[Anthrax--an old disease becomes topical: cutaneous anthrax and the eye]. / Anthrax--altbekannt und hochaktuell Hautmilzbrand am Auge.

BACKGROUND: Anthrax disease and its eye manifestations were rare in the last 100 years, but the threat of terrorist actions has revived its topicality. MATERIALS AND METHODS: After an introductory historical review, the pathogenesis of this disease with regard to the virulence of Bacillus anthracis is reported. On the basis of photos displaying the course of the disease, the symptoms particularly of the cutaneous form of this disease as well as the diagnostic possibilities are described. RESULTS AND CONCLUSIONS: The current status of therapy and research for more effective treatment is discussed, with particular emphasis on the development of new substances with antitoxin properties and better vaccines. Bacillus anthracis is once again an actual threat, and therefore it is necessary for doctors to familiarize themselves with the current knowledge of this infection.

Cell proliferation activity in posterior uveal melanoma after Ru-106 brachytherapy: an EORTC ocular oncology group study.

AIM: To evaluate the cell proliferation activity in posterior uveal melanomas after Ru-106 brachytherapy. METHODS: Eyes containing choroidal or ciliary body melanoma from seven ocular oncology centres, which were enucleated after first being treated by Ru-106 brachytherapy and which had enough melanoma tissue to enable histological assessment, were included. The 57 eligible specimens were divided into a group of 44 eyes that were enucleated because of tumour regrowth, and a non-recurrent group of 13 eyes that were enucleated because of complications such as neovascular glaucoma. 46 non-irradiated eyes harbouring uveal melanoma served as a control group. All specimens underwent routine processing. They were cut into 5 microm sections, and were stained with two main cell proliferation markers: PC-10 for PCNA and MIB-1 for Ki-67. The stained sections were assessed, and the cells that were positive in the immunostaining were counted in each section. The results were evaluated by various statistical methods. RESULTS: The PC-10 score showed a statistically significant difference across the three groups (p = 0.002). The control group showed the highest PC-10 score (median 31.0 PCC/HPF) followed by the tumour regrowth group (median 4.9 PCC/HPF). The lowest PC-10 scores were found in the non-recurrent tumours (median 0.05 PCC/HPF). The MIB-1 score in the control group (median 5.77 PCC/HPF) was similar to the regrowth group (median 5.4 PCC/HPF). In contrast, the MIB-1 score in the non-recurrent tumours was statistically significantly lower (median 0.42 PCC/HPF). The PC-10 and MIB-1 scores were similar in tumours composed of either spindle cells or epithelioid cells in all groups. CONCLUSIONS: The non-recurrent melanomas demonstrate significantly lower cellular proliferation activity than melanomas that showed regrowth or that were not irradiated at all. In our hands, PCNA gave more meaningful information than Ki-67. Our findings strongly support the need for treating regrowing posterior uveal melanoma either by enucleation or re-treatment by brachytherapy. On the other hand, also in the non-recurrent uveal melanomas there are viable cells with potential for proliferation, although fewer in number, with unknown capacity for metastatic spread. Therefore, the irradiated tumours should be followed for many years, probably for life.

The outcome of local radiation injuries: 14 years of follow-up after the Chernobyl accident.

The Chernobyl nuclear power plant accident on April 26, 1986 was the largest in the history of the peaceful use of nuclear energy. Of the 237 individuals initially suspected to have been significantly exposed to radiation during or in the immediate aftermath of the accident, the diagnosis of acute radiation sickness (ARS) could be confirmed in 134 cases on the basis of clinical symptoms. Of these, 54 patients suffered from cutaneous radiation syndrome (CRS) to varying degrees. Among the 28 patients who died from the immediate consequences of accidental radiation exposure, acute hemopoietic syndrome due to bone marrow failure was the primary cause of death only in a minority. In 16 of these 28 deaths, the primary cause was attributed to CRS. This report describes the characteristic cutaneous sequelae as well as associated clinical symptoms and diseases of 15 survivors of the Chernobyl accident with severe localized exposure who were systematically followed up by our groups between 1991 and 2000. All patients presented with CRS of varying severity, showing xerosis, cutaneous telangiectasias and subungual splinter hemorrhages, hemangiomas and lymphangiomas, epidermal atrophy, disseminated keratoses, extensive dermal and subcutaneous fibrosis with partial ulcerations, and pigmentary changes including radiation lentigo. Surprisingly, no cutaneous malignancies have been detected so far in those areas that received large radiation exposures and that developed keratoses; however, two patients first presented in 1999 with basal cell carcinomas on the nape of the neck and the right lower eyelid, areas that received lower exposures. During the follow-up period, two patients were lost due to death from myelodysplastic syndrome in 1995 and acute myelogenous leukemia in 1998, respectively. Other radiation-induced diseases such as dry eye syndrome (3/15), radiation cataract (5/15), xerostomia (4/15) and increased FSH levels (7/15) indicating impaired fertility were also documented. This study, which analyzes 14 years in the clinical course of a cohort of patients with a unique exposure pattern, corroborates the requirement for long-term, if not life-long, follow-up not only in atomic bomb survivors, but also after predominantly local radiation exposure.

Bilateral anterior lenticonus: Scheimpflug imaging system documentation and ultrastructural confirmation of Alport syndrome in the lens capsule.

BACKGROUND: Alport syndrome is a combination of proteinuria, hematuria, and neurosensory high-frequency deafness. Bilateral anterior lenticonus may be a late sign. Diagnosis relies on characteristic electron microscopy changes of glomerular basement membranes in renal biopsy specimens. PATIENT: A 38-year-old man was seen for progressive visual acuity loss (20/400 OU; best-corrected visual acuity, 20/60 OD and 20/50 OS). Findings from slitlamp examination included bilateral anterior lenticonus and central posterior subcapsular cataract, documented using a modified Scheimpflug imaging system. Retinal pathology was not present. On detailed questioning, a history of microhematuria and proteinuria since childhood and progressive high-frequency deafness for years were discovered. The family history was negative for nephropathies, deafness, or eye diseases. Cataract extraction rehabilitated the patient's vision. RESULTS: Electron microscopy of a fragile capsulorhexis specimen showed typical thinned basal lamina with basement membrane disruptions. CONCLUSIONS: Anterior lenticonus is a rare bilateral progressive developmental anomaly. More than 90% of cases are associated with Alport syndrome. For diagnosis of Alport syndrome, the presence of 3 of 4 criteria is required: family history positive for Alport syndrome, progressive intra-auricular deafness, characteristic eye anomalies, and positive findings from glomerular ultrastructural examination. We believe that ultrastructural proof of anterior lenticonus may also be provided in the lens capsule. Arch Ophthalmol. 2000;118:895-897

Localization of myocilin/trabecular meshwork--inducible glucocorticoid response protein in the human eye.

PURPOSE: To study distribution and cellular localization of myocilin/trabecular meshwork-inducible glucocorticoid response protein (TIGR) in the human eye. METHODS: A peptide antibody against a portion of the myosin-like domain of myocilin/TIGR was developed. Different ocular tissues from three human donors were investigated by one- and two-dimensional gel electrophoresis and Western blot analysis. Immunohistochemistry was performed on 25 human eyes enucleated because of posterior choroidal melanoma and on 7 normal human donor eyes. RESULTS: By Western blot analysis, a band at approximately 57 kDa was visualized in cornea, trabecular meshwork, lamina cribrosa, optic nerve, retina, iris, ciliary body, and vitreous humor. By immunohistochemistry, immunoreactivity for myocilin/TIGR was observed in cells of the corneal epi- and endothelium and extracellularly in the corneal stroma and sclera. In the trabecular meshwork, cells of the uveal and corneoscleral meshwork were stained, as was the cribriform area directly adjacent to Schlemm's canal. Positive staining was seen in cells of the ciliary epithelium, ciliary muscle, lens epithelium, and in stromal and smooth muscle cells of the iris. Throughout the entire vitreous body, fine filamentous material was positively labeled. In the retina, staining was seen along the outer surface of rods and cones, in neurons of the inner and outer nuclear layer, and in the axons of optic nerve ganglion cells. Optic nerve axons were stained in the prelaminar, laminar, and postlaminar parts of the nerve. In the region of the lamina cribrosa, astrocytes in the glial columns and cribriform plates were positively labeled. CONCLUSIONS: Myocilin TIGR is expressed in almost every ocular tissue. Depending on the respective tissue, it is observed extra- or intracellularly. The presence of myocilin/TIGR in optic nerve axons and lamina cribrosa astrocytes indicates that the trabecular meshwork might not be the only target of abnormal myocilin/TIGR in GLC1A-linked open-angle glaucoma.

[Long-term radiation damage to the skin and eye after combined beta- and gamma- radiation exposure during the reactor accident in Chernobyl]. / Langzeitstrahlenschäden an Haut und Auge nach kombinierter beta- und gamma-Strahlenexposition während des Reaktorunfalls in Tschernobyl.

BACKGROUND: In April 1986, numerous reactor workers and firemen were exposed to high doses of ionizing radiation during the Chernobyl nuclear power plant accident. Apart from high ambient gamma-ray exposures they received inhomogeneous contamination with beta-rays from fission products, resulting in severe skin exposure. PATIENTS AND METHODS: Sixteen of these so called Liquidators were repeatedly examined between 1991 and 1996. Their doses ranged from 0.35 to 9 Gy, partly confirmed by determination of chromosomal aberrations. Ophthalmologic examination included non-subjective assessment of lenticular radiation damage with an electronic Scheimpflug camera system. Digital image analysis allowed the comparison of opacification units to previous and normal findings. RESULTS: Four Liquidators had posterior subcapsular opacifications in different degrees, one presented only after cataract extraction. One patient had dense corticonuclear cataracts and pseudoexfoliation-like changes. Three men had severe dry eye syndrome. Eight men had no ocular complications. Retinal radiation damages were absent. 15 Liquidators suffered from severe chronic cutaneous radiation damage, which led to amputations in 3 cases. CONCLUSIONS: A relation between ocular and dermatological findings was not expected and could, in fact, not be seen. The comparison of posterior subcapsular opacification and doses revealed no distinct relation, although it indicates a correlation that is here not quantified. The doses represent organ doses for the bone marrow which is primarily exposed to deeper penetrating gamma-radiation. Thus they need not be correlated with combined beta- and gamma-doses in organs such as skin and eye because the superficial exposure due to beta-radiation may differ greatly form the whole body exposure as reflected in bone marrow doses.

[Keratoacanthoma of the eyelid area. Problems and risks in diagnosis and therapy]. / Keratoakanthom im Lidbereich. Probleme und Risiken bei Diagnose und Therapie.

BACKGROUND: Keratoacanthoma of the eyelid is a benign skin lesion. Because it regresses spontaneously observation without surgical intervention is the generally accepted method of management. This concept, which was developed in the sixties, is questioned on the basis of personal experience and a review of the literature. Recommendations for a rational management of the disease are suggested. METHOD: Two patients with clinically diagnosed eyelid keratoacanthomas are reported with their complicated disease course. A review of the dermatological and ophthalmic literature is presented. CONCLUSIONS: For the correct diagnosis a sufficiently large and representative histological specimen is mandatory. The difficulty of differentiating between keratoacanthoma and squamous cell carcinoma is stressed. Surgery of advanced eyelid lesions is so much more destructive that early simple excision is advocated rather than a policy of initial observation.

[Lisch nodules. Markers of neurofibromatosis 1 and immunohistochemical references for neuroectodermal differentiation]. / Lisch-Knötchen. Marker der Neurofibromatose I und immunhistochemische Hinweise für eine neuroektodermale Differenzierung.

Iris nodules in neurofibromatosis I have become an important tool in the differential diagnosis of phakomatoses. The clinical appearance and importance of these nodules first recognized by Karl Lisch in Munich in 1937. The diagnosis and differential diagnosis of Lisch nodules are illustrated. The importance of iris nodules in genetic counselling of patients and their relatives is discussed, with emphasis on monosymptomatic cases. Histologically Lisch nodules are formed by aggregations of oval to round cells that form dome-shaped papules on the anterior layer of the iris. Immunohistochemically these cells are characterized by positive staining with antibodies against vimentin and S-100 protein. This proves their ectodermal differentiation. Thus Lisch nodules can be seen as a direct manifestation of neuroectodermal disturbances in neurofibromatosis I.

Innervation of myofibroblast-like scleral spur cells in human monkey eyes.

PURPOSE: To study the innervation of the presumably contractile, myofibroblast-like scleral spur cells in human and cynomolgus monkey eyes. METHODS: Serial tangential sections of the scleral spur region of the eyes of 16 human donors and 6 cynomolgus monkeys were investigated with immunocytochemical methods. Antibodies against acetylcholinesterase, synaptophysin, alpha-smooth muscle actin, calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY), nitric oxide synthase (NOS), substance P (SP), tyrosine hydroxylase (TH), and vasoactive intestinal peptide (VIP) were used. In addition, sections were processed for glyoxylic acid-induced catecholamine fluorescence (CF) and for NADPH-diaphorase (NADPH-d). RESULTS: In the eyes of both species, circumferentially oriented varicose axons were observed in the scleral spur region of all quadrants. Double labeling showed that most of these scleral spur axons were in close contact with the alpha-smooth muscle actin-positive, myofibroblast-like scleral spur cells. In human eyes, the axons showed like-immunoreactivity (LI) for SP, CGRP, NPY, VIP, and NOS. In addition, numerous scleral spur axons stained for NADPH-d. Most SP-LI scleral spur axons were double-labeled for CGRP-LI, and none for VIP-LI. All NPY-LI scleral spur axons were double labeled for VIP-LI but lacked immunoreactivity to TH. Some VIP-LI axons were not labeled for NPY-LI. Nerve fibers immunoreactive (IR) for TH or positively stained for CF were not observed in association with scleral spur cells. In contrast, in cynomolgus monkey eyes, circumferentially oriented TH-IR and CF-positive varicose axons were observed frequently in the scleral spur region. In addition, SP-LI, CGRP-LI, and NPY-LI/TH-IR axons were present in the chamber angle of monkey eyes, whereas VIP-LI, VIP-LI/NPY-LI, NOS-positive, or NADPH-d-positive nerve fibers were absent. In both species, positive staining for acetylcholinesterase was seen only in the ciliary muscle, not in the scleral spur region. CONCLUSIONS: The close association of varicose axons with the myofibroblast-like scleral spur cells indicates that nervous signals modulate scleral spur cell tone. A sympathetic scleral spur cell innervation is present only in cynomolgus monkeys but seems to be absent in humans. Conversely, scleral spur axons of presumably parasympathetic origin (NOS-IR or NADPH-d-positive, VIP-LI, and VIP-LI/NPY-LI) are absent in the cynomolgus monkeys but present in humans. In both species, a cholinergic innervation of the scleral spur cells seems to be rare or absent.

[The initial clinical manifestations of rhabdomyosarcoma]. / Klinische Erstmanifestationen des orbitalen Rhabdomyosarkoms.

Unilateral proptosis, dislocation of the globe and impairment of motility in childhood are known to be typical presenting signs of rhabdomyosarcoma of the orbit. In a retrospective analysis of 17 patients with rhabdomyosarcoma (1974-1993) only 8 patients presented with typical signs. 9 patients did never show the typical signs which initially lead to a wrong diagnosis in many cases. A 5-year-old boy complained of a conjunctival cyst in the lower fornix of the left eye. Two weeks later the cyst was replaced by a solid tumor. The tumor was not completely resectable, histology revealed an embryonal rhabdomyosarcoma. Presenting signs and symptoms of orbital rhabdomyosarcoma show a sometimes misleading variety including conjunctival cyst formation. In any recent onset of unilateral rapidly progressing alterations of the lid, the conjunctiva or the caruncle in childhood the physician should consider a rhabsomyosarcoma of the orbit.

Paraffinoma of the periorbit--a challenge for the oculoplastic surgeon.

Five patients with a history of sinus surgery with nasal packing and postoperative hemorrhage developed nontender, firm tumors of the periorbit. There was no spontaneous regression. Surgical excision was difficult due to diffuse cellular infiltration and intracutaneous deposits, requiring reoperations in all patients. Histology showed a marked lipogranulomatous reaction to dispersed lipid material with fibrosis. Paraffinoma is a known complication of paraffin injection in dermatology and cosmetic surgery. Reports of it in the ophthalmic literature are rare. This series documents a late complication of sinus surgery, very probably due to the intraoperative nasal packing with paraffin-containing ointments.

Evidence of constriction of optic nerve axons at the lamina cribrosa in the normotensive eye in humans and other mammals.

The ultrastructure of optic nerve axons was examined in several mammals (human, cat, rat, sheep, ox, pig, guinea pig, rabbit). Human material was obtained from normotensive, glaucoma-free eyes and from eyes with a history of glaucoma and raised intra-ocular pressure (IOP). We describe accumulations of organelles (principally mitochondria) in optic nerve axons where they traverse the lamina cribrosa. Accumulations were most prominent in unmyelinated lengths of axons close to lamellae of the lamina cribrosa. Comparable accumulations were not apparent in axons in the retina or optic nerve, suggesting that axoplasmic flow is constricted at the lamina cribrosa. Accumulations were observed both centrally and peripherally to the lamellae, suggesting that flow is constricted in both ortho- and anterograde directions. Accumulations of organelles were more marked in unmyelinated axons than in adjacent, myelinated axons. In the rabbit, in which most axons are myelinated as they traverse the optic nerve head, organelle accumulations were observed only in a sparse population of unmyelinated axons. In human eyes with a history of raised IOP and glaucoma, the accumulations were abnormally large and frequent and in many axons showed dense-body and fibrillar changes not seen in normotensive eyes. It is suggested that chronic, partial constriction of axoplasmic flow is present at the lamina cribrosa of normotensive eyes in a wide range of mammals, including humans, that the constriction results from the pressure gradient across the lamina cribrosa and that the constriction may be a factor in the many cases of primary glaucoma in which IOP is not raised.

Nerve endings with structural characteristics of mechanoreceptors in the human scleral spur.

PURPOSE: The innervation of the scleral spur region was investigated to learn whether mechano-receptors are present in this region. METHODS: Serial tangential sections and whole-mount preparations of the scleral spur region of 18 human eyes of different ages were investigated with electronmicroscopic and immunohistochemical methods. For immunohistochemistry antibodies against neurofilament-proteins, synaptophysin, substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), tyrosine-hydroxylase, dopamine-beta-hydroxylase, and acetylcholinesterase were used. RESULTS: Club- or bulb-shaped nerve endings with a diameter of 5 microns to 25 microns were identified in the scleral spur region throughout the whole circumference of the eyes. The terminals derive from myelinated axons with a diameter of approximately 3 microns and stain with antibodies against neurofilament-proteins and synaptophysin but do not stain for tyrosine-hydroxylase, dopamine-beta-hydroxylase, acetylcholinesterase, NPY, VIP, SP, or CGRP. Electronmicroscopically, the endings contain abundant neurofilaments, granular and agranular vesicles of different sizes, numerous mitochondria, and lysosome-like lamellated structures. The endings are incompletely ensheathed by Schwann cells. Those areas of the cell membrane of the endings that are not covered by Schwann cells are in intimate contact with the fibrillar connective tissue elements of the scleral spur. CONCLUSION: These structural features are highly characteristic for mechanoreceptive nerve endings in other tissues of the human body. The authors therefore hypothesize that the club-or bulb-shaped nerve endings in the human scleral spur are afferent mechanoreceptors that measure stress or strain in the connective tissue elements of the scleral spur. Such changes might be induced by ciliary muscle contraction and/or by changes in intraocular pressure.

[Resorption of post-traumatic cilio-choroid (supra-choroid, sub-scleral) hematoma. A histopathologic study]. / Resorption posttraumatischer ziliochorioidaler (suprachorioidaler, subskleraler) Hämatome. Eine histopathologische Untersuchung.

The healing process of ciliochoroidal (suprachoroidal, subscleral) hematomas was studied histopathologically in 75 eyes enucleated between 1 and 42 days following a traumatic incident. The ciliochoroidal hematomas occur from ruptured vortex veins or ciliary blood vessels located in the suprachoroidal (subscleral) space. Detached ciliary blood vessels and nerves form a network within the hematoma. In early stages there is little fibrin formation and no signs of coagulation are visible. Then hyperemia of uveal blood vessels develops, followed by a perivascular accumulation of polymorphonuclear leukocytes and lymphocytes with edema. About 11 days after the traumatic event a thin mesenchymal cell layer covers the outside of the hematoma, which at this stage shows some hemolysis. After 2 weeks proteinaceous exudate with lipid vacuoles is present and fibroblastic activity is increased on the uveal side of the hematoma and along the septating blood vessels and nerves. After 3 weeks the outer uvea is impregnated by phagocytic cells containing hemosiderin (hemosiderophages). Twenty-eight days after trauma the fibrous lining of the hematoma has increased. In principle a seroma with septum formation has evolved from the suprachoroidal hematoma. This is regarded as a complicated healing process, which hinders surgical drainage of long-standing post-traumatic hemorrhagic ciliochoroidal detachment and therapy of post-traumatic ocular hypotony.

Clinical and immunohistochemical correlation of herpetic keratitis with the expression of HLA-DR antigen.

The corneal buttons after corneal graft of 22 patients with herpetic keratitis were studied (16 male, 6 female; 7-87 years of age). Ten still had active inflammation, while 12 had stabilized by the time of the study. Different degrees of neovascularization were observed in 19 cases. HLA-DR antigen was detected in the corneal epithelium in 7 of 22 cases (32%), in the corneal stroma in 17 of 22 cases (77%), and in the endothelium in 9 cases (41%) by using the immunohistochemical technique. The expression of HLA-DR antigen was more common and more marked in active herpetic keratitis (90%) and in neovascularized corneas (84%). The frequency and density of HLA-DR expression in perforating corneal ulcers were no higher than in other cases, but anterior synechia was accompanied by strong expression of HLA-DR antigen in the corneas. The expression of HLA-DR antigen was not only detected in the peripheral, but also in the central area of the specimens. The cells expressing HLA-DR antigen in corneas were mainly corneal cells. The results showed a close relationship between HSV-keratitis and the expression of HLA-DR antigen, which may be induced during the clinical course of the disease. The expression of HLA-DR might be one of the factors in the recurrent onset of the disease and a significant sign of the prognosis of corneal transplantation for these patients.

[Immunocytochemical and ultrastructural studies of human scleral spur. Characterization of a contractile cell population]. / Immunzytochemische und ultrastrukturelle Untersuchungen am menschlichen Skleralsporn. Charakterisierung einer kontraktilen Zellpopulation.

Contraction of the ciliary muscle induced by cholinergic drugs causes movement of the scleral spur and separation of the trabecular meshwork lamellae. The effect of epinephrine, however, does not seem to be mediated by ciliary muscle tone. We investigated the scleral spur in 37 human eyes (age 17-87 years). Serial tangential sections were studied with ultrastructural and immunocytochemical methods. The ciliary muscle cells do not enter the scleral spur, but their tendons, which consist of elastic fibers, are continuous with the elastic fibers in the scleral spur. Within the scleral spur is found a population of circularly oriented and spindle-shaped cells. The scleral spur cells form no bundles, but are loosely aggregated. They have long cytoplasmic processes and are connected to each other by adherence type and gap junctions. The scleral spur cells show intense staining for smooth-muscle-specific alpha-actin and myosin. Ultrastructurally, the scleral spur cells contain abundant actin filaments, but otherwise do not show the typical ultrastructure of ciliary muscle cells. The scleral spur cells do not express a complete basal lamina. They form individual tendinous connections with the elastic fibers in the scleral spur, which are continuous with the elastic fibers of the trabecular meshwork. The scleral spur cells are in close contact with nerve terminals containing small granular vesicles that are typical for adrenergic terminals. We conclude that the scleral spur cells are contractile myofibroblasts. Their contraction might be involved in the effects of epinephrine on the aqueous outflow.

Progressive loss of cytochrome c oxidase in the human extraocular muscles in ageing--a cytochemical-immunohistochemical study.

Cytochrome c oxidase (complex IV of the respiratory chain) was studied histochemically in autoptic human extraocular muscles (n = 135), revealing randomly distributed single fibers without enzyme activity. The enzyme defect was expressed in all the mitochondria of an involved fiber as evidenced by ultracytochemistry. Succinate dehydrogenase showed normal histochemical reactivity. The defects occurred already in the second decade and were regularly seen from the third decade on. The defect density (defects/mm2) increased from approx. 1/mm2 below the fifth decade to about 4/mm2 in advanced age (P = 0.000). The highest defect density was observed in the levator palpebrae muscle. On the whole, the defect density was about 5-6 times higher in the extraocular muscles than in the limb muscle, diaphragm and heart (Müller-Höcker, 1989, 1990). Immunocytochemical detection of cytochrome c oxidase showed that loss of cytochrome c oxidase activity was due to an almost complete absence of both nuclear and mitochondria subunits of the enzyme. The results document different organ and heterogenic cellular sensitivity to the age-related loss of cytochrome c oxidase. The loss of both mitochondrial and nuclear subunits indicates that nuclear factors are most probably involved in the decline of the respiratory chain function in senescence.

Immunoimaging of choroidal melanoma: assessment of its diagnostic accuracy and limitations in 101 cases.

Immunoscintigraphy (IS) was performed on 101 patients with space occupying intraocular lesions including choroidal melanomas (85), choroidal naevi (11), non-melanoma metastases (three), and other melanoma simulating lesions (two). Scintigraphic images with conventional and emission computer tomography techniques were obtained after the intravenous injection of 99mTc-labelled F(ab')2 fragments of monoclonal antibody (MoAb) 225.28S directed against the high molecular weight-melanoma associated antigen (HMW-MAA). Immunohistochemistry was performed on sections of four out of 10 melanoma-containing eyes to confirm MoAb binding. IS demonstrated positive scans in 66 out of 85 choroidal melanomas, offering a sensitivity of 78%. Sensitivity was dependent on the lesion size. True negative results were obtained in 15 out of 16 non-melanoma lesions (specificity 94%). False positive antibody accumulation was found in one patient with a post-traumatic subretinal haemorrhage. Immunohistochemistry demonstrated positive MoAb 225.28S binding in all melanoma sections. In summary IS offered substantial sensitivity and specificity in the differentiation of intraocular lesions, particularly choroidal melanomas, naevi, and metastases. In combination with other diagnostic procedures such as ultrasound echography and fluorescein angiography IS proved to be a valuable method in the diagnosis of choroidal melanoma.

Quantitative color Doppler imaging in untreated and irradiated choroidal melanoma.

Histological data indicate the importance of tumor vascularization as a determinant of the biological behavior and the response to radiotherapy in choroidal melanoma. Duplex ultrasound and color Doppler imaging, the combination of B-mode ultrasound and pulse-waved Doppler analysis, were used to measure quantitatively neovascular blood flow in 31 patients with choroidal melanoma. Follow-up studies (20 patients) were performed to investigate the change of tumor blood flow in choroidal melanomas after radiotherapy. Blood flow was detected in 30 out of 31 melanomas (size 3.1-17.8 mm) within the tumor and at the tumor base with a mean peak systolic frequency of 1.0 kHz (range 0.3-2.7 kHz), a mean end diastolic frequency of 0.3 kHz (range 0.1-1.0 kHz), and a mean frequency of 0.7 kHz (range 0.2-1.3 kHz). Two and six months after 106Ru/106Rh beta-ray application, 19 patients showed a significant decrease in peak systolic frequency. This occurred with and in advance of the decrease in the tumor size. In one patient, a rising maximum systolic frequency after radiotherapy marked a recurrent tumor growth. Results indicate that the quantitative measurement of tumor blood flow by duplex ultrasound and color Doppler imaging may be a new diagnostic modality for monitoring the effectiveness of radiotherapy in choroidal melanoma.