Prediction of hip fracture risk by quantitative ultrasound in more than 7000 Swiss women > or =70 years of age: comparison of three technologically different bone ultrasound devices in the SEMOF study

To compare the prediction of hip fracture risk of several bone ultrasounds (QUS), 7062 Swiss women > or =70 years of age were measured with three QUSs (two of the heel, one of the phalanges). Heel QUSs were both predictive of hip fracture risk, whereas the phalanges QUS was not. INTRODUCTION: As the number of hip fracture is expected to increase during these next decades, it is important to develop strategies to detect subjects at risk. Quantitative bone ultrasound (QUS), an ionizing radiation-free method, which is transportable, could be interesting for this purpose. MATERIALS AND METHODS: The Swiss Evaluation of the Methods of Measurement of Osteoporotic Fracture Risk (SEMOF) study is a multicenter cohort study, which compared three QUSs for the assessment of hip fracture risk in a sample of 7609 elderly ambulatory women > or =70 years of age. Two QUSs measured the heel (Achilles+; GE-Lunar and Sahara; Hologic), and one measured the heel (DBM Sonic 1200; IGEA). The Cox proportional hazards regression was used to estimate the hazard of the first hip fracture, adjusted for age, BMI, and center, and the area under the ROC curves were calculated to compare the devices and their parameters. RESULTS: From the 7609 women who were included in the study, 7062 women 75.2 +/- 3.1 (SD) years of age were prospectively followed for 2.9 +/- 0.8 years. Eighty women reported a hip fracture. A decrease by 1 SD of the QUS variables corresponded to an increase of the hip fracture risk from 2.3 (95% CI, 1.7, 3.1) to 2.6 (95% CI, 1.9, 3.4) for the three variables of Achilles+ and from 2.2 (95% CI, 1.7, 3.0) to 2.4 (95% CI, 1.8, 3.2) for the three variables of Sahara. Risk gradients did not differ significantly among the variables of the two heel QUS devices. On the other hand, the phalanges QUS (DBM Sonic 1200) was not predictive of hip fracture risk, with an adjusted hazard risk of 1.2 (95% CI, 0.9, 1.5), even after reanalysis of the digitalized data and using different cut-off levels (1700 or 1570 m/s). CONCLUSIONS: In this elderly women population, heel QUS devices were both predictive of hip fracture risk, whereas the phalanges QUS device was not.

Intravitreal triamcinolone acetonide for serous retinal pigment epithelial detachments in exudative age-related macular degeneration

BACKGROUND: Due to the high risk of RPE tears PDT is usually not performed in eyes with serous RPE detachments (sRPED). For this reason this subform of exudative AMD was so far untreatable. PATIENTS AND METHODS: We report on a prospective uncontrolled observational case series. 20 eyes of 20 patients with subfoveal sRPED demonstrated by OCT were treated between June 2005 and April 2006 with intravitreal triamcinolone acetonide (IVTA). In 15 cases there was a primary sRPED, in 5 cases it had developed after one or more sessions of photodynamic therapy with Visudyne. RESULTS: There was a trend for better average visual acuity in the group with primary sRPED from 0.73 logMAR (0.19 Snellen equivalent) at baseline (n = 15) to 0.68 logMAR (0.21 Snellen) after one month (n = 15) (p = 0.19) and to 0.60 logMAR (0.25 Snellen) after three months (n = 14) (p = 0.41). The maximal height of sRPED decreased to an average of 35.3 % after one month (n = 15) and increased again to 56.9 % after 3 months (n = 14). One patient was lost to follow-up. In the group of eyes with sRPED after PDT, one eye developed an RPE tear with severe vision loss two weeks after IVTA. In the remaining four eyes average visual acuity improved from 0.90 logMAR (0.13 Snellen) at baseline to 0.73 logMAR (0.19 Snellen) after one month and to 0.80 logMAR (0.16 Snellen) after 3 months. Complete resolution of sRPED was observed in 8/20 eyes (4/5 eyes with sRPED after PDT and 4/15 eyes with primary sRPED). CONCLUSIONS: IVTA seems to be a therapeutic option in otherwise untreatable eyes with sRPED.

[Does cataract surgery increase the risk of exudative age-related macular degeneration? Results from a large retrospective case-control study]

BACKGROUND: Many epidemiological studies indicate a positive correlation between cataract surgery and the subsequent progression of age-related macular degeneration (AMD). Such a correlation would have far-reaching consequences. However, in epidemiological studies it is difficult to determine the significance of a single risk factor, such as cataract surgery. PATIENTS AND METHODS: We performed a retrospective case-control study of patients with new onset exudative age-related macular degeneration to determine if cataract surgery was a predisposing factor. A total of 1496 eyes were included in the study: 984 cases with new onset of exudative AMD and 512 control eyes with early signs of age-related maculopathy. Lens status (phakic or pseudophakic) was determined for each eye. RESULTS: There was no significant difference in lens status between study and control group (227/984 [23.1 %] vs. 112/512 [21.8 %] pseudophakic, p = 0.6487; OR = 1.071; 95 % CI = 0.8284-1.384). In cases with bilateral pseudophakia (n = 64) no statistically significant difference of the interval between cataract surgery in either eye and the onset of exudative AMD in the study eye was found (225.9 +/- 170.4 vs. 209.9 +/- 158.2 weeks, p = 0.27). CONCLUSIONS: Our results provide evidence that cataract surgery is not a major risk factor for the development of exudative AMD.

Is pseudophakia a risk factor for neovascular age-related macular degeneration?

PURPOSE: To examine the possible association between pseudophakia and neovascular age-related macular degeneration (AMD). METHODS: Reports of all patients undergoing fluorescein angiography in the authors' department over a 6-year period were retrospectively reviewed. Four hundred ninety-nine patients with recent onset of neovascular AMD in one eye and early age-related maculopathy (ARM) in the fellow eye were included in the study. Lens status (phakic or pseudophakic) in both eyes at the time of onset of neovascular AMD and the time between cataract surgeries (if performed) and onset of neovascular AMD were determined. RESULTS: There was no significant difference in lens status between eyes with neovascular AMD and fellow eyes with early ARM (115/499 [23.0%] vs. 112/499 [22.4%] pseudophakic; P = 0.88, odds ratio 1.035, 95% CI 0.770-1.391). Subgroup analysis revealed no difference between the groups with large drusen, small drusen, or pigmentary changes only (respectively, 20.3% vs. 19.6% pseudophakic, P = 0.92; 20.5% vs. 23.3% pseudophakic, P = 0.84; 33.3% vs. 31.7% pseudophakic, P = 1.0). Pseudophakic eyes with neovascular AMD had not been pseudophakic for a significantly longer period at the time of onset of neovascular AMD than their pseudophakic fellow eyes at the same time point (225.9 +/- 170.4 vs. 209.9 +/- 158.2 weeks, P = 0.27). CONCLUSIONS: The results do not support the hypothesis that pseudophakia is a major risk factor for the development of neovascular AMD.

Angiopoietin-2 deficiency decelerates age-dependent vascular changes in the mouse retina

Retinae of aged humans show signs of vascular regression. Vascular regression involves a mismatch between Angiopoietin-2 (Ang-2) and vascular endothelial growth factor (VEGF) expression. We used heterozygous Ang-2 deficient (Ang2LacZ) mice to evaluate murine retinal vascular changes and gene expression of growth factors. Vascular changes were assessed by quantitative retinal morphometry and gene expression levels of growth factors were measured by quantitative PCR. The numbers of endothelial cells and pericytes did not change in the Ang2LacZ retinae with age, whereas they decreased throughout the age spectrum studied in the wild type retinae. Moreover, vascular regression significantly decelerated in the heterozygous Ang2LacZ retinae (200% to 1 month), while the formation of acellular capillaries was significantly increased at 13 months in the wild type retinae (340% to 1 month). Gene expression analysis revealed that VEGF, Ang-1, PDGF-B and Ang2 mRNA levels were decreased in the wild type retinae at 9 month of age. However, the decrease of Ang-2 was smaller compared with other genes. While VEGF levels dropped in wild type mice up to 60% compared to 1 month, VEGF increased in heterozygous Ang-2 deficient retinae at an age of 9 months (141% to 1 month). Similarly, Ang-1 levels decreased in wild type mice (45% to 1 month), but remained stable in Ang2LacZ mice. These data suggest that Ang-2 gene dose reduction decelerates vasoregression in the retina with age. This effect links to higher levels of survival factors such as VEGF and Ang-1, suggesting that the ratio of these factors is critical for capillary cell survival.

Age-dependent differences in demographics, risk factors, co-morbidity, etiology, management, and clinical outcome of acute ischemic stroke

BACKGROUND : Comparisons between younger and older stroke patients including comorbidities are limited. METHODS : Prospective data of consecutive patients with first ever acute ischemic stroke were compared between younger ( 45 years). RESULTS : Among 1004 patients, 137 (14 %) were 9 % versus 65 %; p < 0.0001), coronary heart disease (14 % versus 40 %; p < 0.0001), and a lower mean Charlson co-morbidity index (CCI), (0.18 versus 0.84; p < 0.0001). Tobacco use was more prevalent in the young (39 % versus 26 %; P < 0.0001). Large artery disease (2 % versus 21 %; p < 0.0001), small artery disease (3 % versus 12 %; p = 0.0019) and atrial fibrillation (1 % versus 17 %; p = 0.001) were less common in young patients, while other etiologies (31 % versus 9 %; p < 0.0001), patent foramen ovale or atrial septal defect (44 % versus 26 %; p < 0.0001), and cervical artery dissection (26 % versus 7 %; p < 0.0001) were more frequent. A favorable outcome (mRS 0 or 1) was more common (57.4 % versus 46.9 %; p = 0.023), and mortality (5.1 % versus 12 %; p = 0.009) was lower in the young. After regression analysis, there was no independent association between age and outcome (p = 0.206) or mortality (p = 0.073). Baseline NIHSS score (p < 0.0001), diabetes (p = 0.041), and CCI (p = 0.002) independently predicted an unfavorable outcome. CONCLUSIONS : Younger patients were more likely to be female, had different risk factors and etiologies and fewer co-morbidities. There was no independent association between age and clinical outcome or mortality.

Age-dependent decrease in 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) activity in hypertensive patients

BACKGROUND: The prevalence of arterial hypertension lacking a defined underlying cause increases with age. Age-related arterial hypertension is insufficiently understood, yet known characteristics suggest an aldosterone-independent activation of the mineralocorticoid receptor. Therefore, we hypothesized that 11beta-HSD2 activity is age-dependently impaired, resulting in a compromised intracellular inactivation of cortisol (F) with F-mediated mineralocorticoid hypertension. METHODS: Steroid hormone metabolites in 24-h urine samples of 165 consecutive hypertensive patients were analyzed for F and cortisone (E), and their TH-metabolites tetrahydro-F (THF), 5alphaTHF, TH-deoxycortisol (THS), and THE by gas chromatography-mass spectroscopy. Apparent 11beta-HSD2 and 11beta-hydroxylase activity and excretion of F metabolites were assessed. RESULTS: In 72 female and 93 male patients aged 18-84 years, age correlated positively with the ratios of (THF + 5alphaTHF)/THE (P = 0.065) and F/E (P < 0.002) suggesting an age-dependent reduction in the apparent 11beta-HSD2 activity, which persisted (F/E; P = 0.020) after excluding impaired renal function. Excretion of F metabolites remained age-independent most likely as a consequence of an age-dependent diminished apparent 11beta-hydroxylase activity (P = 0.038). CONCLUSION: Reduced 11beta-HSD2 activity emerges as a previously unrecognized risk factor contributing to the rising prevalence of arterial hypertension in elderly. This opens new perspectives for targeted treatment of age-related hypertension.

Same-day administration of verteporfin and ranibizumab 0.5 mg in patients with choroidal neovascularisation due to age-related macular degeneration

OBJECTIVE: To evaluate safety of same-day administration of verteporfin and ranibizumab. METHODS: Prospective, open-label, multicentre study; patients with predominantly classic (n = 13) or occult (n = 19) choroidal neovascularisation secondary to age-related macular degeneration received standard-fluence verteporfin at baseline and months 3, 6 and 9, based on fluorescein angiography (FA). Ranibizumab 0.5 mg was administered at baseline and months 1, 2 and 3. MAIN OUTCOME MEASURE: The incidence of severe vision loss (best-corrected visual acuity (BCVA) loss > or = 30 letters; primary safety assessment). RESULTS: No severe vision loss due to ocular inflammation or uveitis occurred. One patient had moderate vision loss (BCVA loss > or = 15 letters). Three patients had mild/moderate uveitis. Two serious ocular adverse events occurred (retinal pigment epithelial tear and moderate BCVA decrease). No systemic adverse events occurred. At 9 months, all lesions were inactive with no recurrent leakage on FA and optical coherence tomography; macular oedema and subretinal fluid resolved. The mean BCVA measured at 2 m improved by 6.9 letters at 4 months and 2.4 letters at 9 months. CONCLUSIONS/APPLICATION TO CLINICAL PRACTICE: Same-day verteporfin and ranibizumab was safe and not associated with severe vision loss or severe ocular inflammation. Lesions stabilized, with minimal treatment required after month 3.

The potential effect of population development, smoking and antioxidant supplementation on the future epidemiology of age-related macular degeneration in Switzerland

BACKGROUND: Due to the predicted age shift of the population an increase in the number of patients with late AMD is expected. At present smoking represents the only modifiable risk factor. Supplementation of antioxidants in patients at risk is the sole effective pharmacological prevention. The aim of this study is to estimate the future epidemiological development of late AMD in Switzerland and to quantify the potential effects of smoking and antioxidants supplementation. METHODS: The modelling of the future development of late AMD cases in Switzerland was based on a meta-analysis of the published data on AMD-prevalence and on published Swiss population development scenarios until 2050. Three different scenarios were compared: low, mean and high. The late AMD cases caused by smoking were calculated using the "population attributable fraction" formula and data on the current smoking habits of the Swiss population. The number of potentially preventable cases was estimated using the data of the Age-Related Eye Disease Study (AREDS). RESULTS: According to the mean population development scenario, late AMD cases in Switzerland will rise from 37 200 cases in 2005 to 52 500 cases in 2020 and to 93 200 cases in 2050. Using the "low" and the "high" scenarios the late AMD cases may range from 49 500 to 56 000 in 2020 and from 73 700 to 118 400 in 2050, respectively. Smoking is responsible for approximately 7 % of all late AMD cases, i. e., 2600 cases in 2005, 3800 cases in 2020, 6600 cases in 2050 ("mean scenario"). With future antioxidant supplementation to all patients at risk another 3100 cases would be preventable until 2020 and possibly 23 500 cases until 2050. CONCLUSION: Due to age shift in the population a 2.5-fold increase in late AMD cases until 2050 is expected, representing a socioeconomic challenge. Cessation of smoking and supplementation of antioxidants to all patients at risk has the potential to reduce this number. Unfortunately, public awareness is low. These data may support health-care providers and public opinion leaders when developing public education and prevention strategies.

Age and gender differences in health-related quality of life of children and adolescents in Europe: a multilevel analysis

OBJECTIVES: To determine age and gender differences in health-related quality of life (HRQOL) in children and adolescents across 12 European countries using a newly developed HRQOL measure (KIDSCREEN). METHODS: The KIDSCREEN-52 questionnaire was filled in by 21,590 children and adolescents aged 8-18 from 12 countries. We used multilevel regression analyses to model the hierarchical structure of the data. In addition, effect sizes were computed to test for gender differences within each age group. RESULTS: Children generally showed better HRQOL than adolescents (P < 0.001). While boys and girls had similar HRQOL at young age, girls' HRQOL declined more than boys' (P < 0.001) with increasing age, depending on the HRQOL scale. There was significant variation between countries both at the youngest age and for age trajectories. CONCLUSIONS: For the first time, gender and age differences in children's and adolescents' HRQOL across Europe were assessed using a comprehensive and standardised instrument. Gender and age differences exist for most HRQOL scales. Differences in HRQOL across Europe point to the importance of national contexts for youth's well-being.

Postoperative sepsis in infants below 6 months of age

BACKGROUND: Sepsis is a threatening postoperative complication especially in small infants. Regarding the advances in perinatal medicine, its incidence is unknown to date. We aimed to investigate the incidence, risk factors, laboratory findings and outcome of postoperative sepsis in infants younger than 6 months old. METHODS: We examined postoperative sepsis in babies below 6 months of age during a 4-year period at a tertiary pediatric institution. RESULTS: The rate of postoperative sepsis was 6.9%. Laparotomy with enterotomy, thoracotomy and diaphragmatic hernia repair (P<0.05, respectively) as well as low postnatal age and long operation time (P<0.001, respectively) were correlated with the incidence of sepsis. Significant independent predictors for the development of sepsis were the presence of a central venous catheter and perioperative antibiotic treatment (P<0.001, respectively). Coagulase negative Staphylococci were the major infecting organism associated with postoperative sepsis, accounting for 53% of monomicrobial infections. Complete blood counts with differential were not different between infants with sepsis and controls, who had undergone the same surgical procedures. Outcome was favorable in all cases; however, the length of hospital stay was significantly longer in sepsis patients (P<0.05). CONCLUSIONS: Postoperative sepsis syndrome is a frequent complication in infants below 6 months of age and causes significant prolongation of hospital stay. Adequate prevention and therapeutic strategies warrant further prospective investigations.

Influence of age and genetic risk on anti-tissue transglutaminase IgA titers

OBJECTIVES: False-positive results of anti-tissue-transglutaminase (tTG) IgA autoantibodies have been reported in subjects with a genetic risk for celiac disease (CD). The aims of this retrospective study were to assess the prevalence of false-positive tTG titers in patients at risk of CD compared with symptomatic children and to evaluate the influence of age and indication for testing on tTG titers. PATIENTS AND METHODS: All tTG results measured in our institution during a 33-month period were evaluated. Patients with known CD were excluded. Indications for testing were either symptoms suggestive of CD (group 1) or history of being at risk for CD (group 2). Duodenal biopsies were recommended if titers were positive (> or =10 U/mL) and offered if borderline (> or =4 to <10 U/mL). RESULTS: The final analysis included 2056 patients, 1707 belonged to group 1, and 349 to group 2. All 65 patients with positive tTG results underwent biopsy (group 1: 57, group 2: 8). Celiac disease was confirmed in 61 subjects (median titer: 107.8 U/mL, range 12.0-1748 mL, NS between group 1 and 2), whereas 4 had normal histology (10.2-25.2 U/mL). Three out of 16 patients with borderline results underwent biopsy and had normal histology. Borderline titers were more common in group 2 patients (2.6% vs 0.4%, P<0.001). Multiple regression analysis in patients with negative tTG results (n=1975) revealed that titers were independently related to age (P<0.05) and indication for testing (P<0.001). CONCLUSIONS: The influence of age and genetic predisposition/risk has to be taken into account when interpreting tTG results.

History of Art in the Digital Age: Problems and Possibilities

Ziel der vorliegenden Arbeit ist, einen allgemeinen Überblick über die Wirkung von Computern auf die Kunstgeschichte zu geben. Zu Beginn der Arbeit wird der Charakter der informationstechnologischen Revolution untersucht, einschließlich seiner schon oft festgestellten Parallelen mit der "Gutenberg"- Revolution, deren Ausgangspunkt in der Entwicklung der Druckerpresse liegt. Wie auch bei Gutenberg, ist die Entwicklung der Informationstechnologie technologisch bedingt. Jedoch führt sie durch ihren Schwerpunkt auf Flexibilität und Verbreitung an ein anderes Ziel. Diese Flexibilität ist zweischneidig: während sie viele neue Möglichkeiten eröffnet, scheint sie auch einen bruchstückhafteren, iterativen Ansatz zur Untersuchung des Vorzugs von Information vor Wissen anzuregen. Es bleibt jedoch offen, ob dieser Ansatz als notwendige Konsequenz der Struktur dieser vorhandenen neuen Technologie betrachtet werden kann, oder ob er eher als Produkt eines allgemeinen intellektuellen Wandels, angeregt durch das Aufkommen des postmodernen Diskurses, beschrieben werden soll. Ich werde in dem vorliegenden Artikel für den zweitgenannten Grund argumentieren. Ich bin außerdem der Meinung, dass der in der neuen Technologie enthaltenen Tendenz zur Fragmentierung entgegengewirkt werden kann - vorausgesetzt der Wunsch besteht. Die Entwicklung des Computers hängt eng mit der Nachfrage des Konsumenten zusammen. Aus diesem Grund kann ein neuer Trend in der Nachfrage die Art der Ausweitung und Modifizierung technologischer Vorgänge mitbestimmen.Des weiteren werden in der vorliegenden Arbeit Problemstellungen diskutiert, die speziell Auswirkungen auf die Untersuchung von Bildern haben. Hierbei wird sowohl das Potential digitaler Bilder für neue Formen der Erforschung und Analyse diskutiert, als auch die vielen neuen Möglichkeiten im Zeitalter des Internets.

Effect of regular physical training on age-associated alteration of body composition in men

Body composition changes with increasing age in men, in that lean body mass decreases whereas fat mass increases. Whether this altered body composition is related to decreasing physical activity or to the known age-associated decrease in growth hormone secretion is uncertain. To address this question, three groups of healthy men (n = 14 in each group), matched for weight, height and body mass index, were investigated using dual-energy X-ray absorptiometry, indirect calorimetry and estimate of daily growth hormone secretion [i.e. plasma insulin-like growth factor I (IGF-I-) levels]. Group 1 comprised young untrained subjects aged 31.0 +/- 2.1 years (mean +/- SEM) taking no regular physical exercise; group 2 consisted of old untrained men aged 68.6 +/- 1.2 years; and group 3 consisted of healthy old men aged 67.4 +/- 1.2 years undergoing regular physical training for more than 10 years with a training distance of at least 30 km per week. Subjects in group 3 had for the past three years taken part in the 'Grand Prix of Berne', a 16.5-km race run at a speed of 4.7 +/- 0.6 min km-1 (most recent race). Fat mass was more than 4 kg higher in old untrained men (P < 0.01, ANOVA) than in the other groups (young untrained men, 12.0 +/- 0.9 kg; old untrained men, 16.1 +/- 1.0 kg; old trained men, 11.0 +/- 0.8 kg), whereas body fat distribution (i.e. the ratio of upper to lower body fat mass) was similar between the three groups. The lean mass of old untrained men was more than 3.5 kg lower (P < 0.02, ANOVA) than in the other two groups (young untrained men, 56.4 +/- 1.0 kg; old untrained men, 52.4 +/- 1.0 kg; old trained men, 56.0 +/- 1.0 kg), mostly because of a loss of skeletal muscle mass in the arms and legs (young untrained men, 24.0 +/- 0.5 kg; old untrained men 20.8 +/- 0.5 kg; old trained men, 23.6 +/- 0.7 kg; P < 0.01, ANOVA). Resting metabolic rate per kilogram lean mass decreased with increasing age independently of physical activity (r = -0.42, P < 0.005). Fuel metabolism was determined by indirect calorimetry at rest. Protein oxidation was similar in the three groups. Old untrained men had higher (P < 0.001) carbohydrate oxidation (young untrained men, 13.2 +/- 1.0 kcal kg-1 lean mass; old untrained men, 15.2 +/- 1.3 kcal Kg-1; old trained men, 7.8 +/- 0.8 kcal kg-1), but lower (P < 0.05, ANOVA) fat oxidation (young untrained men, 10.1 +/- 1.2 kcal kg-1 lean mass; old untrained men, 6.5 +/- 1.0 kcal kg-1; old trained men, 13.7 +/- 1.0 kcal kg-1) than the other two groups. Mean plasma IGF-I level in old trained men was higher than in old untrained men (P < 0.05), but was still lower than that observed in young untrained men (P < 0.005) (young untrained men, 236 +/- 24 ng mL-1; old untrained men, 119 +/- 13 ng mL-1; old trained men, 166 +/- 14 ng mL-1). In summary, regular physical training in older men seems to prevent the changes in body composition and fuel metabolism normally associated with ageing. Whether regular physical training in formerly untrained old subjects would result in similar changes awaits further study.