Angiotensin II Inhibits Insulin Receptor Signaling in Adipose Cells.

Angiotensin II (Ang II) is a critical regulator of insulin signaling in the cardiovascular system and metabolic tissues. However, in adipose cells, the regulatory role of Ang II on insulin actions remains to be elucidated. The effect of Ang II on insulin-induced insulin receptor (IR) phosphorylation, Akt activation, and glucose uptake was examined in 3T3-L1 adipocytes. In these cells, Ang II specifically inhibited insulin-stimulated IR and insulin receptor substrate-1 (IRS-1) tyrosine-phosphorylation, Akt activation, and glucose uptake in a time-dependent manner. These inhibitory actions were associated with increased phosphorylation of the IR at serine residues. Interestingly, Ang II-induced serine-phosphorylation of IRS was not detected, suggesting that Ang II-induced desensitization begins from IR regulation itself. PKC inhibition by BIM I restored the inhibitory effect of Ang II on insulin actions. We also found that Ang II promoted activation of several PKC isoforms, including PKCα/ßI/ßII/δ, and its association with the IR, particularly PKCßII, showed the highest interaction. Finally, we also found a similar regulatory effect of Ang II in isolated adipocytes, where insulin-induced Akt phosphorylation was inhibited by Ang II, an effect that was prevented by PKC inhibitors. These results suggest that Ang II may lead to insulin resistance through PKC activation in adipocytes.

Assessment of clinical scoring systems for the diagnosis of Williams-Beuren syndrome.

Williams-Beuren syndrome (WBS) is a genetic disorder characterized by physical and intellectual developmental delay, associated with congenital heart disease and facial dysmorphism. WBS is caused by a microdeletion on chromosome 7 (7q11.23), which encompasses the elastin (ELN) gene and about 27 other genes. The gold standard for WBS laboratory diagnosis is FISH (fluorescence in situ hybridization), which is very costly. As a possible alternative, we investigated the accuracy of three clinical diagnostic scoring systems in 250 patients with WBS diagnosed by FISH. We concluded that all three systems could be used for the clinical diagnosis of WBS, but they all gave a low percentage of false-positive (6.0-9.2%) and false-negative (0.8-4.0%) results. Therefore, their use should be associated with FISH testing.

Characterization of a 1D-imaging high-energy x-ray backlighter driven by the National Ignition Facility Advanced Radiographic Capability laser.

Plastic deformation of samples compressed to Mbar pressures at high strain rates at the National Ignition Facility (NIF) forms the basis of ongoing material strength experiments in conditions relevant to meteor impacts, geophysics, armor development, and inertial confinement fusion. Hard x-ray radiography is the primary means of measuring the evolution of these samples, typically employing a slit-collimated high-Z microdot driven by the NIF laser to generate >40 keV x rays [E. Gumbrell et al., Rev. Sci. Instrum. 89, 10G118 (2018) and C. M. Huntington et al., Rev. Sci. Instrum. 89, 10G121 (2018)]. Alternatively, a dysprosium "micro-flag" target driven by the Advanced Radiographic Capability laser (∼2 kJ, 10 ps) can deliver significantly higher spatiotemporal resolution [M. P. Hill et al., Rev. Sci. Instrum. 92, 033535 (2021)], especially in high-opacity samples. Initial experiments revealed problematic brightness and spectral gradients from this source, but by radiographing a set of diamond-turned, 105 µm-thick Pb test objects and supported by simulations using the 3D Monte Carlo code GEANT4, these geometry-dependent gradients across the field of view are quantified and mitigation strategies are assessed. In addition to significantly enhancing the modulation transfer function compared to the existing system, image stacking from multiple layers of image plate is shown to almost double the signal to noise ratio that will reduce uncertainties in future dynamic strength experiments.

CRF1 Receptor Signaling via the ERK1/2-MAP and Akt Kinase Cascades: Roles of Src, EGF Receptor, and PI3-Kinase Mechanisms.

In the present study, we determined the cellular regulators of ERK1/2 and Akt signaling pathways in response to human CRF1 receptor (CRF1R) activation in transfected COS-7 cells. We found that Pertussis Toxin (PTX) treatment or sequestering Gßγ reduced CRF1R-mediated activation of ERK1/2, suggesting the involvement of a Gi-linked cascade. Neither Gs/PKA nor Gq/PKC were associated with ERK1/2 activation. Besides, CRF induced EGF receptor (EGFR) phosphorylation at Tyr1068, and selective inhibition of EGFR kinase activity by AG1478 strongly inhibited the CRF1R-mediated phosphorylation of ERK1/2, indicating the participation of EGFR transactivation. Furthermore, CRF-induced ERK1/2 phosphorylation was not altered by pretreatment with batimastat, GM6001, or an HB-EGF antibody indicating that metalloproteinase processing of HB-EGF ligands is not required for the CRF-mediated EGFR transactivation. We also observed that CRF induced Src and PYK2 phosphorylation in a Gßγ-dependent manner. Additionally, using the specific Src kinase inhibitor PP2 and the dominant-negative-SrcYF-KM, it was revealed that CRF-stimulated ERK1/2 phosphorylation depends on Src activation. PP2 also blocked the effect of CRF on Src and EGFR (Tyr845) phosphorylation, further demonstrating the centrality of Src. We identified the formation of a protein complex consisting of CRF1R, Src, and EGFR facilitates EGFR transactivation and CRF1R-mediated signaling. CRF stimulated Akt phosphorylation, which was dependent on Gi/ßγ subunits, and Src activation, however, was only slightly dependent on EGFR transactivation. Moreover, PI3K inhibitors were able to inhibit not only the CRF-induced phosphorylation of Akt, as expected, but also ERK1/2 activation by CRF suggesting a PI3K dependency in the CRF1R ERK signaling. Finally, CRF-stimulated ERK1/2 activation was similar in the wild-type CRF1R and the phosphorylation-deficient CRF1R-Δ386 mutant, which has impaired agonist-dependent ß-arrestin-2 recruitment; however, this situation may have resulted from the low ß-arrestin expression in the COS-7 cells. When ß-arrestin-2 was overexpressed in COS-7 cells, CRF-stimulated ERK1/2 phosphorylation was markedly upregulated. These findings indicate that on the base of a constitutive CRF1R/EGFR interaction, the Gi/ßγ subunits upstream activation of Src, PYK2, PI3K, and transactivation of the EGFR are required for CRF1R signaling via the ERK1/2-MAP kinase pathway. In contrast, Akt activation via CRF1R is mediated by the Src/PI3K pathway with little contribution of EGFR transactivation.

Two combined mechanisms responsible to hexavalent chromium removal on active anaerobic granular consortium.

Hexavalent chromium (Cr VI) from industrial wastewaters represents a highly toxic source at low concentrations. Biological treatments with anaerobic granular biomass are a promising alternative for the Cr VI bioremediation. This study evaluated the Cr VI removal in a range of 5-500 mg/L, using an active anaerobic granular consortium. Two removal mechanisms were differentiated from the assays: 1) biological reduction of 70 mg/L to Cr III at a concentration of 250 mg Cr VI/L and 2) physical bioadsorption of 297 mg of Cr VI/L or 31.39 mg of Cr VI/gbiomass at concentration of 500 mg Cr VI /L. The half-maximal inhibitory concentration (IC50) values for the rate and production of methane were 1.4 and 253 mg/L, respectively. In addition, Cr VI is a biostimulant that increase the methane production, in a range from 5 to 100 mg/L, of the anaerobic consortium. This work demonstrates the potential application of the anaerobic granular consortium in metal bioremediation.

Artificial neural networks in neutron dosimetry.

An artificial neural network (ANN) has been designed to obtain neutron doses using only the count rates of a Bonner spheres spectrometer (BSS). Ambient, personal and effective neutron doses were included. One hundred and eighty-one neutron spectra were utilised to calculate the Bonner count rates and the neutron doses. The spectra were transformed from lethargy to energy distribution and were re-binned to 31 energy groups using the MCNP 4C code. Re-binned spectra, UTA4 response matrix and fluence-to-dose coefficients were used to calculate the count rates in the BSS and the doses. Count rates were used as input and the respective doses were used as output during neural network training. Training and testing were carried out in the MATLAB environment. The impact of uncertainties in BSS count rates upon the dose quantities calculated with the ANN was investigated by modifying by +/-5% the BSS count rates used in the training set. The use of ANNs in neutron dosimetry is an alternative procedure that overcomes the drawbacks associated with this ill-conditioned problem.

Entamoeba histolytica contains a gene encoding a homologue to the 54 kDa subunit of the signal recognition particle.

We have determined the nucleotide sequence and predicted amino acid sequence of the 54 kDa subunit of the signal recognition particle (SRP54) from the amitochondrial protist Entamoeba histolytica. The SRP54 gene was isolated from a genomic library using a polymerase chain reaction (PCR) probe. Nucleotide sequence analysis of a 2.3 kb fragment, derived from a 7 kb genomic clone, revealed an open reading frame encoding a protein of 487 amino acids (MW 53.8 kDa). The identities of the predicted amino acid sequence with its homologues from other species were between 24 and 47%. Functional domains previously defined for the SRP54-type proteins were present in the entamoebal sequence, such as the amino-terminal GTP binding domain (G domain) and the carboxy-terminal methionine rich domain (M domain). SRP54 mRNA contains an extra G residue at the 5' end, suggesting that capping of poly-A(+) transcripts is present in E. histolytica. Evolutionary analysis of the SRP54 based on phylogenetic inference placed the E. histolytica sequence as an early divergence of the eukaryotic tree. Although the function of the entamoebal homologue remains to be elucidated, the identification of the SRP54 gene constitutes the first evidence for SRP related proteins in protozoans.

Intraocular neoplastic cyst from mucoepidermoid carcinoma of the conjunctiva.

An 89-year-old woman with recurrent conjunctival mucoepidermoid carcinoma developed intraocular inflammation and an elevated fundus lesion that simulated choroidal detachment in her affected right eye. Intraocular invasion of squamous cell carcinoma was suspected and the eye was enucleated. Pathologic examination of the enucleated eye showed intraocular invasion by conjunctival mucoepidermoid carcinoma that formed a suprauveal cyst lined with malignant epithelial cells. The patient developed an orbital recurrence 1 year later and underwent orbital exenteration. She died 2 years later from an unrelated cause. Conjunctival mucoepidermoid carcinoma can exhibit intraocular invasion and produce an intraocular neoplastic cyst.

Solitary intraosseous infantile myofibroma of the orbital roof.

BACKGROUND: There are several rare tumors that can cause proptosis in an infant, including infantile myofibroma. METHODS: A 3-month-old infant developed a painless, bone-destructive superomedial orbital mass, raising concern for orbital malignant neoplasms. Computed tomography disclosed a bone-destructive mass of the sphenoid wing. On magnetic resonance imaging, the intraosseous mass was well-circumscribed, surrounded by cortical bone, and showed prominent enhancement. RESULTS: Superomedial orbitotomy and biopsy revealed a lesion composed of spindled to stellate cells, without mitotic activity, set in a fibromyxoid stroma. Immunohistochemical stains were positive for vimentin and actin. Ultrastructurally, there were actinlike thin filaments, mitochondria, and rough endoplasmic reticulum confirming a myofibroblastic proliferation and supporting the diagnosis of congenital infantile myofibroma. CONCLUSION: Infantile myofibroma is a benign tumor that occurs rarely in the ocular region but can cause prominent bone destruction, misleading the clinician to suspect a malignant neoplasm.

Adenoma of the iris pigment epithelium: a report of 20 cases: the 1998 Pan-American Lecture.

BACKGROUND: Adenoma of the iris pigment epithelium (IPE) is an uncommon lesion that can simulate iris or ciliary body melanoma, melanocytoma, and pigment epithelial cyst. OBJECTIVES: To evaluate the clinical and pathological features and prognosis of adenoma of the IPE in patients managed by us and to elucidate the features that help to differentiate this tumor from iris melanoma and other similar conditions. PATIENTS AND METHODS: The medical records of 20 patients with adenoma of the IPE were reviewed, and the clinical and histopathologic features were tabulated. RESULTS: Ten patients were male and 10 were female, with a mean age of 60.0 years (range, 11-85 years). All patients were referred because of suspected iris or ciliary body melanoma. All lesions were solitary and unilateral. Sixteen were located in the peripheral iris; 2, in the midzone; and 2, near the pupillary margin. Clinically, all tumors were abruptly elevated, all but 1 were dark gray to black, and all had a smooth, but sometimes multinodular, surface. The tumors caused thinning or complete effacement of the overlying iris stroma, but they did not directly involve the stroma. They typically blocked light with transillumination. On ultrasound biomicroscopy findings, adenoma of the IPE shows a solid tumor pattern, sometimes with small cystoid spaces. The tumor was managed by local resection in 2 patients and observation in 18, all of whom have been stable, with follow-up ranging from 6 months to 9 years. Histopathologic examination revealed a tumor originating in the IPE consisting of cords of pigment epithelial cells separated by septae of connective tissue. CONCLUSIONS: Adenoma of the IPE usually has characteristic features that should differentiate it from iris melanoma, ciliary body melanoma, iris melanocytoma, and iris cyst. Adenoma of the IPE is a benign tumor that may remain relatively stable for years.

Conjunctival melanoma: risk factors for recurrence, exenteration, metastasis, and death in 150 consecutive patients.

OBJECTIVE: To identify the risk factors of conjunctival malignant melanoma that predict local tumor recurrence, orbital exenteration, distant metastasis, and tumor-related mortality. DESIGN: The clinical parameters of the patient, tumor, and treatment were analyzed in a nonrandomized fashion for their relation to 4 main outcome measures using Cox proportional hazards regression models. PARTICIPANTS: One hundred fifty consecutive patients. MAIN OUTCOME MEASURES: Local tumor recurrence, orbital exenteration, distant metastasis, and death from conjunctival melanoma. RESULTS: The Kaplan-Meier estimates of local tumor recurrence was 26% at 5 years, 51% at 10 years, and 65% at 15 years. The mean number of recurrences per patient was 1 (median, 0 recurrences). There was no recurrence in 98 patients (65%), 1 recurrence in 28 patients (19%), 2 recurrences in 11 patients (7%), 3 recurrences in 5 patients (3%), and 4 or more recurrences in 8 patients (5%). Using multivariate analysis, the factors correlated with local tumor recurrence were melanoma location (not touching the limbus) (P =.01) and pathological tumor margins (lateral margin involved) (P =.02). Multivariate analysis for features correlated with ultimate exenteration included initial visual acuity (20/40 OU or worse) (P<. 001), melanoma color red (P =.01), and melanoma location (not touching the limbus) (P =.02). Tumor metastasis was present in 16% of patients at 5 years, 26% of patients at 10 years, and 32% of patients at 15 years. Metastasis was first located in the regional lymph nodes in 17 cases, the brain in 4 cases, the liver in 3 cases, the lung in 2 cases, and was disseminated in 1 case. The risks for metastases using multivariate analysis included pathological tumor margins (lateral margin involved) (P =.002) and melanoma location (not touching limbus) (P =.04). Tumor-related death occurred in 7% patients at 5 years' follow-up and 13% at 8 years' follow-up. The risk factors for death using multivariate analysis included initial symptoms (lump) (P =.004) and pathologic findings (de novo melanoma without primary acquired melanosis) (P =.05). The technique of initial surgery was shown to be an important factor in preventing eventual tumor recurrence (P =.07), metastasis (P =.03), and death (P =.006) in the univariate analysis, but did not reach significance in the multivariate analysis. CONCLUSIONS: Conjunctival malignant melanoma is a potentially deadly tumor. In the present study, metastasis was detected in 26% of patients, and death occurred in 13% of patients at 10 years. Extralimbal melanoma and tumor involvement of the surgical margins were especially poor prognostic factors. Meticulous surgical planning using wide microsurgical excisional biopsy working with the "no touch" technique and supplemental alcohol corneal epitheliectomy and conjunctival cryotherapy is advised. Arch Ophthalmol. 2000;118:1497-1507

Thermotherapy for retinoblastoma.

OBJECTIVE: To evaluate the results of thermotherapy for retinoblastoma. DESIGN: Prospective, nonrandomized analysis of the treatment method. PARTICIPANTS: A total of 188 retinoblastomas in 80 eyes of 58 patients who were treated with thermotherapy. MAIN OUTCOME MEASURES: Tumor response and ocular adverse effects. RESULTS: Of 188 retinoblastomas treated with thermotherapy, mean tumor base was 3.0 mm and tumor thickness was 2.0 mm. Complete tumor regression was achieved in 161 tumors (85.6%), and 27 tumors (14.4%) developed recurrence. Using univariate analysis, the predictors of local tumor recurrence were male sex (P = .005), no color change ("no visible take") in tumor after treatment (P = .01), increasing number of treatment sessions (P = .002), and previous use of chemoreduction (P = .02). By multivariate analysis, the most important predictors of local tumor recurrence were male sex (P = .01) and previous use of chemoreduction (P = .03), the latter likely reflecting the fact that these tumors were initially larger with more ominous findings, and required chemoreduction therapy to reduce them to a size amenable to focal treatment with thermotherapy. When evaluating thermotherapy variables as a function of tumor size, it was apparent that larger tumors (> or =3.0-mm base) required greater energy and time than did smaller tumors (<3.0-mm base). Comparison of treatment variables for larger vs smaller tumors was as follows: number of treatment sessions, 3.3 vs 2.3; spot size, 1.7 vs 1.3 mm; power, 540 vs 370 mW; treatment duration, 49 vs 14 minutes; and coupling of thermotherapy with chemotherapy, 79% vs 48% of cases (P < or =.001 for each variable). Complications of thermotherapy in the 80 eyes included focal iris atrophy in 29 eyes (36%), peripheral focal lens opacity in 19 eyes (24%), retinal traction in 4 eyes (5%), retinal vascular obstruction in 2 eyes (2%), and transient localized serous retinal detachment in 2 eyes (2%). There were no cases of corneal scarring, central lens opacity, iris or retinal neovascularization, or rhegmatogenous retinal detachment. All eyes with focal lens opacity demonstrated adjacent focal iris atrophy. By multivariate analysis, the predictors of thermotherapy-induced focal iris atrophy were increasing number of treatment sessions (P = .001) and increasing tumor base (P = .02). CONCLUSIONS: Thermotherapy is used for relatively small retinoblastomas without associated vitreous or subretinal seeds. This treatment provides satisfactory control for selected retinoblastomas, with 86% of tumors demonstrating lasting regression. Tumors that measure 3.0 mm or larger in base at the time of thermotherapy require more intense treatment than smaller tumors and are at greatest risk for ocular complications such as focal iris atrophy and focal paraxial lens opacity.

Adenoid cystic carcinoma of the lacrimal gland simulating a dermoid cyst in a 9-year-old boy.

Adenoid cystic carcinoma of the lacrimal gland is a malignant neoplasm that is generally found in adults and is usually managed by orbital exenteration and supplemental external beam irradiation or chemotherapy. A recent report has suggested that the tumor may have a less malignant course in children. We describe a case of adenoid cystic carcinoma of the lacrimal gland that simulated a dermoid cyst clinically and radiographically in a 9-year-old boy. The patient was treated with local surgical resection of the mass, followed by orbital plaque brachytherapy. Based on a review of the literature and our recent experience, the advisability of a more conservative approach to this tumor in selected cases is discussed. Although no prognostic conclusions can be drawn on the basis of a single case report with short follow-up, the relatively earlier detection of this tumor made possible by modern orbital imaging studies may allow total removal at an earlier stage and prevent orbital exenteration in a patient with normal vision. Recent developments suggest that there may be a basis for reassessing the advisability of a radical approach to the management of adenoid cystic carcinoma of the lacrimal gland in selected cases.

Transscleral choroidal biopsy in the diagnosis of choroidal lymphoma.

A 57-year-old man with non-Hodgkin's B-cell lymphoma of the abdominal lymph nodes developed moderate cells in the anterior chamber and vitreous, choroidal infiltration, and total nonrhegmatogenous retinal detachment in both eyes while receiving chemotherapy. After a diagnostic vitrectomy in the left eye was nonrevealing, the patient was referred to the oncology service. Fine-needle aspiration biopsy of the choroidal infiltrate was not done because of poor visualization of the choroid through the turbid subretinal fluid. Transscleral choroidal biopsy was performed without complications and disclosed diffuse high-grade B-cell lymphoma and no signs of endogenous infection. Transscleral choroidal biopsy is a useful technique in eyes with choroidal infiltration, especially when hazy media prohibit fine needle biopsy.

Giant cell reparative granuloma of the orbit.

PURPOSE: To report a case of giant cell reparative granuloma occurring in the orbit and to discuss its clinical, radiologic, and histopathologic characteristics in contrast with other similar lesions. METHODS: A 38-year-old man developed pain and mild proptosis of the left eye. Computed tomography and magnetic resonance imaging demonstrated an intraosseous cystic orbital mass. Excisional biopsy disclosed giant cell reparative granuloma of the orbit. RESULT: At 11 months' follow-up, the patient had normal vision, with no tumor recurrence. CONCLUSION: Giant cell reparative granuloma of the orbit is a rare benign fibro-osseous proliferation that is generally seen in young adulthood. It should be considered in the differential diagnosis of orbital fibro-osseous proliferation. Surgical excision and curettage is the therapeutic method of choice.

Iris cysts in children: classification, incidence, and management. The 1998 Torrence A Makley Jr Lecture.

BACKGROUND: Iris cysts in children are uncommon and there is relatively little information on their classification, incidence, and management. METHODS: The records of all children under age 20 years who were diagnosed with iris cyst were reviewed and the types and incidence of iris cysts of childhood determined. Based on these observations recommendations were made regarding management of iris cysts in children. RESULTS: Of 57 iris cysts in children, 53 were primary and four were secondary. There were 44 primary cysts of the iris pigment epithelium, 34 of which were of the peripheral or iridociliary type, accounting for 59% of all childhood iris cysts. It was most commonly diagnosed in the teenage years, more common in girls (68%), was not recognised in infancy, remained stationary or regressed, and required no treatment. The five mid-zonal pigment epithelial cysts were diagnosed at a mean age of 14 years, were more common in boys (83%), remained stationary, and required no treatment. The pupillary type of pigment epithelial cyst was generally recognised in infancy and, despite involvement of the pupillary aperture, also required no treatment. There were nine cases of primary iris stromal cysts, accounting for 16% of all childhood iris cysts. This cyst was usually diagnosed in infancy, was generally progressive, and required treatment in eight of the nine cases, usually by aspiration and cryotherapy or surgical resection. Among the secondary iris cysts, two were post-traumatic epithelial ingrowth cysts and two were tumour induced cysts, one arising from an intraocular lacrimal gland choristoma and one adjacent to a peripheral iris naevus. CONCLUSIONS: Most iris cysts of childhood are primary pigment epithelial cysts and require no treatment. However, the iris stromal cyst, usually recognised in infancy, is generally an aggressive lesion that requires treatment by aspiration or surgical excision.

Radiation therapy for uveal malignant melanoma.

The treatment of uveal melanoma is controversial. The treatment methods include enucleation and other techniques designed to preserve the eye, such as local resection, plaque radiotherapy, charged particle radiotherapy, laser photocoagulation, and thermotherapy. Plaque radiotherapy and charged particle radiotherapy provide tumor control and patient survival comparable with enucleation. Plaque radiotherapy may be associated with fewer anterior segment complications, but the posterior segment complications appear to be similar using either plaque radiotherapy or charged particle radiotherapy. Thermotherapy is emerging as an important adjuvant treatment to maintain control of uveal melanoma after radiotherapy.

Neutron and photon spectra in LINACs.

A Monte Carlo calculation, using the MCNPX code, was carried out in order to estimate the photon and neutron spectra in two locations of two linacs operating at 15 and 18 MV. Detailed models of both linac heads were used in the calculations. Spectra were estimated below the flattening filter and at the isocenter. Neutron spectra show two components due to evaporation and knock-on neutrons. Lethargy spectra under the filter were compared to the spectra calculated from the function quoted by Tosi et al. that describes reasonably well neutron spectra beyond 1 MeV, though tends to underestimate the energy region between 10(-6) and 1 MeV. Neutron and the Bremsstrahlung spectra show the same features regardless of the linac voltage.

Secuencia Moebius. Análisis retrospectivo de 30 pacientes / Moebius syndrome. A retrospective analysis of 30 patients.

Introducción: La secuencia Moebius se caracteriza por el compromiso congénito de los nervios motor ocular externo y facial, y se puede asociar al compromiso de otros pares craneales y a otros defectos congénitos. Su etiología es multifactorial y no bien definida, actualmente la teoría más aceptada es la disrupción vascular durante el desarrollo del romboencéfalo. Su incidencia exacta se desconoce, pero impresiona estar en aumento y asociada a la exposición prenatal a teratógenos. Objetivos: Analizar las historias clínicas de 30 pacientes con secuencia Moebius y las características de su compromiso ocular. Materiales y métodos: Estudio retrospectivo, transversal, observacional y descriptivo. Se analizaron 30 historias clínicas de pacientes con secuencia Moebius atendidos por vez primera entre el mes de Julio de 1999 y Junio de 2012 por el servicio de Oftalmología del Hospital Garrahan. Resultados: Se estudiaron 30 pacientes 15 de sexo femenino y 15 de sexo masculino, dentro de los antecedentes maternos 7 madres refirieron ingesta de misoprostol y 4 tuvieron metrorragias durante el primer trimestre de embarazo. Todos los pacientes tuvieron compromiso del VII nervio; en 20 pacientes fue bilateral y simétrico; y en los restantes asimétrico. Todos los pacientes tuvieron compromiso del VI nervio bilateral, a algunos de los cuáles se les efectuó cirugía de estrabismo otros están en plan de cirugía y unos pocos no la requirieron por presentar fijación de ambos ojos en posición primaria de la mirada. Conclusión: la secuencia Moebius es una rara patología genética y congénita multifactorial y de compromiso multisistémico que ha visto incrementada su frecuencia desde el uso de ciertos fármacos teratógenos y que obliga a una intervención quirúrgica precoz de neuroortopedistas, oftalmólogos, cirujanos plásticos y control clínico multidisciplinario para brindarles a estos niños las mejores posibilidades de desarrollo funcional y estético reparador (AU)

Introduction: Moebius syndrome is characterized by congenital palsy of the external and facial oculomotpr nerves, and may be associated with involvement of other cranial nerves and congenital defects. The etiology is multifactorial and not well defined. Currently, the most widely accepted theory is a rhombencephalic maldevelopment. The true incidence of Moebius syndrome is unknown, but it seems to be increasing associated with prenatal exposure to teratogenic factors. Objectives: To analyze the clinical charts of 30 patients with Moebius syndrome assessing ocular involvement. Material and methods: A retrospective, cross-sectional, observational study. Thirty clinical charts of patients with Moebius syndrome that were first seen at the Department of Ophthalmology of Hospital Garrahan between July 1999 and June 2012 were assessed. Results: Of the 30 patients 15 were female and 15 male. Maternal history showed seven mothers that received misoprostol and four that had metrorrhagia in the first trimester of pregnancy. All patients had VII cranial nerve involvement; the involvement was bilateral and symmetric in 20 and asymmetric in the remaining patients. All patients had bilateral VI nerve involvement, some of whom underwent surgery for strabismus, others are on the list for surgery, and a few do not require surgery because of fixation of both eyes in primary gaze position. Conclusion: Moebius syndrome is a rare multifactorial genetic and congenital pathology with multisystemic involvement and increased incidence because of the use of teratogenic drugs requiring early surgical intervention by neuroorthopedic and plastic surgeons, and ophthalmologists, and a multidisciplinary follow-up to provide these children with the best possibilities for functional development and aesthetic repair (AU)