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1.
Nutrients ; 10(11)2018 Nov 13.
Article in English | MEDLINE | ID: mdl-30428605

ABSTRACT

Dietary methyl donors, including folate, may modify the placenta and size at birth but the influence of maternal body weight has not been widely investigated. We therefore examined whether maternal or fetal folate status, together with indices of placental folate transport, were modulated by either maternal pre-pregnancy body mass index (BMI i.e., overweight: 25 ≤ BMI < 30 or obesity: BMI ≥ 30 kg/m²) and/or gestational diabetes mellitus (GD). We utilised a sub-sample of 135 pregnant women participating in the Spanish PREOBE survey for our analysis (i.e., 59 healthy normal weight, 29 overweight, 22 obese and 25 GD). They were blood sampled at 34 weeks gestation, and, at delivery, when a placental sample was taken together with maternal and cord blood. Placental gene expression of folate transporters and DNA methyltransferases (DNMT) were all measured. Folate plasma concentrations were determined with an electro-chemiluminescence immunoassay. Food diaries indicated that folate intake was unaffected by BMI or GD and, although all women maintained normal folate concentrations (i.e., 5⁻16 ng/mL), higher BMIs were associated with reduced maternal folate concentrations at delivery. Umbilical cord folate was not different, reflecting an increased concentration gradient between the mother and her fetus. Placental mRNA abundance for the folate receptor alpha (FOLR1) was reduced with obesity, whilst DNMT1 was increased with raised BMI, responses that were unaffected by GD. Multi-regression analysis to determine the best predictors for placental FOLR1 indicated that pre-gestational BMI had the greatest influence. In conclusion, the placenta's capacity to maintain fetal folate supply was not compromised by either obesity or GD.


Subject(s)
Body Weight , Diabetes, Gestational/metabolism , Folic Acid/metabolism , Placenta/metabolism , Biomarkers , Female , Humans , Pregnancy
2.
J Clin Endocrinol Metab ; 101(1): 59-68, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26513002

ABSTRACT

CONTEXT: Maternal obesity and gestational diabetes mellitus (GDM) can both contribute to adverse neonatal outcomes. The extent to which this may be mediated by differences in placental metabolism and nutrient transport remains to be determined. OBJECTIVE: Our objective was to examine whether raised maternal body mass index (BMI) and/or GDM contributed to a resetting of the expression of genes within the placenta that are involved in energy sensing, oxidative stress, inflammation, and metabolic pathways. METHODS: Pregnant women from Spain were recruited as part of the "Study of Maternal Nutrition and Genetics on the Foetal Adiposity Programming" survey at the first antenatal visit (12-20 weeks of gestation) and stratified according to prepregnancy BMI and the incidence of GDM. At delivery, placenta and cord blood were sampled and newborn anthropometry measured. RESULTS: Obese women with GDM had higher estimated fetal weight at 34 gestational weeks and a greater risk of preterm deliveries and cesarean section. Birth weight was unaffected by BMI or GDM; however, women who were obese with normal glucose tolerance had increased placental weight and higher plasma glucose and leptin at term. Gene expression for markers of placental energy sensing and oxidative stress, were primarily affected by maternal obesity as mTOR was reduced, whereas SIRT-1 and UCP2 were both upregulated. In placenta from obese women with GDM, gene expression for AMPK was also reduced, whereas the downstream regulator of mTOR, p70S6KB1 was raised. CONCLUSIONS: Placental gene expression is sensitive to both maternal obesity and GDM which both impact on energy sensing and could modulate the effect of either raised maternal BMI or GDM on birth weight.


Subject(s)
Body Weight , Diabetes, Gestational/physiopathology , Placenta/physiopathology , Pregnancy Outcome , Adolescent , Adult , Anthropometry , Birth Weight/genetics , Body Mass Index , Diabetes, Gestational/genetics , Energy Intake/genetics , Female , Gene Expression/genetics , Glucose Intolerance/complications , Glucose Intolerance/genetics , Humans , Infant, Newborn , Inflammation/genetics , Inflammation/pathology , Longitudinal Studies , Metabolic Networks and Pathways/genetics , Middle Aged , Obesity/complications , Obesity/genetics , Oxidative Stress , Placenta/metabolism , Pregnancy , Spain/epidemiology , Young Adult
3.
Rev. esp. anestesiol. reanim ; 62(8): 472-476, oct. 2015. ilus
Article in Spanish | IBECS | ID: ibc-141287

ABSTRACT

El aturdimiento miocárdico neurogénico es una entidad poco frecuente que semeja un síndrome coronario agudo, con alteraciones electrocardiográficas, disfunción cardiaca y aumento de enzimas cardiacas, pero sin evidencia de lesión coronaria. Puede ocurrir en el posoperatorio de neurocirugía. Se presenta el caso de un paciente pediátrico que a las 24 h de ser intervenido de un meduloblastoma de fosa posterior desarrolló un aturdimiento miocárdico neurogénico que evolucionó a taquicardia nodal con repercusión hemodinámica. La evolución fue satisfactoria, aunque precisó tratamiento antiarrítmico, con resolución bioquímica, ecográfica y clínica en menos de una semana (AU)


Neurogenic stunned myocardium is an unusual clinical entity. It mimics an acute coronary syndrome with electrocardiographic abnormalities, cardiac dysfunction and elevated cardiac enzymes with absence of obstructive coronary disease. It may occur after a neurosurgical procedure. A case is presented of neurogenic stunned myocardium occurring in a child after removal of a posterior fossa medulloblastoma. The patient developed nodal tachycardia with hemodynamic impairment. The clinical course was satisfactory due to antiarrhythmic therapy, with biochemical, echocardiographic, and clinical improvement within a week (AU)


Subject(s)
Child , Female , Humans , Myocardial Stunning/complications , Myocardial Stunning/diagnosis , Myocardial Stunning/drug therapy , Electrocardiography/instrumentation , Electrocardiography/methods , Anti-Arrhythmia Agents/therapeutic use , Blood Pressure , Heart Diseases/complications , Medulloblastoma/surgery , Medulloblastoma , Ataxia/complications , Intracranial Pressure/radiation effects , Electrocardiography , Fibroma, Desmoplastic/surgery , Fibroma, Desmoplastic
4.
Rev Esp Anestesiol Reanim ; 62(8): 472-6, 2015 Oct.
Article in Spanish | MEDLINE | ID: mdl-25530429

ABSTRACT

Neurogenic stunned myocardium is an unusual clinical entity. It mimics an acute coronary syndrome with electrocardiographic abnormalities, cardiac dysfunction and elevated cardiac enzymes with absence of obstructive coronary disease. It may occur after a neurosurgical procedure. A case is presented of neurogenic stunned myocardium occurring in a child after removal of a posterior fossa medulloblastoma. The patient developed nodal tachycardia with hemodynamic impairment. The clinical course was satisfactory due to antiarrhythmic therapy, with biochemical, echocardiographic, and clinical improvement within a week.


Subject(s)
Cerebellar Neoplasms/surgery , Infratentorial Neoplasms/surgery , Medulloblastoma/surgery , Myocardial Stunning/etiology , Postoperative Complications/etiology , Acute Coronary Syndrome/diagnosis , Amiodarone/therapeutic use , Child, Preschool , Diagnosis, Differential , Echocardiography , Electrocardiography , Hematoma, Subdural/etiology , Humans , Male , Myocardial Stunning/diagnosis , Myocardial Stunning/diagnostic imaging , Myocardial Stunning/drug therapy , Pneumocephalus/etiology , Postoperative Complications/diagnosis , Postoperative Complications/diagnostic imaging , Postoperative Complications/drug therapy
6.
An. pediatr. (2003, Ed. impr.) ; 79(2): 83-87, ago. 2013. tab, graf
Article in Spanish | IBECS | ID: ibc-116476

ABSTRACT

Introducción: El objetivo del presente trabajo es demostrar si la aplicación del índice biespectral (BIS®) en la monitorización de la anestesia general en respiración espontánea en endoscopias digestivas altas (EDA) diagnósticas en el paciente pediátrico es útil para: a) disminuir la dosis de fármaco necesaria; b) disminuir el tiempo del despertar, y c) mejorar la seguridad del paciente. Pacientes y método: estudio prospectivo cuasi experimental de casos y controles en el ámbito de una unidad de cuidados intensivos pediátricos y neonatales de segundo nivel. Pacientes: niños entre 12 meses y 13 años. Caso: paciente ASA I que precisa EDA diagnóstica; sujetos elegibles 36, participantes 30. Población control: serie histórica de pacientes que precisaron EDA (años 2008-2010): 50 pacientes. Intervenciones: realización de EDA, aplicando protocolo de anestesia, monitorización de constantes vitales, nivel de sedación (escala de Ramsay) y nivel BIS. Variables de interésdosis total de propofol (mg/kg), tiempo de inducción, tiempo de EDA y tiempo de despertar (min); índice BIS al inicio de la EDA (BISi) y durante la EDA; efectos adversos. Resultados: Sin diferencias significativas entre casos (B) y controles (C) respecto a sexo, edad y peso. Sin diferencias significativas en: dosis total de propofol (B 4,9 ± 1,4 mg/kg; C 5,2 ± 1,6 mg/kg, p = 0,492), Tiempo de despertar (B 12,2 ± 4,6 min; C 12,8 ± 4,4 min, p = 0,402), tiempo de procedimiento (B 9,5 ± 4,8 min; C 11,3 ± 6,5 min, p = 0,335) y tiempo de inducción (B 11,1 ± 2,6 min; C 10,1 ± 4,2 min, p = 0,059). BISi 55,4 ± 6,9. Sin diferencias significativas en efectos adversos (2 casos de desaturación leve en el grupo control). Conclusiones: La monitorización anestésica con índice biespectral en endoscopias digestivas altas en respiración espontánea en la población pediátrica es factible, pero no parece disminuir ni la dosis de fármaco necesaria ni el tiempo de despertar. Tampoco disminuye la incidencia de efectos adversos de forma significativa (AU)


Introduction: The objective of this investigation is to determine whether bispectral index (BIS®) monitoring during intravenous anaesthesia with spontaneous breathing for upper gastrointestinal endoscopy (UGE) in a pediatric population is useful for: a) decreasing the amount of drug, b) decreasing the time for awakening, and c) improving patient safety. Patients and method A quasi-experimental case-control prospective study was conducted in the setting of a second level hospital pediatric intensive care unit. Patients: Children aged 1-13 years. Case: ASA I patient who needed a diagnostic UGE; eligible, 36, participants, 30. Control: historical cohort of patients who needed UGE (years 2008-2010): 50 patients. Intervention: UGE performed with anaesthetic protocol, vital signs monitoring, sedation level (Ramsay scale) and BIS monitoring. Variables of interestpropofol total dose (mg/kg), induction time, time in performing the UGE, awakening time (min); initial BIS (iBIS), and BIS during the UGE; adverse effects. Results: There were no significant differences in sex, age or weight between case (B) and control (C) population. No significant differences in total propofol doses: (B 4.9 ± 1.4 mg/kg; C 5.2 ± 1.6 mg/kg, P=.492), awakening time (B 12.2 ± 4.6 min; C 12.8 ± 4.4 min, P=.402), time for execution of UGE (B 9.5 ± 4.8 min; C 11.3 ± 6.5 min, P=.335) and induction time (B 11.1 ± 2.6 min; C 10.1 ± 4.2 min, P=.059), iBIS 55.4 ± 6.9. There were no significant differences in adverse effects: 2 patients suffered from mild desaturation in the control group. Conclusions: BIS monitoring for diagnostic UGE in spontaneous breathing in a pediatric population is feasible, but does not appear to decrease awakening time or the amount of propofol needed. Furthermore, there was no statistically significant decrease in the number of adverse effects (AU)


Subject(s)
Humans , Male , Female , Infant , Child, Preschool , Child , Adolescent , Endoscopy, Digestive System/methods , Anesthesia/methods , Monitoring, Physiologic/methods , Airway Management/methods , Propofol/administration & dosage , Patient Safety , Case-Control Studies
7.
An Pediatr (Barc) ; 79(2): 83-7, 2013 Aug.
Article in Spanish | MEDLINE | ID: mdl-23384651

ABSTRACT

INTRODUCTION: The objective of this investigation is to determine whether bispectral index (BIS®) monitoring during intravenous anaesthesia with spontaneous breathing for upper gastrointestinal endoscopy (UGE) in a pediatric population is useful for: a) decreasing the amount of drug, b) decreasing the time for awakening, and c) improving patient safety. PATIENTS AND METHOD: A quasi-experimental case-control prospective study was conducted in the setting of a second level hospital pediatric intensive care unit. PATIENTS: Children aged 1-13 years. CASE: ASA I patient who needed a diagnostic UGE; eligible, 36, participants, 30. CONTROL: historical cohort of patients who needed UGE (years 2008-2010): 50 patients. INTERVENTION: UGE performed with anaesthetic protocol, vital signs monitoring, sedation level (Ramsay scale) and BIS monitoring. VARIABLES OF INTEREST: propofol total dose (mg/kg), induction time, time in performing the UGE, awakening time (min); initial BIS (iBIS), and BIS during the UGE; adverse effects. RESULTS: There were no significant differences in sex, age or weight between case (B) and control (C) population. No significant differences in total propofol doses: (B 4.9 ± 1.4 mg/kg; C 5.2 ± 1.6 mg/kg, P=.492), awakening time (B 12.2 ± 4.6 min; C 12.8 ± 4.4 min, P=.402), time for execution of UGE (B 9.5 ± 4.8 min; C 11.3 ± 6.5 min, P=.335) and induction time (B 11.1 ± 2.6 min; C 10.1 ± 4.2 min, P=.059), iBIS 55.4 ± 6.9. There were no significant differences in adverse effects: 2 patients suffered from mild desaturation in the control group. CONCLUSIONS: BIS monitoring for diagnostic UGE in spontaneous breathing in a pediatric population is feasible, but does not appear to decrease awakening time or the amount of propofol needed. Furthermore, there was no statistically significant decrease in the number of adverse effects.


Subject(s)
Anesthesia , Consciousness Monitors , Endoscopy, Gastrointestinal , Monitoring, Intraoperative/methods , Adolescent , Case-Control Studies , Child , Child, Preschool , Humans , Infant , Prospective Studies , Respiration
8.
Ultrasound Obstet Gynecol ; 39(6): 685-9, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22173854

ABSTRACT

OBJECTIVES: To assess a new method for numerical quantification of cervical elastography during pregnancy and to evaluate the repeatability of the measurements. METHODS: Cervical elastography was carried out twice by a single operator in 112 singleton pregnancies at a median of 21 (range, 12-40) weeks' gestation. In 50 of the cases a second operator performed another elastography measurement. The intraobserver and interobserver repeatability of measurements in different parts of the cervix were assessed using intraclass correlation coefficients with 95% CI and by Bland-Altman analysis. RESULTS: There were no statistically significant differences in the elastography measurements made by the same and by two different observers in each area measured, except in the area that receives the force of the transducer directly. The distribution of elastographic measurements obtained in different regions of the cervix demonstrated that the external and superior parts were significantly softer than the internal and inferior parts. CONCLUSION: It is possible to provide an objective quantification of elastographic colors in the cervix. The measurements obtained by elastography may be a mere reflection of the force being applied by the transducer to different parts of the cervix. It is too premature to suggest that the measurements of rate-of-change in tissue displacement reflect histological changes that could provide a measure of cervical ripening.


Subject(s)
Cervical Ripening , Cervix Uteri/diagnostic imaging , Elasticity Imaging Techniques/methods , Premature Birth/diagnostic imaging , Adolescent , Adult , Algorithms , Female , Gestational Age , Humans , Middle Aged , Observer Variation , Predictive Value of Tests , Pregnancy , Pregnancy Trimester, Second , Pregnancy Trimester, Third , Reproducibility of Results , Sensitivity and Specificity , Ultrasonography, Prenatal/methods , Young Adult
10.
Ultrasound Obstet Gynecol ; 32(4): 515-9, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18683279

ABSTRACT

OBJECTIVE: To evaluate parameters of fetal breathing movements-displacement of the fetal abdominal wall during inspiration and expiration, time of inspiration and expiration and speed of inspiration and expiration-between 30 and 36 weeks' gestation in normal pregnancies, and in those complicated by gestational diabetes or maternal hypertension. METHODS: Three categories of pregnancy were investigated: 49 were normal, 16 had pregnancy-induced diabetes and 10 were hypertensive. According to their gestational age, the patients were divided into two groups: Group A between 30 and 32 weeks' gestation and Group B between 33 and 36 weeks. Using photogrammetry and a computer-operated algorithm, six parameters of fetal breathing movements were investigated. RESULTS: There were significant differences in the various fetal parameters measured among the three categories of pregnant women. Up until 32 weeks of gestation, the displacements during inspiration and expiration were larger, the speeds of inspiration and expiration were higher, and the times for inspiration and expiration were shorter in the diabetic and hypertensive groups than in the normal group. In the later period, between 33 and 36 weeks, fetuses of pregnancy-induced diabetic patients showed the lowest inspiration and expiration times and the highest speeds of inspiration and expiration. CONCLUSIONS: Photogrammetry in conjunction with a computer-operated algorithm can be used to assess fetal breathing movements. There are significant differences in fetal breathing movements between normal pregnancies and those that are complicated by gestational diabetes or hypertension.


Subject(s)
Fetal Movement/physiology , Fetus/physiology , Pregnancy Complications , Respiratory Mechanics , Adult , Diabetes, Gestational , Female , Fetal Monitoring/methods , Gestational Age , Humans , Hypertension , Photogrammetry/methods , Pregnancy , Pregnancy Complications, Cardiovascular , Pregnancy Trimester, Third
11.
Med. intensiva (Madr., Ed. impr.) ; 32(2): 94-96, mar. 2008. ilus
Article in Es | IBECS | ID: ibc-63855

ABSTRACT

La diálisis peritoneal aguda (DPA) continúa siendo una medida útil en el paciente pediátrico crítico. En el shock séptico el fracaso renal agudo puede precisar medidas invasivas de depuración y aunque la hemofiltración es muy efectiva, en ciertas Unidades de Cuidados Intensivos Pediátricas no se dispone aún de ella. La DPA pediátrica se suele iniciar con pases horarios, permanencias cortas y volumen por pase de unos 10 ml/kg. Mostramos la evolución de la DPA de dos pacientes críticos con fallo renal en los que la monitorización de los cocientes dializado/plasma de urea y creatinina y del cociente de concentración de glucosa del dializado (efluente)/concentración de glucosa de la solución de diálisis infundida fue útil para la prescripción de la DPA


Acute peritoneal dialysis (APD) is still a useful tool in the critical pediatric patient. Acute kidney failure due to septic shock often requires invasive depuration procedures and although hemofiltration is very effective, not all pediatric Intensive Care Units have the equipment necessary to establish it. Pediatric APD is generally initiated with short dwell times, every hour exchanges and 10-20 ml/kg filling volumes. We present the evolution of two critical patients with kidney failure on APD who benefited from the measurement of dialysate-to-plasma (D/P) ratios for creatinine and urea, and dialysate-to-solution ratio for glucose (Dt/Do) to optimize APD prescription


Subject(s)
Humans , Male , Female , Infant , Child, Preschool , Peritoneal Dialysis/methods , Acute Kidney Injury/therapy , Intensive Care Units, Pediatric , Critical Care/methods , Shock, Septic/complications
12.
Med Intensiva ; 32(2): 94-6, 2008 Mar.
Article in Spanish | MEDLINE | ID: mdl-18275758

ABSTRACT

Acute peritoneal dialysis (APD) is still a useful tool in the critical pediatric patient. Acute kidney failure due to septic shock often requires invasive depuration procedures and although hemofiltration is very effective, not all pediatric Intensive Care Units have the equipment necessary to establish it. Pediatric APD is generally initiated with short dwell times, every hour exchanges and 10-20 ml/kg filling volumes. We present the evolution of two critical patients with kidney failure on APD who benefited from the measurement of dialysate-to-plasma (D/P) ratios for creatinine and urea, and dialysate-to-solution ratio for glucose (Dt/Do) to optimize APD prescription.


Subject(s)
Acute Kidney Injury/therapy , Peritoneal Dialysis , Acute Kidney Injury/metabolism , Child, Preschool , Creatinine/metabolism , Female , Glucose/metabolism , Humans , Infant , Male , Urea/metabolism
13.
J Hum Hypertens ; 16 Suppl 1: S93-9, 2002 Mar.
Article in English | MEDLINE | ID: mdl-11986904

ABSTRACT

Angiotensin II receptor blockers represent a class of effective and well tolerated orally active antihypertensive drugs. Activation of AT(1) receptors leads to vasoconstriction, stimulation of the release of catecholamines and antidiuretic hormone and promote growth of vascular and cardiac muscle. AT(1) receptor blockers antagonise all those effects. Losartan was the first drug of this class marketed, shortly followed by valsartan, irbesartan, telmisartan, candesartan, eprosartan and others on current investigation. All these drugs have the common properties of blockading the AT(1) receptor thereby relaxing vascular smooth muscle, increase salt excretion, decrease cellular hypertrophy and induce antihypertensive effect without modifying heart rate or cardiac output. Most of the AT(1) receptor blockers in use controlled blood pressure during the 24 h with a once-daily dose, without evidence of producing tolerance to the antihypertensive effect and being with low incidence of side effects even at long term use. Monotherapy in mild-to-moderate hypertension controls blood pressure in 40 to 50% of these patients; when a low dose of thiazide diuretic is added, 60-70% of patients are controlled. The efficacy is similar to angiotensin-converting enzyme (ACE) inhibitors, diuretics, calcium antagonists and beta-blocking agents. AT(1) receptor blockers are specially indicated in patients with hypertension who are being treated with ACE inhibitors and developed side effects such as, cough or angioedema. The final position in the antihypertensive therapy in this special population and other clinical situations, such as left ventricular hypertrophy, heart failure, diabetes mellitus and renal disease, has to be determined in large prospective clinical trials, some of which are now being conducted and seem promising.


Subject(s)
Angiotensin Receptor Antagonists , Antihypertensive Agents/therapeutic use , Hypertension/drug therapy , Animals , Antihypertensive Agents/pharmacokinetics , Humans , Receptors, Angiotensin/metabolism , Renin-Angiotensin System/drug effects
14.
J Hum Hypertens ; 16 Suppl 1: S114-7, 2002 Mar.
Article in English | MEDLINE | ID: mdl-11986907

ABSTRACT

Calcium antagonists represent an important group of drugs for the treatment of hypertension; they are effective in the whole range of severity of the disease. Dihy- dropyridine derivatives are most frequently used, and can be used in association with other antihypertensive drugs; meanwhile phenylalkylamines and benzothiazepines are contraindicated in association with beta-blocker drugs. Calcium antagonists with slow starting effect and long duration of action are the choice for use in long-term antihypertensive treatment. This group of drugs is specially indicated in elderly patients, in those with diabetes mellitus and in patients with coronary heart disease. Phenylalkylamines and benzothiazepine derivatives are also used in patients with supraventricular arrhythmias. This group of agents is as safe as diuretics, angiotensin-converting enzyme-inhibitors and beta-blocking drugs in the long-term treatment of hypertension.


Subject(s)
Calcium Channel Blockers/therapeutic use , Hypertension/drug therapy , Humans
15.
J Hum Hypertens ; 16 Suppl 1: S142-4, 2002 Mar.
Article in English | MEDLINE | ID: mdl-11986913

ABSTRACT

The objective of this study was to assess the pharmacokientic parameters of regular nimodipine (Bayer), 30 mg, given every 6 h and nimodipine AP (nimodipine in micro particles with programmed action contained in tablets, developed by Biocontrolled-Leti Group Laboratories), 120 mg, given every 24 h. Subjects (19 healthy volunteers, five female; 14 male: age: 21 +/- 0.7 years) received one formulation over 5 days. Then, after a washout period of 7 days, the other formulation was given. The analyst was blinded to the relationship in formulation received. Antecubital blood samples were taken before the first tablet was taken and after 15, 45, 60 min and 2, 4, 6, 8, 12, 13, 18 and 24 h on day 1 and five of each formulation. Nimodipine blood levels were analysed by HPLC. At steady-state regular nimodipine reached a C-max of 10.208 +/- 0.317 ng/ml, at a t-max of 1 h; minimum concentration 6 h after dosage was 1.2929 +/- 0.411 ng/ml, half-life was estimated in 2.9 h. Meanwhile nimodipine AP 120 mg reach a C-max of 11.885 +/- 0.403 ng/ml; a t-max of 1 h with a minimum concentration 24 h after the last dose of 4.2387 +/- 0.353 ng/ml (P < 0.001). Apparent half-life was calculated in 17.8 h (P < 0.001). Area under the curve for the 24 h period was 143.76 ng/ml/min for regular nimodipine and 183.7 ng/ml/min for nimodipine AP 120 mg (P < 0.001), indicating better bioavailability. In conclusion nimodipine in AP formulation 120 mg produced similar peak plasma levels (C-max) than regular nimodipine, but with higher trough (C-min) values and stable plasma levels with one administration every 24 h. This formulation would be more suitable when nimodipine chronic therapy is indicated.


Subject(s)
Calcium Channel Blockers/pharmacokinetics , Nimodipine/pharmacokinetics , Adult , Area Under Curve , Biological Availability , Calcium Channel Blockers/chemistry , Female , Humans , Male , Nimodipine/chemistry , Tablets
16.
Int J Clin Pharmacol Ther ; 39(8): 325-30, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11515706

ABSTRACT

OBJECTIVE: The main objective of this study was to evaluate well-being and physical activity of 248 hypertensive patients, including 177 females, who had previously been included in the Latin-American Study on Lacidipine in Hypertension (LASTLHY). SUBJECTS, MATERIALS AND METHODS: This open study was carried out in 12 clinical centers in Argentina, Brazil, Colombia, Mexico and Venezuela, to compare, over a period of 16 weeks, the antihypertensive action of a fixed-dose, once daily of 4 mg lacidipine administered orally to 120 patients and 30 mg nifedipine GITS (Gastro-Intestinal Therapeutic System) administered to 128 patients, aged between 40 and 65 years. All patients had mild to moderate hypertension and treatment was begun at the end of a one-week placebo run-in period (end of week -1). Well-being and physical activity were assessed by means of single questionnaire, which reflected the physical and cultural diversities amongst the clinical centers and patients. The questionnaire included 13 multiple-choice and 8 contingent open questions. The score of each question was multiplied by a coefficient related to the importance of each question to the patient (semipersonalization); the coefficient was obtained from cultural and socioeconomic data collected at the time of enrollment. The semipersonalization was carried out by a blind psychological study with respect to the medication and had a high repeatability in the assignment of personalized coefficients to the score of each question. The scores of each question were added to obtain an overall well-being and activity scoring. The possible theoretical range for the overall scoring in this study was 10 - 124. RESULTS: See Table 1. CONCLUSION: The study revealed that the administration of calcium channel blockers such as lacidipine and nifedipine GITS, and lacidipine in particular, produced low incidence of side effects, and lacidipine in particular induced significant improvement in the quality of life.


Subject(s)
Antihypertensive Agents/therapeutic use , Calcium Channel Blockers/therapeutic use , Dihydropyridines/therapeutic use , Hypertension/drug therapy , Hypertension/psychology , Nifedipine/therapeutic use , Quality of Life , Activities of Daily Living , Administration, Oral , Adult , Aged , Exercise , Female , Health Surveys , Humans , Male , Middle Aged , Psychometrics
17.
Blood Press Monit ; 6(1): 47-57, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11248761

ABSTRACT

OBJECTIVE: To compare the antihypertensive efficacy of amlodipine and nifedipine gastrointestinal therapeutic system (GITS) measured by office and ambulatory blood pressure monitoring (ABPM) during treatment and, after patients have missed two doses. METHOD: After a single blind run-in 4-week placebo period, 58 patients were randomly allocated to amlodipine (5mg/daily, n=30) or nifedipine GITS (30mg/daily; n=28) in a double-blind, double dummy fashion. Patients received active medication for 4 weeks. Then, to simulate failure of compliance, patients received two single blinded doses of placebo. Ambulatory blood pressure monitoring was carried out at the end of run-in placebo phase, the first day, the last day of active treatment and up to 72h after the last active dose. RESULTS: Diastolic blood pressure was controlled in 61.9% patients on amlodipine and 52.9% on nifedipine GITS. Reductions in blood pressure were similar in both groups. ABPM showed significant reduction in blood pressure from the first day in the nifedipine GITS group, while amlodipine group had marginal effect. Peak reduction in systolic/diastolic blood pressure was 26/15mmHg at 5-6h after ingestion of amlodipine tablets. The trough reduction was 22/13mmHg; with a trough-to-peak ratio of 84.61% for systolic and 86.67% for diastolic blood pressure. Peak reduction in systolic/diastolic blood pressure with nifedipine GITS was 19/15mmHg and the trough reduction was 21/17mmHg, giving a trough-to-peak ratio of 100% for both systolic and diastolic blood pressure. When patients received placebo after 4 weeks of active treatment, simulating a compliance failure, amlodipine maintained reduction in systolic and diastolic blood pressure for at least up to 72h after the last active dose, maintaining 57.71% of the effect for systolic blood pressure and 60.00% for diastolic blood pressure. In contrast, nifedipine GITS effect was rapidly lost during this study phase, with a reduction in systolic and diastolic blood pressure of only 14-16%, 72h after the last active dose. CONCLUSION: This study showed that amlodipine and nifedipine GITS reduce blood pressure to about the same extent during chronic treatment. In the case of compliance failure, such as missing one or two doses, amlodipine maintained significant and important antihypertensive effect with the trough-to-peak ratio still over 50% 72h after the last active dose. On the other hand, the coverage of nifedipine GITS was limited to about 36h after the last active dose.


Subject(s)
Amlodipine/pharmacology , Nifedipine/pharmacology , Treatment Refusal , Antihypertensive Agents/pharmacology , Blood Pressure/drug effects , Blood Pressure Determination , Blood Pressure Monitoring, Ambulatory , Calcium Channel Blockers/pharmacology , Digestive System , Double-Blind Method , Drug Delivery Systems , Female , Humans , Male , Middle Aged , Office Visits , Therapeutic Equivalency , Time Factors
18.
J Hum Hypertens ; 14 Suppl 1: S2-5, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10854072

ABSTRACT

Since 1950 all countries of the Latin-American subcontinent have experienced very important changes in several health indicators, in the demographic, epidemiological, socio-cultural and way of living profiles. The proportion of the population over 65 years old tend to be low in the Latin American countries in contrast to developed countries. Cardiovascular diseases are the main cause of death in most of the Latin American countries at a similar rate to that of the developed world. As infectious diseases are reduced, cardiovascular diseases takes their place as the main cause of death in Latin American countries. Prevalence of hypertension in different reports show variations from 40 to 8% in the adult population, but on average 20 to 23% of the adult population have elevated blood pressure. This prevalence is similar to reports in the developed world. However there is considerable variability in each country and its regions so it is important that local studies of prevalence and local factors in the development of hypertension are investigated. The degree of awareness, treatment and control of hypertension is lower than that reported in the developed world, and it is important to establish programmes to attend to this public health problem, from prevention to treatment, from primary care to higher levels of attention.


Subject(s)
Health Status , Hypertension/epidemiology , Public Health/standards , Age Factors , Cause of Death , Humans , Hypertension/complications , Hypertension/therapy , Latin America/epidemiology , National Health Programs/standards , National Health Programs/trends , Prevalence , Risk Factors , Stroke/epidemiology , Stroke/etiology , Stroke/prevention & control , Survival Rate
19.
J Hum Hypertens ; 14 Suppl 1: S69-72, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10854084

ABSTRACT

Angiotensin II receptor antagonists (AT-1) represent a new group of orally active antihypertensive agents. Activation on AT-1 receptor leads to vasoconstriction, stimulation of the release of catecholamines and antidiuretic hormone with production of thirst, and promote growth of vascular and cardiac muscle; these effects are blocked by AT-1 antagonist agents. The first chemically useful, orally active AT-1 receptor antagonist was losartan, followed by other agents currently in clinical use, such as: valsartan, eprosartan, irbesartan, telmisartan, candesartan, and many others under investigation. AT-1 receptor antagonists are effective in reducing high blood pressure in hypertensive patients. Monotherapy in mild to moderate hypertension controls blood pressure in 40 to 50% of these patients; when a low dose of a thiazide diuretic is added, 60 to 70% of patients are controlled. The efficacy is similar to angiotensin-converting enzyme inhibitors, diuretics, calcium antagonists and beta-blocking agents. Tolerability has been reported to be very good. AT-1 receptor antagonists would be a drug of choice in otherwise well-controlled hypertensive patients treated with angiotensin-converting enzyme inhibitors who developed cough or angioedema. The final position in the antihypertensive therapy in this special population and other clinical situations, such as left ventricular hypertrophy, heart failure, diabetes mellitus and renal disease, has to be determined in large prospective clinical trials, some of which are now being conducted.


Subject(s)
Angiotensin Receptor Antagonists , Antihypertensive Agents/therapeutic use , Hypertension/drug therapy , Antihypertensive Agents/pharmacokinetics , Blood Pressure/drug effects , Humans , Hypertension/complications , Hypertension/metabolism , Hypertrophy, Left Ventricular/etiology , Hypertrophy, Left Ventricular/metabolism , Hypertrophy, Left Ventricular/prevention & control , Losartan/pharmacokinetics , Losartan/therapeutic use , Receptor, Angiotensin, Type 1 , Receptor, Angiotensin, Type 2 , Receptors, Angiotensin/metabolism , Treatment Outcome
20.
J Hum Hypertens ; 14 Suppl 1: S91-5, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10854087

ABSTRACT

With the aim of evaluating the effects on blood pressure, platelet function and insulin sensitivity of the dihydropiridines lacidipine and nifedipine GITS, a parallel double-blind study was carried out in a group of 20 patients with mild to moderate essential hypertension. They received a placebo for 4 weeks; then were divided at random into two groups of 10 patients each. Nifedipine GITS, 30 mg and lacidipine, 4 mg, were given during 16 weeks of active treatment. Blood pressure and heart rate were measured at the clinic in supine, sitting and standing positions, 24 +/- 1 h after the last dose. After the placebo and active phases were carried out, a platelet aggregation test was performed to determine platelet malondialdehyde production and a tolerance to 100 g of glucose by measuring glucaemia and plasma insulin. Both drugs reduced systolic and diastolic blood pressure at the same level, however there were observable differences in the rate of reduction. The nifedipine GITS reduced supine systolic blood pressure by 25 mm Hg in the first week, while the lacidipine did so by 11 mm Hg. At the end of the study period nifedipine reduced supine systolic blood pressure by 28 mm Hg and lacidipine by 20 mm Hg. Heart rate was increased slightly but significantly in the nifedipine GITS group only in the standing position. Both drugs reduced platelet aggregation ex vivo only marginally but they modified the malondialdehyde production, indicating an action on the arachidonic acid metabolic pathway.


Subject(s)
Blood Platelets/physiology , Calcium Channels/therapeutic use , Dihydropyridines/therapeutic use , Hypertension/blood , Nifedipine/therapeutic use , Platelet Aggregation/drug effects , Arachidonic Acid/metabolism , Biomarkers/blood , Blood Platelets/drug effects , Blood Pressure/drug effects , Female , Heart Rate/drug effects , Humans , Hypertension/drug therapy , Male , Malondialdehyde/metabolism , Middle Aged , Posture/physiology , Single-Blind Method
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