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1.
Neuroradiology ; 66(3): 389-398, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38114794

ABSTRACT

PURPOSE: MELAS syndrome is a genetic disorder caused by mitochondrial DNA mutations. We previously described that MELAS patients had increased CSF glutamate and decreased CSF glutamine levels and that oral glutamine supplementation restores these values. Proton magnetic resonance spectroscopy (1H-MRS) allows the in vivo evaluation of brain metabolism. We aimed to compare 1H-MRS of MELAS patients with controls, the 1H-MRS after glutamine supplementation in the MELAS group, and investigate the association between 1H-MRS and CSF lactate, glutamate, and glutamine levels. METHODS: We conducted an observational case-control study and an open-label, single-cohort study with single-voxel MRS (TE 144/35 ms). We assessed the brain metabolism changes in the prefrontal (PFC) and parieto-occipital) cortex (POC) after oral glutamine supplementation in MELAS patients. MR spectra were analyzed with jMRUI software. RESULTS: Nine patients with MELAS syndrome (35.8 ± 3.2 years) and nine sex- and age-matched controls were recruited. Lactate/creatine levels were increased in MELAS patients in both PFC and POC (0.40 ± 0.05 vs. 0, p < 0.001; 0.32 ± 0.03 vs. 0, p < 0.001, respectively). No differences were observed between groups in glutamate and glutamine (Glx/creatine), either in PFC (p = 0.930) or POC (p = 0.310). No differences were observed after glutamine supplementation. A positive correlation was found between CSF lactate and lactate/creatine only in POC (0.85, p = 0.003). CONCLUSION: No significant metabolite changes were observed in the brains of MELAS patients after glutamine supplementation. While we found a positive correlation between lactate levels in CSF and 1H-MRS in MELAS patients, we could not monitor treatment response over short periods with this tool. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04948138; initial release 24/06/2021; first patient enrolled on 1/07/2021. https://clinicaltrials.gov/ct2/show/NCT04948138.


Subject(s)
Glutamine , MELAS Syndrome , Humans , Glutamine/metabolism , MELAS Syndrome/diagnostic imaging , MELAS Syndrome/drug therapy , MELAS Syndrome/metabolism , Creatine/metabolism , Case-Control Studies , Cohort Studies , Magnetic Resonance Spectroscopy/methods , Glutamic Acid/metabolism , Proton Magnetic Resonance Spectroscopy/methods , Lactates , Dietary Supplements
2.
J Environ Manage ; 348: 119069, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-37820434

ABSTRACT

Surface water (SW) quality is particularly vulnerable to increased concentrations of nutrients, and this issue may be exacerbated by climate change. Knowledge of the effects of temperature and rainfall on SW quality is required to take the necessary measures to achieve good SW status in the future. To address this, the aims of this study were threefold: (1) to assess how a changing climate may alter the nitrate, ammonium, phosphorus and biological oxygen demand status (BOD5) of SW; (2) assess the relationship between water quality and flow; and (3) simulate diffuse and point source pollution reduction scenarios in the Júcar River Basin District in the Mediterranean region. A regionalised long-term climate scenario was used following one Representative Concentration Pathway (RCP8.5) with the data incorporated into the coupling of hydrological and water quality models. According to these climate change scenarios, SW with poor nitrate, ammonium, phosphorus and BOD5 status are expected to increase in the future by factors of 1.3, 1.9, 4 and 4, respectively. Furthermore, median ammonium and phosphorus concentration may be doubled in months with low flows. Additional measures are required to maintain current status in the water bodies, and it is necessary to reduce at least 25% of diffuse nitrate pollution, and 50% of point loads of ammonium, phosphorus, and BOD5.


Subject(s)
Ammonium Compounds , Water Quality , Rivers , Climate Change , Nitrates , Phosphorus/analysis
3.
Urolithiasis ; 51(1): 83, 2023 May 30.
Article in English | MEDLINE | ID: mdl-37249658

ABSTRACT

Our objective was to improve the results of extracorporeal shock waves lithotripsy using hydroxycitric acid (HCA) like adjuvant therapy. Double blind randomized clinical trial using hydroxycitric acid versus placebo (ID NCT05525130). Multicenter study of adjuvant exposure to a food supplement with hydroxycitric acid (HCA), vs. placebo in patients with calcium oxalate and calcium phosphate lithiasis with indication for extracorporeal shock wave lithotripsy (ESWL). 81 patients were included in the study to compare the effect of HCA versus placebo. Stone fragmentation, the main efficacy variable. Other variables analyzed were stone size, Hounsfield Unit Stone and tolerability. Statistical study with SPSS, statistical significance p ≤ 0.05. Eighty-one patients were included, 40 in the intervention group with HCA and 41 in the control group with placebo. The average stone area was 174,36 mm2 (SD: 32,83 mm2) and the average hardness was 1128,11 (SD: 257,65), with no statistically significant differences between groups. Significant statistical differences were obtained in the analysis of the population by intention to treat and by protocol of the main variable, no fragmentation vs. fragmentation where 100% of the patients, who were given ESWL and took HCA, presented fragmentation while 17% of the patients with placebo did not reach fragmentation (p = 0.03). The adjuvant use of HCA in patients for whom ESWL has been indicated, facilitates stone fragmentation in all cases, which is not achieved in up to 17% of the patients who did not use HCA. We recommend the use of HCA in patients prior to shock wave treatment to improve their fragmentation in calcium stones.


Subject(s)
Kidney Calculi , Lithotripsy , Humans , Calcium , Lithotripsy/adverse effects , Lithotripsy/methods , Citrates , Kidney Calculi/therapy , Treatment Outcome
4.
J Cancer Res Clin Oncol ; 149(7): 2855-2882, 2023 Jul.
Article in English | MEDLINE | ID: mdl-35790560

ABSTRACT

PURPOSE: Our objectives were to analyze the use of complementary and alternative medicine (CAM) in cancer patients and to describe the incidence and characteristics of interactions between CAM and antineoplastic agents. METHODS: We performed an observational study in cancer outpatients at a university hospital. Variables were collected through a 22-item questionnaire. Potential interactions between CAM and antineoplastic agents were analyzed using the Lexicomp®, the About Herbs®, and the summary of product characteristics. Mechanism of action, reliability, and the potential clinical effect of interactions were analyzed. RESULTS: The study population comprised 937 patients, of whom 65% used CAM (70.6% herbal products, 25.8% dietary supplements, and 3.6% homeopathy). Female sex, younger age, and breast cancer were associated with more frequent use of CAM. The primary source of information about CAM was friends and family (43.5%). A total of 335 (57.1%) patients did not tell their doctor that they took CAM. The five most common CAM were chamomile, green tea, pennyroyal mint, linden, and rooibos. At least one interaction between CAM and antineoplastic agents was reported by 65.0% of CAM users (33.9% of all patients). Depending on the mechanism of action, 80% of CAM diminished the metabolism of the antineoplastic agents. CONCLUSION: Our results reveal a high incidence of interactions between CAM and antineoplastic agents. The most frequent CAM were herbal products. Family and friends were the primary sources of information that led patients to start taking CAM, and more than half of the patients did not tell their doctor that they were taking CAM.


Subject(s)
Antineoplastic Agents , Breast Neoplasms , Complementary Therapies , Humans , Female , Reproducibility of Results , Antineoplastic Agents/therapeutic use , Breast Neoplasms/drug therapy , Dietary Supplements , Surveys and Questionnaires
5.
Eur J Neurol ; 30(2): 538-547, 2023 02.
Article in English | MEDLINE | ID: mdl-36334048

ABSTRACT

BACKGROUND AND PURPOSE: Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome is a genetically heterogeneous disorder caused by mitochondrial DNA mutations. There are no disease-modifying therapies, and treatment remains mainly supportive. It has been shown previously that patients with MELAS syndrome have significantly increased cerebrospinal fluid (CSF) glutamate and significantly decreased CSF glutamine levels compared to controls. Glutamine has many metabolic fates in neurons and astrocytes, and the glutamate-glutamine cycle couples with many metabolic pathways depending on cellular requirements. The aim was to compare CSF glutamate and glutamine levels before and after dietary glutamine supplementation. It is postulated that high-dose oral glutamine supplementation could reduce the increase in glutamate levels. METHOD: This open-label, single-cohort study determined the safety and changes in glutamate and glutamine levels in CSF after 12 weeks of oral glutamine supplementation. RESULTS: Nine adult patients with MELAS syndrome (66.7% females, mean age 35.8 ± 3.2 years) were included. After glutamine supplementation, CSF glutamate levels were significantly reduced (9.77 ± 1.21 vs. 18.48 ± 1.34 µmol/l, p < 0.001) and CSF glutamine levels were significantly increased (433.66 ± 15.31 vs. 336.31 ± 12.92 µmol/l, p = 0.002). A side effect observed in four of nine patients was a mild sensation of satiety. One patient developed mild and transient elevation of transaminases, and another patient was admitted for an epileptic status without stroke-like episode. DISCUSSION: This study demonstrates that high-dose oral glutamine supplementation significantly reduces CSF glutamate and increases CSF glutamine levels in patients with MELAS syndrome. These findings may have potential therapeutic implications in these patients. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT04948138. Initial release 24 June 2021, first patient enrolled 1 July 2021. https://clinicaltrials.gov/ct2/show/NCT04948138.


Subject(s)
Acidosis, Lactic , MELAS Syndrome , Stroke , Adult , Female , Humans , Male , Cohort Studies , Dietary Supplements , Glutamic Acid/therapeutic use , Glutamine/therapeutic use , MELAS Syndrome/drug therapy , MELAS Syndrome/genetics , MELAS Syndrome/metabolism
6.
Eur J Clin Nutr ; 76(9): 1343-1346, 2022 09.
Article in English | MEDLINE | ID: mdl-35194197

ABSTRACT

The Epi-GEICAM study comprises 1017 invasive BC cases matched with controls of similar age (49 ± 9 years) and residence. Diet and OO consumption were collected through a validated food frequency questionnaire. 75% of women referred OO, common (refined) or virgin, as the main fat source. Using conditional logistic regression models, we compared different scenarios of type and frequency of OO consumption, using as reference those women not always using OO for the three culinary practices (seasoning, cooking, and frying) and adding <2 tablespoons (tbsps.) per day during the meal to bread, salad, or dishes. A substantial inverse association was observed in those women always using VOO for the three culinary practices and consuming ≥2 tbsps. of OO per day during meals (adjusted OR, 0.72; 95% CI: 0.51, 1.03; P = 0.07). Potential benefits from OO consumption, at least as regards the protection provided for BC, could be mostly conferred with VOO, and when its consumption is high.


Subject(s)
Breast Neoplasms , Adult , Breast Neoplasms/prevention & control , Case-Control Studies , Cooking , Diet , Female , Humans , Middle Aged , Olive Oil , Plant Oils
7.
Arch Esp Urol ; 74(5): 489-493, 2021 Jun.
Article in Spanish | MEDLINE | ID: mdl-34080568

ABSTRACT

INTRODUCTION: The nutritional supplement called Fagolitos plus® contains hydroxycitric acid as main component, in addition to zinc, magnesium, vitamin A and vitamin B6. It is necessary to study new molecules as chemolytic treatment in calcium lithiasis or that facilitate its fragmentation with the help of other instrumental treatments. OBJECTIVE: The objective of this study is to evaluate the effectiveness of the combined treatment of Fagolitos plus® and extracorporeal lithotripsy in the fragmentation of the lithiasis. MATERIAL AND METHODS: Retrospective case-control study includes 88 patients with lithiasis. Group 1: Treated with 1 session of extracorporeal lithotripsy and Fagoliths plus®. Group 2: Treated with 1 session of extracorporeal lithotripsy. The variables analyzed were: Age, sex, body mass index, maximum diameter of the stone, area of the stone, hounsfield units of the stone measured by axial tomography, location of the stone, result after 1 session of extracorporeal wave lithotripsy shock [complete fragmentation, partial fragmentation (presence of a fragment greater than 5 mm) and absence of fragmentation (same size of the lithiasis)], adverse effects that occurred after taking Fagolitos plus®, days of treatment with Fagolitos plus® and energy shock wave applied to lithiasis. Results were analyzed with SPSS 20.0, p≤0.05. RESULTS: The mean age of the patients included in the study is 53.81 ± 12.62 years in group 1 compared to 56.53 ± 12.37 years in group 2, p=0.31. According to the distribution by sex, there were no statistically significant differences (p=0.5), including 24 men and 24 women in group 1 and 23 men and 17 women in group 2. The mean of body mass index of the patients in group 1 was 28.39 ± 2.27 kg/m2 in group 1 versus 28.39 ± 3.03 kg/m2 in group 2, p=0.9. The maximum diameter of the stone was 11.5 ± 3.91 mm in group 1 compared to 13.15 ± 5.49 mm in group 2, p=0.1. The area of the lithiasis measured by tomography was 104.74 ± 70.56 mm2 in group 1 compared to 141.91 ± 80.95 mm2 in group 2, p=0.3. The Hounsfield units measured by tomography of the lithiasis in group 1 was 1061.98 ± 213.68 compared to 1143.15 ± 172.24 in group 2, p=0.06. Relation to fragmentation, complete fragmentation was observed in 66.7% of group 1 patients, compared to 41% of group 2 patients (p=0.02), between 20-30 days after the first session of Extracorporeal Lithotripsy evaluated by means of a simple X-ray of the Abdomen. CONCLUSIONS: The administration of Fagolitos plus® concomitant to extracorporeal lithotripsy could increase its effectiveness in lithiasis fragmentation, requiring clinical trials and prospective studies to confirm these findings.


INTRODUCCIÓN: El complemento nutricional denominado Fagolitos plus® contiene como principal componente ácido hidroxicítrico, además de zinc, magnesio, vitamina A y vitamina B6. Es necesario estudiar nuevas moléculas como tratamiento quimiolítico en litiasis cálcica o que faciliten su fragmentación con la ayuda de otros tratamientos instrumentales. OBJETIVO: El objetivo de este estudio es evaluar la efectividad del tratamiento combinado de Fagolitos plus® y Litotricia extracorpórea en la fragmentación de la litiasis.MATERIAL Y MÉTODOS: Estudio retrospectivo de casos y controles, incluye 88 pacientes con litiasis. Grupo 1: Tratados con 1 sesión de litotricia extracorpórea y Fagolitos plus®. Grupo 2: Tratados con 1 sesión de litotricia extracorpórea. Las variables analizadas fueron: Edad, sexo, índice de masa corporal, diámetro máximo de la litiasis, área de la litiasis, unidades hounsfield de la litiasis medida por Tomografía axial, localización de la litiasis, resultado tras 1 sesión de Litotricia extracorpórea por ondas de choque [fragmentación completa, fragmentación parcial (presencia de un fragmento mayor a 5 mm) y ausencia de fragmentación (mismo tamaño de la litiasis)], efectos adversos acontecidos tras la toma de Fagolitos plus®, días de tratamiento con Fagolitos plus® y energía de ondas de choque aplicada a la litiasis. Se analizaron resultados con SPSS 20.0, p≤0,05. RESULTADOS: La edad media de los pacientes incluidos en el estudio es de 53,81 ± 12,62 años en el grupo 1 frente a 56,53 ± 12,37 años en el grupo 2, p=0,31. Según la distribución por sexos, tampoco existen diferencias estadísticamente significativas (p=0,5), incluyendo 24 hombres y 24 mujeres en el grupo 1 y 23 hombres y 17 mujeres en el grupo 2. El índice de masa corporal medio de los pacientes del grupo 1 fue de 28,39 ± 2,27 kg/m2 en el grupo 1 frente a 28,39 ± 3,03 kg/m2 en el grupo 2, p=0,9. El diámetro máximo de la litiasis fue de 11,5 ± 3,91 mm en el grupo 1 frente a 13,15 ± 5,49 mm en el grupo 2, p=0,1. El área de la litiasis medida por tomografía computarizada fue de 104,74 ± 70,56 mm2 en el grupo 1 frente a 141,91 ± 80,95 mm2 en el grupo 2, p=0,3. Las unidades Hounsfield medidas por tomografía de la litiasis en el grupo 1 fue de 1061,98 ± 213,68 frente a 1143,15 ± 172,24 en el grupo 2, p=0,06. En relación con la fragmentación, se observó fragmentación completa en el 66,7% de los pacientes del grupo 1, frente al 41% de los pacientes del grupo 2 (p=0,02) entre 20-30 días tras la primera sesión de Litotricia Extracorpórea evaluado mediante Radiografía simple de Abdomen. CONCLUSIONES: La administración de Fagolitos plus® concomitante a la Litotricia extracorpórea podría aumentar su efectividad en la fragmentación de la litiasis, siendo necesarios ensayos clínicos y estudios prospectivos que confirmen estos hallazgos.


Subject(s)
Kidney Calculi , Lithotripsy , Adult , Aged , Case-Control Studies , Female , Humans , Kidney Calculi/diagnostic imaging , Kidney Calculi/therapy , Male , Middle Aged , Prospective Studies , Retrospective Studies , Treatment Outcome
8.
Breast Cancer Res Treat ; 176(2): 377-386, 2019 Jul.
Article in English | MEDLINE | ID: mdl-31041683

ABSTRACT

PURPOSE: EndoPredict (EPclin) is a prognostic test validated to inform decisions on adjuvant chemotherapy to endocrine therapy alone for patients with oestrogen receptor-positive, HER2-negative breast cancer. Here, we determine the performance of EPclin for estimating 10-year distant recurrence-free interval (DRFI) rates for those who received adjuvant endocrine therapy (ET) alone compared to those with chemotherapy plus endocrine therapy (ET + C). METHODS: A total of 3746 women were included in this joint analysis. 2630 patients received 5 years of ET alone (ABCSG-6/8, TransATAC) and 1116 patients received ET + C (GEICAM 2003-02/9906). The primary objective was to evaluate the ability of EPclin to provide an estimate of the 10-year DR rate as a continuous function of EPclin separately for ET alone and ET + C. Cox proportional hazard models were used for these analyses. RESULTS: EPclin was highly prognostic for DR in women who received ET alone (HR 2.79 (2.49-3.13), P < 0.0001) as well as in those who received ET + C (HR 2.27 (1.99-2.59), P < 0.0001). Women who received ET + C had significantly smaller increases in 10-year DR rates with the increasing EPclin score than those receiving ET alone (EPclin = 5; 12% ET + C vs. 20% ET alone). We observed a significant positive interaction between EPclin and treatment groups (P-interaction = 0.022). CONCLUSIONS: In this comparative non-randomised analysis, the rate of increase in DR with EPclin score was significantly reduced in women who received ET + C versus ET alone. Our indirect comparisons suggest that a high EPclin score can predict chemotherapy benefit in women with ER-positive, HER2-negative disease.


Subject(s)
Antineoplastic Agents, Hormonal/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Aged , Breast Neoplasms/metabolism , Chemotherapy, Adjuvant , Clinical Trials as Topic , Combined Modality Therapy , Cyclophosphamide/therapeutic use , Doxorubicin/therapeutic use , Female , Fluorouracil/therapeutic use , Humans , Kaplan-Meier Estimate , Middle Aged , Predictive Value of Tests , Prognosis , Proportional Hazards Models , Receptor, ErbB-2/metabolism , Receptors, Estrogen/metabolism , Retrospective Studies , Risk Assessment , Treatment Outcome
9.
FASEB J ; 33(6): 7168-7179, 2019 06.
Article in English | MEDLINE | ID: mdl-30848931

ABSTRACT

Polymerase γ catalytic subunit (POLG) gene encodes the enzyme responsible for mitochondrial DNA (mtDNA) synthesis. Mutations affecting POLG are the most prevalent cause of mitochondrial disease because of defective mtDNA replication and lead to a wide spectrum of clinical phenotypes characterized by mtDNA deletions or depletion. Enhancing mitochondrial deoxyribonucleoside triphosphate (dNTP) synthesis effectively rescues mtDNA depletion in different models of defective mtDNA maintenance due to dNTP insufficiency. In this study, we studied mtDNA copy number recovery rates following ethidium bromide-forced depletion in quiescent fibroblasts from patients harboring mutations in different domains of POLG. Whereas control cells spontaneously recovered initial mtDNA levels, POLG-deficient cells experienced a more severe depletion and could not repopulate mtDNA. However, activation of deoxyribonucleoside (dN) salvage by supplementation with dNs plus erythro-9-(2-hydroxy-3-nonyl) adenine (inhibitor of deoxyadenosine degradation) led to increased mitochondrial dNTP pools and promoted mtDNA repopulation in all tested POLG-mutant cells independently of their specific genetic defect. The treatment did not compromise POLG fidelity because no increase in multiple deletions or point mutations was detected. Our study suggests that physiologic dNTP concentration limits the mtDNA replication rate. We thus propose that increasing mitochondrial dNTP availability could be of therapeutic interest for POLG deficiency and other conditions in which mtDNA maintenance is challenged.-Blázquez-Bermejo, C., Carreño-Gago, L., Molina-Granada, D., Aguirre, J., Ramón, J., Torres-Torronteras, J., Cabrera-Pérez, R., Martín, M. Á., Domínguez-González, C., de la Cruz, X., Lombès, A., García-Arumí, E., Martí, R., Cámara, Y. Increased dNTP pools rescue mtDNA depletion in human POLG-deficient fibroblasts.


Subject(s)
DNA Polymerase gamma/deficiency , DNA, Mitochondrial/metabolism , Deoxyribonucleotides/pharmacology , Fibroblasts/metabolism , Adenine/analogs & derivatives , Adenine/pharmacology , Adult , Catalytic Domain/genetics , Cells, Cultured , DNA Polymerase gamma/genetics , DNA Replication/drug effects , DNA, Mitochondrial/genetics , Deoxyribonucleotides/metabolism , Ethidium/pharmacology , Female , Fibroblasts/drug effects , Genotype , Humans , Male , Mitochondria, Muscle/genetics , Models, Molecular , Mutation, Missense , Phenotype , Point Mutation , Protein Conformation , Real-Time Polymerase Chain Reaction , Sequence Deletion
10.
Hum Mutat ; 39(10): 1338-1343, 2018 10.
Article in English | MEDLINE | ID: mdl-30011114

ABSTRACT

McArdle disease is a disorder of muscle glycogen metabolism caused by mutations in the PYGM gene, encoding for the muscle-specific isoform of glycogen phosphorylase (M-GP). The activity of this enzyme is completely lost in patients' muscle biopsies, when measured with a standard biochemical test which, does not allow to determine M-GP protein levels. We aimed to determine M-GP protein levels in the muscle of McArdle patients, by studying biopsies of 40 patients harboring a broad spectrum of PYGM mutations and 22 controls. Lack of M-GP protein was found in muscle in the vast majority (95%) of patients, irrespective of the PYGM genotype, including those carrying missense mutations, with few exceptions. M-GP protein biosynthesis is not being produced by PYGM mutations inducing premature termination codons (PTC), neither by most PYGM missense mutations. These findings explain the lack of PYGM genotype-phenotype correlation and have important implications for the design of molecular-based therapeutic approaches.


Subject(s)
Genetic Association Studies , Glycogen Storage Disease Type V/genetics , Mutation, Missense , Adolescent , Adult , Aged , Alleles , Biopsy , Female , Genotype , Glycogen Phosphorylase, Muscle Form/genetics , Glycogen Storage Disease Type V/diagnosis , Humans , Male , Middle Aged , Protein Isoforms , Young Adult
11.
Ann Nucl Med ; 32(8): 568-572, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30051167

ABSTRACT

Large cell neuroendocrine carcinoma of the lung (LCNEC) is a high-grade, poorly differentiated tumor that typically does not express somatostatin receptors. Thus, it does not benefit from treatment with somatostatin analogs and peptide receptor radionuclide therapy (PRRT). The current study objective was to demonstrate that treatment with PRRT may be a valid option in neuroendocrine carcinomas with high expression of somatostatin receptors. This is a case report of a 58-year-old man who was diagnosed with LCNEC and received chemotherapy treatment with little benefit. Extensive hepatic and bone metastasis was detected on 111In-pentetreotide scintigraphy following high uptake of the radionuclide by the tumors. The patient benefitted from neuroendocrine treatment initially and from lutetium Lu 177 dotatate subsequently. A significant clinical and radiological response was observed, along with an improvement in quality of life. The use of PRRT is a valid alternative to chemotherapy in patients with LCNEC involving the expression of somatostin receptors.


Subject(s)
Lung Neoplasms/radiotherapy , Neuroendocrine Tumors/radiotherapy , Octreotide/analogs & derivatives , Organometallic Compounds/therapeutic use , Humans , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Grading , Neuroendocrine Tumors/pathology , Octreotide/therapeutic use , Quality of Life , Treatment Outcome
12.
Future Oncol ; 13(24): 2137-2149, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28758424

ABSTRACT

CDK4/6 inhibitors are a promising new class of drugs for hormone-receptor-positive breast cancer and have been shown to overcome and delay hormone resistance in advanced breast cancer. Ribociclib, a selective oral inhibitor of CDK4/6, was approved by the US FDA for first-line treatment of hormone-receptor-positive/HER2-negative metastatic breast cancer. This review summarizes the clinical evidence available for ribociclib, from preclinical data to the pivotal studies, with a special focus on toxicity and its management. In addition, this article reviews potential new combinations under study, as well as ongoing clinical trials both in the metastatic and early setting. Finally, this review compares ribociclib activity and toxicity with those of the drugs of the same class (palbociclib and abemaciclib).


Subject(s)
Aminopyridines/therapeutic use , Antineoplastic Agents/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Molecular Targeted Therapy , Protein Kinase Inhibitors/therapeutic use , Purines/therapeutic use , Aminopyridines/pharmacology , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Clinical Trials as Topic , Cyclin-Dependent Kinase 4/antagonists & inhibitors , Cyclin-Dependent Kinase 6/antagonists & inhibitors , Drug Evaluation, Preclinical , Female , Humans , Neoplasm Metastasis , Neoplasm Staging , Protein Kinase Inhibitors/chemistry , Protein Kinase Inhibitors/pharmacology , Purines/pharmacology , Receptor, ErbB-2/metabolism , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism
13.
Urol J ; 14(3): 3050-3053, 2017 May 23.
Article in English | MEDLINE | ID: mdl-28537041

ABSTRACT

PURPOSE: The aim of this study is to determine whether antibiotic prophylaxis is required in this outpatient procedure. MATERIALS AND METHODS: A non-randomised, prospective observational study that included 184 patients subjected to flexible cystoscopy divided into three groups: - Group 1:60 patients with prophylaxis of 500 mg of ciprofloxacin;- Group 2:62 patients with prophylaxis of 3 g of phosphomycin; and Group 3:62 without antibiotic prophylaxis. Prior to inclusion in the study, absence of infection was checked by means of a urine culture obtained 7 days before the procedure. An analysis was made of urinary infection after 7 days, the cystoscopy indications and its diagnosis, the presence of comorbidities, and the urinary symptoms during the following 7 days. RESULTS: The mean age of the patients in Group 1 was 65.3 (SD: 12.5) years, 66.7 (10.8) years in Group 2, and 66.9 (10.8) years in Group 3 (P = .7). Bacteriuria was present in 15% of the patients in Group 1, compared to 22.6% in Group 2, and 12.9% in Group 3, with the differences not statistically significant. In multivariate analysis, it was observed that there was no association with the appearance of bacteriuria between the groups for age (P = .8), diabetes (P = .2), smoking (P = .4), lower urinary tract symptoms (P = .7), or immunosuppression (P = .6). CONCLUSION: The use of ciprofloxacin or phosphomycin as prophylaxis does not appear to be indicated in flexible cystoscopy in our health area.


Subject(s)
Ambulatory Care/methods , Anti-Bacterial Agents/therapeutic use , Antibiotic Prophylaxis , Bacteriuria/prevention & control , Ciprofloxacin/therapeutic use , Fosfomycin/therapeutic use , Aged , Bacteriuria/etiology , Cystoscopy/adverse effects , Female , Humans , Male , Middle Aged , Prospective Studies
14.
Arch Esp Urol ; 69(9): 648-653, 2016 Nov.
Article in Spanish, English | MEDLINE | ID: mdl-27845696

ABSTRACT

OBJECTIVE: The goal of this study is to analyze whether there is a need for antibiotic prophylaxis in this outpatient procedure. METHODS: Prospective observational non-randomized study including 100 patients divided into two groups: - Group 1: 48 patients receiving 500 mg of ciprofloxacin prophylaxis 1 hour before urethrocystoscopy; - Group 2: 52 patients without antibiotic prophylaxis. Before inclusion of the patients in the study, we checked the absence of urinary tract infection by means of a urinalysis obtained 3 days before the procedure. We analyze: cystoscopy indication, cystoscopy results, presence of comorbidities, urinalysis 7 days after the procedure, and urinary symptoms within 7 days of the procedure. The statistical analysis was performed using SPSS 20.0 and the statistical significance was p=0.05. RESULTS: The average age of patients in group 1 was 66.7±12.4 versus 65.6±10.8 years in group 2 (p=0.6). There are no differences in the percentage of men/women included in the groups. 14% of patients of group 1 and 12% of group 2 presented bacteriuria, without showing any significant differences. In the multivariate study, it is observed that neither age, nor diabetes, smoking, lower urinary tract symptoms, nor immunosuppression are related with the onset of bacteriuria in the groups. CONCLUSION: We do not consider the use of ciprofloxacin as prophylaxis for flexible cystoscopy is appropriate in this area of health, since it does not reduce the presence of urinary infection or bacteriuria.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Antibiotic Prophylaxis , Ciprofloxacin/therapeutic use , Cystoscopy , Urinary Tract Infections/prevention & control , Aged , Cystoscopes , Equipment Design , Female , Humans , Male , Prospective Studies
15.
Arch. esp. urol. (Ed. impr.) ; 69(9): 648-653, nov. 2016. tab
Article in Spanish | IBECS | ID: ibc-157669

ABSTRACT

OBJETIVO: La uretrocistoscopia flexible es un procedimiento que se realiza de rutina en urología para el seguimiento de tumores vesicales y como diagnóstico en pacientes con síntomas del tracto urinario inferior y hematuria entre otra sintomatología. El objetivo de este estudio es analizar la necesidad o no de profilaxis antibiótica en este procedimiento ambulatorio. MÉTODOS: Estudio observacional prospectivo no aleatorizado en el que se incluyen 100 pacientes divididos en dos grupos: - Grupo 1: 48 pacientes con profilaxis de 500 mg de ciprofloxacino 1 h antes de la uretrocistoscopia; - Grupo 2: 52 pacientes sin profilaxis antibiótica. Previamente a la inclusión en el estudio se comprueba ausencia de infección urinaria mediante urocultivo obtenido 3 días antes del procedimiento. Se analiza indicación de cistoscopia, resultado de cistoscopia, presencia de comorbilidades, urocultivo a los 7 días, síntomas urinarios durante los 7 días siguientes. Análisis estadístico con SPSS 20.0 y significación estadística p≤0,05. RESULTADOS: La edad media de los pacientes del grupo 1 fue de 66,7±12,4 años versus 65,6±10,8 años del grupo 2 (p = 0,6). No hubo diferencias en el porcentaje de hombres/mujeres incluidos entre los grupos. El 14% de los pacientes del grupo 1 presentó bacteriuria frente al 12% del grupo 2, sin diferencias significativas. En el estudio multivariante, se observa que ni la edad, diabetes, tabaquismo, síntomas del tracto urinario inferior ni inmunosupresión se relacionan con la aparición de bacteriuria entre grupos. CONCLUSIÓN: El uso de ciprofloxacino como profilaxis en la cistoscopia flexible no lo consideramos indicado en nuestra área de salud, ya que no disminuye la presencia de infección urinaria o bacteriuria


OBJECTIVE: The goal of this study is to analyze whether there is a need for antibiotic prophylaxis in this outpatient procedure. METHODS: Prospective observational non-randomized study including 100 patients divided into two groups: - Group 1: 48 patients receiving 500 mg of ciprofloxacin prophylaxis 1 hour before urethrocystoscopy; - Group 2: 52 patients without antibiotic prophylaxis. Before inclusion of the patients in the study, we checked the absence of urinary tract infection by means of a urinalysis obtained 3 days before the procedure. We analyze: cystoscopy indication, cystoscopy results, presence of comorbidities, urinalysis 7 days after the procedure, and urinary symptoms within 7 days of the procedure. The statistical analysis was performed using SPSS 20.0 and the statistical significance was p≤0.05. RESULTS: The average age of patients in group 1 was 66.7±12.4 versus 65.6±10.8 years in group 2 (p = 0.6). There are no differences in the percentage of men/women included in the groups. 14% of patients of group 1 and 12% of group 2 presented bacteriuria, without showing any significant differences. In the multivariate study, it is observed that neither age, nor diabetes, smoking, lower urinary tract symptoms, nor immunosuppression are related with the onset of bacteriuria in the groups. CONCLUSION: We do not consider the use of ciprofloxacin as prophylaxis for flexible cystoscopy is appropriate in this area of health, since it does not reduce the presence of urinary infection or bacteriuria


Subject(s)
Humans , Cystoscopy/methods , Antibiotic Prophylaxis/methods , Ciprofloxacin/therapeutic use , Prospective Studies , Urinary Bladder Neoplasms/surgery , Bacteriuria/prevention & control , Urinary Tract Infections/prevention & control
16.
Nanoscale ; 8(32): 15041-7, 2016 Aug 11.
Article in English | MEDLINE | ID: mdl-27477118

ABSTRACT

We have undertaken a magnetic study on the oral biodistribution and biodegradation of nude maghemite nanoparticles of 10 nm average size (MNP) and probiotic bacteria, Lactobacillus fermentum, containing thousands of these same nanoparticles (MNP-bacteria). Using AC magnetic susceptibility measurements of the stomach, small intestine, cecum and large intestine obtained after rat sacrifice, and iron content determination by ICP-OES, we have monitored the biodistribution and biodegradation of the maghemite nanoparticles along the gastrointestinal tract, after oral administration of both MNP and MNP-bacteria. The results revealed that the amount of magnetic nanoparticles accumulated in intestines is sensibly higher when MNP-bacteria were administered, in comparison with MNP. This confirms our initial hypothesis that the use of probiotic bacteria is a suitable strategy to assist the magnetic nanoparticles to overcome the stomach medium, and to achieve their accumulation in intestines. This finding opens doors to different applications. Since iron absorption in humans takes place precisely in the intestines, the use of MNP-bacteria as an iron supplement is a definite possibility. We have actually illustrated how the administration of MNP-bacteria to iron-deficient rats corrects the iron levels after two weeks of treatment.


Subject(s)
Gastrointestinal Tract/metabolism , Iron/analysis , Magnetite Nanoparticles/analysis , Animals , Bacteria , Magnetics , Male , Probiotics , Rats , Rats, Wistar , Tissue Distribution
17.
Arch. esp. urol. (Ed. impr.) ; 69(5): 207-211, jun. 2016. tab
Article in Spanish | IBECS | ID: ibc-153096

ABSTRACT

OBJETIVO: La cistoscopia flexible es una técnica utilizada en el diagnóstico de la patología del tracto urinario inferior. El objetivo de este estudio es evaluar la eficacia del anestésico local intrauretral en la percepción del dolor en el paciente. MÉTODOS: Estudio observacional prospectivo no aleatorizado que incluye 142 hombres a los que se realiza cistoscopia flexible. Se dividen en dos grupos en función del uso o no de anestésico local intrauretral (Grupo 1: 70 hombres con anestésico intrauretral [lidocaína 2%]; Grupo 2: 72 hombres sin anestésico intrauretral). Se analiza escala visual analógica y cuestionario del dolor. Análisis estadístico con SPSS 17.0 y significación estadística p≤0,05. RESULTADOS: La edad media del grupo 1 fue de 64,7±10,3 años frente a 66,7±10,8 años en el grupo 2, sin diferencias significativas. La puntuación en la escala visual analógica en el grupo 1 fue 2,23±2,20 frente a 1,69±1,74 en el grupo 2 (p = 0,1). La intensidad del dolor total y actual en el cuestionario del dolor fue de 1,81 ± 0,87 y 1,66 ± 1,65, respectivamente, en el grupo 1 y de 1,72 ± 0,72 y 1,21±1,45, respectivamente, en el grupo 2 (no diferencias significativas). Tras dividir a los pacientes en función de una puntuación en la escala visual analógica ≤ 2, se observa que la causa que motivó la cistoscopia es un factor independiente asociado a la percepción del dolor, incrementando el riesgo de percibir más dolor en 1,89. CONCLUSIÓN: El uso de anestésico local como lubricante previo a cistoscopia flexible no parece disminuir el dolor y consideramos que no está indicado de rutina en esta técnica diagnóstica


OBJECTIVE: The aim of this study is to evaluate the efficacy of a local intraurethral anesthetic on the pain perceived by the patient during flexible cystoscopy. METHODS: An observational, prospective, nonrandomized, study was conducted on 142 males subjected to a flexible cystoscopy. The patients were divided into two groups: Group 1: 70 patients with intraurethral anesthetic (lidocaine 2%), and Group 2:72 patients without intraurethral anesthetic. The results were scored on a visual analog scale and a pain questionnaire and analyzed. The statistical analysis was performed using SPSS 17.0 and with a statistical significance of p ≤ 0.05. RESULTS: The mean age of Group 1 was 64.7 ± 10.3 years compared to 66.7 ± 10.8 years in Group 2, with no significant differences. The score on the visual analog scale in Group 1 was 2.23 ± 2.20 versus 1.69 ± 1.74 in Group 2 (p = 0.1). The overall and current pain intensity in the pain questionnaire was 1.81 ± 0.87 and 1.66 ± 1.65, respectively, in Group 1, and 1.72 ± 0.72 and 1.21 ± 1.45, respectively, in Group 2 (no significant differences). After dividing the patients into groups according to a visual analog scale score ≤ 2, it was observed that the cause that led to cystoscopy was an independent factor associated with the perception of pain, increasing the risk of perceiving more pain by 1.89. CONCLUSIÓN: The use of local anesthetic as a lubricant prior to flexible cystoscopy does not appear to reduce pain, and we consider that its routine use is not indicated


Subject(s)
Humans , Male , Middle Aged , Pain Perception , Cystoscopy/instrumentation , Cystoscopy/methods , Cystoscopy , Anesthesia, Local , Pain Measurement/instrumentation , Pain Measurement/methods , Urinary Tract , Urinary Tract/pathology , Prospective Studies , Surveys and Questionnaires , Pain Measurement , Pain Measurement/standards , Pain Measurement
18.
Arch Esp Urol ; 69(3): 117-20, 2016 Apr.
Article in Spanish | MEDLINE | ID: mdl-27068369

ABSTRACT

OBJECTIVE: To determine the importance of fasting calcium/creatinine ratio in patients with calcium stones and its relation with hypercalciuria and phospho-calcium metabolism. METHODS: Cross-sectional study including 143 patients divided into two groups according to fasting calcium/creatinine. Group 1: 66 patients (calcium/ creatinine<0.11); Group 2: 77 patients (calcium/ creatinine>0.11). A comparative study is performed between groups including phospho-calcium metabolism parameters and excretion of urinary lithogenic markers. Linear correlation studying calciuria and fasting calcium/ creatinine was performed. SPSS 17.0 statistical analysis software was used, considering p≤0.05. RESULTS: It is noteworthy that group 2 had increased 24 h urine calcium excretion in comparison to group 1 (229.3 vs 158.1; p=0.0001) and calcium/citrate (0.47 vs 0.34; p=0.001). There is a positive and significant correlation between calcium levels in 24 h urine and fasting calcium/creatinine (R=0.455; p=0.0001) and a cutoff is set at 0.127 (sensitivity 72%, specificity 66%) to determine hypercalciuria (>260 mg in 24 h). CONCLUSION: Increased fasting calcium/creatinine determines increased 24 hours calcium excretion, although the sensitivity and specificity to determine hypercalciuria is not high.


Subject(s)
Calcium/urine , Creatinine/urine , Hypercalciuria/etiology , Kidney Calculi/complications , Kidney Calculi/urine , Calcium/metabolism , Cross-Sectional Studies , Fasting , Female , Humans , Male , Middle Aged , Phosphorus/metabolism
19.
Med Sci Sports Exerc ; 48(4): 673-9, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26559449

ABSTRACT

McArdle disease is due to an inborn defect in the muscle isoform of glycogen phosphorylase (or "myophosphorylase"), the enzyme that catalyzes the first step of glycogenolysis. This condition is still not fully understood, and although advances in research would help patients immeasurably, these would also enhance our understanding of exercise metabolism. It has been 10 yr since the first published report demonstrating the benefits of regular aerobic exercise for these patients. However, misconceptions remain and the value of exercise prescription for patients with McArdle disease is still overlooked. Here, we review the role of exercise in McArdle disease with the aim to better inform health-care professionals and thus better serve the interests of patients. Recommendations for regular exercise together with preexercise nutrition in children and adult patients are also provided along with examples of exercise practice and its benefits.


Subject(s)
Exercise Therapy , Glycogen Storage Disease Type V/therapy , Nutritional Physiological Phenomena , Humans
20.
Rev Med Chil ; 143(8): 1001-4, 2015 Aug.
Article in Spanish | MEDLINE | ID: mdl-26436928

ABSTRACT

BACKGROUND: Flexible cystoscopy is a common test in clinical practice done with or without antibiotic prophylaxis. AIM: To evaluate the efficacy of antibiotic prophylaxis with ciprofloxacin to reduce the incidence of urinary infection. MATERIAL AND METHODS: Prospective, non-randomized observational study that included 60 patients divided into two groups. Group 1 received prophylactic ciprofloxacin 500 mg, one hour prior to the procedure and group 2 did not receive prophylaxis. The presence of bacteriuria, symptoms or signs of urinary infection or attending Emergency rooms or primary care for these symptoms were recorded during the seven days after the cystoscopy. RESULTS: In groups 1 and 2, four and one patients had a positive urine culture, respectively. Only one patient in group 1 consulted in primary care for symptoms. No significant differences in symptoms or signs of urinary infection between groups were observed. CONCLUSIONS: In this group of patients, antibiotic prophylaxis with ciprofloxacin 500 mg prior to cystoscopy had no benefit.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Antibiotic Prophylaxis , Bacteriuria/prevention & control , Ciprofloxacin/therapeutic use , Cystoscopy/adverse effects , Urinary Tract Infections/prevention & control , Aged , Bacteriuria/microbiology , Female , Humans , Male , Middle Aged , Prospective Studies , Urinary Tract Infections/microbiology
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