocytes may suggest that ectopic conjunctival epithelium can induce normal patterns of migration of neural crest cells.