Indapamide-induced transient myopia with supraciliary effusion: case report.

BACKGROUND: Ingestion of sulphonamide-derived drugs has been reported to possibly have ocular side-effects. Authors aimed to present a rare case of indapamide-induced transient myopia with ciliary body edema and supraciliary effusion. CASE PRESENTATION: A 39 years old caucasian female patient presented at the Department of Neurology with headache and sudden bilateral loss of distant vision. Neurological assessment and cranial CT scans were unremarkable. For her hypertension, twice a day bisoprolol 2.5 mg and once a day indapamide 1.5 mg tablets were prescribed several days before. At her presenting, ophthalmic findings were as follows: visual acuity 0.08-7.25Dsph = 1.0 and 0.06-7.25Dsph = 1.0; IOP 25 mmHg and 24 mmHg, anterior chamber depth (ACD) 2.32 mm and 2.49 mm, lens thickness (L) 4.02 mm and 4.09 mm in the right and the left eye, respectively. By means of ultrasound biomicroscopy (UBM), thickened (720 / 700 micron) and detached ciliary body, its forward movement (ciliary body-cornea angle 108[prime] / 114[prime]) and forward rotated ciliary processes were seen. Angle opening distance (AOD500) were 300 / 314 microns. By the following days, the myopia gradually diminished, and a week after her first symptoms, her uncorrected visual acuity was 1.0 in both eyes, IOP 13 mmHg and 17 mmHg, ACD 3.68 mm and 3.66 mm, L 3.78 mm and 3.81 mm in the right and the left eye, respectively. Ciliary body edema and detachment disappeared (ciliary body thickness 225 / 230 micron), both of the ciliary body-cornea angle 134[prime] / 140[prime] and the AOD500 (650 / 640 microns) increased. At this point, the patient admitted that she had stopped taking indapamide two days before. CONCLUSIONS: Our case report is the third one in the literature to present indapamide-induced transient myopia, and the first to employ UBM for describing the characteristics of this rare condition. According to the findings, authors suggest that both ciliary muscle contraction and ciliary body edema may play role in the pathomechanism. UBM seems to be a useful tool in the differential diagnosis of acute myopia. Further, authors wish to draw attention to one of the potential adverse effects of this drug which was not listed by its package insert

Mitochondrial DNA Polymorphism A4917G Is Independently Associated with Age-Related Macular Degeneration

The objective of this study was to determine if MTND2*LHON4917G (4917G), a specific non-synonymous polymorphism in the mitochondrial genome previously associated with neurodegenerative phenotypes, is associated with increased risk for age-related macular degeneration (AMD). A preliminary study of 393 individuals (293 cases and 100 controls) ascertained at Vanderbilt revealed an increased occurrence of 4917G in cases compared to controls (15.4% vs.9.0%, p = 0.11). Since there was a significant age difference between cases and controls in this initial analysis, we extended the study by selecting Caucasian pairs matched at the exact age at examination. From the 1547 individuals in the Vanderbilt/Duke AMD population association study (including 157 in the preliminary study), we were able to match 560 (280 cases and 280 unaffected) on exact age at examination. This study population was genotyped for 4917G plus specific AMD-associated nuclear genome polymorphisms in CFH, LOC387715 and ApoE. Following adjustment for the listed nuclear genome polymorphisms, 4917G independently predicts the presence of AMD (OR = 2.16, 95%CI 1.20–3.91, p = 0.01). In conclusion, a specific mitochondrial polymorphism previously implicated in other neurodegenerative phenotypes (4917G) appears to convey risk for AMD independent of recently discovered nuclear DNA polymorphisms

Clinical benefit in Phase-I trials of novel molecularly targeted agents: does dose matter?

Phase-I trials traditionally involve dose-escalation to determine the maximal tolerated dose (MTD). With conventional chemotherapy, efficacy is generally deemed to be dose-dependent, but the same may not be applicable to molecularly targeted agents (MTAs). We analysed consecutive patients included in Phase-I trials at the Royal Marsden Hospital from 5 January 2005 to 6 June 2006. We considered only trials of monotherapy MTAs in which the MTD was defined. Three patient cohorts (A, B, and C) were identified according to the dose received as a percentage of the final trial MTD (0–33%, 34–65%, >66%). Potential efficacy was assessed using the non-progression rate (NPR), that is, complete/partial response or stable disease for at least 3 months by RECIST. A total of 135 patients having progressive disease before enrolment were analysed from 15 eligible trials. Median age was 57 years (20–86); male : female ratio was 1.8 : 1. Cohort A, B, and C included 28 (21%), 22 (16%), and 85 (63%) patients; NPR at 3 and 6 months was 21% and 11% (A), 50% and 27% (B), 31% and 14% (C), respectively, P=0.9. Median duration of non-progression (17 weeks; 95% CI=13–22) was not correlated with the MTD level, P=0.9. Our analysis suggests that the potential for clinical benefit is not confined to patients treated at doses close to the MTD in Phase-I trials of MTAs

Gut evacuation rate and grazing impact of the krill Thysanoessa raschii and T. inermis

Gut evacuation rates and ingestion rates were measured for the krill Thysanoessa raschii and T. inermis in Godthåbsfjord, SW Greenland. Combined with biomass of the krill community, the grazing potential on phytoplankton along the fjord was estimated. Gut evacuation rates were 3.9 and 2.3 h−1 for T. raschii and T. inermis, respectively. Ingestion rates were 12.2 ± 7.5 µg C mg C−1 day−1 (n = 4) for T. inermis and 4.9 ± 3.2 µg C mg C−1 day−1 (n = 4) for T. raschii, corresponding to daily rations of 1.2 and 0.5 % body carbon day−1. Clearance experiments conducted in parallel to the gut evacuation experiment gave similar results for ingestion rates and daily rations. Krill biomass was highest in the central part of the fjord’s length, with T. raschii dominating. Community grazing rates from krill and copepods were comparable; however, their combined impact was low, estimated as <1 % of phytoplankton standing stock being removed per day during this late spring study

Using genetic variation and environmental risk factor data to identify individuals at high risk for age-related macular degeneration

A major goal of personalized medicine is to pre-symptomatically identify individuals at high risk for disease using knowledge of each individual's particular genetic profile and constellation of environmental risk factors. With the identification of several well-replicated risk factors for age-related macular degeneration (AMD), the leading cause of legal blindness in older adults, this previously unreachable goal is beginning to seem less elusive. However, recently developed algorithms have either been much less accurate than expected, given the strong effects of the identified risk factors, or have not been applied to independent datasets, leaving unknown how well they would perform in the population at large. We sought to increase accuracy by using novel modeling strategies, including multifactor dimensionality reduction (MDR) and grammatical evolution of neural networks (GENN), in addition to the traditional logistic regression approach. Furthermore, we rigorously designed and tested our models in three distinct datasets: a Vanderbilt-Miami (VM) clinic-based case-control dataset, a VM family dataset, and the population-based Age-related Maculopathy Ancillary (ARMA) Study cohort. Using a consensus approach to combine the results from logistic regression and GENN models, our algorithm was successful in differentiating between high- and low-risk groups (sensitivity 77.0%, specificity 74.1%). In the ARMA cohort, the positive and negative predictive values were 63.3% and 70.7%, respectively. We expect that future efforts to refine this algorithm by increasing the sample size available for model building, including novel susceptibility factors as they are discovered, and by calibrating the model for diverse populations will improve accuracy

Eccentric Exercise Activates Novel Transcriptional Regulation of Hypertrophic Signaling Pathways Not Affected by Hormone Changes

Unaccustomed eccentric exercise damages skeletal muscle tissue, activating mechanisms of recovery and remodeling that may be influenced by the female sex hormone 17β-estradiol (E2). Using high density oligonucleotide based microarrays, we screened for differences in mRNA expression caused by E2 and eccentric exercise. After random assignment to 8 days of either placebo (CON) or E2 (EXP), eighteen men performed 150 single-leg eccentric contractions. Muscle biopsies were collected at baseline (BL), following supplementation (PS), +3 hours (3H) and +48 hours (48H) after exercise. Serum E2 concentrations increased significantly with supplementation (P<0.001) but did not affect microarray results. Exercise led to early transcriptional changes in striated muscle activator of Rho signaling (STARS), Rho family GTPase 3 (RND3), mitogen activated protein kinase (MAPK) regulation and the downstream transcription factor FOS. Targeted RT-PCR analysis identified concurrent induction of negative regulators of calcineurin signaling RCAN (P<0.001) and HMOX1 (P = 0.009). Protein contents were elevated for RND3 at 3H (P = 0.02) and FOS at 48H (P<0.05). These findings indicate that early RhoA and NFAT signaling and regulation are altered following exercise for muscle remodeling and repair, but are not affected by E2

Multifactor effects and evidence of potential interaction between complement factor H Y402H and LOC387715 A69S in age-related macular degeneration

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