Quantitative morphology of human retrolaminar optic nerve vasculature.

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.

Pathology of the iridocorneal-endothelial syndrome. The ICE-cell.

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.

CD4+ lymphocyte involvement in ocular Behçet's disease.

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.

Cerebral microembolism during cardiopulmonary bypass. Retinal microvascular studies in vivo with fluorescein angiography.

To observe microembolic events in the central nervous system during cardiopulmonary bypass, we subjected 21 patients undergoing elective coronary operations to retinal fluorescein angiograms 5 minutes before cardiopulmonary bypass was discontinued. Patients with diabetes or clinically evident cerebrovascular disease were excluded. Bubble oxygenation and nonpulsatile perfusion were used for bypass. After 31 to 167 minutes of cardiopulmonary bypass, all 21 (100%) patients had retinal microvascular occlusions indicative of microembolism. Control fluorescein angiograms obtained preoperatively and in five patients immediately before bypass but after aortic cannulation showed retinal perfusion. During bypass there was a mean of 3.5 (range 1 to 7) blocked arterioles of less than 50 micron caliber and a mean of 6.3 (range 1 to 10) focal areas of capillary nonperfusion per 30-degree field of retina centered on the macula per patient. Repeat studies 30 minutes after discontinuation of bypass showed partial reperfusion with occlusions in four of the five (80%) patients and a decrease in the mean total microembolic count from 12.6 to 4.8 (38%). In later studies at a median of 8 days postoperatively, only two of 16 (12.5%) patients had persistently occluded retinal vessels. The total microembolic count did not correlate with bypass time (r = 0.14) and was not reduced by arterial line filtration with a Pall 40 micron filter (Ultipore) in a subgroup of 11 patients. Twenty patients completed four standardized psychometric tests. Retinal microvascular occlusions were more numerous in those patients with a psychometric deficit (n = 7) than in those with no deficit (n = 13; p = 0.075). In a dog model of cardiopulmonary bypass, eight of nine (88.9%) had retinal microvascular occlusions after 10 to 90 minutes of bypass. Retinal histologic studies revealed intravascular platelet-fibrin microaggregates 20 to 70 micron in diameter and focal ischemic changes in seven of the nine (77.8%) dogs. Six dogs undergoing sham bypass had normal retinal perfusion and histologic findings. This study demonstrates a very high incidence of microvascular occlusions in the territory of the internal carotid artery during bypass consistent with a microembolic origin. The clinical significance of these findings is uncertain.

Early-onset posterior polymorphous dystrophy.

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.

Evaluation of enzyme linked immunosorbent assay for screening urinary tract infection in elderly people.

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.

Serum C reactive protein in infective endocarditis.

C reactive protein (CRP) was measured serially in 29 patients with infective endocarditis. Twenty one patients were initially treated with antimicrobial drugs. In 13, serial measurement of CRP concentrations showed a progressive return to normal (less than 10 mg/l), which correlated with a satisfactory recovery. Of the remainder (eight patients), five had persistently high concentrations of CRP, indicating a failure to respond to antimicrobial treatment alone. Two of these five patients died and three underwent valve replacement. Of 11 patients treated with antibiotics and valve replacement, CRP concentrations returned to normal in nine. Two patients had infective complications and the CRP concentration did not return to normal. A transient rise in CRP concentration during an otherwise uneventful fall to normal was a sign of allergic reaction in two and of intercurrent infection in three more patients. Serial measurements of CRP concentrations in patients with infective endocarditis may be useful to monitor treatment and also to detect other infections and complications.

Oestrogen receptors in conjunctival malignant melanoma: immunocytochemical study using formalin fixed paraffin wax sections.

In a group of 15 women with conjunctival malignant melanoma six cases (40%) were shown to have oestrogen receptor positivity using a monoclonal antibody to oestrogen receptor related antigen (ER-D5, Amersham RPN.710) on formalin fixed, paraffin wax sections. Receptors were also present in the epithelium of these six cases but not in controls and cases without ER-D5 positivity in their tumours. A subset of these aggressive, intractable unilateral tumours may therefore be amenable to hormone treatment.

Endotoxaemia in septic shock: clinical and post mortem correlations.

The Limulus amoebocyte lysate assay was used as one of a series of laboratory and clinical investigations on a group of 31 patients suffering from septic shock in order to assess the clinical significance of this assay for the detection of circulating endotoxin in clinical gram-negative sepsis. Four patients with cardiogenic shock served as controls. Endotoxin was detected in the bloodstream of all patients with septic shock during the 24 h following referral and was not detected in the control patients. Eventual clinical recovery was associated with the disappearance of endotoxin from the peripheral blood. Blood cultures were unhelpful as a prognostic indicator in these critically ill patients. A quantitative assay of endotoxin in blood may allow a more precise relationship with the clinical manifestations of major sepsis.

Familial malignant melanoma of the uvea and p53: a Victorian detective story.

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.

Effects of staphylococcal products on locomotion and chemotaxis of human blood neutrophils and monocytes.

The effects of staphylococcal products as chemo-attractants for human blood neutrophils and monocytes and as inhibitors of locomotion of these cells were studied with bacterial cells, culture filtrates and isoelectrically focused fractions from culture filtrates of nine strains of Staphylococcus aureus. Little direct chemotactic activity of staphylococcal products for neutrophils was observed, although a chloroform-soluble extract of the whole organisms contained such activity. The major chemotactic effect of staphylococci for neutrophils was indirect, i.e., generated when the organisms or their products were incubated with plasma, perhaps due to activation of complement. In contrast, direct chemotactic activity for monocytes was found in a large number of staphylococcal fractions. Staphylococci also produced inhibitors of locomotion of both neutrophils and monocytes. Isoelectric focusing showed more fractions inhibitory for neutrophils than for monocytes. Some of the inhibitors could be identified. Staphylococcal alpha-toxin inhibited migration of both neutrophils and monocytes. Sphingomyelinase C (beta toxin) inhibited migration of monocytes but not of neutrophils. Leucocidin-rich strains were strongly active as inhibitors of neutrophil locomotion but less so as inhibitors of monocyte locomotion.

How to deal with a hospital outbreak of Legionnaires' disease.

The outbreak of Legionnaires' disease in Glasgow Royal Infirmary is discussed together with the problems such an outbreak poses to the microbiologist. The importance of early diagnosis is stressed. The outbreak was managed by a team drawn up from various disciplines within the hospital. Frank daily reports to the press, together with regular staff meetings with staff representatives helped to allay public anxiety. The subsequent maintenance and monitoring of the wet cooling tower required for the hospital ventilation system have resulted in considerable additional work for the microbiology department but especially for the hospital engineers.

Medulloepithelioma (diktyoma).

Sixteen cases of medulloepithelioma are described. Clinical data and follow-up were available on 15. Four patients underwent iridocyclectomy initially; all later needed enucleation and one had an orbital recurrence. The remaining 12 patients underwent primary enucleation. All 15 patients with follow-up are alive with no evidence of tumour recurrence. It is suggested that enucleation be performed for all but the most localised tumour. Rubeosis was noted in 13 of the 16 eyes, and this may assist in making the diagnosis. The World Health Organisation histological classification of medulloepithelioma was applied, but some problems were encountered, particularly where the presence of heteroplastic brain tissue was used as a criterion for teratoid tumour and where rosettes were used as a criterion for malignancy.

Oestrus ovis ophthalmomyiasis acquired in the UK: case report and scanning electron microscopic study.

A case of external ophthalmomyiasis acquired in the UK is reported. Oestrus ovis infestation of the external conjunctiva is described and a scanning electron microscopic study made of the first stage larvae. To our knowledge this represents only the third case reported of UK acquisition of ophthalmomyiasis.

Spontaneous congenital non-pigmented epithelial cysts of the iris stroma.

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.

Refsum's disease: electron microscopy of an iris biopsy.

Refsum's disease (phytanic acid storage disease) results in an accumulation of lipid as a result of an absence of mitochondrial hydroxylation of phytanic acid. We describe a previously unrecorded electron microscopic study of lipid deposition in the iris pigment epithelium of a patient with Refsum's disease, and lipid was present in other sites within the iris.

Oncocytoma of the eyelid: a case report.

Oncocytic tumours of the eyelids are rare, only one previous case having been reported. This paper describes a second such lid tumour affecting the medial upper lid. We present the clinical features, surgical management, and histology of the lesion.

Type IV melanosomes of the human albino iris.

Electron microscopy of an iris biopsy specimen from a clinically tyrosinase-negative human albino demonstrated type IV mature melanosomes. Possible mechanisms for the formation in this condition of these organelles, which have not previously been described at this site, are discussed.

Intrascleral neurilemmoma.

The case of an anteriorly situated, intrascleral, neurilemmoma in an 11-year-old girl is reported. Only two similar cases have been described in the literature, and the diagnosis was made only after detailed histological examination, including electron microscopy and specialised staining techniques, to differentiate a neurilemmoma (schwannoma) from a neurofibroma.

Multifocal amelanotic conjunctival melanoma and acquired melanosis sine pigmento.

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.