Factors associated with serum/plasma concentrations of vitamins A, C, E and carotenoids in older people throughout Europe: the EUREYE study.

PURPOSE: To report on plasma/serum levels of antioxidant vitamin and carotenoids in older adults resident in multiple countries in Europe and examine relationships with potential modifiers. METHODS: Population-based cross-sectional European Eye Study in 7 centres from northern to southern Europe. In total, 4,133 participants aged 65 years or over, collected by random sampling, were recruited. Questionnaires relating to diet, lifestyle and medical history were administered. Non-fasting blood samples were analysed in a single laboratory for vitamins A, C and E and a panel of carotenoids. Associations were analysed by bootstrapped multivariable regression analysis. RESULTS: Centre and season influenced the serum and plasma concentrations of all antioxidant vitamins and carotenoids. Gender, BMI, smoking, age, education, alcohol consumption and supplement use were also significantly associated with some, but not all, of the antioxidant vitamins and carotenoids examined. The proportion of variance explained ranged from 4.8 % for retinol to 25.2 % for zeaxanthin. CONCLUSIONS: In older people, antioxidant vitamin and carotenoid status varies by centre and season, but is also associated with other behavioural and lifestyle variables. Studies aiming to demonstrate an association between antioxidant vitamins and carotenoid status and chronic disease risk should consider these potential confounders.

The long-term outcome of the cemented Weber acetabular component in total hip replacement using a second-generation cementing technique.

We report the long-term outcome of a modified second-generation cementing technique for fixation of the acetabular component of total hip replacement. An earlier report has shown the superiority of this technique assessed by improved survival compared with first-generation cementing. The acetabular preparation involved reaming only to the subchondral plate, followed by impaction of the bone in the anchorage holes. Between 1978 and 1993, 287 total hip replacements were undertaken in 244 patients with a mean age of 65.3 years (21 to 90) using a hemispherical Weber acetabular component with this modified technique for cementing and a cemented femoral component. The survival with acetabular revision for aseptic loosening as the endpoint was 99.1% (95% confidence interval 97.9 to 100 after ten years and 85.5% (95% confidence interval 74.7 to 96.2) at 20 years. Apart from contributing to a long-lasting fixation of the component, this technique also preserved bone, facilitating revision surgery when necessary.

The additional yield of a periodic screening programme for open-angle glaucoma: a population-based comparison of incident glaucoma cases detected in regular ophthalmic care with cases detected during screening.

AIM: To study the additional yield of a periodic screening programme for open-angle glaucoma (OAG) by comparing, in a population-based setting, incident OAG (iOAG) cases detected in regular ophthalmic care with those detected during screening. METHODS: Participants aged 55 and over from the population-based Rotterdam Study underwent the same ophthalmic examination at baseline (1991-3) and follow-up (1997-9), including visual field testing and simultaneous stereo optic disc photography. Of 3842 participants, 87 (2.3%) developed iOAG during a mean follow-up time of 6.5 years. Of these 87 iOAG cases, 78 (90%) were included in this study. RESULTS: Of the 78 iOAG cases detected at follow-up, 23 (29%) had already been detected before during regular ophthalmic care. The remaining 55 (71%) undetected iOAG cases more often showed glaucomatous optic neuropathy without glaucomatous visual field loss (29 of 55 (53%)) as compared with the detected cases (four of 23 (17%); p = 0.009). Of the undetected iOAG cases, only four had developed significant visual field loss in their better eye. CONCLUSION: The additional yield of a periodic OAG screening programme is lower than expected from published prevalence data. In the discussion, the authors estimate that-in a white population with a low prevalence of pseudoexfoliation-about one in 1000 screened persons could be saved from bilateral end-stage OAG.

Cigarette smoking and age-related macular degeneration in the EUREYE Study.

OBJECTIVE: To examine the association between cigarette smoking and age-related maculopathy (ARM) including age-related macular degeneration (AMD) in the European population. DESIGN: Cross-sectional study. PARTICIPANTS: Four thousand seven hundred fifty randomly sampled > or =65-year-olds from 7 study centers across Europe (Norway, Estonia, United Kingdom, France, Italy, Greece, and Spain). METHODS: Participants underwent an eye examination and digital retinal photography. The images were graded at a single center. Smoking history was ascertained by a structured questionnaire administered by trained fieldworkers. Multinomial and binary logistic regressions were used to examine the association between smoking history and ARM grade and type of AMD, taking account of potential confounders and the multicenter study design. MAIN OUTCOME MEASURES: Photographic images were graded according to the International Classification System for ARM and stratified using the Rotterdam staging system into 5 exclusive stages (ARM 0-3 and ARM 4, also known as AMD). Age-related macular degeneration also was classified as neovascular AMD or geographic atrophy (GA). RESULTS: One hundred fifty-eight cases were categorized as AMD (109 neovascular AMD and 49 GA); 2260 had no signs of ARM (ARM 0). Current smokers had increased odds of neovascular AMD (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.4-4.8) or GA (OR, 4.8; 95% CI, 2.1-11.1), whereas for ex-smokers the odds were around 1.7. Compared with people with unilateral AMD, those with bilateral AMD were more likely to have a history of heavy smoking in the previous 25 years (OR, 5.1; 95% CI, 1.3-20.0). The attributable fraction for AMD due to smoking was 27% (95% CI, 19%-33%). There was no consistent association with ARM grades 1 to 3 and smoking. CONCLUSIONS: These findings highlight the need for increasing public awareness of the risks associated with smoking and the benefit of quitting smoking. Patients with unilateral disease who are current smokers should be advised of the risk of second-eye disease.

Retinal vessel diameters and risk of stroke: the Rotterdam Study.

BACKGROUND: Retinal vessels may provide information on cerebral vascular pathology, because they share many features with cerebral vessels. A smaller ratio of the retinal arteriolar-to-venular diameters reportedly predicts the risk of stroke. It is unclear if this is due to arteriolar narrowing or venular dilation. OBJECTIVE: To investigate whether smaller arteriolar or larger venular diameters are related to the risk of stroke and cerebral infarction. METHODS: This study was based on the prospective population-based Rotterdam Study and included 5,540 participants of 55 years or over, who had gradable fundus transparencies and were free of stroke at baseline (1990 to 1993). For each participant, retinal arteriolar and venular diameters were measured on digitized images of one eye. Follow-up for first-ever stroke was complete until January 1, 2002. RESULTS: After a mean follow-up of 8.5 years, 411 participants had a stroke, of whom 259 had cerebral infarction. Larger venular diameters were associated with an increased risk of stroke (hazard ratio [HR] adjusted for age and sex per SD increase: 1.12 [95% CI: 1.02 to 1.24]) and cerebral infarction (HR: 1.15 [95% CI: 1.02 to 1.29]). Smaller arteriolar diameters were neither related to the risk of stroke (HR per SD decrease: 1.02 [95% CI: 0.93 to 1.13]) nor to the risk of cerebral infarction (HR: 1.02 [95% CI: 0.90 to 1.15]). After additional adjustment for other cardiovascular risk factors, the results did not change. CONCLUSIONS: Larger retinal venular diameters are associated with an increased risk of stroke and cerebral infarction. The role of venules in cerebrovascular disease warrants further exploration.

Intertrochanteric osteotomies do not impair long-term outcome of subsequent cemented total hip arthroplasties.

UNLABELLED: The literature contains contradictory evidence as to whether previous proximal femoral osteotomy impairs the long-term outcomes of total hip arthroplasty. We therefore examined whether our patients with cemented total hip arthroplasties after previous osteotomies had inferior outcomes. We also investigated whether the intraoperative complication rate and the clinical and radiologic outcomes were altered by a previous osteotomy. We compared a group of 121 consecutive patients who had total hip arthroplasties (1974-1993) after osteotomies with a group of 290 consecutive patients who had total hip arthroplasties (1974-1987) without previous surgery. There was no difference in survival rate. There was a 10-year survival rate of 90% compared with 92% for the control group. The 15-year survival rates were 83% and 81%, respectively. There were no differences in radiologic and clinical followups. Intraoperative perforation of the femur occurred more often in patients with a total hip arthroplasty after an osteotomy. Our data suggest the long-term outcome of a cemented total hip arthroplasty is not impaired by a previous well-performed osteotomy. LEVEL OF EVIDENCE: Therapeutic study, Level III (retrospective comparative study). See the Guidelines for Authors for a complete description of levels of evidence.

Total hip replacement with a superolateral bone graft for osteoarthritis secondary to dysplasia: a long-term follow-up.

We evaluated the long-term results of 116 total hip replacements with a superolateral shelfplasty in 102 patients with osteoarthritis secondary to developmental dysplasia of the hip. After a mean follow-up of 19.5 years (11.5 to 26.0), 14 acetabular components (12%) had been revised. The cumulative survival at 20 years was 78%, with revision for loosening of the acetabular component as the end-point. All grafts were well integrated and showed remodelling. In six grafts some resorption had occurred under the heads of the screws where the graft was not supporting the socket. Apart from these 14 revisions, seven acetabular components had possible radiological signs of loosening at a mean follow-up of 14.5 years, one had signs of probable loosening, and five had signs of definite loosening. These results indicate that this technique of bone grafting for acetabular reconstruction in hip dysplasia is a durable solution for cemented acetabular components.

[From gene to disease; primary open-angle glaucoma and three known genes: MYOC, CYP1B1 and OPTN]. / Van gen naar ziekte; primair openkamerhoekglaucoom en 3 bekende genen: MYOC, CYP1B1 en OPTN.

Primary open-angle glaucoma (POAG) is a group of multifactorial diseases that affects 1.5% of the population. If untreated, the disease leads to irreversible damage to the visual system. The clinical features of POAG are excavation of the optic disc and visual field defects, probably due to degeneration of retinal ganglion cells. Important risk factors for POAG are older age, elevated intraocular pressure, the presence of POAG in relatives, and still largely unknown molecular genetic factors. The clinical, genetic and pathological heterogeneity most likely reflects the complex heterogeneous situation at the molecular level. The three genes known to be involved in POAG (MYOC, CYP1B1 and OPTN) account for up to 18% of the POAG cases. These findings result in new possibilities for the presymptomatic molecular diagnosis of POAG.

Methods for a population-based study of the prevalence of and risk factors for age-related maculopathy and macular degeneration in elderly European populations: the EUREYE study.

PURPOSE: The aims of the EUREYE study are to evaluate the prevalence of age-related maculopathy (ARM), including macular degeneration (AMD), in elderly European populations, to investigate risk factors for ARM and AMD, especially solar radiation and diet, and to measure the impact of these conditions on vision-related quality of life. METHODS: A population-based cross-sectional study with retrospective and current exposure measurements. Risk factor assessment is via questionnaires (for lifestyle factors such as smoking and alcohol, dietary risk factors, outdoor exposure) and blood analysis. Participants are people aged 65 and over. The study is carried out in 7 centres with locations spanning north to south Europe. The main outcome measure is grading of fundus photographs (for stage and type of ARM, using the International ARM Epidemiological Study Group grading system).

Weber rotation total hip replacement: a prospective 5- to 20-year followup study.

Between 1974 and 1989, 315 primary total hip replacements (274 patients) were done using the cemented Weber Rotation prosthesis and standardized operative technique, which was modified for the stem in 1978. After the first postoperative year, all patients had routine clinical and radiologic examinations at 2-year intervals. Twenty-one patients (22 hips) were lost to followup. At the most recent followup, 30 of 293 hips (253 patients) had been revised: 24 hips for aseptic loosening, five hips for infection, and one hip for a femoral fracture. Survivorship analyses with revision for aseptic loosening as an end point for the 315 hips showed 93% and 78% survival after 10 and 15 years, respectively. Separate survival analyses for the socket showed 99% and 89% survival after 10 and 15 years, respectively. The stem had a survival of 94% and 81%, respectively, during the same time. Survival at 15 years with radiologic evidence of loosening as an end point was 85% for the socket and 72% for the stem. The cementing technique and the design of the acetabular component significantly influenced the rate of loosening. Survivorship analyses with revision for aseptic loosening of the socket, using a modified second generation cementing technique and a hemispheric socket, showed 100% survival after 10 years and 98% after 13 years.

[Changing perception of hereditary eye diseases]. / Veranderende visie op erfelijke oogaandoeningen.

The authors present the cases of two parents with Usher syndrome type I who appeared to have normal offspring, and two families, one with autosomal dominant retinoblastoma and a RB1-gene mutation and one with primary open angle glaucoma and a myocilin gene mutation, in whom DNA-analysis was used to see whether check-ups were needed. The field of ophthalmogenetics comprises many disorders, both congenital and those with a later onset. Mendelian, mitochondrial, as well as multifactorial heredity is seen. Recent progress in this field, especially in molecular genetics, has created new possibilities, but some situations appear to be more complex than previously assumed. Particularly if there is genetic heterogeneity or multifactorial inheritance, possibilities for counselling and DNA analysis remain limited.

Risk factors for age-related macular degeneration: Pooled findings from three continents.

OBJECTIVE: To assess the prevalence and potential risk factors for late age-related macular degeneration (AMD) in three racially similar populations from North America, Europe, and AUSTRALIA: DESIGN: Combined analysis of population-based eye disease prevalence data. PARTICIPANTS: There were 14,752 participants with gradable photographs from the Beaver Dam Eye Study (n = 4756), Rotterdam Study (n = 6411), and Blue Mountains Eye Study (n = 3585). MAIN OUTCOME MEASURES: AMD diagnosis was made from masked grading of stereo macular photographs. Final classification of AMD cases was agreed by consensus between study investigators. RESULTS: AMD prevalence was strongly age related. Overall, AMD was present in 0.2% of the combined population aged 55 to 64 years, rising to 13% of the population older than 85 years. Prevalence of neovascular AMD (NV) increased from 0.17% among subjects aged 55 to 64 years to 5.8% for those older than 85 years. Prevalence of pure geographic atrophy (GA) increased from 0.04% to 4.2% for these age groups. There were no significant gender differences in the prevalence of NV or GA. Subjects in the Rotterdam population had a significantly lower age-adjusted and smoking-adjusted risk of NV than subjects in the Beaver Dam and Blue Mountains populations. Apart from age, tobacco smoking was the only risk factor consistently associated with any form of AMD in all sites separately and in pooled analyses over the three sites. CONCLUSIONS: These combined data from racially similar communities across three continents provide strong and consistent evidence that tobacco smoking is the principal known preventable exposure associated with any form of AMD.

Is age-related maculopathy associated with Alzheimer's Disease? The Rotterdam Study.

The authors examined the relation between age-related maculopathy and Alzheimer's disease in the Rotterdam Study, a prospective population-based study in the Netherlands. From 1990 to mid-1993, subjects aged 75 years or older (n = 1,438) were screened for the presence of age-related maculopathy and Alzheimer's disease, and follow-up examinations were conducted from mid-1 993 to the end of 1994. Subjects with advanced age-related maculopathy at baseline showed an increased risk of incident Alzheimer's disease (relative risk = 2.1, 95% confidence interval: 1.1, 4.3; adjusted for age and gender), but this risk decreased after additional adjustment for smoking and atherosclerosis (relative risk = 1.5, 95% confidence interval: 0.6, 3.5). These findings suggest that the neuronal degeneration occurring in age-related maculopathy and Alzheimer's disease may, to some extent, have a common pathogenesis.

Age-specific prevalence and causes of blindness and visual impairment in an older population: the Rotterdam Study.

OBJECTIVE: To study the prevalence and causes of blindness and visual impairment in various age categories of a large population-based study. METHODS: For the study, 6775 subjects aged 55 years or older underwent an extensive ophthalmologic screening examination, including measurements of visual acuity and the visual field and fundus photography. The causes of blindness or visual impairment were determined using all screening information and medical records. RESULTS: The prevalence of blindness, according to World Health Organization criteria, ranged from 0.1% in subjects aged 55 to 64 years to 3.9% in subjects aged 85 years or older; the prevalence of visual impairment ranged from 0.1% to 11.8%. For persons younger than 75 years, myopic degeneration and optic neuropathy were the most important causes of impaired vision. For persons aged 75 years or older, age-related macular degeneration was the major cause of the increased prevalence of blindness, whereas age-related cataract predominantly caused the increased prevalence of visual impairment. CONCLUSIONS: The hierarchy of causes of blindness and visual impairment is highly determined by age. As yet, little can be done to reduce the exponential increase of blindness; however, adequate implementation of surgery to treat cataract could reduce visual impairment by one third. Underuse of ophthalmologic care is a prominent cause of the high frequency of untreated cataracts among the elderly.

Elevated plasma fibrinogen: cause or consequence of cardiovascular disease?

An association between increased plasma fibrinogen and an increased risk for myocardial infarction (MI) is well established, but the nature of this association is subject to debate. Our aim was to shed light on the potentially causal nature of this association. We examined whether increased plasma fibrinogen, due to a condition that is independent of cardiovascular events, also increases the risk for MI. A case-control study was performed in 139 subjects with a history of MI and 287 control subjects selected from the Rotterdam Study, a population-based cohort of 7983 subjects aged 55 years and older. The genotype of the -455G/A polymorphism in the fibrinogen beta-gene was determined by polymerase chain reaction. Functional plasma fibrinogen levels were determined according to von Clauss. The plasma level of fibrinogen was significantly higher in subjects with one or two A alleles compared with subjects with the GG genotype: 3.8 (95% confidence interval [CI], 3.6 to 3.9) g/L and 3.6 (3.5 to 3.7) g/L, respectively. With increasing plasma fibrinogen level, the risk for MI increased gradually; a rise in fibrinogen of 1 g/L was associated with a 45% increased risk (odds ratio adjusted for age, sex, and smoking, 1.45; 95% CI, 1.12 to 1.88). There was no association between the genotype of the -455G/A polymorphism and the risk for MI. The -455G/A polymorphism is therefore associated with increased plasma fibrinogen levels but not with an increased risk for MI. These findings indicate that an increased plasma fibrinogen level due to this genetic factor does not increase the risk for MI.

Expression of MAGE, gp100 and tyrosinase genes in uveal melanoma cell lines.

In order to determine the possible use of uveal melanoma cell lines as stimulators in immunotherapy, we evaluated the expression of the human genes for MAGE-1, -2 and -3, gp100 and tyrosinase in uveal melanoma cell lines. mRNA expression of the MAGE-1, -2 and -3, gp100 and tyrosinase genes and the HLA class I specificity were determined in five primary and three metastatic uveal melanoma cell lines. Expression of the examined genes was heterogeneous in the primary and metastatic cell lines. The cell lines OCM-1 and OMM-1 expressed MAGE-1, -2 and -3, whereas EOM-3, MEL202, 92-1 and OMM-3 were negative for these antigens. gp100 was expressed in all cell lines, and tyrosinase in all but three (EOM-29, OMM-2 and OMM-3). Except for EOM-3, the HLA-A type of all the cell lines could be determined by complement-dependent microlymphocytotoxicity assay. Since at least two melanoma-associated antigens can be found in uveal melanoma cell lines, as well as the HLA class I molecules, these cell lines may be applicable as immunogens for specific immunotherapy against metastatic uveal melanoma.