An incidental finding in newborn screening leading to the diagnosis of a patient with ECHS1 mutations.

Short-chain enoyl-CoA hydratase (ECHS1) is a mitochondrial beta-oxidation enzyme involved in the metabolism of acyl-CoA fatty acid esters, as well as in valine metabolism. ECHS1 deficiency has multiple manifestations, including Leigh syndrome early at birth or in childhood with poor prognosis, to cutis laxa, exercise-induced dystonia and congenital lactic acidosis. Here we describe the case of a newborn with mutations in ECHS1 that caught our attention after the incidental finding of 3-hydroxy-butyryl\3-hydroxy-isobutyryl\malonylcarnitine (C4OH\C3DC) and tiglylcarnitine (C5:1) on blood spot in the newborn screening (NBS) program. Diagnosis was suspected based on the analysis of organic acids on dried urine spot. A moderate increase of 2-methyl-2,3-dihydroxybutyric acid, was detected, which is a known marker of this disease. Exome analysis showed c.404A>G (p.Asn135Ser) mutation in homozygosis in the ECHS1 gene. The child was therefore admitted to the hospital. Initial examination showed little response to auditory stimuli and mild hypertonia of the extremities. Clinical deterioration was evident at 4 months of age, including neurological and cardiac involvement, and the patient died at 5 months of age. This case illustrates how an incidental detection in the NBS Program can lead to the diagnosis ECHS1 deficiency. Although it is a severe disease, with no treatment available, early detection would allow adequate genetic counseling avoiding the odyssey that suffered most of these families.

National survey on the indicators of quality in Bioethics of the SEMICYUC in the departments of Intensive Care Medicine in Spain. / Encuesta nacional sobre los indicadores de calidad en Bioética de la SEMICYUC, en los servicios de Medicina Intensiva en España.

INTRODUCTION: Multiple interventions are performed in critical patients admitted to Intensive Care Units (ICUs). This study explores the presence in the daily practice of ICUs of elements related to the 6 bioethics quality indicators of the Spanish Society of Intensive and Critical Care Medicine and Coronary Units, and the participation of their members in the hospital ethics committees. MATERIALS AND METHODS: A multicenter observational study was carried out, using a survey exploring descriptive aspects of the ICUs, with 25 questions related to bioethics quality indicators, and assessing the participation of ICU members in the hospital ethics committees. The ICUs were classified by size (larger or smaller than 10 beds) and type of hospital (public/private-public concerted center, with/without teaching). RESULTS: The 68 analyzed surveys revealed: daily informing of the family (97%), carried out in the information room (82%); end-of-life care protocols (44%); life support limitation form (48.43%); and physical containment protocol (40%). Compliance with the informed consent process referred to different procedures is: tracheostomy (92%), vascular procedures (76%), and extrarenal clearance (25%). The presence of ICU members in the hospital ethics committee is currently frequent (69%). CONCLUSIONS: Information supplied to relatives is adequate, although there are ICUs without an information room. Compliance with the informed consent requirements of various procedures is insufficient. The participation of ICU members in the hospital ethics committees is frequent. The results obtained suggest a chance for improvement in the bioethical quality of the ICU.

Iodine status and thyroid function among Spanish schoolchildren aged 6-7 years: the Tirokid study.

I deficiency is still a worldwide public health problem, with children being especially vulnerable. No nationwide study had been conducted to assess the I status of Spanish children, and thus an observational, multicentre and cross-sectional study was conducted in Spain to assess the I status and thyroid function in schoolchildren aged 6-7 years. The median urinary I (UI) and thyroid-stimulating hormone (TSH) levels in whole blood were used to assess the I status and thyroid function, respectively. A FFQ was used to determine the consumption of I-rich foods. A total of 1981 schoolchildren (52 % male) were included. The median UI was 173 µg/l, and 17·9 % of children showed UI<100 µg/l. The median UI was higher in males (180·8 v. 153·6 µg/l; P<0·001). Iodised salt (IS) intake at home was 69·8 %. IS consumption and intakes of ≥2 glasses of milk or 1 cup of yogurt/d were associated with significantly higher median UI. Median TSH was 0·90 mU/l and was higher in females (0·98 v. 0·83; P<0·001). In total, 0·5 % of children had known hypothyroidism (derived from the questionnaire) and 7·6 % had TSH levels above reference values. Median TSH was higher in schoolchildren with family history of hypothyroidism. I intake was adequate in Spanish schoolchildren. However, no correlation was found between TSH and median UI in any geographical area. The prevalence of TSH above reference values was high and its association with thyroid autoimmunity should be determined. Further assessment of thyroid autoimmunity in Spanish schoolchildren is desirable.

[The association of adherence to a Mediterranean diet during early pregnancy and the risk of gastroschisis in the offspring]. / Asociación de la adherencia a la dieta mediterránea al inicio del embarazo y riesgo de gastrosquisis en la descendencia: un estudio de casos-controles.

OBJECTIVES: The aim of this study was to study the association of adherence to the Mediterranean diet in early pregnancy maternal and the offspring's risk of gastroschisis. METHODS: Case-control study. We describe 11 cases of gastroschisis in the region of Murcia from 2007 to 2012 and 34 concurrent controls. At the time of diagnosis each of the cases completed a validated Food Frequency Questionnaire (FFQ) consisting of 98 items on the periconceptional diet. Confounding factors: smoking, exposure to cannabis / marihuana, age of the parents, BMI, income and educational level. We conducted a descriptive and multivariate logistic regression statistical analysis. RESULTS: Mothers of children with gastroschisis were younger (20.8 years, 95% CI 17.3 to 24.2) and their diet consisted of less caloric intake, saturated fat and monounsaturated fats and proteins than controls. The Odds Ratio (OR) in the multivariate model controlling for confounding factors: maternal age (year) 0.70 (95% CI 0.51 to 0.96), monounsaturated fatty acids (oleic acid, g) 0.79 (95% CI 0.65 to 0, 97) and vegetable intake (rations/week) 0.70 (95% CI 0.48 to 1.00). CONCLUSION: A maternal diet rich in oleic acid and vegetable products may prevent vascular risk of onphalomesenteric arteries reducing the risk of gastroschisis.

Clinical application of midtrimester non-invasive fetal RHD genotyping and identification of RHD variants in a mixed-ethnic population.

OBJECTIVE: This study aims to assess the suitability of non-invasive prenatal RHD genotyping in non-immunized midtrimester pregnant women from a mixed ethnic population, to prevent unnecessary anti-D immunoglobulin prophylaxis and to identify RHD variants METHODS: Rhesus D-negative pregnant women were offered fetal RHD genotyping at 24 gestational weeks. A total of 284 samples were tested for RHD status using multiplex rt-PCR amplification of exons 5 and 7 of the RHD gene and exons 6 and 10 in selected cases. Women carrying RHD-negative fetuses were counseled about their option to avoid routine antenatal anti-D immunoglobulin administration. Diagnostic accuracy of RHD genotyping was compared with postnatal Rhesus D serotyping. RESULTS: A total of 184 positives (65%), 91 negatives (32%) and 7 cases (2.5%) compatibles with RHD variants were detected by RHD genotyping. No false negative results were found, and a single false positive was observed in a twin pregnancy. Genotyping was accepted when offered by 94% of women (284/302), and anti-D immunoglobulin was avoided in 95% (90/95) of RHD-negative fetuses. CONCLUSIONS: Non-invasive routine antenatal RHD genotyping at 24 weeks of pregnancy is a highly accurate method, resulting in the avoidance of 95% of unnecessary administrations of anti-D immunoglobulin, with no false negative results.

Patología, normalidad o 'niños a la carta'; reflexionando en Paidopsiquiatría / Disease, normality or 'children on demand'; reflecting in Paidopsychiatry

En este artículo se plantean las dificultades en el diagnóstico y tratamiento de los trastornos mentales en la infancia. Se manejan habitualmente los criterios del Diagnostic and Statistical Manual of Mental Disorders, que son categóricos y por ello insuficientes. Se expone la dificultad de definir las zonas de ambigüedad entre lo que se considera normal o patológico, ya que los comportamientos son continuos. Se hace una reflexión acerca de los fines de la Medicina, la función parental y los valores sociales. Finalmente, se plantean interrogantes acerca del mejor tratamiento para estos pacientes (AU)

This paper describes some of the complexities associated to the current approach to diagnosing and treating mental disturbances in children. Most of the diagnoses are articulated in DSM categories that are insufficient. DSM´s categories capture heterogeneous overlaps. Because symptoms and impairments are expressed along a continua, there are no bright lines between healthy children and impaired ones. The goals of medicine, parental and social values and improving the best treatment for these patients are also discussed (AU)

Passive mechanical properties of cardiac tissues in heart hypertrophy during pregnancy.

We evaluated changes in passive mechanical properties in cardiac tissues during rat pregnancy. Left and right ventricular free walls were dissected from hearts of nonpregnant, late-pregnant, and postpartum rats. Mechanical experiments in ventricular strips were done by stretch-release cycles using a step motor. The results show that during pregnancy, there is cardiac hypertrophy associated with (1) an increase in myocyte size, particularly of augmented myocyte length, (2) a decrease in passive tension developed by the myocardial walls, and (3) a decrease in both elastic modulus and hysteresis. All changes observed during rat pregnancy were reversed during postpartum. In conclusion, a heart with less ventricular rigidity could contribute to facilitating the ventricular filling in conditions of a greater circulating volume characteristic of pregnancy.

Effect of growth temperature and pH on the aminopeptidase activity of Pseudomonas putida, P. fluorescens and Flavobacterium odoratum; the 4-nitroaniline test is reliable.

No significant difference (p > 0.05) was observed in the specific aminopeptidase activity (SAA) developed by Pseudomonas fluorescens, P. putida and Flavobacterium odoratum either growing at pH 5.0-6.5 or at 7 and 12 degrees C. Nevertheless, a significant difference was found when comparing the SAA of these organisms. The SAA of F. odoratum was lower than those of pseudomonads. The 4-nitroaniline test is reliable to estimate the G(-) load of fresh food products.

Sprint training attenuates the deficits of force and dynamic stiffness in rat soleus muscle caused by eccentric contractions.

We investigated whether sprint training attenuates the deficits in force and dynamic stiffness caused by eccentric contractions to the soleus muscles of Wistar rats. Two groups of male rats were analyzed: sedentary (C, n=8) and trained (T, n=8). T rats were sprint trained for 10 weeks. Subsequently, the right soleus muscles of rats were freed under anesthesia, leaving the bone insertion and blood supply intact. Eccentric contractions were induced by lengthening muscles during tetanic contractions. Force and dynamic stiffness were tested before and after 20 rounds of eccentric contractions. Tension decline was analyzed using a two-state model (first-order kinetics) in the context of Kramer's theory. Training improved the twitch tension (C, 6.44+/-0.6N/cm(2); T, 10.90+/-0.8N/cm(2)), tetanic force (C, 61.74+/-0.6N/cm(2); T, 85.62+/-0.8N/cm(2)), and increased the dynamic stiffness (C, 41.28+/-1.0N/cm(2); T, 49.56+/-3.2N/cm(2)). Twitch tension after eccentric contractions declined to 73% and 75% in C and T groups, respectively, while tetanic tension decreased to 60% and 36% in C and T groups, respectively. After eccentric contractions, dynamic stiffness decreases were smaller in T rats (from 49.56+/-3.2 to 36.09+/-2.1N/cm(2)) than in C rats (from 41.28+/-1.0 to 20.73+/-1.8N/cm(2)). Sprint training increased the dynamic stiffness and tetanic tension of the soleus muscle and protected against the attenuation induced by eccentric contractions. Finally, the two-state model provided evidence that the number of force-generating cross-bridges increases in trained muscle.

[Treatment recommendations at the end of the life of the critical patient]. / Recomendaciones de tratamiento al final de la vida del paciente crítico.

Admission of a patient in the Intensive Care Unit (ICU) is justified when the critical situation can be reverted or relieved. In spite of this, there is high mortality in the ICU in regard to other hospital departments. End-of-life treatment of critical patients and attention to the needs of their relatives is far from being adequate for several reasons: society denies or hides the death, it is very difficult to predict it accurately, treatment is frequently fragmented between different specialists and there is insufficient palliative medicine training, including communication skills. There are frequent conflicts related to the decisions made regarding the critical patients who are in the end of their life, above all, with the limitation of life-sustaining treatments. Most are conflicts of values between the different parties involved: the patient, his relatives and/or representatives, health professionals, and the institution. The SEMICYUC Working Group of Bioethics elaborates these Recommendations of treatment at the end of the life of the critical patient in order to contribute to the improvement of our daily practice in such a difficult field. After analyzing the role of the agents involved in decision making (patient, familiar, professional, and health care institutions), of the ethical and legal foundations of withholding and withdrawal of treatments, guidelines regarding sedation in the end of the life and withdrawal of mechanical ventilation are recommended. The role of advance directives in intensive medicine is clarified and a written form that reflects the decisions made is proposed.

Recomendaciones de tratamiento al final de la vida del paciente crítico / Treatment recommendations at the end of the life of the critical patient

El ingreso de un paciente en la Unidad de Medicina Intensiva (UMI) está justificado cuando es posible revertir o paliar su situación crítica; a pesar de ello, en las UMI se produce una alta mortalidad con respecto a otros servicios hospitalarios. El tratamiento al final de la vida de los pacientes críticos y la atención a las necesidades de sus familiares están lejos de ser adecuados, por diversos motivos: la sociedad niega u oculta la muerte, es muy difícil predecirla con exactitud, con frecuencia el tratamiento está fragmentado entre diferentes especialistas y hay una insuficiente formación en medicina paliativa, incluyendo habilidades de comunicación. Se producen frecuentes conflictos relacionados con las decisiones que se toman en torno a los enfermos críticos que están en el final de su vida, especialmente con la limitación de tratamientos de soporte vital (LTSV). La mayoría son conflictos de valores entre las diversas partes implicadas: el paciente, sus familiares y/o representantes, los profesionales sanitarios y la institución. El Grupo de trabajo de Bioética de la SEMICYUC elabora estas Recomendaciones de tratamiento al final de la vida del paciente crítico con el propósito de contribuir a la mejora de nuestra práctica diaria en tan difícil campo. Tras el análisis del papel de los agentes implicados en la toma de decisiones (pacientes, familiares, profesionales e instituciones sanitarias) y de los fundamentos éticos y legales de la omisión y retirada de tratamientos, se aconsejan unas pautas de actuación en lo referente a la sedación en el final de la vida y la retirada de la ventilación mecánica, se matiza el papel de las instrucciones previas en medicina intensiva y se propone un formulario que refleje de forma escrita las decisiones adoptadas

Admission of a patient in the Intensive Care Unit (ICU) is justified when the critical situation can be reverted or relieved. In spite of this, there is high mortality in the ICU in regard to other hospital departments. End-of-life treatment of critical patients and attention to the needs of their relatives is far from being adequate for several reasons: society denies or hides the death, it is very difficult to predict it accurately, treatment is frequently fragmented between different specialists and there is insufficient palliative medicine training, including communication skills. There are frequent conflicts related to the decisions made regarding the critical patients who are in the end of their life, above all, with the limitation of life-sustaining treatments. Most are conflicts of values between the different parties involved: the patient, his relatives and/or representatives, health professionals, and the institution. The SEMICYUC Working Group of Bioethics elaborates these Recommendations of treatment at the end of the life of the critical patient in order to contribute to the improvement of our daily practice in such a difficult field. After analyzing the role of the agents involved in decision making (patient, familiar, professional, and health care institutions), of the ethical and legal foundations of withholding and withdrawal of treatments, guidelines regarding sedation in the end of the life and withdrawal of mechanical ventilation are recommended. The role of advance directives in intensive medicine is clarified and a written form that reflects the decisions made is proposed

Cerebrospinal fluid composition modifications after neuroendoscopic procedures.

Normal saline solution is currently used as the ventricular irrigation fluid during neuroendoscopic procedures. The aim of this study is to determine the alterations in the cerebrospinal fluid (CSF) composition after neuroendoscopic interventions. Twenty nine patients who underwent a neuroendoscopic procedure under general anaesthesia were studied. Temperature inside the cerebral ventricle was measured and samples of CSF were taken to determinate oxygen and carbon dioxide partial pressures, pH, base excess, ionised calcium, standard bicarbonate, glucose, sodium, potassium, magnesium, total calcium, proteins, chlorine and osmolality before initiating the irrigation and after the neuronavigation. Patient demographics, neuronavigation time, total fluid volume used and temperature of the irrigation solution and complications that appeared in the first 24 hours were collected. Mean age of the patients was 42+/-18 years. The mean neuronavigation time was 21.5+/-15.4 minutes. The mean amount of saline solution used for irrigation was 919.6+/-994.7 mL. All the values studied in the CSF, except osmolality, showed significant variations. There was a significant correlation between the CSF variation of pH, oxygen and carbon dioxide partial pressures, base excess, standard bicarbonate, glucose and total calcium with respect to the total volume of irrigation solution, but not with respect to the neuronavigation time. A cut-off point of 500 mL of irrigation solution (sensitivity 0.7; specificity 0.87) was related with a CSF pH decrease greater than 0.2. The use of saline as irrigation solution during neuroendoscopic procedures produces important changes in CSF.

Value of NT-proBNP determinations in the follow-up of heart transplantation.

BACKGROUND: The N-terminal pro-brain natriuretic peptide (NT-proBNP) has been useful in the diagnosis and follow-up of heart failure. Whether it can be useful in the detection of acute rejection (AR) after heart transplantation (HT) has not been addressed. Our aim was to assess the prognostic value of NT-proBNP determinations after HT. METHODS: We analyzed 137 endomyocardial biopsies (EMB) performed in 51 patients as assessment of AR and correlated them with NT-proBNP determinations. The value of NT-proBNP in the early follow-up of the novo HT was also assessed. RESULTS: AR grade > or =3A was diagnosed in 10 of the 137 performed biopsies. There were no significant differences in NT-proBNP values between patients with or without AR (1047 +/- 629 versus 1886 +/- 3026 pg/mL, P = NS). There were 24 de novo HT, in these patients increased NT-proBNP levels showed an inverse significant correlation with time since HT (r = -0.40, P = .0001). During follow-up, 15 of the novo HT had a descending NT-proBNP curve over time, and in the remaining 9 (37%) a late increase of NT-proBNP values were observed. Those 9 patients had the following complications: AR > or =3A in 5 cases, 1 death, 2 required a permanent pacemaker, and in the last patient a significant EMB could not be obtained. CONCLUSIONS: NT-proBNP values follow a descending curve early after HT. During the first months, a late increase of NT-proBNP value was associated with HT complications, with AR being the most frequent. Isolated increased NT-proBNP levels were not useful for the detection of AR. More studies are needed to establish the prognostic value of NT-proBNP after HT.

Perineal transsphincteric derivation of urine. Experimental study in rabbits.

AIM OF THE STUDY: We present the experimental results of a new technique that makes use of the anal sphincter to achieve urinary continence in individuals with major congenital defects of the urinary sphincter. METHODS: 50 New Zealand White rabbits were assigned to one of 6 groups and a different surgical procedure was carried out for each group under general anaesthesia with isoflurane alone or isoflurane and local anaesthesia. Variables of interest were: number, consistency and morphology of the faeces, number, shape and location of the stains of urine, histological changes and biochemical parameters in blood. RESULTS AND CONCLUSIONS: The best anaesthetic levels were obtained with 2 % isoflurane and local anaesthesia. The surgical procedure demonstrated its usefulness in achieving urinary continence in all rabbits, although an initial self-limited period of incontinence was common. No histologic alterations were detected, but a significant increase in the levels of urea and creatinine in blood was identified, most likely reflecting an obstructive uropathy.

Glucómetros de uso hospitalario: creación de un equipo pluridisciplinar para el proceso de selección y seguimiento Seis años de experiencia / Glucometers for hospital use: creation of a multi-disciplinary team for the selection and monitoring process

This work highlights what the authors consider to be critical aspects for setting up POCT (point-of-care testing) measurements, whether simple ones such as glucometers or critical ones such as those made with blood gas analyser (AU)

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[Cytokines value as a sepsis and mortality predictor in elderly patients with fever]. / Valor de las citocinas proinflamatorias como factor de predicción de sepsis y mortalidad en el anciano con fiebre.

BACKGROUND AND OBJECTIVE: Proinflammatory cytokines (IL-1beta, IL-6, TNF-alpha) are excellent predictive factors of tissue damage, inflammation and infection. However, there is not sufficient data about their usefulness in elderly patients with acute septic pathology. Our objective was to identify the cytokines related to bacteremia and those that predicted a bad prognosis in elderly patients. PATIENTS AND METHOD: Prospective study carried out during 1999. Patients aged >= 60 years with temperature >= 38 C admitted to the emergency ward. We determined IL-1beta, IL-6, TNF-alpha and C-reactive protein (CRP); cultures were done according to the infectious source. On the 4th day, cytokines and CRP were recorded again. The follow-up was completed until cure or death. RESULTS: 50 patients were included (29 males). Median age was 75.6 (SD: 8.98). The etiology was infectious in 44 (88%): respiratory in 29 (66%), urinary in 8 (18%) and other sources in 7. Thirteen patients had bacteremia (32%): Escherichia coli (4), Streptococcus pneumoniae (5) and others (4). Ten patients died (20%). Median values on admission were CRP : 6.67 mg/dl (NV 0.8), TNF-alpha: 29 pg/ml (NV 0-20), IL-1beta: 7 pg/ml (NV 15) and IL-6: 121 pg/ml (NV 5). 4th day values were: 4.23 mg/dl, 22 pg/ml, 1 pg/ml and 41 pg/ml, respectively. The levels of IL-1b in the 2nd determination were significantly lower in females (p = 0.019). Initial TNF-alpha (p = 0.033), IL-1beta (p = 0.013) and IL-6 (p = 0.031) values were significantly higher in bacteremia patients. IL-6 values on the 4th day were higher in patients who died (p = 0.06). In patients who died, IL-6 levels were higher in the 2nd determination (p = 0.09). CONCLUSIONS: Median values of all cytokines were higher in the bacteremia population. Patients who died showed higher levels of IL-6 on the 4th day.

Folding-unfolding of FN-III domains in tenascin: an elastically coupled two-state system.

In a single-molecule atomic force microscopy (AFM) experiment, the tenascin molecule is stretched by an external force causing an elongation which is due to the unfolding of the FN-III modules. The features of the force-extension curves depend on the pulling speed and show a saw-tooth pattern (lower speeds) or a smooth pattern (higher speeds). In any case, the unfolded domains are elastically coupled to the unfolded modules, acting as transmitters of the external force. In this communication, the folding-unfolding process of the FN-III domains in tenascin is studied using reaction rate theory and a simple two-state model. The main hypothesis of the study is that, at microscopic level, the force needed to unfold a domain and the unfolding rate (unfolding velocity) can mimic the macroscopic process of measurement by AFM. As the external force is applied, the probability of unfolding increases as dictated by the reaction rate theory. Within this context, a relationship between the unfolding force and the unfolding velocity is obtained. The latter relation will describe microscopically the process in a phenomenological fashion. Moreover, while relating the results of this study with other experimental (AFM measurements) and theoretical (Monte Carlo simulations) data, we found that the graph of unfolding force-unfolding velocity is similar to that of external force-pulling velocity. The refolding process can also be studied within this model and the results show similar trends. The latter suggests a generic and universal behavior of such kind of molecular domains at least in the light of the proposed model.