[Impact of NGS results on patient outcome with a multiform glioblastoma]. / Analyse de l'impact des résultats du séquençage de nouvelle génération chez les patients atteints de glioblastome.

PURPOSE: Although some genetic alterations in glioblastoma (GBM) have been characterized, the prognostic value of these gene mutations is not yet established in patients treated with standard therapy. PATIENTS AND METHOD: 40 patients with newly diagnosed GBM, treated between July 2017 and December 2019, and who had genomic analysis were analyzed. Next-generation sequencing techniques (NGS) were used with a panel of 26 genes. Patients were grouped according to MGMT status, the presence or absence of at least one mutated gene on the panel, and p53 expression by immunohistochemistry. RESULTS: the median follow-up was 11.5 months (1.0-37). For all patients, the median duration of progression-free survival was 8 months (95% CI, 5.3-10.7) and the median overall survival (OS) was 17 months (95% CI, 7.5-26.5). Progression-free and overall survival were significantly different according to MGMT status but not according to NGS and p53 status. Three groups of patients according to different combined status could be distinguished due to significant differences in overall survival. CONCLUSION: we have shown that the presence of MGMT promoter methylation is a good prognostic factor. By grouping the patients according to their MGMT, NGS and p53 status, three groups of patients could be separated according to their overall survival. However, these results must be confirmed on a larger number of patients.

Cross-cultural adaptation and reliability of the Filipino version of the Attitude to Disability Scale

Background@#Negative attitudes towards disability must be addressed to promote better quality of life for Filipino persons with disability, but measures to identify these attitudes are not available in the local context. The World Health Organization (WHO) Quality of Life Disability Group's Attitude to Disability Scale (ADS) was identified to be a promising tool for this due to the participatory and cross-cultural approach used for its development and its good psychometric properties. @*Objectives@#This study aimed to culturally adapt the ADS – Physical Disability forms to Filipino. The study also aimed to determine the test-retest reliability and internal consistency of the translated forms. @*Methodology@#The translation process followed recommendations from literature and WHO. The translated forms were pre-tested on 12 Filipino participants with similar profiles to target users to refine the translated forms. Data collection on 362 participants in Metro Manila and surrounding provinces was conducted to evaluate internal consistency of the forms using Cronbach's alpha coefficient. Ninety-seven participants underwent retesting to evaluate the test-retest reliability of the translated forms using Intraclass Correlation Coefficient (ICC). @*Results@#The translation process ensured semantic and conceptual equivalence with the original form and experiential appropriateness for Filipino use. Both translated forms demonstrated good internal consistency (Cronbach's α = 0.67 to 0.82). ICC estimates suggest poor to moderate test-retest reliability (ICC = 0.220 to 0.705). @*Conclusion@#The ADS - Physical Disability forms were culturally adapted to Filipino and were found to reliably measure attitudes towards disability of Filipinos, save for some improvements for test-retest reliability. Further studies are also recommended to ascertain the forms' validity.

Clinimetrics of the Upright Motor Control Test in chronic stroke.

INTRODUCTION: Insufficient literature exists regarding the clinimetric properties of the Upright Motor Control Test Knee Extension and Flexion subtests (UMCT-KE and UMCT-KF, respectively). This study examined the interrater and test-retest reliability of these subtests, and determined the relationship between the UMCT-KE and a clinical measure of muscle function in a sample of adults with chronic stroke. METHODS: Three raters independently administered the UMCT-KE and UMCT-KF on adults with chronic stroke with spasticity/abnormal movement patterns. Testing of each participant occurred on two occasions (T1 and T2) separated by a two-week interval. A fourth rater independently administered the Five Times Sit to Stand Test (FTSST), a measure of lower extremity muscle function (power), on T2. RESULTS: Twenty-nine adults aged 55 ± 8 years, comprising 21 men (72%), and who were 9 ± 5 years poststroke, completed the study. Most of the participants (66%, 19/29) did not require an assistive device during walking. The UMCT-KE and UMCT-KF demonstrated substantial interrater reliability (W = 0.63-0.67 and 0.72-0.75, respectively) and substantial to almost perfect test-retest reliability across the raters (W = 0.75-0.82 and 0.85-0.87, respectively). The UMCT-KE showed positive inverse correlation with the FTSST (ρ = -0.52, p = .003). CONCLUSIONS: Scores on both subtests are reproducible within raters and across different raters. The relationship of UMCT-KE scores with FTSST scores implies that the UMCT-KE can provide information that relates with the construct of muscle function in a weight-bearing position.

Epidemiología de las fiebres tifoidea y paratifoidea en España. A propósito de cuatro casos / Epidemiology of typhoid and paratyphoid fever in Spain. A study of four cases

Introducción: La fiebre entérica (término que incluye la fiebre tifoidea y paratifoidea) es una infección sistémica causada por Salmonella typhi y Salmonella paratyphi. En los países desarrollados, la fiebre entérica dejó de ser endémica para convertirse en una enfermedad frecuentemente asociada a los viajes a zonas endémicas. Pacientes y métodos: Revisión de los casos de fiebre entérica confirmados por hemocultivo, en el periodo comprendido entre el 1 de enero de 2009 y el 31 de diciembre de 2010. Resultados: Se recogieron cuatro casos: fiebre tifoidea en una niña de 12 años natural de Pakistán y en una niña de 13 años originaria de la India que residían en Barcelona y viajaron en vacaciones a su país de origen; fiebre paratifoidea en un niño inmigrante procedente de Senegal, y fiebre paratifoidea en un lactante asociada a una tortuga como vector de transmisión. En todos ellos la fiebre se presentó como síntoma y signo principal de la enfermedad. Todos respondieron bien al tratamiento con amoxicilina-ácido clavulánico. Ningún paciente presentó complicaciones graves. Discusión: Los niños inmigrantes que viajan a sus países de origen para visitar a amigos y familiares presentan un mayor riesgo de enfermar. Los reptiles, portadores habituales de diferentes serovariedades de Salmonella, pueden actuar como posibles vectores de transmisión(AU)

Introduction: Enteric fever (term including typhoid and paratyphoid fever) is a systemic infection caused by Salmonella typhi and Salmonella paratyphi. In developed countries, enteric fever is no longer an endemic disease and has become an infection frequently related to travel to endemic areas. Patients and methods: Review of cases of enteric fever confirmed by blood culture, during the period from January 1st2009 to December 31st 2010.Results: We present four cases: typhoid fever in a 12-yearold girl native of Pakistan and in a 13-year old girl from India, who both lived in Barcelona and traveled on vacation to their country of origin; paratyphoid fever in an immigrant child from Senegal and paratyphoid fever in an infant with a turtle as the vector of transmission. In all cases, fever was the main symptomand sign of the disease. All responded well to treatment with amoxicillin-clavulanate. None of the patients had serious complications. Discussion: Immigrant children who travel to their countries of origin to visit friends and/or relatives are at increased risk of disease. Reptiles, which are common carriers of different Salmonella serovars, may act as potential transmission vector(AU)

Proyección del estudiante de Patología y Clínica Estomatológica desde el ámbito del claustro de la Facultad al Hospital Público: Registro retrospectivo de las patologías observadas / Projection of oral pathology and clinical stomatology student from faculty class room to public hospital: retrospective analyse of the observed diseases

Estableciendo las bases del proceso Enseñanza/Aprendizaje de la Estomatología para alumnos del último nivel de la currícula de Odontología, y en especial de la Asignatura Patología y Clínica Estomatológica, se ha diseñado este estudio. El mismo se ha llevado a cabo teniendo en cuenta los siguientes Objetivos: 1) La observación del desempeño de los estudiantes en un hospital público, en donde han realizado su trabajo en terreno. 2) Un relevamiento de las lesiones y enfermedades que se han presentado con la observación y guía por el personal docente y la resolución de los casos clínicos. Material y Métodos: los alumnos del nivel quinto de la Asignatura de Patología y Clínica Estomatológica de la Facultad de Odontología de la Plata, año tras año han sido citados, por comisiones pequeñas (no más de 7alumnos por cada una) con el fin de observar y participar de la tarea hospitalaria que realiza un equipo docente de Estomatología dentro del funcionamiento del Servicio de Odontología de un Hospital de Agudos. Se tomaron los datos correspondientes a un tiempo estimado en horas de 1.800 horas paciente/docente-alumno. De 495 pacientes fueron evaluados los datos de edad, sexo, ocupación, estado civil, hábitos y factores ambientales. Se registraron los datos correspondientes a las lesiones y enfermedades y se realizó el análisis estadístico de los mismos. Resultados: 1) Los alumnos demostraron interés y entusiasmo al concurrir a la Unidad Hospitalaria. Este resultado se midió por la cantidad de alumnos que solicitaron poder concurrir al Hospital fuera de las horas de clases en forma voluntaria: 40%. 2) Del estudio del relevo de datos, las micosis superficiales fueron las más prevalentes seguidas por aftas, líquenes atípicos y carcinomas a células escamosas. Conclusiones: 1) Se observa que el Hospital docente asistencial pareciera brindar al mecanismo de Enseñanza/Aprendizaje, la posibilidad de insertar al alumno en la realidad de la salud pública del medio ambiente al cual pertenece. 2) Las demás especialidades, integradas al Servicio de Odontología/Estomatología, permitirían una acción en conjunto del equipo sanitario, por un fenómeno de retroalimentación. 3) Coincidiendo con otros datos de diversos Servicios Asistenciales y otras Facultades del país, la Candidiasis oral resultó la lesión más frecuentemente observada. 4) La incidencia de Cáncer bucal nos lleva a insistir sobre su diagnóstico temprano y la importancia del reconocimiento de las enfermedades precancerosa y establecer estrategias contra el hábito del tabaquismo, en nuestro medio de referencia (AU)

This study was designed in order to establish basement of Teaching/Learning process in Stomatology, for students of the last step of Curricula in Odontology and, very specially for Patology and Stomatological Clinic’ attenden. Objectives were: 1) Observation of students behaviour in a public hospital, were it takes place, their «work in situ». 2) To stand out diagnosticated lesions and diseases with the guide of experimental teachers and, resolution of clinic cases. Material and methods: Students of the last level of Patology and Clinical Stomatology Asignature, of the Odontology Faculty of La Plata City, year by year were sending in small groups (no more than seven students each), to a Public Hospital, to Odontology Unit, to participate in an equipment composed by Docents of the Faculty that works in this hospitalry Service and in relationship with other medical units of the same Hospital. For this study, data was assesed taking 1.800 hours/patient. 495 patients were evaluated and sex, age, civil state, ocupation, habits and factors of the enviroment were tabulated. Screaning of lesions and diseases were made and an statistic analyse was performed. Results: 1) Students demostrated, most of the time, really interesting and entusiassm. This result was calculated in a frequence of 40% of them, who wanted to state longer overthere and to come back, out of their own study classes and obligations. 2) From lesions and diseases data study, superficial mycosis was the most prevalent disease that it was founded, followed by major afthous and carcinomas of squamous cells. Conclusions: 1) Its was observed that Assistant/Docent/ Hospital educational method woul offer to Teaching/ Learning mechanism, the possibility to insert the students inside their real public health medium. 2) Other medical specialities integrated with Stomatology seems to allow a common sanitary equipment by a retronutritionary phenomem. 3) In agreement with other data of asistant services and other faculties of our country, Oral Candidiasis was the most observed disease. 4) Incidence of Oral cancer advices us to insist about its early diagnosis, the importance of pre-malignant lesions recognition and to improve strategies againts nicotinism, in our environment (AU)

Enhanced ocular hypotensive response to timolol in rabbits with prior dexamethasone treatment.

The purpose of this study was to determine glucocorticoid modulation of ocular pressure to timolol applied topically to rabbit eyes that were pretreated with dexamethasone. Rabbits were pretreated with five applications of topical 0.007% of dexamethasone (0.01% dexamethasone phosphate) or saline drops, administered at ten min intervals. The eyes were then treated with timolol maleate drops at concentrations of free base of 0.00007%, 0.0007%, 0.007% and 0.07%. An additional group of rabbits received dexamethasone pre-treatment only. Intraocular pressure was measured for the next four hr. Enhanced lowering of intraocular pressure was observed with dexamethasone pretreatment. Rabbits receiving the smaller dose of timolol had the least decrease in pressure. The most significant decreases in pressures occurred at 45 min after the administration of timolol with an average difference of 4.8 mm Hg between the timolol- and dexamethasone/timolol-treated eyes for the three largest concentrations of timolol. This synergism between glucocorticoids and beta-adrenergic blockers in lowering IOP may be potentially useful in the therapy of ocular hypertension and glaucoma.

Reduction in tracheal lumen due to endotracheal intubation and its calculated clinical significance.

BACKGROUND: The flow in the human trachea is turbulent. Thus, the tracheal resistance (R) and the pressure gradient (DeltaP) required to maintain a given flow across the trachea is inversely related to its radius raised to the fifth power. If the caliber reduction ratio (X) after endotracheal intubation is calculated as X = radius of the endotracheal tube (rETT)/radius of the trachea (rT), then DeltaP and/or R will be increased by (1/X)(5). STUDY OBJECTIVES: To measure the actual ratio between rETT and rT following endotracheal intubation of pediatric patients with respiratory failure and to calculate the resulting increase in the tracheal R and DeltaP for a given inspiratory flow rate. DESIGN: Retrospective chart review. SETTING: Pediatric ICU in a tertiary-care teaching children's medical center. PATIENT ENROLLMENT: Twenty consecutive pediatric patients (mean [+/- SD] age, 6.4 +/- 7.2 years) whose tracheas had been intubated for various causes of respiratory failure, and who had received a CT scan, were included in our study. All patients received an endotracheal tube the size of which was derived from the following formula: (age in years/4) + 4. MEASUREMENTS AND MAIN RESULTS: rT and rETT were measured from CT scan sections at and around the level of the thoracic inlet, and the average values were used to calculate X. These values ranged from 0.33 to 0.65 (mean, 0. 55 +/- 0.8). The factor (1/X)(5) was calculated for each patient and then was multiplied by the known normal value for tracheal R for adolescents and adults (0.07 cm H(2)O/L/s) to obtain the value of R resulting from the artificial airway, (1/X)(5) x 0.07. Our results showed that tracheal R increased due to caliber reduction of the trachea after endotracheal intubation by 33.9 +/- 52.5-fold (range, 8.6- to 255.5-fold). In order to maintain an inspiratory flow of 1 L/s, the value of P for the intubated trachea would increase from 0. 07 cm H(2)O to a mean of 2.4 +/- 3.7 cm H(2)O (range, 0.6 to 18 cm H(2)O). In two of our patients, the rT/rETT ratios were < 0.5 (0.33 and 0.44, respectively); this translated into a more significant increase in the calculated DeltaPs, 18 and 4.2 cm H(2)O, respectively. CONCLUSIONS: : The common value of X due to endotracheal intubation is between 0.5 and 0.6, which in and of itself results in an increase in R across the intubated trachea up to 32-fold. The calculated increase in P as a result of this is between 2 and 3 cm H(2)O for adolescents or young adults. The addition of pressure support of at least 3 cm H(2)O during spontaneous ventilation via an endotracheal tube, which is common practice in pediatric critical care, should alleviate any respiratory distress emanating from the increased R. However, a value for X < 0.5, which was found in 10% of our patients (2 of 20 patients), results in a much higher calculated increase in the pressure gradient and, therefore, a higher level of pressure support is required to overcome this increase.

Esclerodermatomiositis infantil / Infantile sclerodermatomyositis

La esclerodermatomiositis (EDM) es un síndrome de solapamiento, caracterizado por la presencia de manifestaciones clínicas de esclerosis sistémica y de dermatomiositis, cuyo principal marcador serológico es el anticuerpo anti-PM/Scl. Presentamos el caso clínico de una niña de 10 años diagnosticada de EDM (AU)

Enhanced ocular hypotensive response to epinephrine in rabbits with prior dexamethasone treatment.

The purpose of this study was to determine glucocorticoid modulation of ocular pressure to epinephrine applied topically to rabbit eyes that were pretreated with dexamethasone. Rabbit eyes were pretreated with five applications of topical 0.07% dexamethasone (0.1% dexamethasone phosphate) or saline drops, administered at ten minute intervals. The eyes were then treated with epinephrine bitartrate drops at concentrations of free base epinephrine of 1.1%, 0.27%, 0.05%, 0.027%, 0.005% or 0.0005%. An additional group of rabbits received dexamethasone pretreatment only. Intraocular pressure (IOP) was measured for the next four hours. Enhanced lowering of intraocular pressure was observed with dexamethasone pretreatment. Rabbits receiving the smaller dose of epinephrine with dexamethasone had the largest decrease in IOP at 135 minutes after instillation of the epinephrine drops (0.005% epinephrine, mean difference +/- standard error of mean = 5.4 +/- 1.1 mmHg). Similarly, the duration of significant decrease of the IOP was prolonged in the groups receiving the lower concentrations of epinephrine (0.005% epinephrine, 255 minutes after administration of epinephrine). The synergism between glucocorticoids and adrenergic agonists in lowering IOP may be potentially useful in the therapy of ocular hypertension and glaucoma.

Enhanced acute ocular hypotensive response to timolol with dexamethasone treatment.

PURPOSE: This study was conducted to determine whether low doses of dexamethasone can enhance the lowering of ocular pressure by low doses of timolol. PATIENTS AND METHODS: In 12 patients with untreated ocular hypertension and similar intraocular pressures in each eye, one eye was randomly selected in a masked manner for pretreatment with three applications of topical 0.01% dexamethasone sodium phosphate drops prepared in artificial tears. The other eye was treated with three applications of drops of artificial tears alone. Both eyes were then treated with 0.01% timolol maleate drops. Ocular pressure was measured for the next 100 minutes at 20-minute intervals. The study was done in an outpatient office. Twelve untreated ocular hypertensive patients participated in this study. RESULTS: When compared with eyes treated with timolol drops alone, eyes pretreated with dexamethasone drops showed a significantly greater decrease in ocular pressure (mean +/- SD); the maximal decrease in 12 dexamethasone-treated patients was 3.5 +/- 1.9 mm Hg (15.9% from baseline). Six dexamethasone-treated patients had a response of 4.0 to 6.0 mm Hg, whereas three showed responses < 4 and > 2 mm Hg with three < or = 2 mm Hg. CONCLUSIONS: This synergistic effect of timolol with dexamethasone on lowering of ocular pressure offers a potential therapeutic use in ocular hypertension and glaucoma.

Relationship between corneal edema and topography.

We found that corneal edema can occur without significant concomitant changes in central and peripheral corneal topography. We examined the relationship between corneal edema and corneal topography in 10 subjects with normal ocular examinations. Baseline pachymetry and topographic measurements for both eyes of each patient were obtained. The right eye of each subject was exposed to an anoxic environment for 2 hours using a nitrogen chamber goggle. The left eye served as control. Optical pachymetry and computerized corneal topographic measurements were taken for both eyes immediately after removal of the nitrogen chamber goggle. All corneas exposed to the nitrogen chamber were thickened in all areas after removal of goggles. Average percent thickening per area was: 16.4% centrally, 6.3% nasally, 6.0% temporally, 6.3% superiorly, and 9.2% inferiorly. Corneas exposed to the nitrogen chamber demonstrated no significant topographic changes, except in the nasal area where the corneal power lessened. Furthermore, there was no significant correlation between corneal thickening in any area measured and changes in corneal topography. Control corneas did not thicken or demonstrate significant topographic changes.

Ketomethylureas. A new class of angiotensin converting enzyme inhibitors.

The design rationale for a new series of tripeptide derived angiotensin converting enzyme (ACE) inhibitors, which we term "ketomethylureas", is described. Analogs of tripeptide substrates (i.e. N-benzoyl-Phe-Ala-Pro) in which the nitrogen atom of the scissile amide bond and the adjacent asymmetric carbon atom of the penultimate amino acid residue are formally transposed give rise to this novel class of inhibitors. The most potent ketomethylureas inhibit ACE with I50 values in the nM range.

Cyclic (hydroxyphosphinyl)acyl dipeptides: a new class of angiotensin converting enzyme inhibitors.

Conformationally constrained phenylbutyl(hydroxyphosphinyl)acyl dipeptides are potent inhibitors of angiotensin converting enzyme. The activity enhancement obtained by introducing conformational constraint into these molecules is greater than for related sulfhydryl and carboxyl analogs. The results are interpreted in terms of a binding model which optimally positions both zinc binding and hydrophobic groups for active site binding.

[Acute neurologic dysfunction associated with a hypodensity of the basal ganglia]. / Disfunción neurológica aguda asociada a hipodensidad de los ganglios basales.

A previously healthy five years old boy, following a mild nonspecific upper respiratory infection developed, fever (39 degrees C), vomiting, clouding of consciousness and focal seizures. The CSF showed a mononuclear cell reaction with negative bacterial and viral cultures. A cranial CT scan on the 4th day of admission showed bilateral low density lesions on the basal ganglia region. After 30 days of severe involvement of muscle tone (rigidity) which kept the patient immobilized in bed and without a meaningful communication with his surroundings, improvement was noticed. A repeated CT scan 40 days after admission, was considered normal. Two months after the beginning of disease, patient's physical examination was normal. This case shows striking clinical and radiological similarities to the ones described by Aicardi and Goutieres in 1982 and most likely is explained by bilateral basal ganglia edema complicating viral encephalitis. Mumps virus, being so far, the most commonly implicated.

Design of conformationally constrained angiotensin-converting enzyme inhibitors.

Modification of alanyl proline by introduction of both zinc coordinating and S1 subsite binding interactions affords potent new carboxy- and mercapto-acyl dipeptide angiotensin-converting enzyme (ACE) inhibitors. Design of these inhibitors was guided by an extension of the hypothetical ACE active site model originally used to derive captopril. Significant increases in ACE inhibitory activity were observed by introduction of conformation constraint into acyclic acyl dipeptides, thus further defining the three dimensional structure of the ACE active site.