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Biomedical subjects

E M Graham

Publications and source records attributed to E M Graham.

At least 19 recordsLinked to original sources
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↗
PubMed1998

Systemic corticosteroid therapy--side effects and their management.

The anti-inflammatory effects of corticosteroids cannot be separated from their metabolic effects as all cells use the same glucocorticoid receptor; therefore when corticosteroids are prescribed measures should be taken to minimise their side effects. Clearly, the chance of significant side effects increases with the dose and duration of treatment and so the minimum dose necessary to control the disease should be given. Before embarking on a long term course of corticosteroids the factors summarised in Table 1 should be considered. A full discussion with the patient is necessary in order to explain the benefits and risks of corticosteroid treatment. A patient information leaflet is now provided by the manufacturers of all systemic corticosteroid preparations. As emphasised by the recent publication by the Committee on the Safety of Medicines, advice to patients is the key to the safe use of long term systemic corticosteroids and it recommends discussing the following points with the patient: not to stop taking corticosteroids suddenly to see a doctor if they become unwell of the increased susceptibility to infections, especially chickenpox of the serious side effects that may occur to read and keep the patient information leaflet to always carry the steroid treatment card and to show it to any health professional involved in their treatment. In addition the following suggestions may help to minimise some side effects: a single morning dose early dietary modification--low calorie, low sodium, and high potassium awareness of possible errors of judgment on high doses. Once started on corticosteroids the patient should be regularly reviewed to assess the response to the treatment with adjustments to keep the dose at a minimum.

Adrenal Cortex Hormones↗
PubMed1998

Intrauterine growth retardation in a woman with primary hyperparathyroidism. A case report.

BACKGROUND: Primary maternal hyperparathyroidism leads to increased serum calcium levels, which suppress fetal parathyroid development, leading to hypocalcemia in the neonate. CASE: In a pregnant woman, hypercalcemia was observed to be related to a parathyroid adenoma that was surgically removed at 15 weeks' gestation. Subsequently, hypocalcemia developed, requiring calcium replacement. There was marked premature calcification of the placenta, noted to be grade 3 at 23 weeks, and this was thought to be related to the severe intrauterine growth retardation that later developed. Preterm premature rupture of membranes occurred at 33 weeks, and a growth-retarded neonate with a small, calcified placenta was delivered. CONCLUSION: Pregnancies associated with hyperparathyroidism have been found to be complicated by an increased incidence of spontaneous abortion, stillbirth and neonatal tetany. There may also be an increased risk of fetal intrauterine growth retardation. Serial ultrasonography to evaluate fetal growth and antenatal testing should be considered.

Adenoma↗
PubMed1997

Choroidal abnormalities in birdshot chorioretinopathy: an indocyanine green angiography study.

Birdshot chorioretinopathy is a rare inflammatory disorder with an insidious onset that can slowly progress to severe visual loss. The pathogenesis is unknown. This study used indocyanine green (ICG) angiography to investigate the degree of choroidal vascular involvement with progression of disease and to determine the nature of the birdshot lesions. Seven patients with birdshot chorioretinopathy had ICG angiography performed with a scanning laser ophthalmoscope at various stages of clinical disease. Results were compared with fluorescein fundal angiography (FFA). All large choroidal vessels appeared normal. The birdshot lesions were demonstrated with ICG but not with FFA and were represented by dark areas on ICG angiography. Typically these areas were bordered by large or medium-sized choroidal vessels and their appearance suggested small choroidal vessel hypoperfusion. In disease of recent onset, some lesions masked fluorescence from large underlying choroidal vessels possibly due to inflammatory choroidal infiltrates. In long-standing disease, the choroidal angioarchitecture was relatively normal within the birdshot lesions. This study of birdshot chorioretinopathy demonstrates abnormalities in the small choroidal vessels within the birdshot lesions. ICG angiography detects the birdshot lesions more readily than FFA and may be of benefit in assessing disease activity.

Adult↗
PubMed1997

A new method for studying the selective adherence of blood lymphocytes to the microvasculature of human retina.

PURPOSE: To develop a sensitive and reproducible technique for measuring the adherence of blood lymphocytes to vessel walls exposed in sections of human retina and for examining the role of lymphocyte and vascular adhesion molecules in these events. METHODS: Cryostat sections of human retina were overlaid with blood lymphocytes from healthy subjects, and experimental conditions were sought by which preferential attachment of the cells occurred to blood vessel walls in the retinal sections. Adherent lymphocytes were identified by staining with methyl green-thionine, and transected blood vessels were identified by their structure and by staining of basement membranes with periodic acid-Schiff. The adherence of enriched preparations of CD4+ (T-helper) and CD8+ (T-cytotoxic) lymphocytes, of interleukin-2 (IL-2)-activated cells, and of lymphocytes from patients with ocular Behçet's disease was examined. The distribution of adhesion molecules on retinal vessel walls was determined by immunohistochemistry, and the contribution of leukocyte integrins to lymphocyte binding was studied by blocking experiments with monoclonal antibodies. RESULTS: The optimal selectivity of blood lymphocyte attachment to retinal vessel walls occurred when purified lymphocytes were suspended in culture medium with 10% fetal calf serum and overlaid onto retinal sections for 30 minutes at 23 degrees C with gentle agitation. Under these conditions, 92% of the lymphocytes that adhered to the section were confined to the retinal microvasculature, and CD4+ T cells were more adherent than CD8+ T cells (P < 0.01). Prior exposure of normal lymphocytes to IL-2 enhanced their binding to retinal blood vessels, and lymphocytes from patients with Behçet's disease showed supranormal vascular adherence (P < 0.005). Many transected vessels stained positively for CD31; PECAM (mean 62%), CD54; ICAM-1 (mean 73%), CD62E; E-selectin (mean 35%), CD62P; P-selectin (mean 61%), and CD106; VCAM-1 (mean 42%). However, these vascular adhesion molecules occupied < 20% of the area of the blood vessel walls. Lymphocyte adhesion to the retinal vessels was more dependent on CD29 (the common chain of the beta 1 integrins) expression than either CD11a/CD18 or CD49d. CONCLUSIONS: This technique allows measurements to be made of lymphocyte adherence to vascular and nonvascular structures of retina ex vivo. Extension of this approach to the study of leukocyte adherence to sections of pathologic retina may be of clinical and experimental applicability in understanding mechanisms of retinal inflammation.

Antigens, CD↗
PubMed1996

Modification of the N-methyl-D-aspartate (NMDA) receptor in the brain of newborn piglets following hyperventilation induced ischemia.

The present study tests the hypothesis that cerebral ischemia induced by severe hypocapnia modifies the N-methyl-D-aspartate (NMDA) receptor/ion channel complex in the cerebral cortical cell membranes of newborn piglets. Studies were performed in six newborn piglets subjected to ischemic hypoxia induced by hyperventilation (PaCO2, 9-11 mmHg) for 1 h. Comparisons were made to a normoxic group on room air (n = 6). Following hyperventilation, phosphocreatine decreased 80%, but ATP remained unchanged. NMDA receptor activation was determined by measuring [3H]MK-801 binding at concentrations varying from 2.5 to 50 nM. Following hyperventilation, Bmax decreased 52% to 0.50 +/- 0.04 pmol/mg protein (P = 0.001); however, the Kd value was unchanged at 7.45 +/- 0.79 nM. Spermine and magnesium dependent activation of the NMDA receptor was determined in the hyperventilated and control groups. With spermine concentrations increasing from 2.5 to 50 microM the maximal spermine dependent activation in the normoxic group was 13.7 +/- 7.93% which occurred at a concentration of 3.75 +/- 1.37 microM. In the hyperventilated group maximal activation was 32.4 +/- 23.5% (P = 0.095) at 4.58 +/- 2.46 microM (P = ns). With magnesium concentrations increasing from 2.5 to 100 microM the maximal magnesium dependent activation in the normoxic group was 17.0 +/- 13.6% which occurred at a concentration of 22.5 +/- 6.12 microM. In the hyperventilated group maximal activation was 26.3 +/- 14.9% (P = ns) at 4.58 +/- 2.92 microM (P < 0.0001). These data show that with less severe tissue hypoxia, as evidenced by conservation of ATP, there is less modification of the NMDA receptors. Ischemia induced by hyperventilation leads to an increase in spermine activation of the NMDA receptor, and the NMDA receptor is much more sensitive to magnesium as evidenced by the maximal activation occurring at a significantly lower magnesium concentration. Ischemia induced by hyperventilation modifies the spermine, magnesium, and MK-801 binding sites of the NMDA receptor and may result in increased NMDA receptor mediated neurotoxicity in the newborn brain.

Animals↗
PubMed1996

Optic neuropathy preceding acute retinal necrosis in acquired immunodeficiency syndrome.

OBJECTIVE: To describe the clinical course of varicella-zoster optic neuropathy preceding acute retinal necrosis in patients with acquired immunodeficiency syndrome. DESIGN: Case series. SETTING: Two tertiary care centers in San Diego, Calif, and London, England. PATIENTS: Three human immunodeficiency virus-positive men with previous cutaneous zoster infection, optic neuropathy, and necrotizing retinitis. RESULTS: All patients had an episode of zoster dermatitis treated with acyclovir. Visual loss consistent with an optic neuropathy ensued, followed by typical herpetic retinitis. The cause of visual loss was not suspected to be varicella-zoster until after the retinitis occurred. Despite aggressive medical treatment, 4 of 6 eyes progressed to retinal detachment. CONCLUSIONS: Varicella-zoster may cause an optic neuropathy in patients with acquired immunodeficiency syndrome, especially in those with previous shingles. A high index of suspicion is necessary to establish the diagnosis and begin early antizoster treatment.

AIDS-Related Opportunistic Infections↗
PubMed1996

Inhibition of human plasma and serum butyrylcholinesterase (EC 3.1.1.8) by alpha-chaconine and alpha-solanine.

The purpose of these experiments was to determine the reversibility of alpha-chaconine and alpha-solanine inhibition of human plasma butyrylcholinesterase (BuChE). For the substrate alpha-naphthylacetate, optimal assay conditions were 0.50 M sodium phosphate buffer and a substrate concentration of 3-5 x 10(-4) M. Dibucaine (1 x 10(-5) M) indicated the usual phenotype for all subjects; alpha-chaconine and alpha-solanine at 2.88 x 10(-6) M inhibited BuChE about 70 and 50%, respectively. One- and 24-hr incubations at 1 x 10(-5) M with alpha-chaconine, alpha-solanine, paraoxon, eserine, and ethanol yielded reversible inhibition with dilution except for paraoxon. Twenty-four-hour dialyses of incubations showed no inhibition except for paraoxon. PAGE enzyme activity gels of 1- and 24-hr incubations also showed no inhibition except for paraoxon. alpha-Chaconine and alpha-solanine are reversible inhibitors of human butyrylcholinesterase. At estimated tissue levels, alpha-chaconine, alpha-solanine, and solanidine inhibited BuChE 10-86%. In assays which combined alpha-chaconine, alpha-solanine, and solanidine, inhibition of BuChE was less than additive. No inhibition of albumin alpha-naphthylacetate esterase (an arylesterase) was noted with any inhibitor. The importance of these data to adverse toxicological effects of potato alkaloids is discussed.

Butyrylcholinesterase↗
PubMed1996

Visual outcome of patients with idiopathic ischaemic and non-ischaemic retinal vasculitis.

This study investigated whether patients with ischaemic retinal vasculitis have a worse visual outcome than those with non-ischaemic disease. A retrospective study was made of 53 patients with idiopathic retinal vasculitis (RV), with minimum 5 year follow-up. Patients were categorised into ischaemic and non-ischaemic groups by fluorescein angiography. Visual outcome was determined by visual acuity at their last attendance. Twenty patients (38 eyes) had ischaemic RV; 33 patients (63 eyes) had non-ischaemic RV. At presentation there was no significant difference between the groups in the proportion of eyes with poor vision (6/60 or less). Ischaemic RV patients had a worse visual outcome than those with non-ischaemic RV: 13 of 38 (34%) eyes in the ischaemic group had a final poor vision compared with 4 of 63 (6%) eyes in the non-ischaemic group (Fisher's exact test, p = 0.0005).

Adolescent↗
PubMed1996

Prevention of Rh isoimmunization after spontaneous, massive fetomaternal hemorrhage.

Massive fetomaternal hemorrhage has been associated with numerous risk factors and can occur spontaneously. The risk is probably greater when a woman who is Rh negative has an ABO-compatible fetus. We report the case of a gravid, A-negative unsensitized patient who came to the hospital at term complaining of decreased fetal movement over the previous 24 hours. During evaluation, the fetal heart rate was found to have decreased beat-to-beat variability and repetitive late decelerations, and the mother was delivered of a 3,005 gA-positive neonate (by cesarean section) with a hemoglobin level of 2.9 g/dL. An acid elution test showed 400 mL of fetal blood in the maternal circulation, and the patient received 23 ampules (6,900 micrograms) of Rh immune globulin postpartum. The patient's condition was observed for 156 days after delivery; she did not become sensitized to the Rh factor. A massive fetomaternal hemorrhage can occur without any antecedent risk factors, with a risk of subsequent morbidity to the neonate. Sensitization can be prevented by prompt administration of adequate amounts of Rh immune globulin.

ABO Blood-Group System↗
PubMed1996

Longitudinal analysis of soluble intercellular adhesion molecule 1 in retinal vasculitis patients.

Increased levels of soluble intercellular adhesion molecule 1 (sICAM-1) in serum have been demonstrated in several human disease conditions. We have previously shown, in a point-prevalence study, a positive correlation between sICAM-1 levels and disease relapse in patients with idiopathic retinal vasculitis. We now report a longitudinal study over 1 year in which sICAM-1 levels were compared with clinical disease status in order to determine this relationship further. Serum samples from 11 patients with idiopathic retinal vasculitis were tested for the presence of sICAM-1 by enzyme linked immunosorbent assay. Eight control subjects were also tested. Five out of 11 patients presented with relapse and had raised sICAM-1 levels compared with quiescent periods of their disease. Five out of 11 patients showed no relapse over 1 year and also no increase in sICAM-1 levels. One patient showed increased levels of sICAM-1, but no clinical signs of relapse. These results indicate that sICAM-1 is associated with disease activity in retinal vasculitis patients and could indicate dysfunction of the blood-retina barrier.

Adult↗
PubMed1996

Ocular neuromyotonia.

AIMS/BACKGROUND: Ocular neuromyotonia is characterised by spontaneous spasm of extraocular muscles and has been described in only 14 patients. Three further cases, two with unique features, are described, and the underlying mechanism reviewed in the light of recent experimental evidence implicating extracellular potassium concentration in causing spontaneous firing in normal and demyelinated axons. METHODS: Two patients had third nerve neuromyotonia, one due to compression by an internal carotid artery aneurysm, which has not been reported previously, while the other followed irradiation of a pituitary tumour, a common association in the published reports. Selective activation occurred in both, where neuromyotonic activity was triggered by prolonged voluntary activation of specific extraocular muscles with or without spread of activity to other third nerve muscles. The other patient had fourth nerve involvement, where spasms of the superior oblique muscle were induced only by alcohol, a phenomenon which has not been described. RESULTS: The two patients with third nerve involvement responded to carbamazepine and in one, an improvement in a chronic partial third nerve paresis occurred. The other has not required treatment and remains asymptomatic by refraining from alcohol. CONCLUSIONS: A careful examination, including the effects of prolonged voluntary muscle action is required to initiate episodes and to demonstrate selective activation. Imaging is mandatory to exclude compressive intracranial lesions, particularly where there is no history of pituitary fossa irradiation. A trial of anticonvulsants should be considered in all patients. Extracellular potassium may play a role in spontaneous firing and ephatic transmission in ocular neuromyotonia.

Adult↗