993 resultados para consecutive
Resumo:
Immune haemolytic anaemia (IHA) is a recognised complication after allogeneic stem cell transplantation (SCT) and occurs more frequently if marrow cells have been subjected to T cell depletion (TCD). Among 58 consecutive patients who underwent TCD-allogeneic SCT from volunteer unrelated donors for the treatment of CML at the Hammersmith Hospital during a 3-year period (1 March 1996 to 28 February 1999) we identified nine cases of IHA. All patients had a strongly positive direct and indirect antiglobulin test and in eight patients the serological findings were typical of warm-type haemolysis often with antibody specificities within the Rh system. All nine cases had clinically significant haemolysis and were treated initially with prednisolone and immunoglobulin. The onset of IHA coincided with the occurrence of leukaemic relapse in six cases, and the presence of host haemopoiesis confirmed by lineage-specific chimerism in all four cases studied. Five patients received donor lymphocyte infusions (DLI); in three molecular remission and the restoration of full donor chimerism coincided with resolution of haemolysis. We conclude that in the context of leukaemic relapse, DLI is an effective therapy for IHA following allografts involving TCD.
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We describe a single centre experience of eight consecutive patients with relapsed or refractory Ph+ ALL treated with the FLAG/idarubicin regimen followed by BMT or PBSCT. Following FLAG/idarubicin, one achieved a partial response and seven CR. All patients subsequently received allogeneic transplants: one sibling BMT, three matched unrelated (MUD) BMT and four sibling PBSCT. Two patients received second transplants with PBSC from their original BM donors following FLA/Ida with no further conditioning. Three patients are alive in CR 9, 24 and 32 months after transplant. Seven of eight patients had a cytogenetic response following FLAG/Ida induction and one of seven became bcr-abl negative. All eight patients had a complete cytogenetic response following transplant. Four of five assessable patients became p190 bcr-abl negative after transplant; three of these subsequently relapsed. Both patients with the p210 bcr-abl transcript remained bcr-abl positive in CR after transplant. FLAG/Ida was well tolerated and appears to be effective in inducing remission in relapsed Ph+ ALL. The use of FDR-containing chemotherapy without further conditioning prior to PBSCT deserves further study in heavily pre-treated patients and, in patients with relapsed ALL following BMT, may be a safer option than DLI (donor lymphocyte infusion) by avoiding the associated risk of aplasia.
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In this study we investigate the influence of the implementation of multidimensional engagement on students’ academic, social and emotional outcomes in the teaching of Operations and Supply Chain Management (OSCM) modules. Next to the academic and behavioural engagement dimensions, which are traditionally used to engage students in OSCM courses, we also incorporate a cognitive dimension to enhance integral student engagement. Up to know, integral student engagement is not reported in the OSCM literature. Cognitive engagement is based on implementation of summative self- and peer-assessment of weekly assignments. Our investigation is based on action research, conducted in an OSCM module over two consecutive years. We found that, in general, multidimensional engagement results in higher levels of academic performance, development of relationships with academic staff and their peers and emotional satisfaction. These findings are discussed in relation to several contextual factors: nature of the study material, gender, and the home location of students.
Resumo:
PURPOSE: We conducted a phase I/II clinical trial to determine the safety and feasibility of combining vorinostat with 5-fluorouracil (5-FU) in patients with metastatic colorectal cancer (mCRC) and elevated intratumoral thymidylate synthase (TS).
METHODS: Patients with mCRC who had failed all standard therapeutic options were eligible. Intratumoral TS mRNA expression and peripheral blood mononuclear cell (PBMC) histone acetylation were measured before and after 6 consecutive days of vorinostat treatment at 400 mg PO daily. 5-FU/LV were given on days 6 and 7 and repeated every 2 weeks, along with continuous daily vorinostat. Dose escalation occurred in cohorts of three to six patients.
RESULTS: Ten patients were enrolled. Three dose levels were explored in the phase I portion of the study. Two dose-limiting toxicities (DLTs) were observed at the starting dose level, which resulted in dose de-escalation to levels -1 and -2. Given the occurrence of two DLTs at each of the dose levels, we were unable to establish a maximum tolerated dose (MTD). Two patients achieved significant disease stabilization for 4 and 6 months. Grade 3 and 4 toxicities included fatigue, thrombocytopenia and mucositis. Intratumoral TS downregulation > or = 50% was observed in one patient only. Acetylation of histone 3 was observed in PBMCs following vorinostat treatment.
CONCLUSIONS: The study failed to establish a MTD and was terminated. The presence of PBMC histone acetylation indicates biological activity of vorinostat, however, consistent reductions in intratumoral TS mRNA were not observed. Alternate vorinostat dose-scheduling may alleviate the toxicity and achieve optimal TS downregulation.
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BACKGROUND: Reactive microglia are commonly seen in retinal degenerative diseases, and neurotoxic microglia responses can contribute to photoreceptor cell death. We and others have previously shown that translocator protein (18 kDa) (TSPO) is highly induced in retinal degenerations and that the selective TSPO ligand XBD173 (AC-5216, emapunil) exerts strong anti-inflammatory effects on microglia in vitro and ex vivo. Here, we investigated whether targeting TSPO with XBD173 has immuno-modulatory and neuroprotective functions in two mouse models of acute retinal degeneration using bright white light exposure.
METHODS: BALB/cJ and Cx3cr1 (GFP/+) mice received intraperitoneal injections of 10 mg/kg XBD173 or vehicle for five consecutive days, starting 1 day prior to exposure to either 15,000 lux white light for 1 h or 50,000 lux focal light for 10 min, respectively. The effects of XBD173 treatment on microglia and Müller cell reactivity were analyzed by immuno-stainings of retinal sections and flat mounts, fluorescence-activated cell sorting (FACS) analysis, and mRNA expression of microglia markers using quantitative real-time PCR (qRT-PCR). Optical coherence tomography (OCT), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) stainings, and morphometric analyses were used to quantify the extent of retinal degeneration and photoreceptor apoptosis.
RESULTS: Four days after the mice were challenged with bright white light, a large number of amoeboid-shaped alerted microglia appeared in the degenerating outer retina, which was nearly completely prevented by treatment with XBD173. This treatment also down-regulated the expression of TSPO protein in microglia but did not change the TSPO levels in the retinal pigment epithelium (RPE). RT-PCR analysis showed that the microglia/macrophage markers Cd68 and activated microglia/macrophage whey acidic protein (Amwap) as well as the pro-inflammatory genes Ccl2 and Il6 were reduced after XBD173 treatment. Light-induced degeneration of the outer retina was nearly fully blocked by XBD173 treatment. We further confirmed these findings in an independent mouse model of focal light damage. Retinas of animals receiving XBD173 therapy displayed significantly more ramified non-reactive microglia and more viable arrestin-positive cone photoreceptors than vehicle controls.
CONCLUSIONS: Targeting TSPO with XBD173 effectively counter-regulates microgliosis and ameliorates light-induced retinal damage, highlighting a new pharmacological concept for the treatment of retinal degenerations.
Resumo:
Purpose
To evaluate the impact of the position of an asymmetric multifocal near segment on visual quality.
Setting
Cathedral Eye Clinic, Belfast, United Kingdom.
Design
Retrospective comparative case series.
Methods
Data from consecutive patients who had bilateral implantation of the Lentis Mplus LS-312 multifocal intraocular lens were divided into 2 groups. One group received inferonasal near-segment placement and the other, superotemporal near-segment placement. A +3.00 diopter (D) reading addition (add) was used in all eyes. The main outcome measures included uncorrected distance visual acuity (UDVA), uncorrected near visual acuity (UNVA), contrast sensitivity, and quality of vision. Follow-up was 3 months.
Results
Patients ranged in age from 43 to 76 years. The inferonasal group comprised 80 eyes (40 patients) and the superotemporal group, 76 eyes (38 patients). The mean 3-month spherical equivalent was −0.11 D ± 0.49 (SD) in the inferonasal group and −0.18 ± 0.46 D in the superotemporal group. The mean postoperative UDVA was 0.14 ± 0.10 logMAR and 0.18 ± 0.15 logMAR, respectively. The mean monocular UNVA was 0.21 ± 0.14 logRAD and 0.24 ± 0.13 logRAD, respectively. No significant differences were observed in the higher-order aberrations, total Strehl ratio (point-spread function), or modulation transfer function between the groups. Dysphotopic symptoms measured with a validated quality-of-vision questionnaire were not significantly different between groups.
Conclusion
Positioning of the near add did not significantly affect objective or subjective visual function parameters.
Resumo:
Introduction: Age-related macular degeneration (AMD) is a leading cause of vision loss in the elderly mostly due to the development of neovascular AMD (nAMD) or geographic atrophy (GA). Intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents are an effective therapeutic option for nAMD. Following anti-VEGF treatments, increased atrophy of the retinal pigment epithelium (RPE) and choriocapillaries that resembles GA has been reported. We sought to evaluate the underlying genetic influences that may contribute to this process. Methods: We selected 68 single nucleotide polymorphisms (SNPs) from genes previously identified as susceptibility factors in AMD, along with 43 SNPs from genes encoding the VEGF protein and its cognate receptors as this pathway is targeted by treatment. We enrolled 467 consecutive patients (Feb 2009 to October 2011) with nAMD who received anti-VEGF therapy. The acutely presenting eye was designated as the study eye and retinal tomograms graded for macular atrophy at study exit. Statistical analysis was performed using PLINK to identify SNPs with a P value < 0.01. Logistic regression models with macular atrophy as dependent variable were fitted with age, gender, smoking status, common genetic risk factors and the identified SNPs as explanatory variables. Results: Grading for macular atrophy was available in 304 study eyes and 70% (214) were classified as showing macular atrophy. In the unadjusted analysis we observed significant associations between macular atrophy and two independent SNPs in the APCS gene: rs6695377: odds ratio (OR) = 1.98; 95% confidence intervals (CI): 1.23, 3.19; P = 0.004; rs1446965: OR = 2.49, CI: 1.29, 4.82; P = 0.006 and these associations remained significant after adjustment for covariates. Conclusions: VEGF is a mitogen and growth factor for choroidal blood vessels and the RPE and its inhibition could lead to atrophy of these key tissues. Anti-VEGF treatment can interfere with ocular vascular maintenance and may be associated with RPE and choroidal atrophy. As such, these medications, which block the effects of VEGF, may influence the development of GA. The top associated SNPs are found in the APCS gene, a highly conserved glycoprotein that encodes Serum amyloid P (SAP) which opsonizes apoptotic cells. SAP can bind to and activate complement components via binding to C1q, a mechanism by which SAP may remove cellular debris, affecting regulation of the three complement pathways.
Resumo:
A multiuser dual-hop relaying system over mixed radio frequency/free-space optical (RF/FSO) links is investigated. Specifically, the system consists of m single-antenna sources, a relay node equipped with n≥ m receive antennas and a single photo-aperture transmitter, and one destination equipped with a single photo-detector. RF links are used for the simultaneous data transmission from multiple sources to the relay. The relay operates under the decode-and-forward protocol and utilizes the popular V-BLAST technique by successively decoding each user's transmitted stream. Two common norm-based orderings are adopted, i.e., the streams are decoded in an ascending or a descending order. After V-BLAST, the relay retransmits the decoded information to the destination via a point-to-point FSO link in m consecutive timeslots. Analytical expressions for the end-to-end outage probability and average symbol error probability of each user are derived, while closed-form asymptotic expressions are also presented. Capitalizing on the derived results, some engineering insights are manifested, such as the coding and diversity gain of each user, the impact of the pointing error displacement on the FSO link and the V-BLAST ordering effectiveness at the relay.
Resumo:
OBJECTIVES:
Analysis of screening uptake usually dichotomizes women into attenders and non-attenders, though many women respond positively to some but not all invitations. This paper studies these intermittent attenders.
METHODS:
A cohort of 8,571 women invited for consecutive breast screens in the Northern Ireland Breast Screening Programme were followed in a study linking screening and census records. Multivariate logistic analysis was used to analyze the characteristics of those who attended both times (consistent), once (intermittent or 'one-time only'), or not at all (non-attenders).
RESULTS:
Overall, 15.5% of women attended once and 13.4% were non-attenders. Non-attenders were characteristically disadvantaged (as measured by social renting, car access, and employment status), less likely to be married, and more likely to be healthy. One-time attenders were younger, and suffering poor health, though there was no association with either social renting or employment status. Privately rented accommodation and city living was associated with both one-time attendance and non-attendance.
CONCLUSIONS:
One-time attenders are an important and distinct subgroup of screening invitees in this analysis. Their distinct characteristics suggest that transitory factors, such as change in marital status, ill-health, or addressing difficulties through change of residence are important. These distinct characteristics suggest the need for different approaches to increase attendance, among both intermittent attenders and those not attending at all.
Resumo:
Purpose: To identify factors associated prospectively with increased cataract surgical rate (CSR) in rural Chinese hospitals.
Methods: Annual cataract surgical output was obtained at baseline and 24 months later from operating room records at 42 rural, county-level hospitals. Total local CSR (cases/million population/y), and proportion of CSR from hospital and local competitors were calculated from government records. Hospital administrators completed questionnaires providing demographic and professional information, and annual clinic and outreach screening volume. Independent cataract surgeons provided clinical information and videotapes of cases for grading by two masked experts using the Ophthalmology Surgical Competency Assessment Rubric (OSCAR). Uncorrected vision was recorded for 10 consecutive cataract cases at each facility, and 10 randomly-identified patients completed hospital satisfaction questionnaires. Total value of international nongovernmental development organization (INGDO) investment in the previous three years and demographic information on hospital catchment areas were obtained. Main outcome was 2-year percentage change in hospital CSR.
Results: Among the 42 hospitals (median catchment population 530,000, median hospital CSR 643), 78.6% (33/42) were receiving INGDO support. Median change in hospital CSR (interquartile range) was 33.3% (-6.25%, 72.3%). Predictors of greater increase in CSR included higher INGDO investment (P = 0.02, simple model), reducing patient dissatisfaction (P = 0.03, simple model), and more outreach patient screening (P = 0.002, simple and multiple model).
Conclusions: Outreach cataract screening was the strongest predictor of increased surgical output. Government and INGDO investment in screening may be most likely to enhance output of county hospitals, a major goal of China's Blindness Prevention Plan.
Resumo:
Purpose: To describe sequential phacoemulsification-intraocular lens (IOL) implantation-posterior capsulorhexis-anterior vitrectomy in the management of phakic malignant glaucoma. Methods: Twenty consecutive patients (25 eyes) with phakic malignant glaucoma were enrolled at the Zhongshan Ophthalmic Center, Sun Yat-sen University. All patients underwent phacoemulsification, IOL implantation and posterior capsulorhexis together with anterior vitrectomy via a clear corneal paracentesis. Visual acuity, intraocular pressure (IOP), anterior chamber depth (ACD), surgical complications and medications required after the surgery were recorded. Results: After surgery, the mean LogMAR visual acuity and ACD increased significantly (visual acuity from -1.56 ± 1.17 to -0.54 ± 0.81, p < 0.001; ACD from 0.367 ± 0.397 mm to 2.390 ± 0.575 mm, p < 0.001), and mean IOP decreased significantly (from 39.6 ± 10.6 mm Hg to 14.5 ± 4.1 mmHg, p < 0.001). No serious perioperative complications occurred, and only five eyes required topical glaucoma medications after surgery. Conclusion: Combined phacoemulsification-IOL implantation-posterior capsulorhexis-anterior vitrectomy surgery is a safe and effective method for treating patients with phakic malignant glaucoma. © 2012 The Authors. Acta Ophthalmologica © 2012 Acta Ophthalmologica Scandinavica Foundation.
Resumo:
Purpose: The recently completed Chinese "Million Cataract Surgeries Program" (MCSP) is among the largest such campaigns ever, providing 1.05 million operations. We report MCSP outcomes for the first time, in Jiangxi, the province with the greatest program output. Methods: Ten county hospitals participating in MCSP were selected in Jiangxi (range of gross domestic product per capita US$743-2998). Each hospital sought to enroll 75 consecutive MCSP patients aged ≥50 years. Data recorded included type of cataract procedure, bilateral uncorrected visual acuity (UCVA) and best-corrected visual acuity (BCVA), and refractive error pre- and ≥50 days postoperatively. Results: Among 715 patients (mean age 72.3±9.1 years, 55.5% female), preoperative UCVA was <3/60 (legally blind) bilaterally in 13.3% and unilaterally in the operated eye in 50.9%. No subjects had UCVA >6/18 preoperatively. Small incision cataract surgery was performed in 92.3% patients. Among 662 patients (92.6%) completing follow-up was ≥ 40 days after surgery, BCVA was ≥6/18 in 80.1%, UCVA was ≥6/18 in 57.1% and UCVA was <3/60 in 2.1%. Older age (p<0.001), female sex (p=0.04), worse refractive error (p=0.02) and presence of intra- (p=0.002) and postoperative surgical complications (p<0.001), were independently associated with worse postoperative UCVA. Based on these results, the MCSP cured an estimated 124,950 cases (13.3%×[100-2.1%]×1.05 million) of bilateral and 502,500 (50.9%×[100-2.1%]×1.05 million) of unilateral blindness. Conclusions: Due to relatively good outcomes and the large number of surgeries performed on blind persons, the sight-restoring impact of the MCSP was probably substantial. © Informa Healthcare USA, Inc.
Resumo:
Background: Poor follow-up after cataract surgery in developing countries makes assessment of operative quality uncertain. We aimed to assess two strategies to measure visual outcome: recording the visual acuity of all patients 3 or fewer days postoperatively (early postoperative assessment), and recording that of only those patients who returned for the final follow-up examination after 40 or more days without additional prompting. Methods: Each of 40 centres in ten countries in Asia, Africa, and Latin America recruited 40-120 consecutive surgical cataract patients. Operative-eye best-corrected visual acuity and uncorrected visual acuity were recorded before surgery, 3 or fewer days postoperatively, and 40 or more days postoperatively. Clinics logged whether each patient had returned for the final follow-up examination without additional prompting, had to be actively encouraged to return, or had to be examined at home. Visual outcome for each centre was defined as the proportion of patients with uncorrected visual acuity of 6/18 or better minus the proportion with uncorrected visual acuity of 6/60 or worse, and was calculated for each participating hospital with results from the early assessment of all patients and the late assessment of only those returning unprompted, with results from the final follow-up assessment for all patients used as the standard. Findings: Of 3708 participants, 3441 (93%) had final follow-up vision data recorded 40 or more days after surgery, 1831 of whom (51% of the 3581 total participants for whom mode of follow-up was recorded) had returned to the clinic without additional prompting. Visual outcome by hospital from early postoperative and final follow-up assessment for all patients were highly correlated (Spearman's rs=0·74, p<0·0001). Visual outcome from final follow-up assessment for all patients and for only those who returned without additional prompting were also highly correlated (rs=0·86, p<0·0001), even for the 17 hospitals with unprompted return rates of less than 50% (rs=0·71, p=0·002). When we divided hospitals into top 25%, middle 50%, and bottom 25% by visual outcome, classification based on final follow-up assessment for all patients was the same as that based on early postoperative assessment for 27 (68%) of 40 centres, and the same as that based on data from patients who returned without additional prompting in 31 (84%) of 37 centres. Use of glasses to optimise vision at the time of the early and late examinations did not further improve the correlations. Interpretation: Early vision assessment for all patients and follow-up assessment only for patients who return to the clinic without prompting are valid measures of operative quality in settings where follow-up is poor. Funding: ORBIS International, Fred Hollows Foundation, Helen Keller International, International Association for the Prevention of Blindness Latin American Office, Aravind Eye Care System. © 2013 Congdon et al. Open Access article distributed under the terms of CC BY.
Resumo:
Pediatric ophthalmologists increasingly recognize that the ideal site for intraocular lens (IOL) implantation is in the bag for aphakic eyes, but it is always very difficult via conventional technique. We conducted a prospective case series study to investigate the success rate and clinical outcomes of capsular bag reestablishment and in-the-bag IOL implantation via secondary capsulorhexis with radiofrequency diathermy (RFD) in pediatric aphakic eyes, in which twenty-two consecutive aphakic pediatric patients (43 aphakic eyes) enrolled in the Childhood Cataract Program of the Chinese Ministry of Health were included. The included children underwent either our novel technique for secondary IOL implantation (with RFD) or the conventional technique (with a bent needle or forceps), depending on the type of preoperative proliferative capsular bag present. In total, secondary capsulorhexis with RFD was successfully applied in 32 eyes (32/43, 74.4%, age 5.6±2.3 years), of which capsular bag reestablishment and in-the-bag IOL implantation were both achieved in 30 eyes (30/43, 70.0%), but in the remaining 2 eyes (2/32, 6.2%) the IOLs were implanted in the sulcus with a capsular bag that was too small. Secondary capsulorhexis with conventional technique was applied in the other 11 eyes (11/43, 25.6%, age 6.9±2.3 years), of which capsular bag reestablishment and in-the-bag IOL implantation were both achieved only in 3 eyes(3/43, 7.0%), and the IOLs were implanted in the sulcus in the remaining 8 eyes. A doughnut-like proliferative capsular bag with an extensive Soemmering ring (32/43, 74.4%) was the main success factor for secondary capsulorhexis with RFD, and a sufficient capsular bag size (33/43, 76.7%) was an additional factor in successful in-the-bag IOL implantation. In conclusion, RFD secondary capsulorhexis technique has 70% success rate in the capsular bag reestablishment and in-the-bag IOL implantation in pediatric aphakic eyes, particularly effective in cases with a doughnut-like, extensively proliferative Soemmering ring. © 2013 Luo et al.
Resumo:
Purpose: To assess the demographics and distribution of corneal astigmatism before cataract surgery in Chinese patients. Setting: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China. Design: Clinic-based cross-sectional study. Methods: From July 2009 to May 2011, preoperative bilateral partial coherence interferometry (IOLMaster) was performed in consecutive patients having cataract surgery. Patient demographics and keratometric data were recorded. Results: The mean age of the 2849 patients (4831 eyes) was 70.56 years ± 9.55 (SD); there was a predominance of women patients (64.0%). The mean axial length was 23.58 ± 1.13 mm. The mean corneal astigmatism in this cohort was 1.01 D (range 0.05 to 6.59 D). Corneal astigmatism was between 0.25 D and 1.25 D in 67.7% of eyes, 1.25 D or higher in 27.5% eyes, and less than 0.25 D in 4.8% of eyes. Astigmatism was with the rule in 25.1% of eyes, against the rule (ATR) in 58.2% of eyes, and oblique in 16.7% of eyes. The mean steep keratometry measurement was 44.76 ± 1.56 D. Against-the-rule astigmatism increased significantly with older age. Conclusions: Corneal astigmatism largely fell between 0.25 D and 1.25 D in these predominantly elderly female Chinese patients, and ATR astigmatism increased with age. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. © 2012 ASCRS and ESCRS.
