Francisco J. Morales-Olivas

Management of high blood pressure in children and adolescents: recommendations of the European Society of Hypertension

Hypertension in children and adolescents has gained ground in cardiovascular medicine, thanks to the progress made in several areas of pathophysiological and clinical research. These guidelines represent a consensus among specialists involved in the detection and control of high blood pressure in children and adolescents. The guidelines synthesize a considerable amount of scientific data and clinical experience and represent best clinical wisdom upon which physicians, nurses and families should base their decisions. They call attention to the burden of hypertension in children and adolescents, and its contribution to the current epidemic of cardiovascular disease, these guidelines should encourage public policy makers, to develop a global effort to improve identification and treatment of high blood pressure among children and adolescents.

Adverse drug reactions in children reported by means of the yellow card in Spain

OBJECTIVE To analyze the case reports concerning children (14 years or younger) in the Spanish Pharmacovigilance System over a 10-year period (1982-1991). FINDINGS The study of 1419 reports of adverse drug reaction (9.8% of all those received) showed the most commonly involved organs and systems to be the skin, digestive tract, and nervous system (62.8%). The most commonly involved pharmacological groups were antibiotics, respiratory medications, and vaccines (69%). The absolute number of reports is higher in children between 1 and 4 years of age (37.9%). There were more reports among males than in females. Less than 5% of the reports notified directly life-threatening or fatal reactions. CONCLUSIONS Adverse drug reaction are not common in pediatric patients, and most are mild. However, due to limitations of clinical trials in children, pharmacoepidemiological studies may be the only source of information on the benefit-risk profile of drugs received by these patients, and as such require special attention.

Drug utilization and off-label drug use among Spanish emergency room paediatric patients

ObjectiveTo describe the use of medicines and to determine the frequency of off-label use in emergency room paediatric patients.Patients and methodsA prospective, observational and descriptive study was carried out in the setting of the paediatric emergency room of a Spanish general hospital. Medicines used by children <14 years prior to their emergency room visit were analysed based on information collected from parents/guardians and relatives for each drug prescription. Off-label use was defined as the utilization of a drug at an indication, dosage, frequency or route of administration that differed from the specifications in the Summary of Product Characteristics or by children outside the authorized age group.ResultsThe patient cohort comprised 462 children, among whom 336 children had been prescribed 667 prescriptions. Of the medicines prescribed, 90% fell into only five 5 Anatomical Therapeutic Chemical Classification System groups. The most frequent active principles were ibuprofen and paracetamol. Of a total of 152 different formulations recorded, no paediatric information was provided for 40 formulations, and one formulation was contraindicated in children. Based on the established criteria, 338 prescriptions were off-label: no paediatric information or contraindication in children were available (82 prescriptions); the drug was used for an indication different from the authorized one (111 prescriptions); drug use was inconsistent with age recommendations (16 prescriptions); drug use was inconsistent with dose/frequency (129 prescriptions). Of the 152 formulations, 107 were occasionally used in an off-label manner.ConclusionsAlthough the mean number of drugs used in children is small, off-label use is frequent. Research efforts should target paediatric studies that allow a rational drug use in children.

POTENTIATION BY NALOXONE OF PRESSOR REFLEXES

1 The effect of intravenous naloxone, an opiate antagonist, was studied on the pressor responses elicited by stimulation of afferent nerves (vagus and laryngeal superior nerves) in anaesthetized dogs 2 Although naloxone (0.1 mg/kgi.v.) alone failed to modify basic blood pressure, the pressor responses induced by stimulation of either the vagus or laryngeal nerve were potentiated by naloxone 3 Morphine (0.2mg/kgi.v.) suppressed these two cardiovascular responses. These depressor effects of morphine were reversed by subsequent injection of naloxone (0.1 mg/kg i.v.) 4 The results suggest the involvement of endogenous opiate peptides in pressor reflexes elicited by stimulation of the afferent nerves.

Urinary Albumin Excretion and Glomerular Filtration Rate across the Spectrum of Glucose Abnormalities in Essential Hypertension

The objective of this study was to assess the relationship between urinary albumin excretion (UAE) and GF across the spectrum of the glucose metabolism abnormalities in a large population of patients with hypertension. The Microaluminuria en Pacientes con Glucemia Basal Alterada (MAGAL) is a multicenter, cross-sectional study that was carried out by 1723 primary care physicians. A total of 6227 patients with essential hypertension (in three groups: [1] normal fasting glucose <100 mg/dl, [2] impaired fasting glucose > or =100 to 126 mg/dl, and [3] type 2 diabetes) were analyzed in this substudy. GFR was estimated by using the Modification of Diet in Renal Disease (MDRD) abbreviated equation. A single first-morning urine albumin/creatinine ratio was measured using Bayer reagent strip Microalbustix, a semiquantitative method. Abnormal UAE was defined as an albumin/creatinine ratio > or =3.4 mg/mmol (equivalent to > or =30 mg/g). The prevalence of abnormal UAE, > or =3.4 mg/mmol, increased across the spectrum of glucose abnormalities: 39.7, 46.2, 48.6, and 65.6% for normoglycemic, low-range, and high-range impaired fasting glucose and diabetes, respectively. UAE was positively related to SBP (P = 0.003) and inversely to GFR (P < 0.001). Renal insufficiency (GFR <60 ml/min per 1.73 m2) was present in 21.8% of the patients, more frequently older patients, women, and those with diabetes. The factors that were related to renal insufficiency were UAE > or =3.4 mg/mmol (odds ratio 1.86; 95% confidence interval 1.60 to 2.17) and diabetes (odds ratio 1.62; 95% confidence interval 1.29 to 2.04). There is a close relationship between abnormal UAE and renal insufficiency in essential hypertension. This is more marked in patients with diabetes and moderate in patients with high-range impaired fasting glucose.

Prevalence of Abnormal Urinary Albumin Excretion Rate in Hypertensive Patients with Impaired Fasting Glucose and Its Association with Cardiovascular Disease

The prevalence and significance of microalbuminuria in hypertensive patients with impaired fasting glucose (IFG) has received very little attention. A total of 10,320 hypertensive patients who attended primary care centers were enrolled in this study, and the final analysis was done in 7625 patients: 1459 without IFG (plasma glucose <100 mg/dl), 3010 with IFG (plasma glucose > or =100 mg/dl and <126 mg/dl), and 3156 with type 2 diabetes (plasma glucose >126 mg/dl). Microalbuminuria was determined using the Micro Albustix reactive strip from Bayer (high urinary albumin excretion [UAE]: Albumin/creatinine ratio > or =3.4 mg/mmol). The proportion of patients with high UAE was 39.4, 48.3, and 65.6%, respectively, in the three groups (P < 0.01 for the trend). The differences in UAE between the group with IFG and the group with normal fasting glucose persisted after adjustment for age, gender, systolic BP, fasting plasma glucose, and cardiovascular comorbidity (odds ratio 1.74; 95% confidence interval 1.08 to 2.80). Hypertensive patients with IFG and high UAE showed a higher prevalence of ischemic heart disease, cardiac insufficiency, left ventricular hypertrophy, atrial fibrillation, and renal insufficiency than the group with normal UAE. Global prevalence of cardiovascular conditions was 30.4% in the group with high UAE compared with 21.4% in the group with normal UAE (odds ratio 1.60; 95% confidence interval 1.31 to 1.95). It is concluded that almost half of hypertensive patients with IFG have high UAE and a higher prevalence of associated cardiovascular involvement and renal insufficiency.

Effect of histamine and histamine analogues on human isolated myometrial strips

1 The effect of histamine and histamine H1 and H2‐receptor agonists on isolated myometrium strips of premenopausal women has been examined. The effect of acetylcholine was also determined. 2 Histamine, 2‐pyridylethylamine, 4‐methylhistamine and acetylcholine, but not dimaprit, produced a concentration‐related contractile response in human isolated myometrial strips. Histamine also produced a further contraction in human isolated myometrial strips precontracted with KCl (55 mm). 3 The contractile response to histamine was antagonized by the histamine H1‐receptor angatonist, clemizole (0.1 μm) but was potentiated by the histamine H2‐receptor antagonist, ranitidine (10 μm). Clemizole (0.1 nm to 10 nm) competitively antagonized the contractile effect of 2‐pyridylethylamine (– log KB = 10.5 ± 0.5). The concentration‐response curve for acetylcholine was displaced to the right by atropine 0.1 μm. 4 Atropine (0.1 μm), propranolol (0.1 μm), prazosin (0.1 μm) and indomethacin (1 μm) failed to modify the contractile response to histamine. 5 In human isolated myometrial strips precontracted with KCl (55 mm), clemizole at 1 μm completely abolished the contractile response to histamine and revealed a concentration‐dependent relaxation. Dimaprit alone and 4‐methylhistamine (in the presence of clemizole), produced concentration‐related relaxation with a magnitude similar to that in response to histamine. The relaxant response to dimaprit was antagonized by ranitidine. 6 It is concluded that human isolated uterine strips possess histamine H1‐ and H2‐receptors: the former mediating contraction and the latter relaxation. The predominant response to histamine in this tissue is contraction.

Medicamentos utilizados en pediatría extrahospitalaria : ¿disponemos de información suficiente?

Objetivo Analizar los medicamentos que reciben los pacientes pediatricos en el ambito extrahospitalario y la informacion disponible sobre los mismos. Pacientes y metodos Estudio transversal, observacional y descriptivo realizado en una muestra de pacientes menores de 14 anos atendidos en urgencias del Servicio de Pediatria del Consorcio Hospital General Universitario de Valencia entre junio 2005 y agosto 2006. Se cuantifican y clasifican los medicamentos utilizados antes de acudir a urgencias y se analiza la informacion sobre su uso que contiene el Vademecum Internacional Medicom y la ficha tecnica. Resultados Se recogio informacion sobre 462 ninos con media de edad de 5,2 anos (intervalo de confianza del 95% [IC 95%]: 4,9-5,6). De ellos, 336 reciben 667 medicamentos (152 distintos) que contienen 864 principios activos (161 diferentes). En el 34,3 % de los casos el uso es por automedicacion. Los menores de 4 anos reciben medicamentos en mayor proporcion que los mayores (80,2 y 67,4%, respectivamente). Los pacientes reciben entre 1 y 7 medicamentos (media 2,0). Los que toman 2 o 3 medicamentos son menores que los que toman uno. Cinco grupos terapeuticos de la Clasificacion anatomico-terapeutico-quimica (ATC) incluyen el 93,1% de los medicamentos (R [aparato respiratorio]: 26,5%; M [aparato locomotor]: 23,8%; N [sistema nervioso central]: 22,8 %;J [antiinfecciosos por via general]: 10,6% y A [aparato digestivo y metabolismo]: 10,0%). Para 40 de los 152 medicamentos no hay informacion pediatrica en las fuentes consultadas. Conclusiones Casi tres cuartas partes de los ninos atendidos en urgencias toman medicamentos antes de acudir a este servicio, en muchos casos por automedicacion. La informacion sobre uso pediatrico de medicamentos es incompleta y presenta incongruencias. Es necesario fomentar la investigacion clinica sobre los efectos del tratamiento farmacologico en los ninos para mejorar la informacion sobre su uso.

Pharmacological investigation into the effects of histamine and histamine analogues on guinea-pig and rat colon in vitro

1 The effects of histamine and specific histamine agonists has been examined on isolated longitudinal colon strips of guinea‐pig and rat. 2 Histamine and 2‐pyridyl‐ethylamine but not 4 methylhistamine produced a concentration‐related contractile response in the guinea‐pig colon. 3 The H1‐antagonist clemizole antagonized competitively the effect of histamine but the H2‐antagonist ranitidine did not modify the dose‐response curve to histamine in the guinea‐pig colon. 4 Atropine, hexamethonium, prazosin and propranolol failed to modify the contractile response to histamine. 5 Tone induced with KCl in guinea‐pig isolated colon was not modified by histamine agonists even in tissues pretreated with clemizole or ranitidine. 6 Histamine and histamine analogues were without effect on the isolated longitudinal strip of the rat colon. 7 It is concluded that histamine produced dose‐dependent contractions of the guinea‐pig colon due to direct activation of H1‐histamine receptors. There is no evidence in favour of the existence of H2‐histamine receptors in this preparation. The lack of effect of histamine agonists in rat colon strip argues against the existence of histamine receptors in this preparation.

Studies of the spontaneous motility and the effect of histamine on isolated myometrial strips of the nonpregnant human uterus: The influence of various uterine abnormalities

We investigated the spontaneous uterine activity of isolated corpus uteri myometrial strips from 30 patients with nonpathologic myometrium, 26 patients with uterine myoma, 23 patients with uterine adenomyosis, and three patients with uterine malignancy. We also investigated the influence of these conditions on the response of the uterus to histamine. The results show the same qualitative cyclic changes of the spontaneous motility of isolated myometrial strips throughout the menstrual cycle in all the abnormalities studied. These changes are characterized by a low amplitude and high frequency of spontaneous contractions in the proliferative phase and lower frequency with higher amplitude of contractions in the secretory phase. The isolated strips from patients with myomas present the highest spontaneous activity in reproductive age and preclimacteric women, but not in menopausal women. Histamine produced concentration-related contractions that are not significantly different in all the myometrial strips studied.