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Biomedical subjects

R J Campbell

Publications and source records attributed to R J Campbell.

At least 19 recordsLinked to original sources

Pathology of late endothelial failure: late endothelial failure of penetrating keratoplasty: study with light and electron microscopy.

PURPOSE: Late endothelial failure of penetrating keratoplasty can be defined as gradual decompensation (increasing thickness with loss of clarity) of a previously clear graft without apparent cause. This study examined the possibility that a chronic subclinical rejection process may be occurring in grafts that fail from late endothelial failure. METHOD: Six patients fulfilling the diagnostic criteria for late endothelial failure who underwent repeated keratoplasty were studied. The clinical course and results of specular microscopy were reviewed. The failed corneal graft for each patient was examined by light and electron microscopy. RESULTS: Sequential specular microscopy demonstrated low initial postoperative endothelial cell density with continued decrease in density and increase in corneal thickness over the first 5 postoperative years. Electron microscopy revealed irregular-shaped cells of varying size with many abnormal features, lying on abnormal Descemet's membrane. Degenerating endothelial cells were commonly seen. There was no sign of acute or chronic inflammation. CONCLUSIONS: The pathologic findings are suggestive of an unstable and highly stressed endothelial cell population in late endothelial failure but are nonspecific. There was no evidence of acute or chronic rejection at the time of graft failure.

Adult↗

Microcirculation architecture of metastases from primary ciliary body and choroidal melanomas.

PURPOSE: To describe the microcirculation architecture of metastatic choroidal and ciliary body melanoma. METHOD: Histologic sections of 35 metastases from 19 primary melanomas were stained to demonstrate microcirculation. RESULT: The appearance of microcirculatory networks in metastases is independent of the target organ but associated with the size of the metastatic deposit (estimated coefficient = 0.5959; SE = 0.3024; P = .0488). CONCLUSION: The microcirculatory patterns of primary uveal melanomas that are associated with metastatic behavior appear in foci of metastasis, regardless of the site of dissemination.

Choroid Neoplasms↗

Cost-effectiveness in the diagnosis of sarcoidosis: the conjunctival biopsy.

PURPOSE: Sarcoidosis is a multi-system disease that often affects ocular structures. The definitive diagnosis of sarcoidosis requires tissue biopsy for confirmation. Conjunctival biopsy is a simple and relatively inexpensive diagnostic tool. This study was undertaken to determine the utility and cost of conjunctival biopsy for the diagnosis of sarcoidosis compared with other diagnostic biopsy sites. METHODS: A retrospective study was performed of all conjunctival biopsies taken for sarcoidosis at the Mayo Clinic Rochester between 1982 and 1995. All case histories were reviewed. Data regarding biopsy of tissues confirming sarcoidosis was collected. The costs of performing and evaluating all biopsy techniques were obtained from the estimating department. RESULTS: Forty-one cases of sarcoidosis were identified that had undergone conjunctival biopsies. Twenty-one patients had a positive conjunctival biopsy for sarcoidosis, and 20 patients had a negative conjunctival biopsy but a positive biopsy of another organ. In all positive biopsies, special stains for acid fast organisms and fungi were negative. CONCLUSIONS: Conjunctival biopsy is a simple, relatively inexpensive procedure that may be helpful in establishing the diagnosis of sarcoidosis with a negligible complication rate. Positive results are similar for conjunctival biopsy and mediastinoscopy. About 10 patients can be evaluated with conjunctival biopsy for the cost of one patient undergoing mediastinoscopy. Multiple levels of the tissue must be examined, as distribution of the granulomas may be random. Also, bilateral conjunctival specimens should be obtained to increase the positive yield.

Biopsy↗

Intravitreal invasion of malignant cells from choroidal melanoma after brachytherapy.

We report intravitreal invasion by melanoma cells from a choroidal melanoma after brachytherapy. A malignant melanoma of the choroid with collar-button configuration was treated with iodine 125 brachytherapy. Years later, the collar button developed a dark-chocolate color and began shedding pigmented debris into the vitreous. Coalescence of this debris into spheroidal aggregates suggested the presence of malignant cells; the eye was enucleated. Histologic sections demonstrated a choroidal melanoma with intraretinal and intravitreal invasion by melanoma. Clinical evidence of intraretinal invasion by melanoma cells along with pigmented debris within the vitreous cavity, especially when clustered in spheroidal aggregates, suggests the presence of intravitreal invasion by malignant cells. In this case, intravitreal invasion was verified histologically.

Brachytherapy↗

Histopathologic study of eyes after iodine I 125 episcleral plaque irradiation for uveal melanoma.

OBJECTIVES: To describe the histopathologic findings attributable to irradiation in eyes with uveal malignant melanoma treated with iodine I 125 brachytherapy and to compare these findings with those reviewed in a previous study that compared histopathologic findings in eyes enucleated after proton beam teletherapy with those seen in eyes in a nonirradiated control group. METHODS: The slides from 22 eyes with uveal melanoma that had undergone enucleation after the administration of 125I brachytherapy were studied. The histopathologic features of the tumor and the retina were graded. Results were compared with findings from a previously reported group of 47 proton beam-treated eyes and its control group. RESULTS: Patient age, time between irradiation and enucleation, and ciliary body involvement were similar for the 125I brachytherapy-treated group and the proton beam-treated group and its control group. This allows comparison of the histopathologic findings. Comparing the 125I brachytherapy- and proton beam-treated groups, most histopathologic features were similar with nominally statistically significant differences only for cell type, number of mitotic figures, and fibrous metaplasia of the retinal pigment epithelium adjacent to the tumor. CONCLUSIONS: Irradiation of uveal melanoma induces changes in the tumor and in the surrounding retina. Brachytherapy and charged particle therapy are the 2 principal methods of irradiation. This study demonstrates that similar changes are produced by 125I plaque irradiation and proton beam irradiation.

Adult↗

Vortex keratopathy in a patient with multiple myeloma.

PURPOSE: We report a 52-year-old woman with vortex keratopathy (cornea verticillata) of unknown cause in whom multiple myeloma was found 18 months later. METHODS: Surgical biopsy of conjunctival crystalline deposits, which were stained immunohistologically and analyzed ultrastructurally, as well as hematologic workup for multiple myeloma, were performed. RESULTS: Light microscopy of conjunctival deposits revealed plasmacytoid infiltrates in the conjunctiva, which stained monoclonally for immunoglobulin G (IgG)-kappa light chains. Transmission electron microscopy showed intracellular hexagonal crystalline structures and extracellular microfibrils. Hematologic tests confirmed the diagnosis of multiple myeloma. CONCLUSION: Multiple myeloma is one of the many causes of vortex keratopathy.

Antineoplastic Agents↗

Familial subepithelial corneal amyloidosis--a lactoferrin-related amyloidosis.

PURPOSE: To isolate the protein that collects in increased amounts beneath the corneal epithelium in familial subepithelial corneal amyloidosis (FSCA), also known as gelatinous droplike corneal dystrophy, and to identify it by N-terminal amino acid sequencing. METHODS: Peptides resulting from pepsin digestion of a unique protein isolated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis from frozen tissue from two corneas with FSCA were purified by high-pressure liquid chromatography followed by protein sequence analysis. The protein was identified by amino acid sequencing, Western blotting, and immunohistochemistry. RESULTS: A protein was identified in two corneas with FSCA that was not present in normal corneas or in corneas with other disorders. The amino acid sequences of two peptides derived from this protein were identical to portions of lactoferrin. The unique protein reacted with rabbit antihuman lactoferrin after Western blotting. The presence of lactoferrin in the amyloid within affected corneas was confirmed using the immunoperoxidase method on formalin-fixed, paraffin-embedded tissue sections and lactoferrin antiserum. CONCLUSIONS: Corneal tissue with FSCA contains lactoferrin, and this is the first form of amyloidosis found to be associated with this protein. Because lactoferrin is a product of lacrimal glands, the corneal lactoferrin may be derived from the tears. Because the gene for lactoferrin is on chromosome 3 (3q21-q23), this locus is a potential site for the FSCA gene.

Adolescent↗

Succinate dehydrogenase activity within synaptic and extrasynaptic compartments of functionally-overloaded rat skeletal muscle fibers.

Activity of the mitochondrial enzyme succinate dehydrogenase (SDH) was assessed using quantitative microphotometric techniques within postsynaptic, subsarcolemmal and intermyofibrillar compartments of overloaded soleus muscle fibers. Six weeks of overload, induced via synergist tenotomy, significantly increased soleus muscle mass (23%) and mean fiber cross-sectional area (17%). Despite these increases in cell size, SDH activity within all three intracellular compartments of overloaded muscle fibers was not different from levels in corresponding regions of control fibers. Thus, we show for the first time that activity-related increases in muscle cell volume, and specifically motor endplate area, appear to be coordinated with increased levels of oxidative enzymes within distinct subcellular compartments, including the postsynaptic sarcoplasm.

Animals↗

Regulation of succinate dehydrogenase within muscle fiber compartments by nerve-mediated activity and CNTF.

We investigated the regulatory effects of neural activation and trophic factors on the selective accumulation of succinate dehydrogenase (SDH; EC 1.3.99.1) activity at the endplate, as well as within subsarcolemmal and intermyofibrillar regions of rat soleus muscle fibers. The role of activation was assessed by stimulation of tetrodotoxin (TTX)-inactivated nerves distal to the site of drug application. We also studied whether ciliary neurotrophic factor (CNTF) is involved in regulating the postsynaptic accumulation of SDH. Using quantitative microphotometry, we found that daily stimulation of quiescent but intact nerves prevented the TTX-induced decrease in SDH activity within extrajunctional regions, whereas, at the endplate, the counteraction was partial (30%). Thus it appears that endplate levels of this enzyme are regulated by a complex mechanism involving an interaction between neuromuscular activation and trophic factors. We also found that daily CNTF administration counteracted the denervation-associated loss of SDH activity exclusively within the intermyofibrillar compartment, suggesting that CNTF treatment mimics the effects of activity on SDH levels within the core region of denervated fibers, but under these conditions does not influence the endplate accumulation of this enzyme.

Animals↗

Nerve-dependent regulation of succinate dehydrogenase in junctional and extrajunctional compartments of rat muscle fibres.

1. We studied the distribution of the mitochondrial enzyme succinate dehydrogenase (SDH) within junctional and extrajunctional compartments of rat soleus muscle fibres. Using quantitative microphotometric imaging techniques, we showed that the motor endplate region of soleus fibres displays SDH activity that is two- and threefold higher than in subsarcolemmal (SS) and intermyofibrillar (IM) compartments, respectively, and that essentially all endplate SDH activity is of postsynaptic origin. 2. In addition, we examined the influence of the motor nerve on the regulation of this enzyme within these compartments using denervation and tetrodotoxin (TTX)-induced blockade of nerve impulse conduction. Both models of short-term muscle paralysis reduced SDH activity to a comparable extent (approximately 30%) in both the SS and IM compartments, suggesting that expression of this enzyme is co-ordinately regulated in these two regions. Alternatively, denervation and TTX inactivation led to distinct alterations at the level of the motor endplate. SDH activity at denervated endplates was dramatically reduced (by 60%) in comparison to controls, whereas at endplates of TTX-inactivated counterparts, this reduction was significantly less (35%). 3. These findings suggest that motor activity per se is the key factor regulating expression of SDH in non-innervated regions of muscle fibres and that accumulation of SDH activity within the postsynaptic sarcoplasm is equally subject to local mechanisms involving nerve-derived trophic factors.

Animals↗

Clinicopathologic correlation of a case of adenocarcinoma of the retinal pigment epithelium.

PURPOSE/METHODS: We observed a clinicopathologic correlation of a case of adenocarcinoma of the retinal pigment epithelium. RESULTS/CONCLUSIONS: The ultrasonographic findings of this tumor demonstrated a collar button profile with high internal reflectivity. The ultrasonographic characteristics in this case reflected the variable vascularity and cystic spaces within the tumor.

Adenocarcinoma↗

Immunolocalization of calcitriol receptor, plasma membrane calcium pump and calbindin-D28k in the cornea and ciliary body of the rat eye.

Epitopes of the calcitriol receptor, the ATP-dependent plasma membrane calcium pump (PMCA) and the 28-kD vitamin-D-dependent Ca-binding protein (calbindin-D28k) were detected in sections of the albino rat eye using light microscopy and immunohistochemistry of paraffin-embedded tissues. Calcitriol receptor and calbindin-D28k epitopes were detected in both the inner and outer layers of the ciliary body epithelium. PMCA was present in both epithelial cell layers of the ciliary body but was most prominent in the inner layer. Corneal epithelium and endothelium also contained epitopes for calcitriol receptor, PMCA and calbindin-D28k. These Ca-regulatory proteins may play a role in the cellular physiology of the albino rat eye by maintaining appropriate intracellular and aqueous humor Ca concentrations.

Animals↗

Immuno-localization of the calcitriol receptor, calbindin-D28k and the plasma membrane calcium pump in the human eye.

Using immunohistochemical methods, we detected epitopes of the calcitriol receptor, the ATP-dependent plasma membrane calcium pump and the 28kD vitamin D-dependent calcium-binding protein in sections of the human eye. In retinal photoreceptors, vitamin D receptor, plasma membrane calcium pump and calcium-binding protein epitopes were detected in the outer nuclear layer. Epitopes for the vitamin D receptor and the calcium-binding protein were present in the inner and outer segments of the photoreceptors, where visual transduction occurs. All three proteins were detected in some cells of the ganglion cell layer, the inner nuclear layer, and the retinal pigment epithelium. Epitopes for these proteins also were noted in the ciliary body epithelium. VDR epitopes were seen in lens epithelium. Some immunostaining for VDR, PMCA and calbindin-D28k also was present in the endothelium and in the basal epithelium of the cornea. The presence of these proteins in several tissues of the human eye suggests that the proteins may play a role in the cellular physiology of the eye. Their exact functions in the eye remain undetermined.

Antibodies, Monoclonal↗

A review of 340 orbital tumors in children during a 60-year period.

We reviewed cases of histopathologically verified orbital tumors in children at our institution over 60 years to determine the distribution of various pathologic processes and trends over time. We studied the medical records and pathology specimens from 340 patients aged 18 years or younger who underwent biopsy for orbital mass from 1932 through 1991. The most common tumors were cysts (79 of 340, 23.2%), vascular lesions (60 of 340, 17.6%), optic nerve and meningeal neoplasms (56 of 340, 16.5%), inflammatory masses (29 of 340, 8.5%), osseous and fibrocystic lesions (27 of 340, 7.9%), and rhabdomyosarcomas (24 of 340, 7.1%). The overall frequency of malignancies was 18.2% (62 of 340): 11.5% (39) were primary tumors and 6.8% (23) were secondary and metastatic. The frequency of orbital malignancies was 25.4% (36 of 142) in the first 30 years (1932 through 1961) and 13.1% (26 of 198) in the second 30 years (1962 through 1991). The percentage of primary orbital malignancies was almost identical during the first and second periods (11.9% [17 of 142] and 11.1% [22 of 198], respectively). However, secondary and metastatic orbital neoplasms occurred in 13.4% (19 of 142) of the patients during the first 30 years and in only 2.0% (four of 198) during the second 30 years. The frequency of primary orbital malignancies in biopsy material remained the same over 60 years. However, the overall incidence of orbital biopsy specimens containing a malignancy decreased as a result of a reduction in the number of secondary and metastatic neoplasms that underwent biopsy.

Child↗

Coccidioidomycosis with necrotizing granulomatous conjunctivitis.

A patient with a steroid-resistant conjunctival nodule developed severe necrotizing granulomatous conjunctivitis during aggressive treatment with topical, subconjunctival, and systemic steroids. Culture of the tissue yielded Coccidioides immitis. A cavitary lesion was noted on a chest radiograph, and the same organism was recovered from a lung biopsy specimen. The granulomatous conjunctivitis was controlled only after aggressive debridement of the affected area and months of treatment with topical amphotericin B and oral fluconazole. A review of the literature suggests that subclinical ocular involvement from pulmonary coccidioidomycosis may be more common than generally believed. Conditions that blunt the host immune response may lead to a higher incidence of clinically significant ocular involvement.

Aged↗

Optic nerve sheath decompression for visual loss in patients with acquired immunodeficiency syndrome and cryptococcal meningitis with papilledema.

Visual dysfunction developing in association with acquired immunodeficiency syndrome (AIDS) can be multifactorial. Two patients with this syndrome and cryptococcal meningitis had papilledema and visual loss. Both were treated by optic nerve sheath fenestration. One patient had bilateral nonsimultaneous optic nerve sheath fenestrations; visual function improved in one eye. The other patient had bilateral visual improvement after a unilateral optic nerve sheath fenestration. Cryptococcal organisms were present in the dural sheath specimens of both patients despite ongoing therapy with antifungal medication. Postoperative orbital infectious complications did not occur. Autopsy examination of one patient showed that the sites of fenestration were patent. Medical treatment of cryptococcal meningitis associated with AIDS has a guarded prognosis. Optic nerve sheath fenestration offers a treatment alternative for papilledema and visual loss that occur with cryptococcal meningitis.

AIDS-Related Opportunistic Infections↗

Pathologic findings in the retinal pigment epitheliopathy associated with the amyotrophic lateral sclerosis/parkinsonism-dementia complex of Guam.

BACKGROUND: A pigment epitheliopathy that resembles ophthalmomyiasis interna occurs in approximately 10% of a large sample of the Chamorro population of Guam age 39 years or older; the rate is approximately 50% among those who have amyotrophic lateral sclerosis or Parkinsonism-dementia complex (lytico bodig). METHODS: Since publication of an earlier clinical report of affected patients, several of them have died of their neurologic disease, and their eyes were obtained for pathologic study. This is the first pathologic report of the retinal pigment epitheliopathy seen in the setting of amyotrophic lateral sclerosis/Parkinsonism-dementia complex of Guam and is based on examination of 13 eyes from 7 patients. RESULTS/CONCLUSION: Focal areas of attenuation of the retinal pigment epithelium in association with a reduced amount of intracellular pigment correlated with the funduscopic and gross appearance. No larvae were seen, and there was no evidence of inflammation. The pathogenesis of this pigment epitheliopathy remains undetermined.

Amyotrophic Lateral Sclerosis↗