Effect of a VH81X-expressing IgM antibody on early B-cell development.
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Animals↗
Biomedical subjects
A M Hamilton
Publications and source records attributed to A M Hamilton.
Encephalitis and chorioretinitis associated with neurotropic African horsesickness virus infection in laboratory workers. Part II. Ophthalmological findings.
Four laboratory workers developed uveitis-chorioretinitis, associated with encephalitis in 3 cases. The retinitis was characterised by haemorrhages and areas of retinal oedema, most marked over the posterior polar regions, and was associated with exudative retinal detachments. The lesions progressed over weeks and showed a severe retinal arterial vasculopathy with arteriolar narrowing, ghost vessel formation and the development of optic atrophy. The picture in 2 of the patients resembled that of the acute retinal necrosis syndrome (ARN). Antibodies to African horsesickness (AHS) virus were detected. The serology for AHS virus was positive in all 4 patients as well as in 5 of 15 laboratory workers from the same facility who were clinically and ophthalmologically normal. This is to our knowledge the first description of subclinical and probable clinical neurotropic AHS virus infection in man. AHS is a hitherto-unrecognised possible cause of viral retinitis and the ARN syndrome.
Adolescent↗
Macular oedema and retinal neovascularisation in juvenile diabetics.
Thirteen young diabetic patients with peripheral capillary non perfusion who presented with symptoms of mild maculopathy were reviewed retrospectively. In this group, peripheral retinal ischaemia was often overlooked and a rapidly progressive proliferative retinopathy developed. Fluorescein angiography of the peripheral retina showed capillary closure, but with preservation of arterioles and venules. In this series, half of the eyes lost vision. In seven eyes where the peripheral ischaemia was treated by pan retinal photocoagulation, the maculopathy resolved without any specific laser treatment to the macula. In young diabetics presenting with maculopathy, the peripheral retina should be examined for ischaemia, and if present, pan retinal laser photocoagulation should be performed. Focal treatment for the macular disease can be delayed until after the peripheral photocoagulation, as the maculopathy may remit.
Adolescent↗
Acute tear of the retinal pigment epithelium.
The fluorescein angiographic findings immediately following a tear of the retinal pigment epithelium are presented and the mechanisms of fluid movement from the retina to the choroid are discussed. Our case represents a clinical correlate to recent experimental reports on fluid movement across the retinal pigment epithelium-Bruch's membrane complex.
Acute Disease↗
Extracapsular cataract extraction in diabetics with rubeosis iridis.
We reviewed thirteen operated eyes (twelve diabetic patients) with rubeosis iridis who underwent extracapsular cataract extraction and intraocular lens implantation. Prior to surgery five had active proliferative retinopathy (APR), and eight had non-proliferative retinopathy (NPR), either quiescent proliferative retinopathy (QPR) or background retinopathy (BR). No case with APR was visually improved by surgery. Three cases with NPR achieved a visual acuity of 6/12. After surgery, vitreous haemorrhage or progression of proliferative retinopathy occurred in three cases with APR. Early postoperative fibrinous uveitis was severe in eyes with APR, resulting in permanent fibrin membrane formation in four. We suggest a significant prognostic indicator in diabetic cataract extraction with rubeosis iridis is the status of the underlying retinopathy. With NPR, postoperative visual acuity may be good and early postoperative complications less severe. In the presence of APR the visual outcome is poor, progression of retinopathy likely and early postoperative fibrinous uveitis may be severe enough to prevent postoperative panretinal photocoagulation. Maximum preoperative panretinal ablation is essential in these cases.
Aged↗
Transient vessel wall sheathing in acute retinal vein occlusions.
Three cases are reported which had features similar to, and evolved in a pattern consistent with central retinal vein occlusions and a fourth case is reported which behaved as a hemispheric vein occlusion. However, they differed from classic retinal vein occlusions by having prominent sheathing of the retinal venous vasculature at presentation, which in all four cases resolved within three weeks. There was no evidence for any of these cases having an inflammatory vasculitis. The significance of this transient sheathing is uncertain.
Acute Disease↗
Controlled trial of laser photocoagulation of pigment epithelial detachments in the elderly: 4 year review.
Patients who were enrolled in a controlled treatment trial of laser grid photocoagulation for retinal pigment epithelial detachment as part of age-related maculopathy were reviewed 4 years after entry into the trial. The data imply that the original conclusion that this form of treatment did not improve the visual prognosis at 18 months was also justified at 4 years. It has become clear that lesions with evidence of subpigment epithelial new vessels were included in the trial. In a retrospective study the lesions were separated into those in which there was evidence of subretinal neovascularisation and those in which no such evidence existed. A difference was identified in the behaviour of the treated and untreated lesions designated avascular in that the treated eyes had a poorer visual outcome. These cases accounted for the different behaviour between two management groups in the initial study such that the original conclusion that grid photocoagulation of avascular pigment epithelial detachments in the elderly does not improve the visual prognosis is justified.
Humans↗
Detection of subpigment epithelial neovascularisation in cases of retinal pigment epithelial detachments: a review of the Moorfields treatment trial.
The entry angiograms of 42 eyes with detachment of the retinal pigment epithelium in a treatment trial of laser photocoagulation were reviewed in a masked fashion by three observers in order to assess the possible presence of subpigment epithelial neovascularisation. Vascularity or avascularity was designated with reference to a list of clues believed to imply the presence of subpigment epithelial neovascularisation. As a predictor of outcome the initial assessment achieved a sensitivity and specificity of 77% and 82% respectively. Despite notable parity of the degree of sensitivity and specificity among the three observers, full agreement on the initial assessments was reached in only 23 eyes (55%), 10 with vascular and 13 with avascular outcome. Of these, only one eye which developed new vessels after 4 years had an outcome which differed from that predicted by classification of the entry angiograms.
Aged↗
Development and function of the early B cell repertoire.
The early B cell repertoire is characterized by extensive interconnectivity, autoreactivity and multispecificity. Our preliminary sequence analysis of some of the idiotype specific antibodies is beginning to provide molecular clues to explain the observed multireactivity and the expression of shared idiotypic determinants on immunoglobulins of early B cells. The VH gene rearrangements analyzed are typical of the early pre-B cell and CD5 B cell repertoire. Some of these include shared or identical CDR3 regions resulting from the use of germline VH, D and JH gene segments in the absence of N region addition. As previously described, the most D proximal VH genes are also used most frequently. Collectively these genetic restrictions, together with the lack of somatic mutation, suggest that the characteristic self reactivity of the early B cell repertoire is related to the expression of germline gene segments and limited use of diversification mechanisms. It has also been possible for the first time to isolate hybridomas secreting functional IgM molecules which use the most D proximal VH gene, VH81X. These antibodies and another example from the VH7183 family have a broad multireactivity pattern possibly because of the presence of an unusually high number of charged amino acid groups present in the VH region. These findings are preliminary and more extensive studies are needed to establish if these groups are responsible for the highly cross-reactive nature of these antibodies. Nevertheless, these unusual characteristics signify a unique role for antibodies expressing this VH gene during B cell development. It is also clear that the observed anti-lymphocyte reactivity, another feature of the newborn repertoire, is the result of the prevalence of B cells using similar if not identical VHDJH genes and DJH joins. The development of these B cells appears to occur consistently in early ontogeny and, again, are not found in conventional splenic B cells obtained from the normal adult. Understanding the functional significance of the early appearance of these antibodies may help to clarify and understand their role during development as well as in autoimmunity. We propose that the unique self reactive nature of the early repertoire provides a pattern within which self-assertiveness develops and results in the establishment of the adult repertoire. In doing so, dominant clones are established which may or may not be within, but whose selection and differentiation is directed by the CD5 B cell subset.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Effect of a long-acting somatostatin analogue (BIM23014) on proliferative diabetic retinopathy: a pilot study.
A pilot study on the use of a continuous infusion of somatostatin, by subcutaneous pumps in the management of proliferative diabetic retinopathy is reported. Two patients out of eight with proliferative retinopathy demonstrated improvement. One patient demonstrated regression of disc new vessels and the other a reduced area of retinal capillary non-perfusion, both demonstrated by fluorescein angiography. Control patients showed worsening of fluorescein leakage over the observation period of four to six weeks whereas the other six patients given the somatostatin infusion did not demonstrate any deterioration. The mechanism of action of somatostatin in this study is unknown but it is thought to have direct anti-angiogenic properties as well as inhibiting growth hormone secretion.
Adult↗
Iris clipping of a diode laser beam when performing retinal photocoagulation.
The Microlase infrared diode laser has recently become available for retinal photocoagulation. It uses a laser beam with a large convergence angle (23 degrees). This gives rise to a laser beam with a relatively large cross section at the subject's pupil. In this study the pupillary area required to view the fundus at the slit-lamp with a 90-dioptre lens is determined. It is found that the pupillary area required to view the fundus is smaller than the cross section of the Microlase laser beam at the pupil. Thus iris clipping of the laser beam can occur even though the surgeon has a clear and bright view of the fundus. Care should be taken to use the Microlase only in the presence of a widely dilated pupil.
Fundus Oculi↗
Effects of dibutyryl cyclic AMP, ouabain, and xanthine derivatives on crossbridge kinetics in rat cardiac muscle.
In a previous communication, we showed that beta-adrenergic stimulation of cardiac muscles was associated with an increase in the rate of cycling of crossbridges as measured by perturbation analysis in the frequency domain. In this analysis, the frequency at which dynamic stiffness is a minimum (fmin) is taken as a measure of the rate of crossbridge cycling. In this paper, we test the hypothesis that the beta-adrenergic receptor-induced increase in crossbridge cycling rate is mediated by elevation of the intracellular level of cyclic AMP. The approach taken is to compare the effects on fmin in rat papillary muscles during Ba(2+)-activated contractures of 1) an agonist of cyclic AMP that can easily penetrate the cell, namely, dibutyryl cyclic AMP, 2) agents that block cyclic AMP phosphodiesterase, namely, the xanthine derivatives isobutylmethylxanthine and caffeine, and 3) an inotropic agent that does not affect the intracellular level of cyclic AMP, namely, ouabain. Our results showed that dibutyryl cyclic AMP at a dose of 5 mM has the same actions as beta-adrenergic stimulation: it potentiated the isometric twitch force, reduced the time to peak tension and time to half relaxation, and shifted fmin by a factor of 1.8 +/- 0.1 (n = 5). Isobutylmethylxanthine at up to 1.1 mM also acted in the same manner, increasing fmin by a factor of 1.8 +/- 0.2 (n = 6), but ouabain, at a dose (0.03 mM) sufficient to potentiate twitch force by 40 +/- 2% (n = 4), was without effect on the time course of the twitch nor was fmin changed (n = 4). Our findings support the hypothesis that a beta-adrenergic receptor-mediated increase in crossbridge cycling rate is due to an increase in intracellular cyclic AMP level and illustrate the usefulness of the frequency domain analysis approach in the analysis of the mechanism of action of inotropic agents.
1-Methyl-3-isobutylxanthine↗
Q-switched neodymium YAG laser vitreolysis in the therapy of posterior segment disease.
We describe our experience of ten cases of posterior segment vitreolysis, using the short-pulse neodymium YAG (Yttrium Aluminium Garnate) laser. Eight patients had proliferative diabetic retinopathy, one patient had had an intraocular foreign body removed and one patient had had uveitis. Of the ten, five patients had macular traction retinal detachments, three patients had progressive traction retinal detachments threatening the macula and two patients had recurrent vitreous haemorrhages from mechanical traction on areas of fibrovascular proliferation. Eight of the patients were successfully treated. One macular retinal detachment failed to flatten and a tear was found which may have been iatrogenic. In one patient with a traction retinal detachment significant traction was relieved but the detachment failed to flatten completely. We discuss the indications, techniques, difficulties and complications. Our experience suggests that this technique has an important role in the treatment of selected patients, sparing patients conventional vitrectomy, or making possible the treatment of those for whom vitrectomy has been contraindicated or refused. Anterior defocusing of the YAG would be a useful modification of current laser systems and improved aiming systems desirable for the future.
Adult↗
Treatment of choroidal metastasis from choriocarcinoma. Case report.
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Adult↗
Initial clinical experience using a diode laser in the treatment of retinal vascular disease.
A pilot study has been carried out to investigate the clinical use of an infrared diode laser in the treatment of a number of retinal vascular conditions. A hand-held device was employed initially and subsequently a further prototype was developed for use in conjunction with a standard slit lamp microscope. Thirty-three eyes in thirty patients were treated for conditions such as proliferative diabetic retinopathy, exudative retinopathy and branch and central retinal vein thrombosis. Regression of neovascularisation was observed in 13 of 16 eyes (81%) with proliferative diabetic retinopathy and in six of eight eyes (75%) with branch retinal vein occlusion. Four eyes were successfully treated for established or incipient rubeosis iridis following central vein thrombosis. Focal photocoagulation applied to five eyes for diabetic exudative maculopathy resulted in partial resorption of the exudates. These results are presented together with information on the ease of use of the laser and its reliability. The implications of the development of this instrument in the context of its place in ophthalmic therapy are discussed.
Aged↗
Optic disc neovascularization in dominant exudative vitreoretinopathy.
Dominant exudative vitreoretinopathy (DEVR) is inherited retinal vascular disorder which is characterized by peripheral retinal neovascularization, tractional retinal detachment, subretinal, exudation, and vitreous fibrosis. A milder form of involvement characterized by capillary nonperfusion and straightening of the retinal vessels may be present in asymptomatic individuals. We describe a 15-year-old patient who presented with optic disc neovascularization, a finding not previously reported in association with DEVR. Angiographic evidence of DEVR in successive generations confirmed the diagnosis. The findings in mild and advanced DEVR are reviewed, and the pathogenesis of the capillary nonperfusion is discussed.
Adolescent↗
Extensive argon laser photocoagulation in the treatment of proliferative diabetic retinopathy.
A group of 20 patients (28 eyes) with proliferative retinopathy who required extensive argon laser photocoagulation to induce regression of new vessels is presented. The mean number of burns applied to each eye was 7225, with a maximum of 11,513. These were delivered in a mean of nine sessions over a mean period of 22.9 months. Twenty-five eyes (89%) had a final visual acuity of 6/18 or better. The remaining three eyes (11%) had severely reduced vision attributable to complications of proliferative diabetic retinopathy (traction retinal detachment involving the macula in two eyes and ischaemic maculopathy and a persistent vitreous haemorrhage in the third). Large amounts of confluent argon laser photocoagulation may be necessary for the elimination of new vessels in some patients, and it is our view that laser photocoagulation should be continued until regression of new vessels occurs. This is compatible with the retention of functional vision and good visual acuity.
Adult↗
Adrenaline increases the rate of cycling of crossbridges in rat cardiac muscle as measured by pseudo-random binary noise-modulated perturbation analysis.
The mechanism of action of adrenaline on cardiac contractility in rat papillary muscles containing V1 and V3 isomyosins was analyzed during barium-activated contractures at 25 degrees C by frequency domain analysis using pseudo-random binary noise-modulated perturbations. The analysis characterizes a frequency (fmin) at which dynamic stiffness of a muscle is a minimum, a parameter that reflects the rate of cycling of crossbridges. We have previously shown that fmin for V1- and V3-containing papillary muscles were 2.1 +/- 0.2 Hz (mean +/- SD) (n = 10) and 1.1 +/- 0.2 Hz (n = 8), respectively, and that these values were independent of the level of activation. The present study's goal was to determine whether the inotropic action of adrenaline was associated with an increased rate of crossbridge cycling. The results show that a saturating dose of adrenaline increased fmin in V1 hearts by 49 +/- 2% (n = 11). The action on V3 hearts was significantly less; the increase in fmin was 26 +/- 2% (n = 6). The increase in fmin for V1 hearts was shown to be sensitive to the beta-blocking agent propranolol. These results suggest that adrenaline significantly increases the rate of crossbridge cycling by a beta-receptor-mediated mechanism. We conclude that the increased contractility of the heart in the presence of adrenaline arises not only from more complete activation of the contractile proteins but also from the increased rate at which each crossbridge can transduce energy.
Animals↗