The effect of renin–angiotensin–aldosterone system blockers on the progression of chronic kidney disease in hypertensive elderly patients without proteinuria: PROERCAN study. Rationale and design / Efecto de los bloqueantes del sistema renina-angiotensina-aldosterona en la progresión de la enfermedad renal crónica en pacientes añosos sin proteinuria: ensayo clínico PROERCAN. Diseño y justificación del estudio

INTRODUCTION: Blood pressure (BP) control is fundamental to the care of patients with chronic kidney disease (CKD), and is relevant at all stages of CKD. Renin-angiotensin-aldosterone system (RAAS) blockers have shown to be effective, not only in BP control but also in reducing proteinuria and slowing CKD progression. However, there is a lack of evidence for recommending RAAS blockers in elderly patients with CKD without proteinuria. The primary outcome of the present study is to evaluate the impact of RAAS blockers on CKD progression in elderly patients without proteinuria. MATERIALS AND METHODS: The PROERCAN trial (trial registration, NCT03195023) is a multicentre open-label, randomized controlled clinical trial with 110 participants over 65 years-old with hypertension and CKD stages 3-4 without proteinuria. Patients will be randomized in a 1:1 ratio to either receive RAAS blockers or other antihypertensive drugs, and will be followed up for three years. Primary outcome is the estimated glomerular filtration rate (eGFR) decline at 3 years. Secondary outcomes include BP control, renal and cardiovascular events, and mortality. RESULTS AND CONCLUSIONS: The design of this trial is presented here. The results will show if antihypertensive treatment with RAAS blockers has an impact on CKD progression in elderly patients without proteinuria. Any differences in BP control, cardiovascular events, and mortality with each antihypertensive treatment will be also clarified

INTRODUCCIÓN: El control de la presión arterial (PA) es fundamental para los pacientes con enfermedad renal crónica (ERC) y es relevante en todos los estadios de ERC. Los bloqueantes del sistema renina-angiotensina-aldosterona (BSRAA) han demostrado su efectividad no solo en el control de la PA sino también en la reducción de la proteinuria y de la progresión de la ERC. Sin embargo, no existe evidencia para recomendar el uso de BSRAA en pacientes añosos con ERC sin proteinuria. El objetivo principal del estudio es evaluar el impacto de los BSRAA en la progresión de ERC en pacientes añosos sin proteinuria. MATERIAL Y MÉTODOS: El estudio PROERCAN (NCT03195023) es un ensayo clínico multicéntrico, abierto, aleatorizado de 110 pacientes hipertensos, mayores de 65 años con ERC estadios3 y4 sin proteinuria. Los pacientes son aleatorizados 1:1 a recibir tratamiento con BSRAA u otros antihipertensivos y el seguimiento será de 3años. La variable principal es el descenso del filtrado glomerular estimado durante el tiempo de seguimiento. Las variables secundarias incluyen las cifras de PA, eventos renales y cardiovasculares y mortalidad. RESULTADOS Y CONCLUSIÓN: El diseño del ensayo clínico se desarrolla en el presente artículo. Los resultados determinarán si el tratamiento antihipertensivo con BSRAA tiene un impacto en la progresión de la ERC en pacientes añosos sin proteinuria. Así mismo, se aclararán las diferencias en el control de la PA, los eventos cardiovasculares y la mortalidad con los distintos tratamientos antihipertensivos

The effect of renin-angiotensin-aldosterone system blockers on the progression of chronic kidney disease in hypertensive elderly patients without proteinuria: PROERCAN study. Rationale and design.

INTRODUCTION: Blood pressure (BP) control is fundamental to the care of patients with chronic kidney disease (CKD), and is relevant at all stages of CKD. Renin-angiotensin-aldosterone system (RAAS) blockers have shown to be effective, not only in BP control but also in reducing proteinuria and slowing CKD progression. However, there is a lack of evidence for recommending RAAS blockers in elderly patients with CKD without proteinuria. The primary outcome of the present study is to evaluate the impact of RAAS blockers on CKD progression in elderly patients without proteinuria. MATERIALS AND METHODS: The PROERCAN trial (trial registration, NCT03195023) is a multicentre open-label, randomized controlled clinical trial with 110 participants over 65 years-old with hypertension and CKD stages 3-4 without proteinuria. Patients will be randomized in a 1:1 ratio to either receive RAAS blockers or other antihypertensive drugs, and will be followed up for three years. Primary outcome is the estimated glomerular filtration rate (eGFR) decline at 3 years. Secondary outcomes include BP control, renal and cardiovascular events, and mortality. RESULTS AND CONCLUSIONS: The design of this trial is presented here. The results will show if antihypertensive treatment with RAAS blockers has an impact on CKD progression in elderly patients without proteinuria. Any differences in BP control, cardiovascular events, and mortality with each antihypertensive treatment will be also clarified.

Expansion of a CD26low Effector TH Subset and Reduction in Circulating Levels of sCD26 in Stable Allergic Asthma in Adults.

BACKGROUND AND OBJETIVE: The pathogenesis of asthma is dependent on the balance between regulatory and effector T cells, which display differential expression of CD25 and CD26. Therefore, alteration of circulating levels of sCD25 and sCD26 during allergic asthma could be conditioned by changes in leukocyte phenotype. Objectives: To analyze expression of CD25 and CD26 on T lymphocytes and their soluble derivatives (sCD25, sCD26) during stable phases of moderate-severe allergic asthma. METHODS: Cross-sectional study with 2 adult cohorts of allergic asthmatics. Clinical, anthropometric, pulmonary, hematological, and biochemical parameters were measured. Phenotyping was performed with flow cytometry in both circulating and cultured leukocytes. Dipeptidyl peptidase 4 (DPP4) activity was assayed in culture supernatants. RESULTS: In vitro studies revealed upregulation of CD26 on human T lymphocytes upon activation, especially under TH17-favoring conditions, and a correlation with soluble DPP4 activity (rs=0.641; P<.001). CD26 expression on lymphocytes was higher in asthmatics, while serum sCD26 was lower in women and patients. The latter finding could be associated with an expanded CD25low/CD26low/CD127low subset of effector CD4+ T cells in allergic asthma, with no changes in Treg percentages. However, women showed an increased Teff/Treg ratio, which could explain their greater susceptibility to asthma. CONCLUSIONS: Allergic asthma causes an increment in CD25lowCD26low helper T cells detected in stable stages. These changes are mirrored in serum and should be considered in the light of the downmodulating role of CD26 in major chemokines related to the pathogenesis of asthma such as CCL11 (eotaxin), CCL5 (RANTES), and CXCL12a (SDF-1α).

Expansion of a CD26 low effector TH subset and reduction in circulating levels of sCD26 in stable allergic asthma in adults

Background: The pathogenesis of asthma is dependent on the balance between regulatory and effector T cells, which display differential expression of CD25 and CD26. Therefore, alteration of circulating levels of sCD25 and sCD26 during allergic asthma could be conditioned by changes in leukocyte phenotype. Objectives: To analyze expression of CD25 and CD26 on T lymphocytes and their soluble derivatives (sCD25, sCD26) during stable phases of moderate-severe allergic asthma. Methods: Cross-sectional study with 2 adult cohorts of allergic asthmatics. Clinical, anthropometric, pulmonary, hematological, and biochemical parameters were measured. Phenotyping was performed with flow cytometry in both circulating and cultured leukocytes. Dipeptidyl peptidase 4 (DPP4) activity was assayed in culture supernatants. Results: In vitro studies revealed upregulation of CD26 on human T lymphocytes upon activation, especially under TH17-favoring conditions, and a correlation with soluble DPP4 activity (rs=0.641; P<.001). CD26 expression on lymphocytes was higher in asthmatics, while serum sCD26 was lower in women and patients. The latter finding could be associated with an expanded CD25 low/CD26 low /CD127 low subset of effector CD4 + T cells in allergic asthma, with no changes in Treg percentages. However, women showed an increased Teff/Treg ratio, which could explain their greater susceptibility to asthma. Conclusions: Allergic asthma causes an increment in CD25 low CD26Low helper T cells detected in stable stages. These changes are mirrored in serum and should be considered in the light of the downmodulating role of CD26 in major chemokines related to the pathogenesis of asthma such as CCL11 (eotaxin), CCL5 (RANTES), and CXCL12a (SDF-1alfa) (AU)

Introducción: La patogénesis del asma depende del equilibrio entre células T reguladoras y T efectoras, las cuales presentan distintos niveles de CD25 y CD26. Por tanto, la alteración de la concentración de sCD25 y sCD26 durante el asma alérgica podría estar condicionada por cambios en el fenotipo de los leucocitos. Objetivos: Analizar la expresión de CD25 y CD26 en linfocitos T y sus derivados solubles (sCD25 y sCD26) durante asma alérgica moderada-severa y en fases estables. Métodos: Estudio transversal con dos cohortes de adultos con asma alérgica. Se han medido parámetros clínicos, antropométricos, de función pulmonar, hematológicos y bioquímicos. Se ha hecho el fenotipado de leucocitos circulantes y en cultivo mediante citometría de flujo. Se ha analizado la actividad Dipeptidil peptidasa 4 (DPP4) en sobrenadantes de cultivo. Resultados: Los estudios in vitro mostraron un aumento de expresión de CD26 en linfocitos T humanos tras activación, especialmente en condiciones favorables para TH 17, y una correlación con la actividad DPP4 soluble (rs=0,641; p < 0,001). La expresión de CD26 en linfocitos fue mayor en asmáticos, mientras que sCD26 estaba reducido en sueros de mujeres y pacientes. Este último hallazgo podría ser relacionado con la expansión de una subpoblación CD25 low/CD26 low/CD127 low de células T CD4 + efectoras en asma alérgica, sin cambios en los porcentajes de Treg. Sin embargo, las mujeres mostraron un incremento del cociente Tef/Treg, lo cual podría explicar su mayor susceptibilidad al asma. Conclusiones: El asma alérgica causa un incremento de células TH CD25 low CD26 low durante fases no activas. Estos cambios se reflejan en suero y deberían tenerse en cuenta a la luz de la función inhibidora de CD26 sobre quimioquinas importantes relacionadas con la patogénesis del asma, como CCL11 (eotaxina), CCL5 (RANTES) o CXCL12a (SDF-1alfa)

Accelerated Osteogenic Orthodontics™ for retreatment of a patient with diminished root length and absence of the maxillary central incisor.

An 18-year-old female patient visited a university orthodontics department with a chief complaint of an unesthetic appearance of her teeth, including a protruded upper central incisor and unsatisfactory results from previous orthodontic treatment. Pretreatment records showed a Class II skeletal and dental relation with proclined upper and lower incisors, replacement of an absent upper left central incisor with the left upper cuspid, presence of the upper left deciduous cuspid, mild crowding, and 4 mm of overbite and overjet. The panoramic radiograph showed shortened roots of multiple teeth. Accelerated Osteogenic Orthodontics™ (AOO™) was recommended as an approach to reduce the treatment time and the risk of further root shortening. Despite being more expensive and requiring a surgical procedure, this treatment option was very attractive to the patient. The overall treatment time was 14 months. Facial balance was improved, and good occlusal relationships were achieved from the functional and esthetic perspectives. In conclusion, surgically facilitated orthodontics (specifically, AOO™) is an efficient and safe therapeutic tool for treating or retreating orthodontic patients with diminished root length.

Perphenazine as a Cause of Mother-to-Daughter Contact Dermatitis and Photocontact Dermatitis

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Hypersensitivity to penicillin V with good tolerance to other beta-lactams.

A 24 year-old man developed an anaphylactic reaction within thirty minutes of an oral administration of penicillin V. He suffered from recurrent streptococal pharyngitis that was usually treated with penicillin V with good tolerance. Skin prick and intradermal tests with penicilloyl-polylysine, minor determinant mixture, amoxicillin, ampicillin and cefuroxima were negative. However, a skin prick test with penicillin V was positive in the patient and negative in 10 controls. Determination of specific (Immunogloblulin (Ig) E to penicillin V was 0.64 kU/L. Specific IgE to penicillin G, amoxicillin and ampicillin were all negative. Single blind controlled oral challenge with amoxicillin and cefuroxime were both negative. This is an exceptional case of an anaphylactic reaction induced by phenoxymethylpenicillin with positive allergologic study in vivo and in vitro tests and with negative allergological study to other beta-lactams.

Medical audit on asthma in an emergency department.

BACKGROUND: To determine the management of acute bronchial asthma in an adult emergency department. METHODS: A retrospective medical audit of 46 consecutive adult patients with acute asthma exacerbations was performed. We collected information from 48 episodes of acute asthma over a 5-month period. Using classical audit methodology, four indicators were examined: severity evaluation, diagnostic tests, specific treatment, and discharge treatment plans. RESULTS: The least recorded severity indicators were respiratory rate (27 %), heart rate (50 %) and peak expiratory flow (20 %). Heart and respiratory auscultation were recorded in all patients and oxygen saturation was recorded in 93 %. Laboratory blood test and chest radiograph were performed in all patients. Arterial blood gas was tested in 57 %, electrocardiography in 17 %, and coagulation in 39 %. No treatment was provided in 12 % of patients. Bronchodilator medications were administered in all treated patients and oxygen was prescribed in 60 %. Systemic corticosteroids (methylprednisolone or hydrocortisone) were administered in 80 % of treated patients. Seventeen percent of patients were discharged from hospital with no change to their usual treatment. CONCLUSIONS: The following weak points were identified: 1) Severity assessment is inadequate, 2) use of diagnostic tests is excessive, 3) patients discharged to home with no treatment plan. Opportunities for improvement consisted of: 1) greater availability of peak expiratory flow meters, 2) individualized use of diagnostic tests, and 3) management protocols.

Medical audit on asthma in an emergency department / Revisión del control del asma en el servicio de urgencias

Background: To determine the management of acute bronchial asthma in an adult emergency department. Methods: A retrospective medical audit of 46 consecutive adult patients with acute asthma exacerbations was performed. We collected information from 48 episodes of acute asthma over a 5-month period. Using classical audit methodology, four indicators were examined: severity evaluation, diagnostic tests, specific treatment, and discharge treatment plans. Results: The least recorded severity indicators were respiratory rate (27 %), heart rate (50 %) and peak expiratory flow (20 %). Heart and respiratory auscultation were recorded in all patients and oxygen saturation was recorded in 93 %. Laboratory blood test and chest radiograph were performed in all patients. Arterial blood gas was tested in 57 %, electrocardiography in 17 %, and coagulation in 39 %. No treatment was provided in 12 % of patients. Bronchodilator medications were administered in all treated patients and oxygen was prescribed in 60 %. Systemic corticosteroids (methylprednisolone or hydrocortisone) were administered in 80 % of treated patients. Seventeen percent of patients were discharged from hospital with no change to their usual treatment. Conclusions: The following weak points were identified: 1) Severity assessment is inadequate, 2) use of diagnostic tests is excessive, 3) patients discharged to home with no treatment plan. Opportunities for improvement consisted of: 1) greater availability of peak expiratory flow meters, 2) individualized use of diagnostic tests, and 3) management protocols

Objetivo: Conocer el control de la crisis de asma en el área de urgencias hospitalarias. Método: Revisión (audit) retrospectiva de la asistencia de las exacerbaciones del asma en 46 pacientes adultos. Se recogió información sobre 48 episodios agudos de asma durante un período de 5 meses. Siguiendo la metodología clásica, se recogieron cuatro indicadores: valoración de la gravedad, recursos diagnósticos, tratamiento específico y condiciones al alta. Resultados: datos pocas veces anotados, fueron la frecuencia respiratoria (27%), frecuencia cardiaca (50%) y pico flujo (20%). En todos los pacientes se efectuó auscultación cardiaca y pulmonar y en el 93% la saturación arterial de O2. Estudio analítico en sangre y RX de tórax se efectuó en todos los pacientes. En el 57% se verificó la gasometría arterial, el ECG en el 17% y la coagulación en el 39%. En el 12% no se estimó que necesitaran tratamiento. Broncodilatadores se administraron en todos los demás y el 60% de ellos necesitó oxigenoterapia. El 80% necesitó corticoides sistémicos (metilprednisolona, hidrocortisona). Al 17% de los pacientes se les dio de alta sin cambios en su tratamiento habitual. Conclusiones: Puntos débiles: 1) inadecuada valoración de la gravedad; 2) excesivos medios diagnósticos; 3) pacientes remitidos a su domicilio sin tratamiento. Recomendaciones de mejora: 1) medidores de pico flujo; 2) uso de recursos diagnósticos individualizados; 3) deben haber protocolos de control de la crisis de asma en todos los servicios de urgencia

Total serum IgE: adult reference values in Valencia (1981-2004). Usefulness in the diagnosis of allergic asthma and rhinitis.

BACKGROUND: The reference values for total serum IgE are accepted to vary according to the geographical area involved. In 1981 we published the reference values for a donor population in the city of Valencia (Spain) and its metropolitan area. Since then, we have noted an increase in the prevalence of asthma and rhinitis in countries with a Western lifestyle, including Spain. AIM: To update the adult reference values for total serum IgE in the city of Valencia and its metropolitan area, and to determine their diagnostic usefulness in asthma and allergic rhinitis. MATERIAL AND METHODS: We studied two groups of 69 and 100 individuals each. One group comprised apparently healthy blood donors, as assessed by a routine blood bank study protocol and the application of a questionnaire to exclude perceived allergic or parasitic diseases, while the other group consisted of individuals with atopic respiratory disease (bronchial asthma and allergic rhinitis) studied in our service in the same time period (spring 2004). Total serum IgE was determined by the UniCAP method developed by Pharmacia. RESULTS: The geometric mean of total serum IgE among blood donors was 46.65 kU/l (95% CI: 15.5-77.8) versus 204.29 kU/l (95% CI: 93.3-515) among allergic subjects. The difference between the two groups was statistically significant. No significant difference was found between our donor sample in 1981 and the sample in the present study. Establishing an arbitrary cut-off point of 1.65 standard deviations (SD)(equivalent to 95 % of the donor population), we obtained a figure of > 183 kU/l whereby 44% of all allergic individuals presented a value below this cut-off point. To practical effects, these allergic patients behaved as low responders (LRs) in relation to total IgE, whereas the remaining individuals were high responders (HRs) in relation to total IgE. CONCLUSIONS: Our data confirm the current validity of the reference values obtained in 1981, which continue to be significantly different from those of the UniCAP method for Swedish donors. The population of allergic subjects can be divided into two subgroups: subjects with total IgE levels similar to those of the donors, which we refer to as LRs, and which represent 44% of all allergic subjects, and a second subgroup with total IgE values above those of the donors (HRs), who would therefore be the only subjects that would be identified by individual serum IgE study.

Total serum IgE: adult reference values in Valencia (1981-2004). Usefulness in the diagnosis of allergic asthma and rhinitis

Background: The reference values for total serum IgE are accepted to vary according to the geographical area involved. In 1981 we published the reference values for a donor population in the city of Valencia (Spain) and its metropolitan area. Since then, we have noted an increase in the prevalence of asthma and rhinitis in countries with a Western lifestyle, including Spain. Aim: To update the adult reference values for total serum IgE in the city of Valencia and its metropolitan area, and to determine their diagnostic usefulness in asthma and allergic rhinitis. Material and methods: We studied two groups of 69 and 100 individuals each. One group comprised apparently healthy blood donors, as assessed by a routine blood bank study protocol and the application of a questionnaire to exclude perceived allergic or parasitic diseases, while the other group consisted of individuals with atopic respiratory disease (bronchial asthma and allergic rhinitis) studied in our service in the same time period (spring 2004). Total serum IgE was determined by the UniCAP® method developed by Pharmacia®. Results: The geometric mean of total serum IgE among blood donors was 46.65 kU/l (95 % CI: 15.5-77.8) versus 204.29 kU/l (95 %CI: 93.3-515) among allergic subjects. The difference between the two groups was statistically significant. No significant difference was found between our donor sample in 1981 and the sample in the present study. Establishing an arbitrary cut-off point of 1.65 standard deviations (SD)(equivalent to 95 % of the donor population), we obtained a figure of > 183 kU/l whereby 44 % of all allergic individuals presented a value below this cut-off point. To practical effects, these allergic patients behaved as low responders (LRs) in relation to total IgE, whereas the remaining individuals were high responders (HRs) in relation to total IgE. Conclusions: Our data confirm the current validity of the reference values obtained in 1981, which continue to be significantly different from those of the UniCAP® method for Swedish donors. The population of allergic subjects can be divided into two subgroups: subjects with total IgE levels similar to those of the donors, which we refer to as LRs, and which represent 44 % of all allergic subjects, and a second subgroup with total IgE values above those of the donors (HRs), who would therefore be the only subjects that would be identified by individual serum IgE study

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Acrylates induced rhinitis and contact dermatitis.

Acrylates are a well-known cause of occupational contact dermatitis due to its widespread use in several settings such as dentistry, orthopaedic surgery, graphic industry and cosmetics. We describe the case of a manicurist who developed occupational rhinitis and allergic contact dermatitis induced by the application of acrylic-sculptured nails.

Incapacidad funcional en una población de ancianos en el medio comunitario / Functional impairment in elderly comunity dweling

Objetivos: Conocer la prevalencia de incapacidad funcional en actividades básicas e instrumentales de la vida diaria en una población de ancianos residentes en el medio comunitario, determinar aquellas actividades para las que se incapacitan un mayor número de sujetos e identificar aquellas variables que pudieran estar asociadas a la incapacidad funcional. Método: Diseño; estudio epidemiológico transversal. Sujetos: mayores de 74 años registrados en el padrón municipal del Concejo de Gozón del año 1996. La población de estudio se obtuvo del total de sujetos mayores de 74 años empadronados (n =1.227), extrayendo una muestra de 348 sujetos mediante un muestreo aleatorio simple. Variables de estudio: sociodemográficas (edad, sexo, estado civil, convivientes, nivel de estudios y puntuación en la escala sociofamiliar de Gijón), clínicas (existencia de enfermedades potencialmente incapacitantes y número de enfermedades y fármacos), asistenciales (utilización de ayuda a domicilio formal, teleasistencia y centro de día), funcionales (evaluadas mediante los índices de Barthel y Lawton) y mentales (puntuaciones en la escala de Pfeiffer y la escala de depresión geriátrica).Resultados: 275 ancianos fueron incluidos en el estudio (81,4 años, 62,5 por ciento mujeres). La prevalencia de incapacidad funcional en actividades básicas de la vida diaria (ABVD) fue de 22,9 por ciento y en actividades instrumentales de la vida diaria (AIVD) del 73,5 por ciento, siendo las actividades más afectadas las relacionadas con la movilidad y las labores de la casa. En el análisis de regresión logística se mostraron como predictoras de incapacidad funcional en ABVD las variables: edad (OR 1,14), sexo femenino (OR 5,51), número de enfermedades (OR 1,42) y puntuación en el índice de Lawton (0,52). Asimismo, permanecieron como predictoras de incapacidad en AIVD las variables: edad (OR 1,2), sexo femenino (OR 0,03), número de enfermedades (OR 1,38) y puntuación en el Pfeiffer (1,53). Conclusiones: Para nuestra población de estudio, las variables edad, sexo, número de enfermedades y puntuaciones en el índice de Lawton y la escala de Pfeiffer, parecen comportarse como variables independientes capaces de predecir el riesgo de incapacidad funcional en ABVD y AIVD. Estas variables podrían ser útiles para seleccionar grupos de ancianos con riesgo, que pudieran beneficiarse de intervenciones especializadas dirigidas a prevenir/reducir la incapacidad funcional (AU)

Widening choice.

PIP: Widening the choice of methods available is regarded as a way to increase the overall acceptability of family planning. All methods of contraception currently available have drawbacks, whether in terms of cost, reliability, or ease of use. Some methods are legally restricted. Although it is generally agreed that no one form of contraception is likely to assume the role of the majority method in the near future, major emphasis is being placed on the development of new techniques. Scientists are aiming for methods that are safe, reliable, inexpensive, and do not necessarily require medical supervision. Much of this research is centered on finding alternative ways of introducing contraceptive steroids into the woman's reproductive system. Research in this area has involved implant techniques, contraceptive-releasing vaginal rings, and biodegradable plastic capsules that can be implanted under the skin. Scientists are also trying to impregnate IUDs with hormones to control the heavy menstrual bleeding associated with IUD use. Other research is focused on inhibiting ovulation by mimicking the brain's signals to the pituitary gland. In fact, it may be possible to develop drugs that act directly on parts of the brain itself. In contrast to the Western world, where it is not unusual for it to cost US$50 million to develop a new drug, contraceptive research in China has focused on naturally occurring substances such as mucilage and gossypol. International researchers working under the auspices of the World Health Organization have so far identified 30 plants with contraceptive potential.^ieng