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Biomedical subjects

E M Graham

Publications and source records attributed to E M Graham.

At least 37 records · Page 2Linked to original sources
PubMed2001

Early Neurodegeneration after Hypoxia-Ischemia in Neonatal Rat Is Necrosis while Delayed Neuronal Death Is Apoptosis.

We used silver staining to demonstrate neuronal cell body, axonal, and terminal degeneration in brains from p7 rat pups recovered for 0, 1.5, 3, 6, 24, 48, 72 h, and 6 days following hypoxia-ischemia. We found that initial injury is evident in ipsilateral forebrain by 3 h following hypoxia-ischemia, while injury in ventral basal thalamus develops at 24 h. A secondary phase of injury occurs at 48 h in ipsilateral cortex, but not until 6 days in basal ganglia. Initial injury in striatum and cortex is necrosis, but in thalamus the neurodegeneration is primarily apoptosis. Degeneration also occurs in bilateral white matter tracts, and in synaptic terminal fields associated with apoptosis in regions remote from the primary injury. These results show that hypoxia-ischemia in the developing brain causes both early and delayed neurodegeneration in specific systems in which the morphology of neuronal death is determined by time, region, and potentially by patterns of neuronal connectivity.

Animals↗
PubMed2001

Intravitreal triamcinolone for uveitic cystoid macular edema: an optical coherence tomography study.

PURPOSE: To investigate the use of intravitreal injection of triamcinolone acetonide (TA) for the treatment of refractory uveitic cystoid macular edema (CME). DESIGN: Prospective, nonrandomized, self-controlled comparative trial. PARTICIPANTS: Six patients with chronic CME resistant to treatment with systemic steroids, orbital floor steroids, and cyclosporine A. Three patients were followed for more than 1 year, and the other three for between 3 and 9 months. INTERVENTION: Injection of 2 mg of TA into the vitreous cavity. TESTING: Optical coherence tomography scanning of the fovea before and after injection and logarithmic minimal angle of resolution visual acuity. MAIN OUTCOME MEASURES: Visual acuity, retinal thickness, cystoid space height, and intraocular pressure. RESULTS: There was complete anatomic resolution of CME in five of the six cases within 1 week after injection. Cystoid spaces began to return between 6 weeks and 3 months after injection. Two patients with longer term follow-up responded to further orbital floor steroid injection and had no CME 1 year later. One patient had raised intraocular pressure develop, requiring a trabeculectomy. Mean improvement in visual acuity after 12 months was 0.27 (range, 0.14-0.42). CONCLUSIONS: Complete anatomic and, to some extent, functional recovery can be induced by intravitreal TA despite long-term refractory inflammatory CME. Optical coherence tomography aids in the management of these cases.

Adult↗
PubMed2001

Effect of gestational age and hypoxia on activity of ribonucleic acid polymerase in fetal guinea pig brain.

OBJECTIVE: The aim of this study was to determine the effect of gestational age and hypoxia on the activity of ribonucleic acid polymerase in fetal guinea pig brain. STUDY DESIGN: Fetal cerebral cortical neuronal nuclei were isolated at 40, 50, and 60 days (term) of gestation to determine the effect of gestational age on the activity of ribonucleic acid polymerase I, II, and III. Pregnant guinea pigs at 60 days' gestation were randomly assigned to a normoxic or hypoxic group to determine the effect of hypoxia on ribonucleic acid polymerase activity. The fetal neuronal nuclei were pooled from 6 pregnant animals in each group. In the normoxic group the pregnant guinea pigs were exposed to room air before delivery. In the hypoxic group delivery occurred after the pregnant guinea pig had been exposed to 7% oxygen for 60 minutes. The fetuses were delivered by cesarean, and the fetal cerebral cortical neuronal nuclei were isolated immediately. Ribonucleic acid polymerase activity was determined with nuclei suspended in a buffer containing adenosine triphosphate, guanosine triphosphate, cytidine triphosphate, and tritiated uridine triphosphate. Dactinomycin (actinomycin D) and polydeoxyadenylic-thymidylic acid were used to determine the activity of bound and free ribonucleic acid polymerase. alpha-Amanitin was used to determine the activity of ribonucleic acid polymerase II. RESULTS: The activity of total (bound and free) ribonucleic acid polymerase I and III increased from 85.4 +/- 9.4 fmol of tritiated uridine triphosphate incorporated per milligram of protein per hour at 40 days' gestation to 233.3 +/- 82.1 fmol at 50 days and to 343.4 +/- 231.6 fmol at 60 days (P =.02). Total ribonucleic acid polymerase II activity increased from 19.9 +/- 6.0 fmol of tritiated uridine triphosphate incorporated per milligram of protein per hour at 40 days to 123.8 +/- 53.0 fmol at 50 days and to 200.9 +/- 77.8 fmol at 60 days (P <.01). In the term fetal guinea pig brain the activity of bound ribonucleic acid polymerase I and III decreased from 116.8 +/- 107.2 fmol of tritiated uridine triphosphate incorporated per milligram of protein per hour under normoxic conditions to 92.8 +/- 76.0 fmol in hypoxic fetal brain, a decrease of 20.5%. Free ribonucleic acid polymerase I and III activity decreased from 199.2 +/- 115.2 fmol of tritiated uridine triphosphate incorporated per milligram of protein per hour in normoxic fetal brain to 132.0 +/- 66.4 fmol in hypoxic fetal brain, a decrease of 33.8%. Free ribonucleic acid polymerase II activity decreased from 62.4 +/- 70.4 fmol of tritiated uridine triphosphate incorporated per milligram of protein per hour in normoxic fetuses to 13.6 +/- 9.6 fmol in hypoxic fetal brain, a decrease of 78.2%. In contrast, however, in term fetal guinea pig brain, bound ribonucleic acid polymerase II activity increased from 8.0 +/- 10.4 fmol of tritiated uridine triphosphate incorporated per milligram of protein per hour under normoxic conditions to 35.2 +/- 8.8 fmol in hypoxic fetal brain, an increase of 340% (P <.01). CONCLUSION: The activity of ribonucleic acid polymerases I, II, and III increases throughout the latter half of gestation, from 40 to 60 days, in the fetal guinea pig brain. Hypoxia in utero is associated with a decrease in ribonucleic acid polymerase I and III activity. Although hypoxia is associated with a decrease in free ribonucleic acid polymerase II activity, we observed a marked increase in bound ribonucleic acid polymerase II activity, which may represent a hypoxia-induced alteration of gene expression.

Amanitins↗
PubMed2001

Acute retinal necrosis in children caused by herpes simplex virus.

PURPOSE: To report the diagnosis, management, and outcome of acute retinal necrosis syndrome in children. METHOD: Case series of three consecutive children aged 11 years and younger who were diagnosed with acute retinal necrosis. In addition to full ocular and systemic examinations, the children underwent vitreous biopsy (Patients 1 and 2) or aqueous tap (Patient 3) for polymerase chain reaction analysis. RESULTS: All patients had unilateral retinitis that was associated with preexisting chorioretinal scars, and two patients (Patients 1 and 3) had concurrent extraocular central nervous system abnormalities. Intraocular herpes simplex virus was detected in all three children: Type 1 in Patient 1 and Type 2 in Patients 2 and 3. In addition, all three children had a history of extraocular herpes simplex virus infection. CONCLUSIONS: Retinitis associated with preexisting chorioretinal scars and detectable intraocular herpes simplex virus on polymerase chain reaction was common to all three children with acute retinal necrosis.

Acyclovir↗
PubMed2001

Urinary neopterin in idiopathic retinal vasculitis.

AIMS: To determine whether urinary neopterin:creatinine (UNC) ratios relate to disease activity in idiopathic retinal vasculitis (RV). METHODS: 18 patients with RV were prospectively recruited into a year long longitudinal study. Patients collected first morning urine samples on a weekly basis and on the same day completed a diary which documented their subjective view of RV activity and any concurrent infection. They were examined in clinic on a 6-8 weekly basis and an objective assessment was made of RV disease activity. 14 healthy controls collected urine samples in the same way. RESULTS: UNC ratios were significantly higher in patients than in controls (p=0.004, Mann-Whitney U test). UNC ratios were significantly higher when, according to their diaries, the patients had a subjective flare up of RV (p=0.001, Mann-Whitney U test). Subjective increased RV activity occurred more often when the patients had a concurrent infection (p<0.0001, chi(2) test). There was no significant difference in the UNC ratio between objective clinical relapse and non-relapse of RV. There was moderate agreement between the clinical assessment and patients' subjective impression of RV activity (kappa=0.48). CONCLUSIONS: Higher neopterin levels reflect cell mediated disease that occurs in RV, but UNC ratios are not recommended as a means of monitoring clinical disease activity in RV.

Adult↗
PubMed2000

Comparison between optical coherence tomography and fundus fluorescein angiography for the detection of cystoid macular edema in patients with uveitis.

PURPOSE: To compare optical coherence tomography (OCT) with fundus fluorescein angiography (FFA) for the detection of cystoid macular edema (CME) in patients with uveitis. DESIGN: Prospective comparative observational series. PARTICIPANTS: One hundred twenty-one eyes of 58 patients with uveitis of varied causes (seven patients were studied twice). TESTING: Patients with suspected CME underwent OCT scanning followed by FFA at the same visit. MAIN OUTCOME MEASURES: Detection and distribution of macular edema. RESULTS: One hundred eight eyes had similar results on both OCT and FFA in that 67 eyes had CME and 41 eyes had no CME. In 10 eyes subretinal fluid was detected on OCT but not FFA. Five of these eyes had CME on FFA but not OCT. Three other eyes had CME that was detected by FFA but not by OCT. Compared with FFA, the OCT sensitivity for detecting CME was 96% (including the eyes with subretinal fluid), and the OCT specificity was 100%. CONCLUSIONS: OCT is as effective at detecting CME as is FFA but is superior in demonstrating axial distribution of fluid.

Exudates and Transudates↗
PubMed2000

Hypopyon uveitis and iris nodules in non-Hodgkin's lymphoma: ocular relapse during systemic remission.

We report the case history of a patient with peripheral non-Hodgkin's lymphoma in systemic remission, who presented with a pseudohypopyon and iris nodules. Iris biopsy confirmed the presence of intraocular tumour, which subsequently responded to orbital radiation. Ocular remission, however, was soon followed by a systemic relapse, suggesting that the eye may act as a sanctuary site for tumour cells during chemotherapy, and that cells may metastasize from the eye back to the periphery during systemic remission.

Adult↗
PubMed1999

The ocular and systemic prognosis of patients presenting with sarcoid uveitis.

PURPOSE: To describe the visual and systemic outcomes in patients presenting with sarcoid uveitis. METHODS: Seventy-five patients with definite or presumed sarcoid uveitis were followed up for a median of 4 years. The patients came from a primary ophthalmic referral centre and a specialist uveitis centre. The prognostic value of demographic and clinical features at the onset of disease were studied. Baseline and outcome variables were analysed by survival analysis. RESULTS: After 10 years, 54% of patients retained normal visual acuity and 4.6% had lost vision to less than 6/36 in both eyes. Fifty-one per cent required oral steroids for uveitis and a further 11% needed additional immunosuppressants. Twenty-one per cent of patients had undergone a surgical procedure. At the onset of uveitis the lung was the most common organ involved (35%). After 10 years follow-up disease spread to other organs in 13 patients (17%); in 8 of 13 patients this was the central nervous system. The only outcome associated with baseline variables was bilateral visual loss, which was more likely in those over 40 years at presentation (p = 0.004). CONCLUSIONS: The ocular prognosis of sarcoid uveitis is unrelated to the extent of disease at onset. Patients with extraocular disease fared no differently from those with isolated ocular disease. Patients with sarcoid uveitis are at risk of neurological involvement for at least 15 years.

Adolescent↗
PubMed1999

Ocular manifestations of rheumatologic disorders.

In the past year, advances have been made in our understanding of the genetics of Behçet disease. Indocyanine green angiography has allowed us to look at the pathologic changes seen in Behçet disease and sarcoidosis in more detail. New steroid-sparing treatment strategies for the control of ocular inflammatory disease are becoming better understood and better used, and their applications in sarcoidosis and juvenile chronic arthritis are reviewed here. The role of antiphospholipid antibodies in ocular disease has received attention, particularly in the context of systemic lupus erythematosus. Outcomes in HLA-B27-positive patients with uveitis and in ocular disease associated with the systemic vasculitides are discussed here, and scalp necrosis in giant-cell arteritis is reviewed.

Diagnosis, Differential↗
PubMed1999

The pituitary-adrenal axis in idiopathic retinal vasculitis.

AIMS: To determine whether patients with idiopathic retinal vasculitis have altered production of cortisol and dehydroepiandrosterone sulphate (DHEA-S), and whether differences in these variables occur between those who are sensitive (SS) and resistant (SR) to steroids. METHODS: 20 patients with retinal vasculitis (off treatment) and 10 control subjects were prospectively recruited. Morning cortisol and DHEA-S levels were measured, and cortisol secretion rates and short synacthen tests (SST) carried out in patients before treatment, when on prednisolone 20 mg/day, and in controls. RESULTS: There were no differences in any variables between patients and controls. For retinal vasculitis patients pretreatment, the SST was lower in SR patients (p=0.02). More of the SR patients had ischaemic retinal vasculitis ( p<0.001). CONCLUSIONS: Cortisol and DHEA-S are not involved in the pathogenesis of retinal vasculitis. SR in retinal vasculitis may be associated with a defective hypothalamic-pituitary-adrenal axis.

Adult↗
PubMed1999

Symptomatic anterior uveitis in HIV-positive patients.

Symptomatic anterior uveitis is rare in HIV-positive patients. The uveitis associated with cytomegalovirus retinitis (CMVR), the commonest ocular manifestation in AIDS patients, is rarely symptomatic and patients do not typically present with a red painful eye in conjunction with blurred vision. In this article we report 12 cases of symptomatic anterior uveitis in HIV-positive patients and discuss the aetiology. The case notes of all HIV-positive patients presenting to the eye department with symptoms of uveitis over a 4-year period were studied retrospectively. The notes were analysed for age, sex, race, risk factors of HIV, features of the uveitis, concurrent disease and CD4 counts. Only 12 patients were identified to have symptomatic uveitis out of a total 172 patients. There were 9 males and 3 females with an average age of 35 years. None of these patients were taking either rifabutin, protease inhibitors or cidofovir. Seven out of the 12 patients had granulomatous uveitis. Of these 7 patients, 4 had CD4 counts over 200 and no other concurrent illness whilst 3 patients, with CD4 counts between 130-200, were subsequently found to have an underlying aetiology namely lymphoma, tuberculosis and candida. The remaining 5 patients, all with CD4 counts below 40, had a history of systemic illness with herpes zoster preceding the onset of the uveitis. HIV-positive patients with symptoms of uveitis do not have active CMVR and the ophthalmologist must search for other causes such as tuberculosis or lymphoma in those with granulomatous uveitis or herpes zoster in those with non-granulomatous uveitis. The CD4 count may be helpful.

AIDS-Related Opportunistic Infections↗
PubMed1998

The role of azathioprine in the management of retinal vasculitis.

PURPOSE: Azathioprine is commonly used as a second-line immunosuppressive agent in the management of patients with retinal vasculitis. The aim of this study was to determine the efficacy of azathioprine by evaluating its effect on relapse rate, clinical outcome and maintenance steroid dose. METHODS: A retrospective analysis was performed of 34 patients presenting over 15 years to the Medical Eye Unit at St Thomas Hospital. Relapse rate, steroid dosage, inflammatory score and visual acuity were assessed before and during treatment with azathioprine. RESULTS: Thirty-four patients (23 male) aged 17-70 years (median 41.4, median 38) were enrolled. Fifteen had idiopathic retinal vasculitis, 12 had Behçet's disease, 2 sarcoidosis, 2 sympathetic ophthalmia, 1 birdshot retinochoriodopathy, 1 Still's disease and 1 Harada's disease. The principal indications for azathioprine treatment were uncontrolled disease despite appropriate steroid therapy in 28 patients (82%) or to permit a decrease in steroid dosage in 6 patients (18%). Frequency of relapse was assessed in 10 patients whose pre-treatment and treatment periods with azathioprine were of 1 year or greater. All were found to have a decreased relapse rate. In 60%, reduction of steroid dosage was achieved. Ocular inflammatory score decreased in 56% of eyes and visual acuity was improved or maintained in 64%. In 8 patients treatment had to be stopped due to side effects. CONCLUSION: Within the limitations of a retrospective study, we found azathioprine when used in combination with systemic steroids to be most effective at reducing the relapse rate of retinal vasculitis, but only partially effective in allowing a reduction in steroid dosage.

Adolescent↗