Patterns of uveitis in children presenting at a tertiary eye care centre in south India

PURPOSE: To study the patterns of uveitis in the paediatric age group in a referral eye care centre in south India. MATERIALS AND METHODS: Thirty-one patients 15 years or younger with uveitis, examined in the year 2000, were included in this study. The uveitis was classified according to the anatomical site of ocular involvement and the most probable aetiological factor. The final diagnosis was based on clinical manifestations and results of specific laboratory investigations. RESULTS: A total 31 (6.29%) paediatric uveitis cases were seen among the 493 uveitic cases in the year 2000. The male:female ratio was 17:14. Anterior (9 cases), intermediate (9 cases) and posterior uveitis (9 cases) were seen in equal number. Four patients had panuveitis. Twenty-seven patients had visual acuity of 6/36 or better at presentation. Approximately 25% (8 of 31) patients had cataract secondary to inflammation. Immunosuppressives were administered in 4 patients and one patient required cataract surgery. CONCLUSION: Uveitis in children comprises approximately 6% of uveitis cases in a referral practice in south India. Anterior, intermediate and posterior uveitis are seen in equal numbers. We recommend that intermediate uveitis be ruled out in all cases of anterior uveitis by careful clinical evaluation including examination under anesthesia (EUA) when required.     

The risk of radiation-induced carcinogenesis after external beam radiotherapy of Graves' orbitopathy

PURPOSE: In order to estimate the risk of radiation-induced carcinogenesis after external beam radiotherapy of Graves' orbitopathy, we made dosimetric measurements with thermoluminescent dosimeters in a male Rando phantom using our treatment technique. METHODS: We produced dose-volume histograms from 5-mm CT slices using our treatment planning system. In this way we estimated the irradiation dose received by the main surrounding organs such as the brain, the bone and the eyeball. We use 6-MV X-ray for the treatment of Graves' orbitopathy and our total dose is 2,000 cGy, 200 cGy per fraction. Clinical target volume was limited to the retrobulbar orbital content and medial rectus muscle, sparing the lenses, lacrimal glands and the sella turcica. All dosimetric measurements with thermoluminescent dosimeters were made 3 times. RESULTS: We found that the dose to the right lens was 101.6 mGy and to left lens 103.4 mGy. Average absorbed doses to red bone marrow, thyroid, lung, esophagus, bone surface, skin and brain, respectively, were estimated to be 523, 21, 4, 5, 81, 29, 47 mGy. Then, using tissue weighting factors specified by the International Commission of Radiation Protection, the resulting total effective dose was calculated to be 66.8 mSv. CONCLUSION: The risk factor for fatal cancer development derived from human epidemiological data is presently assumed to be 10% per Gy. In patients treated by our method of retro-orbital external beam radiotherapy for Graves' orbitopathy, there is a 0.0067 (or 7 per 1,000 persons or 0.7%) risk of developing fatal radiation-induced cancer.     

Novel role for a complement regulatory protein (CD46) in retinal pigment epithelial adhesion

PURPOSE: There is increasing evidence that the complement system may play a significant role in one of the leading diseases causing blindness in the elderly population, age-related macular degeneration. In this study, a novel role in the retina for a regulatory protein in the complement system, CD46, is proposed. METHODS: The retinal pigment epithelium (RPE) was obtained from human donor eyes as well as human immortalized RPE cell lines (ARPE19). Immunohistochemistry and confocal microscopy were used to immunolocalize CD46 and beta1 integrin. Immunoprecipitation experiments with antibodies to either CD46 or beta1 integrin were performed on RPE cell lysates. A cell adhesion assay was used to determine the proportion of RPE cells that adhere to Bruch's membrane explants from donor eyes. RESULTS: Immunohistochemistry and confocal microscopy demonstrated that CD46 was polarized to the basal surface of the RPE along with beta1 integrin, shown previously to be involved in RPE adhesion. Immunoprecipitation experiments demonstrated that CD46 and beta1 integrin coprecipitated from RPE cell lysates when either protein was used as the precipitating antibody. The adhesion assay showed that antibodies to either CD46 or beta1 integrin reduced RPE adhesion to the surface of Bruch's membrane compared with the control. CONCLUSIONS: These findings suggest that this complement regulatory protein, which protects host cells from autologous complement attack, may have a functional interaction with beta1 integrin in the eye that is related to RPE adhesion to its basement membrane and Bruch's membrane.     

Tegaderm transparent dressing (3M) for the treatment of chronic exposure keratopathy

We report an effective alternative treatment of profound chronic exposure keratopathy in a proptotic eye due to intraorbital extension of basal cell carcinoma. The corneal surface gradually reepithelialized in a 6-week period after the first application of Tegaderm transparent dressing (3M, St. Paul, MN, U.S.A.) with instillation of antibiotic ointment on the ocular surface. The patient has been comfortable with an intact epithelial surface, a vascularized cornea, and nonirritated surrounding skin after changing the Tegaderm dressing daily for 15 months. There was no evidence of recurrent corneal ulceration or infiltrations. We conclude that Tegaderm represents a useful treatment of exposure keratopathy due to chronic proptosis.     

Immunization with tumor-derived ER chaperone grp170 elicits tumor-specific CD8+ T-cell responses and reduces pulmonary metastatic disease

Glucose-regulated protein (grp) 170 is a molecular chaperone localized in endoplasmic reticulum (ER), which has been demonstrated to interact with the peptides translocated by transporter associated with antigen presentation (TAP). In our study, we have evaluated the therapeutic efficacy of tumor-derived grp170 against the highly metastatic and poorly immunogenic murine melanoma B16F10. Immunization of mice with grp170 preparations from autologous tumor significantly delayed progression of the primary cancer and reduced established pulmonary metastases, which was associated with the prolonged survival of metastases-bearing mice. However, grp170 from normal liver or antigenically distinct tumor failed to exhibit therapeutic effect. In addition, tumor-derived grp170 elicited a potent cytotoxic T-lymphocyte response specific for B16F10 tumor, which correlates with in vivo protective effects. Adoptive transfer of splenocytes obtained from B16F10-grp170-primed animals remarkably suppressed pulmonary metastases. Depletion of either CD4(+) or CD8(+) T cells in priming phase significantly abrogated the tumor immunity induced by the B16F10-grp170. However, the vaccine activity was intact when CD4(+), not CD8(+), T cells were depleted in effector phase. It suggests that CD4(+) T helper cells play an important role in the generation of effective antitumor response, whereas CD8(+) T cells are predominantly involved in direct killing of tumor cells. These observations have strong clinical implications for using tumor-derived grp170 as a therapeutic vaccine against metastatic diseases.     

Splenic tuberculosis presenting as hypersplenism

A 9-year-old girl with a 5-6-month history of abdominal distension and fever was found to have massive splenomegaly with features of hypersplenism. Apart from a strongly positive Mantoux test, all investigations for massive splenomegaly proved negative. Splenectomy was carried out and histopathological examination of the spleen revealed granulomatous lesions suggestive of tuberculosis. The child improved after splenectomy and anti-tuberculous therapy and is doing well on follow-up. Splenic tuberculosis should be considered as an unusual cause of massive splenomegaly and hypersplenism.     

Expression, tissue distribution, and cellular localization of the antiapoptotic TIP-B1 protein

TIP-B1 is a novel 27-kDa protein isolated from the cytosol of tumor necrosis factor (TNF)-stimulated cells. Cells preincubated with TIP-B1 are protected from TNF-induced apoptosis. This study showed that, as with normal fibroblasts and U937 histiocytic lymphoma, human MCF7 mammary adenocarcinoma cells were protected from TNF in a concentration-dependent manner by pretreatment with either TNF or purified TIP-B1. Immunoblot and immunohistochemical analyses indicated expression of both TIP-B1 mRNA and protein in MCF7 cells and heart, kidney, brain, liver, ovary, uterus, thymus, spleen, lymph node, and mammary gland cells throughout their development. Expression of TIP-B1 was heterogeneous, with staining of specific cell types within tissues. Based on the ability of TIP-B1 to protect both normal and tumor cells from TNF-induced apoptosis and its broad tissue distribution, with expression only in select cells within those tissues, a role for TIP-B1 in the regulation of TNF-induced effects is strongly indicated.     

Lipopolysaccharide-induced-neuroinflammation increases intracellular accumulation of amyloid precursor protein and amyloid beta peptide in APPswe transgenic mice

The present study was designed to examine whether brain inflammation caused by systemic administration of lipopolysaccharides (LPS) alters the expression/processing of amyloid precursor protein (APP) and increases the generation of amyloid beta peptide (Abeta). APPswe transgenic (Tg) mice were treated with either LPS or phosphate-buffered saline (PBS). In LPS-treated APPswe mice, Abeta1-40/42 was 3-fold and APP was 1.8-fold higher than those in PBS-treated mice (P < 0.05) by ELISA, Western blots and immunoprecipitation-mass spectrometry (IP-MS) ProteinChip analysis. Numbers of Abeta- and APP-immunoreactive neurons (Abeta(+) and APP(+) neurons) increased significantly in LPS-treated APPswe mice; APP(+) and Abeta(+) neurons in neocortex were associated with an increased number of F4/80-immunoreactive microglia (F4/80(+) microglia) in their anatomical environment. Our findings demonstrate that experimental neuroinflammation increases APP expression/processing and causes intracellular accumulation of Abeta. It remains to be seen whether such events can cause neuronal dysfunction/degeneration and, with time, lead to extracellular Abeta deposits, as they occur in Alzheimer's disease.     

Urinary incontinence after pelvic trauma: A case report

Stress and urge urinary incontinence may develop after a pelvic trauma especially after pelvic bone fractures. Incontinence may persist eventhough any type of bladder neck suspension is performed if malunion occurs between fracture ends. In stress and urge urinary incontinence developed after pelvic trauma, patients should also be evaluated for malunion of fractures which may lead to bone spurs and during any type of bladder neck suspension these should also be removed. This revised version was published online in September 2006 with corrections to the Cover Date.