Search

PURPOSE:: The purpose of this article was to review the current state of knowledge regarding the efficacy of adjuvant therapy for melanoma. PATIENTS AND METHODS:: We reviewed the published literature, focusing on randomized clinical trials. RESULTS:: There have been no meaningful trials addressing adjuvant chemotherapy in melanoma because all trials have been underpowered. Adjuvant interferon-alpha has been tested both at high dose and at lower doses. None of the trials have shown a reproducible benefit in survival, although the high-dose trials and some of the low-dose trials have shown improvement in time to relapse. These experiences raise the question of whether chronic administration is more important than dose. An adjuvant pegylated interferon-alpha trial using a 5-year treatment period is currently under investigation. At least 7 randomized adjuvant vaccine trials have been published, but none have shown a beneficial effect on relapse-free or overall survival except in subset analyses. CONCLUSIONS:: To date, no adjuvant therapy has resulted in improved overall survival. To be attractive as an adjuvant therapy, experience from other tumor types indicates that a chemotherapy regimen should have a response rate of at least 20% in metastatic melanoma. Currently, biochemotherapy is being tested as an adjuvant treatment but other, less toxic, regimens should be sought. Once such a regimen with acceptable toxicity is identified, it would be reasonable to test it as an adjuvant therapy in a properly powered randomized trial. High-dose interferon-alpha for 1 year remains the only U.S. Food and Drug Administration-approved adjuvant therapy for melanoma, but long-term chronic dosing of interferon-alpha may prove more effective than short-term dose schedules. Development of melanoma vaccines remains an appealing and important goal. New technologies and understanding of the immune response against melanoma are leading to novel vaccine strategies designed to break immunologic tolerance against melanoma. [ABSTRACT FROM AUTHOR]

Despite the high burden of mental disorders in low- and middle-income countries (LMICs), less than 25% of those in need have access to appropriate services, in part due to a scarcity of locally relevant, evidence-based interventions and models of care. To address this gap, researchers from India and the United States and the Indian Council of Medical Research (ICMR) collaboratively developed a "Grantathon" model to provide mentored research training to 24 new principal investigators (PIs). This included a week-long didactic training, a customized web-based data entry/analysis system and a National Coordination Unit (NCU) to support PIs and track process objectives. Outcome objectives were assessed via scholarly output including publications, awards received and subsequent grants that were leveraged. Multiple mentorship strategies including collaborative problem-solving approaches were used to foster single-centre and multicentre research. Flexible, approachable and engaged support from mentors helped PIs overcome research barriers, and the NCU addressed local policy and day-to-day challenges through informal monthly review meetings. Bi-annual formal review presentations by all PIs continued through the COVID-19 pandemic, enabling interim results reporting and scientific review, also serving to reinforce accountability. To date, more than 33 publications, 47 scientific presentations, 12 awards, two measurement tools, five intervention manuals and eight research grants have been generated in an open-access environment. The Grantathon is a successful model for building research capacity and improving mental health research in India that could be adopted for use in other LMICs., (© 2023. The Author(s).)

Introduction: India's National Mental Health Programme (NMHP) was initiated in 1982. In 2016, the Indian Council of Medical Research (ICMR) organized a Brainstorming Meeting on Prioritization of Mental Health Research. Recognizing the need for improving mental healthcare by building a cadre of mental health researchers based on focus areas of the NMHP, the ICMR organized a research training cum capacity building workshop in collaboration with the Cross-Fertilized Research Training Programme (funded by Fogarty International Centre, NIH, USA) in 2016. The workshop successfully prepared and reviewed 12 single and multicenter research proposals in priority areas of mental health research, which were awarded by the ICMR to middle- and junior-level research faculty and NGO., Methods: A National Coordination Unit (NCU) was set up to mentor investigators and to coordinate, train, and monitor the progress of their projects. Investigators were paired with senior mentors and also participated in four capacity building workshops focusing on proposal-writing, evaluation, and process tracking., Results: Following discussions with ICMR program officers, the NCU formulated standard operating procedures for ethical conduct, data collection, data sharing, progress reporting procedures, and manuscript preparation for all research projects. Regularly scheduled long-distance communications with investigators using social media and group communications were planned. NCU partnered with the ICMR Database Management Unit to build a shared online platform for real-time data entry and storage, and organized two project review meetings where it also coordinated with US faculty to organize public workshops on manuscript writing and qualitative research., Conclusions: The NCU will ensure timely completion of research projects, data entry and analysis, and reports and project publications. It is feasible to evaluate progress with the NMHP through coordinated multisite research that also enables research capacity building. Results from these projects will help in formulating policies by the Ministry of Health Government of India for achieving objectives of the NMHP., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2020 Indian Psychiatric Society - South Zonal Branch.)

Background & Objectives: Comprehension and process of consent are important for persons with mental illness as they may not be impaired in considering research participation. The American Psychiatric Association developed a detailed Cultural Formulation Interview (CFI). The present study was a part of field testing of CFI, aimed to standardize cultural information affecting the patients' management in India. This paper describes the process and conclusions from the consent-seeking process of this study., Methods: The purpose and procedures about field trial of the CFI were introduced and the patient and caregiver were requested for participation. Consent process was carried out step by step, by reading out the consent form to the first new patient of the day in the psychiatry outpatients department of a tertiary care hospital in north India, inviting questions followed by the 'comprehension' questions. The entire process was audiotaped without any personal identifiers. The process was repeated if not comprehended., Results: A total of 67 patients consented, 11 refused and majority were educated more than secondary school. Some concerns shown by the patients and caregivers included risk of participation, loss or benefits of participation, privacy, etc. All types of mentally ill patients participated in the study., Interpretation & Conclusions: Translations of consent forms used simple words, consonant with understanding of the potential participants. Patients' belief that participating in this long process would improve their care, and serve humanity, influenced their decision to participate. Except for intoxication and severe psychosis, patients could understand and comprehend issues around consent. Main issues were confidentiality and culture. Our experience in the psychiatry OPD refutes the commonly held belief that mentally ill persons lack comprehension and ability to consent., Competing Interests: None

Purpose: To compare the development of posterior capsule opacification (PCO) between eyes with and without posterior capsule plaque after single-piece hydrophobic acrylic intraocular lens (IOL) implantation 5 years postoperatively., Design: A prospective observational case-control study., Methods: One hundred one consecutive eyes with posterior capsule plaque (cases) were compared with the same number of cataractous eyes without posterior capsule plaque (controls). A detailed preoperative evaluation was done to detect the presence of posterior capsule plaque. Histomorphology of posterior capsule plaque was evaluated. Postoperatively, digital retroillumination photographic documentation was performed at 1 month and 1, 2, 3, and 5 years and analyzed for PCO using the Evaluation of Posterior Capsule Opacification (EPCO) software; EPCO scores and areas were calculated. The development of PCO and the influence of the anterior capsule cover (total and partial) on the IOL optic were compared., Results: Posterior capsule plaque on histomorphology showed a large amount of collagenous, fibrous extracellular matrix, and immunofluorescence staining was positive for alpha smooth muscle actin. In the development of PCO, there was no difference between cases and controls at 1 month and 1, 2, 3, and 5 years. Between the 2 groups, there was no difference in the development of PCO within total cover and within partial cover of the anterior capsule on the IOL up to 5 years., Conclusions: The presence of posterior capsule plaque did not increase the incidence of PCO at 5 years., (Copyright© 2017 Asia-Pacific Academy of Ophthalmology.)

Background: Treatment with doxorubicin is a present standard of care for patients with metastatic soft-tissue sarcoma and median overall survival for those treated is 12-16 months, but few, if any, novel treatments or chemotherapy combinations have been able to improve these poor outcomes. Olaratumab is a human antiplatelet-derived growth factor receptor α monoclonal antibody that has antitumour activity in human sarcoma xenografts. We aimed to assess the efficacy of olaratumab plus doxorubicin in patients with advanced or metastatic soft-tissue sarcoma., Methods: We did an open-label phase 1b and randomised phase 2 study of doxorubicin plus olaratumab treatment in patients with unresectable or metastatic soft-tissue sarcoma at 16 clinical sites in the USA. For both the phase 1b and phase 2 parts of the study, eligible patients were aged 18 years or older and had a histologically confirmed diagnosis of locally advanced or metastatic soft-tissue sarcoma not previously treated with an anthracycline, an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, and available tumour tissue to determine PDGFRα expression by immunohistochemistry. In the phase 2 part of the study, patients were randomly assigned in a 1:1 ratio to receive either olaratumab (15 mg/kg) intravenously on day 1 and day 8 plus doxorubicin (75 mg/m(2)) or doxorubicin alone (75 mg/m(2)) on day 1 of each 21-day cycle for up to eight cycles. Randomisation was dynamic and used the minimisation randomisation technique. The phase 1b primary endpoint was safety and the phase 2 primary endpoint was progression-free survival using a two-sided α level of 0.2 and statistical power of 0.8. This study was registered with ClinicalTrials.gov, number NCT01185964., Findings: 15 patients were enrolled and treated with olaratumab plus doxorubicin in the phase 1b study, and 133 patients were randomised (66 to olaratumab plus doxorubicin; 67 to doxorubicin alone) in the phase 2 trial, 129 (97%) of whom received at least one dose of study treatment (64 received olaratumab plus doxorubicin, 65 received doxorubicin). Median progression-free survival in phase 2 was 6.6 months (95% CI 4.1-8.3) with olaratumab plus doxorubicin and 4.1 months (2.8-5.4) with doxorubicin (stratified hazard ratio [HR] 0.67; 0.44-1.02, p=0.0615). Median overall survival was 26.5 months (20.9-31.7) with olaratumab plus doxorubicin and 14.7 months (9.2-17.1) with doxorubicin (stratified HR 0.46, 0.30-0.71, p=0.0003). The objective response rate was 18.2% (9.8-29.6) with olaratumab plus doxorubicin and 11.9% (5.3-22.2) with doxorubicin (p=0.3421). Steady state olaratumab serum concentrations were reached during cycle 3 with mean maximum and trough concentrations ranging from 419 μg/mL (geometric coefficient of variation in percentage [CV%] 26.2) to 487 μg/mL (CV% 33.0) and from 123 μg/mL (CV% 31.2) to 156 μg/mL (CV% 38.0), respectively. Adverse events that were more frequent with olaratumab plus doxorubicin versus doxorubicin alone included neutropenia (37 [58%] vs 23 [35%]), mucositis (34 [53%] vs 23 [35%]), nausea (47 [73%] vs 34 [52%]), vomiting (29 [45%] vs 12 [18%]), and diarrhoea (22 [34%] vs 15 [23%]). Febrile neutropenia of grade 3 or higher was similar in both groups (olaratumab plus doxorubicin: eight [13%] of 64 patients vs doxorubicin: nine [14%] of 65 patients)., Interpretation: This study of olaratumab with doxorubicin in patients with advanced soft-tissue sarcoma met its predefined primary endpoint for progression-free survival and achieved a highly significant improvement of 11.8 months in median overall survival, suggesting a potential shift in the treatment of soft-tissue sarcoma., Funding: Eli Lilly and Company., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Purpose: To evaluate the long-term effect of a single-piece hydrophobic acrylic intraocular lens (IOL), AcrySof SN60AT (Alcon Laboratories, Fort Worth, Texas, USA), on the development of posterior capsule opacification (PCO) 5 years postoperatively., Design: Prospective, observational, consecutive, case series., Methods: setting: Iladevi Cataract and IOL Research Center, Ahmedabad, India., Study Population: Three hundred and ninety eyes with uncomplicated age-related cataract were included. Patients with diabetes mellitus, glaucoma, high myopia, pseudoexfoliation, traumatic cataract, subluxated cataract, previous ocular surgeries, and allergy to dilating drops were excluded. intervention procedures: Digital retroillumination photographic documentation was performed and analyzed for PCO using Evaluation of Posterior Capsule Opacification software. The scores and areas were calculated., Main Outcome Measures: PCO development and the influence of the anterior capsule cover (total on and part on) on the IOL optic was studied within the capsulorrhexis margin and the central 3.0 mm optic area., Results: There was a significant increase in PCO up to 3 years. No significant change in PCO was observed between 3 and 5 years within the capsulorrhexis margin and central 3.0 mm optic area. In the total on group, within the capsulorrhexis margin, significantly lower scores and areas were observed when compared with part-on scores and areas., Conclusion: The increase in PCO up to 3 years was significant. Stabilization in PCO was observed between 3 and 5 years with no difference at 5 years. There was a low incidence of PCO in eyes with total anterior capsule cover over the IOL optic., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Aim: To compare the development of posterior capsule opacification (PCO) between eyes with and without diabetes mellitus after single-piece hydrophobic acrylic intraocular lens implantation 4 years postoperatively., Methods: In this prospective, observational case-control study carried out at Iladevi Cataract and IOL Research Centre, Ahmedabad, India, 75 consecutive eyes with diabetes mellitus (cases) were compared with 75 age-matched eyes with age-related cataract (controls). A detailed, preoperative and posterior segment evaluation was carried out in eyes with diabetes mellitus to detect the presence or absence of diabetic retinopathy (DR). The Mann-Whitney U-test was applied to compare the differences in the development of PCO between the two groups., Results: There was no difference in median PCO between cases and controls at 1 month (2.0 vs 1.50, P<0.068), but cases had a higher median PCO at 12 months (2.95 vs 1.30, P<0.001). At 4 years, there was no significant difference in median PCO between cases and controls (3.75 vs 2.25, P=0.273). The duration of diabetes increased the incidence of PCO at 4 years (P=0.02). Severity of DR had no influence on the progress of PCO at 4 years (P=0.69)., Conclusion: Diabetes mellitus did not increase the incidence of PCO at 4 years. The duration of diabetes increased the risk of PCO. The severity of retinopathy did not influence the development of PCO.

Purpose: To determine the incidence of intraoperative posterior capsule striae after implantation of a 1-piece hydrophobic acrylic intraocular lens (IOL), study the clinical impact on the patients' vision, and assess whether the presence of posterior capsule striae increases the risk for posterior capsule opacification (PCO)., Setting: Iladevi Cataract & IOL Research Centre, Ahmedabad, India., Design: Case-control study., Methods: Part 1 of this study evaluated consecutive adult eyes having cataract surgery performed using standardized techniques with in-the-bag 1-piece hydrophobic acrylic IOL implantation. Posterior capsule striae details were noted at the end of surgery. Part 2 was a case-control study comprising all patients with intraoperative striae and an age- and biometry-matched control group without striae, which was selected on a 1:1 ratio., Results: Intraoperative posterior capsule striae were observed in 68 (13.6%) of 500 eyes. A single stria was seen in 43 eyes [63.2%], and multiple striae were seen in 25 eyes [36.7%]). There was no significant difference in logMAR corrected distance visual acuity at baseline (P=.881) or at 3 years (P=.191) between cases and controls. At 3 years, there was no statistically significant between-group difference in the median Evaluation of Posterior Capsule Opacification score or area values in the capsulorhexis margin (P=.36 and P=.39, respectively) or in the central 3.0 mm optic area (P=.40 and P=.42, respectively)., Conclusion: The incidence of posterior capsule striae was 13.6%. Intraoperative striae did not influence visual acuity or the development of PCO at the 3-year follow-up., (Copyright © 2011 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the rotational stability of a toric intraocular lens (IOL) using purpose-designed software and to determine the influence of axial length (AL) and in-the-bag IOL alignment on IOL rotation., Setting: Iladevi Cataract & IOL Research Centre, Ahmedabad, India., Design: Prospective observational case series., Methods: This study enrolled eyes that had AcrySof toric IOL implantation. The AL was measured using optical coherence biometry or immersion A-scan biometry. Corneal astigmatism was determined by manual keratometry and topography. The IOL alignment was vertical, horizontal, or oblique. Rotational stability was measured using the purpose-designed software, and the mean absolute difference was determined. The effect of AL and IOL alignment on rotational stability was determined 6 months postoperatively., Results: The study evaluated 168 eyes (168 patients). The mean AL was 23.86 mm ± 1.63 (SD), (range 19.50 to 29.03 mm). The median IOL rotation was 0.3 degree from baseline to 1 week, 1.0 degree from 1 week to 1 month, 0.2 degree from 1 to 3 months, and 0.1 degree from 3 to 6 months. The maximum rotation occurred between 1 week and 1 month. There was a strong correlation between AL and IOL rotation at 6 months (r = 0.93, P<.001). The mean absolute difference at 6 months was not significantly different between the 3 axis placement categories when correlated with the rotation (P=.102, analysis of variance)., Conclusions: Toric IOL rotation was greater in eyes with a longer AL. Alignment of the IOL in the capsular bag had no influence on rotation., (Copyright © 2011 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate posterior capsule opacification (PCO) development after cataract surgery in eyes with or without a history of steroid use., Setting: Iladevi Cataract & IOL Research Centre, Ahmedabad, India., Design: Comparative case series., Methods: This study comprised consecutive patients with a history of steroid intake (oral, inhaled, injectable, or topical) for at least 4 months who developed posterior subcapsular cataract (PSC) (study group) and patients without a history of steroid intake with uncomplicated PSC (control group). Standardized surgery was performed in both groups. Digital retroillumination photographic documentation was performed 1 month and 1 year postoperatively. The digital images were analyzed for PCO using Evaluation of Posterior Capsule Opacification (EPCO) software; the entire intraocular lens (IOL) optic and the central 3.0 mm optic area were evaluated. The EPCO score and EPCO area were determined., Results: One year postoperatively, the mean EPCO score was statistically significantly higher in the study group (n = 30) than in the control group (n = 60) (0.33 ± 0.37 [SD] versus 0.15 ± 0.26), as was the mean EPCO area (0.323 ± 0.36 versus 0.15 ± 0.26) (both P<.04). Within the central 3.0 mm optic area, the mean EPCO scores (0.149 ± 0.309 versus 0.003 ± 0.016 P<.04) and mean EPCO area values (0.149 ± 0.309 versus 0.003 ± 0.016) were statistically significantly higher in the study group (P<.04)., Conclusion: Steroid-induced PSC was associated with a higher risk for PCO after cataract surgery at the 1-year follow-up., Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned., (Copyright © 2011 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Background: We treated melanoma patients with temozolomide (TMZ) in the neoadjuvant setting and collected cryopreserved tumor samples before and after treatment. The primary objective was to determine whether the response proportion was higher than previously reported in widely metastatic patients. A secondary objective was to test the feasibility of obtaining adequate tissue before and after treatment for genetic testing., Materials and Methods: Chemotherapy-naive melanoma patients who were candidates for surgical resection were eligible. TMZ was administered orally at 75 mg/m(2)/day for 6 weeks of every 8-week cycle. Cycles were repeated until complete response (CR), progression, or stable disease (SD) for two cycles., Results: Of 19 assessable patients, 2 had CRs and 1 had partial response. Four patients had SD; 12 progressed. Tumor O-6-methylguanine-DNA methyltransferase (MGMT) promoter was unmethylated in all nine patients analyzed including from the two CR patients. Pretreatment tumor microarray results were obtained in 16 of 19 patients., Conclusions: The response proportion to TMZ in the neoadjuvant setting was 16%, not different than in the metastatic setting. Responses were seen even in tumors with a methylated MGMT promoter. Pretreatment cryopreserved tumor adequate for microarray analysis could be obtained in most, but not all, patients. Post-treatment tumor was unavailable in complete responders.

Purpose: The aim of this study was to identify risk factors for the development of cataract in young patients., Settings: The study was undertaken at Iladevi Cataract and IOL Research Centre, Ahmedabad, Gujarat, India., Methods: In a clinic-based observational study, 340 consecutive patients in the age group of 30-45 years presenting with nuclear, cortical, posterior subcapsular (PSC), mixed, and posterior polar cataract were prospectively studied. A detailed history regarding sunlight exposure, atopy, diabetes, steroid intake, myopia, glaucoma, and uveitis was elicited., Results: The mean age of the patients was 40.2+/-4.6 years; there were 202 men. The major risk factors were atopy (25.6%), idiopathic (19.1%), high myopia (12.4%), atopy with steroid intake (10.9%), steroid usage (7.4%), sunlight exposure (3.8%), and diabetes mellitus (3.2%). PSC was observed in 53.5% eyes. Multinomial logistic regression revealed that atopy (P=0.016), steroid usage (P=0.100), and diabetes mellitus (P=0.076) documented higher odds for PSC. High myopia (P<0.001) and sunlight exposure (P=0.003) documented higher odds for nuclear cataract., Conclusion: Atopy was found to be the most common risk factor associated with the development of cataract in young individuals. PSC was the predominant type of cataract prevalent in young patients.

A large body of evidence suggests that the platelet-derived growth factor (PDGF) family and associated receptors are potential targets in oncology therapeutic development because of their critical roles in the proliferation and survival of various cancers and in the regulation and growth of the tumor stroma and blood vessels. Several small molecules that nonspecifically target the PDGF signaling axis are in current use or development as anticancer therapies. However, for the majority of these agents, PDGF and its receptors are neither the primary targets nor the principal mediators of anticancer activity. IMC-3G3, a fully human monoclonal antibody of the immunoglobulin G subclass 1, specifically binds to the human PDGF receptor alpha (PDGFRalpha) with high affinity and blocks PDGF ligand binding and PDGFRalpha activation. The results of preclinical studies and the frequent expression of PDGFRalpha in many types of cancer and in cancer-associated stroma support a rationale for the clinical development of IMC-3G3. Currently, IMC-3G3 is being evaluated in early clinical development for patients with several types of solid malignancies., ((c) 2010 American Cancer Society.)

Purpose: To determine whether axial myopia affects posterior capsule opacification (PCO) in eyes with high myopia (axial length [AL] > or = 26.00 mm) 4 years after implantation of an AcrySof single-piece intraocular lens (IOL)., Setting: Clinical practice, Ahmedabad, India., Methods: In a prospective masked trial, consecutive eyes with high axial myopia (myopia group) and age-matched eyes with a normal AL (21.00 to 23.99 mm) (control group) had phacoemulsification and in-the-bag IOL implantation. Postoperatively, PCO was documented by standardized digital retroillumination images. The PCO area behind the IOL optic was scored (scale 0% to 100%) using the POCO software system. The presence of PCO within the central 3.0 mm of the optic was assessed with the Evaluation of Posterior Capsule Opacification software system. The incidence of neodymium:YAG (Nd:YAG) capsulotomy was determined., Results: The median PCO in the myopia group and control group, respectively, was 3.2% and 5.6% at 1 month (P = .2), 2.2% and 1.6% at 12 months (P = .079), 7.0% and 2.3% at 24 months (P = .079), 3.7% and 3.6% at 36 months (P = .78), and 10.0% and 2.3% at 48 months (P = .61). By 4 years, PCO had encroached onto the central 3.0 mm of the optic in 38% in the myopia group and 20% in the control group (P = .04). One eye (2%) in each group had an Nd:YAG capsulotomy, at 3.2 years and 3.9 years, respectively., Conclusion: Axial myopia did not significantly increase the area or incidence of PCO at 4 years.

Aims: To evaluate the effect of anterior capsule polishing on the development of anterior capsule opacification (ACO) in patients undergoing cataract surgery., Methods: This prospective randomized observational double-masked clinical trial comprised 120 eyes of 60 consecutive patients with bilateral age-related cataract who underwent phacoemulsification. The patients were randomly assigned to one of the two groups: One eye received a 360 degree anterior capsule polishing (group 1 (cases)) and the fellow eye was without anterior capsule polishing (group 2 (controls)) The primary observation was to observe the development of ACO between the 2 groups, whereas the secondary observation was to measure uveal inflammation. ACO was evaluated at 1 week, 1 month, and 6 months., Results: At the 1-week follow-up, there was no significant difference in the development of ACO between the two groups. At 1 month, 54 (90%) eyes developed ACO in controls and 26 (43.3%) eyes in cases (P<0.001). However, at 6 months, there was no significant difference in the development of ACO between controls and cases (P=0.500). The odds of having cells and flare were significantly more in cases compared with controls at first postoperative day (cells: OR, 39.27; 95% CI, 13.49-114.26 and flare: OR, 48.0; 95% CI, 15.57-147.97)., Conclusions: ACO was significantly lower at 1 month in cases compared with controls. However, the difference in ACO between the two groups was insignificant at 6 months. A significant difference in anterior segment inflammation was documented in cases on the first postoperative day. There was no detectable benefit of performing scraping on the anterior capsule to avoid opacification after phacoemulsification.E

A specially designed grid and software used to assess the postoperative rotation of a toric intraocular lens (IOL) are described. Postoperatively, a digital retroillumination image of the patient is taken and this image is superimposed on the grid. The software determines the center of the IOL. A prominent episcleral vessel is identified, and the axis of the toric IOL and the episcleral vessel are documented using the grid. These values act as references for aligning the images taken during the follow-up period.

Reports suggest reasonable efficacy and minimal myelosuppression from combination imatinib and hydroxyurea for recurrent malignant glioma. We retrospectively reviewed 16 patients treated with this regimen who were evaluable for toxicity; 14 were also evaluable for response. The incidence of grade 3-4 hematologic toxicity was 25%. The best radiographic response, by Macdonald criteria, was partial response (PR) in three patients (21%), stable disease (SD) in four (29%), and progressive disease (PD) in seven (50%). One patient with a PR developed therapy-limiting hematologic toxicity on day 19 of treatment, progressing to grade 4 on day 64, and persisting until death on day 127 despite discontinuing both drugs. Another patient with PR and two of four patients with SD also developed grade 3 hematologic toxicity. All patients with grade 3-4 hematologic toxicity had disease control (PR or SD) as best radiographic response, whereas none with PD suffered grade 3-4 hematologic toxicity. Combining imatinib with hydroxyurea is effective in some patients with malignant glioma. However, myelosuppression can persist for months after discontinuing the regimen, precluding further chemotherapy. Disease control may also correlate with hematologic toxicity (p = 0.08), suggesting that glioma and marrow stem cells may share a common sensitivity to this chemotherapy regimen.

Background: Treatment options for patients with recurrent central nervous system (CNS) metastases are limited. Rapid infusion of high-dose intravenous methotrexate (HD IV MTX) penetrates the blood-brain barrier (BBB) and has reported activity in leptomeningeal metastases., Methods: Medical records were reviewed for all patients treated with HD IV MTX (3.5 g/m2) for CNS parenchymal or leptomeningeal metastases. Radiographic response rate, survival, and toxicity were determined., Results: Thirty-one women and one man with a median age of 52 years (range 33-76) were treated with a total of 141 cycles (median 4, range 1-13). Twenty-nine patients had breast cancer, and one each had cancer of unknown primary (CUP), squamous cell carcinoma of the head and neck, and non-small cell lung cancer (NSCLC). An objective radiographic response and stable disease were each observed in nine patients (28%), and 13 (44%) patients progressed. Prior treatment with low-dose MTX for systemic disease did not affect response (P = 0.8). The median overall survival (n = 32) was 19.9 weeks (range 2.9-135.4+) with one patient alive at 135.4 weeks. Myelosuppression and elevated serum hepatic transaminases were the most common acute toxicities (21% and 9% of HD IV MTX cycles, respectively)., Conclusions: HD IV MTX is effective in the treatment of CNS metastases with disease control (response or stable) as a best response in 56% of assessable patients. Further study is warranted.

The Response Evaluation Criteria in Solid Tumors, or RECIST criteria (one-dimensional [1D] measurement), are widely used to measure response in tumors, but there are few studies evaluating these criteria in brain tumors. We compared linear and volumetric measurements in adult high-grade supratentorial enhancing gliomas to determine the agreement between measurements, in defining responses and in their subsequent relation to survival. We hypothesized that the 1D RECIST criteria maybe suitable for response assessment in adult high-grade gliomas. Tumor size on MRI scans in 104 patients with high-grade enhancing gliomas treated on clinical trial protocols was measured by using 1D (greatest length), 2D (two-dimensional: product of the two longest perpendicular diameters), 3D (three dimensional: product of the longest perpendicular diameters in one plane and the longest orthogonal diameter to that plane), enhancing volume (EV), and total volume (TV). A total of 388 T1 postgadolinium MRI scans (104 baseline and 284 follow-up scans) were evaluated. Volumetric analysis (EV and TV) was performed with commercially available software. Intraobserver and interobserver correlations (rho) were high for all modalities (rho > 0.92 and rho > 0.71, respectively). Correlation was excellent (rho > 0.9) among all modalities except for 3D (rho < 0.6). Patient response rates ranged from 12% to 26%. Median progression-free survival (mPFS) and six-month progression-free survival (6mPFS) were not significantly different among the methods (range, 5.3 months to 5.9 months and 42% to 48%, respectively). Landmark analyses of response at two months using linear methods predicted overall survival with hazard ratios of 0.19 to 0.29 (P < 0.005). These results suggest high concordance among 1D, 2D, TV, and EV, but not 3D, methods in assessing enhancing tumor progression and in estimating mPFS and 6mPFS in adult brain tumor patients. The tumor response at two months assessed by linear methods correlated better with overall survival. Thus, linear methods are comparable to volumetric methods, but simpler to implement for routine clinical use and for designing clinical trials of brain tumors.

Primary central nervous system lymphoma (PCNSL) describes a malignant non-Hodgkin's lymphoma (NHL) whose sole site of involvement is the central nervous system (CNS). The diagnosis of PCNSL must be differentiated from systemic NHL with metastasis to the CNS, which usually occurs late in the course of systemic disease. PCNSL accounts for approximately 4% to 7% of primary brain tumors, and its incidence has been increasing since the mid-1970s. Compared with other more common malignant primary brain tumors, PCNSL tends to be more amenable to radiotherapeutic and chemotherapeutic intervention. In this article, the authors review the standard treatment for upfront and recurrent PCNSL.

Microelectrode studies in nonhuman primates and other mammals have demonstrated that many neurons in auditory cortex are excited by pure tone stimulation only when the tone's frequency lies within a narrow range of the audible spectrum. However, the effects of auditory cortex lesions in animals and humans have been interpreted as evidence against the notion that neuronal frequency selectivity is functionally relevant to frequency discrimination. Here we report psychophysical and anatomical evidence in favor of the hypothesis that fine-grained frequency resolution at the perceptual level relies on neuronal frequency selectivity in auditory cortex. An adaptive procedure was used to measure difference thresholds for pure tone frequency discrimination in five humans with focal brain lesions and eight normal controls. Only the patient with bilateral lesions of primary auditory cortex and surrounding areas showed markedly elevated frequency difference thresholds: Weber fractions for frequency direction discrimination ("higher"-"lower" pitch judgments) were about eightfold higher than Weber fractions measured in patients with unilateral lesions of auditory cortex, auditory midbrain, or dorsolateral frontal cortex; Weber fractions for frequency change discrimination ("same"-"different" pitch judgments) were about seven times higher. In contrast, pure-tone detection thresholds, difference thresholds for pure tone duration discrimination centered at 500 ms, difference thresholds for vibrotactile intensity discrimination, and judgments of visual line orientation were within normal limits or only mildly impaired following bilateral auditory cortex lesions. In light of current knowledge about the physiology and anatomy of primate auditory cortex and a review of previous lesion studies, we interpret the present results as evidence that fine-grained frequency processing at the perceptual level relies on the integrity of finely tuned neurons in auditory cortex.

We report the case of a 44-year-old right-handed woman who experienced her first convulsion while taking bupropion. Electroencephalography showed frequent bilateral independent temporal lobe epileptiform discharges that resolved when bupropion was discontinued. This is the first well-documented case of epileptiform discharges induced by bupropion in humans.