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Biomedical subjects

E T Cunningham

Publications and source records attributed to E T Cunningham.

At least 73 records · Page 4Linked to original sources

Acute multifocal retinitis.

PURPOSE: To describe the clinical presentation, ophthalmoscopic and fluorescein angiographic findings, and natural history of 14 eyes in nine otherwise healthy, young-to-middle-age adults with idiopathic, acute, multifocal retinitis. METHODS: A retrospective review of the clinical and photographic records of nine patients. RESULTS: Five of the nine patients reported a flu-like illness 1 to 2 weeks before the onset of visual symptoms. Ophthalmoscopic findings included mild vitritis (11 of 14), mild optic nerve edema (seven of 14), macular star (two of 14) or localized neurosensory retinal detachment (two of 14) caused by adjacent focus of retinitis, and small branch-artery occlusion (two of 14). Fluorescein angiography showed early blocking hypofluorescence with late staining hyperfluorescence of all areas of retinitis. In patients with optic nerve edema, the disk showed late leakage. Specific tests for collagen vascular disorders, as well as systemic syphilis and toxoplasmosis titers, were negative in all patients. Five of six patients with histories of cat exposure tested negative for systemic Bartonella henselae antibodies. One patient with a history of cat exposure refused testing. Clinical courses were self-limited, with complete return of vision without treatment in all but one eye, which developed a juxtafoveal scar and localized traction retinal detachment in an area of prior retinitis. CONCLUSIONS: Idiopathic acute multifocal retinitis should be considered in any otherwise healthy, young-to-middle-age adult with acute loss of vision in the presence of multifocal retinitis, particularly when accompanied by an antecedent flu-like illness. Patients with idiopathic acute multifocal retinitis usually have favorable clinical course.

Acute Disease↗

Microsporidial keratoconjunctivitis in a patient without human immunodeficiency virus infection.

PURPOSE: To describe a case of microsporidial keratoconjunctivitis in a patient without human immunodeficiency virus (HIV) infection. METHODS: Case report. An epithelial corneal scraping from a woman with chronic bilateral keratoconjunctivitis was evaluated by Giemsa stain. RESULTS: Giemsa stain of an epithelial corneal scraping disclosed intracellular and extracellular spores characteristic of microsporidia. An HIV enzyme-linked immunosorbent assay (ELISA) test was negative. The signs and symptoms of the bilateral keratoconjunctivitis resolved after treatment with albendazole. CONCLUSION: Microsporidia may cause a chronic epithelial keratoconjunctivitis in the absence of HIV infection.

Adult↗

Localization of tumor necrosis factor receptor messenger RNA in normal and herpes simplex virus-infected mouse eyes.

PURPOSE: To investigate the distribution of p75 and p55 tumor necrosis factor receptor (TNFR) mRNA in normal mouse eyes and in mouse eyes acutely infected with McKrae strain herpes simplex virus (HSV). METHODS: In situ hybridization with antisense 35S-labeled riboprobes for p55 and p75 TNFR subtypes was used in uninfected and HSV-infected mouse eyes. Controls included the use of sense riboprobes and corneas inoculated with vehicle alone. RESULTS: In uninfected and infected mouse eyes, in situ hybridization produced an autoradiographic signal for mRNA, encoding both p75 and p55 over the corneal endothelium, iris, ciliary body, choroid, and arachnoid layers of the optic nerve sheath. In addition, the signal was observed over scattered cells at the vitreoretinal interface. Signal for p75, but not p55, was observed over cells in the retinal ganglion cell layer. Acute HSV infection was accompanied by an intense leukocytic infiltrate in the conjunctiva, the corneal subepithelium and stroma, the anterior and posterior chambers, the iris root and ciliary body, and the vitreous cavity. In this setting, increased p75 and p55 mRNA signal was correlated closely with the number and location of receptor-bearing white blood cells. Signal over control sections hybridized with sense p75 and p55 TNFR cRNA probes was comparable to background. Signal over control eyes inoculated with sterile vehicle showed slight increased signal in the immediate vicinity of the traumatic keratitis, but otherwise it was comparable to that observed in uninfected animals. CONCLUSIONS: The observed distribution of p75 and p55 TNFR mRNA in normal and acutely infected mouse eyes, and particularly over the heavily vascularized uveal tract and over cells at the vitreoretinal interface, supports a role for TNF as a mediator of intraocular inflammation, perhaps as a key regulator of the blood-ocular barrier.

Acute Disease↗

Acquired immunodeficiency syndrome--associated herpes simplex virus retinitis. Clinical description and use of a polymerase chain reaction--based assay as a diagnostic tool.

OBJECTIVES: To describe 2 patients with acquired immunodeficiency syndrome who experienced a rapidly progressive, bilateral retinitis due to herpes simplex virus (HSV) (1 case due to HSV type 1 [HSV-1] and 1 case due to HSV type 2 [HSV-2] and to present a novel diagnostic polymerase chain reaction (PCR)-based assay. METHODS: The presentation, clinical course, and diagnostic PCR-based assay used to make the diagnosis of HSV retinitis in 2 patients with acquired immunodeficiency syndrome are described. RESULTS: Both patients experienced a rapidly progressive, bilateral retinal necrosis associated with intraretinal hemorrhages and a diffuse vasculitis. The PCR-based assays demonstrated HSV DNA in the vitreous specimens from the 2 patients. Restriction analysis on the amplified DNA showed HSV-1 in 1 patient and HSV-2 in the second patient. The diagnosis was supported in both patients by the occurrence of a herpes simplex-like encephalitis, and in 1 patient by a positive vitreous culture. The HSV-1-associated vasculitis affected primarily the retinal arterioles, with marked capillary dropout and occlusion of larger arcade vessels. In contrast, the HSV-2-associated vasculitis affected the retinal veins more than the arterioles, and was associated with an exudative retinal detachment. CONCLUSIONS: To our knowledge, these are the first 2 patients with acquired immunodeficiency syndrome in whom HSV has been implicated as the sole cause of a rapidly progressing, necrotizing retinitis. Combined PCR and restriction analysis of vitreous samples from such patients is a useful and highly specific means of diagnosing HSV-1 and HSV-2 retinitis.

AIDS-Related Opportunistic Infections↗

Bone marrow transplantation retinopathy in the absence of radiation therapy.

PURPOSE: To describe a case of bone marrow transplantation retinopathy in a patient in the absence of prior radiation therapy. METHODS: Case report. RESULTS: Bilateral scotomata developed in a 26-year-old woman because of a retinal microvasculopathy two years after receiving an autologous bone marrow transplantation for acute promyelocytic leukemia. No prior radiation therapy had been given. CONCLUSIONS: Certain combinations of antimetabolites used during induction and transplantation may themselves be toxic to the retinal microvasculature. Patients who undergo bone marrow transplantation would benefit from regular and complete eye examinations, even in the absence of prior radiation therapy.

Adult↗

Central serous chorioretinopathy in patients with systemic lupus erythematosus.

PURPOSE: To describe three patients with systemic lupus erythematosus in whom ophthalmoscopic and fluorescein angiographic evidence of central serous chorioretinopathy developed. METHODS: The authors retrospectively reviewed the clinical and photographic records of three patients with systemic lupus erythematous in whom central serous chorioretinopathy developed. RESULTS: Ophthalmoscopic changes observed in these patients with systemic lupus erythematosus included discrete areas of clumping and mottling of the retinal pigment epithelium (RPE), focal RPE detachments, serous elevations of the neurosensory retina, and late subretinal fibrosis with scar formation. Fluorescein angiographic findings included transmission hypofluorescence and hyperfluorescence corresponding to focal RPE alterations, early punctate intense hyperfluorescence corresponding to RPE leaks with progressive filling of sub-RPE detachment spaces, and slow late filing of subretinal detachment spaces. CONCLUSION: Patients with systemic lupus erythematosus are at increased risk to have central serous chorioretinopathy develop. The pathogenetic implications for an association between systemic lupus erythematosus and central serous chorioretinopathy as well as the similarity to the chorioretinopathy seen with accelerated hypertension, pregnancy, hemodialysis, organ transplantation, and exogenous and endogenous hypercortisolism are discussed. Focal choroidal vasculature compromise with secondary dysfunction of overlying RPE cells is the proposed common mechanism.

Adult↗

Vogt-Koyanagi-Harada syndrome in a 4-year old child.

PURPOSE: We studied a case of severe bilateral Vogt-Koyanagi-Harada syndrome in a 4-year-old boy. METHODS: We evaluated the patient's clinical course. RESULTS: The patient had severe bilateral, nongranulomatous uveitis and mild uveitic glaucoma. Initial examination and laboratory evaluation failed to provide a diagnosis. The patient subsequently developed areas of vitiligo, alopecia, and poliosis, suggesting the diagnosis of Vogt-Koyanagi-Harada syndrome. This diagnosis was confirmed by the eventual development of bilateral neurosensory retinal detachments. Vision was lost despite aggressive therapy with corticosteroids and chlorambucil. CONCLUSION: Although uncommon, Vogt-Koyanagi-Harada may affect young children, and may be severe.

Alopecia↗

TrkA expression in the CNS: evidence for the existence of several novel NGF-responsive CNS neurons.

NGF acts as a neurotrophic factor by binding and activating its receptor on certain neuronal populations in the CNS and PNS. TrkA is a receptor for NGF. Recent findings in vitro indicate that this NGF-activated receptor tyrosine kinase transduces the NGF signal. To further define NGF actions in the CNS, we examined trkA expression in the adult rat brain. We found that trkA mRNA and immunoreactivity (IR) coincided in specific, defined neuronal populations in the forebrain and brainstem. In addition to cholinergic neurons in the basal forebrain and neostriatum, trkA expression was found in noncholinergic neurons in (1) the paraventricular anterior and reuniens thalamic nuclei, (2) the rostral and intermediate subnuclei of the interpeduncular nucleus (IPN), (3) scattered neurons in the ventrolateral and paramedian medulla, (4) the prepositus hypoglossal nucleus, and (5) the area postrema. NGF responsiveness was demonstrated for each of these populations. In contrast to trkA, p75NGFR was found only in a minority of NGF-responsive populations. Our data provide further evidence that expression of trkA marks NGF-responsive CNS neurons and suggests novel roles for NGF in the brain.

Animals↗

The relationship of efferent projections from the area postrema to vagal motor and brain stem catecholamine-containing cell groups: an axonal transport and immunohistochemical study in the rat.

The area postrema has been implicated as a major station for the processing of visceral sensory information, involved primarily in eliciting rapid homeostatic responses to fluid and nutrient imbalances. Yet the precise relationship of efferent projections from the area postrema to medullary motor and relay nuclei involved in such functions remains unclear. In this study, axonal transport and immunohistochemical techniques were used to investigate the relationship of efferent projections from the area postrema to vagal motor neurons and medullary catecholamine-containing cell groups in the rat. The results may be summarized as follows: (1) The area postrema gives rise to dense inputs to the commissural and medial parts of the nucleus of the solitary tract. Many of these projections are intimately associated with catecholamine-containing neurons in the A2 and C2 cell groups, including a particularly prominent input to a caudally placed cluster of adrenergic neurons (the C2d cell group) in the dorsal aspect of the medial part of the nucleus of the solitary tract. (2) The area postrema provides a dense input to the external lateral part of the parabrachial nucleus. (3) The area postrema does not project significantly to vagal motor neurons in either the dorsal motor nucleus or the nucleus ambiguus, although the possibility for inputs to distal dendrites of dorsal vagal motor neurons cannot be excluded. (4) En route to the parabrachial nucleus, axons of area postrema neurons traverse the regions of the A1, C1 and A5 cell groups, although these fibers make few arborizations, suggesting little functional contact. Together, these results suggest that sensory information received by the area postrema is dispatched to a restricted set of neurons in the commissural, medial, and dorsal parts of the nucleus of the solitary tract, most probably including catecholamine-containing cells in the A2, C2, and C2d cell groups, and to the external lateral portion of the parabrachial nucleus. The targets of area postrema projections are, in turn, in a position to effect adaptive changes in the activities of hypothalamic neurosecretory neurons, vagal motor neurons, and limbic forebrain regions in response to perturbations in fluid and nutrient homeostasis.

Animals↗

Inferior branch oculomotor nerve palsy. A case report.

We describe a 34-year-old man with acute, nontraumatic inferior branch oculomotor nerve palsy. Complete ophthalmologic, neurologic, and systemic examinations were otherwise normal. The oculomotor nerve palsy resolved, but the patient subsequently developed bilateral upper extremity numbness and painful dysesthesias in the distribution of the median nerves. These observations suggest that inferior branch oculomotor nerve palsy, although uncommon, may occur as part of a more generalized neurologic disorder, presumed in our patient to be either vasculitic or demyelinating in nature.

Acute Disease↗

Interleukin 1 receptors in the brain and endocrine tissues.

Immune activation is often accompanied by profound alterations in neurological and endocrine function, such as fever, increased somnolence, decreased appetite, activation of the hypothalamic-pituitary-adrenal axis, and suppression of the hypothalamic-pituitary-gonadal and hypothalamic-pituitary-thyroid axes. These well-recognized systemic responses to injury and infection have been attributed to circulating pro-inflammatory cytokines, the best characterized of which is interleukin 1 (IL-1). Here Emmett Cunningham and Errol De Souza discuss the mechanisms by which blood-borne IL-1 might affect such changes in the nervous and neuroendocrine systems.

Animals↗

Vagal reflexes referred from the upper aerodigestive tract: an infrequently recognized cause of common cardiorespiratory responses.

OBJECTIVE: To review the physiologic basis for normal and abnormal vagal reflexes arising from the pharynx, larynx, and esophagus, as well as the relevance of vagal reflexes to the pathogenesis of such clinically common cardiorespiratory responses as bradycardia, tachycardia, dysrhythmia, coronary angiospasm, bronchospasm, laryngospasm, prolonged apnea, and singultus (hiccups). DATA SOURCES: Pertinent articles and reviews were identified through a MEDLINE search (April 1966 to October 1991). Older studies and others not identified in the MEDLINE search were found through a manual search of the bibliographies of the retrieved articles. STUDY SELECTION: Experimental studies in both humans and animals, as well as case series and single case reports, were selected for evaluation and citation. In instances where a similar phenomenon was described in multiple independent reports, only studies that provided a novel finding or interpretation were cited. More authoritative book chapters and peer-reviewed summaries were also cited in support of commonly accepted principles. DATA EXTRACTION AND SYNTHESIS: Most of the clinical data are derived from case reports and small case series and are therefore anecdotal; equal weight was given to all such studies. Reports of conflicting observations or interpretations were clearly identified and were cited without exception. CONCLUSIONS: Stimulation of the upper aerodigestive tract can lead to clinically significant cardiorespiratory responses. Although the prevalence of and risk factors for such responses have not been established, we suggest that a pharyngeal, a laryngeal, or an esophageal source for abnormal cardiorespiratory responses be sought whenever a detailed clinical evaluation fails to reveal a cause, particularly when there are concurrent symptoms or signs of upper aerodigestive tract disease, such as dysphagia or gastroesophageal reflux.

Cardiovascular System↗

Distribution of type I interleukin-1 receptor messenger RNA in testis: an in situ histochemical study in the mouse.

The cytokine interleukin-1 (IL-1) has been reported to inhibit the hypothalamic-pituitary-gonadal axis, both through actions in brain and at the gonadal level. Recently, high affinity binding sites for 125I-recombinant human IL-1 alpha have been identified in the mouse testis with characteristics similar to those of type I IL-1 receptors on T lymphocytes and fibroblasts. The present study employed in situ hybridization histochemistry with 35S-labeled antisense cRNA probes derived from a murine type I IL-1 receptor cDNA to identify type I IL-1 receptor mRNA in the mouse testis. An intense signal was observed over interstitial cells, and over the cytoplasm of the epithelium of epididymal ducts, most prominently in the head region. The signal over seminiferous tubules, and over sperm cells within tubules and epididymal ducts, was comparable to background. This distribution of type I IL-1 receptor mRNA was similar to that recently reported for 125(I)I-IL-1-alpha binding sites, and supports evidence implicating IL-1 as a direct regulator of gonadal function.

Animals↗

In situ histochemical localization of type I interleukin-1 receptor messenger RNA in the central nervous system, pituitary, and adrenal gland of the mouse.

The cytokine interleukin-1 (IL-1) has a number of biologic activities, including pronounced effects on the nervous and neuroendocrine systems. In this study, in situ histochemical techniques were used to investigate the distribution of cells expressing type I IL-1 receptor mRNA in the CNS, pituitary, and adrenal gland of the mouse. Hybridization of 35S-labeled antisense cRNA probes derived from a murine T-cell IL-1 receptor cDNA revealed a distinct regional distribution of the type I IL-1 receptor, both in brain and in the pituitary gland. In the brain, an intense signal was observed over the granule cell layer of the dentate gyrus, over the entire midline raphe system, over the choroid plexus, and over endothelial cells of postcapillary venules throughout the neuraxis. A weak to moderate signal was observed over the pyramidal cell layer of the hilus and CA3 region of the hippocampus, over the anterodorsal thalamic nucleus, over Purkinje cells of the cerebellar cortex, and in scattered clusters over the external-most layer of the median eminence. In the pituitary gland, a dense and homogeneously distributed signal was observed over the entire anterior lobe. No autoradiographic signal above background was observed over the posterior and intermediate lobes of the pituitary, or over the adrenal gland. This study therefore provides evidence for discrete receptor substrates subserving the central effects of IL-1, thus supporting the notion that IL-1 acts as a neurotransmitter/neuromodulator in brain. It also supports studies suggesting that IL-1-mediated activation of the hypothalamic-pituitary-adrenal axis occurs primarily at the level of the brain and/or pituitary gland.

Adrenal Glands↗