Increased ratios of complement factors C3a to C3 in aqueous humor and serum mark glaucoma progression.

INTRODUCTION: We recently performed a combined analysis of publicly available proteomic studies of aqueous humor (AH) of patients with primary open angle glaucoma (POAG). This analysis revealed changes in complement protein concentrations in the AH of progressive POAG patients, which suggested that the complement system may play a role in POAG progression. As the proteomic studies could not provide information on the activity of the complement system, we addressed this question in the current study. METHODS: Blood serum and AH were obtained from 30 patients: 10 progressive POAG, 10 stable POAG and, as controls, 10 cataract patients. Glaucoma patients with a visual field Mean Deviation (MD) change of at least 1.0 dB/year were considered progressive; a MD change of less than 0.5 dB/year was considered stable. The ratio between the levels of complement factors C3a and C3 was used as indicator for activation of the complement cascade. The factors were measured with commercially available ELISA kits. RESULTS: AH levels of complement factors C3 and C3a did not significantly differ between groups. In serum, complement factor C3 did not differ between groups whereas C3a was significantly elevated in progressive POAG patients compared to controls (p < 0.05). The resulting complement C3a/C3 ratio was significantly higher in progressive POAG patients in both AH (p < 0.05) and serum (p < 0.01), and this ratio significantly correlated between the two body fluids (p < 0.001). Furthermore, there was a strong correlation between disease progression and C3a/C3 activation ratio both in AH (p < 0.01) and in serum (p < 0.001). The higher the complement C3a/C3 ratio, the faster the disease progression. CONCLUSION: Significant increases in AH and serum complement C3a/C3 ratios were observed in progressive POAG patients but not in stable POAG patients. Furthermore, the complement C3a/C3 ratio correlated strongly with the rate of disease progression in both AH and serum. These findings suggest that activation of the complement system plays a role in glaucoma progression and that progressive glaucoma patients may have systemic changes in complement activation.

Eliciting preferences in glaucoma management-a systematic review of stated-preference studies.

BACKGROUND: In most cases, glaucoma patients require long-term medical and/or surgical treatment. Preference studies investigate how different aspects of glaucoma management, such as health or process outcomes, are valued and herewith help stakeholders make care more responsive to patients' needs. As, to our knowledge, no overview of these studies is currently available, this study aims to systematically review and critically appraise these studies. METHODS: A systematic literature review was conducted using keywords for stated-preference studies and glaucoma up to October 2021. Studies were included if they were original research and used a stated-preference methodology to investigate preferences in patients or healthcare professionals for different aspects of glaucoma management. Data were extracted and summarized. Furthermore, a quality appraisal of the included studies was performed using two validated checklists. RESULTS: The search yielded 1214 articles after removal of duplicates. Of those, 11 studies fulfilled the inclusion criteria. Studies aimed to elicit preferences for glaucoma treatment (27%), glaucoma related health state valuation (36%), and services (36%) from the patient (91%) or ophthalmologists' perspective (9%). Altogether studies included 69 attributes. The majority of attributes were outcome related (62%), followed by process (32%) and cost attributes (6%). Outcome attributes (e.g., effectiveness) were most often of highest importance to the population. CONCLUSIONS: This systematic review provides an up-to-date and critical review of stated-preference studies in the field of glaucoma, suggesting that patients have preferences and are willing to trade-off between characteristics, and revealed that outcome attributes are the most influential characteristics of glaucoma management.

[Bluish-gray discoloration of skin and conjunctiva]. / Blaugraue Verfärbung von Haut und Bindehaut.

Colloidal silver used as a suspension for (alternative) therapeutic purposes or silver exposure due to environmental or working conditions can lead to irreversible deposits of silver granules in the skin (bluish-gray hue of the skin), mucosa, cornea, retina and internal organs. Silver-induced discoloration of the conjunctiva should therefore be taken into account when a bluish-gray discoloration raises the suspicion of conjunctival melanoma.

Electron paramagnetic resonance spectrum of the FCO2 radical isolated in noble gas matrices.

The EPR spectra of the fluoroformyloxyl radical FCO(2) isolated in noble gas matrices at temperatures from 5 to 30 K have been investigated. This study provides principal g values and (19)F hyperfine coupling constants of FCO(2) measured in Ar matrices at 5 K, and yields isotropic values at 30 K. A detailed analysis of the coupling parameters obtained from the EPR and a concomitant high resolution spectroscopic MMW study supported by quantum chemical calculations rationalized the fine and hyperfine interactions of this simple fluorooxyl radical.

Matrix-isolation and comparative far-IR investigation of free linear [Cl3]- and a series of alkali trichlorides.

Here we discuss the reaction products of laser ablated alkali chlorides and elemental chlorine. Salt ablation using this technique combined with matrix-isolation spectroscopy allows for the formation and characterization of novel anionic species. The laser ablation of solid MCl with M = Cs, Rb, and K in the presence of Cl2 produced free [Cl3]- ions which were isolated in solid noble-gas matrices. For M = Cs, Rb, K, and Na, the ion pairs M+[Cl3]- are the main reaction products. Trends in the formation and bonding of these trichloride anions will be discussed. In contrast to the trifluoride analogues, the isolated ion pairs M+[Cl3]- feature a systematic distortion due to metal coordination.

Knowledge base and preferred methods of obtaining knowledge of glaucoma patients.

PURPOSE: To gather information regarding patient's understanding of glaucoma and the manner in which patients wish to learn about the disease with the intent of improving patient education. METHODS: Forty-four of sixty randomly selected ophthalmologists (73%) asked four of their patients consecutively to complete a questionnaire about glaucoma. The selection of questions was based on focus group interviews and suggestions from several experts. Topics included knowledge about glaucoma and its treatment, the need for information, and preferred providers and methods of patient education. RESULTS: Fifty percent of the patients had 49% or less correct answers to questions about glaucoma or its treatment. Per item the correct answers ranged from 5% to 90%. Lack of knowledge was associated with low level of education, short duration of glaucoma, high age, and no preference for the Internet as method of supplying information. These variables, however, did not identify groups with a considerable lack of knowledge sufficiently accurately to target patient education. A high need for information was observed and included information about the patient's own glaucoma. Almost all patients preferred the ophthalmologist and many also a nurse or a representative of the Glaucoma Patient Society as providers of information. Written material was the preferred method. CONCLUSIONS: Patient education should address all patients. A patient education program should cover a wide range of topics with a focus on general information through written material and information tailored to the individual glaucoma patient's needs. The ophthalmologist is a key- person, but others could play an important role in patient education.

Ultrastructural identification of trigeminal nerve endings in the rat cornea and iris.

Trigeminal nerve terminals in the rat cornea and iris were ultrastructurally identified using anterograde tracing with Phaseolus vulgaris-leukoagglutinin (PHA-L). Electron microscopic immunohistochemistry was used to demonstrate the presence and localization of calcitonin gene-related peptide (CGRP) in cornea and iris. In the cornea and iris, nerve fibers were labelled with PHA-L throughout the stroma. Labelling was most obvious within varicosities, densely packed with mainly clear and a few granular vesicles and containing dark mitochondria. Numerous fibers in the stroma of cornea and iris were CGRP-positive. CGRP-positive staining was most intense within varicosities, containing mainly clear and incidentally granular vesicles and dark mitochondria, similar to the structures labelled with PHA-L. CGRP-positive varicosities packed with mainly clear and few granular vesicles also were demonstrated in fibers adjacent to the sphincter and dilator muscles of the iris. In the corneal epithelium, small terminals containing vesicles were CGRP-positive. Trigeminal nerve fibers innervating the rat cornea and iris contained numerous varicosities packed with vesicles. These areas are CGRP-positive, so it can be implied that CGRP is released from these varicosities as a response to triggering impulses. This agrees with the hypothesis that in addition to their afferent function, sensory fibers also exert an efferent modulating function.

Ultrastructural identification of trigeminal nerve terminals in the pterygopalatine ganglion of rats: an anterograde tracing and immunohistochemical study.

Trigeminal nerve terminals in the rat pterygopalatine ganglion (PPG) were ultrastructurally identified using anterograde tracing with Phaseolus vulgaris-leucoagglutinin (PHA-L). Electron microscopic immunohistochemistry was used to demonstrate the presence of substance P (SP) and calcitonin gene-related peptide (CGRP) in nerve terminals of the PPG. Adjacent to the rostral part of the PPG an additional minor area was described. Perikarya in this minor rostral part were more spherical and had irregular outlines. Ultrastructurally, the glial enwrapment of the nerve terminals seemed to be more loosely arranged in comparison to that in the major rostral part of the PPG. With PHA-L, numerous labelled nerve fibres and terminals were found in all parts of the PPG. The ultrastructure of these terminals was uniform, many of them showing synaptic contacts. Numerous terminals in the PPG were SP-positive, whereas only a few were CGRP-positive. Fibres stained positive for both neuropeptides. The PPG is shown to be synaptically innervated by sensory fibres arising in the trigeminal ganglion, with the strong suggestion of SP and CGRP acting as neurotransmitters. A modulatory interaction between the autonomic and sensory system, resembling an axon reflex mechanism in the peripheral nervous system is endorsed.

The peripheral and central projections of the Edinger-Westphal nucleus in the rat. A light and electron microscopic tracing study.

The peripheral and central efferent projections of the rostral part of the Edinger-Westphal nucleus in the rat were investigated at the light and electron microscopic level by means of iontophoretic injections of the anterograde tracer Phaseolus vulgaris-leucoagglutinin and retrograde tracer injections of Fast blue and Nuclear yellow into the facial nucleus and into the principal olive. Two pathways leaving the rostral part of the Edinger-Westphal nucleus were studied, a peripheral and a central descending pathway. Fluorescent experiments demonstrated that the central pathway fibers originated from distinct individual Edinger-Westphal neurons. These neurons were mainly distributed throughout the rostral part of the Edinger-Westphal nucleus and had fusiform cell bodies. The neurons rarely form collateral projections. The central descending pathway left the Edinger-Westphal nucleus medially and terminated bilaterally in the principal olive, in the subnuclei A, B and C of the inferior olive and ipsilaterally in the medial accessory olive. The central pathway also terminated contralaterally in the lateral parabrachial nucleus, the facial nucleus, the trigeminal brainstem nuclear complex, the lateral reticular nucleus and the rostroventral reticular nucleus. The projection to the facial nucleus provides evidence for the existence of a polysynaptic loop forming the central part of the corneal blink reflex. Projections from the Edinger-Westphal nucleus to the cerebellar cortex or the deep nuclei, as described in cat and primate, could not be confirmed. The peripheral pathway left the Edinger-Westphal nucleus ventrally and terminated on dendrites of ciliary ganglion cells, along smooth muscle cells of ciliary ganglion associated arterioles and in the proximity of ciliary ganglion associated venules. The central and peripheral terminals that originate in the Edinger-Westphal nucleus all had similar ultrastructural features: clear, round vesicles and electron dense mitochondria. The terminals originating from the central descending pathway were often found to be arranged in glomerular-like structures. The central and peripheral terminals made asymmetric synaptic membrane specializations (Gray type one), except terminals innervating the ciliary ganglion associated vessels, which showed no synaptic contacts.

Collaborative study on the use of motility enrichment on modified semisolid Rappaport-Vassiliadis medium for the detection of Salmonella from foods.

A collaborative study was performed in 15 laboratories to evaluate the use of motility enrichment on modified semisolid Rappaport-Vassiliadis (MSRV) medium for rapid Salmonella detection in a variety of food products. The results of this procedure were compared with those obtained by the cultural procedure using Rappaport-Vassiliadis (RV) broth as selective enrichment and modified brilliant green agar for selective plating. The tests were performed with Salmonella reference samples (SRS) as well as with naturally contaminated food products. When SRS were used without added food the productivity of both MSRV and RV was 96%. When SRS were combined with reference samples containing competitive bacteria the productivity was 98% for MSRV and 95% for RV. In the tests with food samples the productivity of MSRV was 92% with SRS added to food and 96% with naturally contaminated samples, while the productivity of RV was 88% and 90%, respectively. Statistical analysis showed that there was no significant difference between the procedures.

The effects of mutual interaction and host diet on the growth rates of the bacteria Actinomyces viscosus and Streptococcus mutans during colonization of tooth surfaces in di-associated gnotobiotic rats.

The bacteria were simultaneously inoculated into the mouths of germ-free rats. The maximum growth rates attained by Strep. mutans (doubling time td = 1.4 h) or A. viscosus (td = 2.7 h) were approximately the same as in mono-associated gnotobiotic rats [td = 1.1 and 2.8 h, respectively (Beckers and van der Hoeven, 1982a)]. The presence of glucose or sucrose did not affect the maximum growth rates. In starved rats, the accumulation of microorganisms tended to decline sooner, suggesting that the growth was limited by the availability of nutrients. No interaction between the two organisms was detected at the stage of initial adherence to the tooth surfaces or during the first 24 h of growth. After that, the increase of A. viscosus was retarded in the presence of Strep. mutans T2, but not with Strep. mutans OMZ176. The retardation was more pronounced in the rats fed on glucose than on sucrose. Yet, at 24 days after inoculation. A. viscosus had increased in the glucose more than in the sucrose group. Hence sucrose did not stimulate the accumulation of Strep. mutans more than glucose.

Disposition of single oral doses of butylated hydroxytoluene in man and rat.

The kinetics and metabolism of butylated hydroxytoluene (BHT) in man and rats have been compared. Single oral doses of 200, 63 or 20 mg BHT/kg body weight were administered to rats and a single oral dose of 0.5 mg/kg body weight was ingested by human volunteers (non-smoking males). In rats, kinetic parameters (area under the plasma concentration-time curve, plasma BHT peak levels) showed a dose-dependent increase. Plasma BHT levels after oral administration were about four times higher than those that have been reported for another synthetic food antioxidant, butylated hydroxyanisole (BHA; Verhagen et al., Fd Chem. Toxic. 27, 151-158). This may be a reflection of a smaller volume of distribution for BHT, since there were no differences in plasma elimination half-life or plasma clearance between BHT and BHA. In man, the mean plasma concentration-time profile after oral BHT intake was well below the BHT profiles observed for rats and closely followed plasma BHA kinetics in man. In rats, the simultaneous administration of BHT (200 mg/kg body weight) and BHA (200 mg/kg) significantly decreased the absorption of BHT from the gastro-intestinal tract in the first few hours after treatment; the plasma kinetics of BHA were not influenced by the simultaneous administration of BHT. In human female volunteers no alterations in plasma BHT or BHA profiles were seen after the simultaneous ingestion of BHT (0.25 mg/kg body weight) and BHA (0.25 mg/kg). Rats excrete about 10% of an oral dose of 200 mg BHT/kg as unchanged BHT in the faeces, whereas in man no BHT could be detected in the faeces. Urinary excretion of (un)conjugated 3,5-di-tert-butyl-4-hydroxybenzoic acid (BHT-COOH) accounts for only a small percentage of the administered dose in both rats and humans. It is concluded that the plasma BHT concentrations reached after the administration of a single medium to high dose of BHT to rats or a single low dose to man are very different.

Inter-observer variation in the assessment of skin ulceration.

Six observers (three physicians and three nurses) assessed 27 wounds of different types in 20 elderly patients, using five different classification systems. Using classification by colours, inter-observer agreement was moderate when six colours were used (70% agreement, group kappa 53%), and good if this was reduced to three (80% agreement, group kappa 64%). Results were only moderate using the Shea scoring system (68% agreement, group kappa 42%). Assessment for signs of infection was fair to moderate (75-85% agreement, group kappa 29-55%), but there was high inter-observer agreement for size and area (analysis of variance, p > or = 0.88).

Public health aspects of microbial contaminants in food.

Food-borne diseases affect the health and welfare of hundred thousands of people and result in considerable economic loss. Salmonella and Campylobacter are by far the most important causes of food-borne illness. Raw foods of animal origin are the major sources of these pathogens. Mishandling of foods in kitchens contributes to food-borne disease outbreaks. More education is necessary. But because of the inevitable risk of recontamination of cooked foods in every kitchen, more emphasis should be placed on pathogen-free raising of food animals and good manufacturing practices during slaughter. This will minimise contamination of raw foods of animal origin, thus reducing the contamination pressure in the kitchen and more effectively controlling food-borne diseases.

[Modification of the risk profile of obese essential hypertensive patients by the group "hypertension discussion" program]. / Beeinflussung des Risikoprofils von adipösen essentiellen Hypertonikern durch das Gruppenprogramm "Hypertonie im Gespräch".

The programme "Discussions on Hypertension" is a programme for group treatment of obese essential hypertensives in medical practices on the basis of behavioural therapy. A co-operation model was developed between the Department for General Medicine of the "Medizinische Hochschule Hannover", the Institute for Medical Psychology of the "Philipps-Universität Marburg" and the company Galenus Mannheim and was offered to doctors in general practice. The effects of the programme on the modifying of the risk profile for coronary heart disease was investigated in a controlled study in 137 patients by nine general practitioners. 81 patients were enrolled in the experimental group and 56 patients were assigned to a control group that was not using the programme. The experimental and control groups were comparable with respect to sociodemographic, psychological and medical parameters. Three months after completing the programme, the results of the study was shown in specific effect both on the psychological criteria of success (well-being, health knowledge, healthy behaviour, salt use and compliance) and in a reduction of the diastolic blood pressure in spite of a reduction of the antihypertensive drug treatment. The blood lipid levels (cholesterol and triglycerides) and the blood glucose level were also favourably affected. Patients in the experimental group had reduced their weight by an average of 5.6 kg. The patients in the control group only by 0.8 kg. Overall, there was a marked reduction in the proportion of patients with several risk factors in the experimental group, so that the programme can be attributed a preventive effect.

[Standardization of the isolation of Salmonella from food and feed stuff]. / Standaardisatie van de isolatie van Salmonella uit voedings- en voedermiddelen.

Developments in the standardization of the methods used in the isolation of Salmonella are reviewed from the sixties when it was noticed for the first time that different results were obtained when different methods were used, via the seventies when a single method was standardized and ultimately internationally accepted in the late seventies, followed by the finding that differences in results between laboratories were still obtained despite standardization and that this could only be overcome by the development of reference samples, with which each laboratory could check the performance of the standard method. Once reference material had been developed in the early eighties, the need for a standard method came to an end. Everyone can use the method of his choice today as long as reproducibility of the results is ensured. Reproducibility may be tested with the reference material.

[Food poisoning due to country sausage]. / Voedselvergiftiging door boerenmetworst.

Six children became seriously ill after eating dry sausages. The clinical symptoms and laboratory test suggested a case of poisoning by Staphylococcus aureus enterotoxin. The problems of enterotoxin analysis and the responsibility of the industry are discussed.

The relationship between visual field loss in glaucoma and health-related quality-of-life.

PURPOSE: to investigate the relationship between visual field loss and health-related quality-of-life (HRQOL) in patients with ocular hypertension (OHT) or primary open-angle glaucoma (POAG). METHODS: we conducted a cross-sectional study among 537 OHT and POAG patients from seven hospitals in The Netherlands. Clinical information was obtained from medical files. Patients completed a questionnaire, containing generic HRQOL instruments (EQ-5D and Health Utilities Index mark 3), vision-specific National Eye Institute Visual Functioning Questionnaire (VFQ-25), and glaucoma-specific Glaucoma Quality-of-Life questionnaire (GQL-15). The impact of visual field loss on HRQOL scores was analysed with multiple linear regression analyses. RESULTS: a relationship between mean deviation (MD) and HRQOL was found after adjusting for age, gender, visual acuity, medication side effects, laser trabeculoplasty, and glaucoma surgery. We found interaction between MD in both eyes for GQL and VFQ-25 scores. The relationship between MD and utility was non-linear, with utility only affected at MD-values below -25 dB in the better eye. Visual acuity, side effects, and glaucoma surgery independently affected HRQOL. Binocular MD and MD in the better eye had similar impacts on HRQOL, whereas MD in the worse eye had an independent effect. HRQOL was affected more by binocular defects in the inferior than in the superior hemifield. CONCLUSION: visual field loss in progressing glaucoma is independently associated with a loss in both disease-specific and generic quality-of-life. It is important to prevent progression, both in early and in advanced glaucoma, especially in patients with inferior hemifield defects and severe defects in either eye.