Biomedical subjects
M D Sanders
Publications and source records attributed to M D Sanders.
Vertical gaze palsy due to a resolving midbrain lesion.
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Leber's optic neuropathy and mitral valve prolapse.
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A point prevalence study of 150 patients with idiopathic retinal vasculitis: 1. Diagnostic value of ophthalmological features.
This paper describes the ophthalmological features of 150 patients with idiopathic retinal vasculitis, 67 of whom had isolated retinal vasculitis (RV) and 83 had RV associated with systemic inflammatory disease (RV + SID). The diagnosis of retinal vasculitis was made by ophthalmoscopy and fluorescein angiography, and patients with any identifiable cause (infection, ischaemia, or malignancy) were excluded from the study. Patients with isolated RV tended to have peripheral vascular sheathing, macular oedema, and diffuse capillary leakage. Those with RV accompanying Behçet's disease often had branch vein retinal occlusions and retinal infiltrates together with macular oedema and diffuse capillary leakage; the retinal infiltrates were pathognomonic for Behçet's disease. In sarcoidosis the retina typically showed features of periphlebitis associated with focal vascular leakage. Patients with uveomeningitis, multiple sclerosis, arthritis, or systemic vasculitis showed diffuse retinal capillary leakage associated with a mixture of the other features. Poor visual function was particularly associated with macular oedema and branch vein retinal occlusion, while the retina appeared to 'withstand' the impact of vascular sheathing, periphlebitis, or neovascularisation alone. Within the limitations of a point prevalence study it was concluded that different patterns of retinal vasculitis occur in different systemic inflammatory diseases, and that in isolated retinal vasculitis there is a particular association between peripheral vascular sheathing, macular oedema, and diffuse capillary leakage. In Part 2 we describe the results of examining the sera of these patients for the presence of antiretinal antibodies and circulating immune complexes.
A point prevalence study of 150 patients with idiopathic retinal vasculitis: 2. Clinical relevance of antiretinal autoimmunity and circulating immune complexes.
This study describes the occurrence of antiretinal antibodies and circulating immune complexes in the sera of a large series of patients with idiopathic retinal vasculitis whose ophthalmological and clinical features are presented in Part 1. Antiretinal antibodies were measured by indirect immunofluorescence and passive haemagglutination, and circulating immune complexes were measured by polyethylene glycol precipitation and Clq binding. The occurrence of antiretinal antibodies and that of circulating immune complexes were analysed in relation to each other, to severity of retinal disease, to the type of associated systemic inflammatory disease, and to the presence of individual features of retinal inflammation. In patients with retinal vasculitis together with systemic inflammatory disease circulating immune complexes were usually accompanied by antiretinal antibodies. However, those patients with antiretinal antibodies in the absence of circulating immune complexes tended to have more severe retinal vasculitis, a feature particularly evident in Behçet's disease (p = 0.028). In patients with isolated retinal vasculitis, severity of disease was associated with antiretinal antibody (p = 0.013), as well as with the occurrence of both antiretinal antibody and circulating immune complexes together (p = 0.010). In the series as a whole there was a tendency for individual features of retinal vasculitis to be associated with antiretinal antibodies unaccompanied by circulating immune complexes; especially in macular oedema (p = 0.028). In isolated retinal vasculitis there was also an additive effect of antiretinal antibodies and circulating immune complexes in relation to disease severity; in contrast, in patients with systemic inflammatory disease, the coexistence of antiretinal antibodies and concluded that both antiretinal autoimmunity and circulating immune complexes may act as immunopathogenetic factors in idiopathic retinal vasculitis but that, in certain patients, circulating immune complex formation seems to protect against the more severe forms of autoimmune retinal inflammatory disease.
Ocular inflammatory changes in established multiple sclerosis.
Fifty consecutive patients with clinically definite multiple sclerosis were studied to assess the prevalence of concomitant uveitis. Asymptomatic ocular inflammatory changes were found in nine patients (18%) and appeared to show a positive correlation with severe and progressive disease. Conversely uveitis was uncommon in the presence of established optic atrophy which suggests a negative influence on its pathogenesis. In the absence of optic atrophy inflammatory changes in the eye may be a valuable index of disease activity.
Ptosis and supranuclear downgaze paralysis.
A patient developed the unusual combination of a supranuclear downward gaze paralysis and bilateral ptosis. It was caused by a single midbrain glioma. Other ocular motor functions were intact. The neuropathologic examination showed a tumor growing mainly around the third ventricle and the aqueduct. The findings agree with recent experimental evidence that a network of neural elements involved in eyelid control lies in the supraoculomotor area immediately dorsal to the oculomotor nucleus.
Arterial oxygen desaturation following intravenous injection of midazolam.
The water soluble benzodiazepine derivative, midazolam, is used almost exclusively at our institution to produce sedation for numerous surgical procedures. Mild arterial oxygen desaturation has been reported in patients who have received as little as .04 mg/kg. A time series design study was undertaken to determine if there was any correlation between the decline in arterial oxygen percent saturation (SaO2) and the time at which sedation occurred and to establish the presence of any statistical significance in this decline. Thirty-one ASA I and II patients consisting of 8 females and 23 males requiring various minor orthopedic and general surgical procedures were studied. The total mean age of the population was 32.29 +/- 12.43 years (mean +/- SD). Fourteen patients had a smoking history, while 15 patients did not (2 patients were eliminated from the study for failure to demonstrate sedation, as characterized by either Verrill's sign or thickened speech following intravenous administration of midazolam). All patients arrived in the operating room unpremedicated and were administered .04 mg/kg midazolam intravenously. Arterial oxygen saturation was measured over a 10-minute period using pulse oximetry. Results were analyzed using regression analysis, a t-test for independent groups, and a one-way analysis of variance. There was no statistically significant difference in the decline in SaO2 between smokers and nonsmokers. Our study has shown that the mean onset of sedation using a dose of .04 mg/kg occurred between 3 and 4 minutes, with the peak fall in SaO2 occurring at the 3-minute interval irrespective of smoking history. The greatest mean drop in SaO2 was 95.84%. Midazolam, like its parent drug, diazepam, alters ventilatory mechanics.(ABSTRACT TRUNCATED AT 250 WORDS)
Differential effect of Bordetella pertussis on experimental posterior uveitis in the black-hooded Lister rat.
The effect of an additional adjuvant, Bordetella pertussis, on the clinical and histopathologic features of experimental autoimmune uveitis in black-hooded Lister rats was investigated. Disease was induced by a single footpad injection of purified retinal S-antigen in Freund's complete adjuvant. In those animals that did not receive B Pertussis the clinical features were those of a retinal vasculitis with disc edema, periphlebitis, and deep retinal infiltrates. In contrast, animals that received B pertussis developed lesions in the pigment epithelium and choroid. Histopathologic studies disclosed focal photoreceptor necrosis associated with mononuclear cell infiltration in both groups of animals. However, in the group that did not receive B pertussis the disease was predominantly a retinitis associated with perivascular infiltration of retinal vessels, whereas in the group that did receive B pertussis the main feature was a focal choroiditis, with superficial retinal lesions being rarely observed. Retinal photoreceptors were the target tissue in both groups of rats, but the route by which they were damaged was altered from predominantly retinal to choroidal by the addition of Bordetella pertussis as an adjuvant. This change may be ascribed to the ability of B pertussis toxin to sensitize vascular endothelium to local mast cell products, these cells being plentiful around choroidal vessels but absent in the retinal circulation.
A longitudinal study of clinical and immunological findings in 52 patients with relapsing retinal vasculitis.
Fifty-two patients with retinal vasculitis--26 with idiopathic disease and 26 with associated systemic inflammatory disease--were followed up for periods ranging from six months to 12 years. The aim of the study was to determine the relationship between relapse of uveitis, visual outcome, and the occurrence of circulating immune complexes (CIC) and antiretinal antibodies. In a total of 69 relapses, CIC were increased in one-third of patients and antiretinal antibodies in one-half. In those 34 patients who expressed antiretinal antibodies 27 (79%) of the relapses were characterised by antiretinal antibodies in the absence of raised CIC levels (p less than 0.01). These findings support our previous hypothesis that CIC may have a protective role in autoimmune retinal vasculitis and that antiretinal autoimmunity is of pathogenetic importance in relapse. In individual patients the visual outcome was not related to the number of relapses or to the CIC-autoantibody pattern, suggesting the operation of additional features which merit identification.
Retinal vasculitis.
Evidence is now accumulating on both clinical and experimental grounds that the retina is an a priori source of inflammatory activity. Reactive inflammation in the retina may produce many of the clinical signs previously ascribed to uveal inflammation. Autoimmune mechanisms are probably responsible for the majority of cases of retinal vasculitis. Autoimmune retinal vasculitis occurs without other classical signs of inflammatory response in any other parts of the body. When associated systemic manifestations occur they may reflect different underlying immunopathogenic abnormalities. Thus in diseases with predominantly arterial involvement (e.g. systemic lupus erythematosus, polyarteritis nodosa) the retinal arteries bear the brunt of this disease. In Behçet's disease the systemic involvement is usually venous and ocular involvement produces diffuse capillary and venous inflammation with areas of retinal necrosis and major vascular occlusion. The retinal appearances differ from sarcoidosis in which a granulomatous response produces characteristic periphlebitis. Finally, autoimmune retinal vasculitis produces diffuse capillary and venous damage, without any systemic signs. In the next decade the search will be for the identification of the specific antigens initiating these disparate retinal features. Retinal S antigen is a potent antigen, but rhodopsin, interphotoreceptor binding protein, and transducin all need further experimental investigation. Precise documentation will herald the dawn of new therapeutic measures based on a sound immunological fabric.
An improved method for the purification of retinal S-antigen using selective hydrophobic adsorption chromatography.
This paper describes the use of phenyl-Sepharose CL-4B as a solid-phase hydrophobic adsorbent in the purification of S-antigen from protein extracts of bovine, porcine and human retina. Chromatographic conditions were ascertained whereby the majority of contaminating proteins were bound to the adsorbent leaving S-antigen in the liquid phase. In combination with size fractionation on Ultrogel AcA, the method conveniently yielded porcine and bovine S-antigen preparations up to 100% purity. Immunogenicity of purified S-antigens was verified by induction of experimental autoimmune uveoretinitis in albino Lewis rats. The method is preparative in scale, fast in performance and yields S-antigen in high purity and antigenic potency.
Comparative biochemical analysis of purified S-antigen from human, bovine, porcine and rat retina.
Highly purified S-antigen from human, bovine, porcine and rat retina was used to ascertain the molecular weights, isoelectric points, amino-acid composition and presence of carbohydrate moieties. All S-antigen preparations comigrate to 50,000 MW on SDS-polyacrylamide gels and demonstrate microheterogeneity upon isoelectric focusing. Human S-antigen exhibits two bands at pH 5.9 and 5.6, whilst with bovine S-antigen a broad band at pH 5.9 was observed. Porcine and rat S-antigen gave four bands, focusing between pH 5.0-5.6. Two-dimensional gel analysis revealed that all the four focused porcine polypeptides migrate to 50,000 MW. Western-blot analysis following isoelectric focusing of human and porcine S-antigen showed that all polypeptide bands react specifically with polyclonal and monoclonal antibodies to S-antigen. The reasons for the apparent heterogeneity of S-antigen by isoelectric focusing are discussed. All S-antigen preparations were weakly positive for periodic acid Schiff staining, and specifically bound radiolabelled Lens culinaris lectin on Western-blot analysis. These results confirm the glycoprotein nature of S-antigen which may explain the finding of multiple bands found on isoelectric focusing. Amino-acid analysis reveals the high percentage of non-polar amino acids and may explain the apparent hydrophobic behaviour of the isolated protein.
Anterior uveitis associated with Campylobacter jejuni infection.
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Retinal vasculitis: correlation of animal and human disease.
A form of experimental retinal vasculitis was induced in black hooded Lister rats by the inoculation of retinal S-antigen. Comparison of this disease with retinal vasculitis in man showed striking clinical, angiographic and pathological similarities. Clinically disc oedema, periphlebitis and retinal infiltrates were observed with corresponding leakage of dye on fluorescein angiography. Pathologically the disease showed perivascular lymphocytic infiltrates with focal photoreceptor necrosis. These characteristic features make this an ideal model for the study of the pathogenesis of retinal vasculitis in man.
Duke-Elder lecture. Retinal arteritis, retinal vasculitis and autoimmune retinal vasculitis.
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Cyclosporin A in the treatment of severe Behçet's uveitis.
Twelve patients with active Behçet's uveitis with marked deterioration of visual acuity in at least one eye were treated with cyclosporin A (CyA). An initial improvement in the severity of ocular inflammation and systemic features occurred in all cases and persisted until the dose was reduced or the drug withdrawn when a rapid recurrence of symptoms was noted. The visual acuity also initially improved in ten patients and this was maintained in seven cases until the dose of CyA was reduced. At this time, acuity was unchanged in two patients and was worse in three others-two of the latter as a result of vitreous haemorrhage in the absence of active inflammation. Seven of the 12 patients had therapy stopped because of complications; severe malaise and nausea (three cases), decreased renal function (three cases), and blindness (one case). Cyclosporin A is of value in the control of Behçet's uveitis but toxicity limits its use and the benefits only last while the patient is on this therapy.
Neovascularisation associated with posterior uveitis.
Twenty-six patients (39 eyes) with retinal neovascularisation associated with ocular inflammation were identified from the retinal vasculitis clinic at St Thomas's Hospital. Eight patients had sarcoidosis, seven patients Behçet's disease, and 11 had idiopathic retinal vasculitis. Twenty-three patients had required systemic therapy to control the inflammation and 11 patients received laser photocoagulation. Fluorescein angiography showed significant capillary closure in 15 eyes and diffuse microvascular leakage in the remaining 24 eyes. All patients had posterior vitreous detachment. The visual prognosis was good despite vitreous haemorrhage being the presenting feature in 22 eyes, and the new vessels resolved in 70% of cases. However, laser treatment was followed by a significant increase in cystoid macular oedema (p less than 0.01). This retrospective study suggests that medical therapy is the first line of treatment in this group of patients. Photocoagulation should be performed when the eye is quiet and should be reserved for patients with recurrent vitreous haemorrhages and significant capillary closure.