Lopez, R. (Rafael)
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- Association of increased erythrocyte Na+/H+ exchanger with renal Na+ retention in patients with essential hypertension(Nature publishing group, 1995) Arrazola, A. (Arantxa); Fortuño, A. (Ana); Diez-Martinez, J. (Javier); Gomez-Alamillo, C. (Carlos); Alonso, A. (Amalia); Garciandia, A. (Ana); Lopez, R. (Rafael)The goal of this study was to investigate the activity of the Na+/H+ exchanger in erythrocytes of patients with essential hypertension and its relation with urinary Na+ excretion. The study was performed in cells from 27 untreated hypertensive patients and 30 normotensive controls with similar age and sex distribution. All subjects were studied after 4 days on a controlled Na+ diet (145 mmol/day). The activity of the Na+/H+ exchanger was determined by acidifying cell pH and measuring the initial rate of the net Na(+)-dependent H+ efflux. The activity of the Na+/H+ exchanger was higher in hypertensive patients than in controls (301 +/- 45 v 162 +/- 23 mmol/L cells/h, mean +/- SEM; P < .01). With the upper limit of the normotensive population as a cut-off point (385 mmol/L cells/h), a subgroup of 12 hypertensive patients had an abnormally high activity of Na+/H+ exchanger. Compared with controls and with patients with normal exchanger activity, patients with increased exchanger activity were characterized by lower net (P < .01) and fractional (P < .05) Na+ excretion. The accumulative Na+ balance was higher (P < .01) in hypertensive patients with increased activity of the exchanger (39.90 +/- 3.47 mmol) than in the remaining hypertensive patients (0.59 +/- 6.96 mmol) or in the normotensive population (-5.71 +/- 6.12 mmol). After analyzing the relationship of renin activity with Na+ excretion it was observed that renin activity was inappropriately low in 9 (75%) patients with increased exchanger, in 6 (40%) patients with normal exchanger, and in 6 (20%) normotensives, these differences being significant (P<.01).
- Enhanced Na(+)-H+ exchanger activity and NHE-1 mRNA expression in lymphocytes from patients with essential hypertension(American heart association, 1995) Arrazola, A. (Arantxa); Fortuño, A. (Ana); Diez-Martinez, J. (Javier); Tisaire, J. (Javier); Garciandia, A. (Ana); Lopez, R. (Rafael); Bueno, J. (José)It has been demonstrated that the activity of the sodium-proton exchanger (NHE-1 isoform) is increased in lymphocytes and other blood cells from patients with essential hypertension. In the present study, we investigated whether an increased level of NHE-1-specific mRNA in lymphocytes from patients with essential hypertension would explain the enhanced transport activity. Twenty-two hypertensive patients and 21 normotensive subjects were studied. Basal cytosolic pH was measured by the pH-sensitive fluorescent probe 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein. Maximal sodium-proton exchange activity was determined by acidifying cell pH and measuring the initial rate of the net sodium-dependent proton efflux driven by an outward proton gradient. The transcript level of NHE-1 was measured by reverse transcription-polymerase chain reaction in comparison with a constitutively expressed reference gene (beta-actin). Intracellular pH was lower in hypertensive patients than normotensive subjects (7.34 +/- 0.01 versus 7.39 +/- 0.01, mean +/- SEM, P < .001). The maximal activity of the sodium-proton exchanger was higher in hypertensive patients than in normotensive subjects (1262 +/- 100 versus 881 +/- 56 mmol/L cells per hour, P < .01). NHE-1 mRNA was increased in hypertensive patients compared with normotensive subjects (ratio of NHE-1 mRNA to beta-actin mRNA, 0.16 +/- 0.01 versus 0.12 +/- 0.02, P < .05). These data suggest that the increased sodium-proton exchange activity in essential hypertension may be related to the de novo synthesis of exchanger protein.
- Angiotensin converting enzyme inhibition corrects Na+/H+ exchanger overactivity in essential hypertension(Nature publishing group, 1997) Fortuño, A. (Ana); Diez-Martinez, J. (Javier); Tisaire, J. (Javier); Lopez, R. (Rafael); Bueno, J. (José)In this study, we investigated whether antihypertensive treatment with the angiotensin converting enzyme inhibitor quinapril modifies Na+/H+ exchanger activity or NHE-1 (isoform of the exchanger) mRNA expression in lymphocytes from patients with essential hypertension. Thirty-three hypertensive patients and 27 normotensive subjects were studied. Maximal sodium-proton exchange activity was determined by acidifying cell pH and measuring the initial rate of the net sodium-dependent proton efflux driven by an outward proton gradient. The transcript level of NHE-1 was measured by reverse transcription-polymerase chain reaction in comparison with a constitutively expressed reference gene (beta-actin). With the 100% confidence (upper) limit of the normotensive population as a cutoff point, a subgroup of 11 hypertensive patients had an abnormally high lymphocyte Na+/H+ exchange activity (group A). The activity of the exchanger was within the normal range in the remaining patients (group B). After 6 months of quinapril treatment the activity of the exchanger decreased to normal values (P < .001) in patients from group A, but remained unchanged in patients from group B. The NHE-1 mRNA expression was not modified with treatment neither in patients from the group A, nor in patients from the group B. These results suggest that chronic angiotensin enzyme inhibition with quinapril abolishes Na+/H+ exchange overactivity present in lymphocytes from a subgroup of hypertensive patients. This effect appears to be independent of changes in the expression of the mRNA encoding for the NHE-1 isoform of the exchanger.
- Impact of the COVID-19 pandemic on the diagnosis and treatment of onco-hematologic patients: a discussion paper(2023) García-Gutiérrez, V. (Valentín); Trilla, A. (Antoni); Palomo, E. (Esteban); Ruiz-Galiana, J. (Julián); García-Sanz, R. (Ramón); Martin-Delgado, M.C. (Mari Cruz); Martínez, J. (Joaquin); Rodríguez-Lescure, Á. (Álvaro); Bouza, E. (Emilio); Tejerina-Picado, F. (Francisco); Pozo, J.L. (José Luis) del; Barragán, B. (Begoña); Guillem, V. (Vicente); Aragonés, N. (Nuria); Martín, M. (Miguel); Gracia, D. (Diego); Sureda-Balari, A. M. (Anna Maria); Zapatero, A. (Antonio); Lopez, R. (Rafael); Cámara, R. (Rafael) de la; San-Miguel, J.F. (Jesús F.); Alés, J.E. (José Enrique); Jiménez-Yuste, V. (Víctor)We do not know the precise figure for solid organ tumors diagnosed each year in Spain and it is therefore difficult to calculate whether there has been a decrease in cancer diagnoses as a consequence of the pandemic. Some indirect data suggest that the pandemic has worsened the stage at which some non-hematological neoplasms are diagnosed. Despite the lack of robust evidence, oncology patients seem more likely to have a poor outcome when they contract COVID-19. The antibody response to infection in cancer patients will be fundamentally conditioned by the type of neoplasia present, the treatment received and the time of its administration. In patients with hematological malignancies, the incidence of infection is probably similar or lower than in the general population, due to the better protective measures adopted by the patients and their environment. The severity and mortality of COVID-19 in patients with hematologic malignancies is clearly higher than the general population. Since the immune response to vaccination in hematologic patients is generally worse than in comparable populations, alternative methods of prevention must be established in these patients, as well as actions for earlier diagnosis and treatment. Campaigns for the early diagnosis of malignant neoplasms must be urgently resumed, post-COVID manifestations should be monitored, collaboration with patient associations is indisputable and it is urgent to draw the right conclusions to improve our preparedness to fight against possible future catastrophes.
- Palbociclib combined with endocrine therapy in heavily pretreated HR+/HER2(-) advanced breast cancer patients: Results from the compassionate use program in Spain (PALBOCOMP)(Elsevier, 2020) Manso, L. (Luis); Servitja, S. (Sónia); Llombart-Cussac, A. (Antonio); Bratos, R. (Raquel); Ruiz-Borrego, M. (Manuel); Gonzalez-Cao, M. (María); Echarri, M.J. (María J.); Gonzalez-Cortijo, L. (Lucía); Vega, E. (Estela); Gallegos, I. (Isabel); Hernando, B.A. (Blanca A.); Robles, C.E. (Carlos E.); Oliveira, M. (Mafalda); Galan, M. (María); Andres, R. (Raquel); Santisteban, M. (Marta); Alvarez-Busto, I. (Iñaki); Alés-Martínez, J.E. (José E.); Rodríguez, C.A. (C.A.); Echeverría, I. (Isabel); Moreno, F. (Fernando); Delgado-Mingorance, J. (Juan I.); Oltra, A. (Amparo); Blanch, S. (Salvador); Legeren, M. (Marta); Hernando, C. (Cristina); García-Garre, E. (Elisa); Aguirre, E. (Elena); Galve, E. (Elena); Ballesteros, A. (Ana); Reboredo, C. (Cristina); Lopez, R. (Rafael); Morales, S. (Serafín); Malón, D. (Diego); Cabrera, M.A. (Miguel A.)Background: This study evaluated efficacy and safety of palbociclib, a CDK4/6 inhibitor, in heavilypretreated hormone receptor-positive and human epidermal growth factor receptor 2-negative (HRþ/ HER2- ) metastatic breast cancer (mBC) patients during the compassionate use program in Spain from February 2015 to November 2017. Patients and methods: Patient data were collected retrospectively from 35 hospitals in Spain. Patients with HRþ/HER2- mBC who had progressed on 4 treatments for advanced disease were eligible. Results: A total of 219 patients received palbociclib in combination with aromatase inhibitors (110; 50.2%), fulvestrant (87; 39.7%), tamoxifen (8; 3.6%) or as single agent (10; 4.6%). Mean age of the patients was 58 years; 31 patients (16.1%) were premenopausal and 162 (83.9%) were postmenopausal at the beginning of treatment with palbociclib. Patients had received a median of 3 previous lines of endocrine therapy (ET) for advanced disease. Real-world tumor response (rwTR) and clinical benefit rate were 5.9% (n ¼ 13) and 46.2% (n ¼ 101), respectively. The median real world progression-free survival (rwPFS) was 6.0 months (95% CI 5.7e7.0) and the median overall survival was 19.0 months (95% CI 16.4e21.7). Subgroup analysis revealed a significant difference in median rwPFS in patients treated with palbociclib plus fulvestrant depending on the duration of prior treatment with fulvestrant monotherapy (>6 versus 6 months; HR 1.93, 95% CI 1.37e2.73, p < 0.001). The most frequently reported toxicities were neutropenia, asthenia, thrombopenia and anemia. Conclusions: Palbociclib can be an effective and safe treatment option in patients with heavily pretreated endocrine-sensitive mBC, especially in those with longer PFS to previous ET.