Is 125I iothalamate an ideal marker for glomerular filtration?

Is 125I iothalamate an ideal marker for glomerular filtration? The triiodinated angiographic contrast medium, iothalamate, has (usually labelled 125I) been used extensively as a marker for glomerular filtration. We have studied the renal handling of 125I iothalamate (IOT) in vivo and in vitro in several species. In renal cortical slices from chicken, rabbit, rat, and monkey, the tissue-to-medium ratio of IOT was twice that of 51Cr-EDTA (EDTA) at 37°C; a difference that was abolished at 0°C and markedly reduced by added o-iodohippurate or iodipamide. In five chickens the steady-state renal clearance of IOT (CIOT) was twice (P < 0.05) that of EDTA (CEDTA) or 3H inulin (C1); a difference that was abolished by administration of 100 mg/kg/hr of novobiocin, an organic anion transport inhibitor. CEDTA was similar to C1 before as well as after transport inhibition. Utilizing the Sperber technique the mean apparent tubular excretion fraction (ATEF) of IOT was 8%, while that of EDTA was 1% (P < 0.01; N = 10). After novobiocin coinfusion (new steady-state) ATEFIOT was significantly reduced (P < 0.01) and not different from that of EDTA (-1%). In the same animals the total urinary recovery of IOT was 84 and 57% (P < 0.01) before and after novobiocin, respectively, while corresponding values for EDTA was unchanged by the inhibitor. In seven rats the renal extraction of IOT was reduced from 29 to 17% (P < 0.05) by coinfusion of probenecid (5 mg/kg/hr). Corresponding extractions were 82 to 34% (P < 0.005) and 22% (unchanged) for PAH and EDTA, respectively. In six healthy volunteers the renal clearance of unlabelled IOT (HPLC method) equated that of creatinine but exceeded that of inulin with 38% (P < 0.01). This difference was reduced 34% (P<0.05) by probenecid (1 g i.v.). In nineteen patients with a single or two kidneys the average plasma clearance (single injection technique; slope-intercept method) of IOT was 13% higher than that of EDTA (P < 0.001); a difference which was significantly (P < 0.01) reduced to half after pretreatment with probenecid (1 g i.v.); in some patients this difference was marked. The results show that IOT is subject to a significant and in some cases marked renal tubular secretion in chicken, rats, and humans. IOT, therefore, is not an ideal marker for glomerular filtration.Le 125I iothalamate est-il un marqueur idéal de la filtration glomérulaire? L'iothalamate, un produit de contraste angiographique tri-iodé a été largement utilisé (habituellement marqué à 125I) comme marqueur de la filtration glomérulaire. Nous avons étudié l'excrétion rénale du 125I iothalamate (IOT) in vivo et in vitro dans différentes espèces. Dans des tranches corticales de rein de poulet, de lapin, de rat, et de singe, le rapport tissu sur milieu de l'IOT était le double de celui du 51Cr-EDTA (EDTA) à 37°C; une différence abolie à 0°C et réduite de façon marquée par l'addition de O-iodohippurate ou d'iodipamide. Chez cinq poulets la clearance rénale à l'équilibre d'IOT (CIOT) était le double (P < 0,05) de celle de l'EDTA (CEDTA) ou de 3H inuline (CI); une différence abolie par l'administration de 100 mg/kg/hr de novobiocine, un inhibiteur du transport des anions organiques. CEDTA était identique à CI avant comme après l'inhibition du transport. En utilisant la technique de Sperber, la fraction d'excrétion tubulaire apparente moyenne (ATEF) de l'IOT était de 8%, alors que celle de l'EDTA était de 1% {P < 0,01; N = 10). Après coperfusion de novobiocine (nouvel équilibre) ATEFIOT était significativement réduite (P < 0,01) et non différente de celle de l'EDTA (- 1%). Chez les mêmes animaux, la récupération urinaire totale d'IOT était de 84 et 57% (P < 0,01) avant et après novobiocine, respectivement, alors que les valeurs correspondantes pour l'EDTA étaient inchangées par l'inhibiteur. Chez sept rats, l'extraction rénale d'IOT était réduite de 29 à 17% (P < 0,05) par coperfusion de probénécide (5 mg/kg/hr). Les extractions correspondant étaient de 82 à 34% (P < 0,005) et de 22% (inchangées) pour le PAH et l'EDTA, respectivement. Chez six volontaires sains, la clearance rénale de l'IOT non marqué (méthode HPLC) était égale à celle de la créatinine mais dépassait celle de l'inuline de 38% (P < 0,01). Cette différence était réduite de 34% (P < 0,05) par le probénécide (1 g i.v.). Chez dix-neuf malades avec un ou deux reins, la clearance plasmatique moyenne (technique par injection unique; méthode d'interception de la courbe) de l'IOT était 13% plus élevée que celle de l'EDTA (P < 0,01); une différence qui était significativement (P < 0,01) réduite de moitié après prétraîtement par le probénécide (1 g i.v.); chez certains malades cette différence était marquée. Ces résultats montrent que l'IOT est sujet à une sécrétion tubulaire rénale significative et parfois marquée chez le poulet, le rat, et l'homme. L'IOT n'est donc pas un marqueur idéal de la filtration glomérulaire

Intratumor Heterogeneity of the Estrogen Receptor and the Long-term Risk of Fatal Breast Cancer.

Background:Breast cancer patients with estrogen receptor (ER)-positive disease have a continuous long-term risk for fatal breast cancer, but the biological factors influencing this risk are unknown. We aimed to determine whether high intratumor heterogeneity of ER predicts an increased long-term risk (25 years) of fatal breast cancer. Methods:The STO-3 trial enrolled 1780 postmenopausal lymph node-negative breast cancer patients randomly assigned to receive adjuvant tamoxifen vs not. The fraction of cancer cells for each ER intensity level was scored by breast cancer pathologists, and intratumor heterogeneity of ER was calculated using Rao's quadratic entropy and categorized into high and low heterogeneity using a predefined cutoff at the second tertile (67%). Long-term breast cancer-specific survival analyses by intra-tumor heterogeneity of ER were performed using Kaplan-Meier and multivariable Cox proportional hazard modeling adjusting for patient and tumor characteristics. Results:A statistically significant difference in long-term survival by high vs low intratumor heterogeneity of ER was seen for all ER-positive patients (P &lt; .001) and for patients with luminal A subtype tumors (P = .01). In multivariable analyses, patients with high intratumor heterogeneity of ER had a twofold increased long-term risk as compared with patients with low intratumor heterogeneity (ER-positive: hazard ratio [HR] = 1.98, 95% confidence interval [CI] = 1.31 to 3.00; luminal A subtype tumors: HR = 2.43, 95% CI = 1.18 to 4.99). Conclusions:Patients with high intratumor heterogeneity of ER had an increased long-term risk of fatal breast cancer. Interestingly, a similar long-term risk increase was seen in patients with luminal A subtype tumors. Our findings suggest that intratumor heterogeneity of ER is an independent long-term prognosticator with potential to change clinical management, especially for patients with luminal A tumors

Up-to-date on mortality in COPD - report from the OLIN COPD study

<p>Abstract</p> <p>Background</p> <p>The poor recognition and related underdiagnosis of COPD contributes to an underestimation of mortality in subjects with COPD. Data derived from population studies can advance our understanding of the true burden of COPD. The objective of this report was to evaluate the impact of COPD on mortality and its predictors in a cohort of subjects with and without COPD recruited during the twenty first century.</p> <p>Methods</p> <p>All subjects with COPD (n = 993) defined according to the GOLD spirometric criteria, FEV₁/FVC < 0.70, and gender- and age-matched subjects without airway obstruction, non-COPD (n = 993), were identified in a clinical follow-up survey of the Obstructive Lung Disease in Northern Sweden (OLIN) Studies cohorts in 2002-2004. Mortality was observed until the end of year 2007. Baseline data from examination at recruitment were used in the risk factor analyses; age, smoking status, lung function (FEV₁% predicted) and reported heart disease.</p> <p>Results</p> <p>The mortality was significantly higher among subjects with COPD, 10.9%, compared to subjects without COPD, 5.8% (p < 0.001). Mortality was associated with higher age, being a current smoker, male gender, and COPD. Replacing COPD with FEV₁% predicted in the multivariate model resulted in the decreasing level of FEV₁being a significant risk factor for death, while heart disease was not a significant risk factor for death in any of the models.</p> <p>Conclusions</p> <p>In this cohort COPD and decreased FEV₁were significant risk factors for death when adjusted for age, gender, smoking habits and reported heart disease.</p

Diabetes : Käypä hoito -suosituksen päivitystiivistelmä

English summar

Clinical Characteristics of Microscopic Colitis in Korea: Prospective Multicenter Study by KASID

Background/Aims: Microscopic colitis (MC) encompasses collagenous and lymphocytic colitis and is characterized by chronic diarrhea. In cases of MC, colonic mucosae are macroscopically normal, and diagnostic histopathological features are observed only upon microscopic examination. We designed a prospective multicenter study to determine the clinical features, pathological distribution in the colon and prevalence of MC in Korea. Methods: We prospectively enrolled patients having watery diarrhea no more than 3 times a day between March 2008 and February 2009. We obtained patient histories and performed colonoscopies with random biopsies at each colon segment. Results: A total of 100 patients with chronic diarrhea were enrolled for a normal colonoscopy and stool exam. MC was observed in 22 patients (22%) (M:F 1.2:1; mean age, 47.5 years). Of those 22 patients, 18 had lymphocytic colitis and 4 had collagenous colitis. The entire colon was affected in only 3 cases (13.6%), the ascending colon in 6 cases (27.2%), the transverse colon in 3 cases (13.6%), and the left colon in 3 cases (13.6%). More than 2 segments were affected in 7 cases (31.8%). Nonsteroidal anti-inflammatory drug-associated MCs were observed in 4 cases (18.2%), 3 of which showed improved diarrhea symptoms following discontinuation of the medication. Frequently associated symptoms were abdominal pain and weight loss. Autoimmune diseases were observed in 4 cases (18.2%). Half of the 22 patients with MC improved with conservative care by loperamide or probiotics. Conclusions: In a prospective multicenter study of Korean patients with chronic diarrhea, the frequency of MC was found to be approximately 20%, similar to the percentage observed in Western countries. Therefore, the identification of MC is important for the adequate management of Korean patients with chronic diarrhea. (Gut Liver 20115:181-186

Swedish snuff and incidence of cardiovascular disease. A population-based cohort study

<p>Abstract</p> <p>Background</p> <p>The relationship between smoking and an increased incidence of cardiovascular diseases is well known. Whether smokeless tobacco (snuff) is related to myocardial infarction (MI) or stroke is still controversial. Aim of this study was to explore whether snuff users have an increased incidence of MI or stroke.</p> <p>Methods</p> <p>A total of 16 754 women and 10 473 men (aged 45–73 years), without history of cardiovascular disease (CVD), belonging to the population-based "Malmö Diet and Cancer" study were examined. Incidence of MI and stroke were monitored over 10.3 years.</p> <p>Results</p> <p>Snuff was used by 737 (7.0%) men and 75 (0.4%) women, respectively. Among men, snuff was significantly associated with low occupation level, single civil status, high BMI and with current and former smoking. In women, snuff was associated with lower systolic blood pressure. A total of 964 individuals (3.5%), i.e.544 men (5.3%) and 420 (2.5%) women suffered a MI during the follow-up period. The corresponding numbers of incident stroke cases were 1048, i.e. 553 men (5.3%) and 495 (3.0%) women, respectively. Snuff was not associated with any statistically significant increased risk of MI or stroke in men or women. The relative risks (RR) in male snuff users compared to non-users were 1.05 (95% confidence interval (CI): 0.8–1.4, p = 0.740) for incident MI and 0.97 (0.7–1.4, p = 0.878) for stroke, after taking age and potential confounders into account. In women none of the 420 (2.5%) women who were snuff users had a MI and only one suffered a stroke during the follow-up.</p> <p>Conclusion</p> <p>Several life-style risk factors were more prevalent in snuff-users than in non-users. However, the present study does not support any relationship between snuff and incidence of cardiovascular disease in men.</p

Interpopulation Variation in Contour Feather Structure Is Environmentally Determined in Great Tits

Background: The plumage of birds is important for flying, insulation and social communication. Contour feathers cover most of the avian body and among other functions they provide a critical insulation layer against heat loss. Feather structure and composition are known to vary among individuals, which in turn determines variation in the insulation properties of the feather. However, the extent and the proximate mechanisms underlying this variation remain unexplored. Methodology/Principal Findings: We analyzed contour feather structure from two different great tit populations adapted to different winter regimes, one northern population in Oulu (Finland) and one southern population in Lund (Sweden). Great tits from the two populations differed significantly in feather structure. Birds from the northern population had a denser plumage but consisting of shorter feathers with a smaller proportion containing plumulaceous barbs, compared with conspecifics from the southern population. However, differences disappeared when birds originating from the two populations were raised and moulted in identical conditions in a common-garden experiment located in Oulu, under ad libitum nutritional conditions. All birds raised in the aviaries, including adult foster parents moulting in the same captive conditions, developed a similar feather structure. These feathers were different from that of wild birds in Oulu but similar to wild birds in Lund, the latter moulting in more benign conditions than those of Oulu. Conclusions/Significance: Wild populations exposed to different conditions develop contour feather differences either due to plastic responses or constraints. Environmental conditions, such as nutrient availability during feather growth play a crucial role in determining such differences in plumage structure among populations

Publisher Correction: Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability.

Correction to: Nature Communications https://doi.org/10.1038/s41467-020-19366-9, published online 5 January 2021. The original version of this Article contained an error in Fig. 2, in which panels a and b were inadvertently swapped. This has now been corrected in the PDF and HTML versions of the Article