Vascular angiotensin AT1 receptor neuromodulation in fetal programming of hypertension.

Fetal stress increases the susceptibility to cardiovascular diseases in adult age, including hypertension, a process known as fetal programming of hypertension (FPH). This study intends to investigate the interplay between vascular sympathetic nervous system (SNS) and RAS, namely the neuromodulatory role exerted by Angiotensin II (Ang II) receptor-1 (AT1) in FPH, and respective contribution for hypertension. METHODS: 6-month old Sprague-Dawley offspring from mothers fed ad-libitum (CONTROL) or with 50% intake during the second half of gestation (maternal undernutrition, MUN) were used. Sympathetic neurotransmission was studied in mesenteric/tail arteries and mesenteric veins by electrically-evoked [3H]-noradrenaline release experiments using RAS drugs. AT1 receptors in sympathetic nerves of mesenteric arteries were investigated by immunohistochemistry and Laser Scanning Confocal Microscopy. RESULTS: Ang II facilitated noradrenaline release in the vessels studied from MUN and CONTROL rats. Losartan induced a tonic facilitation only in MUN vessels. Sympathetic innervation was larger in MUN versus CONTROL vessels. AT1 receptors on sympathetic nerves were present in higher amounts in MUN versus CONTROL vessels. CONCLUSIONS: Findings support that FPH is associated with a vascular hyper-sympathetic activation, involving a tonic facilitation of prejunctional AT1 receptors by endogenous Ang II, which can justify, at least in part, the development of hypertension.

Effect of fetal undernutrition and postnatal overfeeding on rat adipose tissue and organ growth at early stages of postnatal development.

Intrauterine and perinatal life are critical periods for programming of cardiometabolic diseases. However, their relative role remains controversial. We aimed to assess, at weaning, sex-dependent alterations induced by fetal or postnatal nutritional interventions on key organs for metabolic and cardiovascular control. Fetal undernutrition was induced by dam food restriction (50 % from mid-gestation to delivery) returning to ad libitum throughout lactation (Maternal Undernutrition, MUN, 12 pups/litter). Postnatal overfeeding (POF) was induced by litter size reduction from normally fed dams (4 pups/litter). Compared to control, female and male MUN offspring exhibited: 1) low birth weight and accelerated growth, reaching similar weight and tibial length by weaning, 2) increased glycemia, liver and white fat weights; 3) increased ventricular weight and tendency to reduced kidney weight (males only). Female and male POF offspring showed: 1) accelerated growth; 2) increased glycemia, liver and white fat weights; 3) unchanged heart and kidney weights. In conclusion, postnatal accelerated growth, with or without fetal undernutrition, induces early alterations relevant for metabolic disease programming, while fetal undernutrition is required for heart abnormalities. The progression of cardiac alterations and their role on hypertension development needs to be evaluated. The similarities between sexes in pre-pubertal rats suggest a role of sex-hormones in female protection against programming.

Analysis of patients referred to a lung transplantation unit.

This cross-sectional, concurrent and descriptive study presents the decisions regarding patients referred to our Lung Transplantation Unit (LTxU). Each patient is discussed in a multidisciplinary clinical session (phase I), rejecting some and accepting others for assessment in our LTxU (phase II) according to criteria of the National and International Guidelines for Transplantation. A protocol assessment in phase II, leads to a decision to reject, accept, or follow-up the candidate for LTx. Among 214 evaluation requests received in our unit from May 2008 to December 2011, 37 patients (17%) were rejected based on the information sent to our LTxU. Among the patients evaluated in phase II, 62 (28.9%) were put on the waiting list, 125 (58.4%) were rejected, and twenty-seven (12.6%) were postponed for future reconsideration, results that were similar to those described in the literature. The main disease referred for LTx was obstructive airflow (n = 98; 45.7%), followed by interstitial lung disease (ILD; n = 66; 30.8%), cystic fibrosis or bronchiectasis (n = 20; 9.3%), or primary pulmonary hypertension group 1 (n = 20; 9.3%). Ten patients (4.6%) were diagnosed with other respiratory diseases. Most patients (n = 165; 77.1%) lived in the region of our hospital (Madrid). The main reasons to reject patients for LTx were malnutrition, severe disease in other organs, toxic habits, and refusal of treatment. Finally, one out of four referred patients was accepted for LTx. In addition to serious comorbidities in various organs, a high percentage of patients who were not accepted for LTx because of these factors might have been of accepted had these conditions been corrected before patient referral.

Recommendations on the use of everolimus in lung transplantation.

The antiproliferative effect of everolimus provides a therapeutic option in the immunosuppression therapy of lung transplantation, by reducing both the risk of acute rejection and the process of progressive fibrosis that determines chronic graft rejection. However, few data on the use of everolimus in lung transplantation have been published to date, and the specific indications of the drug, along with the most adequate time for its introduction or dosing, have not been defined yet. The aim of this article is to propose recommendations for the use of everolimus in lung transplant recipients, including indications, dosing schedules and the use of concomitant immunosuppression. This consensus document has been developed by experts of all the Spanish lung transplant groups from the review of the existing literature and the clinical experience.

Development of a non-heart-beating donor program and results after the first year.

Our lung transplant unit began activity in October 2008. We have performed 37 lung transplants with a hospital mortality of 2.7% (n = 1). The need for a greater number of donors and the presence of an already existent non-heart-beating donor (NHBD) program for abdominal grafts and tissues encouraged us to consider assessing lung grafts from these donors. It was necessary to develop a new multiorgan preservation methodology, "bithermia preservation." The clinical experience with which during the first year June 2010 to July 2011, including 15 NHBDs is presented herein. The chest x-ray was normal in 6 donors (40%) and 7 had pulmonary infiltrates. Bronchoscopy was normal in 8 donors (53%) but 3 had abundant bleeding airway secretions and signs of bronchoaspiration. Preservation procedures were performed in 6 donors. Pulmonary functional evaluation in 4 donors showed gas measurements to be adequate in 75% of cases. Three double-lung grafts were judged to be valid for implantation, among which we performed 3 lung transplantations, 1 bilateral and 2 unilaterals, while 2 grafts were offered to the National Transplant Organization for other units. No transplant suffered primary graft dysfunction; all 3 showed excellent function allowing early extubation in 2 cases. There was no in-hospital mortality. All 3 patients are alive and leading normal lives; none has bronchiolitis obliterans syndrome. In conclusion, the "bithermia preservation" methodology achieved adequate lung preservation in NHBDs, allowing liver, kidneys, and lungs to be obtained from the same donor.

[Lung transplant therapy for suppurative diseases]. / Trasplante pulmonar en enfermedades supurativas.

OBJECTIVE: Lung transplantation is a valid therapeutic approach for patients with bronchiectasis. The objective of the present study was to evaluate our experience with bronchiectasis patients and compare the results in patients with cystic fibrosis to results in those with bronchiectasis caused by other processes. PATIENTS AND METHOD: We carried out a retrospective study of bronchiectasis patients treated by lung transplantation in order to analyze demographic, functional and microbiological characteristics before and after transplantation, and survival. RESULTS: From 1991 to 2002 lung transplants were performed on 171 patients, 44 of whom had suppurative lung disease (27 had cystic fibrosis and 17 had bronchiectasis caused by other processes). There were no significant differences in the demographic variables between the 2 groups. At transplantation, lung function variables showed severe bronchial obstruction (mean [SD] forced expiratory volume in 1 second of 808 [342] mL and forced vital capacity of 1,390 [611] mL) and respiratory insufficiency (PaO2 at 52 [10] mm Hg and PaCO2 at 48 [9] mm Hg). Only PaO2 was significantly lower in patients with bronchiectasis from causes other than cystic fibrosis. Airway colonization was present in 91% of the patients; Pseudomonas spp germs were detected in 64% of the cases and were multiresistant in 9%. In the early postoperative period germs were isolated in 59% of the cases, half of which involved the same germ as had been isolated before transplantation. One year after lung transplantation, 34% of the patients continued to have bronchial colonization. Survival at 1 year was 79% and at 5 years, 49%, with no significant difference between the patients with cystic fibrosis and those with other suppurative diseases, nor between the patients with and without Pseudomonas colonization. Only 2 patients had died of bacterial pneumonia at 1 month after transplantation. CONCLUSIONS: Although airway colonization in patients with suppurative diseases complicates postoperative management, the results in terms of survival are good.

Is gammaglobulin anti-CMV warranted in lung transplantation?

UNLABELLED: The usefulness of anti-CMV hyperimmune gammaglobulin (IgG-CMV, Cytotec) in lung transplant patients (LTx) is controversial. The objective of this study was to analyze the effectiveness of IgG-CMV in our LTx receptors. PATIENTS AND METHODS: A retrospective study of LTx recipients treated with IgG-CMV as prophylaxis or as treatment for invasive disease. We used IgG-CMV associated with IV ganciclovir (GCV) as treatment for invasive disease. High-risk patients (CMV-negative recipients from CMV-positive donors; CMV-/+) were also with IgG-CMV prophylaxis during the first year. Other prophylactic uses of IgG-CMV were as an alternative to GCV in patients with related GCV toxicity, and as preemptive therapy in cases of persistent positive viral load (antigenemia > or = 1 cell and/or a PCR > or = 400) although oral GCV administration. RESULTS: Between January 2000 and August 2003, 14 of the 74 lung transplant recipients (19%) received IgG-CMV as treatment for invasive disease (4 cases: 2 gastritis, 1 esophagitis, 1 hepatitis) and/or as prophylaxis (14 cases). All patients treated for invasive disease evolved favorably. No therapeutic failure were observed in CMV-/+ patients during treatment. Three of the six patients treated with IgG-CMV developed positive antigenemia despite treatment. The four patients treated for persistent antigenemia while receiving oral GCV achieved neutralization during the first month of treatment. CONCLUSION: IgG-CMV associated with Gancyclovir is effective as treatment for invasive disease and as pre-emptive therapy in patients with persistent positive viral load. In CMV-/+ recipients, IgG-CMV prevents pneumonitis and delays the development of invasive disease after the first year.

MAO activity in serotonergic endings of rat major cerebral arteries.

The present work studies the existence of monoamine oxidase (MAO) activity in serotonergic endings present in rat major cerebral arteries. Enzymatic activity was appraised in vivo by serotonin (5-HT) accumulation or 5-hydroxyindole acetic acid (5-HIAA) disappearance with time after systemic administration of MAO inhibitors. Pargyline (75 mg/Kg, ip) brought about significant 5-HT increase and 5-HIAA decrease in major cerebral arteries 30 and 60 min after its administration. Clorgyline (75 mg/Kg, ip) also induced 5-HT enhancement and 5-HIAA decline in these arteries 30 and 60 min after its injection. However, treatment with deprenyl (75 mg/Kg, ip) only evoked a significant 5-HT increase at 60 min. When either clorgyline (5 mg/Kg, ip) or deprenyl (5 mg/Kg, ip) were administered 5-HT and 5-HIAA levels remained unaffected. Two weeks after performing electrolytical lesion of dorsal raphe nucleus and 60 min after clorgyline (75 mg/Kg, ip) injection 5-HT and 5-HIAA levels appeared significantly reduced in cerebral arteries and striatum when compared to sham-lesioned controls. These results suggest that MAO-A isoform acting on endogenous 5-HT is present in rat major cerebral arteries and is located in nerve endings of fibers arising from dorsal raphe nucleus.

Rapamycin in lung transplantation: preliminary results.

INTRODUCTION: Rapamycin is a potent immunosuppressive agent with a different mechanism of action and different adverse effects from those of calcineurin inhibitors (CNIs). OBJECTIVE: To analyze our experience with rapamycin in patients undergoing lung transplantation and heart-lung transplantation in our center. PATIENTS AND METHODS: Patients were treated with rapamycin when showing chronic rejection and/or toxicity associated with the CNI after lung transplantation or heartlung transplantation. Patients with chronic rejection were administered rapamycin in combination with CNIs, whereas the CNIs were eliminated in patients with toxicity. RESULTS: Since October 2001, 7 patients (4 women), of mean age 45+/-15 years, received treatment with rapamycin (heart-lung transplantation, 2 cases; lung transplantation, 5 cases). The indications were chronic rejection in 4 patients and CMIs toxicity in 3 patients (kidney failure in 2 cases and optic neuropathy in 1 case). Pulmonary function stabilization was observed in 3 of 4 patients receiving rapamycin for chronic rejection. In the 3 patients with CNIs toxicity elimination of these drugs did not result in pulmonary functional deterioration. Patients with kidney failure showed an improvement in creatinine levels; visual acuity improved in the patient with optic neuropathy. We observed 2 infectious complications (pneumococcal pneumonia and pulmonary aspergillosis), which resolved with treatment. CONCLUSION: Rapamycin is an alternative for lung-transplant recipients who develop chronic rejection and/or CNIs toxicity.

[Pulmonary sarcoidosis and antiphospholipid syndrome]. / Sarcoidosis pulmonar y síndrome antifosfolipídico.

Pulmonary sarcoidosis is an idiopathic granulomatosis with a clinical picture involving dyspnea, coughing, chest pain and characteristic radiologic changes. A review of English and Spanish language publications (PubMed 1990 through 2002) suggests that our report of a case of pulmonary sarcoidosis associated with primary antiphospholipid syndrome is the first one in the literature for this period. The patient was a 35-year-old man with venous thrombosis who later developed pulmonary sarcoidosis. The clinical course was not favorable in spite of good prognostic factors. We conclude that the association of these two clinical conditions is rare and that the presence of antiphospholipid syndrome may lead to greater morbidity and mortality.

Measurement of pleural pressure during therapeutic thoracentesis.

The aim of therapeutic thoracentesis (TT) is to aspirate as much pleural fluid as possible. Monitoring pleural pressure (PlP) during TT has been proposed to avoid the adverse effects due to an unintended sharp drop in PlP. The objectives of this study are to ascertain the diagnostic value of the PlP measurement, to find a predictive variable of the amount of fluid that can be removed, to obtain insight into the characteristics of the PlP curve and pleural elastance (PE) during TT, and to describe the complications of TT. Sixty-one unselected patients were studied. Only the four patients with suspected trapped lung had an initial PlP lower than -4 cm H(2)O and a PE higher than 33 cm H(2)O/L. There was a weak correlation (r = 0.52) between PE during the first 0.5 L aspirated and the total amount of fluid aspirated. Partial PE values were 10, 7.5, and 14 cm H(2)O/L at the early, intermediate, and late phases of TT. No complications were found except for nine pneumothoraces. In conclusion, the technique was clinically helpful because large amounts of pleural fluid could be aspirated with few and mild complications, and because it allows clinicians to support the preliminary diagnosis of trapped lung. None of the studied variables was found to predict the suitability of aspirating more than 1.5 L. Rather than being monotonically descendent, the PlP curve shows a three-part line with the deepest slopes at the first and last phases of the thoracentesis.

[Aspergillosis in pulmonary transplantation]. / Aspergilosis en el trasplante pulmonar.

BACKGROUND: Fungal infections are a frequent cause of morbidity an mortality in transplant recipients. Aspergillus spp. is an ubiquitous fungus capable of producing diverse clinical entities with varying severity. OBJECTIVE: To study the incidence and severity of Aspergillus spp. infections in lung transplantation, analysing the different clinical presentations and response to antifungal drugs. METHODS: A review was made of the clinical histories of all patients undergoing lung transplantation who developed positive Aspergillus spp. cultures in our centre between June 1991 and December 1996. RESULTS: Eleven of 49 transplanted patients (22%) developed Aspergillus spp. infections. Four patients presented invasive aspergillosis forms and 7 tracheobronchitis. In spite of antifungal treatment 3 patients (30%) died of invasive aspergillosis as a direct consequence of the infection. Of the 7 patients with tracheobronchitis, 2 were ulcerative and 1 pseudomembranous, all responded to antifungal treatment. Three patients (10.3%) developed Aspergillus spp. infections despite prophylaxis with itraconazole. CONCLUSION: Invasive aspergillosis in the immediate posttransplant period was mortal despite treatment. As opposed, aspergillar tracheobronchitis have been overcome using combined treatments of liposomal or lipidic amphotericin, itraconazole and nebulised amphotericin.

Prevalence of cutaneous manifestations in 200 patients with eating disorders.

BACKGROUND: Eating disorders are increasing and show a variety of symptoms. They mainly include anorexia nervosa (AN), bulimia nervosa (BN), and eating disorders not specified (EDNOS). They predominate in females and represent an important danger, especially in teenagers. In serious cases, they may be life-threatening. Objective To determine the prevalence of cutaneous findings in patients with eating disorders and to compare the results with those found in the literature. METHODS: An observational, transverse, and prospective study was performed. Two hundred patients of recent admission to ALUBA (association that fights against BN and AN), a psychiatric unit for eating disorders, were included: 122 BN; 62 AN; 16 EDNOS. RESULTS: Patients with eating disorders show dermatologic manifestations (alopecia, xerosis, hypertrichosis, caries, nail fragility) that are secondary to starvation. Russell's sign, seen as calluses on the dorsal aspect of the hands, is a consequence of self-induced vomiting and the local trauma of the superior incisors. This sign represents a compensatory behavior to overeating and predominates in the BN group. CONCLUSION: The recognition of dermatologic signs could be of immense value and could lead to the early diagnosis and treatment of these eating disorders.

Local treatments of dorsal raphe nucleus induce changes in serotonergic activity in rat major cerebral arteries.

BACKGROUND AND PURPOSE: Rat major cerebral arteries seem to receive serotonergic fibers originating from the dorsal raphe nucleus (DRN), but little is known about their function. The aim of our present work was to establish a functional relationship between this brain stem nucleus and the cerebral blood vessels by studying the effects of several treatments in the DRN on cerebrovascular serotonergic activity. METHODS: Serotonin, clomipramine, 8-OH-DPAT, and WAY-100635 were administered in DRN. A stereotaxically localized electrode allowed the electrical stimulation of this brain stem nucleus. Serotonergic activity was appraised in major cerebral arteries, striatum, and hippocampus from 5-hydroxytryptophan accumulation after aromatic L-amino acid decarboxylase inhibition with NSD-1015. RESULTS: Serotonin significantly decreased serotonergic activity in major cerebral arteries and striatum without affecting it in hippocampus. This reduction was blocked by previous injection of WAY-100635 in DRN. Local administration of 8-OH-DPAT or clomipramine elicited an effect similar to that of serotonin, whereas that of WAY-100635 did not modify serotonergic activity in either of the tissues. Electrical stimulation of DRN significantly increased serotonergic activity in major cerebral arteries and striatum but not in hippocampus. CONCLUSIONS: These results confirm the presence of a serotonergic innervation in rat major cerebral arteries functionally related to DRN. 5-HT(1A) receptor activation partly mediates the action of serotonin in DRN. A serotonergic tone acting on these somatodendritic receptors was not clearly found.

[Chronic obstructive pulmonary disease and lung transplants: results in Spain]. / EPOC y trasplante pulmonar: resultados en España.

OBJECTIVE: To determine the outcome of lung transplantation in patients with chronic obstructive pulmonary disease (COPD) in Spain. METHODS: In all COPD patients transplanted at four Spanish hospitals over a period of seven years, we studied actuarial survival rates retrospectively using the Kaplan Meier test in relation to demographic characteristics, type of transplant, underlying disease, lung function evolution in terms of forced vital capacity (FVC), maximum expiratory flow in 1 second (FEV1) and gasometric evolution (PaO2 and PaCO2). RESULTS: Seventy-four transplants were performed in COPD patients over a five-year period. Mean age was 47 +/- 7 years (26-61) and 77% of the patients were men. A diagnosis of emphysema was made in 58%, alpha-1 antitrypsin deficiency emphysema in 14% and chronic bronchitis in 28%. The likelihood of survival was 75% for the first year, 63% for two years and 41% for the third year. Lung function and blood gases improved significantly by the third month after transplantation: FVC was 1677 +/- 637 ml before transplantation and 2631 +/- 670 ml afterwards; FEV1 was 585 +/- 189 ml before transplantation and 2118 +/- 673 ml afterwards (p < 0.001). Double lung transplants achieved significantly greater improvement in function variables than did single-lung transplants (FVC 2843 +/- 681 ml and FEV1 2543 +/- 620 ml by the third month in DLT patients versus FVC 2402 +/- 587 ml and FEV1 1659 +/- 350 ml for SLT), with no significant differences in blood gases after the two types of transplant. Half the sing-lung transplant patients developed hyperinflation of the native lung and reached maximum lung function values, which tended to be lower than those for patients who did not experience this complication (FEV1 1638 +/- 349 ml versus 1930 +/- 307 ml, p = 0.051). CONCLUSIONS: First-year mortality in patients with COPD undergoing lung transplantation in Spain is similar to that described in the International Transplant Registry. We found no differences between double- and single-lung transplant patients. Functional change is good for both types of transplantation, although this aspect of outcome is significantly better when two lungs are transplanted.

Manifestaciones cutáneas de la anorexia y bulimia / Dermatological aspects in bulimia and anorexia nervosa

Se analizan los aspectos dermatológicos de 100 pacientes con patología de la conducta alimentaria, de los cuales 60 correspondieron a bulimia nerviosa (BN) y 40 a anorexia nerviosa (AN). La mayoría eran de sexo femenino, con edad promedio de 17 años. Fueron características comunes de ambas patologías xerosis, acné, alopecia y caries, destacándose en BN dermatitis artefacta, carotenodermia y signo de Russell y en AN hipertricosis y amenorrea. Se enfatiza la importancia del reconocimiento de estos cuadros que están en crecimiento y donde el diagnóstico precoz es fundamental para iniciar un tratamiento adecuado

[The 1898 crisis and the new scientific institutions: the creation of Ramón y Cajal's biological research laboratory]. / El Noventayocho y las nuevas instituciones científicas. La creación del Laboratorio de Investigaciones Biológicas de Ramón y Cajal.

The neglect of science was considered to be one of the causes of the 1898 crisis and therefore the production of science was regarded at the end of the last century as one of the principal measures to achieve national regeneration. The creation of research institutions, especially for outstanding researchers like Cajal, became a national goal. The press contributed greatly to bring about this goal, and in the case of Cajal, was not only the reporter but also the instigator of the campaign to provide him with his own research centre: the Biological Research Laboratory. This paper analyses the start, development and culmination of this campaign.