Silicon substituted hydroxyapatite/VEGF scaffolds stimulate bone regeneration in osteoporotic sheep.

Silicon-substituted hydroxyapatite (SiHA) macroporous scaffolds have been prepared by robocasting. In order to optimize their bone regeneration properties, we have manufactured these scaffolds presenting different microstructures: nanocrystalline and crystalline. Moreover, their surfaces have been decorated with vascular endothelial growth factor (VEGF) to evaluate the potential coupling between vascularization and bone regeneration. In vitro cell culture tests evidence that nanocrystalline SiHA hinders pre-osteblast proliferation, whereas the presence of VEGF enhances the biological functions of both endothelial cells and pre-osteoblasts. The bone regeneration capability has been evaluated using an osteoporotic sheep model. In vivo observations strongly correlate with in vitro cell culture tests. Those scaffolds made of nanocrystalline SiHA were colonized by fibrous tissue, promoted inflammatory response and fostered osteoclast recruitment. These observations discard nanocystalline SiHA as a suitable material for bone regeneration purposes. On the contrary, those scaffolds made of crystalline SiHA and decorated with VEGF exhibited bone regeneration properties, with high ossification degree, thicker trabeculae and higher presence of osteoblasts and blood vessels. Considering these results, macroporous scaffolds made of SiHA and decorated with VEGF are suitable bone grafts for regeneration purposes, even in adverse pathological scenarios such as osteoporosis. STATEMENT OF SIGNIFICANCE: For the first time, the in vivo behavior of scaffolds made of silicon substituted hydroxyapatites (SiHA) has been evaluated under osteoporosis conditions. In order to optimize the bone regeneration properties of these bioceramics, 3D macroporous scaffolds have been manufactured by robocasting and implanted in osteoporotic sheep. Our experimental design shed light on the important issue of the biological response of nano-sized bioceramics vs highly crystalline bioceramics, as well as on the importance of coupling vascularization and bone growth processes by decorating SiHA scaffolds with vascular endothelial growth factor.

Synergistic effect of Si-hydroxyapatite coating and VEGF adsorption on Ti6Al4V-ELI scaffolds for bone regeneration in an osteoporotic bone environment.

The osteogenic and angiogenic responses to metal macroporous scaffolds coated with silicon substituted hydroxyapatite (SiHA) and decorated with vascular endothelial growth factor (VEGF) have been evaluated in vitro and in vivo. Ti6Al4V-ELI scaffolds were prepared by electron beam melting and subsequently coated with Ca10(PO4)5.6(SiO4)0.4(OH)1.6 following a dip coating method. In vitro studies demonstrated that SiHA stimulates the proliferation of MC3T3-E1 pre-osteoblastic cells, whereas the adsorption of VEGF stimulates the proliferation of EC2 mature endothelial cells. In vivo studies were carried out in an osteoporotic sheep model, evidencing that only the simultaneous presence of both components led to a significant increase of new tissue formation in osteoporotic bone. STATEMENT OF SIGNIFICANCE: Reconstruction of bones after severe trauma or tumors extirpation is one of the most challenging tasks in the field of orthopedic surgery. This scenario is even more complicated in the case of osteoporotic patients, since their bone regeneration capability is decreased. In this work we present a porous implant that promotes bone regeneration even in osteoporotic bone. By coating the implant with osteogenic bioceramics such as silicon substituted hydroxyapatite and subsequent adsorption of vascular endothelial growth factor, these implants stimulate the bone ingrowth when they are implanted in osteoporotic sheep.

Response of macrophages and neural cells in contact with reduced graphene oxide microfibers.

Graphene-based materials are revealing a great promise for biomedical applications and demonstrating attractiveness for neural repair. In the context of neural tissue damage, the dialogue between neural and immune cells appears critical for driving regeneration, thus making the understanding of their relations pivotal. Herein, the acute response of RAW-264.7 macrophages on nanostructured reduced graphene oxide (rGO) microfibers has been evaluated through the analysis of cell parameters including proliferation, viability, intracellular content of reactive oxygen species, cell cycle, apoptosis, and cell size and complexity. The influence of the direct contact of rGO microfibers on their polarization towards M1 and M2 phenotypes has been studied by analyses of both M1 (CD80) and M2 (CD163) markers and the secretion of the inflammatory cytokines TNF-α and IL-6. Finally, the capability of these rGO microfibers to regulate neural stem cell differentiation has been also evaluated. Findings reveal that rGO microfibers inhibit the proliferation of RAW-264.7 macrophages without affecting their viability and cell cycle profiles. The presence of M1 and M2 macrophages on these microfibers was confirmed after 24 and 48 h, respectively, accompanied by a decrease in TNF-α and an increase in IL-6 cytokine secretion. These rGO microfibers were also able to support the formation of a highly interconnected neural culture composed of both neurons (map2+ cells) and glial cells (vimentin+ cells). These findings encourage further investigation of these microfibers as attractive biomaterials to interact with immune and neural cells, attempting to support wound healing and tissue repair after implantation.

Management of Pregnancy and Delivery in Patients With Hereditary Angioedema Due to C1 Inhibitor Deficiency.

BACKGROUND AND OBJECTIVE: There is little information on pregnancy and delivery in patients with hereditary angioedema due to C1 inhibitor deficiency (C1INH-HAE). The aim of this study was to describe the effect of pregnancy and deliveries on symptoms of C1INH-HAE and review the need for and safety of treatments available during the study period. METHODS: Retrospective review using a purpose-designed questionnaire of 61 C1INH-HAE patients from 5 hospitals specialized in the management of HAE in Spain. The outcomes measured were number of pregnancies, changes in symptoms during pregnancy and delivery, mode of delivery, type of anesthesia during delivery, treatments received, and tolerance of treatments. RESULTS: We reviewed 125 full-term pregnancies (89 without a prior diagnosis of C1INH-HAE), 14 miscarriages, and 4 induced abortions. Patients reported an increased frequency of C1INH-HAE symptoms in 59.2% of pregnancies (74/125) and the presence of symptoms throughout pregnancy in 40% (50/125). Prophylactic C1INH-HAE therapy was used during 9 (7.2%) of the 125 pregnancies. Nine patients--in 11 pregnancies (8.8 %)--received treatment for acute attacks. Most deliveries (n=110, 88%) were vaginal. A cesarean section was necessary in 15 cases (12%). Short-term prophylaxis with pdhC1INH was administered before 14 deliveries (11.2 %); 111 deliveries (88.8 %) were performed without premedication and were well tolerated. Anesthesia was used in 51 deliveries (40.8%). CONCLUSIONS: Pregnancy has a variable influence on the clinical expression of C1INH-HAE. Attacks tend to occur more frequently but not to increase in severity. Vaginal delivery was mostly well tolerated. pdhC1INH prophylaxis should be administered prior to cesarean delivery and is also recommended before vaginal delivery if there are additional risk factors. pdhC1INH should always be available in the delivery room.

Estimating influenza vaccine effectiveness in Spain using sentinel surveillance data.

We aimed to estimate influenza vaccine effectiveness (VE) against laboratory-confirmed influenza during three influenza seasons (2010/11 to 2012/2013) in Spain using surveillance data and to compare the results with data obtained by the cycEVA study, the Spanish component of the Influenza Monitoring Vaccine Effectiveness (I-MOVE) network. We used the test-negative case­control design, with data from the Spanish Influenza Sentinel Surveillance System (SISS) or from the cycEVA study. Cases were laboratory-confirmed influenza patients with the predominant influenza virus of each season, and controls were those testing negative for any influenza virus. We calculated the overall and age-specific adjusted VE. Although the number of patients recorded in the SISS was three times higher than that in the cycEVA study, the quality of information for important variables, i.e. vaccination status and laboratory results, was high in both studies. Overall, the SISS and cycEVA influenza VE estimates were largely similar during the study period. For elderly patients (> 59 years), the SISS estimates were slightly lower than those of cycEVA, and estimates for children (0­14 years) were higher using SISS in two of the three seasons studied. Enhancing the SISS by collecting the date of influenza vaccination and reducing the percentage of patients with incomplete information would optimise the system to provide reliable annual influenza VE estimates to guide influenza vaccination policies.

Clinical Pattern and Acute and Long-term Management of Hereditary Angioedema Due to C1-Esterase Inhibitor Deficiency.

BACKGROUND: Hereditary angioedema due to C1-esterase inhibitor deficiency (HAE-C1-INH) is a life-threatening disease. OBJECTIVES: To describe the clinical characteristics and management of patients with HAE-C1-INH during routine clinical practice. METHODS: An observational, retrospective study was performed in patients with HAE-C1-INH. Demographic, clinical, and analytical data were collected from 2 periods: period A (October 2009-September 2010) and period B (October 2007-September 2009). RESULTS: We studied 112 patients with HAE-C1-INH (57.1% females). Age at onset of symptoms was 14.4 years (lower in patients who had experienced attacks in the previous year). In period B (n=87), 62.1% of patients presented at least 1 edema attack (median, 3.5 attacks/patient/2 years), and 19.1% of attacks were treated. In period A (n=77), 58.4% of patients were on maintenance therapy. Stanozolol was the most widely used drug (48.9%), with a mean weekly dose of 6.7 mg. At least 1 attack was recorded in 72.7% of patients (median, 3.0 attacks/patient/year), and 31.5% of the attacks were treated. Treatment of acute attacks increased by 12.4%. CONCLUSION: Age at onset of symptoms is associated with clinical expression of disease. The higher age at onset of symptoms, the fewer number of attacks per patient and year, and the lower dose of attenuated androgens necessary to control the disease than in other series lead us to hypothesize that HAE-C1-INH could have a less severe expression in Spain. Acute attacks seem to be treated increasingly often.

Piperacillin-induced DRESS: distinguishing features observed in a clinical and allergy study of 8 patients

Background: DRESS (drug reaction with eosinophilia and systemic symptoms) syndrome is characterized by fever, rash, eosinophilia, and multiorgan failure. Previous reports have described differences in clinical and laboratory findings of DRESS syndrome depending on the inducing drug. Piperacillin has been reported as the drug responsible for this syndrome in 3 patients. Objective: To analyze and describe the clinical, laboratory, and allergy study findings of piperacillin-induced DRESS. Patients and Methods: Retrospective case series of patients diagnosed with DRESS associated with piperacillin-tazobactam (Pip/Taz) according to the Kardaun diagnostic score criteria. Assessment of causality was established using the Spanish Pharmacovigilance System and the lymphocyte transformation test (LTT). The allergy study included skin and epicutaneous tests. Results: Eight patients were diagnosed with DRESS due to Pip/Taz (3 probable and 5 definite cases). Skin rash was observed in all cases and facial edema in 50%; the mean latency period was 18 days. Fever was present in 7 patients. Liver and kidney injuries were detected in 6 and 3 patients, respectively. All patients had eosinophilia and a full recovery. The LTT to Pip/Taz was strongly positive in all patients, with a stimulation index of over 6. Three of 3 patients had a positive intradermal test to Pip/Taz, and 1 of 4 had a positive patch test. All patients had a negative LTT to carbapenems. Conclusions: We have reported on the first case series of piperacillin-induced DRESS. A latency period of 18 days, skin rash, eosinophilia, fever, liver injury, and good prognosis were the most common features. The allergy study, and the LTT in particular, was highly useful for identifying Pip/Taz as the culprit drug and piperacillin as the responsible active ingredient (AU)

Antecedentes: El síndrome DRESS se caracteriza por fiebre, erupción cutánea, eosinofilia y afectación multiorgánica. Publicaciones previas han descrito diferencias en la presentación clínica y analítica de este síndrome dependiendo del fármaco inductor. Se han publicado 3 casos de DRESS inducidos por Piperacilina. Objetivo: Analizar y describir las características clínicas, analíticas y el estudio alergológico del DRESS inducido por Piperacilina. Pacientes y métodos: Estudio retrospectivo de una serie de pacientes diagnosticados de DRESS (de acuerdo a escala diagnóstica de Kardaun) por Piperacilina-Tazobactam (Pip/Taz). El establecimiento de causalidad se estableció según el algoritmo del Sistema Español de Farmacovigilancia y el Test de Transformación Linfocitaria (TTL). El estudio alergológico incluyó también pruebas cutáneas y epicutáneas. Resultados: Ocho pacientes diagnosticados de DRESS por Pip/Taz (3 diagnóstico probable y 5 definitivo). Todos los casos presentaron erupción cutánea y el 50% edema facial, tiempo medio de latencia de 18 días. 7 presentaron fiebre y se detectó afectación hepática y renal en 6 y 3 pacientes, respectivamente. Todos los pacientes presentaron eosinofilia y una recuperación completa. El TTL a Pip/Taz fue muy positivo en todos los pacientes con un Índice de Estimulación > 6. 3/3 pacientes presentaron prueba intradérmica positiva a Pip/Taz y 1/4 parche positivo. Todos los pacientes tuvieron TTL negativo a carbapenémicos. Conclusiones: Presentamos la primera serie de casos de DRESS inducido por Piperacilina. Un tiempo de latencia de 18 días, erupción cutánea, eosinofilia, fiebre y afectación hepática junto a un buen pronóstico fueron las características más comunes. El estudio alergológico, principalmente el TTL, fue muy útil para identificar a la Piperacilina/Tazobactam como el fármaco responsable y concretamente a la Piperacilin (AU)

Piperacillin-induced DRESS: distinguishing features observed in a clinical and allergy study of 8 patients.

BACKGROUND: DRESS (drug reaction with eosinophilia and systemic symptoms) syndrome is characterized by fever, rash, eosinophilia, and multiorgan failure. Previous reports have described differences in clinical and laboratory findings of DRESS syndrome depending on the inducing drug. Piperacillin has been reported as the drug responsible for this syndrome in 3 patients. OBJECTIVE: To analyze and describe the clinical, laboratory, and allergy study findings of piperacillin-induced DRESS. PATIENTS AND METHODS: Retrospective case series of patients diagnosed with DRESS associated with piperacillin-tazobactam (Pip/Taz) according to the Kardaun diagnostic score criteria. Assessment of causality was established using the Spanish Pharmacovigilance System and the lymphocyte transformation test (LTT). The allergy study included skin and epicutaneous tests. RESULTS: Eight patients were diagnosed with DRESS due to Pip/Taz (3 probable and 5 definite cases). Skin rash was observed in all cases and facial edema in 50%; the mean latency period was 18 days. Fever was present in 7 patients. Liver and kidney injuries were detected in 6 and 3 patients, respectively. All patients had eosinophilia and a full recovery. The LTT to Pip/Taz was strongly positive in all patients, with a stimulation index of over 6. Three of 3 patients had a positive intradermal test to Pip/Taz, and 1 of 4 had a positive patch test. All patients had a negative LTT to carbapenems. CONCLUSIONS: We have reported on the first case series of piperacillin-induced DRESS. A latency period of 18 days, skin rash, eosinophilia, fever, liver injury, and good prognosis were the most common features. The allergy study, and the LTT in particular, was highly useful for identifying Pip/Taz as the culprit drug and piperacillin as the responsible active ingredient.

3D free-standing porous scaffolds made of graphene oxide as substrates for neural cell growth.

The absence of efficient therapies for the treatment of lesions affecting the central nervous system encourages scientists to explore new materials in an attempt to enhance neural tissue regeneration while preventing inhibitory fibroglial scars. In recent years, the superlative properties of graphene-based materials have provided a strong incentive for their application in biomedicine. Nonetheless, a few attempts to date have envisioned the use of graphene for the fabrication of three-dimensional (3D) substrates for neural repair, but none of these involve graphene oxide (GOx) despite some attractive features such as higher hydrophilicity and versatility of functionalization. In this paper, we report novel, free-standing, porous and flexible 3D GOx-based scaffolds, produced by the biocompatible freeze-casting procedure named ISISA, with potential utility in neural tissue regeneration. The resulting materials were thoroughly characterized by Fourier-transform infrared, Raman, and X-ray photoelectron spectroscopies and scanning electron microscopy, as well as flexibility testing. Embryonic neural progenitor cells were then used to investigate adhesion, morphology, viability, and neuronal/glial differentiation. Highly viable and interconnected neural networks were formed on these 3D scaffolds, containing both neurons and glial cells and rich in dendrites, axons and synaptic connections, and the results are in agreement with those obtained in initial studies performed with two-dimensional GOx films. These results encourage further investigation in vivo on the use of these scaffolds as guide substrates to promote the repair of neural injuries.

New development on materials and techniques used in the heraldic designs of illuminated Manueline foral charters by multi-analytical methods.

In the illuminated foral charters commissioned by D. Manuel I, King of Portugal (1495-1521), heraldry played a prominent role. In this work, royal emblems corresponding to the third heraldic design, applied to the Charter of Couto de Teixedo, are studied by means of EDXRF, SEM-EDS, micro-Raman, micro-FTIR and HPLC-DAD to characterize the materials and techniques used to produce this masterpiece of Portuguese Renaissance. By comparing this data with the results previously obtained in other three charters, this research allows for the first time an accurate insight into the reformed manuscripts production, especially since the illuminated charters under consideration were all investigated on the basis of similar micro-spectroscopic techniques. Inks, metal coatings, pigments, organic dyes, fillers or extenders, and binding media are discussed, and their use enlightened by the politic and legal messages the foral charters had to convey. Parchment analysis allowed us to identify the animal species, and all undertaken processes along its preparation. HPLC-DAD allowed us to differentiate the gums used. CaSO4 was observed in the parchment as a degradation product of CaCO3 used in parchment production in the presence of metal sulfates coming from the ink. Pigments used in the different colors as well as some specific phases for some colors were identified. Silvering and gilding processes, metal caratage and silver oxidation compounds were also objects of the present study.

Management of dental-oral procedures in patients with hereditary angioedema due to C1 inhibitor deficiency.

BACKGROUND: Hereditary angioedema due to C1 inhibitor deficiency (HAE-C1-INH) has considerable implications for dental health care providers, since dental procedures may trigger severe and even life-threatening episodes. The aim of the present study was to analyze the efficacy and safety of premedication with attenuated androgens (AAs), plasma-derived human C1 esterase inhibitor concentrate (pdhC1INH), or both to prevent the development of upper airway angioedema after dental-oral procedures in patients with HAE-C1-INH. MATERIAL AND METHODS: All dental-oral procedures performed on patients with HAE-C1-INH who were followed up at La Paz University Hospital, Madrid, Spain were reviewed. Demographic data, maintenance treatment, preprocedure prophylaxis, disease severity, and occurrence of upper airway angioedema were recorded. RESULTS: Twenty-four patients (14 male/10 female; mean age, 42.6 years) underwent 66 procedures. Most procedures were performed on patients with severe HAE-C1-INH (20 procedures) or moderate HAE-C1-INH (26 procedures). Only 9 procedures were performed without short-term prophylaxis. Mild upper airway angioedema developed after 3 procedures performed without short-term prophylaxis in patients with minimal or asymptomatic HAE-C1-INH. A statistically significant association was found between development of mild postprocedure upper airway angioedema and lack of maintenance treatment with AA, lack of increased dose of preprocedure AA, and failure to administer preprocedure pdhC1INH (P = .002, Fisher exact test). CONCLUSIONS: Increased doses of prophylactic AA, administration of pdhC1INH, or both were good options for ambulatory management of dental-oral procedures in patients with HAE-C1-INH. Prophylaxis with pdC1INH or increased doses of AA is advisable before dental-oral procedures, even in patients with low disease severity.

Management of Dental-Oral Procedures in Patients With Hereditary Angioedema due to C1 Inhibitor Deficiency

Antecedentes: El angioedema hereditario por déficit de C1 Inhibidor (AEH-C1-INH) tiene unas importantes implicaciones para los profesionales de la salud bucodental ya que una cirugía dental puede desencadenar episodios de angioedema potencialmente mortales. El objetivo del estudio fue analizar la eficacia y seguridad de los andrógenos atenuados (AAs) y/o del concentrado plasmático de C1 Inhibidor derivado de humanos (pdhC1INH) para prevenir el desarrollo de angioedema de vías respiratorias superiores tras procedimientos odontoestomatológicos en pacientes con AEH-C1-INH. Material y métodos: Se revisaron los procedimientos odontoestomatológicos realizados en el Hospital Universitario La Paz. Se consideraron datos demográfi cos, tratamiento de mantenimiento, profi laxis pre-procedimiento, grado de severidad de la enfermedad y aparición de angioedema faringolaríngeo. Resultados: Veinticuatro pacientes (14H/10M) (edad media: 42,6 años) se sometieron a 66 procedimientos. La mayor parte se realizaron en pacientes con estadio grave (20 procedimientos) o moderado (26 procedimientos) de la enfermedad. Sólo nueve procedimientos se realizaron sin profilaxis de corto plazo (PCP). En tres procedimientos realizados sin PCP se desarrolló angioedema faríngeo leve ocurriendo en pacientes en estadio asintomático o mínimo de la enfermedad. Se encontró una asociación estadísticamente significativa entre desarrollo mínimo de angioedema de vías respiratorias superiores y ausencia de tratamiento de mantenimiento con AA, ausencia de incremento de dosis y no-administración de pdhC1INH preprocedimiento (Test exacto de Fisher: P=.002). Conclusiones: El aumento de dosis preprocedimiento de AA y/o la administración de pdhC1INH son buenas opciones para el manejo ambulatorio de los procedimientos odontoestomatológicos en pacientes con AEH-C1-INH. El tratamiento profiláctico con pdC1INH o el incremento de dosis de AA es recomendable antes de la manipulación dental, incluso en pacientes con estadio bajo en la escala de gravedad de la enfermedad (AU)

Background: Hereditary angioedema due to C1 inhibitor deficiency (HAE-C1-INH) has considerable implications for dental health care providers, since dental procedures may trigger severe and even life-threatening episodes. The aim of the present study was to analyze the efficacy and safety of premedication with attenuated androgens (AAs), plasma-derived human C1 esterase inhibitor concentrate (pdhC1INH), or both to prevent the development of upper airway angioedema after dental-oral procedures in patients with HAE-C1-INH. Material and Methods: All dental-oral procedures performed on patients with HAE-C1-INH who were followed up at La Paz University Hospital, Madrid, Spain were reviewed. Demographic data, maintenance treatment, preprocedure prophylaxis, disease severity, and occurrence of upper airway angioedema were recorded. Results: Twenty-four patients (14 male/10 female; mean age, 42.6 years) underwent 66 procedures. Most procedures were performed on patients with severe HAE-C1-INH (20 procedures) or moderate HAE-C1-INH (26 procedures). Only 9 procedures were performed without short-term prophylaxis. Mild upper airway angioedema developed after 3 procedures performed without short-term prophylaxis in patients with minimal or asymptomatic HAE-C1-INH. A statistically significant association was found between development of mild postprocedure upper airway angioedema and lack of maintenance treatment with AA, lack of increased dose of preprocedure AA, and failure to administer preprocedure pdhC1INH (P=.002, Fisher exact test). Conclusions: Increased doses of prophylactic AA, administration of pdhC1INH, or both were good options for ambulatory management of dental-oral procedures in patients with HAE-C1-INH. Prophylaxis with pdC1INH or increased doses of AA is advisable before dental-oral procedures, even in patients with low disease severity (AU)

Consensus statement on the diagnosis, management, and treatment of angioedema mediated by bradykinin. Part II. Treatment, follow-up, and special situations.

BACKGROUND: There are no previous Spanish guidelines or consensus statements on bradykinin-induced angioedema. AIM: To draft a consensus statement on the management and treatment of angioedema mediated by bradykinin in light of currently available scientific evidence and the experience of experts. This statement will serve as a guideline to health professionals. METHODS: The consensus was led by the Spanish Study Group on Bradykinin-Induced Angioedema, a working group of the Spanish Society of Allergology and Clinical Immunology. A review was conducted of scientific papers on different types of bradykinin-induced angioedema (hereditary and acquired angioedema due to C1 inhibitor deficiency, hereditary angioedema related to estrogens, angioedema induced by angiotensin-converting enzyme inhibitors). Several discussion meetings were held to reach the consensus. RESULTS: Treatment approaches are discussed, and the consensus reached is described. Specific situations are addressed, namely, pregnancy, contraception, travelling, blood donation, and organ transplantation. CONCLUSIONS: A review of and consensus on treatment of bradykinin-induced angioedema is presented.

Consensus statement on the diagnosis, management, and treatment of angioedema mediated by bradykinin. Part I. Classification, epidemiology, pathophysiology, genetics, clinical symptoms, and diagnosis.

BACKGROUND: There are no Spanish guidelines or consensus statement on bradykinin-induced angioedema. AIM: To review the pathophysiology, genetics, and clinical symptoms of the different types of bradykinin-induced angioedema and to draft a consensus statement in light of currently available scientific evidence and the experience of experts. This statement will serve as a guideline to health professionals. METHODS: The consensus was led by the Spanish Study Group on Bradykinin-Induced Angioedema (SGBA), a working group of the Spanish Society of Allergology and Clinical Immunology. A review was conducted of scientific papers on different types of bradykinin-induced angioedema (hereditary and acquired angioedema due to C1 inhibitor deficiency, hereditary angioedema related to estrogens, angioedema induced by angiotensin-converting enzyme inhibitors). Several discussion meetings of the SGBA were held in Madrid to reach the consensus. RESULTS: The pathophysiology, genetics, and clinical symptoms of the different types of angioedema are reviewed. Diagnostic approaches are discussed and the consensus reached is described. CONCLUSIONS: A review of bradykinin-induced angioedema and a consensus on diagnosis are presented.

Pregnancy protects against antiangiogenic and fibrogenic effects of angiotensin II in rat hearts.

AIM: To investigate the difference between physiological and pathological cardiac remodelling induced, respectively, by pregnancy and angiotensin (Ang) II, and to test the hypothesis that pregnancy protects against Ang II effects. METHODS: Female Wistar rats, pregnant (n = 12) and non-pregnant (n = 12), were implanted with mini-pumps containing saline (sham) or 150 ng kg(-1) min(-1) Ang II. Ten days later echocardiography and blood pressure measurement were performed. Expression of 22 genes was assessed using RT-PCR. Microscopic sections of LV were prepared to determine collagen content (Sirius Red staining), vessel density (ß-actin immunolabelling) and myocytes diameter (Toluidine Blue). RESULTS: Heart weight (HW) was increased in Ang II treated groups compared with their controls. Furthermore, HW of Ang II treated pregnant rats (1.0 ± 0.03 g) was higher than that in non-pregnant sham (0.7 ± 0.02 g), pregnant (0.8 ± 0.01 g) and Ang II treated non-pregnant (0.8 ± 0.02 g) rats. Relative LV wall thickness showed similar pattern. Aortic pressure was significantly increased in Ang II groups. Collagen content was increased in Ang II (4.0 ± 0.5%) compared with sham (1.5 ± 0.1%) but reduced again when treated rats were pregnant (2.8 ± 0.4%). Vessel density was reduced by 47.8% after Ang II treatment in non-pregnant and by only 13.9% in pregnant rats. Gene expression analysis showed increased expression of atrial natriuretic factor (ANF), brain natriuretic peptide (BNP), anykrin repeat domain-containing protein 1 (Ankrd-1), protein kinase C-α and -δ and tumour suppressor gene TP53 (p53) in Ang II treated groups and upregulation of ANF, BNP and Ankrd-1 remained when pregnancy was combined with Ang II. Pregnancy reduced expression of: α-myosin heavy chain, tumour necrosis factor-α, p53, endothelial nitric oxide synthase and inducible nitric oxide synthase. CONCLUSION: Pregnancy seems to counteract the detrimental effects of Ang II on fibrosis and angiogenesis in heart. In addition, pregnancy and Ang II lead to partly opposite changes in the expression of some genes important for heart function.

Use of the lymphocyte transformation test in the diagnosis of DRESS syndrome induced by ceftriaxone and piperacillin-tazobactam: two case reports.

Drug-related rash with eosinophilia and systemic symptoms (DRESS) syndrome, or drug-induced hypersensitivity syndrome (DIHS), is a life-threatening multiorgan systemic reaction characterized by rash, fever, lymphadenopathy, hepatitis, and leukocytosis with eosinophilia. Aromatic anticonvulsant drugs and allopurinol have been reported to be the most frequent eliciting agents. Our search of the literature revealed only 2 cases induced by piperacillin and 1 case by ceftriaxone.We present 2 cases of DRESS syndrome induced by the beta-lactam drugs ceftriaxone and piperacillin-tazobactam. An allergological workup including skin prick test, intradermal tests, patch tests, and lymphocyte transformation test (LTT) was performed. LTT was shown to be a useful technique in both cases to help to identify the drugs involved.

Multiple acute parasitization by Anisakis simplex.

Hypersensitivity to Anisakis is an increasingly prominent medical problem throughout the world, due to a better understanding of diseases induced by parasites and to modern culinary habits of eating raw or undercooked fish. We describe the case of a patient who presented epigastric pain, wheals, erythema, and pruritus 3 hours after the ingestion of fish. More than 200 larvae were obtained by endoscopy. However, the patient only developed an immune response with specific immunoglobulin E and eosinophilia peaking at day 18 and decreasing during the 17-month follow-up. Only eosinophilia reached normal limits.

Mejora de la calidad de la especificación de la inclusión en ensayo clínico sobre prescripciones en quimioterapia / Improving the specification quality of inclusion criteria of patients in chemotherapy clinical trials

Objetivos: Evaluar la mejora de la calidad de las prescripciones de quimioterapia para pacientes en ensayo clínico (EC) y analizar si en la orden médica se especifica la participación en el ensayo tras determinar los principales factores de riesgo y mediante la aplicación de medidas correctoras. Método: Estudio retrospectivo de omisiones recogidas durante 2006 y 2007. Con los datos del 2006 se analizaron los factores de riesgo y se implantaron medidas de mejora (información a prescriptores e inicio de prescripción electrónica). Posteriormente, se evaluaron los datos del 2007. Variables analizadas: EC, número de prescripciones, investigador principal, prescriptor, servicio, antineoplásicos y enfermedad. Resultados: Los servicios de Oncología y Hematología realizaron el 57,1% de los ensayos del hospital. En 2006 se recibieron 1.625 prescripciones y se detectaron 151 incorrectas (9,3%), y en 2007 se recibieron 1.858 prescripciones y se detectaron 65 incorrectas (3,5%). En 2006 se observó mayor frecuencia de prescripciones incorrectas en Hematología (34,1%) que en Oncología (8,6%). En 2007 Hematología apenas tuvo omisiones (1,8%) y en Oncología disminuyeron al 3,6%. Respecto a la enfermedad, la tasa de error desapareció prácticamente en mieloma múltiple (del 34,1 al 2,2%) y disminuyó en mama (del 10,8 al 4,4%). El incumplimiento siempre fue mayor cuando el prescriptor difería del investigador principal. Conclusiones: La frecuencia de las prescripciones con error se redujo (pasó del 9,3 al 3,5%). Destaca la reducción extraordinaria en Hematología relacionada con ensayos en mieloma múltiple. Las medidas correctoras han resultado útiles en la mejora de la calidad (AU)

Objectives: To assess the quality improvement of chemotherapy prescriptions for patients included in clinical trials (CT) analyzing whether the prescription is specified for patient participation, after having identified the major risks factors and the appropriate corrective measures are applied. Methods: Retrospective study of omissions collected during 2006 and 2007. After collecting all the information, we analyzed the risks factors and introduced improvement measures (information to prescribers and the beginning of electronic prescription). The 2007 data were then evaluated. Variables analyzed: CT, number of prescriptions, principal investigator, prescriber, department, anti-neoplastic involved and pathology. Results: Oncology and Haematology make up 57.1% of hospital trials. In 2006, 1625 chemotherapy prescriptions were received and there were 151 incorrect prescriptions (9.3%), and in 2007, 1858 prescriptions with 65 (3.5%) incorrect. In 2006, there was a higher frequency of incorrect prescriptions in Haematology (34.1%) and (Oncology (8.6%)). In 2007 Hematology had just 1.8% of omissions and in Oncology it decreased to 3.6%. As regards the pathology, the error rate has virtually disappeared in multiple myeloma prescriptions (34.1 to 2.2%) and decreased in breast cancer (10.8 to 4.4%). The non-fulfilment rate is higher when the prescriber is not the principal investigator. Conclusions: The overall frequency of prescriptions with errors decreased significantly from 9.3% to 3.5%, with an extraordinary reduction in Haematology (34.1% to 1.8%) related to the multiple myeloma trials. The corrective measures implemented have proved to be useful in CT (AU)