Years In Healthy Subjects Research Articles

Umbilical Cord-derived Mesenchymal Stem Cells (CLV-100) Infusion in Healthy Subjects: a 5-Year Follow-up Study on Safety and Immunomodulatory Effect

Abstract Purpose Umbilical cord-derived mesenchymal stem cells (UCMSCs) have garnered significant attention in the field of regenerative medicine, specifically in inflammation-related diseases. Our team has previously demonstrated that a single infusion of allogeneic UCMSCs by Cytopeutics® (CLV-100), at both low dose (65 million cells) and high dose (130 million cells), in 11 healthy volunteers was safe up to 6 months with a dose-dependent immunomodulatory effect. In this present follow-up study, we investigated the medium-term safety and efficacy of intravenous administration of CLV-100 in the same healthy subjects. Methods All 11 subjects were enrolled in this 5-year follow-up, and none dropped out (NMRR-13–1152-17400, 28/09/2016). Clinicians conducted consultations to assess overall health indicators. Blood samples and serum were collected for laboratory testing and biomarker analysis, respectively. Results Five years after the CLV-100 infusion, all subjects remained healthy, with no reported side effects or major health conditions. Levels of cancer markers also remained within normal ranges. The anti-inflammatory effect of CLV-100 remained statistically significant in the high-dose group. Notably, major organ health parameters, including those subjects aged over 60 years, remained stable even after 5 years. Conclusion The findings demonstrated the medium-term safety of a single CLV-100 infusion and persistent dose-dependent immunomodulatory effects. CLV-100 may also confer protection against age- and inflammation-related frailty. Lay Summary The current follow-up study provides insight into the safety and immunomodulatory effects of a single infusion of allogeneic umbilical cord-derived mesenchymal stem cells (CLV-100) for up to 5 years in healthy subjects. The effects on the inflammatory cytokines CLV-100 were more pronounced in the high-dose group. In addition, other biomarker levels were comparable between the older and younger age groups. CLV-100 is therefore safe over the medium-term with sustained anti-inflammatory effect in a dose-dependent manner.

Androgen receptor CAG repeat polymorphism might be a possible cause of familial constitutional delay of growth and puberty.

Induction of puberty in boys with constitutional delay of growth and puberty (CDGP) through a short course of low-dose testosterone therapy indicates the critical interaction between testosterone and the androgen receptor (AR) during the activation and maturation of the hypothalamic-pituitary-gonadal axis at puberty onset. Previous studies have shown an inverse relationship between the CAG repeat length and the transactivation function or expression level of the AR gene. We aimed to investigate whether the AR CAG repeat polymorphism has any implications on pubertal delay. Thirty-three male patients with CDGP were enrolled in the study group, while 53 age-matched healthy individuals who had entered puberty on time were included in the control group. The CAG repeat length was determined through direct DNA sequencing analysis. The median chronological age of boys with CDGP was 14.2 (14.1-14.6) years, compared to 14.2 (13.65-14.8) years for healthy subjects (p = 0.5). In the CDGP group, 22 (66.7%) children had a family history of the condition. There was no significant difference between the groups in terms of AR CAG repeat length (median AR CAG repeat length: 21 (20-24.5) and 20 (20-24), respectively, p = 0.1). However, in boys with CDGP with a similar family history (n = 22), a significantly longer AR CAG repeat length was found compared to the control group (n = 53) (median AR CAG repeat length: 22 (20-25) and 20 (20-24), respectively, p = 0.03). The median AR CAG repeat length in boys without a family history was 21 (20-22) triplets. Although boys with a family history had a slightly longer AR CAG repeat length than those without, the difference was not statistically significant (p = 0.07). Additionally, no significant differences were observed between boys with non-familial CDGP and control subjects (p = 0.8). Furthermore, no significant differences in anthropometric characteristics or hormonal parameters were found when patients with CDGP were categorized by AR CAG repeat length quartiles. This is the first study to investigate the role of AR CAG polymorphism in the etiopathogenesis of CDGP. Our findings suggest that the AR CAG repeat length may be associated with familial CDGP.

Brain Protection after Anoxic Brain Injury: Is Lactate Supplementation Helpful?

While sudden loss of perfusion is responsible for ischemia, failure to supply the required amount of oxygen to the tissues is defined as hypoxia. Among several pathological conditions that can impair brain perfusion and oxygenation, cardiocirculatory arrest is characterized by a complete loss of perfusion to the brain, determining a whole brain ischemic-anoxic injury. Differently from other threatening situations of reduced cerebral perfusion, i.e., caused by increased intracranial pressure or circulatory shock, resuscitated patients after a cardiac arrest experience a sudden restoration of cerebral blood flow and are exposed to a massive reperfusion injury, which could significantly alter cellular metabolism. Current evidence suggests that cell populations in the central nervous system might use alternative metabolic pathways to glucose and that neurons may rely on a lactate-centered metabolism. Indeed, lactate does not require adenosine triphosphate (ATP) to be oxidated and it could therefore serve as an alternative substrate in condition of depleted energy reserves, i.e., reperfusion injury, even in presence of adequate tissue oxygen delivery. Lactate enriched solutions were studied in recent years in healthy subjects, acute heart failure, and severe traumatic brain injured patients, showing possible benefits that extend beyond the role as alternative energetic substrates. In this manuscript, we addressed some key aspects of the cellular metabolic derangements occurring after cerebral ischemia-reperfusion injury and examined the possible rationale for the administration of lactate enriched solutions in resuscitated patients after cardiac arrest.

Yüksek sol atriyal hacim indeksi ve diyastolik disfonksiyonunda sol atriyum fonksiyonel parametrelerindeki değişiklikler

Purpose: Previous studies have shown the relationship between left ventricular diastolic dysfunction (DD) and left atrial volume index (LAVi). However, limited studies have been reported have been reported on the relationship of functional parameters of left atrium (LA) with LAVi and DD. Therefore, we aimed to examine the changes of functional parameters of LA in high LAVi and DD in this study. Materials and methods: Transthoracic echocardiography was performed in 81 healty subjects (LAVi<30 ml/m2) and 81 patients with DD (LAVi>30 ml/m²). Maximum, minimum and preatrial volumes were measured using area-length method. The functional parameters of LA and other parameters including miyocardial performance index (MPI), left ventricular mass index, relative wall thickness, max LAVi/A’, LA sphericity index, the total atrial conduction time (PA-TDI) were calculated and DD was determined by using transmitral and pulmoner ven inflow, pulsed wave Doppler and tissue Doppler. Results: Initially; max LAVi, min LAVi, preA LAVi, max LAVi/A’, LA sphericity index, LA total emptying volume (EV) index, LA active EV index, LA passive EV index, PA-TDI, left ventricular relative wall thickness, left ventricular mass index and MPI were significantly higher in patients with DD and high LAVi (p<0.05). The groups had similar total LA emptying fraction (LAEF) when age difference was removed with Ancova test analysis. LA expansion index decreased with age in patients with DD and high LAVi in correlation analysis (r=-0.408, p<0.001). Conclusion: Max LAVi, min LAVi, preA LAVi, max LAVi/A’, LA sphericity index, LA total EV index, LA active EV index, LA passive EV index, PA-TDI, relative wall thickness, left ventricular mass index and MPI were higher in DD and high LAVi regardless of age. Although LA expansion index and total LAEF did not show significant alterations until 57 years in healthy subjects in this study, both of them may decrease in patients with DD and high LAVi, especially in advanced ages, due to prolonged exposure to high filling pressure of left ventricle.

Analysis of the Corneal Anterior and Posterior Surface in Patients With Peripheral Hypertrophic Subepithelial Corneal Opacification.

To characterize the corneal changes in peripheral hypertrophic subepithelial corneal opacification (PHSCO) considering elevation of the anterior and posterior corneal surface, corneal astigmatism, tear secretion, and endothelial cell density. Thirty-eight eyes of 22 patients with PHSCO on at least 1 eye and 38 eyes of 22 age- and sex-matched healthy subjects were included in this retrospective cross-sectional study. Using the Pentacam system (Oculus, Wetzlar, Germany), measurement of the anterior and posterior corneal surface was performed. In addition, the Schirmer test was conducted, and endothelial cells were counted in the central cornea with a specular microscope (SP-3000P; Topcon, Tokyo, Japan). The mean age was 55.2±11.7 years in patients with PHSCO and 54.1±12.4 years in healthy subjects. The corneas of patients with PHSCO showed higher corneal astigmatism of both the corneal anterior and posterior surface (2.9/0.5 vs. 0.8/0.3 D, PHSCO vs. controls, P=<0.001/<0.01). The cornea was thickest in the peripheral 12-o'clock position and the peripheral superior nasal area. Remarkably, central endothelial cell density was markedly reduced in patients with PHSCO (2,372.6 cell/mm±328.1 vs. 2,673 cells/mm±287.6, P<0.01, PHSCO vs. controls). Also, the Schirmer test revealed lower tear secretion in patients with PHSCO (9.8±4.4 mm vs. 14.3±5.7 mm, P<0.001, PHSCO vs. controls). The astigmatism of both the anterior and posterior corneal surface is increased in patients with PHSCO. Intriguingly, tear secretion and central endothelial cell density are reduced in patients with PHSCO. These measurements may become useful to assess the impact of morphological changes on vision and to track disease progression in PHSCO.

Ambulatory arterial stiffness index is increased in obese children.

One way to measure arterial stiffness is the ambulatory arterial stiffness index (AASI), which is the relationship between diastolic and systolic ambulatory blood pressure (BP) over 24-hours. We studied the difference in AASI between obese and lean children. AASI was calculated from 24- hour ambulatory blood pressure monitoring in 53 obese children (33 girls) and compared with age-matched 42 healthy subjects (20 girls). Hypertension was defined according to the criteria of the American Heart Association. To evaluate inflammation, the blood level of high-sensitive C-reactive protein was measured. The mean age was 10.6 ± 2.83 years in obese children and 11.3 ± 3.17 years in healthy subjects. Hypertension was determined in three (5.6%) obese children. The median heart rate-SDS, pulse pressure and blood pressure values did not differ between the two groups. The mean AASI was significantly higher in obese children compared to healthy subjects (0.42 ± 0.15 vs. 0.29 ± 0.18, p < 0.001). AASI significantly correlated with nighttime SBP-SDS, nighttime SBP-load, systolic and diastolic nocturnal dipping, with no independent predictor. This study confirms that AASI is increased in obese children. AASI calculation is a useful, costeffective, and an easy method to evaluate arterial stiffness. Early detection of increased arterial stiffness can help clinicians come up with preventive measures in the management of patients.

Ultrasonographic assessment of quadriceps and patellar tendon thicknesses in patients with patellofemoral pain syndrome

ObjectiveThe aim of this study was to compare ultrasonographically measured quadriceps and patellar tendon thicknesses between Patellofemoral Pain Syndrome (PFPS) patients and age- and gender-matched healthy controls. MethodsAmong patients who presented to physical therapy and rehabilitation outpatient clinic in January–December 2016, 61 volunteers (28 men and 33 women; mean age: 30.79 ± 6.55 years) who were eligible considering the inclusion and exclusion criteria were enrolled. 30 were diagnosed with PFPS, and the remaining were age- and gender-matched healthy volunteers. Mean age was 30.03 ± 5.67 years in healthy subjects and 45.2% were of male gender. The patient group had mean age of 31.57 ± 7.37 years and 46.7% of the patients were male. Q angles were measured at standing, supine and sitting positions. Patellar and femoral tendon thicknesses and areas were measured ultrasonographically. Kujala questionnaire were used to evaluate the functional status of the participants. ResultsNo significant difference was detected between groups regarding profession, educational background, and body mass indices (BMI) (p > 0.05). Q angle values were significantly higher in the patient group when compared to controls at standing (17.03 ± 3.84 vs. 13.87 ± 1.75°, p < 0.001), supine (16.20 ± 3.74 vs. 13.45 ± 1.79°, p = 0.001) and sitting (16.50 ± 3.28 vs. 13.71 ± 1.72°, p < 0.001) positions. Kujala score was significantly lower in the PFPS group when compared to controls (70.57 ± 8.37 vs. 98.58 ± 2.05, p < 0.001). Patellar (0.39 ± 0.08 vs. 0.32 ± 0.05 cm, p < 0.001) and quadriceps (0.64 ± 0.10 vs. 0.52 ± 0.09 cm, p < 0.001) tendon thicknesses were significantly higher in the PFPS group when compared to controls. There was no significant difference between groups regarding patellar tendon areas (p > 0.05). Patellar tendon thickness values of ≥0.35 cm were found to have 66.7% sensitivity and 67.7% specificity for PFPS diagnosis in the ROC curve analysis (area under curve: 0.771, 95% confidence interval: 0.655–0.887, p < 0.001). Quadriceps tendon thickness values of ≥0.54 cm were found to have 80% sensitivity and 71% specificity for PFPS diagnosis in the ROC curve analysis (area under curve: 0.824, 95% confidence interval: 0.710–0.939, p < 0.001). In PFPS patients, quadriceps tendon thickness had significant positive correlation with age (r = 0.405, p = 0.027) and BMI (r = 0.450, p = 0.013); and significant negative correlation with Kujala score (r = −0.441, p = 0.015). In the multivariate regression analysis, quadriceps tendon thickness was independently associated with the presence of PFPS (Exp (B): 3.089, 95% confidence interval: 1.344–7.100, p = 0.008). ConclusionOur study demonstrates that ultrasonographically measured patellar and quadriceps tendon thicknesses are significantly higher in subjects with PFPS and particularly, quadriceps tendon thickness may be used for the diagnosis. Level of EvidenceLevel III, Therapeutic Study.

MON-576 Ultrasound Changes of Healthy Thyroides over Six Years in Adults

Background. The need to re-test adults with negative thyroid ultrasound has not been elucidated yet. The aim of this study was to evaluate the incidence of thyroid disease in patients with previously negative thyroid US and to find any possible correlation with anamnestic or clinical features, and pituitary-thyroid axis function changes. Methods. Subjects who resulted without thyroid nodules in a screening study (1) were re-tested after at least 5 years. Anamnestic (familiarity, radiation therapy, previous pregnancies, smoking habit) and physical data (thyroid palpation, anthropometric measurements, blood pressure) were collected. Neck ultrasound evaluation was performed by an experienced endocrinologist who recorded detailed thyroid and nodules characteristics. When nodules were present, American Thyroid Association classification for prediction of thyroid cancer risk was applied. Serum samples were collected for measurement of TSH, free thyroid hormones, calcitonin and anti-thyroid antibodies. Clinical and anamnestic, physical, sonographic and serological characteristics were analyzed with logistic regression analysis for subjects with nodules versus those without nodules. Results. A total of 111 subjects were enrolled (43 M, 68 F). Half of them presented new thyroid nodules, mostly smaller than 1 cm and not suspicious. The 4% had high levels of anti-thyroid antibodies. Ninety-seven percent were euthyroid. Incidence of thyroid diseases was higher in women, especially in nulliparous. Comparing clinical characteristics of subjects with and without nodules, the only statistically significant difference concerned thyroid volume adjusted for body weight or surface (p<0.05). Finally, none of the anamnestic, physical, sonographic or serological values were predictive of the risk of developing thyroid nodules at logistic regression analysis. Conclusions. These results suggest that it is not indicated to repeat thyroid US after only 6 years in healthy subjects, even if they might develop small and clinically irrelevant thyroid nodules. (1) Gnarini VL, Brigante G, Della Valle E, Diazzi C, Madeo B, Carani C, Rochira V, Simoni M 2013 Very high prevalence of ultrasound thyroid scan abnormalities in healthy volunteers in Modena, Italy. J Endocrinol Invest 36:722-728.

CLASSIFICATION OF HALLER VESSEL ARRANGEMENTS IN ACUTE AND CHRONIC CENTRAL SEROUS CHORIORETINOPATHY IMAGED WITH EN FACE OPTICAL COHERENCE TOMOGRAPHY

To compare the prevailing patterns of Haller vessel arrangements at the posterior pole between healthy eyes and those with central serous chorioretinopathy (CSC) using en face optical coherence tomography. Eyes of normal subjects and patients with acute or chronic CSC underwent optical coherence tomography imaging (RTVue 100; Optovue Inc, Fremont, CA). En face sections at the level of the Haller layer were classified by two masked graders into five mutually exclusive morphologic categories (temporal herringbone, branched from below, laterally diagonal, double arcuate, and reticular). The relative prevalence of each Haller vessel arrangement pattern was determined for each phenotype. Numbers of eyes examined were as follows: 154 eyes of 77 normal subjects; 41 eyes of 31 patients with acute CSC; and 39 eyes of 33 patients with chronic CSC. The mean age of participants was 44.4 ± 14.6 years for healthy subjects (M:F = 37:40), 48.5 ± 8.2 years (M:F = 24:7) for acute CSC, and 65.3 ± 13.1 years (M:F = 28:5) for chronic CSC. The relative prevalence of each Haller vessel arrangement pattern differed by phenotype. The temporal herringbone pattern was most prevalent in healthy eyes (49.2%), whereas a reticular pattern was most prevalent in eyes with acute and/or chronic CSC (combined, 48.8%). A significant difference was observed in the prevalence of respective Haller vessel arrangement patterns between eyes of normal subjects and those of patients with either acute or chronic CSC. Although further study is needed to determine the mechanistic factors underlying these differences, and the hemodynamic implications, our data suggest that en face optical coherence tomography may find a formal role in choroidal disease classification.

Pattern noise (PANO): a new automated functional glaucoma test.

To present a newly developed visual field device (pattern noise: PANO) designed to be sensitive to glaucoma defects, cost-effective, material-practical and easy to repair and therefore particularly suited for low-income countries, where glaucoma can be highly prevalent (e.g. sub-Saharan Africa). This is primarily a descriptive paper, but it also includes a prospective matched case-control pilot study. Hardware, stimulus, target configuration, testing strategy and result sheet are described. The main outcome measure is the contrast level (range 2-64). Targets are composed of bright/dark pixels flickering with 18Hz and have a size of 5°. Pixel size is approximated to the hill of vision. Average luminance of targets is constant and equals background luminance.The study was performed in the West Region in Cameroon. Twenty eyes of 20 newly presenting patients with glaucomatous optic disc cupping on funduscopy were compared with 20 eyes of 20 normal patients matched in age and laterality of eye. Mean age was 32.9±18.8 years for glaucoma patients and 32.2±15.6 years for healthy subjects. Mean contrast threshold was significantly higher in eyes with abnormal disc (16.2±14.3 vs. 4.4±0.8, P=0.002). Correlation of mean contrast thresholds and cup-to-disc ratio was significant (r=0.59; P=0.006). Average examination time was significantly longer for glaucoma eyes compared to healthy eyes (8.2 vs. 6.1min, P<0.001), whereas error rate did not differ (4.8±2.5% vs. 4.1±1.8%, P=0.33). PANO demonstrated visual field defects in patients with glaucomatous optic disc. Defects correlated significantly with glaucomatous optic nerve head morphological alterations. Healthy eyes obtained normal results. More studies are needed to establish PANO.

Monocyte Mitochondrial Function in Calcium Oxalate Stone Formers

To investigate whether mitochondrial function is altered in circulating immune cells from calcium oxalate (CaOx) stone formers compared to healthy subjects. Adult healthy subjects (n = 18) and CaOx stone formers (n = 12) were included in a pilot study. Data collection included demographic and clinical values from electronic medical records. Bioenergetic function was assessed in monocytes, lymphocytes, and platelets isolated from blood samples using the Seahorse XF96 Analyzer. Plasma interleukin-6 (IL-6) was measured using enzyme-linked immunosorbent assay. All participants were age matched (44.5 ± 3.0 years for healthy subjects vs 42.3 ± 4.8 years for CaOx stone formers, P = .6905). CaOx stone formers did not have urinary tract infection, ureteral stones, or obstructing renal stones. Monocyte mitochondrial function was decreased in CaOx stone formers compared to healthy subjects. Specifically, mitochondrial maximal respiration (P = .0011) and reserve capacity (P < .0001) were significantly lower. In contrast, lymphocyte and platelet mitochondrial function was similar between the 2 groups. The bioenergetic health index, an integrated value of mitochondrial function, was significantly lower in monocytes from CaOx stone formers compared to healthy subjects (P = .0041). Lastly, plasma IL-6 levels were significantly increased (P = .0324). The present pilot study shows that CaOx stone formers have decreased monocyte mitochondrial function. Plasma IL-6 was also increased in this cohort. These data suggest that impaired monocyte mitochondrial function and inflammation may be linked to CaOx kidney stone formation. Further studies are needed to confirm these findings in a larger cohort of patients.

Differences in subchondral bone size after one year in osteoarthritic and healthy knees

Increase of subchondral bone area (tAB) in OA has been reported, but it remains unclear if this is specific to OA. We investigated differences in knee tAB after one year in healthy subjects and in those with radiographic OA (rOA). MR images of 899 right knees from the OA Initiative were acquired at baseline and one year follow-up (year-1). Medial and lateral tibial cartilage (MT and LT) and weight-bearing femoral cartilage (cMF and cLF) were segmented and tAB computed. Subjects were stratified into: healthy controls, pre-rOA (K&L grades 0 and 1, with OA risk factors), established rOA (K&L grades 2-4), and independently with regards to joint space narrowing (without, with medial, lateral and bilateral JSN). Primary analysis tested if tAB was different between baseline and year-1 in rOA. Exploratory analyses investigated whether: (1) tAB changes differed between healthy controls and those with rOA; (2) tAB differences were greater in higher K&L grades; and (3) tAB was different between baseline and year-1 in JSN. Significance was set at P<0.0125. Differences in tAB were found in rOA in MT, cMF and cLF (ranging from+0.2% to+0.4%; P<0.001), but not in healthy controls or pre-rOA. Rates of change did not differ between groups. Within the JSN groups differences of 0.2-0.4% were found in the femur (P<0.05). We find that knee tABs differ in rOA between baseline and year-1, but the change was not greater than in healthy knees, and is restricted to the femur in JSN.

Carbon loading in airway macrophages to traffic-derived particulate matter air pollution

Background and aims Epidemiological studies indicate that the health outcomes of exposure to urban air pollution are driven by exposure to elemental carbon (EC) emitted from traffic-related fuel combustion. One possible method for assessing chronic exposure to EC in individual subjects consists of estimating the amount of carbonaceous particles present in alveolar macrophages (AM)s. However, a number of issues remain to be solved regarding this biomarker. We studied the reproducibility and the kinetics of this biomarker by making repeated measurements over one year in healthy subjects, with some of them having moved from a highly polluted area (PM10 > 30 μg/m ) to a moderately polluted area (PM10 20-30 μg/m ).

AB0981 Tendon Involvement in Patients with Gout. an Ultrasound (US) Prevalence Study

BackgroundChronic gout is characterized by urate monosodium crystals (MSU) deposition in different tissues, mostly in soft tissues and the joints of lower extremities. The prevalence of tendon involvement by gout...

AB0610 Difference in Skin Elasticity between Diffuse and Limited Systemic Sclerosis

BackgroundSystemic sclerosis (SSc) is a chronic autoimmune disease characterized by vascular damage and severe fibroproliferative phenotype, which affects skin and internal organs. To date, the modified Rodnan Skin Score (mRSS)...

Age-Related Changes In Female and Male Cerebral Volumes: A Study of Whole-Brain Tissue Using the Stereological Method

The stereological techniques based on the Cavalieri methods are used in many studies to estimate volumes of anatomical structures in an unbiased fashion. This is a rapid, inexpensive approach that provides a correct volumetric calculation using magnetic resonance (MR) brain images. We investigated and age-sex-related volumetric changes in human brain using Cavalieri method. Three-dimensional MR imaging was obtained 120 healthy volunteers to 10 person from each age and gender-decade group. The Cavalieri method of modern design stereology was used to measure the cerebral volumes. To estimate this volume, the point counting approach was preferred. In our study, it was found that significant decreases in whole-brain volume (p<0.05) emerge progressively with increasing age. The most remarkable alteration was observed in older people’s brain volume. There was significant volumetric effect of gender on normalized brain volumes. Furthermore, both women and men showed statistically significant asymmetries in hemisphere volume. This quantitative volumetric study demonstrated a possible normal increase and then decrease in brain volume from age 0 to 60 years in healthy subjects. The differences in the brain sizes between the male and female subjects may be mainly attributable to the differences in total brain volume. A better understanding of this process may help to distinguish normal age-related alterations from neurodegenerative diseases. NeuroQuantology | March 2012 | Volume 10 | Issue 1 | Page 132-139

The Bile Acid Turnover Rate Assessed with the 75SeHCAT Test Is Stable in Chronic Diarrhoea but Slightly Decreased in Healthy Subjects After a Long Period of Time

The stability of bile acid turnover rate was evaluated retrospectively using repeat SeHCAT tests in patients with chronic diarrhoea and prospectively for 16 years in healthy subjects. The SeHCAT values were stable in 39 patients with chronic diarrhoea, as shown by a comparison of the test results [data presented as median and (25th-75th percentile)]: 18% (8-23) in the first test versus 14% (9-21) in the second test [n = 39, P = 0.37, time interval 44 months (16-68), repeatability index >95%]. In contrast, they were reduced after 16 years in healthy subjects: 38% (30-49.5) in the first test versus 31% (21-49.5) in the second test (P < 0.03). In healthy subjects, the body mass index increased by 13% from 23.2 kg/m(2) (21-24.6) to 26.2 kg/m(2) (22.5-27.8) (P < 0.01) during the 16 years. There was a negative correlation between hepatic bile acid synthesis and the SeHCAT values (r = -0.615, P = 0.02, n = 14). In conclusion, the turnover rate of bile acids is stable over a long period of time in patients with chronic diarrhoea irrespective of bile acid malabsorption, suggesting that a repeat SeHCAT test is dispensable. There is a significant negative correlation between bile acid synthesis and SeHCAT test results in healthy subjects. The SeHCAT test values are slightly reduced in healthy subjects after 16 years.

Jahreszeitliche Schwankungen und Einfluss der Ernährung auf die makuläre Pigmentdichte

We have previously reported on measuring macular pigment density (MPD) with a scanning laser ophthalmoscope (HRA, Heidelberg Engineering, Heidelberg, Germany). This study war undertaken to evaluate the variation of MPD over a period of 1 year in healthy subjects. We used autofluorescence images recorded with a HRA to evaluate MPD with a 2 degrees circle centered on the fovea. Healthy subjects were included in the study and MPD measurements were repeated every 2 months over a period of 1 year. We included a total of 30 healthy subjects aged 19-34 years (mean: 23+/-2 years). Mean MPD at time point 1 was 0.215+/-0.056 density units (DU), at time point 2 0.235+/-0.051 DU, at time point 3 0.218+/-0.055 DU, at time point 4 0.228+/-0.057 DU, at time point 5 0.225+/-0.053 DU, and at time point 6 0.203+/-0.050 DU. The statistical analysis revealed no significant variation of MPD over the follow-up period of 1 year. This study demonstrates that MPD shows no variation over a period of 1 year in healthy subjects.

The natural course of MRI white matter hyperintensities

The rate and extent of progression of white matter hyperintensities (WMH) over time in elderly subjects is yet unclear. These abnormalities may represent an early form of subcortical vascular dementia. As to whether such changes could be used, as a surrogate marker for this subtype of vascular dementia remains to be determined. So far there exists only a very limited number of studies determining the rate, clinical predictors and cognitive consequences of WMH evolution. There is evidence that these changes do progress over time, however the results of the different studies cannot be compared due to methodological differences. The Austrian Stroke Prevention Study reported that 17.9% of normal individuals show progression over time. The only published quantitative data demonstrated an absolute increase of 1.1 cm 3 over an observational period of 4 years in healthy subjects. Diastolic blood pressure, early confluent or confluent WMH at baseline and genetic variants in the angiotensinogen gene are so far the only known predictors of WMH progression. The Austrian Stroke Prevention Study did not find an association between the evolution of WMH and cognitive functioning but the statistical power of this analysis was small and the relationship needs to be further explored.