[Revista Chilena de Pediatría/Andes Pediatrica in the new millennium. Bibliometric analysis]. / Revista Chilena de Pediatría/Andes Pediatrica en el nuevo milenio. Análisis bibliométrico.

INTRODUCTION: Andes Pediatrica/Revista Chilena de Pediatría (AP/RChP), maintains a document profile that covers all scientific publication formats, from Original Articles (OAs) to Letters to the Editor. Adequate editorial planning requires a long-term bibliometric analysis. OBJECTIVE: To describe the profile of OAs published in AP/RChP in the last two decades. METHODOLOGY: From a controlled vocabulary list, the thematic and methodological descriptors of the documents from 2000 to 2020 were standardi zed. Nationality, sex, and profession of the authors, document typology, and design of the OAs were analyzed, as well as the descriptors cited in Google Scholar and the most visited descriptors on the journal's website in recent years. RESULTS: 1738 manuscripts were published, 580 (33.4%) were OAs, with an increase from 59 to 129 OAs between the first and last three years. The average number of authors was higher for OAs (4.7) than for non-originals (3.0). In 2020, there were nine multicenter collaborations from different countries. The number of OAs by foreign authors increased from 3.3% to 28.7%, the first authorship by non-medical professionals increased from 15% to 31%, and there was a predominance of female first authors (ratio 1.4/1). Of the OAs, 9.1% were experimental, 3.3% were qualitative and the rest were quantitative observational. The most published descriptors were Nutrition, Infectious Diseases, Neonatology, and Pneumonology, while the most cited descriptors were Nutrition, Neonatology, and Oral Health, with no trend among the most visited. 44% of the most cited articles and 35% of the most visited articles were OAs. CONCLUSIONS: A significant increase in published OAs stands out, with a low frequency of experimental designs. Authors of different na tionalities and professions participated. OAs represent one-third of the visits and almost half of the citations, with no correlation between the most published and most cited descriptors.

Ocuparse del bienestar de los profesionales de la salud: un desafío pendiente / Taking care of health care professional's well-being: a pending challenge

Este estudio de caso tiene como objetivo general, escribir las características laborales asociadas al Síndrome de Burnout en un Equipo de Cuidados Paliativos Oncológicos del Servicio de Salud Metropolitano Norte, en el año 2013” Las variables evaluadas son Síndrome de Burnout, carga mental y factores de riesgo psicosociales, las que fueron evaluadas mediante pautas estandarizadas: Maslach Burnout Inventory (MBI), NASA-TLX e ISTAS 21, respectivamente, además de un cuestionario de datos personales. La población de estudio está conformada en su mayoría por mujeres. Seis son médicos, cuatro son enfermeras y dos son técnicos en enfermería. Los principales hallazgos son que: todos los participantes tienen Síndrome de Burnout o se encuentran en riesgo de padecerlo, las principales fuentes de carga mental son las exigencias mentales y temporales, y los principales factores de riesgo psicosociales se relacionan con las exigencias psicológicas y la doble presencia. De los resultados obtenidos se concluye la importancia de intervenir no sólo con pacientes oncológicos, sino también con los equipos de salud, ya que este puesto de trabajo se ve expuesto a altas exigencias que pueden perjudicar la calidad de vida laboral y personal de los trabajadores.

The main purpose of this case study is to describe the work conditions related to the development of Burnout Syndrome in an Oncology and Palliative Care unit of the North Metropolitan Health Service, in the year 2013. This study evaluated the presence of Burnout Syndrome, Mental Workload and Psychosocial Risk Factors, which were assessed with three standardized tests: Maslach Burnout Inventory, NASA TLX and ISTAS 21, respectively, besides a personal data questionnaire. The study population was formed by twelve people, mainly women. Six were doctors, four were nurses and two were nursing technicians. The main results are: all individuals suffered from Burnout Syndrome or were in risk of developing it. The main mental workload causes were mental and timing requirements, and exposition to psychosocial risk factors related to psychological requirements and “double – presence”. These results highlight the importance of making an intervention not only with oncology patients, but also with the health team, who are exposed to many requirements, which can affect the professional’s work and personal quality of life.

Producción bacteriana de betalactamasas de espectro extendido en pacientes de la unidad de cuidados intensivos del Hospital de Caldas, 2003 / Bacterial production of extended spectrum betalactamases in patients of the intensive care unit of the Hospital de Caldas, 2003

La resistencia bacteriana a los antimicrobianos va en aumento, lo que implica generación de problemas a las instituciones de salud y la comunidad en general como: elevación del gasto para medicamentos, sobreinfecciones, alteración de la microflora y la macroflora, y disminución en la calidad de atención en salud. Esta resistencia es más marcada cuando hay presencia de microorganismos gram negativos productores de betalactamasas de espectro extendido (BLEE). En el presente trabajo se buscó determinar el tipo, la frecuencia y la distribución de microorganismos productores de BLEE, por técnicas tradicionales y moleculares, y determinar los factores médicos o quirúrgicos asociados con dicha producción, en la Unidad de Cuidados Intensivos (UCI) del Hospital de Caldas, con el fin de aportar la información necesaria para tomar medidas epidemiológicas y plantear estrategias sobre el uso apropiado de los antibióticos y el tratamiento de las infecciones más frecuentes. Se realizó un estudio analítico de casos y controles: 11 pacientes (5 casos y 6 controles), con infección primaria o intrahospitalaria, en quienes se realizó aislamiento de microorganismos productores de BLEE, resistentes o no, a las cefalosporinas de tercera generación, respectivamente. Estas muestras se sometieron a análisis microbiológico, isoenzimático y molecular. Se identificaron dos cepas de Eschericcia. coli, P. aeruginosa y Acinetobacter baumanii sospechosas de producir BLEE; sin embargo, no fueron confirmadas con otras pruebas como VITEK, puntos isoeléctricos y reacción en cadena de la polimerasa. No hubo diferencias significativas para los factores de riesgo en los casos y los controles.

Oceanographic conditions in North and Northwest Iberia and their influence on the Prestige oil spill.

Oceanographic conditions at the time of the Prestige oil spill (November 2002) and following months are analyzed based on a set of hydrographic cruises. The ship sank off one of the flanks of the Galician Bank, an offshore seamount, and a major oil spill drifted to the N and NW Iberian coast mainly driven by dominant winds. Coastal circulation was characterized by freshwater plumes and the poleward slope current, and could have affected the fate of the oil spill and influenced stranding places. Seasonal evolution of oceanographic conditions in this particular year is compared with the long-term average and reveals specific features that need to be taken into account in studies of the impact of the oil spill on populations. Spring conditions commenced earlier than other years in the Southern Bay of Biscay, contrastingly in western Iberia. The lack of subsurface intrusion of subtropical waters suggests a low intense penetration of the poleward current in Spanish Biscay slopes. In western Iberia, the slope poleward current observed in late autumn weakens and is exported off slope during upwelling pulses in the spring, with no strong intrusion of the poleward current on the slope at the time of the spring bloom. A description of current velocities near the wreck on the Galician Bank is obtained after the analysis of a mooring line.

Non invasive evaluation of central venous pressure using echocardiography in the intensive care--specific features of patients with right ventricular enlargement and chronic exacerbated pulmonary disease.

OBJECTIVES: To determine the possibility of non-invasive estimation of central venous pressure (CVP) through inferior vena cava (IVC) analysis, using transthoracic echocardiography (TTE). DESIGN: A prospective 3-year study. SETTING: A 16-bed medical/surgical Intensive Care Unit (ICU). METHODS: Patients admitted to the ICU were enrolled. CVP measurement and TTE (determining cardiac chambers dimension and left ventricular shortening fraction) with IVC analysis (maximum dimension and IVC index) were performed simultaneously. Parametric and non-parametric statistical analysis was performed to establish correlations between variables. RESULTS: 560 patients were admitted to the study, including 477 in whom IVC was analysed, aging 62.2 +/- 17.3 years, a mean ICU stay 11.9 +/- 18.7 days, a APA- CHE II score 23.9 +/- 8.9 and a SAPS II score 55.7 +/- 20.4. Through linear regression analysis CVP was influenced by IVC index (p=0.001), IVC maximum dimension (p=0.013) and presence of mechanical ventilation (p=0.002). A statistically significant correlation was found between the following parameters: an IVC index < 25% and a CVP > 13 mmHg; an IVC index and a CVP 26%-50%; an IVC index > 51% and CVP < 7 mmHg; an IVC maximum dimension > 20mm and a CVP > 13 mmHg; an IVC maximum dimension < 10 mmHg and CVP < 7 mmHg. Patients with right ventricle enlargement presented a lack of agreement between IVC maximum dimension and CVP > 7 mmHg was observed, and in patients with chronic respiratory failure (who presented a high prevalence of right ventricular enlargement) a lack of agreement between IVC index > 50% and CVP < 7 mmHg was also observed. CONCLUSIONS: IVC analysis is a possible way to non-invasively estimate CVP in a medical /surgical ICU. However, patients with right ventricular enlargement and admitted with chronic respiratory failure present a lack of agreement between IVC parameters and low values of CVP. IVC dimension is a marker of chronic disease and IVC index correlated better with CVP.

cDNA microarray analysis of changes in gene expression induced by neuronal hypoxia in vitro.

We used cDNA microarray gene expression profiling to characterize the transcriptional response to exposure of cultured mouse cerebral cortical neurons to hypoxia for 24 hr. Of 11,200 genes examined, 1,405 (12.5%) were induced or repressed at least 1.5-fold, whereas 26 known genes were induced and 20 known genes were repressed at least 2.5-fold. The most strongly induced genes included genes coding for endoplasmic reticulum proteins (Ero1L/Giig11, Sac1p, Ddit3/Gadd153), proteins involved in ubiquitination (Arih2, P4hb), proteins induced by hypoxia in non-neuronal systems (Gpi1, Aldo1, Anxa2, Hig1), and proteins that might promote cell death (Gas5, Egr1, Ndr1, Vdac2). These findings reinforce the importance of endoplasmic reticulum-based mechanisms and of protein-ubiquitination pathways in the neuronal response to hypoxia.

Weight gain in women with breast cancer treated with adjuvant cyclophosphomide, methotrexate and 5-fluorouracil. Analysis of resting energy expenditure and body composition.

BACKGROUND: Weight gain is a common side effect observed in women undergoing adjuvant chemotherapy for breast cancer. Among possible causes a direct effect of chemotherapy on metabolism has been proposed. Body composition variations after adjuvant chemotherapy suggest the occurrence of sarcopenic obesity, possibly due to ovarian failure. We investigated acute and chronic effects of adjuvant chemotherapy on body weight, resting energy expenditure (REE) and plasma catecholamines in a group of menopausal women. PATIENTS AND METHODS: Thirty menopausal women with stage I-II breast cancer were recruited for the study. We measured REE and respiratory quotient (RQ) and body composition at the beginning and after 3 and 6 months of adjuvant cyclophosphomide, methotrexate, and 5-fluorouracil (CMF). REE, RQ, and plasma catecholamines were assessed before and after each chemotherapy session. At each session food intake was also assessed in all patients, by a food diary. Seven patients out of the group of 30 were also evaluated after a placebo infusion (saline). RESULTS: A significant weight gain was observed in all women (70.5 +/- 3 v.s. 67.7 +/- 3 kg, p < 0.001), with increase in both fat-free mass (FFM) (45.2 +/- 1.5 v.s. 43.6 +/- 1.3 kg, p < 0.001) and fat-mass (FM) (25.3 +/- 1.7 v.s. 24.1 +/- 1.8 kg, p < 0.005). A decrease in REE and RQ was observed both during CMF and placebo infusion (p < 0.05). During acute CMF and placebo infusion a reduction of plasma levels of noradrenaline was observed at the first and last session. REE increased progressively during the study period. CONCLUSIONS: CMF therapy apparently has no effect on REE either acutely or during a 6-month-period; the increased REE observed in the long-term is likely due to the concomitant increase in FFM. The lack of evidence of sarcopenic obesity, at variance with previous literature, is likely due to different patient selection.

A ligand-receptor pair that triggers a non-apoptotic form of programmed cell death.

Several receptors that mediate apoptosis have been identified, such as Fas and tumor necrosis factor receptor I. Studies of the signal transduction pathways utilized by these receptors have played an important role in the understanding of apoptosis. Here we report the first ligand-receptor pair-the neuropeptide substance P and its receptor, neurokinin-1 receptor (NK(1)R)-that mediates an alternative, non-apoptotic form of programmed cell death. This pair is widely distributed in the central and peripheral nervous systems, and has been implicated in pain mediation and depression, among other effects. Here we demonstrate that substance P induces a non-apoptotic form of programmed cell death in hippocampal, striatal, and cortical neurons. This cell death requires gene expression, displays a non-apoptotic morphology, and is independent of caspase activation. The same form of cell death is induced by substance P in NK(1)R-transfected human embryonic kidney cells. These results argue that NK(1)R activates a death pathway different than apoptosis, and provide a signal transduction system by which to study an alternative, non-apoptotic cell death program.

Riesgo anestésico y tipo de heridas asociados a infección intrahospitalaria en pacientes quirúrgicos: Modelo logístico / Anesthesic risk and type of injury associated to intrahospitalary infection in surgical patients: Logistic pattern

Con el fin de evaluar la asociación entre edad del paciente, el riesgo anestésico (ASA), el tipo de herida (limpia, limpia-contaminada, contaminada y sucia), y la duración del procedimiento quirúrgico con la presentación de infección intrahospitalaria (infección de herida quirúrgica, neumonía, infección del tracto urinario, infección de piel, conjuntivitis e infección de quemadura), se desarrolló un estudio controlado con 104 casos y 144 controles seleccionados aleatoriamente de los pacientes que ingresaron al piso quirúrgico del Hospital de Caldas (Cirugía General, Neurocirugía, Ortopedia, Urología). Se tomaron como criterios de infección intrahospitalaria (IIH) los que están estandarizados por el Centro de Control de Enfermedades de Atlanta (CDC). Mediante regresión lineal se escogieron las variables explicativas que fueron ingresadas al modelo de regresión logística (RL). De este último se excluyeron la edad del paciente y la duración del procedimiento por falta de significancia. En una fase posterior se diseñaron variables dummy para el ASA y el tipo de herida, evidenciándose asociación de la IIH con el ASA 3, el ASA 4, el ASA 5, la herida contaminada y la sucia. Cuando se corrió el modelo de RL con todas las variables independientes, tomando solo como variable respuesta la infección de la herida quirúrgica (IHQ) se encontró que ningún factor estaba asociado. El riesgo de IIH es alto para pacientes que ingresaron al hospital de Caldas y que poseen riesgos anestésicos altos (ASA 3, 4 y 5) y su tipo de herida es contaminada o sucia

Mining DNA microarray data using a novel approach based on graph theory.

The recent demonstration that biochemical pathways from diverse organisms are arranged in scale-free, rather than random, systems [Jeong et al., Nature 407 (2000) 651-654], emphasizes the importance of developing methods for the identification of biochemical nexuses--the nodes within biochemical pathways that serve as the major input/output hubs, and therefore represent potentially important targets for modulation. Here we describe a bioinformatics approach that identifies candidate nexuses for biochemical pathways without requiring functional gene annotation; we also provide proof-of-principle experiments to support this technique. This approach, called Nexxus, may lead to the identification of new signal transduction pathways and targets for drug design.

Coupling endoplasmic reticulum stress to the cell death program. Mechanism of caspase activation.

The endoplasmic reticulum (ER) is the site of assembly of polypeptide chains destined for secretion or routing into various subcellular compartments. It also regulates cellular responses to stress and intracellular Ca(2+) levels. A variety of toxic insults can result in ER stress that ultimately leads to apoptosis. Apoptosis is initiated by the activation of members of the caspase family and serves as a central mechanism in the cell death process. The present study was carried out to determine the role of caspases in triggering ER stress-induced cell death. Treatment of cells with ER stress inducers such as brefeldin-A or thapsigargin induces the expression of caspase-12 protein and also leads to translocation of cytosolic caspase-7 to the ER surface. Caspase-12, like most other members of the caspase family, requires cleavage of the prodomain to activate its proapoptotic form. Caspase-7 associates with caspase-12 and cleaves the prodomain to generate active caspase-12, resulting in increased cell death. We propose that any cellular insult that causes prolonged ER stress may induce apoptosis through caspase-7-mediated caspase-12 activation. The data underscore the involvement of ER and caspases associated with it in the ER stress-induced apoptotic process.

APAP, a sequence-pattern recognition approach identifies substance P as a potential apoptotic peptide.

We have previously described a novel cancer chemotherapeutic approach based on the induction of apoptosis in targeted cells by homing pro-apoptotic peptides. In order to improve this approach we developed a computational method (approach for detecting potential apoptotic peptides, APAP) to detect short PAPs, based on the prediction of the helical content of peptides, the hydrophobic moment, and the isoelectric point. PAPs are toxic against bacteria and mitochondria, but not against mammalian cells when applied extracellularly. Among other peptides, substance P was identified as a PAP and subsequently demonstrated to be a pro-apoptotic peptide experimentally. APAP thus provides a method to detect and ultimately improve pro-apoptotic peptides for chemotherapy.

Resting metabolic rate, fat-free mass and catecholamine excretion during weight loss in female obese patients.

The reduction in resting metabolic rate (RMR) during weight loss exceeds that accounted for by changes in body composition by 15%, suggesting that factors other than fat-free mass (FFM) explain the metabolic adaptation during food restriction in obesity. Our study aimed to establish if changes in the sympathoadrenal system activity, as inferred from an integrated measure such as 24 h urinary excretion of catecholamines, may play a role in the RMR adaptation observed during dietary restriction in obese patients. Ninety-three obese female subjects consumed a low-energy diet (LED) (2930 kJ/d (700 kcal/d)) for a 3-week period. At the beginning and at the end of the study, 24 h urinary excretion of catecholamines, FFM and RMR were measured. The LED induced a significant reduction in body weight (-3.3 (SEM 0.4) kg; P < 0.01), FFM (-1.9 (SEM 0.7) kg; P < 0.01) and in the fat mass (-1.2 (SEM 0.5) kg; P < 0.01). Noradrenalin excretion (24 h) decreased during the LED from 264 (SEM 26) during a weight-maintenance period to 171 (SEM 19) nmol/24 h after consumption of the LED for 3 weeks (P < 0.001); mean 24 h adrenalin excretion did not change during the LED (22 (SEM 3) during the weight-maintenance period v. 21 (SEM 3) nmol/24 h after consumption of the LED for 3 weeks; NS). The LED induced a significant decrease in RMR (7300 (SEM 218) v. 6831 (SEM 138) kJ/24 h; P < 0.001). The only independent variable that significantly explained variations in RMR both before and after consumption of the LED for 3 weeks, was FFM (r2 0.79 and r2 0.80 respectively). Urinary noradrenalin excretion explained a further 4% of the variability in RMR, but only before the diet, so that a role of sympathoadrenal system on RMR seems to be present in obese patients in basal conditions but not at the end of the LED.

The effects of transdermal estradiol on the response to mental stress in postmenopausal women: a randomized trial.

PURPOSE: Estrogens inhibit adrenomedullary catecholamine release and catecholamine-mediated responses to stress. We examined whether estrogen supplementation reduces the sympathoadrenal response to mental stress in postmenopausal women. MATERIALS AND METHODS: We compared the effects of 3-week treatment with transdermal 17-beta-estradiol and placebo in 10 postmenopausal women using a randomized, blinded, crossover design. We measured plasma catecholamine levels and the cardiovascular and metabolic responses to a 15-minute stress with mental arithmetic. Treatments were compared using repeated measures analysis of variance. RESULTS: During placebo treatment, mean (+/- SD) epinephrine levels reached a peak of 431 +/- 135 pmol/liter after 15 minutes of stress; the epinephrine response was blunted during estradiol treatment, with a peak of 357 +/- 77 pmol/liter (P <0.05). Estradiol also blunted the diastolic blood pressure response to stress (baseline levels of 78 +/- 15 mm Hg vs peak of 90 +/- 6 mm Hg during placebo; baseline of 80 +/- 8 mm Hg vs peak of 84 +/- 6 mm Hg during estradiol; P <0.05). Estradiol treatment also blunted the decrease in the standard deviation of the mean of the electrocardiographic RR intervals and the increase in the ratio between the low-frequency and high-frequency bandwidths. CONCLUSION: We observed a moderate, although significant, reduction in markers of the stress response to mental arithmetic in postmenopausal women treated with transdermal 17-beta-estradiol.

Adrenomedullary function and its regulation in obesity.

Sympathoadrenal system (SAS) represents a major contributor to body homeostasis, regulating blood pressure heart rate, energy balance and intermediary metabolism. Thus, it is not unexpected that in last decades a consistent literature has been focused on the possible role of sympathoadrenal system in the pathogenesis of human obesity. There are, however, many factors confounding comparison of sympathoadrenal system activity between lean and obese subjects. Among these, one should be aware that SAS should be functionally separated into sympathetic nervous system (SNS) and adrenal medulla (AM), and that each of these two systems can be activated independently from the other by distinct physiological stimuli; this phenomenon in fact underlies the discordant pattern of findings for adrenomedullary and sympathetic activity in human obesity. While, in fact, obese subjects often display an increased basal SNS activity, there are numerous reports of blunted AM function in obese. Recent evidence suggests that this reduced adrenaline secretion is an acquired feature of human obesity, a finding that fits in well with the hypothesis that hormonal milieu, particularly sex steroids and cortisol, plays a role in the determination of blunted AM activity. Catecholamines have been recently demonstrated to play a role also in the regulation of whole energy balance. Adrenaline in fact acutely reduces both leptin mRNA as well as circulating leptin in human obese subjects, suggesting that catecholamines may influence the cross-talk between energy stores and the centrally mediated modulation of food intake. In summary, the study of adrenomedullary function and of possible mechanisms of its disturbances in human obesity, appears of great interest, and surely deserves further investigations.

Influence of exogenous melatonin on catecholamine levels in postmenopausal women prior and during oestradiol replacement.

OBJECTIVE: In young individuals melatonin administration reduces circulating norepinephrine. Some effects of melatonin are reduced in elderly women and are modulated by gonadal steroids. Accordingly, the influence of melatonin on catecholamine levels was investigated in postmenopausal women without and with oestradiol replacement. DESIGN: Prior to and after 2 months of transdermal oestradiol (50 microg/day), women were studied on two consecutive days, on which they received placebo or 1 mg of melatonin orally in a randomised and double-blind fashion. PATIENTS: Fourteen healthy postmenopausal women. MEASUREMENTS: Resting levels of epinephrine and norepinephrine and their responses to both a cold stimulus, performed by placing a hand in a basin of water and ice for 2 minutes, and to 10 minutes of upright position (upright test). RESULTS: Prior to oestradiol, melatonin did not modify baseline or stimulated catecholamine levels. In contrast, during oestradiol, melatonin tended to reduce, although not significantly, baseline norepinephrine levels (P = 0.053), and significantly reduced peak values (P = 0.0061) and integrated norepinephrine response (P = 0.0076) to the cold stimulus. Responses of norepinephrine to the upright test were not modified, while those of epinephrine were increased (P = 0.042). During, but not prior to oestradiol replacement, modifications induced by melatonin (melatonin day-placebo day) in the norepinephrine response to the cold (r2 = 0. 457; P = 0.0079) and the upright (r2 = 0.747; P = 0.0001) tests were linearly and inversely related to the responses of the placebo day. CONCLUSIONS: Melatonin does not modulate adrenergic activity in postmenopausal women without hormone replacement therapy. Oestradiol replacement restores the capability of melatonin to modulate adrenergic activity, particularly the norepinephrine response to stimuli.

Metabolic effects of fluoxetine in obese menopausal women.

Our objective was to assess thermogenic action of fluoxetine (FL) in obese menopausal women, evaluating the effect of FL administration on resting energy expenditure (REE) and on glucose-induced thermogenesis both after acute administration (40 mg in single dose the evening before measurements) and after a 12- week period of diet treatment plus FL (60 mg per day) or placebo. It was a double-blind, placebo-controlled design both in acute and in chronic study. The subjects were 32 obese, otherwise healthy, menopausal women. The patients were assigned randomly to three groups, one performing an acute study protocol, in which resting and glucose-induced thermogenesis was measured after FL and placebo administration, performed in randomised order. The other two groups underwent dietary plus pharmacological treatment (FL or placebo, PL). Resting and glucose-induced thermogenesis was measured at baseline and after 12 weeks of treatment. The results showed that acute FL administration caused an increase in resting energy expenditure (PL: 5.35+/-0.18 vs FL: 5.53+/-0.24 KJ/min, p<0.05). A significant decrease of REE was observed in the PL group after 12 weeks (p<0.03), while a slight, but not significant, decrease was observed in the FL group (p=NS). FL did not affect thermic response to oral glucose neither after acute nor chronic administration (p=NS for all groups studied). The conclusion was that our data give support to thermogenic actions of FL after acute administration, suggesting also that chronic FL treatment may restrain to some degree the metabolic adaptation expected during weight loss in obese subjects. At variance with what observed with other drugs, such as dexfenfluramine, an increased thermic effect of oral glucose does not seem to be involved in the thermogenetic action of FL.

alpha2-adrenoceptor regulation of the hypothalamic-pituitary-adrenocortical axis in obesity.

BACKGROUND: Abdominal obesity is associated with hyper-responsiveness of the hypothalamic-pituitary-adrenocortical (HPA) axis to stimulatory neuropeptides and to stress. Catecholamines are involved in the regulation of the HPA axis, particularly during stress, via alpha-adrenoceptor modulation. DESIGN: In this study, we investigated the effects of pre-treatment with an alpha2-adrenoceptor agonist, clonidine (2 microg/kg over 10 minutes) and antagonist, yohimbine (0.125 mg/kg bolus, followed by 0. 001 mg/kg/minutes per 90 minutes infusion) on the HPA axis, measured by ACTH and cortisol response to combined CRH (human, 100 microg) plus AVP (0.3 IU) administration, and on noradrenalin (NA) and adrenalin (A) blood levels, in a group of obese women with abdominal (A-BFD) or peripheral (P-BFD) body fat distribution and in nonobese controls. RESULTS: During the control CRH + AVP test the ACTH but not the cortisol response was higher (P < 0.05) in obese A-BFD women than in controls, with minor and transient variations of NA levels. Neither the control test nor clonidine or yohimbine influenced basal or post CRH + AVP A concentrations. Clonidine pretreatment similarly and significantly decreased NA levels in all women and, compared to the control test, marginally influenced the ACTH response to CRH + AVP. Conversely, during yohimbine infusion NA levels steadily and similarly increased to values more or less double baseline values in all groups. Compared to the control test, however, the ACTH response to the CRH + AVP test performed during yohimbine infusion significantly decreased in the control subjects whereas a tendency to a further increase occurred in the obese groups and, specifically, in the A-BFD group significantly (P < 0.05) more than in the P-BFD group. CONCLUSIONS: This study shows that alpha2-adrenoceptor regulation of the HPA axis is different in obese and nonobese women, particularly in stressed conditions. We suggest that the abnormal ACTH response to CRH + AVP challenge with increased noradrenergic tone may represent a specific pathophysiological aspect of the abnormal response to stress or to other specific stimulatory factors in obese women, particularly those with abdominal body fat distribution.

Sympathoadrenal response of postmenopausal women prior and during prolonged administration of estradiol.

OBJECTIVE: Cardiovascular disease seems to increase after the menopause and is thought to be reduced by estrogen replacement therapy. Among the many studies which have tried to define the multifactorial mechanisms of estrogens cardiovascular prevention, very few have focused on their possible modulation of adrenergic activity. In the present study we investigated whether prolonged estradiol replacement via transdermal patches is able to modulate cardiovascular and adrenergic responses to stimuli. METHODS: Baseline and responses to a cold stimulus and to the upright position of catecholamines (epinephrine and norepinephrine), heart rate, systolic and diastolic blood pressure were investigated in 15 healthy volunteer postmenopausal women both prior to and after 2 months of treatment with patches rated to deliver 50 microg/day of estradiol. RESULTS: Basal norepinephrine levels (P<0.005), as well as their integrated responses to the cold stimulus (P<0.02) were lower during estradiol. By contrast, responses of norepinephrine to the upright test, as well as basal and responses to stimuli of epinephrine and circulatory parameters were not different before and during estradiol. CONCLUSIONS: Estradiol replacement at low doses significantly decreases overall sympathetic output, both in basal conditions and under specific stimuli. These effects whether maintained or magnified in the long term may play a role in the prevention of the postmenopausal cardiovascular risk.

Baseline and stimulated catecholamine secretion in normotensive patients with active acromegaly: acute effects of continuous octreotide infusion.

OBJECTIVE: Alterations in catecholamine plasma levels may contribute to the cardiovascular complications of acromegaly. Since few data are available on the catecholamine secretory dynamics in active acromegaly and no evidence exists on catecholamine variations during GH decrease, we studied acromegalic patients before and during octreotide administration. METHODS: We evaluated the catecholamine responses to upright posture and a cold pressure test (CPT) in 11 acromegalic (A) patients before and during continuous administration of octreotide (500 microgram/24h by s.c. pump) compared with 11 normal (N) subjects. RESULTS: All the acromegalic patients showed left ventricular cardiac hypertrophy. The cardiovascular responses to upright posture were similar between normal subjects and acromegalics both before and during octreotide treatment. The basal levels of norepinephrine (NE) were significantly higher in A patients compared with N subjects (423+/-45 vs 264+/-32pg/ml, P<0. 05) and decreased during therapy (291+/-32pg/ml; P<0.01). The increase in plasma NE during upright posture was significantly lower in A than in N subjects (P<0.01), but was restored to normal during octreotide treatment. CPT increased systolic and diastolic blood pressure, pulse rate and NE plasma levels in N (P<0.05) but not in A subjects both before and during octreotide treatment. CONCLUSIONS: Our data demonstrate the presence of increased basal NE levels in acromegalic patients with a defective sympathetic response to stimuli. Short-term octreotide infusion is able to induce a reduction in the basal levels of NE and a normalization of the catecholamine response to posture.