Early local activation of complement in aqueous humour of patients with age-related macular degeneration.

OBJECTIVE: To investigate complement activation in aqueous humour of patients with early, intermediate and neovascular age-related macular degeneration (AMD). PATIENTS AND METHODS: Aqueous humour of 79 AMD patients (early, intermediate and neovascular) and 77 age-matched controls was prospectively collected. The levels of the complement protein 3 (C3), activation products complement factor 3a (C3a) and Ba, C3b/iC3b, complement factors B, H and I (CFB, CFH and CFI), and total protein concentration were measured. Data were modelled using covariate analysis to assess the impact of age and glaucoma status of patients and total protein concentration of samples on complement protein concentration across groups. RESULTS: C3a concentration was significantly increased in the aqueous humour of early (p = 0.016), intermediate (p = 0.003) and neovascular (p = 0.018) AMD patients, whilst C3 concentration was significantly increased in early AMD patients only (p = 0.019). Levels of CFB and CFH were significantly increased in the aqueous humour of neovascular AMD patients (p = 0.023 and p = 0.018, respectively). CONCLUSIONS: Our findings provide evidence for early local complement dysregulation in AMD patients, suggesting that complement pathway inhibition may be a clinically relevant intervention for early stages of AMD.

[Cancer-associated retinopathy (CAR) in neuroendocrine carcinoma of the uterus]. / Karzinomassoziierte Retinopathie (CAR) bei neuroendokrinem Uteruskarzinom.

A 75-year-old female patient presented with bilateral progressive loss of vision. Best corrected visual acuity (BCVA) was hand movements in the right eye and 1/50 in the left eye. The spectral domain optical coherence tomography (SD-OCT) showed thinning of the outer retina suspected to be due to autoimmune retinopathy. A neuroendocrine carcinoma of the uterus was diagnosed during tumor screening. Under systemic therapy with corticosteroids the visual acuity improved to 20/200 in the right eye and 20/80 in the left eye. Cancer-associated retinopathy (CAR) is a paraneoplastic autoimmune retinopathy.

Local complement activation in aqueous humor in patients with age-related macular degeneration.

PurposeTo investigate complement activation in aqueous humor and in plasma of patients with neovascular age-related macular degeneration (nAMD).Patients and methodsAqueous humor and EDTA-plasma of 31 nAMD patients and 30 age-matched controls was collected. The levels of the complement factor 3 (C3), the regulators factor H (FH), and factor I (FI), and of the complement activation products Ba, C3a, and the terminal complement complex (sC5b-9) were measured. Associations between complement levels and phenotype were determined using Mann-Whitney U-test.ResultsIn plasma, no significant differences were found between the nAMD group and the control group. In aqueous humor, significantly increased levels of Ba (P=0.002), and C3a (P=0.002) indicate local complement activation in nAMD patients and a trend for a concomitant upregulation of the complement regulators FH (P=0.02) and FI (P=0.04).ConclusionsOur findings provide strong evidence for a local complement dysregulation in nAMD patients.

[Design of the ORCA module in the OCEAN study : Evaluation of SD-OCT results in daily routine practice]. / Design des ORCA-Moduls der OCEAN-Studie : Evaluierung der SD-OCT-Befunderhebung in der täglichen Praxisroutine.

BACKGROUND: The prevalence of blindness as defined by law could be reduced by the introduction of anti-vascular endothelial growth factor (VEGF) therapy. Because the treatment is governed by patient needs, mostly using morphological criteria, imaging diagnostics are of particular importance. The non-interventional OCEAN study investigates the treatment with ranibizumab in the clinical routine practice. In a subgroup of patients the interpretation of spectral domain optical coherence tomography (SD-OCT) scans by the treating physicians will be analyzed (ORCA module). METHODS: Over a period of 24 months data from patients with exudative age-related macular degeneration (AMD), macular edema due to retinal vein occlusion or diabetes mellitus, who are receiving intravitreal injections of ranibizumab, will be assessed. Information on examinations, visual acuity, treatment and recordings from imaging techniques will be documented using a questionnaire. The SD-OCT scans, fluorescence angiography and fundus photography will be independently analyzed by the ophthalmologist of the study center and by three reading centers (CIRCL Cologne, GRADE Bonn and M3 Münster). Automated measurements of retinal thickness by the manufacturers' software will be checked and if necessary manually corrected. A qualitative interpretation in terms of morphological criteria for (further) treatment will be performed. CONCLUSION: A thorough assessment of SD-OCT images during anti-VEGF therapy provides the basis for the best possible needs-oriented treatment regimen. The control of the quality of data from daily routine practice may indicate possible weaknesses allowing explicit training and therefore optimization of patient treatment.

Extramacular drusen are highly associated with age-related macular degeneration, but not with CFH and ARMS2 genotypes.

BACKGROUND: To evaluate the association of extramacular drusen (EMD) with age-related macular degeneration (AMD) and with complement factor H (CFH rs1061170) and age-related maculopathy susceptibility 2 (ARMS2 rs10490924) polymorphisms in individuals with and without AMD. METHODS: In this case-control study, AMD staging was performed in 622 individuals. EMD were defined as ≥10 drusen (including ≥1 intermediate drusen) outside the Early Treatment of Diabetic Retinopathy Study Grid within field 2. Genotype associations for CFH and ARMS2 variants were assessed using logistic regression analysis. RESULTS: EMD (n=213) showed a strong association with AMD (OR=3.85; p=1.66×10(-13)). AMD (n=316) was strongly associated with CFH (p=1.78×10(-7)) and ARMS2 genotypes (p=1.67×10(-8)). After adjustment for AMD, age and gender, EMD were neither associated with CFH (p=0.11) nor with ARMS2 (p=0.45) genotypes. In individuals without AMD, the groups with and without EMD showed no differences regarding both genetic variants. CONCLUSIONS: The strong association between drusen within and outside of the macula suggests a common pathogenesis. However, EMD were not AMD-independently associated with CFH or ARMS2 genotypes. Our results indicate that patients without AMD but with EMD can serve as controls in studies evaluating AMD risk factors. Further studies are required to elucidate the aetiology and clinical relevance of EMD.

[Rebound tonometry after vitreoretinal surgery]. / Reboundtonometrie nach vitreoretinaler Chirurgie.

PURPOSE: The aim of this study was to analyze the practicability and comparability of the Icare rebound tonometer (RT) versus the Schiötz indentation tonometer (SIT) and the Goldmann applanation tonometer (GAT) for measuring intraocular pressure (IOP) in patients after pars plana vitrectomy (PPV). METHODS: A total of 100 eyes from 100 patients who underwent vitreoretinal surgery in the Department of Ophthalmology, University of Cologne were included in this prospective analysis. The IOP was measured using RT preoperatively, on the day of surgery and 2 days after surgery, using SIT on the day of surgery and GAT preoperatively and 2 days after surgery. For the evaluation eyes were divided into subgroups with respect to the endotamponade selected and the IOP level. RESULTS: The mean preoperative IOP for all enrolled eyes was 15.4 ± 8.0 mmHg for RT and 16.1 ± 7.9 mmHg for GAT. Bland-Altman analysis revealed a bias between RT and GAT of - 0.6 mmHg. Bland-Altman analysis for the postoperative course of all eyes revealed a bias of 3.0 mmHg between RT and SIT on the day of surgery and no bias between RT and GAT in the further postoperative follow-up. CONCLUSION: Rebound tonometry seems to provide precise IOP values after vitreoretinal surgery. Divergence from SIT values on the day of surgery is presumably due to a general tendency of SIT to underestimate IOP values. Therefore, RT can be used in the clinical routine after vitreoretinal surgery as an alternative to GAT.

Comparison of Seven Commonly Used Agents for Prophylaxis of Seasickness.

The objective of the study was to compare the efficacy and tolerability of seven drugs frequently used for the prevention of seasickness: the drugs were namely cinnarizine, cinnarizine with domperidone, cyclizine, dimenhydrinate with caffeine, ginger root, meclozine with caffeine, and scopolamine. The design was a randomized, double-blind study with two arms. On ethical grounds, a placebo group was not included as in a previous study, in the same setting, 80% of the passengers not receiving prophylactic drugs were seasick. The setting was in Andenes (Norway) during a time period from July to September 1992. Subjects were 1741 tourist volunteers who were joining a whale safari. The main outcome measures were vomiting, malaise (modified Graybiel criteria), and subjective reports of adverse events. Follow up was possible in 1489 volunteers (85.5%). In each active treatment group, 4.1-10.2% experienced vomiting and 16.4-23.5% experienced malaise (not significant). Equally, there was no significant difference in the incidence and characteristics of adverse events reported in the various medication groups. Scopolamine Transdermal Therapeutic System (TTS) users exhibited slightly more visual problems and the agent tended to be less effective. Six of the seven medications may be recommended for prevention of seasickness; scopolamine TTS seems the least attractive.

In the market for ethics. Marketing begins with values.

High-quality care and concern for the poor are among the core values that all Catholic healthcare facilities share. And marketing is a proven tool for extending those values. In times past, healthcare providers, including Catholic facilities, were concerned about whether healthcare marketing was ethical. Much of the concern focused on advertising and promotion. A number of ethical violations do appear in hospital advertising. But government and professional organizations have established guidelines for ethics in advertising. Hospitals should encourage their marketing professionals to personally adhere to these codes. To ensure marketing activities are conducted ethically, a hospital must clearly articulate its commitment to ethical marketing; ensure that marketing professionals adhere to this commitment; and monitor activity. These steps should extend to a hospital's strategic plan, particularly its mission statement. Although strategic planning has many critical elements, the heart of the plan and the process is the mission statement, the expression of an organization's distinctiveness. For a Catholic hospital, this distinctiveness is found in two tiers of value: the core Catholic values, as articulated by its religious sponsors, and the institution's specific values flowing from its history, location, and services. If a religious healthcare provider is really committed to its values, it will actively affirm them in its marketing.

Plasma membrane expansion terminates in Saccharomyces cerevisiae secretion-defective mutants while phospholipid synthesis continues.

Phospholipid synthesis activity and plasma membrane growth have been studied in the Saccharomyces cerevisiae temperature-sensitive, secretion-defective mutants isolated by Novick and Schekman (Proc. Natl. Acad. Sci. U.S.A. 76:1858-1862, 1979; Novick et al., Cell 21:205-215, 1980). The mutants, sec1 through sec23, do not grow at 37 degrees C and exhibit lower rates of phospholipid synthesis than does the wild-type strain X2180. None of the mutants exhibits a decline in lipid synthesis rapid enough to explain secretion failure. Plasma membrane growth was assessed indirectly by examining the osmotic sensitivity of spheroplasts derived from cultures transferred from 24 to 37 degrees C. Spheroplasts from the normal-growing strain X2180 exhibited a small rapid increase in osmotic sensitivity and stabilized at a more sensitive state. Spheroplasts from the sec mutants exposed to the same temperature shift exhibited progressively increasing osmotic sensitivity. Cycloheximide treatment prevented progressive increases in osmotic fragility. These data are compatible with the hypothesis that plasma membrane expansion is restricted in the sec mutants. During incubation at 37 degrees C, the accumulation of intracellular materials within the no-longer expanding plasma membrane exerts osmotic stress on the membrane, increasing with time. The gene products defective in Novick and Schekman's sec mutants appear to be required for both extracellular protein secretion and plasma membrane growth in yeast cells.

Nonuniform epicardial depolarizations during coronary occlusion in dogs.

Epicardial electrograms were recorded before and after occlusion of the left anterior descending coronary artery. The greatest difference between the post-occlusion and pre-occlusion depolarization times were determined. These times were referred to as the normalized times of greatest disparity, delta tmax. It was found that following both one- and two-stage occlusion of the LAD there was a significant increase in delta tmax in the ischemic area of the myocardium. This indicates increased asynchrony of depolarization. However, no significant change in depolarization times occurred in the unaffected area. In one-stage occlusion with an increase in delta t max there was a linear correlation with the development of ventricular arrhythmias, especially ventricular premature beats and tachycardia. Thus, there is evidence which links the increase in depolarization times with the mechanism of reentry and ventricular arrhythmias.

Detection of cardiac disturbances following thoracic trauma with high-frequency analysis of the electrocardiogram.

High-frequency electrocardiograms (HF-ECG) were recorded from rabbits before and after delivery of blunt, nonpenetrating thoracic trauma. The conventional electrocardiographic record showed transient changes following the blow; the HF-ECG showed distinct notching and slurring in the QRS complex in most cases, which persisted throughout the course of the experiment. At autopsy, a contusive lesion of the right ventricle was always found.