Progesterone receptor expression is associated with longer overall survival within high-grade histotypes of endometrial carcinoma: A Canadian high risk endometrial cancer consortium (CHREC) study.

OBJECTIVE: To assess the association of hormone receptor expression with outcome in high-grade endometrial carcinomas. METHODS: This study included three sites participating in the Canadian High Risk Endometrial Cancer (CHREC) consortium. Sections from tissue microarrays containing cases with a diagnosis of endometrioid grade 3 (EC3) and endometrial serous carcinoma (ESC) were assessed for estrogen (ER) and progesterone receptor (PR) expression by immunohistochemistry. Expression was considered present if >1% of tumor cell nuclei were labeled. Associations with overall survival were assessed. RESULTS: ER expression was present in 168/216 (78%) of EC3 and 124/192 (65%) of ESC. PR expression was present in 148/212 (70%) of EC3 and 83/196 (42%) of ESC. PR expression was significantly associated with favorable overall survival in EC3 and ESC (log rank, p=0.018 and p=0.0024) but ER expression was not. PR expression was significantly associated with favorable overall survival in EC3 independent of age, stage, center and lymph-vascular invasion (hazard ratio=0.457, 95% CI 0.257-0.811, p=0.0075) as well as in stage I and II ESC (hazard ratio=0.266, 95% CI 0.094-0.750, p=0.0123). CONCLUSION: Our data provide support for the assessment of the PR expression status in EC3 and ESC. Future work will be required to determine how PR expression may be incorporated into management of patients with EC3 and ESC.

Treatment related outcomes in high-risk endometrial carcinoma: Canadian high risk endometrial cancer consortium (CHREC).

OBJECTIVE: The lack of randomized clinical data pertaining to optimal surgery and adjuvant treatment in women with high-risk histotypes of endometrial cancer has resulted in selective management based on institutional policies. The objective of this study was to assess differences in treatment strategies and their outcomes among various institutions. METHOD: High-risk endometrial cancer cases (2000-2012) with corresponding clinicopathologic data were collected from 7 academic cancer centers. Histotypes included grade 3 endometrioid (EC3), serous (ESC), clear cell (CCC) and carcinosarcoma (CS). Associations with overall survival were performed using Cox proportional hazard regression. RESULTS: 1260 patients treated between 2000 and 2012 were included in the study: 398 EC3, 449 ESC, 91 CCC, 236 CS and 83 'other'. The use of adjuvant chemotherapy, adjuvant radiation, and extent of surgical staging were statistically different among the 7 centers (P<0.001). Histotype was independently associated with overall survival (OS) in patients with stage 1 and 2 disease who underwent surgical staging (P=0.0324). Adjuvant radiation was associated with improved OS for EC3 and CCC and adjuvant chemotherapy was associated with improved OS for ESC and CS. There was a high rate of recurrence (17.8% and 21.4%) in completely staged, stage 1A patients with ESC and CS respectively. CONCLUSION: There exists a wide variation in practice and outcomes for high-risk histotypes of endometrial cancer. The relative impact of adjuvant therapy appears to be histotype dependent and prospective studies examining adjuvant treatment in high-risk histotypes should use caution combining them together.

Canadian high risk endometrial cancer (CHREC) consortium: analyzing the clinical behavior of high risk endometrial cancers.

OBJECTIVES: The objective of this study is to analyze the clinical behavior of endometrial carcinomas by high risk(HR) histotype, including stage, overall survival, recurrence free survival and patterns of failure. METHODS: This is a retrospective multi-institutional cohort study performed at 7 tertiary care centers across Canada between 2000 and 2012 and included: grade 3 endometrioid (EC3), endometrial serous cancer (ESC), clear cell carcinomas (CCC) and carcinosarcoma (CS). Clinicopathological and outcome data was collected. RESULTS: 1260 women with endometrial carcinoma with 1013 having staging procedures were identified; 398 EC3, 449 ESC, 236 CS and 91 CCC. 51.8% had lymphovascular space invasion (LVSI) and 18.5% had omental involvement with a statistically significant difference between tumor types (p=0.0005 and 0.0047 respectively); ESC had a significantly greater rate of omental involvement compared to EC3 (22% to 9%, p=0.0005). Within the entire cohort 49.3% were stage 1, 10.6% were stage 2, 27.4% were stage 3 and 12.7% were stage 4. Overall survival and recurrence free survival were significantly different between histotypes (p<0.0001) with CS having the worst outcome. Overall 31.5% of patients recurred. CS and ESC had a higher distant recurrence rate compared to EC3 (29.6%, 31.0% compared to 16.4%, p=0.0002 and p<0.001). CONCLUSION: This study is one of the largest clinical cohorts of HR endometrial cancers. We have further clarified the impact of histotype and stage on recurrence and survival, and the high likelihood of distant recurrence. However, the differences are modest and risk prediction models will require additional molecular markers.

Neighborhood disadvantage and parenting predict longitudinal clustering of uncinate fasciculus microstructural integrity and clinical symptomatology in adolescents.

Parenting behaviors and neighborhood environment influence the development of adolescents' brains and behaviors. Simultaneous trajectories of brain and behavior, however, are understudied, especially in these environmental contexts. In this four-wave study spanning 9-18 years of age (N=224 at baseline, N=138 at final assessment) we used longitudinal k-means clustering to identify clusters of participants with distinct trajectories of uncinate fasciculus (UF) fractional anisotropy (FA) and anxiety symptoms; we examined behavioral outcomes and identified environmental factors that predicted cluster membership. We identified three clusters of participants: 1) high UF FA and low symptoms ("low-risk"); 2) low UF FA and high symptoms ("high-risk"); and 3) low UF FA and low symptoms ("resilient"). Adolescents in disadvantaged neighborhoods were more likely to be in the resilient than high-risk cluster if they also experienced maternal warmth. Thus, neighborhood disadvantage may confer neural risk for psychopathology that can be buffered by maternal warmth, highlighting the importance of considering multiple environmental influences in understanding emotional and neural development in youth.

An interleukin-4-induced transcription factor: IL-4 Stat.

Interleukin-4 (IL-4) is an immunomodulatory cytokine secreted by activated T lymphocytes, basophils, and mast cells. It plays an important role in modulating the balance of T helper (Th) cell subsets, favoring expansion of the Th2 lineage relative to Th1. Imbalance of these T lymphocyte subsets has been implicated in immunological diseases including allergy, inflammation, and autoimmune disease. IL-4 may mediate its biological effects, at least in part, by activating a tyrosine-phosphorylated DNA binding protein. This protein has now been purified and its encoding gene cloned. Examination of the primary amino acid sequence of this protein indicates that it is a member of the signal transducers and activators of transcription (Stat) family of DNA binding proteins, hereby designated IL-4 Stat. Study of the inhibitory activities of phosphotyrosine-containing peptides derived from the intracellular domain of the IL-4 receptor provided evidence for direct coupling of receptor and transcription factor during the IL-4 Stat activation cycle. Such observations indicate that IL-4 Stat has the same functional domain for both receptor coupling and dimerization.

PEDF induces p53-mediated apoptosis through PPAR gamma signaling in human umbilical vein endothelial cells.

OBJECTIVE: Pigment epithelial-derived factor (PEDF) is a potent anti-angiogenic factor whose effects are partially mediated through the induction of endothelial cell apoptosis. The pathway mediating endothelial cell apoptosis has not been fully established. Here we investigated the participation of peroxisome proliferator-activated receptor gamma (PPARgamma) and p53 in the apoptosis of human umbilical vein endothelial cells (HUVECs). METHODS AND RESULTS: HUVECs pretreated with either PPARgamma antagonist or PPARgamma small interfering RNA (siRNA) suppressed PEDF-induced apoptosis as determined by TUNEL assay, annexin V-FITC/PI staining, and cleavage of procaspase-8, -9, -3. PEDF sequentially induced PPARgamma and p53 expression as observed in immunoblotting and immunofluoresence assays. PEDF also increased the transcriptional activity of PPARgamma as evident from electromobility shift assays, and p53 as determined by the phosphorylation and acetylation of p53 and the induction of Bax. The induction of p53 by PEDF was abolished by either PPARgamma antagonist or PPARgamma siRNA. PEDF-mediated HUVEC apoptosis and cleavage of procaspases were significantly attenuated by p53 siRNA. CONCLUSIONS: Our observations indicate that PEDF induces HUVECs apoptosis through the sequential induction of PPARgamma and p53 overexpression. With the growing interest in anti-angiogenesis as a novel approach to cancer therapy, defining the mechanism of PEDF-mediated HUVEC apoptosis may facilitate the development of new therapeutics.

Visual outcomes for high myopic patients with or without myopic maculopathy: a 10 year follow up study.

AIM: To evaluate the visual outcomes for high myopic patients aged 40 years and older with or without myopic maculopathy. METHODS: 552 high myopic (spherical equivalent < or =-6.0D or axial length > or =26.5 mm) patients were enrolled in the study, 230 cases with myopic maculopathy (at least lacquer cracks were identified) and 322 cases without maculopathy. The initial and final visual acuity (VA) (after 10 years) was compared between two groups. Additionally, the relation between sex, age, refraction, and axial length was analysed to find out the possible risk factors associated with visual outcome in myopic maculopathy. RESULTS: In 92% of patients aged 40-49, final VA was better than 20/40 after 10 years of follow up. However, it was less than 40% in those older than 60 years. For more than 50% of patients older than 40 years of age with maculopathy, their vision had decreased more than two lines in Snellen VA after 10 years of follow up, compared to only 4.3% of analogues without myopic maculopathy. Patchy atrophy and choroidal neovascularisation in myopic macular degeneration groups showed poorer visual outcome than lacquer cracks in the macular lesion group. Other prognostic factors of visual outcomes were myopic refraction, axial length, and ageing. CONCLUSIONS: Clearly, prognosis for patients with maculopathy is poorer than for those without maculopathy. Refractive status, axial length, and ageing are the main factors involved in determining the visual outcomes. The macular grading also affects the visual outcome for high myopic patients.

The development and evolution of full thickness macular hole in highly myopic eyes.

PURPOSE: To evaluate the morphological changes before and after the formation of a full-thickness macular hole (MH) in highly myopic eyes. PATIENTS AND METHODS: Retrospective observational case series. From 2006 to 2013, clinical records of patients with MH and high myopia who had optical coherence tomography (OCT) before the development of MH were reviewed. All patients had been followed for more than 1 year since MH formation to observe the morphological changes. RESULTS: Twenty-six eyes of 24 patients were enrolled. The initial OCT images could be classified into four types: (1) normal foveal depression with abnormal vitreo-retinal relationship (eight cases), (2) macular schisis without detachment (six cases), (3) macular schisis with concomitant/subsequent detachment (nine cases), and (4) macular atrophy with underlying/adjacent scar (three cases). After MH formation, one case in type 1 and one case in type 4 group developed retinal detachment (RD). In type 2 group, four cases developed RD at the same time of MH formation. The preexisting detachment in type 3 group extended in eight cases and improved in one case. Among all the cases, 14 eyes received vitrectomy and 7 eyes received gas injection. MH sealed in nine eyes after vitrectomy and four eyes by gas injection. CONCLUSION: The study revealed four pathways of MH formation in highly myopic eyes. MH from macular schisis tended to be associated with detachment. However, the evolution and the results of surgical intervention were not always predictable.

Peripheral telomere length and hippocampal volume in adolescents with major depressive disorder.

Several studies have reported that adults with major depressive disorder have shorter telomere length and reduced hippocampal volumes. Moreover, studies of adult populations without major depressive disorder suggest a relationship between peripheral telomere length and hippocampal volume. However, the relationship of these findings in adolescents with major depressive disorder has yet to be explored. We examined whether adolescent major depressive disorder is associated with altered peripheral telomere length and hippocampal volume, and whether these measures relate to one another. In 54 unmedicated adolescents (13-18 years) with major depressive disorder and 63 well-matched healthy controls, telomere length was assessed from saliva using quantitative polymerase chain reaction methods, and bilateral hippocampal volumes were measured with magnetic resonance imaging. After adjusting for age and sex (and total brain volume in the hippocampal analysis), adolescents with major depressive disorder exhibited significantly shorter telomere length and significantly smaller right, but not left hippocampal volume. When corrected for age, sex, diagnostic group and total brain volume, telomere length was not significantly associated with left or right hippocampal volume, suggesting that these cellular and neural processes may be mechanistically distinct during adolescence. Our findings suggest that shortening of telomere length and reduction of hippocampal volume are already present in early-onset major depressive disorder and thus unlikely to be only a result of accumulated years of exposure to major depressive disorder.

Plasma interleukin-6 and C-reactive protein levels in reactive versus clonal thrombocytosis.

PURPOSE: Evaluate the discriminatory value of plasma interleukin-6 or C-reactive protein levels in clonal thrombocytosis compared with those in reactive thrombocytosis. PATIENTS AND METHODS: A comparative analysis of quantitatively measured laboratory values in a prospectively studied group of consecutive patients. The setting was a tertiary referral center consisting of two hospitals and an outpatient clinic. Plasma interleukin-6 and C-reactive protein levels were measured in 91 consecutive patients with thrombocytosis (platelet count > or = 600 x 10(9)/L). The cause of thrombocytosis was determined by reviewing the medical histories and follow-up data without knowledge of the corresponding laboratory values. Sixty-four patients had reactive thrombocytosis, 20 had clonal thrombocytosis, and 7 had clonal thrombocytosis plus reactive thrombocytosis. Plasma interleukin-6 was measured by an enzyme-linked immunosorbent assay, and C-reactive protein was measured with rate immunonephelometry. RESULTS: Interleukin-6 levels were undetectable in all the patients with clonal thrombocytosis, whereas they were increased in 60% of the patients with reactive thrombocytosis or clonal thrombocytosis plus reactive thrombocytosis. There was a correlation between interleukin-6 and C-reactive protein levels (r = .6), and the median and range values of both levels differed significantly between the clonal thrombocytosis group and the other two groups (P < 0.0001). In 81% of the patients with reactive thrombocytosis, levels of either interleukin-6 or C-reactive protein were elevated. There was no correlation between interleukin-6 and C-reactive protein levels and the platelet count. CONCLUSIONS: An elevated interleukin-6 level is rare in uncomplicated clonal thrombocytosis and suggests reactive thrombocytosis. However, an isolated normal value has little discriminatory value. Measurement of C-reactive protein level may be used as a less expensive surrogate for measurement of interleukin-6. Repeatedly low levels of both interleukin-6 and C-reactive protein are most consistent with clonal thrombocytosis.

Reattachment of cultured human retinal pigment epithelium to extracellular matrix and human Bruch's membrane.

PURPOSE: To determine the mechanism of reattachment of harvested human retinal pigment epithelium (RPE) to RPE-derived extracellular matrix and Bruch's membrane. METHODS: Confluent first-to third-passage human RPE were harvested from tissue culture and plated onto RPE-derived extracellular matrix or human Bruch's membrane exoplants denuded of cells by treatment with 0.02 N ammonium hydroxide. The authors measured RPE reattachment to uncoated surfaces or surfaces precoated with extracellular matrix proteins (fibronectin, laminin, vitronectin, or type IV collagen), antibodies to extracellular matrix-proteins, or the synthetic peptide RGDS (arginine-glycine-aspartate-serine). Some RPE were pretreated with anti-beta 1 integrin antibodies before plating onto either substrate. RESULTS: Coating the surface of either RPE-derived extracellular matrix or Bruch's membrane with fibronectin, laminin, vitronectin, or type IV collagen increased the RPE attachment rate. Exposing RPE to anti-beta 1 integrin antibodies or RGDS or precoating the surface with antibodies to fibronectin, laminin, vitronectin, or type IV collagen decreased the RPE attachment rate to both surfaces. The RPE attachment rate to Bruch's membrane was lower when the exoplants were harvested from the macula of older (age, 70 to 90 years) versus younger (age, 30 to 40 years) persons (52.4 +/- 3.6% versus 64.3 +/- 3.5%, respectively; P < 0.05). CONCLUSIONS: The attachment of cultured human RPE cells to human Bruch's membrane or to RPE-derived extracellular matrix is mediated by an interaction between the beta 1-subunit of integrin on the RPE surface and ligands in the extracellular matrix that include laminin, fibronectin, vitronectin, and type IV collagen. The lower rate of RPE reattachment to the macula from older human cadaveric eyes may have implications for studies aimed at RPE transplantation in elderly persons.

Acute lymphocytic leukemia in adults: a retrospective study and analysis of current management options.

OBJECTIVE: To examine current therapeutic modalities for acute lymphocytic leukemia (ALL) in adults, analyze prognostic variables, and offer treatment recommendations. DESIGN: We reviewed our experience with 90 adult patients with ALL examined at the Mayo Clinic between 1982 and 1992 and used it as a background for discussion of prognostic factors and management options in adult patients with ALL. MATERIAL AND METHODS: The pretreatment characteristics of patients, types of induction chemotherapy, and postremission treatment, including bone marrow transplantation (BMT), were analyzed for prognostic significance for each of three outcomes: complete remission (CR) rate, duration of CR, and overall survival of patients. RESULTS: Of the 90 study patients, 80 had received induction chemotherapy. Overall long-term survival for treated patients was 25%. None of the 10 patients younger than 18 years of age underwent BMT, and their long-term survival was 80%. Of the other 70 patients, who were 18 years old or older, 42 (60%) had a CR with induction chemotherapy. Of these 42 patients, 31 did not undergo BMT, and their long-term survival was less than 13%. BMT was done in six patients during a first CR (with 100% survival), in four during a later CR (with 50% survival), and in six with disease (with 17% survival). The median age of patients who received chemotherapy was 50 years (range, 19 to 87) and that of patients who underwent BMT was 34 years (range, 18 to 46). Overall, age was the only significant prognostic factor. CONCLUSION: With our application of current chemotherapy, the outcome in adult patients (18 years old or older) with ALL was dismal. The results were considerably better in patients younger than 18 years of age or in those who underwent BMT as post-remission therapy. Comprehensive assessment of our experience and that in the literature, however, did not resolve issues about current management. Participation of patients in comparative trials is critical for determining the best therapy for ALL in adults.

Impact of age, various forms of cataract, and visual acuity on whole-field scotopic sensitivity screening for glaucoma in rural Taiwan.

OBJECTIVE: To evaluate the impact of age, various forms of cataract, and visual acuity on whole-field scotopic sensitivity screening for glaucoma in a rural population. DESIGN: Clinic-based study with population-based recruitment. SETTING: Jin Shan Township near Taipei, Taiwan. SUBJECTS: Three hundred forty-six residents (ages, > or = 40 years) of Jin Shan Township. INTERVENTIONS: Whole-field scotopic testing, ophthalmoscopy with dilation of the pupils, cataract grading against photographic standards, and screening visual field testing in a random one-third subsample. MAIN OUTCOME MEASURES: Whole-field scotopic sensitivity (in decibels) and diagnostic status as a case of glaucoma, glaucoma suspect, or normal. RESULTS: Participants in Jin Shan Township did not differ significantly in the rate of blindness, low visual acuity, or family history of glaucoma from a random sample of nonrespondents. Scotopic sensitivity testing detected 100% (6/6) of subjects with open-angle glaucoma at a specificity of 80.2%. The mean +/- SE scotopic sensitivity for six subjects with open-angle glaucoma (32.78 +/- 1.51 dB) differed significantly from that of 315 normal individuals (38.51 +/- 0.22 dB), when adjusted for age and visual acuity (P = .05, t test). With linear regression modeling, factors that correlated significantly with scotopic sensitivity were intraocular pressure, screening visual field, best corrected visual acuity, presence of cortical cataract, and increasing age. CONCLUSIONS: Although cataract affects the whole-field scotopic threshold, it appears that scotopic testing may be of value in field-based screening for glaucoma.

A new route to spirooxindoles.

[reaction: see text]Reaction of indole amides 5 with tributylstannane gave spiroindolenines 9 which are readily converted into spiropyrrolidinyloxindoles. This tricyclic system is found in a number of interesting natural products.

The role of venous hypertension in the pathogenesis of Legg-Perthes disease. A clinical and experimental study.

Thirty-two patients in whom Legg-Perthes disease apparently involved only one hip were examined with venography, measurement of intraosseous and intra-articular pressures, arthrography, and dynamic triphasic bone-imaging with 99mTc methylene diphosphonate. The arterial flow of blood in the affected femoral head was slightly decreased, but the difference from that on the normal side was not statistically significant. However, there was marked disturbance of the venous drainage in the diseased hip, elevated intraosseous pressure in the affected femoral neck, and increased intra-articular pressure in the involved hip compared with the normal side. An animal model was then created in twenty immature dogs, venous drainage was obstructed, and intraosseous pressure of the femoral head and neck was elevated by injection of four milliliters of semiliquid silicone into the femoral neck. In eleven of the dogs, areas of avascular necrosis resembling those associated with Legg-Perthes disease developed in the femoral head.

THC: YAG Laser Sclerostomy with Preoperative Mitomycin-C Subconjunctival Injection in Rabbits.

SUMMARY: Subconjunctival fibrosis is one of the major causes of most bleb failures. To inhibit the wound-healing process and to achieve a better intraocular pressure (IOP) lowering effect as well as bleb formation, we performed a sclerostomy using a THC:YAG laser (thulium, holmium, and chromium-doped yttrium-aluminum-garnet crystal) and a subconjunctival injection of mitomy-cin-C given 24 h or 5 days before a filtering operation or soon after the filtering process in rabbits. A 1-mm conjunctiva wound was made 12 mm away from the sclerostomy site to allow for entry of an optic probe for delivering energy. Forty-eight rabbits were divided into four groups. Group I received a subconjunctival injection of 0.2 ml of 0.2 mg/ml of mitomycin-C 24 h before the operation. The same dosage of mitomycin-C was given to Group II 5 days before the operation and to Group III immediately following the operation. Group IV served as a control, and only 0.2 ml of normal saline solution was given 24 h preoperatively. One eye of each rabbit was randomly selected for the experiment, while the other eye served as a control. The bleb lasted 30.9 $pM 15.7 days in Group I, 16.0 $pM 6.4 days in Group II, 15.5 $pM 6.5 days in Group III, and 2.3 $pM 0.7 days in Group IV. The IOP lowering effect was parallel to bleb formation. The results demonstrate that a subconjunctival mitomycin-C injection given 24 h before a filtering operation is more effective in prolonging the filtering effect produced by the THC:YAG laser than one given postoperatively.

Effect of mitomycin-C on human retinal pigment epithelium in culture.

PURPOSE: To determine the effect of mitomycin-C on confluent and non-confluent human retinal pigment epithelium (RPE) in tissue culture. METHODS: The effect of mitomycin-C on confluent RPE was determined by treating first passage confluent cells with 0.01, 0.1, 1, 10, 100 or 1000 micromolar (microM) mitomycin-C for 1, 3, or 7 days. The cell viability after treatment was determined by using an esterase stain. The effect of mitomycin-C on proliferating RPE was determined by incubating non-confluent cells with the above concentrations of mitomycin-C for 20 min, 1 hour or 24 hours. RESULTS: Mitomycin-C can be toxic to a confluent RPE monolayer, and the LD50 is 421, 28.8 or 0.0632 microM when cells are continually exposed to mitomycin-C for 1, 3 or 7 days, respectively. Exposure to mitomycin-C at concentrations > or = 10 microM for 20-60 min significantly inhibits proliferation of non-confluent RPE. A 24 hour exposure of RPE to 1 microM mitomycin-C markedly inhibits proliferation of non-confluent RPE with minimal toxicity to confluent RPE. CONCLUSIONS: Since exposure of human RPE to mitomycin-C for 24 hours can inhibit cell proliferation at concentrations which are well-tolerated by confluent RPE, mitomycin-C may be a suitable agent for inhibiting RPE proliferation in vivo.

En bloc transfer of extracellular matrix in vitro.

PURPOSE: Extracellular matrix (ECM) plays a major role in the development and regeneration of various epithelial cells including retinal pigment epithelium (RPE), and attachment to ECM inhibits RPE apoptosis. Transplantation of ECM prior to the transplantation of RPE may modulate the survival and subsequent proliferation of transplanted RPE. Thus, we have developed a technique to harvest and transfer native ECM produced by bovine, porcine and human cell lines. METHODS: ECM was prepared by treating a confluent monolayer of cells with 0.02 N ammonium hydroxide. The ECM was then coated with a thin 100 mu layer of 12% gelatin and cooled to 4 degrees C. Patches of the ECM were isolated and transferred to another culture plate. The transferred ECM was characterized by immunohistochemistry. We determined the ability of cultured RPE to reattach to the harvested ECM, and the ability of the harvested ECM to inhibit RPE apoptosis. RESULTS: Native ECM can be transferred to another location en bloc with this technique. Immunohistochemistry demonstrates that the transferred ECM contains fibronectin, laminin and collagen IV. The reattachment rate of human RPE to each type of transferred ECM is higher (83.6 +/- 2.8%) than RPE reattachment to bare tissue culture plastic (57.6 +/- 9.8%). The apoptotic rate of attached RPE cells on transferred bovine corneal endothelial ECM (4.3 +/- 1.4%) is lower than their apoptotic rate on bare plastic (69.3 +/- 4.1%). The apoptotic rates of unattached cells are 80.3 +/- 4.4% on transferred bovine corneal endothelial ECM and 79.2 +/- 3.4% on bare plastic. CONCLUSIONS: We conclude that ECM produced by various cell lines can be harvested and transferred by this technique. The transferred ECM promotes cell reattachment and inhibits RPE cell apoptosis. Harvesting and transfer of ECM at the time of RPE transplantation may inhibit apoptosis and promote survival of the transplant.

The effectiveness of 0.5% atropine in controlling high myopia in children.

Twenty highly myopic children (> or = -6.0 D) were treated with 0.5% atropine eyedrops once per night. Twelve subjects were initially treated with a short-acting cycloplegic agent, tropicamide (0.5%) (Group A), and the other eight subjects did not receive any myopic therapy before atropine (Group B). These cases were followed for up to five years. In Group A, the mean myopic progression rate after 0.5% atropine treatment was -0.01 +/- 0.04 D/M (Diopter/Month), which was significantly lower than that of the period during tropicamide treatment (-0.12 +/- 0.09 D/M) (p < 0.05). In Group B, the mean myopic progression rate after atropine therapy was begun was -0.04 +/- 0.06 D/M, which was also significantly slower than that of non-medication, -0.14 +/- 0.07 D/M (p < 0.05). The results suggested that 0.5% atropine is effective for slowing down myopic progression, even in highly myopic children.

Effects of different concentrations of atropine on controlling myopia in myopic children.

Although 1% atropine effectively slows myopia progression, it is associated with adverse effects, including photophobia, blurred near vision, and poor compliance. We investigated whether lower doses of atropine would control myopia progression. One hundred and eighty-six children, from 6 to 13 years of age, were treated each night with different concentrations of atropine eye drops or a control treatment for up to 2 years. The mean myopic progression in each of the groups was 0.04 +/-0.63 diopter per year (D/Y) in the 0.5% atropine group, 0.45+/-0.55 D/Y in the 0.25% atropine group, and 0.47+/-0.91 D/Y in the 0.1% atropine group. All atropine groups showed significantly less myopic progression than the control group (1.06+/-0.61 D/Y) (p<0.01). Our study also showed that 61% of students in the 0.5% atropine group, 49% in the 0.25% atropine group and 42% in the 0.1% atropine group had no myopic progression. However, 4% of children in the 0.5% atropine group, 17% in the 0.25% atropine group, and 33% in the 0.1% atropine group still had fast myopic progression (>-1.0 D/Y). In contrast, only 8% of the control group showed no myopic progression and 44% had fast myopic progression. These results suggest that all three concentrations of atropine had significant effects on controlling myopia; however, treatment with 0.5% atropine was the most effective.