Publications by authors named "Isabel Galan"

21 Publications

  • Page 1 of 1

Impact of Serum Magnesium Levels on Kidney and Cardiovascular Prognosis and Mortality in CKD Patients.

J Ren Nutr 2020 Dec 9. Epub 2020 Dec 9.

Hospital General Universitario Gregorio Marañón, Madrid, Spain.

Introduction: In the general population, hypomagnesemia has been associated with cardiovascular events and hypermagnesemia with overall mortality. In chronic kidney disease (CKD) the evidence is not so strong. The objective of our study was to investigate the relationship between serum magnesium (SMg) concentration and cardiovascular morbidity and mortality, all-cause mortality, and the progression to kidney failure in a population with CKD.

Methods: Observational study of a cohort of 746 patients with CKD. Baseline characteristics and analytical profile were collected at the first visit, and patients were followed for a mean of 42.6 months.

Results: A cohort of 746 patients were analyzed, age 70 ± 13 years, 62.9% were male, 45.2% had CKD grade 3, and 35.9% grade 4. The mean SMg concentration was 2.09 ± 0.33 mg/dL, with a close correlation between SMg concentration and serum creatinine, phosphorus, and intact parathyroid hormone (iPTH) values. Use of calcitriol was associated with higher SMg (SMgH) concentration, while calcium supplements and proton pump inhibitors (PPIs) were associated with lower SMg concentration. For risk of cardiovascular events, patients with hypermagnesemia had an overall higher risk on a crude analysis (Log Rank 4.83, P = .28) and adjusted analysis (HR = 1.34, CI 1.02-1.77, P = .037). For risk of all-cause mortality, patients with hypermagnesemia had an overall higher risk on crude analysis (Log Rank 13.11, P > .001) and adjusted analysis (HR = 1.5424, IC = 1.002-2.319, P = .049). After performing a propensity score matching for SMg concentration, we achieved two comparable groups of 287 patients, finding again higher all-cause mortality in the hypermagnesemia group (LogRank 15.147, P < .001), that persisted in the Cox model adjusted for calcium, phosphorus, and iPTH. No association was found between SMg concentration and initiation of kidney replacement therapy (KRT).

Conclusions: Magnesium concentration increases with decreasing kidney function. Hypermagnesemia predicts cardiovascular events and all-cause mortality in this same population. Thus, magnesium supplementation should be used with caution in these patients.
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http://dx.doi.org/10.1053/j.jrn.2020.09.004DOI Listing
December 2020

Filler Effect in Shotcrete.

Materials (Basel) 2019 Oct 1;12(19). Epub 2019 Oct 1.

Institute of Technology and Testing of Building Materials, Graz University of Technology, 8010 Graz, Austria.

The effects of fine limestone powder on the early hydration of cementitious systems accelerated by means of alkali-free aluminum sulfate based products, commonly used for shotcrete applications, were investigated in the course of laboratory and real scale tests. In binary (CEM I + limestone) and ternary (CEM I + limestone + slag) systems the addition of fine limestone led to an enhancement of the hydration degree and strength development at early times (<24 h). The formation of ettringite, aluminate hydrates, and C-S-H is affected by the joint action of the setting accelerator and the fine limestone. Accelerator and limestone, in combination with the cement, can be optimized to enhance ettringite and silicate reaction, in some cases coupled with aluminate reaction inhibition, to produce mixes suitable for sprayed concrete applications. Such optimization can help to reduce the cement content in the mixes without compromising the early strength development of the shotcrete.
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http://dx.doi.org/10.3390/ma12193221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6803996PMC
October 2019

High convective volumes are associated with improvement in metabolic profile in diabetic patients on online haemodiafiltration.

Nefrologia 2019 Mar - Apr;39(2):168-176. Epub 2018 Nov 19.

Servicio de Nefrología, Hospital Gregorio Marañón, Madrid, España.

Background And Objective: Online haemodiafiltration (OL-HDF) with high convective transport volumes improves patient survival in haemodialysis. Limiting the amount of convective volume has been proposed in patients with diabetes mellitus due to glucose load that is administered with replacement fluid. The objective of the study was to analyse the influence of substitution volume on the evolution of the metabolic profile and body composition of incident diabetic patients on OL-HDF.

Material And Methods: Prospective observational study in 29 incident diabetic patients on postdilution OL-HDF. Baseline data included clinical and demographic data, laboratory parameters (metabolic, nutritional and inflammatory profile) and body composition with bioimpedance spectroscopy (BIS). Laboratory parameters and mean substitution volume per session were collected every 4 months, and in 23 patients a further BIS was performed after a minimum of one year. Variations in glycosylated haemoglobin (HbA1c), triglycerides, total cholesterol, LDL-c, HDL-c, albumin, prealbumin and C reactive protein (CRP) were calculated at one year, 2 years, 3 years, and at the end of follow-up. Quarterly and annual variations were calculated as independent periods, and changes in body composition were analysed.

Results: Age at baseline was 69.7±13.6 years, 62.1% were male, 72.3±13.9kg, 1.78±0.16m, with 48 (35.5-76) months on dialysis. Approximately 81.5% received insulin, 7.4% antidiabetic drugs and 51.9% statins. Mean substitution volume was 26.9±2.9L/session and follow-up period (time on OL-HDF) was 40.4±26 months. A significant correlation was observed between mean substitution volume and the increase in HDL-c (r=0.385, p=0.039) and prealbumin levels (r=0.404, p=0.003) throughout follow-up. Moreover, substitution volume was correlated with a reduction in CRP levels at one year (r=-0.531, p=0.005), 2 years (r=-0.463, p=0.046), and at the end of follow-up (r=-0.498, p=0.007). Patients with mean substitution volume >26.9L/session had a higher reduction in triglycerides and CRP, and an increase in HDL-c levels. These patients with >26.9L/session finished the study with higher HDL-c (48.1±9.4mg/dL vs. 41.2±11.6mg/dL, p=0.025) and lower CRP levels (0.21 [0.1-2.22] mg/dL vs. 1.01 [0.15-6.96] mg/dL, p=0.001), with no differences at baseline. Quarterly comparisons between substitution volume and laboratory changes [n=271] showed a significant correlation with a reduction in HbA1c (r=-0.146, p=0.021). Similar findings were obtained with annual comparisons [n=72] (r=-0.237, p=0.045). An annual mean substitution volume over 26.6L/session (29.3±1.7L/session vs. 23.9±1.9L/session) was associated with a reduction in HbA1c (-0.51±1.24% vs. 0.01±0.88%, p=0.043). No correlation was observed between substitution volume and changes in weight, body mass index or BIS parameters.

Conclusion: There is not enough evidence to restrict convective transport in diabetic patients on OL-HDF due to the glucose content of the replacement fluid.
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http://dx.doi.org/10.1016/j.nefro.2018.08.005DOI Listing
January 2020

Impact of the application of the JNC 8 and KDIGO-2013 guidelines on hypertension and lipid control in a Nephrology outpatient clinic.

Nefrologia 2018 Jul - Aug;38(4):379-385

Hospital General Universitario Gregorio Marañón, Madrid, España.

Objective: Observational retrospective study with consecutive patients with CKD to assess the degree of accomplishment of the therapeutic objectives in hypertension and dyslipidaemia recommended by JNC 8 and KDIGO-2013 CKD guidelines the impact of their implementation compared with previous guidelines.

Results: 618 patients were included, mean age 67±15 years, 61.33% male. Mean eGFR was 45.99±18.94ml/min, with median albumin/creatinine 26 (0-151)mg/g. A total of 87.6% received antihypertensive treatment and 50.2% received statins. According to KDIGO guidelines, 520 patients (84.14%) should receive statins, but only 304 (58.46%) were receiving them. Patients on statin treatment had more diabetes and hypertension, and a greater cardiovascular history and lower levels of total and LDL-cholesterol. A total of 97.7% of patients were under 60 years of age or had eGFR<60ml/min/1.73m or were diabetic, so according to the JNC 8 report, they should have a target blood pressure<140/90mmHg. A total of 289 patients did (47.85%). According to the JNC 7 report, this group had a tighter target blood pressure<130/90mmHg, reducing the number of patients who fulfilled the target: 136 (22.52%). Patients reclassified were older, had a greater cardiovascular history and less DM.

Conclusion: The new KDIGO guidelines for dyslipidaemia treatment increase the indication of statin therapy, especially in patients at high cardiovascular risk. The JNC 8 guidelines improve the percentage of patients with controlled blood pressure, especially the elderly and patients with increased cardiovascular risk, in whom the target blood pressure is currently controversial.
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http://dx.doi.org/10.1016/j.nefro.2017.10.003DOI Listing
April 2019

Comparison of urea recirculation and thermodilution for monitoring of vascular access in patients undergoing hemodialysis.

J Vasc Access 2018 May 7;19(3):283-290. Epub 2018 Mar 7.

1 Department of Nephrology, Hospital General Universitario Gregorio Marañón, Madrid, Spain.

Introduction It is important to monitor vascular access in patients with stage 5 chronic kidney disease receiving hemodialysis. Access recirculation can help to detect a need for intervention.

Objectives: To compare urea recirculation with recirculation by thermodilution using blood temperature monitoring to predict a need for intervention of vascular access over a 6-month period.

Methods: We analyzed urea recirculation and blood temperature monitoring simultaneously in 61 patients undergoing hemodialysis. During the 6-month follow-up, we recorded all cases of angioplasty or surgery (thrombectomy or reanastomosis). In line with previous studies, we considered a value to be positive when urea recirculation was >10% and blood temperature monitoring >15%. Receiver operating characteristic curves were constructed.

Results: Mean urea recirculation was 9.5% ± 6.6% and mean blood temperature monitoring 12.9% ± 4.3% (p = 0.001). Urea recirculation >10% had a sensitivity of 80% and specificity of 78%. Blood temperature monitoring >15% had a sensitivity of 33% and specificity of 85%. During follow-up, 25% of patients developed need for intervention of vascular access. We found an association between vascular access dysfunction and urea recirculation. The Kaplan-Meier analysis confirmed an association between urea recirculation and risk of vascular access dysfunction (log rank = 17.2; p = 0.001). We were unable to confirm this association with blood temperature monitoring (log rank = 0.879; p = 0.656).

Conclusion: Urea recirculation is better predictor of vascular access dysfunction than thermodilution.
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http://dx.doi.org/10.1177/1129729817747536DOI Listing
May 2018

Hyperuricemia is associated with progression of chronic kidney disease in patients with reduced functioning kidney mass.

Nefrologia 2018 Jan - Feb;38(1):73-78. Epub 2017 Aug 30.

Hospital General Universitario Gregorio Marañón, Spain.

Background And Objectives: Hyperuricemia plays a major role in the development and progression of chronic kidney disease (CKD). Many large observational studies have indicated that increased serum uric acid level predicts the development and progression of CKD in some population, however this hypothesis has not been yet studied in patients with reduced renal mass.

Design, Setting, Participants, & Measurements: Retrospective study with a cohort of 324 patients with reduced renal mass from an outpatient basis, followed during 60 (36-98) months. Demographics variables, cardiovascular factors, concomitant medications, albuminuria and uric acid levels were recorded yearly. The primary endpoint was the annual fall of estimated glomerular filtration rate (eGFR) by MDRD-4. The sample was divided into three successive groups (A1: patients with fall of eGFR lower than median, A2: greater than median, B: without fall of eGFR). Factors associated and predictors of kidney function decline were analyzed.

Results: One hundred and seventy out of 324 patients suffered a fall of eGFR (group A), (median of fall -1.6ml/min/1.73m/year (-3.0, -0.7)). Male gender, albuminuria>100mg/day and higher pulse pressure were associated to progression in our cohort (group A). Hyperuricemia was more frequent among patients with higher kidney disease progression (group A2) (33% vs 49%, p=0.04) when comparing to lower progression (group A1). Adjusted Cox regression models showed that hyperuricemia, pulse pressure and albuminuria were independent predictors of kidney disease progression (HR 1.67 (1.06-2.63), p=0.023; 1.02 (1.01-1.03), p=0.001 and HR: 2.14 (1.26-3.64), p=0.005, respectively). Kidney disease progression was higher in patients with unilateral renal atrophy or agenesis than nephrectomy (log rank: 7.433, p=0.006).

Conclusions: Hyperuricemia is independently associated with kidney disease progression in patients with reduce functioning renal mass.
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http://dx.doi.org/10.1016/j.nefro.2017.04.006DOI Listing
October 2018

Low lean tissue mass is an independent risk factor for mortality in patients with stages 4 and 5 non-dialysis chronic kidney disease.

Clin Kidney J 2017 Apr 8;10(2):170-175. Epub 2017 Feb 8.

Nephrology Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain.

Mortality in patients with stages 4 and 5 chronic kidney disease (CKD) is higher than in the general population. Body composition predicts mortality. Our objective was to evaluate the effect of body composition on mortality in patients with stages 4 and 5 non-dialysis CKD. We performed a prospective study of 356 patients with stages 4 and 5 non-dialysis CKD. At baseline, we recorded general characteristics, history of cardiovascular events, body composition, serum inflammatory markers, nutrition and cardiac biomarkers. Body composition was analysed using bioimpedance spectroscopy. We recorded the lean tissue index (LTI), fat tissue index (FTI) and overhydration (OH). During a median (range) follow-up of 22 (3-49) months, we recorded mortality, cardiovascular events and progress to renal replacement therapy. At baseline, mean (± standard deviation) age was 67 ± 13 years (men 64%; diabetes 36%). Mean body mass index was 28.2 ± 12.8 kg/m, the FTI was 12.3 ± 5.6 kg/m, the LTI was 15.7 ± 3.4 kg/m and median (interquartile range) OH was 0.6 (-0.4 to 1.5) L. Sixty-four (18%) patients died during follow-up. The univariate Cox analysis showed an association between mortality and age, low LTI, high Charlson comorbidity index, previous cardiovascular events, OH, low albumin and prealbumin levels, and high C-reactive protein levels. Kaplan-Meier analysis revealed higher survival in patients with a higher LTI (log-rank, 9.47; P = 0.002). The multivariate Cox analysis confirmed an association between mortality and low LTI (P = 0.031), previous cardiovascular events (P = 0.003) and high Charlson comorbidity index (P = 0.01). We did not find any association between body composition and cardiovascular events or renal replacement therapy. A low LTI is an independent factor for mortality in patients with stages 4 and 5 CKD.
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http://dx.doi.org/10.1093/ckj/sfw126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5381238PMC
April 2017

Prevalence and characteristics of patients with resistant hypertension and chronic kidney disease.

Nefrologia 2016 Sep - Oct;36(5):523-529. Epub 2016 Jul 18.

Departamento Nefrología, Hospital General Universitario Gregorio Marañón, Madrid, España.

Resistant hypertension (RH) is a common problem in patients with chronic kidney disease (CKD). A decline in the glomerular filtration rate (GFR) and increased albuminuria are associated with RH; however, there are few published studies about the prevalence of this entity in patients with CKD.

Objective: To estimate the prevalence of RH in patients with different degrees of kidney disease and analyse the characteristics of this group of patients.

Methods: A total of 618 patients with hypertension and CKD stages i-iv were enrolled, of which 82 (13.3%) met the criteria for RH.

Results: RH prevalence increased significantly with age, the degree of CKD and albuminuria. The prevalence of RH was 3.2% in patients under 50 years, 13.8% between 50-79 years and peaked at 17.8% in patients older than 80 years. Renal function prevalence was 4, 15.8 and 18.1% in patients with an estimated glomerular filtration rate (GFR) of > 60, 30-59 and < 30ml/min/1.73 m, respectively, and 8.9, 15.9 and 22.5% for a urine albumin to creatinine ratio (UACR) < 30, 30-299 and > 300mg/g respectively. In a logistic regression model, the characteristics associated with resistant hypertension were age, history of cardiovascular disease, GFR, albuminuria and diabetes mellitus. A total of 47.5% of patients with resistant hypertension had controlled BP (<140/90mmHg) with 4 or more antihypertensive drugs. These patients were younger, with better renal function, less albuminuria and received more aldosterone antagonists.

Conclusion: RH prevalence increases with age, the degree of CKD and albuminuria. Strategies such as treatment with aldosterone receptor antagonists are associated with better blood pressure control in this group of patients, leading to reduced prevalence.
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http://dx.doi.org/10.1016/j.nefro.2016.04.003DOI Listing
April 2018

Interarm systolic blood pressure as a predictor of cardiovascular events in patients with chronic kidney disease.

Nephrol Dial Transplant 2015 May 9;30(5):801-6. Epub 2015 Mar 9.

Nephrology Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain.

Background: Increased interarm systolic blood pressure difference (IASBPD) is associated with mortality and cardiovascular (CV) events both in the general population and in patients at high CV risk. The aim of the present study was to assess the value of IASBPD ≥ 10 mmHg for predicting CV events in patients with chronic kidney disease (CKD).

Methods: The study sample comprised 652 patients with CKD (age 67 ± 15 years, 58.1% men). Follow-up was 19 ± 5 months. We recorded increased IASBPD and related factors and assessed the predictive value of this variable for CV events.

Results: We recorded diabetes mellitus in 136 patients (20.8%), history of CV disease in 213 (32.6%) and dyslipidaemia in 327 (50.1%). The mean glomerular filtration rate was 45.9 ± 18.9 mL/min/1.73 m(2), and the median albumin/creatinine ratio was 26(0-151) mg/g. IASBPD was ≥10 mmHg in 184 patients (28.1%). The factors associated with IASBPD ≥10 mmHg were age, systolic blood pressure levels, history of congestive heart failure, lower levels of high-density lipid cholesterol and higher use of hypertensive drugs. Fifty-eight patients (8.5%) developed a CV event during the follow-up. IASBPD ≥10 mmHg [HR, 1.802, 95%CI (1.054-3.079); P = 0.031] was an independent predictor of CV events.

Conclusions: Increased IASBPD is an independent predictor of CV events in CKD patients.
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http://dx.doi.org/10.1093/ndt/gfv059DOI Listing
May 2015

A Spanish multicentric study to evaluate the clinical activity of nephrology fellows during in-hospital on-call shifts.

Clin Kidney J 2013 Oct 1;6(5):556-60. Epub 2013 Aug 1.

Hospital General Universitario Gregorio Marañón , Madrid , Spain.

Background: Nephrologists develop their work in diverse scenarios. A training programme must qualify trainees to assist different kinds of problems. The aim of this study was to characterize patients and pathologies that Spanish nephrology fellows face while on-call.

Methods: This is a descriptive study with clinical and demographic data gathered with a form by 10 nephrology fellows of five university hospitals of Madrid (Spain), throughout their in-hospital 24 h on-call shifts in February and March 2013.

Results: We collected 409 episodes over 338 patients, through 72 shifts. Among these, 16.7% had previous normal renal function, 24.6% chronic kidney disease, 39.5% were on dialysis and 18.2% had a kidney transplant. Most of the consults came from the emergency room (35.9%) or the previous on-call team (13.7%). Afterwards, the most usual destiny was admittance to a nephrology department (32.8%) or discharge (20.5%). The most frequent reason for consulting was a decline in renal function (31.6%) and the second motive an infection. Thirty-four episodes (8.3%) were related to dialysis access problems. Medical treatment was prescribed in 79.2% of the cases, primarily fluids (47.2%) and antibiotics (42.2%). The fellow had to place a central venous catheter in 24 cases (5.9%). Renal replacement therapy was prescribed in 19.8% of the episodes.

Conclusions: Specific renal reasons for consulting nephrologists are common, such as acute kidney injury or dialysis access complications. These patients benefit from a specialized approach to their problems. Clinical activities during in-hospital out-of-hours shifts are a priceless tool as part of the training programme of nephrology fellows.
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http://dx.doi.org/10.1093/ckj/sft080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4438395PMC
October 2013

Candidate biomarkers for acute rejection of pregnancy after in-utero cell-based therapy in pre-immune embryos via ultrasound-guided celocentesis.

Am J Reprod Immunol 2012 Aug 15;68(2):181-4. Epub 2012 May 15.

Department of Obstetrics and Gynecology, University of Medicine and Dentistry New Jersey-Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA.

Problem: A maternal serum biomarker profile analysis was performed to determine potential indicators of acute rejection of pregnancy following in-utero cell-based treatments in pre-immune embryos.

Method Of Study: We used an established non-human primate model for in-utero stem cell therapy at 38-42 days from fertilization. The maternal serum concentrations of nine candidate biomarkers for acute rejection of pregnancy were determined before and after the injection of different cocktails of human umbilical cord blood stem cells into the gestational sac. All animals were then followed until delivery.

Results: Twenty-four hours after celocentesis, two of the animals aborted. These two animals received a cocktail of haemopoietic stem cells with the highest concentration of human CD3(+) cells and showed a twofold increase in maternal serum IL-6 and a threefold increase in prolactin after the procedure. The remaining six animals delivered at term live and normal newborns and only demonstrated an increase in prolactin after the celocentesis procedure.

Conclusion: IL-6 and prolactin are master immunoregulators with pleiotropic biological functions that have different maternal serum concentrations depending on pregnancy outcome. These findings suggest that increases in maternal serum prolactin and IL-6 concentration may be associated with acute rejection of pregnancy after in-utero stem cell therapy.
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http://dx.doi.org/10.1111/j.1600-0897.2012.01150.xDOI Listing
August 2012

The ability of sperm selection techniques to remove single- or double-strand DNA damage.

Asian J Androl 2011 Sep 4;13(5):764-8. Epub 2011 Jul 4.

Unidad de Genética, Departamento de Biología, Universidad Autónoma de Madrid, Madrid 28049, Spain.

A wide variety of techniques for the preparation of sperm are currently available, of which the most commonly employed are density-gradient centrifugation (DGC) and swim-up (SUP). To date, these methods appear to be effective in selecting functional sperm for assisted reproduction techniques (ART), but they may have negative effects on sperm DNA. In this study, the ability of these semen processing techniques to eliminate spermatozoa containing single- and double-strand DNA damage was assessed by the two-tailed comet assay and the sperm chromatin dispersion test in 157 semen samples from patients seeking assisted reproduction treatment. Our results indicated that SUP and DGC are equally efficient in eliminating spermatozoa containing double-strand DNA damage and sperm with highly damaged (degraded) DNA, as characterized by the presence of both single- and double-strand DNA breaks. However, DGC is more efficient than SUP in selecting spermatozoa that are free from single-strand DNA damage. Future studies should characterise the importance of the various types of DNA damage and examine the sperm processing protocols used in each laboratory to determine their ability to eliminate DNA damage and hence, prevent the potential transmission of genetic mutations via ART.
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http://dx.doi.org/10.1038/aja.2011.46DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3739591PMC
September 2011

Sequestration of CO2 by concrete carbonation.

Environ Sci Technol 2010 Apr;44(8):3181-6

Eduardo Torroja Institute IETcc-CSIC, Serrano Galvache 4, 28033 Madrid, Spain, Oficemen, Jose Abascal 53, Madrid 28003, Spain.

Carbonation of reinforced concrete is one of the causes of corrosion, but it is also a way to sequester CO2. The characteristics of the concrete cover should ensure alkaline protection for the steel bars but should also be able to combine CO2 to a certain depth. This work attempts to advance the knowledge of the carbon footprint of cement. As it is one of the most commonly used materials worldwide, it is very important to assess its impact on the environment. In order to quantify the capacity of cement based materials to combine CO2 by means of the reaction with hydrated phases to produce calcium carbonate, Thermogravimetry and the phenolphthalein indicator have been used to characterize several cement pastes and concretes exposed to different environments. The combined effect of the main variables involved in this process is discussed. The moisture content of the concrete seems to be the most influential parameter.
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http://dx.doi.org/10.1021/es903581dDOI Listing
April 2010

A study to determine if human umbilical cord hematopoietic stem cells can survive in baboon extra-embryonic celomic fluid: a prerequisite for determining the feasibility of in-utero stem cell xeno-transplantation via celocentesis.

Fetal Diagn Ther 2007 28;22(2):131-5. Epub 2006 Nov 28.

Center for Fetal Medicine and Prenatal Genetics, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, MA 02115, USA.

Objectives: To determine if: (1) human umbilical cord stem cells could survive for 20 h in extra-embryonic celomic fluid obtained at 40 days of development from baboon pregnancies by ultrasound-guided celocentesis and, (2) human hematopoietic stem cell survival could be enhanced by adding increasing concentrations of hematopoietic stem cell culture medium to the celomic fluid.

Methods: CD34+ cells were isolated from umbilical cord blood using a magnetic activated cell sorter and flow cytometry. Cells were then cultured in five platforms containing different combinations of baboon extra-embryonic celomic fluid and hematopoietic stem cell culture medium to determine cell survival kinetics over a 20-hour period in each of the conditions.

Results: Human umbilical cord stem cells can survive for at least 20 h in baboon's celomic fluid. Chi-square for linear trends demonstrated that the number of viable cells was significantly enhanced by adding the increasing concentrations of culture medium to the celomic fluid (29% cell survival in pure celomic fluid, 48% at 1:8, 50% at 1:2, 54.5% at 1:1, 61% in pure culture medium; p < 0.001).

Conclusions: Human umbilical cord stem cells survive in baboon celomic fluid and cell survival improves when the celomic fluid is mixed with greater concentrations of hematopoietic stem cell culture medium. Based on these findings, future in-vivo experiments in the pregnant baboon animal model can be directed at determining whether in-utero injection of human hematopoietic stem cells prior to 10 weeks of pregnancy can lead to permanent chimeras.
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http://dx.doi.org/10.1159/000097112DOI Listing
March 2007

Effect of the ABO blood group on the proliferative and clonogenic capacity of umbilical cord stem cells.

Transfus Apher Sci 2006 Oct 11;35(2):119-23. Epub 2006 Oct 11.

Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Wayne State University, Hutzel Women's Hospital, Box #4, 3990 John R., Detroit, MI 48201, USA.

Possible effects of the ABO blood group on the proliferative and self-renewal capacity of umbilical cord CD34+ cells were evaluated. A, B and O (all Rh D+) CD34+ cells isolated from three placental blood samples were cultured in four platforms with hematopoietic growth factors on a 3-dimensional biocompatible matrix. Results from this study suggest that proliferation of CD34+ cells with the O phenotype may be greater than that of cells with the A or B phenotypes. Further ex vivo studies are required to confirm this finding and to determine the effect of the number and type of other genetically determined cell surface antigens on the capacity of hematopoietic stem cells to respond to cytokines. In addition, clinical studies aimed at determining if the CD34+ donor blood group affects the time to functional hematological reconstitution are recommended.
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http://dx.doi.org/10.1016/j.transci.2006.05.012DOI Listing
October 2006

Prenatal diagnosis of FRA10A: a case report and literature review.

Am J Med Genet A 2005 Jul;136(1):63-5

Department of Obstetrics and Gynecology, Division of Reproductive Genetics, Fetal Medicine and Ultrasound, Texas Tech University Health Science Center, Amarillo, Texas 79106, USA.

We report on the prenatal diagnosis of a familial fra10(q23)/del(10)(q23) detected after cellular cultures in non-folic deprived medium.
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http://dx.doi.org/10.1002/ajmg.a.30093DOI Listing
July 2005

Immunological changes after highly active antiretroviral therapy with lopinavir-ritonavir in heavily pretreated HIV-infected children.

AIDS Res Hum Retroviruses 2005 May;21(5):398-406

Laboratorio de Inmuno-Biología Molecular, Hospital General Universitario Gregorio Marañón, Madrid, Spain.

We evaluated the effect of salvage antiretroviral therapy with lopinavir/ritonavir (LPV/r) on the immune system of heavily antiretroviral pretreated HIV-infected children. We carried out a longitudinal study in 20 antiretroviral experienced HIV-infected children to determine the changes in several immunological parameters (T cell subsets, thymic function) every 3 months during 18 months of follow-up on salvage therapy with LPV/r. Statistical analyses were performed with the Wilcoxon test, taking as a reference the basal value at the entry in the study. HIV-infected children showed an increase of CD4+ T cells, a decrease in CD8+ T cells, and an increase in T cell rearrangement excision circle (TRECs) levels. The percentage of HIV children with undetectable viral load (VL < or = 400 copies/ml) increased significantly (p = 0.007) and the percentage with SI viral phenotype decreased significantly (p = 0.002) at the end of the study. Thus, the viral phenotype changed to NSI/R5 after salvage therapy with LPV/r. Interestingly, we observed a significant decrease of memory (CD4+ CD45RO+) and a moderate decrease of activated (CD4+ HLA-DR+, CD4+ HLA-DR+CD38, CD4+, CD45RO+HLA-DR+) CD4+ T cells during the follow-up. On the other hand, memory (CD8+ CD45RO+ and CD8+ CD45RO+CD38+), activated (CD8+ HLA-DR+CD38+, CD8+ HLA-DR+, CD8+ CD38+), and effector (CD8+ CD57+, CD8+ CD28(-)CD57+) CD8+ T cells had a very significant decrease during follow-up. Our data indicate an immune system reconstitution in heavily pretreated HIV-infected children in response to salvage therapy with LPV/r as a consequence of a decrease in immune system activation and an increase in thymic function.
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http://dx.doi.org/10.1089/aid.2005.21.398DOI Listing
May 2005

[Changes in CD4+ and CD8+ T-cell subsets in HIV-infected children differently correlate with viral replication and thymic function].

Med Clin (Barc) 2004 Oct;123(14):527-31

Laboratorio de Inmunobiología Molecular, Hospital General Universitario Gregorio Marañón, Madrid, Spain.

Background And Objective: We intended to study the relationship between T-cell subsets with plasmatic detectable viral load (VL) and T-receptor excision circles (TREC).

Patients And Method: Twenty HIV-infected children on highly active antiretroviral therapy (HAART) were recruited in a 1-year longitudinal retrospective study. We analyzed the relationship between changes in peripheral blood T-cell subsets, VL and TREC markers by lineal regression.

Results: Memory and activated CD4+ T-cells increases had a negative association with log10 TRECs increases. However, naive CD4+ T-cells increases had a positive association with log10 TRECs increases. In contrast, memory, activated and effector CD8+ T-cells increases positively correlated with log10 VL increases. On the other hand, naive CD8+ T-cells increases had a negative association with log10 VL increases.

Conclusions: CD4+ and CD8+ T-cells subsets change in a different way as a response to the changes produced by HAART in HIV vertically infected children. CD4+ T-cells are more dependent on thymic function and CD8+ T-cells are more dependent on viral replication. Thus, the decline in cellular activation would allow the production of more naive T-cells by the thymus.
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http://dx.doi.org/10.1016/s0025-7753(04)74585-6DOI Listing
October 2004

Immunity in HIV-1-infected adults with a previous state of moderate-severe immune-suppression and more than 500 CD4+ T cell after highly active antiretroviral therapy.

J Clin Immunol 2004 Jul;24(4):379-88

Laboratorio de Immuno-Biología Molecular, Hospital General Universitario Gregorio Marañón, C/Doctor Esquerdo 46, 28007 Madrid, Spain.

We evaluated phenotypic and functional parameters of immune restoration of 27 HIV-infected patients on highly active antiretroviral therapy (HAART) (HIV-cases) with HIV-RNA levels below detectable limits at least during 18 months, and CD4+ cell per microliter higher than 500 at the moment of the study and lower than 300 anytime before. These patients were compared with 11 HIV-controls that never had less than 500 CD4+ cell per microliter and 20 healthy-controls (HIV seronegative subjects) in a cross-sectional study. HIV-cases had lower counts of naïve CD4+ than HIV-controls and healthy-controls. HIV-patients (both HIV-cases and HIV-controls) showed higher values of naïve and memory CD8+ counts than healthy-controls. TREC-bearing cell levels were significantly lower in HIV-cases than in healthy-controls. Peripheral blood mononuclear cells (PBMC) cultures, HIV-cases had lower values in proliferation to streptokinase (SK) and tetanus toxin (TT) than in healthy-controls. HIV-cases had lower IFN-gamma and higher IL-5 production with pokeweed than healthy-controls ( P < 0.01). However, IL-5 production of HIV-cases after TT stimulation was lower than in HIV-controls and healthy-controls. Total IgG and IgG1 levels were significantly higher in HIV-cases than in HIV-controls and healthy-controls. Also, IgM levels were significantly higher in HIV-cases than in healthy-controls. Nevertheless, IgG2 levels were significantly lower in HIV-cases and HIV-controls than in healthy-controls. The levels of specific Igs antipneumococcal capsular polysaccharide and TT were significantly lower in HIV-cases than in healthy-controls. HIV-patients with a previous state of severe-moderate immunosuppression normalizing their CD4+ counts have a incomplete immune reconstitution after HAART. Long-term consequences of this subclinical immune deficiency remain to be determined.
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http://dx.doi.org/10.1023/B:JOCI.0000029112.82425.59DOI Listing
July 2004

Virological phenotype switches under salvage therapy with lopinavir-ritonavir in heavily pretreated HIV-1 vertically infected children.

AIDS 2004 Jan;18(2):247-55

Laboratorio de Inmuno-Biología Molecular and Servicio de Pediatría, Hospital General Universitario Gregorio Marañón, Madrid, Spain.

Objective: To investigate the effects of salvage therapy with lopinavir-ritonavir on HIV-1 phenotype in heavily antiretroviral experienced HIV-infected children.

Design: Twenty antiretroviral experienced HIV-infected children were studied during a mean of time of 16.1 months from initiation of the treatment with lopinavir-ritonavir.

Methods: Besides CD4 T cells, viral load and clinical status, we analyzed 91 serial viral isolates to study the phenotype, and biological clones derived from co-cultivation techniques.

Results: We observed an increase in CD4 T cells, a statistically significant decrease in viral load and clinical benefits from 3 months after treatment. Ninety per cent of children had SI/X4 bulk isolates in peripheral blood mononuclear cells at study entry. The viral phenotype changed to non syncitium-inducing (NSI)/R5 in 94% of the children after a mean of 5.7 months (95% confidence interval, 2.1-9.3 months) of salvage therapy. The remaining 10% of children had NSI/R5 isolates at entry and at all follow-up study. Similar results were found at the clonal level. Thus, at study entry in PBMC of three children with bulk syncitium-inducing (SI) phenotype, we recovered 65 biologic clones, 56 being SI and nine NSI. After salvage therapy bulk isolates changed to NSI and of 40 biologic clones recovered only five were SI and the rest were NSI.

Conclusions: Our data suggest that lopinavir-ritonavir salvage therapy led not only to a viral load decrease but also to a phenotypic change. X4 virus appeared to be preferentially suppressed. Shifts in co-receptor usage may thereby contribute to the clinical efficacy of anti-HIV drugs in vertically infected infants.
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http://dx.doi.org/10.1097/00002030-200401230-00014DOI Listing
January 2004

Characterizing the immune system after long-term undetectable viral load in HIV-1-infected children.

J Clin Immunol 2003 Jul;23(4):279-89

Laboratorio de Inmuno-Biología Molecular, Hospital General Universitario Gregorio Marañón, Madrid, Spain.

Thirty two HIV-infected children, on highly active antiretroviral therapy (HAART) and > 500 CD4+ T cells/mm3, were rated according to the time-course of viral load (VL) during the whole follow-up period (> 18 months) in a longitudinal retrospective study. (a) uVL group: 15 children with VL below 400 copies/mL; (b) dVL group: 17 children with higher VL. The uVL group showed higher memory (CD4+CD45RO+) T cells than did dVL group, and higher number of memory activated CD4+CD45RO+HLA-DR+ than did control group (healthy age-matched uninfected children), whereas CD4+CD45RA(hi)+CD62L+ was similar. However, TCR rearrangement excision circles (TRECs) were higher in uVL group than in dVL group. uVL Group showed CD8+CD45RO+ and CD8+CD45RO+CD38- higher number than the control group, but lower than the dVL group. The percentage of CD8+CD45RA(hi)+CD62L+, CD8+CD45RA+, CD8+CD62L-, and CD8+CD28+ was higher in uVL group than in dVL group, and lower than in control group. The uVL group showed higher number of activated (HLA-DR+CD38+, HLA-DR+, HLA-DR+CD38-) CD4+ T cells and lower percentages of CD4+HLA-DR-CD38+ than dVL group. In activated CD8- T cell, the uVL group had lower CD8+HLA-DR+CD38+, CD8+HLA-DR+, and CD8+CD38+ than the dVL group. Preeffector (CD8+CD57-CD28- and CD8+CD45RA-CD62L-) T cells were lower in the uVL group than in dVL group. In the effector (CD8+CD57+, CD8+CD57+CD28-, and CD8+CD45RA+CD62L-) T cells, HIV-infected-children had higher values than control group. HIV-infected-children who respond to HAART had TRECs reconstitution, decreased immune activation, and lower effector CD8+ T cells. Moreover, successful HAART allow the increment of activated CD4+ T cells.
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http://dx.doi.org/10.1023/a:1024536816684DOI Listing
July 2003