Estudio del gen BMPR2 en pacientes con hipertensión arterial pulmonar

Introduction

Mutations of the gene that code bone morphogenic protein type 2 receptor (BMPR2) are involved in the pathogenesis of pulmonary arterial hypertension (PAH), both in its familial (FPAH) and its idiopathic (IPAH) forms.

Method

With the aim of increasing the knowledge of these genetic factors in our area, the BMPR2 gene was studied in 17 patients with PAH, 8 with FPAH and 9 with sporadic IPAH. Additionally, a study was made to see whether the presence of BMPR2 mutations was associated with changes in the CO diffusing CO (DL_CO) with the aim of evaluating the interest in this measurement in the pre-clinical diagnosis.

Results

R491Q y R211X mutations were detected in 2 patients with FPAH (prevalence, 25%), and the R332X mutation in one case of IPAH (prevalence, 11%). The familial study of the patient with the R491Q mutation, 14 of the 28 subjects studied had the mutation, and 4 had the diseases (penetration, 36%). A decrease in the DL_CO/alveolar volume (K_CO) ratio was observed in asymptomatic family members who expressed the mutation, compared to those who did not express it (88±5% and 104±9% of the reference value, respectively; P<0.01).

Conclusion

We conclude that the frequency of mutations in the BMPR2 gene in the patients studied with FPAH is lower than was previously described. The decrease in the K_CO observed in asymptomatic carriers of the mutation suggests a certain level of pulmonary vascular changes, therefore its measurement could be useful in the familial study of FPAH.     

Contaminación del aire y síntomas recientes de asma,rinitis alérgica y eccema atópico en escolares de 6 y 7 años

Objective

The objective of the study was to analyze the relationship between air pollutants and the prevalence of recent symptoms of asthma, allergic rhinitis, and atopic eczema in schoolchildren aged between 6 and 7 years.

Patients and Methods

The prevalence of recent (previous 12 months) symptoms of allergic diseases was obtained by means of the questionnaire of the International Study of Asthma and Allergies in Childhood (ISAAC), Spain, with the participation of 7 centers (Asturias, Barcelona, Bilbao, Cartagena, La Coruña, Madrid, and Valencia) and 20 455 schoolchildren aged between 6 and 7 years, from 2002 to 2003. The pollutant detection systems of the aforementioned centers provided the mean annual concentrations of sulfur dioxide (SO₂), nitrogen dioxide (NO₂), carbon monoxide (CO), and total suspended particulate matter.

Results

The annual average concentration of SO₂ showed a significant association with a higher prevalence of recent severe asthma (adjusted odds ratio [aOR] between level-1 and level-3 pollution, 1.32; 95% confidence interval [CI], 1.01–1.73), rhinitis (aOR, 1.56; 95% CI, 1.39–1.75), and rhinoconjunctivitis (aOR, 1.70; 95% CI, 1.45–2.00). The annual average concentration of CO was associated with a higher prevalence of rhinitis (aOR, 1.65; 95% CI, 1.34–2.04), rhinoconjunctivitis (aOR, 1.76; 95% CI, 1.31–2.37), and eczema (aOR, 1.55; 95% CI, 1.17–2.04). The annual average concentration for NO₂ and total suspended particulate matter showed inverse associations with the prevalence of nocturnal dry cough.

Conclusions

Findings suggest that air pollutants such as SO₂ and CO increase the risk of recent symptoms of asthma and allergic rhinitis in schoolchildren aged between 6 and 7 years in Spain.     

Identificación bacteriana directamente del hemocultivo mediante una técnica rápida de espectrometría de masas Matrix-Assisted Laser Desorption-Ionisation Time-of-Flight

Introduction

Matrix-Assisted Laser Desorption-Ionisation Time-of-Flight (MALDI-TOF) Mass Spectrometry is rapid and accurate for the bacterial identification.

Methods

We have evaluated a less laborious and less time consuming method for microorganism identification directly from positive blood cultures.

Results

When we considered the scores ≥ 1.7 and ≥ 1.4 for acceptable identification of species and genus, the percentage of identification was 77.5% and 93.9%, respectively.

Conclusions

This method is reliable, rapid and cost-effective for implementation in routine use in clinical microbiology laboratories.     

Óxido nítrico en el condensado de aire espirado de individuos voluntarios sanos recolectado a través de un dispositivo reutilizable

Background

The analysis of exhaled breath condensate (EBC) is a non-invasive technique that enables the determination of several volatile and nonvolatile substances produced in the respiratory tract, whose measurement may be useful for the diagnosis and monitoring of several respiratory diseases.

Objective

The aim of this study was to produce a low-cost reusable device in order to sample exhaled breath condensate in healthy adult volunteers, and to determine the concentration of nitric oxide in the sample collected.

Material and methods

The apparatus was made with a U-shaped tube of borosilicate glass. The tube was placed in a container with ice, and unidirectional respiratory valves were fitted to the distal end. Afterwards, nitric oxide was measured in the exhaled breath condensate (EBC) by chemiluminescence.

Results

The total cost of the device was $120.20. EBC samples were obtained from 116 volunteers of both sexes, aged between 20 and 70. The mean volume of exhaled breath condensate collected during 10 minutes was 1.0 ± 0.6 mL, and the mean level of nitric oxide was 12.99 ± 14.38 μM (median 8.72 μM). There was no correlation between the nitric oxide levels in the exhaled breath condensate and age or gender.

Conclusion

We demonstrate that it is possible to fabricate a low-cost, efficient, reusable device in order to collect and determine nitric oxide levels in EBC. We have identified no correlation between the nitric oxide levels present in the EBC obtained with this method with either age or sex.     

Predicción en tiempo real de la malignidad de ganglios linfáticos mediastínicos mediante ecografía endobronquial

Objective

To evaluate the utility of different ultrasonographic (US) features in differentiating benign and malignant lymph node (LN) by endobronchial ultrasound (EBUS) and validate a score for real-time clinical application.

Methods

208 mediastinal LN acquired from 141 patients were analyzed. Six different US criteria were evaluated (short axis ≥ 10 mm, shape, margin, echogenicity, and central hilar structure [CHS], and presence of hyperechoic density) by two observers independently. A simplified score was generated where the presence of margin distinction, round shape and short axis ≥ 10 mm were scored as 1 and heterogeneous echogenicity and absence of CHS were scored as 1.5. The score was evaluated prospectively for real-time clinical application in 65 LN during EBUS procedure in 39 patients undertaken by two experienced operators. These criteria were correlated with the histopathological results and the sensitivity, specificity, positive and negative predictive values (PPV and NPV) were calculated.

Results

Both heterogenicity and absence of CHS had the highest sensitivity and NPV (≥ 90%) for predicting LN malignancy with acceptable inter-observer agreement (92% and 87% respectively). On real-time application, the sensitivity and specificity of the score > 5 were 78% and 86% respectively; only the absence of CHS, round shape and size of LN were significantly associated with malignant LN.

Conclusions

Combination of different US criteria can be useful for prediction of mediastinal LN malignancy and valid for real-time clinical application.     

Validez y aplicabilidad de un nuevo método de registro para la hipertensión arterial

Introduction and objectives

Blood pressure measurement methods and conditions are determinants of hypertension diagnosis. A recent British guideline recommends systematic 24-h ambulatory blood pressure monitoring. However, these devices are not available at all health centers and they can only be used by 1 patient per day. The aim of this study was to test a new blood pressure recording method to see if it gave the same diagnostic results as 24-h blood pressure monitoring.

Methods

One-hour blood pressure monitoring under routine clinical practice conditions was compared with standard method of day time recording by analyzing the coefficient of correlation and Bland-Altman plots. The Kappa index was used to calculate degree of agreement. Method sensitivity and specificity were also analyzed.

Results

Of the 102 participants, 89 (87.3%) obtained the same diagnosis regardless of method, with high between-method agreement (κ= 0.81; 95% confidence interval, 0.71-0.91). We observed robust correlations between diastolic (r = 0.85) and systolic blood pressure (r = 0.76) readings. Sensitivity and specificity for the new method for diagnosing white coat hypertension were 85.2% (95% confidence interval 67.5%-94.1%) and 92% (95% confidence interval, 83.6%-96.3%), respectively.

Conclusions

One-hour blood pressure monitoring is a valid and reliable method for diagnosing hypertension and for classifying hypertension subpopulations, especially in white coat hypertension and refractory hypertension. This also leads to a more productive use of monitoring instruments.Full English text available from:www.revespcardiol.org/en     

Características clínicas y supervivencia de los pacientes nunca fumadores con cáncer de pulmón

Introduction and objective

To analyze the frequency, clinical characteristics and survival of patients with lung cancer (LC) who have never smoked in comparison to patients who smoke.

Patients and methods

A retrospective study in patients diagnosed with LC by cytohistology between 1999 and 2011. Survival was estimated by the Kaplan-Meier method. The χ² test was used to estimate the relationship between the variables.

Results

A total of 2161 patients were diagnosed with LC, 396 (18.3%) of whom had never smoked. The mean age (± standard deviation) in this group was 72.85 ± 10.52; 64.6% were women and 35.4% men. According to the cytohistology, 55.6% were adenocarcinoma, 20.5% squamous cell, 15% small cell, 2.7% large cell and 6.2% other subtypes. The diagnosis was made in advanced stage (iv) in 61.4%, and 14.4% of the patients received surgical treatment. Survival was 12.4%, with no differences between the two groups. In the group of never smokers, women had better survival than men.

Conclusions

Of the patients diagnosed with LC, 18.3% had never smoked. It was diagnosed mainly in women, at advanced stages and the most common histological type was adenocarcinoma. There were no survival differences compared to the group of smokers.     

Implantación de una prueba rápida de VIH en Asturias (España)

Introduction

The aim of the study was to analyze the implementation of a rapid HIV test in Asturias (Spain).

Methods

The study was conducted in two STI Units using the Determine^® HIV-1/2 test.

Results

A total of 1011 people were tested, of whom 65.3% had never been tested for HIV previously, and 71.4% were heterosexual men. Twenty-one tests were confirmed positive by Enzyme Immunoassay/Western Blot (EIA/WB) assay An increase was observed in the diagnosis of HIV.

Conclusion

Awareness campaigns and rapid tests could be effective methods for the early diagnosis of HIV.     

Prevalencia y distribución del depósito pulmonar de amianto en población urbana española

Introduction

The purpose of the present study is to analyse the prevalence and distribution of asbestos lung residue in the Barcelona urban population.

Material and methods

Lung autopsy samples were obtained from 35 individuals who had lived in Barcelona. The close family were interviewed in order to rule out asbestos exposure. Samples were obtained from three areas of the right lung during the autopsy: upper lobe apex, lower lobe apex, and lower lobe base. The samples were treated to remove organic material. The inorganic residue was analysed using a light microscope. The results were expressed as asbestos bodies (AB) per gram of dry tissue. Levels greater than 1000 AB/g of dry tissue were considered as potentially causing disease.

Results

AB were detected in 29(83%) of the subjects, of which 86% had levels less than 300 AB/g. Only one individual (3%) had values greater than 1000 AB/g dry tissue. The asbestos residue was higher in the lower lung lobe in 17 individuals (48%) than in the rest, although no significant differences were seen as regards AB residue in the three lung areas studied.

Conclusions

The results of this study show that the urban population of Barcelona have asbestos levels in the lung that vary between 0 and 300 AB/g dry tissue. No differences in the asbestos residues were detected in the lung areas studied in this population.     

Características de los pacientes con infección crónica por el virus de la hepatitis B. Análisis de una serie de 474 pacientes

Objective

To determine the clinical, laboratory, serological and histologic characteristics of chronic hepatitis B virus carriers in our environment.

Material and methods

A retrospective cohort study was performed that included chronic AgHBs carriers aged more than 13 years attending our service since January 2000.

Results

A total of 474 patients were included. At diagnosis, 55.49% were men, with a mean age of 41.05±13.93 years. Alanine aminotransferase (ALT) levels were within the normal range in 57.17% of the patients, and 87.76% were AgHBe(−). Hepatitis C and D virus coinfection was found in 3.62% and 1.86%, respectively. Liver biopsy was performed in 31.22%; varying grades of inflammation-fibrosis were found in 63.51% and cirrhosis was found in 12.84%. Compared with AgHBe(−) patients, those who were AgHBe(+) were younger and had greater disease activity. This difference was statistically significant. Patients in the immunotolerant phase were the least numerous (5.26%), while AgHBe(−) patients with chronic HBV infection were the most numerous (48.32%). Patients in the immunoreactive phase showed greater histological involvement (16.67% cirrhosis). A familial history of chronic HBV was found in 21.52%. The percentage of non-Spanish patients increased in the last few years and accounted for 18.78%.

Conclusion

Chronic HBV infection in our environment occurs mainly in middle-aged persons. GPT values are normal in more than 50%, most are AgHBe(−), and approximately half are inactive carriers. The incidence of chronic infection has increased in the non-Spanish population in recent years.     

Evaluación inicial del programa de prevención de la transmisión materno-infantil de la infección por el virus de la inmunodeficiencia humana en Guinea Ecuatorial

Background

The prevalence of human immunodeficiency virus (HIV)-infected pregnant women in Equatorial Guinea (EG) has been reported as 7.3%. In 2008 an updated version of the PMTCT protocol was accepted according to the current WHO guidelines. The aim of this study was to describe the characteristics and outcome of children exposed to HIV after the introduction of the protocol.

Methods

A retrospective review was conducted on the clinical characteristics of the infants born to HIV-infected mothers in the Hospital Regional de Bata and Primary Health Care Centre Maria Rafols in Bata (EG) between June 2008 and November 2011. The diagnosis of HIV infection in children was based on rapid serology tests.

Results

A total of 103 children were included, of which 47 were males. Fifty three patients (51%) completed the follow-up (51%). Fourteen children (26%) were diagnosed with HIV infection (11 presumptive diagnosis, 3 due to persistence of antibodies at 18 months). Six children (12%) died before a definitive diagnosis. Just over than half (52%) of mothers received antiretroviral therapy (ART) during pregnancy. The transmission rate in children whose mothers received ART was 16% (3/19), compared with 43% (10/23) in children whose mothers did not receive it. Only one child was infected (8%) when the mother received ART, and child received postnatal prophylaxis.

Conclusions

The PMTCT protocol compliance was still very low. Antiretroviral therapy in pregnant women decreased the rate of vertical transmission, but the rate still remains very high. Many children were lost to follow-up. Strategies to prevent loss to follow-up and methods for earlier virological diagnostic are needed.     

Variabilidad circadiana de la oximetría de pulso en niños sanos menores de 7 años

Background

Peripheral oxygen saturation (SpO₂) measured by pulse oximetry is widely used in clinical practice, but its fluctuations over the course of the 24 h of a day have not been explored at length. Recently, we reported that children hospitalized due to non-cardiopulmonary causes had a circadian variation in SpO₂. This finding needed to be corroborated in healthy children, which is the objective of the present study.

Patients and methods

Healthy children residing in a state foster home were studied with pulse oximetry every 2 h for 24 h.

Results

Eighty two children were included in the study, ranging in age from one month to 6.5 years (average ± standard error of 3.06 ± 0.16 years), with a weight-for-length/height percentile of 65.5 ± 2.9. In 65 (79.3%) children, the SpO₂ levels followed a sinusoidal curve suggesting circadian rhythm. The total group of sinusoidal curves in this population had a mesor of 95.10 ± 0.08% SpO₂, period of 21.05 ± 0.54 h (in 53.8% of these children, the period was between 20 and 28 h). The maximum SpO₂ was reached at 3:14 PM ± 16 min, and the minimum at 5:16 AM ± 48 min. When the 24 h were divided into four periods, it was demonstrated that the highest SpO₂ levels were reached between 2 PM and 8 PM.

Conclusions

In this population of clinically healthy children, there was a circadian variation in pulse oximetry, with maximum values in the late afternoon and minimal values in the early morning.     

Técnica modificada de obtención de muestras del mediastino mediante punción transbronquial bajo guía de ecografía endobronquial: resultados de un estudio prospectivo observacional

Background

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a widely-accepted method for obtaining both benign and malignant mediastinal lymph node samples. We present the results obtained with a modification that simplifies sampling, known as fine-needle capillary sampling or EBUS-FNC.

Methods

A prospective observational study with 44 consecutive patients who underwent EBUS at the University of Navarra Clinic in Pamplona (Spain). All samples were obtained by EBUS-FNC instead of by conventional EBUS-TBNA. No suction was used, and the internal stylus was not completely withdrawn at any time.

Results

The examination of the mediastinum by means of EBUS identified the presence of lymphadenopathies or mediastinal masses in 38 patients (86.4%). Samples were taken from more than one lymph node in 23 patients (52.3%). EBUS-FNC provided adequate and representative material for interpretation in all patients, and diagnostic performance was 87%. Sensitivity for the detection of lung cancer with EBUS-FNC was 84%. Mild complications were only recorded in two patients (4.5%).

Conclusions

Our study suggests that EBUS-FNC is a safe technique, comparable to EBUS-TBNA in efficacy, and is able to obtain adequate samples.     

Estudio de la repetición del pentanucleótido CCTTT en el gen de la sintasa inducible del óxido nítrico en pacientes con hipertensión arterial pulmonar

Introduction

One of the pathways involved in pulmonary arterial hypertension (PAH) is the nitric oxide (NO) pathway. A polymorphism in the inducible NO synthase (NOS2) gene has been described, consisting of the CCTTT pentanucleotide repeat, which causes a reduction in NO production. The aim of this study was to determine if this polymorphism increases susceptibility to developing PAH.

Methods

Sixty four patients with a diagnosis of PAH groups i and iv and 50 healthy controls were compared. DNA genotyping of the samples for this polymorphism was performed using PCR. The distribution between both groups was compared and correlated with clinical and haemodynamic parameters and therapeutic response.

Results

A significantly different distribution was observed in the number of repeats between patients and controls (P < .0001). When the samples were categorised by short forms (both alleles with less than 12 repeats) and long forms (≥ 12 repeats), it was observed that the former had an almost 4-fold risk of developing PAH (odds ratio: 3.83; 95% CI: 1.19-12.32, P = .024). There were no differences between the most common types of PAH, either in therapeutic response or survival. There was no correlation between haemodynamic parameters and the number of repeats in the patients, and only a weak correlation with systolic PAH.

Conclusions

There are significant differences in the distribution of the NOS2 promotor CCTTT polymorphism between patients with PAH and the healthy population. A minor CCTTT pentanucleotide repeat in the NOS2 gene may increase the risk of developing PAH.     

Valores pretratamiento e inducidos por el tratamiento de enolasa específica de neurona en pacientes con cáncer de pulmón microcítico: estudio prospectivo,abierto

Background

Neuron-specific enolase (NSE) is the most sensitive tumor marker for small-cell lung carcinoma (SCLC) at the time of diagnosis. The main purpose of this study was to review the usefulness of serum NSE level as a prognostic factor in patients with SCLC and to determine the correlation between the NSE level and the stage of disease and response to chemotherapy.

Methods

In this prospective study, patients with SCLC were evaluated for response to chemotherapy, survival without disease progression, and overall survival. The end point was designated at patient death due to SCLC. NSE assays were performed before and after completion of chemotherapy.

Results

Sixty-five patients were included in study. NSE levels were significantly higher in patients who died of SCLC. The pre-treatment NSE levels in patients who responded to treatment were significantly lower. The post-treatment NSE levels were not significantly correlated with response to chemotherapy, progression-free survival, overall survival, and prognosis of patients. Change in the NSE level between the pre- and post-treatment periods was not significantly correlated with response to treatment, progression-free survival, and overall survival.

Conclusions

NSE levels might not be related with the stage of the disease. However, a low pre-treatment NSE level might be used in predicting good response to chemotherapy in patients with SCLC. The post-treatment serum NSE levels and the rate of change between pre- and post-treatment serum levels of NSE were not related with response to chemotherapy, progression-free survival, and overall survival.     

Ventilación mecánica no invasiva en una población anciana que ingresa en una unidad de monitorización respiratoria: causas,complicaciones y evolución al año de seguimiento

Objective

To determine the usefulness of non-invasive ventilation (NIV) in elderly patients (≥75) admitted to a respiratory monitoring unit (RMU) during hospitalization and one year later in comparison with the results from the younger age group (<75).

Material and methods

Ours is a prospective observational study carried out at the Hospital Universitario La Princesa (Madrid, Spain). We recruited all patients who were ≥75 years old and were admitted to our RMU during the period 2008-2009 with respiratory acidosis (pH <7.35 and PaCO₂ >45 mmHg) requiring NIV. We gathered data for basic variables as well as sociodemographics, history of previous pathologies, reason for hospitalization and severity, analysis upon admission and the evolution of blood gases at the start of NIV (within the first hour and after 24 hours), complications and evolution at the one-year follow-up.

Results

Mean age of the sample was 80.6 years. The Charlson index was 3.27. About half of the patients had some limitation for performing daily activities. The main reasons for admission were COPD exacerbation and heart failure. There were complications in 36% of the cases (11 renal failure and 6 atrial fibrillation). The survival rate at the one-year follow-up was 63.21%.

Conclusions

NIV is a good alternative in elderly patients admitted to the hospital with respiratory acidosis. We did not detect differences in mortality during admission between the two groups. The elderly patients were more frequently re-admitted than the younger group in the 6-12 months after hospital discharge. This could be due to their poorer functional state after hospitalization requiring NIV.     

Características de pacientes asmáticos ingresados en una unidad de cuidados respiratorios intermedios

Introduction

Intermediate respiratory care units (IRCU) provide continuous monitoring and non-invasive mechanical ventilation (NIMV) in patients with severe respiratory failure who are usually admitted to intensive care units (ICU). The usefulness of IRCU in managing severe asthma exacerbations has never been evaluated.

Methods

Clinical data were prospectively and systematically compiled from patients admitted to the IRCU with a principal diagnosis of bronchial asthma exacerbation. We assessed therapeutic failure (intubation or exitus) and patient evolution up until 6 months after discharge compared with a group of patients admitted to a conventional hospital ward, paired for age and sex, and with the same principal diagnosis.

Results

A total of 74 asthma patients were included (37 admitted to IRCU and 37 to the hospital ward) with a mean age (± SD) of 58 ± 20 years, who were predominantly women (67%), with previous diagnosis of asthma and persistent asthma treatment. The main cause of admittance to the IRCU was severe respiratory failure. The patients who were admitted to the IRCU presented more radiological affectation (alveolar infiltrates) and had significantly higher pCO₂. Ten patients admitted to the IRCU required NIMV. There were no differences between the two groups regarding either therapeutic failure or the 6-month follow-up after discharge.

Conclusions

Patients with severe asthma exacerbations can be managed in an IRCU while avoiding hospitalization in an ICU and demonstrating a prognosis similar to milder exacerbations treated in conventional hospital wards.