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.

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.

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.

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.

[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.

Microbiology and food hygiene in mass catering.

Serious consequences can arise from lack of hygiene in mass catering. The uncritical use of routine microbiological tests purporting to measure hygiene merely creates a false sense of security. The microbiological safety of food is achieved by as far as possible ensuring the absence of pathogenic microorganisms and by all means preventing their multiplication. The Hazard Analysis Critical Control Point concept is used to identify microbiologically vulnerable points in the food production process and to determine the most appropriate methods of control to be applied, usually such methods as improved handling techniques, monitoring of temperature and more intensive supervision. Microbiological testing is of value in the initial analysis, at appropriate intervals for verifying the effectiveness of control measures, and in demonstrating to food handlers the reality of the microbial risk if good hygienic standards are not maintained.

Incidence of Foodborne Disease in the Netherlands: Annual Summary - 1980.

Data on the incidence of foodborne disease in 1980 are presented. A total of 272 incidents affecting 1298 ill persons were analysed. In 64 incidents (337 cases), the etiology was established; micro-organisms appeared to be the main causative agents. Salmonella was responsible for 15 of these incidents (55 cases), Staphylococcus aureus for 6 (106), Clostridium perfringens for 8 (57), Bacillus cereus for 17 (88) and Campylobacter jejuni for 4 (9). Three episodes (4 cases) were caused by Yersinia enterocolitica , Escherichia coli and Vibrio sp. In 11 episodes (18 cases) illness resulted from ingestion of food contaminated with chemical substances. Cases of foodborne disease recorded by the Chief Medical Inspectorate included infections from Salmonella (6347) C. jejuni (531) and Y. enterocolitica (264). However, these could not be analysed further due to a lack of epidemiological information. About 60% of the outbreaks were associated with only two food items: meat and meat products (15%) and Chinese foods (44%). Mishandling of food in foodservice establishments resulted in about two-thirds of the incidents. It is supposed that there is an "over-reporting" of incidents involving Chinese foods from take-away restaurants, compared to episodes involving other foods from other locations, especially from private households. The role of viruses in outbreaks of foodborne gastroenteritis with an incubation period of more than 24 h is discussed.

Influence of xylitol on growth, establishment, and cariogenicity of Streptococcus mutans in dental plaque of rats.

The influence of xylitol on glucose metabolism of Streptococcus mutans C67-1S was studied in vitro and in rats in vivo. In vitro there was an inhibition by xylitol of the growth rate and acid production of S. mutans C67-1S, but in vivo no effect on the initial growth rate could be demonstrated. In vivo there was a delay in the start of growth of S. mutans which resulted in a 10-day delay of establishment. The isolated xylitol-resistant mutant of C67-1S, S. mutans C67-1S XR, showed no difference in glucose metabolism in batch cultures. S. mutans C67-1S and S. mutans C67-1S XR were both used to study caries development in SPF Osborne Mendel rats. The rats were housed under programmed feeding conditions and were fed a glucose or a glucose-xylitol diet. In the case of S. mutans C67-1S, there was a remarkable inhibition of fissure caries lesions in the presence of xylitol compared to the glucose group. But also in the S. mutans C67-1S XR groups there were fewer lesions in the presence of xylitol. These results indicated that the anticariogenic properties of xylitol do not only depend on an inhibition of bacterial metabolism, but in part on other mechanisms.