Familial exudative vitreoretinopathy associated with nonneovascular chronic angle-closure glaucoma

Purpose: Cases of angle-closure glaucoma in patients with familial exudative vitreoretinopathy have been reported secondary to neovascularization of the anterior segment. Cases secondary to nonneovascular mechanisms have not been previously reported. Methods: Two cases are presented of angle-closure glaucoma as a result of a nonneovascular mechanism. Results: Neovascularization was found to be a very unlikely explanation for the angle closure in these two cases. Conclusion: There may be an association between familial exudative vitreoretinopathy and angle-closure glaucoma as a direct result of a retrolental process or more likely a relative lens-iris pupillary block with a large lens.

Evaluation of Microcollimated Pars Plana External Beam Radiation in the Porcine Eye

Purpose: To evaluate the clinical and histological side effects of a prototype stereotactic radiotherapy system delivering microcollimated external beam radiation through pars plana in porcine eyes.

Methods: Five Yucatan mini-swine (10 eyes) were randomized to five treatment groups. Eight eyes were dosed with X-ray radiation on Day 1, and two eyes served as untreated controls. Treated eyes received doses up to 60 Gy to the retina and up to 130 Gy to the sclera using single or overlapping beams. The treatment beams were highly collimated such that the diameter was approximately 2.5 mm on the sclera and 3 mm on the retinal surface. Fundus photography, fluorescein angiography (FA), and spectral domain optical coherence tomography (SD-OCT) were obtained on days 7, 30, 60, and 110. Images were examined by a masked grader and evaluated for abnormalities. Animals were sacrificed on day 111 and gross and histopathological analysis was conducted.

Results: Histological and gross changes to eye structures including conjunctiva and lens were minimal at all doses. Fundus, FA, and SD-OCT of the targeted region failed to disclose any abnormality in the control or 21 Gy treated animals. In the 42 and 60 Gy animals, hypopigmented spots were noted after treatment on clinical exam, and corresponding hyperfluorescent staining was seen in late frames. No evidence of choroidal hypoperfusion was seen. The histological specimens from the 60 Gy animals showed photoreceptor loss and displacement of cone nuclei.

Conclusion: Transcleral stereotactic radiation dosing in porcine eyes can be accomplished with no significant adverse events as doses less than 42 Gy.

Rat clonidine mydriasis model:Imidazoline receptors are not involved

The clonidine mydriasis model in rats has been widely applied in preclinical research to characterize a -adrenoceptor antagonistic properties of drugs. The present study was undertaken to pharmacologically determine if imidazoline I receptors are also involved in this model system. Sigmoid dose-response curves for pupillary dilation were produced in pentobarbital anesthetized rats by intravenous administration of increasing doses of agonists (guanabenz for a -adrenoceptors, clonidine for both a - adrenoceptors and imidazoline I receptors, and rilmenidine for imidazoline I receptors). Two antagonists (RS 79948 for a -adrenoceptors and efaroxan for imidazoline I receptors) were used to antagonize the mydriasis elicited by those three agonists, with antagonistic potencies calculated. In additional experiments, we examined the effect of the selective imidazoline I receptor antagonist, AGN 192403, on clonidine-induced mydriasis. The results showed that pupillary response curves elicited by guanabenz, clonidine and rilmenidine were competitively antagonized by both RS 79948 (0.03-1 mg/kg) and efaroxan (0.03-1 mg/kg) in a dose-related fashion. The potencies of either antagonist against the three agonists were not significantly different. AGN 192403 (5 mg/kg) did not significantly shift the clonidine mydriasis curve. These results suggest that imidazoline I receptors are not functionally involved in the rat clonidine mydriasis model and support this in vivo system as a useful model for studies of a -adrenoceptors. © 2004 Elsevier B.V. All rights reserved.

α-adrenoceptors do not mediate reflex mydriasis in rabbits

The aim of this study was to identify receptors that mediate reflex mydriasis in pentobarbital-anesthetized rabbits, in which the cervical sympathetic nerve was sectioned unilaterally. Voltage-response curves of pupillary dilation were generated bilaterally by stimulation of the sciatic nerve. Evoked mydriatic responses were mediated mainly by efferent parasympathetic innervation, and, to a lesser extent, by sympathetic innervation. The a-adrenergic antagonist, phenoxybenzamine (0.3 mg/kg, intravenously (i.v.)), antagonized mydriasis of the neurally intact eye, but not that on the sympathectomized side. The a- adrenergic antagonist, RS 79948 (0.3 mg/kg, i.v.), potentiated mydriasis of the normal eye, but was without either a potentiating or inhibitory effect on the mydriasis of the sympathectomized eye. In addition, the dopamine-receptor antagonist, haloperidol (1 mg/kg, i.v.), inhibited evoked mydriasis of the sympathectomized eye. These results suggest that, unlike some other species (cats and rats), a-adrenoceptors do not mediate reflex mydriasis elicited by sciatic-nerve stimulation in the rabbit, and support the previous finding in humans that dopamine receptors may mediate this response.

Studies of alpha-adrenoceptor antagonists on sympathetic mydriasis in rabbits

This study was undertaken to identify the alpha-adrenergic receptor type responsible for sympathetically evoked mydriasis in pentobarbital-anesthetized rabbits. Frequency-response curves of pupillary dilation were generated by stimulation of the preganglionic cervical sympathetic nerve (1-64 Hz). Evoked mydriatic responses were inhibited by systemic administration of nonselective alpha-adrenergic antagonists, phentolamine (0.3-10 mg/kg) and phenoxybenzamine (0.03-0.3 mg/kg), as well as the selective alpha(1)-adrenergic antagonist, prazosin (0.1-1 mg/kg). The alpha(2)-adrenergic antagonist, RS 79948 (0.3 mg/kg, i.v.) was without inhibitory effect, but potentiated the mydriatic response. In addition, the selective alpha(1A)-adrenoceptor antagonist, 5-methylurapidil (0.1-1 mg/kg, i.v.), antagonized the elicited mydriasis in a dose-dependent fashion. Unlike previous observations that prazosin does not block the adrenoceptor in rabbit iris dilator muscle, our results suggest that prazosin is effective in inhibiting neuronally elicited mydriasis in this species, and that alpha(1A)-adrenoceptors appear to mediate the response.

Histamine H3 receptor-mediated inhibition of sympathetically evoked mydriasis in rats

This study was designed to determine if the histamine H3 receptor agonist R-alpha-methylhistamine would play a role in modulation of sympathetically evoked mydriasis in anesthetized rats, and if so, to ascertain the specific receptor subtype(s) involved. Reproducible frequency-response curves of pupillary dilation were generated by stimulation of the cervical preganglionic sympathetic nerve (1-32 Hz). Systemic administration of R-alpha-methylhistamine (0.3-3.0 mg kg(-1)) produced a dose-related inhibition of the evoked mydriasis. The greatest inhibition was seen at lower frequency levels, with about 43% depression observed at 2 Hz. The specific histamine H3 receptor antagonist, clobenpropit (3.0 mg kg(-1), i.v.), blocked the inhibitory effect of R-alpha-methylhistamine, whereas neither the histamine H2 receptor antagonist, cimetidine (5.0 mg kg(-1), i.v.), nor the histamine H1 receptor antagonist, chlorpheniramine (0.5 mg kg(-1), i.v.), was effective. The histamine H2 receptor agonist, dimaprit (10 mg kg(-1), i.v.), was also without effect on the evoked mydriasis. R-alpha-methylhistamine (3.0 mg kg(-1)) did not inhibit phenylephrine-induced mydriasis. These results support the conclusion that R-alpha-methylhistamine produces inhibition of sympathetically evoked mydriasis via histamine H3 receptor stimulation, presumably by an action on presynaptic histamine H3 receptors.

Limits of Dissent, Perils of Activism: Spaces of Resistance and the New Security Logic

On 26 December 2003 an Israeli activist was shot by the Israeli Army while he was participating in a demonstration organized by Anarchists Against the Wall (AAtW) in the West Bank. This was the first time Israeli Soldiers have deliberately shot live bullets at a Jewish-Israeli activist. This paper is an attempt to understand the set of conditions, the enveloping frameworks, and the new discourses that have made this event, and similar shootings that soon followed, possible. Situating the actions of AAtW within a much wider context of securitization—of identities, movements, and bodies—we examine strategies of resistance which are deployed in highly securitized public spaces. We claim that an unexpected matrix of identity in which abnormality is configured as security threat render the bodies of activists especially precarious. The paper thus provides an account of the new rationales of security technologies and tactics which increasingly govern public spaces.

Haunted Seasons: Television Ghost Stories for Christmas and Horror for Halloween

Why do the English have ghost stories at Christmas? Why does US television have special Halloween episodes? Is this all down to Dickens, or is it a hangover of an ancient, pagan past? Why does it survive? Haunted Seasons explores these and related questions, examining the history and meaning of seasonal horror. It reaches back through archaeological evidence of ancient beliefs, through Shakespeare, and Victorian ghost stories, and the works of M.R.James, and onwards to radio and television. The broader genre of supernatural television is considered in relation to the irruptions of abnormality into the normal, along with the significance of time and the seasons in these narratives and their telling. Particular focus is placed on the BBC Ghost Story for Christmas strand and the Halloween episodes of The Simpsons to help us interpret the continued use of these seasonal horror stories and their place in society, from fireside to television.

Severe aplastic anaemia in association with a unique constitutional translocation 46,XY,t(6;10)(q13;q22)c

Severe aplastic anaemia (SAA) is an uncommon disorder which may be associated with several congenital syndromes. However, it has rarely been described in association with a constitutional karyotypic abnormality. The breakpoint of the balanced t(6:10)(q13:q22) translocation described here does not disrupt any currently recognized gene of haemopoietic or stromal importance. This report also highlights the problems inherent in the use of bone marrow transplantation (BMT) for treating multiply transfused aplastic anaemia patients.

Donor leukemia following allogeneic bone marrow transplantation

Although allogeneic bone marrow transplantation has been shown to be a highly effective treatment for acute and chronic leukemia, leukemic relapse remains a significant problem. Leukemic relapse occurs in recipient cells in the majority of cases, but the paucity of donor cell leukemias may reflect the sensitivity of the investigative technique. We have developed a highly sensitive technique to identify the origin of all hematopoietic cells in the post transplant state which is based on PCR amplification of microsatellites, polymorphic tandem repetitive elements. We have identified donor leukemia (AML M5) following a sex matched BMT for severe aplastic anemia, verified a previously reported case of donor leukemia following BMT for chronic granulocytic leukemia and recently identified an acquired cytogenetic abnormality(del 11q23) in donor cells four years following an apparently successful BMT for AML. In all cases the donors have remained healthy. Postulated mechanisms include transfer to the transplanted marrow of a dormant oncogene residing in the DNA of either a virus, the chromosomes of degenerating irradiation damaged host leukemic cells or in the marrow stroma which is radioresistant and host in origin following BMT. Using sensitive techniques donor leukemia has been shown to be a more common event than was previously thought and an understanding of its pathogenesis may allow us to elucidate leukemogenic mechanisms in man.

Attitudes of physicians, patients, and village health workers toward glaucoma and diabetic retinopathy in rural China:A focus group study

Objective: To understand the knowledge and attitudes of rural Chinese physicians, patients, and village health workers (VHWs) toward diabetic eye disease and glaucoma. Methods: Focus groups for each of the 3 stakeholders were conducted in 3 counties (9 groups). The focus groups were recorded, transcribed, and coded using specialized software. Responses to questions about barriers to compliance and interventions to remove these barriers were also ranked and scored. Results: Among 22 physicians, 23 patients, and 25 VHWs, knowledge about diabetic eye disease was generally good, but physicians and patients understood glaucoma only as an acutely symptomatic disease of relatively low prevalence. Physicians did not favor routine pupillary dilation to detect asymptomatic disease, expressing concerns about workflow and danger and inconvenience to patients. Providers believed that cost was the main barrier to patient compliance, whereas patients ranked poorly trained physicians as more important. All 3 stakeholder groups ranked financial interventions to improve compliance (eg, direct payment, lotteries, and contracts) low and preferred patient education and telephone contact by nurses. All the groups somewhat doubted the ability of VHWs to screen for eye disease accurately, but patients were generally willing to pay for VHW screening. The VHWs were uncertain about the value of eye care training but might accept it if accompanied by equipment. They did not rank payment for screening services as important. Conclusions: Misconceptions about glaucoma's asymptomatic nature and an unwillingness to routinely examine asymptomatic patients must be addressed in training programs. Home contact by nurses and patient education may be the most appropriate interventions to improve compliance.

Responsiveness of dark-adaptation threshold to vitamin A and beta-carotene supplementation in pregnant and lactating women in Nepal.

BACKGROUND: Impaired dark adaptation occurs commonly in vitamin A deficiency. OBJECTIVE: We sought to examine the responsiveness of dark-adaptation threshold to vitamin A and beta-carotene supplementation in Nepali women. DESIGN: The dark-adapted pupillary response was tested in 298 pregnant women aged 15-45 y in a placebo-controlled trial of vitamin A and beta-carotene; 131 of these women were also tested at 3 mo postpartum. Results were compared with those for 100 nonpregnant US women of similar age. The amount of light required for pupillary constriction was recorded after bleaching and dark adaptation. RESULTS: Pregnant women receiving vitamin A had better dark-adaptation thresholds (-1.24 log cd/m(2)) than did those receiving placebo (-1.11 log cd/m(2); P: = 0. 03) or beta-carotene (-1.13 log cd/m(2); P: = 0.05) (t tests with Bonferroni correction). Dark-adaptation threshold was associated with serum retinol concentration in pregnant women receiving placebo (P: = 0.001) and in those receiving beta-carotene (P: = 0.003) but not in those receiving vitamin A. Among women receiving placebo, mean dark-adaptation thresholds were better during the first trimester (-1.23 log cd/m(2)) than during the second and third trimesters (-1.03 log cd/m(2); P: = 0.02, t test). The mean threshold of nonpregnant US women (-1.35 log cd/m(2)) was better than that of all 3 Nepali groups (P: < 0.001, t test, for all 3 groups). CONCLUSIONS: During pregnancy, pupillary dark adaptation was strongly associated with serum retinol concentration and improved significantly in response to vitamin A supplementation. This noninvasive testing technique is a valid indicator of population vitamin A status in women of reproductive age.

Physiologic indicators of vitamin A status.

Physiologic indicators reflect the functional consequences of vitamin A deficiency and may be particularly useful for detecting early perturbations in vitamin A status. In conjunctival impression cytology (CIC), epithelial morphology and the presence or absence of mucin spots and goblet cells allow samples, obtained by applying filter paper to the temporal conjunctiva, to be characterized as normal or typical of vitamin A-deficient keratinizing metaplasia. The validity of CIC has been established with reference to other indicators of vitamin A status, and a prevalence of > or =20% abnormal results has been suggested as indicative of a public health problem. However, interpretation of specimens requires considerable training, and nonresponsiveness to supplementation is a frequent problem, which limits the utility of CIC as a method for evaluating the impact of intervention programs. Several simplified field protocols for dark adaptation have been developed, including one in which dark adaptation is assessed by the responsiveness of the pupil to light. Night blind subjects have consistently shown abnormal results on this test, and a significant response to placebo-controlled dosing has been demonstrated for children and pregnant women. Scores have correlated significantly with serum retinol and relative dose response. Pupillary dark adaptation testing is acceptable to most children as young as 2 y old. Limitations of this technique include a time course for recovery after dosing as long as 4-6 wk, a testing time of 20 min, and the need for 1-3 d of training. Given its low cost, noninvasive nature, and lack of the need to transport samples, pupillary dark adaptation offers advantages over other techniques for assessing a population's vitamin A status.

Validation of night blindness reports among children and women in a vitamin A deficient population in rural Tanzania.

OBJECTIVE: This study validates different definitions of reported night blindness (XN) in a vitamin A deficient African population with no local term for XN. DESIGN: Case-control study with follow-up after treatment. SETTING: Eight primary schools and health centres in rural Tanzania. SUBJECTS: A total of 1214 participants were screened for reported XN and other eye signs of xerophthalmia: 461 children aged 24-71 months, 562 primary school-age children and 191 pregnant or breast-feeding women. All 152 cases of reported XN were selected for the validation study and group matched with 321 controls who did not complain of XN. XN reports were validated against serum retinol concentrations and pupillary dark adaptation measurements in cases and controls. INTERVENTION: All children and women who reported XN or had other signs of active xerophthalmia were treated with vitamin A and followed up 3-4 weeks later. Half of the untreated control group who had their serum retinol examined in the baseline examination were also followed up. RESULTS: The overall prevalence of reported XN was 12.5%. At baseline, mean pupillary threshold (-1.52 vs -1.55 log cd/m(2), P=0.501) and median serum retinol concentrations (0.95 vs 0.93 micromol/l, P=0.734) were not significantly different in cases and controls either overall or in each population group. More restricted case definitions reduced the prevalence of reported XN to 5.5% (P<0.001), but there was still no significant difference between cases and controls although the results were in the expected direction. After treatment, the median serum retinol concentration improved significantly only in the most deficient group, the young children. Dark adaptation improved in all the subgroups but the difference was only significant for young children and primary school-age children when the restricted case definitions were used. CONCLUSIONS: XN reports are a poor indicator of vitamin A deficiency in this population. SPONSORSHIP: Task Force Sight and Life, Basel, Switzerland.

Pupil constriction can alter the accuracy of dark room provocative test.

BACKGROUND: Primary angle-closure glaucoma (PACG) is a major cause of visual morbidity in East Asia. Dark-room provocative test (DRPT) has been used to determine which narrow angles have the risk to develop angle closure. However, the accuracy of DRPT might be altered because that after emerging from the dark room, the configuration of the angle is affected by the light of the slit-lamp and the appositionally closed angle reopens. The aim of this study was to examine the pupillary diameter in different light conditions and use it as a parameter to assess the accuracy of dark-room provocative test. METHODS: Patients with suspected primary angle-closure glaucoma undergoing DRPT were recruited. The anterior chamber angle was examined by anterior segment optical coherence tomography under the following conditions: (1) in standard room illumination; (2) after short-term dark-adaptation and (3) after DRPT. Mean values of pupil size and numbers of appositionally closed angle under different conditions were compared. RESULTS: A total of 47 eyes of 47 patients were analyzed. The pupil size after DRPT was smaller than that after short-term dark-adaptation (P < 0.001) and smaller than that in standard room illumination (P = 0.026). The numbers of appositionally closed angles after short-term dark-adaptation were significantly larger than those after DRPT (P < 0.001). There was no significant difference between the numbers of appositionally closed angles in standard room illumination and after DRPT (P = 0.157). CONCLUSIONS: Constriction of pupil size immediately after prolonged dark room provocative test may lead to change in the angle configuration, which may lead to false negative results. We suggest a modified protocol of recording intraocular pressure immediately after DRPT and performing gonioscopy following short-term dark adaptation to improve the accuracy of angle closure assessment.