Successful treatment of severe recalcitrant vernal keratoconjunctivitis and atopic dermatitis associated with elevated IgE levels with omalizumab.

We report the clinical case of an atopic patient with important manifestations impacting the quality of life at the cutaneous and ocular site. The condition resisted conventional treatments, and omalizumab had to be used to treat the disease successfully.

Análisis de las características clínicas y patológicas de pacientes HER2 positivo: estudio en dos poblaciones socioculturales diferentes / Analysis of clinical and pathological features of HER2-positive patients: study in two different socio-cultural populations

Introducción: La sobreexpresión del receptor de membrana HER2/neu se ha asociado a un pronóstico más desfavorable. La importancia clínica de medición, radica en que la sobreexpresión de la proteína sugiere peor pronóstico; por lo tanto, se ha convertido en mandatorio su estudio. Objetivo: Analizar las cualidades clínicas y patológicas de tumores que sobreexpresan HER2 en dos poblaciones con diferente nivel sociocultural y económico, subagrupadas acorde a su atención hospitalaria o a través de una cobertura médica. Resultados: Se observó que la proteína se encontraba sobreexpresada en un 13,42%,con una mediana de edad de 59,19 años. La mediana de tamaño tumoral fue de 22,58 mm, encontrándose una diferencia significativa entre el grupo hospitalario (27,76 mm) y el de atención privada (17,15 mm). Un 65,10% de estas pacientes presentaban un tamaño tumoral menor a 1 cm, pero un 55,82% de las pacientes presentaban compromiso ganglionar axilar y un 11,63% eran estadio IV. Al analizar el compromiso metastásico, se observó un mayor porcentaje en el subgrupo HER+ con respecto al RH+ HER–, pero menor al subgrupo TN (11,63% vs. 7,48% vs. 37,03%), teniendo valor estadísticamente significativo (p<0,0001). Conclusión: A pesar de no encontrar datos fidedignos que nos permitan aseverar la vinculaciónentre el "ambioma" a través de mecanismos epigenéticos, en la diferenciación tumoral, creemos probable que las diferencias socioculturales tengan injerencia directa o indirectamente en la promoción, supresión o diferenciación tumoral.

Factores asociados a recidiva en tratamiento conservador del cáncer de mama invasivo / Factors associated with recurrence in conservative treatment of breast invasive cancer

Introducción: el tratamiento de elección en los estadios iniciales del cáncer de mama invasivo es el conservador. La tasa de recidiva local/regional luego del mismo varía entre 3% y 18%. Objetivo: determinar la tasa y características de recidiva en tratamiento conservador de cáncer de mama invasivo y analizar los factores relacionados con el aumento de riesgo de las mismas.Material y métodos: el presente es un estudio analítico, retrospectivo, de casos y controles, en el cual se incluyen 413 pacientes operadas en el período 01/01/1990 al 31/12/2006. Con un seguimiento a 124 meses, se presentaron 37 mujeres con recidiva local/ regional (8,96%). Resultados: en la rama que presentó recurrencia de enfermedad, el 45,9% (n=17) eran pacientes en premenopausia y el 51,3% (n=19) tenían menos de 55 años. Por el contrario, en la rama contraria, el 15,9% (n=60) eran pacientes en premenopausia y el 28,9% (n=109) eran menores de 55 años. Con relación a los márgenes quirúrgicos pequeños, el 62,2% (n=23) de las pacientes con recaída tenía como antecedente margen quirúrgico menor a 5 mm, lo cual sólo ocurría en el 25,8% (n=97) del grupo restante. Conclusión: los factores de riesgo que presentaron diferencias estadísticamente significativas fueron la edad, £55 años (p=0,0054), el estado de premenopausia(p=0,000056) y los márgenes de resección quirúrgica menores a 5 mm(p=0,000009)

Factores asociados a recidiva en tratamiento conservador del cáncer de mama invasivo / Factors associated with recurrence in conservative treatment of breast invasive cancer

Introducción: el tratamiento de elección en los estadios iniciales del cáncer de mama invasivo es el conservador. La tasa de recidiva local/regional luego del mismo varía entre 3% y 18%. Objetivo: determinar la tasa y características de recidiva en tratamiento conservador de cáncer de mama invasivo y analizar los factores relacionados con el aumento de riesgo de las mismas.Material y métodos: el presente es un estudio analítico, retrospectivo, de casos y controles, en el cual se incluyen 413 pacientes operadas en el período 01/01/1990 al 31/12/2006. Con un seguimiento a 124 meses, se presentaron 37 mujeres con recidiva local/ regional (8,96%). Resultados: en la rama que presentó recurrencia de enfermedad, el 45,9% (n=17) eran pacientes en premenopausia y el 51,3% (n=19) tenían menos de 55 años. Por el contrario, en la rama contraria, el 15,9% (n=60) eran pacientes en premenopausia y el 28,9% (n=109) eran menores de 55 años. Con relación a los márgenes quirúrgicos pequeños, el 62,2% (n=23) de las pacientes con recaída tenía como antecedente margen quirúrgico menor a 5 mm, lo cual sólo ocurría en el 25,8% (n=97) del grupo restante. Conclusión: los factores de riesgo que presentaron diferencias estadísticamente significativas fueron la edad, ú55 años (p=0,0054), el estado de premenopausia(p=0,000056) y los márgenes de resección quirúrgica menores a 5 mm(p=0,000009)

Estudio epidemiológico de la incidencia de la sobreexposición de HER2 en pacientes portadoras de cáncer de mama de reciente diagnóstico en estados iniciales / An epidemiological study of the incidente of HER2 overexpression in recently diagnosed inicial-stage breast cancer patients

Introducción: la posibilidad de identificar pacientes HER2 positivo y poder ofrecerles una terapia específica ha cambiado el pronóstico y la evolución de las mismas, es por ello que la determinación de sobreexpresión de HER2 es una factor clave para la toma de decisiones en el tratamiento del cáncer de mama. Objetivo: recolectar datos locales de la incidencia de la sobreexpresión de HER2 en la población con cáncer de mama de reciente diagnóstico y datos de anatomía patológica y la relación de los mismos con la sobreexpresión de HER2. Materiales y método: estudio epidemiológico que recolecta datos de las fichas de anatomía patológica y de las historias clínicas de pacientes con cáncer de mama operadas entre agosto de 2006 y agosto de 2007. De las biopsias previamente realizadas de rutina en pacientes operadas, se tomó un extendido para la determinación de HER2 por inmunohistoquímica (IHQ) con un anticuerpo policlonal anti HER2 (Dako), recuperación antigénica en microondas, sistema de detección En Vision (Dako) y revelado con diaminobenzidina. Para interpretar los resultados se usó el score de ASCO/CAP. Resultados: ingresaron 342 pacientes, HER negativo, 285 pacientes (83%); dudoso, 19 pacientes (6%); y HER2 positivo, 38 pacientes (11%). La edad promedio fue de 63,7 años. Se compararon las características clínicas y anatomopatológicas de ambas poblaciones (Tabla I). Conclusiones: la incidencia de HER2 positivo fue inferior (11%) a las reportadas en otras series, probablemente influida por el tamaño de la muestra o por el estadio inicial de las pacientes.

Estudio epidemiológico de la incidencia de la sobreexposición de HER2 en pacientes portadoras de cáncer de mama de reciente diagnóstico en estados iniciales / An epidemiological study of the incidente of HER2 overexpression in recently diagnosed inicial-stage breast cancer patients

Introducción: la posibilidad de identificar pacientes HER2 positivo y poder ofrecerles una terapia específica ha cambiado el pronóstico y la evolución de las mismas, es por ello que la determinación de sobreexpresión de HER2 es una factor clave para la toma de decisiones en el tratamiento del cáncer de mama. Objetivo: recolectar datos locales de la incidencia de la sobreexpresión de HER2 en la población con cáncer de mama de reciente diagnóstico y datos de anatomía patológica y la relación de los mismos con la sobreexpresión de HER2. Materiales y método: estudio epidemiológico que recolecta datos de las fichas de anatomía patológica y de las historias clínicas de pacientes con cáncer de mama operadas entre agosto de 2006 y agosto de 2007. De las biopsias previamente realizadas de rutina en pacientes operadas, se tomó un extendido para la determinación de HER2 por inmunohistoquímica (IHQ) con un anticuerpo policlonal anti HER2 (Dako), recuperación antigénica en microondas, sistema de detección En Vision (Dako) y revelado con diaminobenzidina. Para interpretar los resultados se usó el score de ASCO/CAP. Resultados: ingresaron 342 pacientes, HER negativo, 285 pacientes (83%); dudoso, 19 pacientes (6%); y HER2 positivo, 38 pacientes (11%). La edad promedio fue de 63,7 años. Se compararon las características clínicas y anatomopatológicas de ambas poblaciones (Tabla I). Conclusiones: la incidencia de HER2 positivo fue inferior (11%) a las reportadas en otras series, probablemente influida por el tamaño de la muestra o por el estadio inicial de las pacientes.

Cattle nematodes resistant to macrocyclic lactones: comparative effects of P-glycoprotein modulation on the efficacy and disposition kinetics of ivermectin and moxidectin.

The role of the drug efflux pump, known as P-glycoprotein, in the pharmacokinetic disposition (host) and resistance mechanisms (target parasites) of the macrocyclic lactone (ML) antiparasitic compounds has been demonstrated. To achieve a deeper comprehension on the relationship between their pharmacokinetic and pharmacodynamic behaviors, the aim of the current work was to assess the comparative effect of loperamide, a well-established P-glycoprotein modulator, on the ivermectin and moxidectin disposition kinetics and efficacy against resistant nematodes in cattle. Fifty (50) Aberdeen Angus male calves were divided into five (5) experimental groups. Group A remained as an untreated control. Animals in the other experimental Groups received ivermectin (Group B) and moxidectin (Group C) (200 microg/kg, subcutaneously) given alone or co-administered with loperamide (0.4 mg/kg, three times every 24 h) (Groups D and E). Blood samples were collected over 30 days post-treatment and drug plasma concentrations were measured by HPLC with fluorescence detection. Estimation of the anthelmintic efficacy for the different drug treatments was performed by the faecal egg count reduction test (FECRT). Nematode larvae were identified by pooled faecal cultures for each experimental group. Cooperia spp. and Ostertagia spp. were the largely predominant nematode larvae in pre-treatment cultures. A low nematodicidal efficacy (measured by the FECRT) was observed for both ivermectin (23%) and moxidectin (69%) in cattle, which agrees with a high degree of resistance to both molecules. Cooperia spp. was the most abundant nematode species recovered after the different drug treatments. The egg output reduction values increased from 23% to 50% (ivermectin) and from 69% to 87% (moxidectin) following their co-administration with loperamide. Enhanced systemic concentrations and an altered disposition of both ML in cattle, which correlates with a tendency to increased anthelmintic efficacy, were observed in the presence of loperamide. Overall, the in vivo modulation of P-glycoprotein activity modified the kinetic behavior and improved the efficacy of the ML against resistant nematodes in cattle. The work provides further evidence on the high degree of resistance to ML in cattle nematodes and, shows for the first time under field conditions, that modulation of P-glycoprotein may be a valid pharmacological approach to improve the activity and extend the lifespan of these antiparasitic molecules.

Constraints on new physics from the quark mixing unitarity triangle.

The status of the unitary triangle beyond the standard model including the most recent results on Deltam[s] on dilepton asymmetries and on width differences is presented. Even allowing for general new physics loop contributions the unitarity triangle must be very close to the standard model result. With the new measurements from the Fermilab Tevatron, we obtain for the first time a significant constraint on new physics in the Bs sector. We present the allowed ranges of new physics contributions to DeltaF=2 processes and of the time-dependent CP asymmetry in Bs-->J/psivarphi decays.

Visual recognition time in strabismus: small-angle versus large-angle deviation.

PURPOSE: To measure the possible differences in monocular detection time of a threshold visual acuity stimulus (recognition time [RT]) between patients with small-angle and large-angle strabismus. METHODS: Ten patients with free alternating esotropia were tested (10 to 18 years old): five with small-angle esotropia (< or = 7 degrees), five with large-angle esotropia (15 degrees to 20 degrees). Six age-matched normal subjects served as controls. The RT of the threshold stimulus was measured in both eyes sequentially for stimuli presented in the center of a computer monitor (RT 1). Moreover, we measured the time necessary for identifying the same threshold visual acuity stimulus generated on the computer screen in the moment in which fixation is taken up by one eye after occlusion of the second eye (RT 2). Using the same setting, RT was also measured monocularly in all strabismic and normal subjects who were originally looking at a luminous fixation point positioned horizontally at 6.5 and 15 degrees from the center of the monitor (RT 3). RESULTS: The multivariate analysis of variance for repeated measures indicated that there was no statistical difference in RT 1 between groups. The mean RT 2 was significantly longer (p<0.001) in large-angle strabismic eyes when compared with that of normal control eyes. The mean RT 2 in small-angle strabismic eyes did not differ significantly from that of normal eyes. Finally, RT 3 (both at 6.5 degrees and 15 degrees of eccentricity) did not show any significant difference in the three different study groups. CONCLUSIONS: The authors hypothesized that alternating strabismus patients may have a significant advantage in maintaining a small-angle deviation, as a large-angle deviation would require longer RT in the moment the deviated eye takes up fixation. It can be speculated that the extension of re-fixation movement, obviously shorter in small-angle strabismus patients, is the main factor responsible for longer RT occurring in large-angle strabismus patients.

Surgical management of anomalous head posture because of horizontal gaze palsy or acquired vertical nystagmus.

PURPOSE: To confirm the effectiveness of the Kestenbaum-Anderson principle in the surgical management of compensatory head posture because of horizontal gaze palsy and acquired vertical nystagmus. METHODS: Nine patients with anomalous head posture because of horizontal gaze palsy, and four patients with acquired vertical nystagmus and oscillopsia and compensatory torticollis underwent surgery according to the Kestenbaum-Anderson principle. As in the treatment of congenital nystagmus, the eyes have to be shifted in the orbits, in the direction of anomalous head posture. Homonymously based prisms were used preoperatively to assess the potential benefit of surgery. At the time of surgery, the clinical conditions of the patients had been stable for at least 1 year. RESULTS: After surgery, compensatory head posture and visual performances improved in all cases and the results remained stable for at least 2 years. CONCLUSIONS: Contrary to what is generally believed, the ocular condition of the patients with compensatory head posture secondary to neurological causes can be often improved with surgery. The aim of surgery is obviously not to modify ocular motility, but rather to improve the head position.

Bilateral Parry-Romberg syndrome associated with retinal vasculitis.

PURPOSE: To describe an unusual case of bilateral progressive facial hemiatrophy (Parry-Romberg syndrome (PRS)) associated with retinal vasculitis. METHODS: In a 37-year-old man with bilateral PRS, retinal vasculitis of the right eye was evident on fundus examination and fluorescein angiography. Right temporalis muscle biopsy and needle electromyography of the masseter muscles were performed. The patient underwent immunosuppressive therapy and retinal laser photocoagulation. RESULTS: Biopsy specimens showed large fibrosis with focal lymphohistiocytic infiltration of the muscle fibers. Electromyographic findings are consistent with a primary muscle disease. Visual acuity improved from 20/25 to 20/20 in the right eye with a follow-up of one year. CONCLUSIONS: The evidence of retinal vasculitis and the histologic findings of facial changes observed in this PRS case could support the pathogenetic model of a chronic inflammatory process as a plausible explanation for progressive facial hemiatrophy.

Paralytic strabismus.

In the last year, published works on paralytic strabismus have concerned many topics. New advances have been made in the knowledge of epidemiology of ocular nerve palsies in children, muscular causes of paralytic strabismus, and neuroimaging management of patients with third nerve palsy who are at risk of cerebral aneurysms. The author describes reports on rare associations of oculomotor imbalances and neurologic diseases as well as atypical orbital localizations of tumors. He also discuss new neuroimaging findings in congenital superior oblique muscle palsy and new acquisitions on cyclofusion deterioration in acquired trochlear palsy.

Up-shoot in adduction has no prognostic value for decompensation in refractive accommodative esotropia.

PURPOSE: To assess whether up-shoot (elevation) in adduction has any prognostic value for the functional outcome of binocular vision in fully refractive accommodative esotropia (RAET). METHODS: A retrospective study was performed on 58 patients initially diagnosed with RAET who were followed for at least 4 years. RESULTS: Without glasses, up-shoot in adduction with or without a V pattern was detected in 22 of 51 patients who maintained normal binocular alignment during the whole follow-up and in 3 of 7 patients who lost normal binocular vision and showed a manifest esotropia despite glasses at any time of the follow-up. Up-shoot in adduction was still present through glasses only in 3 patients among these 25 cases. Two of these remained fully compensated with glasses during the considered period. The third case developed up-shoot in adduction after decompensation of a previously compensated strabismus. CONCLUSIONS: Up-shoot in adduction is not a common sign in RAET. When present, it does not necessarily represent a negative prognostic sign for preservation of normal binocular vision through glasses in this condition. Up-shoot in adduction can develop after the loss of alignment in some decompensated patients. There is therefore no evidence in favour of a cause-effect relationship between up-shoot in adduction and loss of binocularity in RAET.

Critical age of botulinum toxin treatment in essential infantile esotropia.

PURPOSE: To assess the results of botulinum toxin treatment in 60 consecutive children with essential infantile esotropia. METHODS: Bilateral simultaneous injection of botulinum toxin into the medial rectus muscle was performed in 60 patients under direct visualization with an "open sky" technique. Fluothane/sevoflurane insufflation anesthesia was used. Each patient underwent a single bilateral botulinum toxin injection. Patient age at the time of injection ranged from 5-8 months. RESULTS: Mean patient age at the time of treatment for the 88% of patients who gained a good alignment (within +10 prism diopters [delta] of residual esotropia) was 6.5 months, while mean patient age at time of injection for the 12% of patients who were undercorrected or the deviation relapsed was 7.8 months. Follow-up averaged 5.2 years (range: 2-9 years, SD 2). No variation of the angle of strabismus was observed after 6 months from injection. In some patients with hyperopic refraction, plus lens corrections were prescribed during follow-up to stabilize the alignment. CONCLUSION: Botulinum toxin can be effective in essential infantile esotropia when children are treated by age 7 months.

Cytidine-5'-diphosphocholine improves visual acuity, contrast sensitivity and visually-evoked potentials of amblyopic subjects.

PURPOSE: Cytidine-5'-diphosphocholine (CDP-choline) therapy is currently used to improve the consciousness level in patients with brain lesions and as a complement to levodopa therapy in Parkinson's disease. Recently, the substance has been shown to improve the visual acuity (VA) of both eyes of adults with amblyopia. This study aims at establishing whether Contrast Sensitivity (CS) and visually-evoked potentials (VEPs) also change after CDP-choline treatment. METHODS: VA, CS, and VEPs were measured in a group of amblyopic volunteers (n = 10, mean age 24.8 years) before treatment with Neuroton (CDP-choline, 1 g/day intramuscularly [IM] for 15 days) and the day after termination of the same. CS was evaluated, using a forced-choice, automatic procedure (QUEST: Watson and Pelli, 1983). Steady-state VEPs were recorded in response to counterphased (8 Hz) sinusoidal gratings (2 c/deg) of different contrasts. RESULTS: On average, after treatment, VA improved 1.4-1.5 lines in the amblyopic eyes and 0.4 lines in the normal eyes. CSs improved in both dominant and amblyopic eyes by about 3 dB. VEPs increased in amplitude (about 30%) and advanced in phase (about 0.2 pi rad). Amplitude and phase changes were not correlated. CONCLUSIONS: Treating adult amblyopes with CDP-choline has the effect of improving their VA, CS and VEPs. Changes occur in both eyes, although to different extents, and resemble those previously reported for levodopa treatment.

Binocular vertical perceptual adaptation in essential infantile esotropia.

This study assessed whether dissociated vertical deviation, corresponding to an occasional elevation of the deviated eye, is accompanied by a binocular vertical perceptual adaptation. Dissociated vertical deviation was elicited by means of neutral filters in 16 patients, 8 who had undergone operations for the disorder of essential infantile esotropia and 8 who had not. Neutral filters elicited dissociation vertical deviation, which was accompanied by binocular vertical perceptual adaptation. This effect was significantly greater for patients who had operations and was enhanced by the filter density. Surgical elimination of inhibitory mechanisms for dissociated vertical deviation in patients with essential infantile esotropia appears to facilitate a loose sensory adaptation, which permits a binocular vertical perceptual adaptation.

Comitant strabismus.

This article reviews 14 of the past year's important published works on comitant strabismus, referring to the most interesting developments related to subjects such as epidemiology of comitant strabismus and prevalence of esotropia and exotropia in pathologic conditions like cerebral palsy, Down syndrome, and prematurity-factors influencing the surgical success in strabismus and functional outcomes of early surgery in essential infantile esotropia. Relevant anatomic and physiologic findings on extraocular muscle function are also discussed, which may contribute to our knowledge on the pathophysiology of congenital strabismus.

Brain pathology and strabismus.

This article reviews some of the past year's important papers, with particular emphasis on interesting connections between congenital pathology of the central nervous system and infantile strabismus, neuroimaging findings in meningomyelocele sustaining A-pattern strabismus, surgical outcome in strabismic children with cerebral palsy, and oculomotor problems in cerebral vascular diseases. Oculographic findings in myasthenic ocular palsies and a new form of congenital ocular fibrosis are also reviewed.