Histopathologic analysis of 232 eyes with retinoblastoma conducted in an Indian tertiary-care ophthalmic center

PURPOSE: To study the histopathologic features of 232 enucleated eyes with retinoblastoma. MATERIALS AND METHODS: Two hundred thirty-two enucleated eyes with retinoblastoma in a tertiary-care institute from 1982 to 2001 were reviewed. Data were collected and analyzed about the type of growth and the presence or absence of vitreous or subretinal seeding, rosettes and fleurettes, necrosis, calcification, iris neovascularization, and invasion of the anterior chamber, iris, choroid, optic nerve, and sclera. Choroidal invasion was graded using a new system. Results were analyzed for statistical significance. RESULTS: The endophytic growth pattern was common in 118 (51%) of the eyes. Vitreous seeds were present in 109 (47%) of the tumors, 23 (10%) of the tumors had subretinal seeds, and 14 (6%) of the tumors had both. Poorly differentiated tumors were present in 134 (58%) of the eyes. Iris neovascularization was noted in 71 (31%) of the eyes and choroidal invasion was observed in 78 (34%) of the eyes. Of these 78 eyes, full-thickness (stage 4) choroidal invasion was present in 51 (65%). Optic nerve invasion was observed in 75 (32%) of the eyes, of which prelaminar involvement occurred in 40 (53%) and postlaminar involvement occurred in 22 (29%). CONCLUSION: A higher incidence of choroidal and optic nerve infiltration was noted among Asian Indian children than among children from the West. This could be due to delayed diagnosis or to a difference in the biological behavior of tumors occurring in the Asian Indian population.     

Role of the dorsolateral pontine nucleus in short-term adaptation of the horizontal vestibuloocular reflex

The dorsolateral pontine nucleus (DLPN) is a major component of the cortico-ponto-cerebellar pathway that carries signals essential for smooth pursuit. This pathway also carries visual signals that could play a role in visually guided motor learning in the vestibular ocular reflex (VOR). However, there have been no previous studies that tested this possibility directly. The aim of this study was to determine the potential role of the DLPN in short-term VOR gain adaptation produced by viewing a scene through lenses placed in front of both eyes. In control experiments, adaptation of VOR gain was achieved by sinusoidal rotation (0.2 Hz, 30 degrees /s) for 2 h while the monkey viewed a stationary visual surround through either magnifying (x2) or minifying (x0.5) lenses. This led to increases (23-32%) or decreases (22-48%) of VOR gain as measured in complete darkness (VORd). We used injections of muscimol, a potent GABA(A) agonist (0.5 microl; 2%), to reversibly inactivate the DLPN, unilaterally, in three monkeys. After DLPN inactivation, initial acceleration of ipsilateral smooth-pursuit was reduced by 35-68%, and steady-state gain was reduced by 32-61%. Despite these significant deficits (P < 0.01) in ipsilesional smooth pursuit, the VOR during lens viewing was similar to that measured in preinjection control experiments. Similarly, after 2 h of adaptation, VORd gain was not significantly different (P > 0.61) from control adaptation values for either ipsi- or contralesional directions of head rotation. This was the case even though a stable ipsilesional smooth pursuit deficit persisted throughout the full adaptation period. Our results suggest that visual error signals for short-term adaptation of the VOR are derived from sources other than the DLPN perhaps including other basilar pontine nuclei and the accessory optic system.     

Fractal properties of sympathetic nerve discharge

Fano factor analysis and dispersional analysis were used to characterize time series of single and multifiber spikes recorded from the preganglionic cervical sympathetic nerve and cardiac-related slow-wave activity of the whole postganglionic sympathetic vertebral nerve (VN) in anesthetized cats. Fluctuations in spike counts and interspike intervals for single preganglionic fibers proved to be fractal (i.e., time-scale invariant), as reflected by a power law relationship between indices of the variance of these properties and the window size used to make the measurements. Importantly, random shuffling of the data eliminated the power law relationships. Fluctuations in spike counts in preganglionic multifiber activity also were fractal, as were fluctuations in the height and of the area of cardiac-related slow waves recorded from the whole postganglionic VN. These fractal fluctuations were persistent (i.e., positively correlated), as reflected by a Hurst exponent significantly >0.5. Although fluctuations in the interval between cardiac-related VN slow waves were random, those in the interval between heart beats were fractal and persistent. These results demonstrate for the first time that apparently random fluctuations in sympathetic nerve discharge are, in fact, dictated by a complex deterministic process that imparts "long-term" memory to the system. Whether such time-scale invariant behavior plays a role in generating the fractal component of heart rate variability remains to be determined.     

Immunopolarization of CD4+ and CD8+ T cells to Type-1-like is associated with melanocyte loss in human vitiligo

Vitiligo is an autoimmune condition characterized by loss of epidermal melanocytes. High frequencies of melanocyte-reactive cytotoxic T cells in the peripheral blood of vitiligo patients and the observed correlation between perilesional T-cell infiltration and melanocyte loss in situ suggest the important role of cellular autoimmunity in the pathogenesis of this disease. We isolated T cells from both perilesional and nonlesional skin biopsies obtained from five vitiligo patients, then cloned and analyzed their profile of cytokine production after short-term, nonspecific expansion in vitro. Perilesional T-cell clones (TCC) derived from patients with vitiligo exhibited a predominant Type-1-like cytokine secretion profile, whereas the degree of Type-1 polarization in uninvolved skin-derived TCC correlated with the process of microscopically observed melanocyte destruction in situ. Detailed analysis of broad spectrum of cytokines produced by perilesional- and nonlesional-derived CD4+ and CD8+ TCC confirmed polarization toward Type-1-like in both CD4 and CD8 compartments, which paralleled depigmentation process observed locally in the skin. Furthermore, CD8+ TCC derived from two patients also were analyzed for reactivity against autologous melanocytes. The antimelanocyte cytotoxic reactivity was observed among CD8+ TCC isolated from perilesional biopsies of two patients with vitiligo. Finally, in two of five patients, tetramer analysis revealed presence of high frequencies of Mart-1-specific CD8 T cells in T-cell lines derived from perilesional skin. Altogether our data support the role of cellular mechanisms playing a significant part in the destruction of melanocytes in human autoimmune vitiligo.     

Cell-mediated immune responses of healthy laboratory volunteers to sonicate antigens prepared from the most prevalent strains of Mycobacterium tuberculosis from South India harboring a single copy of IS6110

Our restriction fragment length polymorphism (RFLP) studies have shown that the most prevalent (40%) strains of Mycobacterium tuberculosis from South India contain a single copy of the IS6110 insertion sequence and are of importance in studying virulence and immunity. Sonicate antigens from seven such strains were used to study in vitro T-cell proliferation and gamma interferon (IFN-gamma) and interleukin-12 (IL-12) secretion as markers of protective immunity in 25 healthy subjects positive for purified protein derivative (PPD). The standard PPD and heat-killed H37Rv antigens induced the maximum levels of T-cell proliferation and IFN-gamma secretion but low levels of IL-12. All sonicate antigens induced T-cell proliferation and IFN-gamma secretion with strong positive correlation. Our results suggest that sonicate antigens from the most prevalent and recent strains of M. tuberculosis from clinical isolates have the potential to induce T-cell activation and may allow newer and specific antigens to be further characterized for diagnosis and vaccine development.     

Virulence genes and neutral DNA markers of Helicobacter pylori isolates from different ethnic communities of West Bengal,India

Virulence-associated genes and neutral DNA markers of Helicobacter pylori strains from the Santhal and Oroan ethnic minorities of West Bengal, India, were studied. These people have traditionally been quite separate from other Indians and differ culturally, genetically, and linguistically from mainstream Bengalis, whose H. pylori strains have been characterized previously. H. pylori was found in each of 49 study participants, although none had peptic ulcer disease, and was cultured from 31 of them. All strains carried the cag pathogenicity island and potentially toxigenic s1 alleles of vacuolating cytotoxin gene (vacA) and were resistant to at least 8 micro g of metronidazole per ml. DNA sequence motifs in vacA mid-region m1 alleles, cagA, and an informative insertion or deletion motif next to cagA from these strains were similar to those of strains from ethnic Bengalis. Three mobile elements, IS605, IS607, and ISHp608, were present in 29, 19, and 10%, respectively, of Santhal and Oroan strains, which is similar to their prevalence in Bengali H. pylori. Thus, there is no evidence that the gene pools of H. pylori of these ethnic minorities differ from those of Bengalis from the same region. This relatedness of strains from persons of different ethnicities bears on our understanding of H. pylori transmission between communities and genome evolution.     

Uterine contraction frequency before and after successful tocolytic therapy for preterm uterine contractions

OBJECTIVE: To examine the association between prelabor uterine contraction frequency (UCF) and the success of tocolytic therapy for preterm labor (PTL). STUDY DESIGN: Eleven centers conducted a prospective, observational study of UCF recorded between 22(0/7) and 36(6/7) weeks' gestational age or until delivery > or = 2 times/d on > or = 2 d/wk in women with singleton pregnancies with and without risk factors for preterm birth. Uterine contraction data obtained from patients diagnosed with PTL allowed comparison of mean UCF both before and after an acute episode of PTL treated with either intravenous, subcutaneous or oral tocolysis. The signed rank test was used to analyze differences in UCF before and after tocolytic therapy and between women who were or were not successfully treated with a labor-inhibiting agent. RESULTS: Of 454 enrolled women, 128 were diagnosed with PTL, and 74 were successfully treated with a labor-inhibiting agent. The mean UCF preceding PTL was not different between those women successfully treated and those who delivered as a consequence of the PTL episode. There was no difference (P = .653) in mean UCF between the week before PTL (UCF 0.60 +/- 0.8, median 0.30) and the first week of monitoring after successful tocolysis (UCF 0.82 +/- 1.4, median 0.27). CONCLUSION: The mean UCF immediately preceding PTL does not predict tocolytic success or failure.