In vivo experience with peroral endoscopic myotomy: An essential activity for developing the technique in humans. / Miotomía endoscópica peroral, experiencia in vivo: imprescindible para desarrollo de la técnica en humanos.

INTRODUCTION AND OBJECTIVES: Achalasia is the most widely studied esophageal motility disorder. No treatment has achieved completely satisfactory results. The laparoscopic Heller esophagomyotomy is currently the most accepted technique. With the advent of minimally invasive surgery, the appearance of peroral endoscopic myotomy (POEM) has promising results. The primary aim of our study was to perform peroral endoscopic esophagomyotomy in animal experimentation models to perfect the technique and later apply it to humans. The secondary aims were to evaluate the intraoperative and postoperative complications and to describe the anatomopathologic findings. MATERIALS AND METHODS: An experimental study was conducted on 8 live porcine models that were followed for 30 days to identify postoperative complications. Necropsy was then performed to evaluate the histopathologic findings. The international requirements and regulations for animal experimentation were met. RESULTS: The technique was carried out in all the models. There was one intraoperative death. Pneumothorax was observed in 50% of the units in experimentation and subcutaneous cervical emphysema in 75%, with no significant clinical repercussions. Histologic muscle layer (myotomy) involvement was above the gastroesophageal junction in 87% of the cases and below it in 25%. CONCLUSION: Peroral endoscopic esophagomyotomy is a feasible, albeit complex, procedure that requires advanced training, and thus should be performed in highly specialized centers. Specific skills in advanced therapeutic endoscopic procedures of this type must continue to be developed through continuing education (ideally in in vivo models), to then be performed on humans.

Onicomicosis subungueal proximal en paciente tratado con inhibidores del factor de necrosis tumoral alfa / Proximal subungual onychomycosis in a patient treated with tumor necrosis factor alpha blockers

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Adrenalectomía bilateral laparoscópica por metástasis asincrónica de melanoma: comunicación de un caso con sobrevida prolongada / Bilateral adrenalectomy for asynchronous metastases of a malignant melanoma

Clinical case: we report a 70 years old male with a history of an ear lobe melanoma with was excised seven years ago, who had a bronchial relapse and required a right pneumonectomy. During a follow up abdominal CAT scan, a 9 cm tumor in the left adrenal gland was detected. The patient was operated, performing a left adrenalectomy and nephrectomy. The pathologic study confirmed the presence of a fusocellular melanoma. One year later, a right adrenal mass was detected and excised. The pathological study of the piece again confirmed a metastasis of a malignant melanoma. The patient died due to progression of the disease, 10 years after the adrenalectomy.

Objetivo: presentar un caso de metástasis suprarrenal bilateral asincrónica de melanoma cutáneo tratado con adrenalectomía laparoscópica bilateral. Caso clínico: paciente de 70 años con antecedente de melanoma del pabellón auricular extirpado 7 años antes de su consulta urológica. Posteriormente, presenta una recidiva bronquial tratada con quimioterapia, radioterapia y neumonectomía derecha. En sus exámenes de seguimiento una Tomografía computada muestra el hallazgo incidental de una lesión tumoral de 9 cm en la glándula suprarrenal izquierda. Se realizó nefrectomía y adrenalectomía izquierda laparoscópica en bloque sin incidencias. El análisis histopatológico confirmó el hallazgo de una metástasis de melanoma fuso-celular. Un año después el paciente presenta un nuevo hallazgo incidental de un tumor de 3 cm en la glándula suprarrenal derecha, la cual fue tratada con adrenalectomía laparoscópica, y cuyo análisis histopatológico demostró metástasis de melanoma maligno. El paciente fallece por progresión de su enfermedad 10 años después de su cirugía suprarrenal. Conclusiones: en los pacientes con metástasis suprarrenal de melanoma, la adrenalectomía incrementa la supervivencia cáncer especifica en relación a los pacientes tratados sin cirugía. El abordaje laparoscópico constituye una alternativa terapéutica con menor morbilidad que la cirugía abierta en cirujanos con experiencia laparoscópica.

Human limbal epithelial progenitor cells express αvß5-integrin and the interferon-inducible chemokine CXCL10/IP-10.

Stem cell (SC) therapy is the main treatment modality for patients with limbal stem cell deficiency. If limbal epithelial stem cells (LESC) can be more readily identified, isolated and maintained ex vivo, patients could be treated with better quality grafts. With prior knowledge that vitronectin (VN) is present within the LESC niche and that it supports LESC in vitro, we postulated that VN receptors (integrins αvß3/5) are expressed by, and can be used to identify and isolate LESC. Immunolocalization studies were conducted on human corneas. Corneas were also used to expand limbal epithelial cells from either biopsies or enzyme-dissociated tissue and αvß3/5 expression determined by flow cytometry. Integrin expressing cells were isolated by magnetic activated cell sorting then assessed by immunocytology, colony forming efficiency, RT-PCR and microarray analysis. Integrin αvß5(+) cells co-localized to N-cadherin(+)/CK-15(+) putative LESC. αvß5 was restricted to less than 4% of the total limbal epithelial cells, which expressed higher levels of CK-15 and formed more colonies compared to αvß5(-) cells. Transcriptional profiling of αvß5(+/-) cells by microarray identified several highly expressed interferon-inducible genes, which localize to putative LESC. Integrin αvß5 is a candidate LESC marker since its expression is restricted to the limbus and αvß5(+) limbal epithelial cells have phenotypic and functional properties of LESC. Knowledge of the niche's molecular composition and the genes expressed by its SC will facilitate isolation and maintenance of these cells for therapeutic purposes.

Tratamiento de epicondilitis refractaria con neurotoxina botulínica tipo A libre de complejo proteínico / No disponible

Introducción: La epicondilitis o “codo de tenista” es un cuadro que se caracteriza por dolor en la inserción proximal del músculo extensor radial corto del carpo. El tratamiento de este cuadro clásicamente se ha basado en fisioterapia e infiltración con corticoides, así como el uso de ortesis. La cirugía se recomienda cuando las estrategias conservadoras no controlan los síntomas después de 6-12 meses de tratamiento. La toxina botulínica es una opción terapéutica cuando fracasan medidas conservadoras. Material y métodos: Presentamos 3 pacientes diagnosticados previamente de epicondilitis de más de 6 meses de evolución y que habían sido sometidos de forma ambulatoria a los tratamiento habituales sin éxito, a los cuales se les administró toxina botulínica A libre de complejo proteico (50 UI) en un solo punto de aplicación. Se evaluó la intensidad del dolor en ambos pacientes usando una escala analógica visual (EVA), en la que el 0 representa ningún dolor y 10 significa el dolor más intenso que han experimentado tanto a la palpación como con la maniobra de extensión resistida de la muñeca. Resultados: Se obtuvo una reducción importante del dolor en los 3 pacientes tratados al primer mes de su administración, con resolución total del mismo a los 3 meses. Este beneficio se mantuvo al menos durante los 6 meses de estudio. Conclusiones: La epicondilitis refractaria a tratamientos conservadores puede ser tratada eficazmente con toxina botulínica A libre de complejo proteínico (AU)

Introduction: Epicondylitis or “tennis elbow” is a condition characterized by pain in the proximal insertion of the extensor Carpi radialis brevis muscle. Treatment of this condition has classically been based on physiotherapy and infiltration with corticosteroids, as well as the use of orthoses. Surgery is recommended when the conservative strategies do not control symptoms after 6-12 months of treatment. Botulin toxin is a therapeutic option when conservative measures are failing Material and methods: We present 3 patients diagnosed of epicondylitis for more than 6 months, and which had been subjected to the usual treatment without success, which will manage with free protein complex botulinum toxin (50 IU) at a single point of application on an outpatient basis. The intensity of the pain in the 3 patients were evaluated using an analog scale visual (EVA) in which 0 represents no pain and 10 means more intense pain experienced with resisted wrist extension maneuver both palpation. Results: We obtained a significant reduction of pain in 3 patients treated to the first month of his administration with total resolution at 3 months. This benefit was maintained at least during 6 months. Conclusions: refractory to conservative treatment can be effectively treated with free protein complex botulinum toxin (AU)

Detection of noncalcified pulmonary nodules on low-dose MDCT: comparison of the sensitivity of two CAD systems by using a double reference standard.

PURPOSE: This study compared the sensitivity of two commercial computer-aided detection (CAD) systems in identifying noncalcified pulmonary nodules on low-dose multidetector computed tomography (MDCT) scans by using a double reference standard. MATERIALS AND METHODS: Three chest low-dose MDCT scans of patients who had undergone lung cancer screening were retrospectively analysed using two distinct commercial CAD systems: LungCAD VC10A, Siemens Medical Solutions (CAD1) and LungVCAR, GE Healthcare (CAD2). The exact location of each finding suggested by each system was recorded by an independent reader according to spatial coordinates (x, y, z). Two panels of experienced thoracic radiologists from two different institutions independently established two reference standards (RS1, RS2) by identifying the true positive findings with spatial coordinates without using CAD. Sensitivity of the two CAD systems, defined by lesionlevel analysis, was tested and sensitivities compared. RESULTS: RS1 identified 34 noncalcified pulmonary nodules, whereas RS2 identified 54. The total number of findings detected by the two CAD systems was 684. CAD1 correctly identified 13/34 nodules (sensitivity 38%) for RS1 and 17/54 (sensitivity 30%) for RS2, whereas CAD2 correctly identified 11/34 nodules (sensitivity 35%) for RS1 and 13/54 (sensitivity 23%) for RS2. Comparison between the two CAD systems did not show a statistically significant difference in terms of sensitivity (p<0.05) for both RS1 (p=0.42) and RS2 (p=0.33). CONCLUSIONS: The two commercial CAD systems had similar sensitivity in detecting noncalcified pulmonary nodules on low-dose MDCT of the chest.

Chronic 17beta-estradiol treatment improves skeletal muscle insulin signaling pathway components in insulin resistance associated with aging.

Insulin resistance is a common feature of aging in both humans and rats. In the case of females, it seems to be related to loss of gonadal function, due mainly due to a decrease in plasma estrogen levels. Several causes have been postulated for this insulin resistance, among them changes in several steps of the insulin pathway. In view of these findings, the purpose of the present study was to examine the role of chronic 17beta-estradiol treatment on insulin sensitivity during the aging process, and its effects on levels of the insulin-sensitive glucose transporter Glut4 (both total and plasma membrane localized), the interaction between p85alpha subunit of PI3-k and IRS-1, Tyr- and Ser-612 phosphorylation of IRS-1 levels, and Ser-473 phosphorylation of Akt. The present findings indicate that 17beta-estradiol treatment is able to minimize the deleterious effect of aging on insulin sensitivity, at least at the level of plasma membrane localized Glut4. Nevertheless further research is needed to determine this conclusively.

17beta-Estradiol and/or progesterone protect from insulin resistance in STZ-induced diabetic rats.

Recent clinical and experimental evidences suggest that sex steroids protect from insulin resistance associated with diabetes. Therefore, we have assessed the influence of E2 and/or P4 on insulin sensitivity by euglicaemic-hyperinsulinaemic clamp in ovariectomized streptozotocin-induced diabetic rats, focusing on key proteins of insulin signaling in skeletal muscle. Although low plasma levels of E2 (days 6 and 11) increased Glut-4 plasma membrane content and subsequent improved insulin sensitivity, they could not fully reverse hyperglycaemia negative effects on p85alpha-IRS-1 association and IRS-1 content during 11 days. However, high plasma levels of E2 (day 16) could reverse hyperglycaemia effects not only on Glut-4 plasma membrane content but also on p85alpha-IRS-1 association and IRS-1 protein content level. In contrast, P4 treatment only improved insulin sensitivity when its plasma concentration was low (days 6 and 11) and its effects were not associated with any proteins study in this paper. The combined therapy had a synergic effect on insulin sensitivity when their plasma levels were low (day 6) or high (day 16), that could be associated with Glut-4 plasma membrane content modulation, p85alpha-IRS-1 association and IRS-1 amount. These new findings improve our understanding of biochemical basis of insulin resistance due to hyperglycaemia and could open up new possibilities of treatment in uncontrolled type 1 DM.

Úlceras herpéticas perianales en un paciente con infección por el virus de la inmunodeficiencia humana no diagnosticado previamente / Perianal herpetic ulcers in a patient with previously undiagnosed human immunodeficiency virus

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[Epidemiological study of attempted suicide managed at the hospital emergency department]. / Estudio epidemiológico de las tentativas de suicidio atendidas en la urgencia hospitalaria.

PURPOSE: The authors investigate psychiatric and sociodemographic characteristics of the patients attended at the emergency department in the General Hospital of Mostoles, after their suicidal intent, and of those who repeated a suicidal intent in the first year of follow-up. METHODOLOGY: It is a prospective study, with a duration of one year, in a real sample with 119 patients randomized as a stratified sample from the population attended after their intent. Data recollection was made with a psychiatric semi-structured interview and Beck's letality and suicidal intent scales. Recruitment and follow-up periods were one year long for each of them. Statistical analysis was realized with the chi square test and Fischer's exact test to evaluate associations among cualitative variable and the variance analysis of the relations between qualitative and quantitative variable. RESULTS: Suicide intent ratio was 82/100,000 inhabitants, being in 83% by medicament ingestion. 71% were women, 66% were between 15 and 30 years old, 50% were unmarried and 12% were separated. 33% suffered from a affective disorder, and 23% were alcohol abusers. 6% of them bad a psycotic disorder. 52% of the patients had previous psychiatric disorders and 43% had been in treatment. 46% of them had someone in their families with a psychiatric disorder. 29% were repeaters after a previous attempt. Concerning to a prior contact with the Mental Health Services in the preceding month Significant differences were observed by age, but no significant differences were observed by sex. 26% used alcohol prior to the intent, mainly men. EIB and ELB ratings were significatively higher in retired than in students. Among the patients who repeated their intent (14.5%) of the followed, 78% were women, with an age between 30 and 56 years old. 61% were diagnosed having an affective disorder and 10% had psycotic disorders. 88% of the repeaters were in psychiatric treatment for five years or more.

[Quality assurance in diagnostic radiology using an automated system. Experience and results]. / Garanzia di qualità in radiodiagnostica con l'impiego di un sistema automatico. Esperienza e risultati.

The authors report their personal experience with the use of an integrated quality control system in the radiology department. The system we used was the RTI DIGI-X Plus, a Swedish-made product, allowing a wide range of parameters to be measured on diagnostic X-ray units for general radiography, mammography and fluoroscopy. Data can be retrieved with a minimum number of measurements. The "oRTIgo" software improves the quality assurance system and ensures document compliance with international recommendations. The equipment consists of a detector unit, a processor and a display unit. The detector consists of a rotating holder with 12 combinations of metal filters of various thickness mounted in front of two photo-diodes covered with identical X-ray intensifying gadoliniumoxysulfide screens. This unit is connected to a data acquisition system controlled by a microcomputer. Peak tube voltage and total tube filtration are derived from the ratio of detector signals. The relationship between this ratio and the measured quantity is determined by a calibration procedure. Furthermore, exposure time "mAs" value, "mAs" linearity and exposure (or kerma in air) can be measured. Digital storage can be performed and input signals displayed. A serial interface is used to communicate with a PC for QC management purposes. An error propagation model is used to determine the inaccuracy of peak tube voltage measurements. With the DIGI-X Plus system, measurements can be carried out in a shorter time and the stored data reprocessed later on. After QA testing on 20 X-ray units in the radiology department, in vivo doses were measured using a TLD Harshaw 100 on 46 randomly selected patients undergoing chest examinations. The results are reported and analyzed following the NRPB protocol and show high agreement with the recommended values.

Chagas' disease: polyspecificity of antibodies against Trypanosoma cruzi acidic antigens.

The aim of this work was to study the reactivity of chagasic patient sera against a panel of natural antigens and its relationship with the immune response against T. cruzi acidic antigens. The presence of IgG and IgM antibodies reactive with myosin, myoglobin, actin and thyroglobulin was investigated in sera with positive serology for Chagas' disease classified into groups (G) I, n = 7, with normal electrocardiogram (ECG) and no signs or symptoms of the disease; GII, n = 7, with ECG abnormalities but without cardiomegaly and GIII, n = 7, with cardiomegaly and congestive heart failure. Healthy individual sera were analyzed in parallel as controls. In the three groups of chagasic patients, a high proportion of sera exhibited an enhancement of IgG response anti actin ranging from 71 to 100%. IgM against this antigen was found positive in GI, 21%; GII and GIII, 57%. The antibodies binding to myosin and myoglobin were mainly of IgM type. When myosin was assayed, the frequency of reactive sera was gradually diminished as heart involvement increased: GI 57%, GII 28% and GIII 14%. Only IgG antibodies against thyroglobulin were detected in the three groups of chagasic patients ranging from 43 to 86%. IgG natural antibodies showed to be polyreactive, since a diminished reactivity against each one of the natural antigens assayed and against T. cruzi acidic antigens (FIV) was observed in the sera absorbed with any of the selected antigens irrespective of the absorbing ones. Moreover, the antibodies against FIV parasite's antigens purified by immunoabsorption showed a similar reactivity with FIV, myosin and actin, and a slight lower reactivity with thyroglobulin. These results indicate that in chagasic patients, the specific humoral response against FIV is associated with an increase of the natural autoantibodies along with their polyspecificity.

Enhancement of natural antibodies in mice immunized with exoantigens of pI 4.5 from Trypanosoma cruzi.

This paper deals with the enhancement of natural antibodies in mice immunized with a previously purified exoantigen of Trypanosoma cruzi from infected mouse plasma by isoelectric focusing, called Ea 4.5. A simultaneous rinse of IgG antibodies recognizing acidic sciatic nerve antigen (SNA) and other conserved antigens such as myoglobin, actin, thyroglobulin, and tubulin was observed. The highest level of antibodies was revealed when myoglobin was used as antigen in the ELISA test. Good correlation was found between the level of antibodies reactive with SNA and with highly conserved antigens. Furthermore, absorption experiments showed that a fraction of antibodies binding SNA are polyreactive and also react with the highly conserved antigens. The histological studies of sciatic nerve, heart and skeletal muscle performed 1 month after the last immunization revealed no modifications with respect to the control animals. Based on these and a previous result [1], indicating that injection of Ea 4.5 induced in mice a partial protection against T. cruzi, the possibility exists that a percentage of antibodies induced by Ea 4.5 may correspond to the natural autoantibody type and take part in protective and/or pathogenic effects.

Chagas' disease cardioneuropathy: association of anti-Trypanosoma cruzi and anti-sciatic nerve antibodies.

The aim of this work was to study whether Trypanosoma cruzi infection could elicit humoral immune response to the well-defined parasite antigen acidic fraction separated from T. cruzi cytosol by isoelectric focusing and designated fraction IV (FIV) and whether this response could account for some of the autoreactive immune response against peripheral nerve components. Chagasic patients with positive serology for Chagas' disease were classified as group I (n = 12) with normal electrocardiograms (ECG) and no signs of disease, group II (n = 12) with ECG abnormalities but without cardiomegaly, and group III (n = 12) with cardiomegaly and congestive heart failure. Sera from patients in group II showed the highest frequency of positive reactivity against FIV. Ninety-two percent had titers higher than 1/400 while the percentage for groups I and III was 50%. The autoreactive response against human sciatic nerve saline extract (SNS) was studied. The binding of IgG to SNS was positive in groups I (58%), II (66%), and III (75%) patients. The treatment of SNS with periodate diminished the ability of antigens to fix IgG from these chagasic patients. Absorption studies were performed to investigate whether FIV and SNS could have cross-reactive epitopes. Preabsorption of positive sera with FIV inhibited 48-69% of samples' reactivity against antigen. In contrast, preabsorption of positive sera with SNS inhibited only 12-23% of samples' reactivity against antigen. Overall, these results suggest that FIV-T. cruzi and sciatic nerve components possess some epitopes, possibly of a carbohydrate nature, in common. Thus, infection in Chagas' disease could overcome the tolerance to self components and could lead to autoimmunity.

The clinical utility of serum creatinine measurement vs calculated glomerular filtration rate in the assessment of renal function in the premature infant.

The ability to assess the glomerular filtration rate (GFR) without the necessity of collecting urine in premature infants would be of significant clinical benefit. In 1986, the modified Schwartz formula (MSF = 0.33 x length (cm)/plasma creatinine (mg/dL)) was developed. In the MSF, GFR was estimated in premature infants during the first post-natal year. The goal of the present study was to test the applicability of the MSF in premature infants during the neonatal period and to evaluate the clinical use of serum creatinine (Cr) as a predictor of GFR. In 42 premature infants of mean (+/-SD) birthweight 1506.6 (+/-388.8) g, gestational age 31.3 (+/-1.7) wks and post-natal age 14.7 (+/-8.3) d, the correlation between GFR, estimated by endogenous creatinine clearance (ECrC), was compared with the serum Cr and with GFR estimated by the MSF. The correlation coefficient between ECrC and serum Cr was 0.6789 and between estimated GFR derived from ECrC and MSF, 0.4657. In premature infants during the neonatal period, serum Cr has a better correlation with GFR than with MSF. When serum Cr is less than 0.9 mg/dL, the 95% confidence interval suggests that at least 89% of the infants can be expected to have an ECrC within the normal range.

Indice de adelantamiento de la tuberosidad anterior de la tibia: correlación clínico-radiográfica / Rate of advancement of the anterior tibial tubercle: clinical-radiographic correlationship

Basados en la alta incidencia de alteraciones mecánicas y anatómicas del mecanismo extensor como causa de dolor de la rodilla en pacientes jovénes y activos, y ante la observación radiográfica de estos casos, encontramos frecuentemente un mal o nulo desarrollo de la tuberosidad anterior de la tibia. Los autores revisaron la literatura tratando de encontrar un parámetro radiográfico indicador de adelantamiento natural de esta prominencia ósea. En un estudio prospectivo se revisaron 60 pacientes entre 16 y 45 años de edad, de uno y otro sexo, sin antecedentes quirúrgicos en la articulación de la rodilla, 30 de ellos con dolor femorapatelar y los otros 30 totalmente asintomáticos (voluntarios elegidos al azar). Nuestra hipótesis se fundamenta en las bases biomecánicas del tratamiento de la osteoartritis femoro-rotuliana, estableciendo que existe un índice natural de adelantamiento de l tuberosidad anterior de la tibia que tiene una relación inversa con la incidencia de alteraciones femoro-rotulianas. Los resultados obtenidos confirman nuestra hipótesis ya que en el grupo en estudio de adelantamiento natural fue de 0.0 a 3.0 mm con un promedio de 1.51 mm y en el grupo testigo la variación fue de 1.0 a 6.0 mm con un promedio de 3.4 mm. determinamos, además, un ángulo de adelantamiento que en el primer grupo fue menor de 20 grados y en el grupo testigo de 21 grados, en promedio. Concluimos que estos parámetros radiográficos son útiles para valorar problemas femoro-rotulianos y nos orientan en los casos en los cuales sería útil adelantar quirúrgicamente la inserción distal del tendón rotuliano.