Changes in renal tri-iodothyronine and thyroxine handling during fasting

OBJECTIVE: Liver handling of thyroid hormones (TH) has been known to alter significantly during fasting. This study investigates whether renal handling of TH is also changed during fasting. METHODS: We measured urinary excretion rates and clearances of free tri-iodothyronine (T(3)) and free thyroxine (T(4)) in healthy subjects prior to and on the third day of fasting. RESULTS: During fasting, both mean T(3) and T(4) urinary excretion decreased significantly to a mean value of 42% of control. Also, total and free (F) serum T(3) concentrations declined significantly, but serum T(4) did not change. Both FT(3) and FT(4) clearance decreased significantly during fasting (62% and 42% of control). The fasting-induced decrease in uric acid clearance correlated well with the decrease in FT(3) clearance (r=0.94; P<0.001). Serum concentrations of non-esterified fatty acids (NEFA) were significantly elevated during fasting. CONCLUSIONS: The findings cannot be fully explained by the fasting-induced decrease in serum T(3), a

Preconception maternal gastric bypass surgery and the impact on fetal growth parameters

Background: Bariatric surgery is increasingly performed in women of reproductive age. As bariatric surgery will result in postoperative rapid catabolic weight loss which potentially leads to fetal malnutrition and directly related impaired intra-uterine growth, it is advised to postpone pregnancy for at least 12–18 months after surgery. Objectives: To investigate the consequences of preconception gastric bypass surgery (pGB) on fetal growth parameters and maternal pregnancy outcome. Setting: Maasstad Hospital, The Netherlands, general hospital and Erasmus Medical Center, The Netherlands, university hospital. Methods: We included 97 pGB pregnancies (Maasstad hospital) and 440 non-bariatric pregnancies (Rotterdam Periconception cohort, Erasmus Medical Center). Longitudinal second and third trimester fetal growth parameters (head circumference, biparietal diameter, femur length, abdominal circumference, estimated fetal weight) were analyzed using linear mixed models, adjusting for covariates and possible confounders. Fetal growth and birthweight in pGB pregnancies were compared to non-bariatric pregnancies and Dutch reference curves. Maternal pregnancy outcome in the pGB group was compared to non-bariatric pregnancies. Results: All fetal growth parameters of pGB pregnancies were significantly decreased at 20 weeks’ gestation (P &lt; .001) and throughout the remaining part of pregnancy (P &lt; .05) compared with non-bariatric pregnancies (crude and adjusted models). In our cohort, gestational weight gain was not significantly associated with birthweight corrected for gestational age. Birthweight was significantly lower in pGB pregnancies (estimate –241 grams [95% CI, –342.7 to –140.0]) with a 2-fold increased risk of small-for-gestational-age (SGA) (adjusted odds ratio 2.053 [95% CI, 1.058 to 3.872]). Compared to the non-bariatric pregnancies, we found no significant differences in maternal pregnancy outcome. Conclusions: PGB is associated with overall reduced fetal growth trajectories and a 2-fold increased risk of SGA, without significant adverse consequences for maternal pregnancy outcome. We recommend close monitoring of fetal growth after pGB.</p

Dynamical Evolution of AGN Host Galaxies - Gas In/Out-Flow Rates in 7 NUGA Galaxies

To examine the role of the host galaxy structure in fueling nuclear activity, we estimated gas flow rates from several kpc down to the inner few 10 pc for seven nearby spiral galaxies, selected from the NUGA sample (NUclei of GAlaxies). We calculated gravitational torques from near-IR images and determined gas in/out-flow rates as a function of radius and location within the galactic disks, based on high angular resolution interferometric observations of molecular (CO using PdBI) and atomic (HI using the VLA) gas. The results are compared with kinematic evidence for radial gas flows and the dynamical state of the galaxies (via resonances) derived from several different methods. We show that gravitational torques are very efficient at transporting gas from the outer disk all the way into the galaxies centers at ~100 pc; previously assumed dynamical barriers to gas transport, such as the Corotation Resonance of stellar bars, seem to be overcome by gravitational torque induced gas flows from other non-axisymmmetric structures. The resulting rates of gas mass inflow range from 0.01 to 50 solar masses per year and are larger for the galaxy center than for the outer disk. Our gas flow maps show the action of nested bars within larger bars for 3 galaxies. Non-circular streaming motions found in the kinematic maps are larger in the center than in the outer disk and appear to correlate only loosely with the in/out-flow rates as a function of radius. We demonstrate that spiral gas disks are very dynamic systems that undergo strong radial evolution on timescales of a few rotation periods (e.g. 5 times 10^8 yrs at a radius of 5 kpc), due to the effectiveness of gravitational torques in redistributing the cold galactic gas.Comment: 83 pages, 13 figures, accepted for publication in ApJ. The full-resolution version is available at http://www.mpia.de/homes/haan/research.htm

Study protocol of KLIMOP: a cohort study on the wellbeing of older cancer patients in Belgium and the Netherlands

<p>Abstract</p> <p>Background</p> <p>Cancer is mainly a disease of older patients. In older cancer patients, additional endpoints such as quality of survival and daily functioning might be considered equally relevant as overall or disease free survival. However, these factors have been understudied using prospective designs focussing on older cancer patients. Therefore, this study will focus on the impact of cancer, ageing, and their interaction on the long-term wellbeing of older cancer patients.</p> <p>Methods/Design</p> <p>This study is an observational cohort study. We aim to recruit 720 cancer patients above 70 years with a new diagnosis of breast, prostate, lung or gastrointestinal cancer and two control groups: one control group of 720 patients above 70 years without a previous diagnosis of cancer and one control group of 720 cancer patients between 50 - 69 years newly diagnosed with breast, prostate, lung or gastrointestinal cancer. Data collection will take place at inclusion, after six months, after one year and every subsequent year until death or end of the study. Data will be collected through personal interviews (consisting of socio-demographic information, general health information, a comprehensive geriatric assessment, quality of life, health locus of control and a loneliness scale), a handgrip test, assessment of medical records, two buccal swabs and a blood sample from cancer patients (at baseline). As an annex study, caregivers of the participants will be recruited as well. Data collection for caregivers will consist of a self-administered questionnaire examining depression, coping, and burden.</p> <p>Discussion</p> <p>This extensive data collection will increase insight on how wellbeing of older cancer patients is affected by cancer (diagnosis and treatment), ageing, and their interaction. Results may provide new insights, which might contribute to the improvement of care for older cancer patients.</p

CDK19 is disrupted in a female patient with bilateral congenital retinal folds, microcephaly and mild mental retardation

Microcephaly, mental retardation and congenital retinal folds along with other systemic features have previously been reported as a separate clinical entity. The sporadic nature of the syndrome and lack of clear inheritance patterns pointed to a genetic heterogeneity. Here, we report a genetic analysis of a female patient with microcephaly, congenital bilateral falciform retinal folds, nystagmus, and mental retardation. Karyotyping revealed a de novo pericentric inversion in chromosome 6 with breakpoints in 6p12.1 and 6q21. Fluorescence in situ hybridization analysis narrowed down the region around the breakpoints, and the breakpoint at 6q21 was found to disrupt the CDK19 gene. CDK19 was found to be expressed in a diverse range of tissues including fetal eye and fetal brain. Quantitative PCR of the CDK19 transcript from Epstein–Barr virus-transformed lymphoblastoid cell lines of the patient revealed ~50% reduction in the transcript (p = 0.02), suggesting haploinsufficiency of the gene. cdk8, the closest orthologue of human CDK19 in Drosophila has been shown to play a major role in eye development. Conditional knock-down of Drosophila cdk8 in multiple dendrite (md) neurons resulted in 35% reduced dendritic branching and altered morphology of the dendritic arbour, which appeared to be due in part to a loss of small higher order branches. In addition, Cdk8 mutant md neurons showed diminished dendritic fields revealing an important role of the CDK19 orthologue in the developing nervous system of Drosophila. This is the first time the CDK19 gene, a component of the mediator co-activator complex, has been linked to a human disease