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1.
Article in English | MEDLINE | ID: mdl-38491935

ABSTRACT

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

2.
Arch Cardiol Mex ; 2024 Feb 15.
Article in Spanish | MEDLINE | ID: mdl-38359441

ABSTRACT

Chronic thromboembolic pulmonary hypertension (CTEPH) is a subtype of pulmonary hypertension characterized by the obstruction of pulmonary arteries secondary to chronic thromboembolism. Pulmonary thromboendarterectomy surgery (PTE) is the main treatment for patients with CTEPH, as it removes the chronic thrombi from the pulmonary arteries. Pulmonary reperfusion syndrome is a common complication of the surgery, which involves the development of pulmonary edema in the area where blood perfusion improves after the surgery. The incidence of this syndrome varies from 8 to 91% depending on the criteria used for diagnosis, and it is one of the most serious complications of pulmonary thromboendarterectomy. In such cases, circulatory support with extracorporeal membrane oxygenation (ECMO) has become a valuable therapeutic modality. We present the case of a 60-year-old woman with a history of acute pulmonary embolism due to deep vein thrombosis of the right pelvic limb who was diagnosed later with CTEPH who was admitted for scheduled surgical treatment involving bilateral PTE. However, during the immediate postoperative period, she developed cardiogenic shock and refractory hypoxemia secondary to pulmonary reperfusion syndrome following the surgical procedure. As a result, she required veno-venous ECMO circulatory support for 6 days, leading to resolution of the pulmonary condition and clinical improvement.


La hipertensión pulmonar tromboembólica crónica (HPTEC) es un subtipo de hipertensión pulmonar caracterizada por la obstrucción de las arterias pulmonares secundaria a tromboembolias crónicas. La cirugía de tromboendarterectomía pulmonar (TEAP) es el tratamiento principal para los pacientes con HPTEC, elimina los trombos crónicos de las arterias pulmonares. El síndrome de reperfusión pulmonar es una complicación común de la cirugía, se trata del desarrollo de edema pulmonar en el área en la que la perfusión sanguínea mejora después de la cirugía. La incidencia del síndrome varía del 8 al 91% según los criterios utilizados para diagnosticarlo y es una de las complicaciones más graves de la tromboendarterectomía pulmonar. En tales casos, el soporte circulatorio con oxigenación por membrana extracorpórea (ECMO) se ha convertido en una valiosa modalidad terapéutica. Presentamos el caso de una paciente de 60 años de edad con antecedente de tromboembolia pulmonar aguda secundaria a trombosis venosa profunda de miembro pélvico derecho a quien durante el seguimiento se realizó el diagnóstico de HPTEC e ingresó de manera programada para tratamiento quirúrgico con realización de TEAP bilateral, sin embargo durante el posquirúrgico inmediato presentó choque cardiogénico e hipoxemia refractaria secundarios a síndrome de reperfusión pulmonar, por lo cual requirió soporte circulatorio con ECMO venovenosa durante seis días, con resolución del cuadro pulmonar y mejoría clínica.

3.
bioRxiv ; 2023 Oct 09.
Article in English | MEDLINE | ID: mdl-37808660

ABSTRACT

Accumulating evidence suggests that rapid eye movement sleep (REM) supports the consolidation of extinction memory. REM is disrupted in PTSD, and REM abnormalities after traumatic events increase the risk of developing PTSD. Therefore, it was hypothesized that abnormal REM in trauma-exposed individuals may pave the way for PTSD by interfering with the processing of extinction memory. In addition, PTSD patients display reduced vagal activity. Vagal activity contributes to the strengthening of memories, including fear extinction memory, and recent studies show that the role of vagus in memory processing extends to memory consolidation during sleep. Therefore, it is plausible that reduced vagal activity during sleep in trauma-exposed individuals may be an additional mechanism that impairs extinction memory consolidation. However, to date, the contribution of sleep vagal activity to the consolidation of extinction memory or any emotional memory has not been investigated. To test these hypotheses, we examined the association of extinction memory with REM characteristics and REM vagal activity (indexed as high-frequency heart rate variability; HF-HRV) in a large sample of trauma-exposed individuals (n=113). Consistent with our hypotheses, REM sleep characteristics (increased REM density and shortened REM latency) were associated with poorer physiological and explicit extinction memory. Furthermore, higher HF-HRV during REM was associated with better explicit extinction memory. These findings support the notion that disrupted REM may contribute to PTSD by impairing the consolidation of extinction memory and indicate the potential utility of interventions that target REM sleep characteristics and REM vagal activity in fear-related disorders.

4.
J Extra Corpor Technol ; 55(3): 134-137, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37682212

ABSTRACT

The following case report analyses a patient with extracorporeal membrane oxygenation (ECMO), who suffered from a severe Acute Respiratory Distress Syndrome (ARDS) due to COVID-19 pneumonia. ARDS is defined as a diffuse and inflammatory injury of the lungs; classifying this as severe when the ratio of arterial oxygen tension to a fraction of inspired oxygen (PaO2/FiO2) is equal to or lower than 100 mmHg. To decide if the patient was suitable for the use of ECMO therapy, the ELSO criteria were used; and in this case, the patient matched with the criteria of hypoxemic respiratory failure (with a PaO2/FiO2 < 80 mmHg) after optimal medical management, including, in the absence of contraindications, a trial of prone positioning. During hospitalization, the patient presented a Central Diabetes Insipidus (CDI), probably explained by the damage hypoxia generated on the central nervous system. There are few reports of this complication produced by COVID-19. The case is about a 39-year-old woman, who started with ECMO 6 days after the beginning of Invasive Mechanical Ventilation (IMV), because of a severe ARDS. On the fifth day of ECMO, the patient started with a polyuria of 7 L in 24 h. A series of paraclinical studies were made, but no evidence of central nervous system lesions was found. After treatment with desmopressin was initiated and the ARDS was solved, polyuria stopped; with this, CDI was diagnosed. There are many complications secondary to the evolution of COVID-19 infection, and some of them are not yet well explained.


Subject(s)
COVID-19 , Diabetes Insipidus, Neurogenic , Diabetes Mellitus , Extracorporeal Membrane Oxygenation , Respiratory Distress Syndrome , Female , Humans , Adult , COVID-19/complications , COVID-19/therapy , Polyuria , Oxygen , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/therapy
6.
J Cardiol Cases ; 27(6): 245-247, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37283911

ABSTRACT

Perioperative myocardial infarction is a complication of cardiac surgery, and the cause can be multifactorial. Injury of the left circumflex coronary artery has been described, particularly after mitral valve replacement. We present the case of a 72-year-old woman who underwent mitral valve replacement but developed a lesion in the proximal circumflex coronary artery related to partial mechanical kinking caused by a suture. The therapeutic options are surgical or percutaneous. In this patient, the percutaneous strategy was successful. Learning objective: • Percutaneous coronary intervention is an option in cases involving kinking of the left circumflex coronary artery after mitral valve replacement.• If unable to cross the lesion with a workhorse guide wire, one alternative is to use wires with good support properties and avoid very high tip loads to reduce the risk of perforation.In patients at high risk of bleeding, use of a drug-eluting stent and short-duration dual antiplatelet therapy is recommended.

8.
Int. microbiol ; 25(3): 639-647, Ago. 2022. ilus
Article in English | IBECS | ID: ibc-216221

ABSTRACT

In addition to the UPR pathway, yeast cells require components of the HOG pathway to respond to ER stress. In this work, we found that unphosphorylated Sln1 and Ssk1 are required to mount an appropriate response to Tn. We also found that the MAPKKKs Ssk2 participates in the Tn response, but its osmo-redundant protein Ssk22 does not. We also found that the Pbs2 docking sites for Ssk2 (RDS-I and KD) are partially dispensable when mutated separately; however, the prevention of Ssk2 binding to Pbs2, by the simultaneous mutation of RDS-I and KD, caused strong sensitivity to Tn. In agreement with the lack of Hog1 phosphorylation during Tn treatment, a moderate resistance to Tn is obtained when a Pbs2 version lacking its kinase activity is expressed; however, the presence of mutual Pbs2-Hog1 docking sites is essential for the Tn response. Finally, we detected that Tn induced a transcriptional activation of some components of the SLN1 branch. These results indicate that the Tn response requires a complex formed by the MAPK module and components of the SLN1 branch but not their canonical osmoregulatory activities.(AU)


Subject(s)
Humans , Endoplasmic Reticulum , Tunicamycin , Glycosylation , Transcriptome , Microbiology
9.
Int Microbiol ; 25(3): 639-647, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35597864

ABSTRACT

In addition to the UPR pathway, yeast cells require components of the HOG pathway to respond to ER stress. In this work, we found that unphosphorylated Sln1 and Ssk1 are required to mount an appropriate response to Tn. We also found that the MAPKKKs Ssk2 participates in the Tn response, but its osmo-redundant protein Ssk22 does not. We also found that the Pbs2 docking sites for Ssk2 (RDS-I and KD) are partially dispensable when mutated separately; however, the prevention of Ssk2 binding to Pbs2, by the simultaneous mutation of RDS-I and KD, caused strong sensitivity to Tn. In agreement with the lack of Hog1 phosphorylation during Tn treatment, a moderate resistance to Tn is obtained when a Pbs2 version lacking its kinase activity is expressed; however, the presence of mutual Pbs2-Hog1 docking sites is essential for the Tn response. Finally, we detected that Tn induced a transcriptional activation of some components of the SLN1 branch. These results indicate that the Tn response requires a complex formed by the MAPK module and components of the SLN1 branch but not their canonical osmoregulatory activities.


Subject(s)
Intracellular Signaling Peptides and Proteins/metabolism , Protein Kinases/metabolism , Saccharomyces cerevisiae Proteins/metabolism , Saccharomyces cerevisiae , Endoplasmic Reticulum Stress , MAP Kinase Kinase Kinases/metabolism , Mitogen-Activated Protein Kinase Kinases/genetics , Mitogen-Activated Protein Kinase Kinases/metabolism , Mitogen-Activated Protein Kinases/genetics , Mitogen-Activated Protein Kinases/metabolism , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/metabolism , Saccharomyces cerevisiae Proteins/genetics , Tunicamycin/metabolism , Tunicamycin/pharmacology
11.
Front Psychiatry ; 12: 766647, 2021.
Article in English | MEDLINE | ID: mdl-34867552

ABSTRACT

Sleep disturbances are common in post-traumatic stress disorder (PTSD), although which sleep microarchitectural characteristics reliably classify those with and without PTSD remains equivocal. Here, we investigated sleep microarchitectural differences (i.e., spectral power, spindle activity) in trauma-exposed individuals that met (n = 45) or did not meet (n = 52) criteria for PTSD and how these differences relate to post-traumatic and related psychopathological symptoms. Using ecologically-relevant home sleep polysomnography recordings, we show that individuals with PTSD exhibit decreased beta spectral power during NREM sleep and increased fast sleep spindle peak frequencies. Contrary to prior reports, spectral power in the beta frequency range (20.31-29.88 Hz) was associated with reduced PTSD symptoms, reduced depression, anxiety and stress and greater subjective ability to regulate emotions. Increased fast frequency spindle activity was not associated with individual differences in psychopathology. Our findings may suggest an adaptive role for beta power during sleep in individuals exposed to a trauma, potentially conferring resilience. Further, we add to a growing body of evidence that spindle activity may be an important biomarker for studying PTSD pathophysiology.

12.
Cir Cir ; 88(6): 805-817, 2020.
Article in English | MEDLINE | ID: mdl-33254199

ABSTRACT

The severe acute respiratory syndrome (SARS-Cov-2) is a clinical entity generated by this new virus a Coronavirus (COVID-19). Disease called COVID-19 (CoronaVIrus Disease 2019) by the World Health Organization. Its presentation is acute respiratory failure characterized by hyperinflation of the lung that leads to an increase in capillaries and epithelial permeability, with loss of ventilation of lung tissue and increases lung stiffness. These disturbances lead to imbalances between ventilation and perfusion ratio, which ultimately result in hypoxemia and impaired carbon dioxide clearance. For this review, a search of PubMed and Trip Database was performed. Due to the scarcity of publications, a specific search algorithm was not used. The objective is to review, the evidence and the recommendations of national and international experts, of the hemodynamic and ventilatory management of these patients.


El coronavirus del síndrome respiratorio agudo grave 2 (SARS-CoV-2, conocido previamente como nCoV-2019) es el agente causal de una nueva enfermedad denominada COVID-19 (COronaVIrus Disease 2019) por la Organización Mundial de la Salud. Su presentación es la insuficiencia respiratoria aguda caracterizada por una hiperinflación del pulmón que conduce a un incremento de los capilares y permeabilidad epitelial, con pérdida de la aireación de tejido pulmonar e incremento de la rigidez pulmonar. Estas alteraciones conducen a desequilibrios entre la ventilación y la relación de perfusión, que finalmente resultan en hipoxemia y deterioro de la depuración de dióxido de carbono. Para la presente revisión se realizó una búsqueda en PubMed y Trip Database. Debido a la escasez de publicaciones no se utilizó un algoritmo de búsqueda específico. El objetivo es dar a conocer, de acuerdo con la evidencia y las recomendaciones de expertos nacionales e internacionales, el manejo hemodinámico y ventilatorio de estos pacientes.


Subject(s)
COVID-19/therapy , Hemodynamics , Respiration , SARS-CoV-2 , COVID-19/blood , COVID-19/complications , COVID-19/physiopathology , Extracorporeal Membrane Oxygenation , Humans , Hypoxia/etiology , Lung/pathology , Phenotype , Positive-Pressure Respiration, Intrinsic , Prone Position/physiology , Respiration, Artificial/methods , Respiratory Distress Syndrome/etiology , Severity of Illness Index , Supine Position/physiology , Time Factors , Ultrasonography , Ventilator Weaning , Ventricular Dysfunction, Left/diagnosis
13.
Front Microbiol ; 11: 1742, 2020.
Article in English | MEDLINE | ID: mdl-32793173

ABSTRACT

The rhizosphere microbiome (rhizobiome) plays a critical role in plant health and development. However, the processes by which the constituent microbes interact to form and maintain a community are not well understood. To investigate these molecular processes, we examined pairwise interactions between 11 different microbial isolates under select nutrient-rich and nutrient-limited conditions. We observed that when grown with media supplemented with 56 mM glucose, two microbial isolates were able to inhibit the growth of six other microbes. The interaction between microbes persisted even after the antagonistic microbe was removed, upon exposure to spent media. To probe the genetic basis for these antagonistic interactions, we used a barcoded transposon library in a proxy bacterium, Pseudomonas putida, to identify genes which showed enhanced sensitivity to the antagonistic factor(s) secreted by Acinetobacter sp. 02. Iron metabolism-related gene clusters in P. putida were implicated by this systems-level analysis. The supplementation of iron prevented the antagonistic interaction in the original microbial pair, supporting the hypothesis that iron limitation drives antagonistic microbial interactions between rhizobionts. We conclude that rhizobiome community composition is influenced by competition for limiting nutrients, with implications for growth and development of the plant.

14.
Rev. mex. anestesiol ; 43(2): 140-144, abr.-jun. 2020. tab, graf
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1347702

ABSTRACT

Resumen: Todo en medicina debe fundamentarse y equilibrarse en tres pilares. El primero es: un fuerte principio fisiológico; una explicación de qué provoca el fenómeno patológico al que nos estamos enfrentando y con la cual encontremos cómo puede ser revertida dicha patología. El segundo pilar es: una adecuada corroboración estadística; un principio fisiológico puede ser cierto, pero ello no implica que el desenlace que buscamos (disminución de la mortalidad) sea el resultado de nuestras intervenciones. El tercer pilar es un protocolo clínico, lo que implica la parte más importante de todas, el trabajar unidos. De nada sirve creer conocer la verdad, si es que es así, si no se tiene las mismas metas en todos los turnos, corremos el riesgo de caer en la falacia de que «lo que yo hago es lo correcto y los demás se equivocan¼; si no estamos unidos en cada turno de atención al paciente, nunca sabremos qué es lo mejor para él, sólo tendremos un buen pretexto para afirmar que la culpa nunca es nuestra. Durante las crisis emergentes se puede trabajar sin la estadística mientras ésta se va construyendo, pero nunca sin fisiología y unidad (protocolos), la explicación fisiológica aquí vertida es lo más exacta posible, el protocolo es una inducción derivada de dicha fisiológica en espera de tener pronto una estadística que nos diga si lo que hacemos es de utilidad o no. En conclusión, lo que el lector tiene en sus manos son conjeturas en búsqueda de refutaciones. Al momento de escribir este artículo la única respuesta correcta es «Aún no lo sabemos¼.


Abstract: Everything in medicine must be based and balanced on three pillars, the first is: a strong physiological principle; an explanation of what causes the pathological phenomenon that we are facing with which we find how this pathology can be reversed, the second pillar is an adequate statistical corroboration; a physiological principle may be true, but this does not imply that the outcome we seek (decrease in mortality) is the result of our interventions. The third pillar is a clinical protocol, which implies the most important part of all, working together. It is useless to believe that you know the truth, if that is the case, if you do not have the same goals in every shift, we run the risk of falling into the fallacy that «what I do is right and others are wrong¼, if we are not united in each shift of patient care we will never know what is best for the patient, we will only have a good pretext to affirm that the fault is never ours. During emerging crises you can work without statistics while it is being built, but never without physiology and unity (protocols), the physiological explanation given here is as accurate as possible, the protocol is an induction derived from said physiology, waiting to have Soon a statistic will tell us if what we do is useful or not. In conclusion, what the reader has in his hands are conjectures in search of refutations. At the time of writing this article the only correct answer is «We don't know yet¼.

15.
Environ Toxicol Chem ; 38(9): 1911-1922, 2019 09.
Article in English | MEDLINE | ID: mdl-31107972

ABSTRACT

Advances in engineering biology have expanded the list of renewable compounds that can be produced at scale via biological routes from plant biomass. In most cases, these chemical products have not been evaluated for effects on biological systems, defined in the present study as bioactivity, that may be relevant to their manufacture. For sustainable chemical and fuel production, the industry needs to transition from fossil to renewable carbon sources, resulting in unprecedented expansion in the production and environmental distribution of chemicals used in biomanufacturing. Further, although some chemicals have been assessed for mammalian toxicity, environmental and agricultural hazards are largely unknown. We assessed 6 compounds that are representative of the emerging biofuel and bioproduct manufacturing process for their effect on model plants (Arabidopsis thaliana, Sorghum bicolor) and show that several alter plant seedling physiology at submillimolar concentrations. However, these responses change in the presence of individual bacterial species from the A. thaliana root microbiome. We identified 2 individual microbes that change the effect of chemical treatment on root architecture and a pooled microbial community with different effects relative to its constituents individually. The present study indicates that screening industrial chemicals for bioactivity on model organisms in the presence of their microbiomes is important for biologically and ecologically relevant risk analyses. Environ Toxicol Chem 2019;38:1911-1922. © 2019 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.


Subject(s)
Arabidopsis/drug effects , Biofuels , Ecotoxicology/methods , Rhizobium/growth & development , Soil Pollutants/toxicity , Sorghum/drug effects , Agriculture , Arabidopsis/growth & development , Biomass , Plant Roots/microbiology , Sorghum/growth & development
17.
Rev. colomb. reumatol ; 21(2): 99-103, abr. 2014. ilus, tab
Article in Spanish | LILACS | ID: lil-717045

ABSTRACT

La fibrosis retroperitoneal es una entidad clínica, de presentación poco frecuente,caracterizada por un trastorno fibroso e inflamatorio crónico, que rodea estructurasabdominales, principalmente los aspectos peri vasculares de las mismas, y que esexplicada por diferentes etiologías, siendo las más importantes la fibrosis retroperitonealidiopática y la fibrosis secundaria a trastornos relacionados con la subclase de IgG4. Por suparte, la hiperostosis cortical generalizada pertenece a un grupo de enfermedades raras depatologías metabólicas óseas osteocondensantes. En este caso, se presenta una pacientede 45 años de edad con fibrosis retroperitoneal, de etiología no establecida, asociada ahiperostosis cortical generalizada. La asociación de estas dos patologías, no reportadaanteriormente en la literatura, parece ser una relación espuria, sin embargo, existenalgunos mecanismos patogénicos entrelazados.


Retroperitoneal fibrosis is a rare clinical condition, characterized by a fibro-inflammatory disorder that surrounds abdominal structures, principally at perivascular level, and that is explained by different etiologies like idiopathic fibrosis and IgG4 related disorders. Generalized cortical hyperostosis belongs to a group of rare metabolic bone condensation diseases.The case is presented of a 45 year old female patient with a retroperitoneal fibrosis of unknown origin associated with generalized cortical hyperostosis. The association of these two conditions has not previously reported in the literature. This appears to be a spurious relationship, although some pathogenic mechanisms are intertwined.


Subject(s)
Humans , Osteochondrodysplasias , Retroperitoneal Fibrosis
18.
Acta méd. colomb ; 35(1): 3-7, ene.-mar. 2010. ilus, tab
Article in Spanish | LILACS | ID: lil-635291

ABSTRACT

Habitualmente se ha solicitado la hemoglobina/hematocrito después de las seis horas como parámetro para evaluar el resultado terapéutico de la transfusión sin que exista evidencia clara para hacerlo. Objetivo: determinar la concordancia de los niveles de hemoglobina/hematocrito en los primeros 15 minutos de terminada la transfusión comparado con la toma de éstos a las seis horas en pacientes con anemia crónica sin sangrado activo, hemólisis o hiperesplenismo. Materiales y métodos: se realizó un estudio, observacional, analítico de concordancia que analizó la consistencia entre dos mediciones de hemoglobina/hematocrito tomada dentro de los primeros 15 minutos de terminada la transfusión y seis horas después en 41 pacientes con anemia de origen médico, sin sangrado activo. Resultados: se encontró concordancia significativa alta entre la hemoglobina a los 15 minutos y seis horas después de la transfusión (p<0.0001) con un coeficiente de correlación intraclase de 0.8793 (IC 95: 0.7817, 0.9349); igualmente se encontró concordancia significativa alta entre el hematocrito a los 15 minutos y a las seis horas después de la transfusión (p<0.0001) con un coeficiente de correlación intraclase de 0.8456 (IC 95%: 0.7301, 0.9144). Conclusiones y discusión: aunque es una práctica habitual la toma de hemoglobina-hematocrito seis horas después de la transfusión, sin evidencia en la literatura que lo respalde, este estudio encontró que existe concordancia alta, significativa entre la toma de la hemoglobina/hematocrito 15 minutos y seis horas después de terminada la transfusión en pacientes con anemia de origen médico, lo que permite una toma inmediata, ahorrando tiempo en la decisión clínica (Acta Med Colomb 2010; 35: 2-7).


Measurement of hemoglobin/hematocrit is usually carried out 6 hours after transfusion, as a parameter allowing the assessment of therapeutic result. However, there is no clear evidence to support this practice. Objective: to determine the concordance of the levels of hemoglobin/hematocrit 15 minutes after termination of transfusion, with regard to those measured 6 hours after the procedure, in patients with chronic anemia and without active bleeding, hemolysis, or hypersplenism. Materials and methods: an observational, analytic, concordance study was carried out in order to analyze the concordance between 2 measurements of hemoglobin/hematocrit: 15 minutes after transfusion and 6 hours after transfusion. This was done in 41 diagnosed with anemia of medical origin, without active bleeding. Results: a highly significant concordance was found between hemoglobin at 15 minutes and 6 hours after transfusion (p<0.0001), with an intraclass correlation coefficient of 0.8793 (IC 95: 0.7817, 0.9349); highly significant concordance was also found between hematocrit at 15 minutes and 6 hours after transfusion (p<0.0001), with an intraclass correlation coefficient of 0.8456 (IC 95%: 0.7301, 0.9144). Conclusions and discussion: although it is common practice to determine hemoglobin/hematocrit 6 hours after transfusion (without supporting evidence reported in the literature), this study found a high, significant correlation between measurements carried out at 15 minutes and 6 hours after transfusion in patients with anemia of medical origin. Immediate measurement saves time in clinical decisions (Acta Med Colombiana 2010; 35: 2-7).

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