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Biomedical subjects

E T Cunningham

Publications and source records attributed to E T Cunningham.

At least 19 recordsLinked to original sources
PubMed1999

Mooren ulcer in South India: serology and clinical risk factors.

PURPOSE: To investigate the rate of undiagnosed rheumatologic diseases and hepatitis C infection among patients with the clinical diagnosis of Mooren ulcer seen at Aravind Eye Hospital, Madurai, South India. METHODS: Twenty-one patients with the clinical diagnosis of Mooren ulcer and 44 control patients underwent a complete ophthalmic history and examination, as well as serologic testing for antinuclear antibodies, rheumatoid factor, antineutrophil cytoplasmic antibodies, herpes simplex virus 1 antibodies, and hepatitis C virus antibodies. RESULTS: There were no statistically significant differences in the rates of seropositivity for antinuclear antibodies, rheumatoid factor, antineutrophil cytoplasmic antibodies, herpes simplex virus 1 antibodies, and hepatitis C virus antibodies between patients with Mooren ulcer and control patients. Two patients with Mooren ulcer and four control patients were found to have a rheumatoid factor titer of greater than 1:20. One of the control patients, but none of the patients with Mooren ulcer, was found to have serologic evidence of hepatitis C infection. A history of corneal trauma, surgery, or infection was reported by 68% of patients with Mooren ulcer, compared with 20% of control patients (P < .001). Among patients with Mooren ulcer, bilateral disease occurred in 37% of patients, visual acuity was reduced to light perception in 15% of eyes, and perforation occurred in 19% of eyes. CONCLUSIONS: Nineteen (90%) of 21 patients with the clinical diagnosis of Mooren ulcer were found to have no evidence of an underlying rheumatologic disease by history, examination, or serologic testing, and none was seropositive for hepatitis C. However, patients with Mooren ulcer were more likely than control patients to report a history of corneal trauma, surgery, or infection.

Adolescent↗
PubMed1999

Vogt-Koyanagi-Harada syndrome after cutaneous injury.

OBJECTIVE: To describe three patients who developed Vogt-Koyanagi-Harada syndrome (VKH) after cutaneous injury. DESIGN: Retrospective case series. PARTICIPANTS: Three patients seen in the uveitis clinic at Aravind Eye Hospital and Postgraduate Institute of Ophthalmology, Madurai, India, participated. MAIN OUTCOME MEASURES: The history, evaluation, and management of the three patients were summarized. RESULTS: Three patients developed VKH syndrome shortly after cutaneous injury. In each case, the affected area of skin became vitiliginous on healing and simultaneous with the onset of ocular symptoms. One patient developed additional ectopic areas of vitiligo. All three patients developed chronic, bilateral, diffuse uveitis, one associated with an exudative retinal detachment and two with Dalen-Fuchs-like nodules. Well-recognized complications of VKH syndrome that occurred in the authors' patients included geographic atrophy of the retinal pigment epithelium (3 of 3), cataract (3 of 3), and glaucoma (1 of 3). Ocular inflammation was well controlled in each patient with local or systemic corticosteroids or both. In one patient, the area of vitiligo showed increased pigmentation in response to systemic corticosteroid treatment. CONCLUSIONS: Vogt-Koyanagi-Harada syndrome may follow cutaneous injury, supporting the notion that this disorder may result from systemic sensitization to shared melanocytic antigens.

Adult↗
PubMed1999

The proto-oncogene Cot kinase participates in CD3/CD28 induction of NF-kappaB acting through the NF-kappaB-inducing kinase and IkappaB kinases.

The proto-oncogene Cot/Tpl-2 encodes a MAP3K-related serine-threonine kinase. Expression of wild type Cot activates the IkappaB kinases (IKK) leading to induction of NF-kappaB. Conversely, expression of kinase-deficient Cot inhibits CD3/CD28 but not TNF alpha induction of NF-kappaB. These findings suggest the selective involvement of Cot/Tpl-2 or a closely related kinase in the CD3/CD28 costimulatory pathway leading to induced nuclear expression of NF-kappaB. In contrast, a kinase-deficient mutant of the NF-kappaB-inducing kinase (NIK) inhibits both CD3/CD28 and TNF alpha signaling, indicating that these pathways converge at or prior to the action of NIK. Consistent with such a sequential function of these two kinases, Cot physically assembles with and phosphorylates NIK in vivo.

CD28 Antigens↗
PubMed1999

Haemophilus influenzae associated scleritis.

AIMS: To describe the clinical course and treatment of Haemophilus influenzae associated scleritis. METHODS: Retrospective case series. RESULTS: Three patients developed scleritis associated with ocular H influenzae infection. Past medical history, review of systems, and laboratory testing for underlying collagen vascular disorders were negative in two patients. One patient had arthritis associated with an antinuclear antibody titre of 1:160 and a Westergren erythrocyte sedimentation rate of 83 mm in the first hour. Each patient had ocular surgery more than 6 months before developing scleritis. Two had cataract extraction and one had strabismus surgery. Nodular abscesses associated with areas of scleral necrosis were present in each case. Culture of these abscesses revealed H influenzae in all patients. Treatments included topical, subconjunctival, and systemic antibiotics. Scleral inflammation resolved and visual acuity improved in each case. CONCLUSION: H influenzae infection may be associated with scleritis. Accurate diagnosis and treatment may preserve ocular integrity and good visual acuity.

Aged↗
PubMed1999

Tuberculous neuroretinitis.

OBJECTIVES: To describe a patient with tuberculous neuroretinitis. MATERIALS AND METHODS: Retrospective case report. RESULTS: We describe a 43-year-old otherwise asymptomatic woman with a known exposure to tuberculosis who had unilateral optic disc edema and a partial macular star (neuroretinitis). This was followed approximately 1 year later by the development of an exudative retinal detachment in the setting of bilateral multifocal choroiditis. Laboratory testing revealed a marked positive cutaneous reaction to purified protein derivative (PPD). Treatment with antituberculosis medicine alone resulted in prompt resolution of the choroidal infiltrates and complete flattening of the exudative detachment. CONCLUSIONS: Tuberculosis should be considered in the differential diagnosis for patients with neuroretinitis.

Adult↗
PubMed1998

Familial Axenfeld-Rieger anomaly, atrial septal defect, and sensorineural hearing loss: a possible new genetic syndrome.

OBJECTIVE: To describe the clinical and ocular histopathological findings in multiple members of a family with congenital Axenfeld-Rieger anomaly, atrial septal defect, and sensorineural hearing loss. METHODS: We performed a retrospective review of the medical charts and the ocular histopathological material of multiple members of a family. RESULTS: Congenital Axenfeld-Rieger anomaly and glaucoma were inherited by both the proband and her male half-sibling from a phenotypically positive father and 2 different phenotypically negative mothers, suggesting an autosomal dominant inheritance. The proband's male half-sibling and her father also had atrial septal defects and sensorineural hearing loss. The proband's paternal grandmother had severe glaucoma. Histopathological analysis of blind, painful eyes removed from the proband's father and paternal grandmother showed incomplete development of the anterior chamber angle with iris stromal hypoplasia, prominent posterior embryotoxon with iris adhesions, and abnormal position and insertion of the ciliary muscles. CONCLUSIONS: This is the first description of coexisting Axenfeld-Rieger anomaly, atrial septal defect, and sensorineural hearing loss in multiple members of a single family. The iris, trabecular meshwork, and large portions of the cardiac intraventricular septum all arise from neural crest anlagen, thus supporting the notion that anterior segment dysgenesis represents a developmental disorder of the neural crest.

Abnormalities, Multiple↗
PubMed1998

Intraocular coccidioidomycosis diagnosed by skin biopsy.

OBJECTIVE: To describe ocular findings in 2 patients with disseminated coccidioidomycosis diagnosed by skin biopsy. METHODS: The clinical and histopathologic findings of the 2 patients were reviewed retrospectively. RESULTS: One patient had a unilateral, granulomatous iridocyclitis with multiple iris nodules and a large vascularized anterior chamber mass, in the setting of pulmonary, cutaneous, and skeletal infection by Coccidioides immitis. The second patient developed papilledema and multifocal chorioretinitis accompanied by pulmonary, cutaneous, and meningeal C immitis infection. In each case, examination of the skin biopsy specimen revealed C immitis spherules. Treatments included local and systemic amphotericin B and oral fluconazole. CONCLUSIONS: Although rare, intraocular involvement can occur in the setting of disseminated coccidioidomycosis. A thorough systemic evaluation and biopsy of suspicious skin lesions can aid in the diagnosis.

Adult↗
PubMed1998

Cystoid macular edema associated with cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome.

PURPOSE: To describe the clinical and fluorescein angiographic appearance of cystoid macular edema associated with cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome (AIDS). METHODS: We retrospectively examined the clinical and photographic records of four patients with AIDS and cytomegalovirus retinitis who developed cystoid macular edema. RESULTS: Seven eyes of four patients with AIDS and cytomegalovirus retinitis experienced decreased vision associated with cystoid macular edema. Vitreous inflammation was mild in each patient. In all eyes, the retinitis involved zone 1, and in all but one eye, the cytomegalovirus retinitis was inactive. In one eye, the cystoid macular edema was worsened by formation of a dense juxtafoveal epiretinal membrane. CONCLUSIONS: Although infrequently recognized, cystoid macular edema can cause visual loss in patients with AIDS and cytomegalovirus retinitis. Fluorescein angiography should be considered in any patient with cytomegalovirus retinitis and unexplained visual loss.

AIDS-Related Opportunistic Infections↗
PubMed1998

Complex limbal choristomas in linear nevus sebaceous syndrome.

OBJECTIVE: This study aimed to describe the clinical and histopathologic findings in four patients with complex limbal choristomas associated with linear nevus sebaceous syndrome (LNSS), a rare disorder including nevus sebaceous, seizures, and mental retardation, and often accompanied by ocular anomalies. DESIGN: Small observational case series. METHODS: A retrospective review of the clinical and histopathologic records of four patients. RESULTS: Each of four patients had complex limbal choristomas in the setting of clinical and histopathologic LNSS. The limbal choristomas were multiple in three patients and bilateral in two patients. Most choristomas involved the superotemporal limbus (6 of 10), although nasal (3 of 10) and inferior (1 of 10) limbal tumors also were present. Three patients had significant corneal astigmatism or involvement of the central cornea requiring surgical removal of their choristomas, one accompanied by a lamellar keratoplasty and another accompanied by two consecutive penetrating keratoplasties. Each graft eventually vascularized, reducing vision. One patient's vision was limited by amblyopia and another by occipital cortical dysgenesis with visual impairment. Histopathologic examination of the excised choristomas showed foci of lacrimal gland (3 of 4 patients), adipose tissue (3 of 4), neural tissue (1 of 4), cartilage (1 of 4), lymphoid follicles (1 of 4), skin adnexal tissue (1 of 4), and smooth muscle (1 of 4). Other associated ocular findings included an eyelid mass (1 of 4), colobomas of the eyelid (3 of 4), colobomas of the choroid and retina (2 of 4), nonparalytic strabismus (2 of 4), scleral ectasia (1 of 4), partial oculomotor palsy with ptosis and anisocoria (1 of 4), microphthalmia (1 of 4), hypertelorism (1 of 4), and cortical visual impairment (1 of 4). CONCLUSIONS: Complex limbal choristomas, although rare, can occur in the setting of LNSS and can be associated with multiple ocular and systemic abnormalities. Visual prognosis appears poor in most cases despite aggressive management.

Child, Preschool↗
PubMed1998

Vogt-Koyanagi-Harada syndrome in children.

PURPOSE: To describe the clinical presentation and natural history of Vogt-Koyanagi-Harada (VKH) syndrome in children, an often unrecognized cause of pediatric uveitis. METHODS: We performed a clinic-based cross-sectional survey and retrospective review of pediatric patients with VHK seen in the uveitis clinic at the Aravind Eye Hospital, Madurai, India, between January 1993 and December 1995. RESULTS: A total of 98 patients with VKH syndrome were seen in the uveitis clinic at the Aravind Eye Hospital during the three years covered by the survey, of whom three (about 3%, with an approximate incidence of 1 case/year) were children 16 years of age or younger. Initial symptoms included eye pain, redness, and blurred vision in all three patients. Headache and dysacusis accompanied the onset of visual symptoms in one patient. Each patient eventually developed areas of vitiligo and poliosis, although these signs were not present at the time of presentation in any of our patients. Signs of active uveitis included anterior chamber and vitreous inflammation, optic disc edema, exudative retinal detachments, and Dalen-Fuchs'-like nodules. All three patients developed cataracts, two developed retinal pigment epithelium atrophy, and one developed glaucoma. Each patient responded well, with good visual recovery, to topical and/or systemic corticosteroids. CONCLUSIONS: Although frequently unrecognized, VKH syndrome may affect children. As with adults, visual loss occurs most typically as the result of cataract, glaucoma, or retinal pigment epithelium atrophy.

Atrophy↗
PubMed1998

Molecular determinants of NF-kappaB-inducing kinase action.

NF-kappaB corresponds to an inducible eukaryotic transcription factor complex that is negatively regulated in resting cells by its physical assembly with a family of cytoplasmic ankyrin-rich inhibitors termed IkappaB. Stimulation of cells with various proinflammatory cytokines, including tumor necrosis factor alpha (TNF-alpha), induces nuclear NF-kappaB expression. TNF-alpha signaling involves the recruitment of at least three proteins (TRADD, RIP, and TRAF2) to the type 1 TNF-alpha receptor tail, leading to the sequential activation of the downstream NF-kappaB-inducing kinase (NIK) and IkappaB-specific kinases (IKKalpha and IKKbeta). When activated, IKKalpha and IKKbeta directly phosphorylate the two N-terminal regulatory serines within IkappaB alpha, triggering ubiquitination and rapid degradation of this inhibitor in the 26S proteasome. This process liberates the NF-kappaB complex, allowing it to translocate to the nucleus. In studies of NIK, we found that Thr-559 located within the activation loop of its kinase domain regulates NIK action. Alanine substitution of Thr-559 but not other serine or threonine residues within the activation loop abolishes its activity and its ability to phosphorylate and activate IKKalpha. Such a NIK-T559A mutant also dominantly interferes with TNF-alpha induction of NF-kappaB. We also found that ectopically expressed NIK both spontaneously forms oligomers and displays a high level of constitutive activity. Analysis of a series of NIK deletion mutants indicates that multiple subregions of the kinase participate in the formation of these NIK-NIK oligomers. NIK also physically assembles with downstream IKKalpha; however, this interaction is mediated through a discrete C-terminal domain within NIK located between amino acids 735 and 947. When expressed alone, this C-terminal NIK fragment functions as a potent inhibitor of TNF-alpha-mediated induction of NF-kappaB and alone is sufficient to disrupt the physical association of NIK and IKKalpha. Together, these findings provide new insights into the molecular basis for TNF-alpha signaling, suggesting an important role for heterotypic and possibly homotypic interactions of NIK in this response.

Amino Acid Sequence↗
PubMed1998

Human T-cell leukemia virus type 1 Tax induction of NF-kappaB involves activation of the IkappaB kinase alpha (IKKalpha) and IKKbeta cellular kinases.

Tax corresponds to a 40-kDa transforming protein from the pathogenic retrovirus human T-cell leukemia virus type 1 (HTLV-1) that activates nuclear expression of the NF-kappaB/Rel family of transcription factors by an unknown mechanism. Tax expression promotes N-terminal phosphorylation and degradation of IkappaB alpha, a principal cytoplasmic inhibitor of NF-kappaB. Our studies now demonstrate that HTLV-1 Tax activates the recently identified cellular kinases IkappaB kinase alpha (IKKalpha) and IKKbeta, which normally phosphorylate IkappaB alpha on both of its N-terminal regulatory serines in response to tumor necrosis factor alpha (TNF-alpha) and interleukin-1 (IL-1) stimulation. In contrast, a mutant of Tax termed M22, which does not induce NF-kappaB, fails to activate either IKKalpha or IKKbeta. Furthermore, endogenous IKK enzymatic activity was significantly elevated in HTLV-1-infected and Tax-expressing T-cell lines. Transfection of kinase-deficient mutants of IKKalpha and IKKbeta into either human Jurkat T or 293 cells also inhibits NF-kappaB-dependent reporter gene expression induced by Tax. Similarly, a kinase-deficient mutant of NIK (NF-kappaB-inducing kinase), which represents an upstream kinase in the TNF-alpha and IL-1 signaling pathways leading to IKKalpha and IKKbeta activation, blocks Tax induction of NF-kappaB. However, plasma membrane-proximal elements in these proinflammatory cytokine pathways are apparently not involved since dominant negative mutants of the TRAF2 and TRAF6 adaptors, which effectively block signaling through the cytoplasmic tails of the TNF-alpha and IL-1 receptors, respectively, do not inhibit Tax induction of NF-kappaB. Together, these studies demonstrate that HTLV-1 Tax exploits a distal part of the proinflammatory cytokine signaling cascade leading to induction of NF-kappaB. The pathological alteration of this cytokine pathway leading to NF-kappaB activation by Tax may play a central role in HTLV-1-mediated transformation of human T cells, clinically manifested as the adult T-cell leukemia.

Adult↗