Nonequilibrium Pair Breaking in Ba(Fe_{1-x}Co_{x})_{2}As_{2} Superconductors: Evidence for Formation of a Photoinduced Excitonic State.

Ultrafast terahertz (THz) pump-probe spectroscopy reveals an unusual out-of-equilibrium Cooper pair nonlinear dynamics and a nonequilibrium state driven by femtosecond (fs) photoexcitation of superconductivity (SC) in iron pnictides. Following fast SC quench via hot-phonon scattering, a second, abnormally slow (many hundreds of picoseconds), SC quench regime is observed prior to any recovery. Importantly, a nonlinear pump fluence dependence is identified for this remarkably long prebottleneck dynamics that are sensitive to both doping and temperature. Using quantum kinetic modeling we argue that the buildup of excitonic interpocket correlation between electron-hole (e-h) quasiparticles (QP) quenches SC after fs photoexcitation leading to a long-lived, many-QP excitonic state.

Demonstration of vasoproliferative activity from mammalian retina.

Vasoproliferative activity has been demonstrated in extracts of retinas from human, bovine, and feline sources. These retinal extracts are capable of stimulating (a) proliferation and thymidine uptake of bovine vascular endothelial cells in culture and (b) neovascularization on the chick chorioallantoic membrane. Extracts of skeletal muscle, cardiac muscle, and liver lack similar stimulatory activity. The activity is nondialyzable, stable at 56 degrees C, and inactivated at 100 degrees C. Retinal extracts stimulate the proliferation of corneal fibroblasts but have no effect on the proliferation of vascular smooth muscle cells. Indirect evidence suggests the liberation of a vasoproliferative factor from retina in several ocular disorders. The data in this report represent the first direct demonstration of vasoproliferative activity from mammalian retina.

[Radiation exposure with 3D rotational angiography of the skull]. / Strahlenexposition bei der 3D-Rotationsangiographie des Schädels.

PURPOSE: Determination and comparison of radiation exposure for examinations of the skull with unsubtracted 3D Rotational Angiography (3D RA) and 2D Digital Subtraction Angiography (2D DSA). MATERIALS AND METHODS: Measurements were carried out with a skull of an Alderson phantom for 3D RA and for 2D DSA in p. a. and lateral projections using an Innova 4100 angiography system with a digital flat panel detector from GE Healthcare. 45 thermoluminescent dosimeters TLD 100H from Harshaw were placed inside the phantom to measure organ doses. In addition the dose area product was recorded and the effective dose was calculated using the Monte Carlo program PCXMC. RESULTS: For a biplanar DSA run (lateral and p. a. projection), the organ doses were 4 to 5 times higher and the effective dose was 4 times higher than for a 3D RA even though the number of images for the two DSA runs was only half of that for 3D RA. CONCLUSION: The radiation exposure for unsubtracted 3D RA using a flat panel detector is significantly lower than for biplanar DSA. Using 3D RA in place of 2D DSA can reduce the radiation exposure of patients in neuroradiology procedures.

Prolonged tumor dormancy by prevention of neovascularization in the vitreous.

Tumors release a diffusible substance that stimulates neovascularization. To study the neovascularization that occurs in diabetic retinopathy, we implanted V2 carcinomas and mouse ependymoblastomas into the vitreous of experimental animals. In the vitreous, unlike previous sites, the tumors failed to stimulate neovascularization. They grew for weeks as small, unvascularized, three-dimensional aggregates of cells. Explosive growth into a large, vascularized mass occurred when the avascular tumors reached the retinal surface. The vitreous proved to be a valuable model for observing the in vivo growth of small, solid tumors. Xenografts survived for months without evidence of immune rejection. The consequence of the prolonged avascular state is the restriction of tumor size. The normal vitreous may act to inhibit capillary proliferation. An understanding of the mechanism for maintaining the avascular state may lead to therapeutic blockade of neovascularization. This would be important in the management of diabetic retinopathy and neoplasia.

PaO2 levels and retrolental fibroplasia: a report of the cooperative study.

The relation between PaO2 and retrolental fibroplasia (RLF) was studied prospectively in 719 premature infants born in or treated in the intensive care units of a group of university hospitals. Blood gas studies were performed on 589 of these infants, 66 of whom had a diagnosis of RLF; in 27 of these 66, some grade of mostly nonblinding cicatricial disease developed. The frequency of RLF was highest among infants of lowest birth weight. A multivariate statistical method was used to analyze simultaneously the effect of possible etiologic factors associated with RLF. The occurrence of RLF was found to be unrelated to PaO2, as determined by the limited information available from intermittent sampling. RLF is associated with concentration of oxygen administered in the lightest birth weight group, but the strongest association, aside from birth weight, was with time in oxygen. None of the other variables involving blood chemical values appeared to be associated with RLF. The severity of cicatricial RLF is clearly greater in infants weighing less than 1,200 g at birth. Conservative administration of oxygen may have been responsible for failure to demonstrate quantitative association between PaO2 levels and disease. Agreement between the observed and predicted numbers of infants with RLF demonstrate the strength of the multivariate technique employed in making the statistical analyses.

Studies on retinal neovascularization. Friedenwald Lecture.

Evidence supporting the original concept of Michaelson and Ashton of a vasoproliferative or angiogenesis factor responsible for retinal neovascularization is discussed. The oxygen model of retinal neovascularization is described as a key example in this evidence. Newer studies on experimental retinal neovascularization and its control are summarized.

Jonas S. Friedenwald, man of science.

Jonas S. Friedenwald, a quiet and modest person, was one of the most distinguished research scientists of his era. As a brilliant mathematician, physicist and chemist he applied these basic disciplines to his research studies in ophthalmology. His contributions encompassed the entire field of ophthalmic investigation ranging from his classic textbook on ophthalmic pathology to the development of the Friedenwald ophthalmoscope. His pioneer studies on the pathogenesis of glaucoma, the standardization of tonometers, enzyme chemistry, corneal wound healing, and diseases of the retina laid the groundwork for future generations of investigators.

Vitreous: an inhibitor of retinal extract-induced neovascularization.

One of the major problems in assessing neovascularization in mammalian experimental animal models is the immunologic response of the host to stimuli from nonautologous species. Hence, crude bovine vitreous and retinal extracts may produce a complex immune reaction when tested in the rabbit. To circumvent this problem, the chicken chorioallantoic membrane (CAM) assay is most appropriate. In this study the CAM assay for angiogenesis has been modified to study antiangiogenic substances. The modified assay is described in detail and used to demonstrate for the first time the inhibition by adult bovine vitreous of neovascularization induced by extracts of adult bovine retina. In addition to vitreous, three common glycosaminoglycans (keratan sulfate, chondroitin sulfate C, and hyaluronic acid) were assayed for antiangiogenic activity. The results indicate that vitreous inhibition of retinal extract-induced neovascularization is dose dependent, while the sulfated glycosaminoglycans tested had no antiangiogenic activity. A commercial preparation of bovine vitreous hyaluronic acid exhibited a slight, but not statistically significant, inhibitory activity. When vitreous extracts were digested with hyaluronidase, no loss of antiangiogenic activity occurred. These results suggest that the inhibitor of angiogenesis from adult vitreous is probably not a common glycosaminoglycan. The results are consistent with the hypothesis that antiangiogenic substance(s) in vitreous and angiogenic components from retina may act as natural antagonists in controlling the process of retinal neovascularization.

A corneal micropocket assay for angiogenesis in the rat eye.

A corneal micropocket assay for angiogenesis in the rat eye is described in detail. With our test system, a partially purified, low molecular-weight endothelial cell growth stimulatory factor isolated from the Walker 256 rat carcinosarcoma is demonstrated to have potent angiogenic activity in vivo. The advantages and applications of our rat corneal assay are discussed.

Cystoid maculopathy in diabetics.

Three patients with long-standing diabetes manifested reduced visual acuity and notable bilateral symmetrical cystoid maculopathy, with no other sign of meaningful background diabetic retinopathy, eg, minimal to no microaneurysms, hemorrhages, or exudates. Results of fluorescein angiography showed that the entire retinal capillary bed in the macula was dilated and leaked fluorescein diffusely and profusely, but also showed that there was excellent capillary perfusion. Argonlaser photocoagulation was applied to one eye of each patient in an attempt to resolve the cystoid maculopathy. The laser treatment effectively resolved the edema in the specific areas of treatment, but the foveal and perifoveal areas, which were not treated, showed no areas of resolution of the cystoid edema in two cases and no improvement (and no decrease) in visual acuity in all three cases.

The relationship of puberty to diabetic retinopathy.

The presence of background and preproliferative retinopathy in 70 patients with type I diabetes was correlated with their pubertal development. Pubertal status was assessed by pediatricians using the sexual maturity ratings of Tanner. In young diabetics with comparable disease duration (5 to 10 years), postpubertal children had a greater prevalence of retinopathy than those who were not sexually mature. After adjusting for duration of diabetes and sex, the relative odds of having retinopathy in the postpubescent group relative to the prepubescent or pubescent groups was 4.8 (95% confidence interval: 1.5 to 15.3). This study suggests that minimal retinopathy in children is not rare and that postpubescent children have a greater prevalence of diabetic retinopathy than do prepubescent children with similar diabetes duration.

Interval between onset of mild nonproliferative and proliferative retinopathy in type I diabetes.

OBJECTIVE: To describe the interval between first appearance of mild nonproliferative diabetic retinopathy (NPDR) and first appearance of neovascularization (NV) in type I diabetes. SETTING: A longitudinal study of 269 patients followed up annually. PARTICIPANTS: Participants had insulin-dependent diabetes and were free of proliferative diabetic retinopathy in both eyes at the baseline visit. MAIN OUTCOME MEASURE: Stereoscopic color fundus photographs of each eye at each study visit, graded for features of retinopathy. RESULTS: Among the 305 eyes for which the duration of diabetes at the first appearance of mild NPDR could be determined, NV developed in 28 by the end of the study. Survival analysis showed that the later the onset of mild NPDR was, the shorter the time from onset of mild NPDR to onset of NV (relative hazard for each additional year to onset of mild NPDR, 1.22; 95% confidence interval, 1.10-1.35). Adjustment for systolic and diastolic blood pressure, proteinuria, and glycosylated hemoglobin (Hgb A10) levels did not change the relative hazard estimate for onset of mild NPDR. Higher levels of Hgb A10 were associated with a shorter time from onset of mild NPDR to onset of NV (relative hazard, 1.26; 95% confidence interval, 1.05-1.51 [after adjusting for time at onset of mild NPDR]), as were higher levels of diastolic blood pressure, although not significantly (relative hazard for 10-mm Hg increase in diastolic blood pressure, 1.52; 95% confidence interval, 0.82-2.83 [adjusting for onset of mild NPDR, Hgb A10 level, systolic blood pressure, and proteinuria]). Neither proteinuria nor systolic blood pressure had an effect on time from onset of mild NPDR to onset of NV, after adjustment for time at onset of mild NPDR, Hgb A10 level, and diastolic blood pressure. CONCLUSION: Later onset of mild NPDR is not necessarily associated with delayed development of NV in patients with type I diabetes. Caution must therefore be used in assessing the value of interventions that delay the onset of mild NPDR without evidence of delayed onset of NV.

Correlation of clinicopathologic findings in a patient. Congenital night blindness, branch retinal vein occlusion, cilioretinal artery, drusen of the optic nerve head, and intraretinal pigmented lesion.

The ocular clinicopathologic features of this unique patient were congenital stationary night blindness, drusen of the optic nerve head, cilioretinal artery, intraretinal pigmented lesion, and branch retinal vein occlusion. Photocoagulation therapy led to total disappearance of the neovascular tissue, clinically and histopathologically. Histopathologic examination showed an occluded branch vein associated with a sclerotic retinal arteriole. Peripheral to the site of venous occlusion, inner ischemic retinal atrophy was present. The normal complement of rod and cone photoreceptors supports the view that the night blindness in this case was an abnormality in the neural transmission and not on a morphological basis. The pigmented intraretinal lesion proved to be a localized area of retinal and choroidal neovascularization with anastomosis and secondary retinal pigment epithelial hyperplasia. This lesion was identical to Fuchs' dot of myopia but out patient was hyperopic.

Retinal branch vein occlusion.

Obstruction of a major temporal branch vein, or one of its macular tributaries, presents a significant threat to vision. Visual acuity may be reduced by macular edema or the consequences of retinal neovascularization, and these afflictions frequently become irreversible. Since the complicating macular edema and retinal neovascularization respond, at least in part, to argon laser therapy in some other conditions, some investigators have begun to treat branch vein occlusions with this modality. However, since the pathogenesis and natural history of the disorder have not yet been elucidated by prospective studies, it is not clear whether such treatment is indicated. Clinical and experimental studies are reviewed, and treatment rationale and techniques are discussed. The authors emphasize the need for well-controlled randomized studies to evaluate the natural history of branch vein occlusion and the efficacy of photocoagulation in its treatment.

Macular edema. A complication of diabetic retinopathy.

Diabetic macular edema is the leading cause of decreased vision from diabetic retinopathy. This decreased vision is caused by an increase in extracellular fluid within the retina distorting the retinal architecture and frequently taking on a pattern of cystoid macular edema. This fluid accumulates within the retina because of the breakdown of the barriers within the retinal blood vessels and possibly the pigment epithelium. Diabetic macular edema tends to be a chronic disorder. Although spontaneous recovery is not an uncommon occurrence, over one-half of diabetics with macular edema will lose two or more lines of visual acuity within two years. The most promising treatment for diabetic macular edema has been photocoagulation. It is recommended that in all patients with diabetic macular edema attempts be made to normalize elevated blood glucose, decrease elevated blood pressure, and improve cardiac or renal status. Reduction of serum lipids by diet or pharmacologic means is an unproven treatment at this time. The Early Treatment Diabetic Retinopathy Study hopefully will provide more definitive information as to whether photocoagulation is effective in various subgroups of patients with diabetic macular edema.

Observations on the retinopathy of prematurity.

The fourfold to fivefold increased survival rate since 1950 of premature infants with birthweights of less than 1,000 g apparently explains the increase in cases of retinopathy of prematurity in recent years. A new international classification permits standardized grading of the retinopathy of prematurity based on severity, anterior-posterior location, and the meridians involved. Previously reported clinical trials on the role of vitamin E in the prevention of retinopathy of prematurity have given conflicting results.

Clinical and experimental studies on retinal neovascularization. XXXIX Edward Jackson Memorial Lecture.

Retinal neovascularization is a serious complication of the retinopathy associated with diabetes, branch vein occlusion, sickle cell anemia, and retrolental fibroplasia. Retinal capillary nonperfusion, demonstrated on fluorescein angiography, precedes the development of neovascularization in each of these conditions. Our working hypothesis is that the nonperfused (ischemic or hypoxic) retina liberates a vasoproliferative or angiogenic substance. Although I have delineated the clinical and experimental observations relating to the hypothesis of an ischemic-mediated angiogenesis substance, other postulated mechanisms for the development of retinal neovascularization may be involved. Recent observations on the experimental model of retrolental fibroplasia have demonstrated the markedly abnormal persistence and apparent proliferation of the hyaloid vessels in mice following oxygen-induced retinal vascular closure.

Retrolental fibroplasia in hypoxic newborn.

A premature infant with hypoxia caused by severe cardiac malformations developed stage IB retrolental fibroplasia, which was documented after death. Despite arterial oxygen partial pressures of 91 mm Hg or less the classical histologic changes were observed in the temporal periphery of each eye.

Dominant slowly progressive macular dystrophy.

Twenty-three members of one white family were studied for a new form of dominant slowly progressive macular dystrophy in which visual acuity remained good until the seventh decade. Ten patients had positive signs of this entity. Eight patients had possible early forms. Five had no signs. Several patients had visual acuity fluctuations, documented by their ophthalmologists who saw associated pigment epithelial alterations in some cases. Obvious macular changes included perifoveal pigment epithelial atrophy, posterior pole flecks, and fundus lesions resembling an atrophic form of senile macular degeneration. We suggest a possible hereditary predisposition to senile macular degeneration in our patients.

Vascular tufts of pupillary margin of iris.

A 71-year-old woman complained of "smoky" vision, which was found to be caused by a hyphema with blood dripping from a vascular tuft located in the 12 o'clock meridian of the iris. Fluorescein angiography delineated vascular tufts and argon laser photocoagulation eradicated one of the tufts that bled. Histopathologic studies of iris obtained at the time of cataract extraction showed an aggregate of small vessels at the pupillary margin. Most patients with vascular tufts of the pupillary margin have no systemic disease but they are also observed in diabetes mellitus and myotonic dystrophy.