Improving Vaccination Documentation Rates Among Patients With Breast Cancer Through Patient Outreach.

BACKGROUND: Patients with cancer are at high risk for infection-related morbidity and mortality; vaccinations reduce this burden. In 2021, vaccination documentation rates were low at an academic medical center breast clinic. OBJECTIVES: The purpose of this pilot quality improvement project was to evaluate an education intervention to increase vaccination documentation among patients with breast cancer. METHODS: During a 16-week period, the 4 Pillars™ Practice Transformation Program was implemented. The oncology nurse navigator assessed and documented vaccination history, discussed recommendations with the provider, and recommended concurrent vaccinations. Within a two-week period, the oncology nurse navigator completed and documented vaccination follow-up via telephone. FINDINGS: Vaccination follow-up and documentation for influenza, shingles, and pneumococcal vaccines increased substantially. Findings indicate that an education and outreach program can increase vaccination documentation rates among patients with breast cancer.

Diversification of plasmids in a genus of pathogenic and nitrogen-fixing bacteria.

Members of the agrobacteria-rhizobia complex (ARC) have multiple and diverse plasmids. The extent to which these plasmids are shared and the consequences of their interactions are not well understood. We extracted over 4000 plasmid sequences from 1251 genome sequences and constructed a network to reveal interactions that have shaped the evolutionary histories of oncogenic virulence plasmids. One newly discovered type of oncogenic plasmid is a mosaic with three incomplete, but complementary and partially redundant virulence loci. Some types of oncogenic plasmids recombined with accessory plasmids or acquired large regions not known to be associated with pathogenicity. We also identified two classes of partial virulence plasmids. One class is potentially capable of transforming plants, but not inciting disease symptoms. Another class is inferred to be incomplete and non-functional but can be found as coresidents of the same strain and together are predicted to confer pathogenicity. The modularity and capacity for some plasmids to be transmitted broadly allow them to diversify, convergently evolve adaptive plasmids and shape the evolution of genomes across much of the ARC. This article is part of the theme issue 'The secret lives of microbial mobile genetic elements'.

Unexpected conservation and global transmission of agrobacterial virulence plasmids.

The accelerated evolution and spread of pathogens are threats to host species. Agrobacteria require an oncogenic Ti or Ri plasmid to transfer genes into plants and cause disease. We developed a strategy to characterize virulence plasmids and applied it to analyze hundreds of strains collected between 1927 and 2017, on six continents and from more than 50 host species. In consideration of prior evidence for prolific recombination, it was surprising that oncogenic plasmids are descended from a few conserved lineages. Characterization of a hierarchy of features that promote or constrain plasticity allowed inference of the evolutionary history across the plasmid lineages. We uncovered epidemiological patterns that highlight the importance of plasmid transmission in pathogen diversification as well as in long-term persistence and the global spread of disease.

Ocular features of Townes-Brocks syndrome.

Townes-Brocks syndrome (TBS) is a rare genetic syndrome associated with heterozygous mutations in SALL1 and characterized by abnormalities of the anus, ear, and thumb. Ophthalmic findings have been rarely reported and include congenital cataract, microphthalmia, optic nerve atrophy, coloboma, epibulbar dermoid, and dysinnervation patterns, such as Duane syndrome and gustatory lacrimation. We report a case of genetically confirmed TBS showing a spectrum of ocular anomalous innervations, including bilateral type 1 Duane syndrome and Möbius sequence, left-sided Marcus Gunn jaw winking, left eye gustatory lacrimation, and lack of emotional tearing bilaterally. Magnetic resonance imaging of brain and orbit showed absence of the abducens nerve bilaterally and of the left facial nerve.

Comparative effectiveness and safety of direct oral anticoagulants (DOACs) versus conventional anticoagulation for the treatment of cancer-related venous thromboembolism: A retrospective analysis.

PURPOSE: The standard of care for the treatment of cancer-related venous thromboembolism (VTE) is a low molecular weight heparin (LMWH) formulation. The recent development of direct oral anticoagulants (DOACs) and their approval for the treatment of VTE has resulted in several new options for treatment. If equivalent to LMWH in terms of safety and effectiveness, the use of DOACs in the treatment of cancer-related VTE would reduce the risk of VTE recurrence while potentially improving the quality of life of many cancer patients. METHODS: We performed a retrospective analysis of adult patients with cancer-related VTE treated in our benign hematology clinic. Among the 153 patients included in our final analysis, 123 (80%) were treated with LMWH and 30 (20%) were treated with DOACs. Patients had 36 different histological types of cancer. The primary outcome was the rate of recurrence of VTE evaluated at 6 and 12months after the initiation of anticoagulation. Secondary outcomes were the rate of anticoagulant-associated clinically relevant bleeding and event-free survival for VTE recurrence. RESULTS: In comparing the 2 treatment groups, there was no statistically significant difference in the cumulative rates of VTE recurrence at 6 and 12months or in the rates of major or non-major bleeding at both 6 and 12months. The median VTE recurrence-free survival rates were not reached and they were not statistically different. CONCLUSION: DOACs appear to be as safe and effective as conventional therapy for the treatment of cancer-related VTE. Results of ongoing randomized clinical studies may provide definitive evidence and clarify the role of the DOACs in the setting of malignancy.

Teratogen exposure and congenital ocular abnormalities in Brazilian patients with Möbius sequence / Exposição à teratógenos e anormalidades oculares congênitas em pacientes brasileiros portadores da sequência de Möbius

Purpose: To assess the sociodemographic profiles, teratogen exposures, and ocular congenital abnormalities in Brazilian patients with Möbius sequence. Method: Forty-four patients were recruited from the Brazilian Möbius Sequence Society. This cross-section comprised 41 patients (age, mean ± standard deviation, 9.0 ± 5.5 years) who fulfilled the inclusion criteria. The parent or caregiver answered a questionnaire regarding sociodemographic data and pregnancy history. Patients underwent ophthalmological assessments. They were subdivided into groups according to misoprostol exposure during pregnancy, and the two groups were compared. Results: Mothers/caregivers reported unplanned pregnancies in 36 (88%) cases. Of these, 19 (53%) used misoprostol during their first trimesters. A stable marital status tended to be more frequent in the unexposed group (P=0.051). Incomplete elementary school education was reported by two (11%) mothers in the exposed group and by three (14%) mothers in the unexposed group (P=0.538). The mothers' gestational exposures to cocaine, marijuana, alcohol, and cigarettes were similar in both groups (P=0.297, P=0.297, P=0.428, and P=0.444, respectively). One (5%) case of Rubella infection during pregnancy was found in the unexposed group. The main malformations in the exposed and unexposed groups were the following: strabismus (72% and 77%, respectively), lack of emotional tearing (47% and 36%, respectively), and lagophthalmos (32% and 41%, respectively). Conclusion: Stable marital statuses tended to be more frequent among mothers that did not take misoprostol during pregnancy. Exposures to other teratogens and the main ocular abnormalities were similar in both groups. .

Objetivo: Descrever o perfil sóciodemográfico, exposição à teratógenos e anormalidades oculares congênitas em pacientes brasileiros portadores da sequência de Möbius Método: Quarenta e quatro pacientes recrutados da Sociedade Brasileira de Sequência de Möbius foram examinados. Este estudo transversal incluiu 41 pacientes que preencheram os critérios de inclusão do estudo (média das idades: 9,0 ± 5,5 anos). Mãe/responsável dos pacientes responderam a um questionário sobre perfil sóciodemográfico e história gestacional. Foi realizado exame oftalmológico de todos os pacientes. Eles foram agrupados em dois grupos de acordo com a exposição ao misoprostol durante a gestação e seus dados foram comparados. Resultados: Mães/responsáveis referiram gravidez indesejada em 36 (88%) dos casos. Destas, 19 (53%) fizeram uso de misoprostol no primeiro trimestre de gestação. Houve uma tendência do grupo de mães não expostas ao misoprostol de terem um estado civil estável (P=0,051). Duas (11%) mães do grupo de expostas ao misoprostol relataram primeiro grau incompleto e três (14%) do grupo de não expostas (P=0,538). A exposição das mães à cocaína, maconha, álcool e cigarro foi similar em ambos os grupos (P=0,297, P=0,297, P=0,428, P=0,444, respectivamente). Houve um caso (5%) de Rubéola no grupo de mães não expostas. As principais malformações associadas nos pacientes expostos e não expostos foram, respectivamente: estrabismo (72% e 77%), e diminuição da lágrima emocional (47% e 36%) e lagoftalmia (32% and 41%). Conclusão: Estado civil estável foi mais frequente em mães que não fizeram uso de misoprostol durante a gestação. Exposição à outros ...

Prevalence of refractive errors in Möbius sequence / Prevalência de erros refrativos na sequência de Möbius

PURPOSE: To assess the prevalence of refractive errors in Möbius sequence. METHODS: This study was carried out during the Annual Meeting of the Brazilian Möbius Society in November 2008. Forty-four patients diagnosed with the Möbius sequence were submitted to a comprehensive assessment, on the following specialties: ophthalmology, neurology, genetics, psychiatry, psychology and dentistry. Forty-three patients were cooperative and able to undertake the ophthalmological examination. Twenty-two (51.2 %) were male and 21 (48.8%) were female. The average age was 8.3 years (from 2 to 17 years). The visual acuity was evaluated using a retro-illuminated logMAR chart in cooperative patients. All children were submitted to exams on ocular motility, cyclopegic refraction, and fundus examination. RESULTS: From the total of 85 eyes, using the spherical equivalent, the major of the eyes (57.6%) were emmetropics (>-0.50 D and <+2.00 D). The prevalence of astigmatism greater than or equal to 0.75 D was 40%. CONCLUSION: The prevalence of refractive errors, by the spherical equivalent, was 42.4% in this studied group.

OBJETIVO: Avaliar a prevalência de erros refrativos em crianças portadoras da sequência de Möbius. MÉTODOS: Trabalho realizado durante o encontro anual da Associação Möbius do Brasil (AMoB) em novembro de 2008. Quarenta e quatro pacientes com diagnóstico de sequência de Möbius foram submetidos a avaliação multidisciplinar: oftalmológica, neurológica, genética, psiquiátrica, psicológica e odontológica. Quarenta e três pacientes colaboraram com exame oftalmológico. Vinte e dois (51,2 %) eram do sexo masculino e 21 (48,8 %) do sexo feminino. A idade média foi de 8,3 anos (2 a 17 anos). A medida da acuidade visual foi realizada com tabela logMAR retro-iluminada, nos pacientes que colaboravam. Todas as crianças foram submetidas a exame da motilidade ocular, refração sob cicloplegia e fundo de olho. RESULTADOS: Do total de 85 olhos estudados, usando o equivalente esférico, a maioria dos olhos (57,6%) são emétropes (>-0,50 D e <+2,00 D). A prevalência de astigmatismo maior que 0,75D foi 40%. CONCLUSÃO: A prevalência de erros refrativos, pelo equivalente esférico, no grupo estudado foi de 42,4%.

Profile of ocular and systemic characteristics in Möbius sequence patients from Brazil and Italy / Perfil de características oculares e sistêmicas de pacientes com a sequência de Möbius do Brasil e da Itália

PURPOSE: To compare the profiles and clinical findings of a series of patients with Möbius sequence from Brazil with a series from Italy. METHODS: This is a multicenter study, which includes 46 Möbius sequence patients from Brazil and 20 from Italy. Socio-demographic, gestational, and neonatal profile characteristics were collected from interviews with the guardians of the Möbius sequence patients and compared. The Möbius sequence patients were submitted to an ophthalmologic examination and systemic malformations were also evaluated. RESULTS: Misoprostol was used in the first trimester of pregnancy by 26 (56.5%) of the mothers of the Möbius sequence patients in the Brazilian series and was not used by any of the Italian mothers. The mean age of the Brazilian Möbius sequence patients was 89.95 ± 7.79 months and the mean age of the Italian patients was 102.6 ± 22.94 months (P=0.6105; Mann-Whitney test). Brazilian mothers had a significantly lower education level (P=0.0002; Fisher's exact test) and Italian mothers had significantly more stable relationships (p=0.0002; Fisher's exact test). The frequency of ocular and systemic abnormalities was similar in both series. CONCLUSION: Adverse events during pregnancy varied between both groups. A history of misoprostol use during early pregnancy was present only in Brazilian mothers, who had lower levels of education and less frequent stable marital statuses. Clinical findings were similar between both groups of patients.

OBJETIVO: Comparar o perfil de características oculares e sistêmicas de uma série de pacientes com sequência de Möbius do Brasil com uma da Itália. MÉTODOS: Esse estudo multicêntrico incluiu 46 pacientes com sequencia de Möbius do Brasil e 20 da Itália. As características dos perfis sociodemográfico, gestacional e neonatal foram coletadas a partir de entrevistas com os responsáveis dos pacientes e comparadas. Os pacientes foram submetidos a um exame oftalmológico e malformações sistêmicas foram avaliadas. RESULTADOS: O misoprostol foi usado no primeiro trimestre da gestação por 26 (56,5%) mães brasileiras e por nenhuma italiana. A média de idade dos pacientes brasileiros com sequência de Möbius foi de 89,95 ± 7,79 meses e dos italianos 102,6 ± 22,94 meses (P=0,6105; teste de Mann-Whitney). Mães brasileiras tinham significantemente menor escolaridade (P=0,0002; teste exato de Fisher) e mães italianas tinha relacionamentos estáveis mais frequentemente (P=0,0002; teste exato de Fisher). A frequência de anormalidades oculares e sistêmicas foi semelhante entre as séries. CONCLUSÃO: Eventos adversos durante a gestação variaram entre os grupos. O uso de misoprostol pelas mães precocemente na gestação foi relatado apenas por mães brasileiras, que tinham menor escolaridade e status conjugal estável menos frequentemente. Achados clínicos foram semelhantes entre os grupos.

Macular thinning associated with unilateral optic nerve hypoplasia.

The authors present the case of an 8-year-old boy with a long-term diagnosis of unilateral optic nerve hypoplasia (ONH) of unknown cause in the right eye. Spectral-domain optical coherence tomography (SD-OCT) of the central macula was consistent with hypoplasia greatest in the inner retinal layers, but also involving the outer retinal layers when compared with the unaffected contralateral eye. Although ONH is commonly associated with hypoplasia of the nerve fiber and ganglion cell layers, it can also be associated with hypoplasia of other layers in the inner and outer retina, including the outer nuclear and photoreceptor inner/outer segment layers, as evidenced by SD-OCT.

Resposta humoral ao vírus dengue em mães/filhos: relação com a sequência de Mõbius / Humoral immune response to dengue virus in mothers/children: relation with Mõbius sequence

OBJETIVO: Investigar a resposta humoral para o vírus dengue em pacientes com sequência de Mõbius e suas mães, analisando a relação entre a infecção na gestação e o nascimento de portadores da sequência de Mõbius. MÉTODOS: Foram revisados os prontuários dos pacientes atendidos em centro de referência. Aplicou-se um questionário estruturado a cada genitora. Sorologia por Elisa para IgG de dengue foi efetuada em 35 pacientes e suas mães. O teste de neutralização por redução em placas foi feito nas que referiram infecção viral na gestação e em seus filhos, para determinar o sorotipo viral causador da infecção. RESULTADOS: Febre, cefaléia e/ou dor retro-orbitária foi referida por 18 (51,4 por cento) mães. Três (8,6 por cento) referiram dengue no primeiro ou início do segundo trimestre de gestação. Cruzando-se as informações das sorologias das mães e crianças observou-se que em 57,1 por cento dos casos há positividade sorológica para o vírus do dengue na mãe e no filho. Das três mães com infecção na gestação, uma e seu filho, apresentou teste de neutralização por redução em placa positivo para o vírus dengue tipo três (DENV-3), entretanto o sorotipo apenas foi introduzido em Pernambuco em 2002, o que exclui a possibilidade de ter ocorrido transmissão vertical da doença. CONCLUSÃO: As sorologias dos casos que tiveram diagnóstico clínico de dengue na gravidez revelaram-se incompatíveis com a hipótese de ter ocorrido transmissão vertical da doença. Portanto, na amostra estudada, a infecção pelo vírus do dengue não pode ser considerada como fator implicado na gênese da sequência de Mõbius.

PURPOSE: To investigate the humoral immune response to dengue virus in patients with Mõbius sequence and their mothers, assessing the relation between this infection during pregnancy and Mõbius sequence. METHODS: The medical records were reviewed, and a questionnaire was answered by each mother. IgG ELISA was performed in 35 patients and their mothers. A plaque reduction neutralization test was further done in the mothers who reported a viral infection during pregnancy and in their children for determining which dengue serotype virus had caused the infection. RESULTS: Fever, headache and/or retrobulbar pain during pregnancy was referred by eighteen (51.4 percent) mothers. Three (8.6 percent) reported dengue during the first or second quarteers of pregnancy. When cross analyzing the mothers and their respective children serological results, 57.1 percent of them matched. Of the three mothers with clinical diagnosis of viral infection during pregnancy, one and its respective children had a positive plaque reduction neutralization test for dengue serotype three (DENV-3), this serotype reached Pernambuco in 2002, which excludes the possibility of a vertical transmission to the children. CONCLUSION: The serology of the cases that had clinical diagnosis of dengue during pregnancy proved to be incompatible with the hypothesis of the disease vertical transmission. Therefore, in the present serie, the dengue virus infection can not be considered as a factor involved in the genesis of Mõbius sequence.

Oculo-auriculo-vertebral spectrum: associated anomalies, functional deficits and possible developmental risk factors.

Swedish patients with the oculo-auriculo-vertebral (OAV) spectrum participated in a prospective multidisciplinary investigation. The aims of the study were to describe their systemic and functional defects, especially autism spectrum disorders, and to search for possible etiologic risk factors. Available medical records were studied and the mothers answered a questionnaire on history of prenatal events. A clinical examination evaluating systemic findings, vision, hearing, speech, oral and swallowing function, and neuropsychiatric function, especially autism, was made. Eighteen patients, (11 males, 7 females) aged 8 months to 17 years with OAV were studied. Most frequent systemic malformations included, ear abnormalities (100%), ocular malformations (72%), vertebral deformities (67%), cerebral anomalies (50%), and congenital heart defects (33%). Functional defects consisted of hearing impairment (83%), visual impairment (28%), both visual and hearing impairment (28%), difficulties in feeding/eating (50%), speech (53%), mental retardation (39%), and severe autistic symptoms (11%). Three children were born following assisted fertilization (two intracytoplasmatic sperm injection, one in vitro fertilization), two mothers reported early bleedings, and six (33%) mothers had smoked during pregnancy.

Autism spectrum disorder and underlying brain mechanism in the oculoauriculovertebral spectrum.

As part of a multidisciplinary study, the rate of autism spectrum disorder (ASD), learning disability (LD), and brain abnormalities was examined in 20 participants (12 males, 8 females; age range 8mo-17y, mean age 8y 1mo) diagnosed as falling within the oculoauriculovertebral spectrum (OAV). A neuropsychiatric examination was performed, including standardized autism diagnostic interviews. Two individuals met diagnostic criteria for autism, one for autistic-like condition, and five for autistic traits. Four patients had mild LD, three severe LD, two profound LD, and two borderline intellectual functioning. Neuroimaging indicated cerebral abnormalities in more than half of the patients. Abnormalities of white/grey matter were found in more than half of examined individuals; enlargement of ventricles in more than a third. Results indicate that at least a subgroup of ASD may be associated with errors in early embryonic brain development. Awareness of the coexistence of OAV/ASD is important in habilitation care of individuals with OAV.

Prevalence of diabetes mellitus in patients receiving depot neuroleptics or clozapine.

This retrospective study compared the prevalence of diabetes mellitus/hyperglycemia between patients receiving treatment with clozapine (n = 24) and patients receiving treatment with depot (n = 27) neuroleptics in a Department of Veterans Affairs outpatient mental health clinic in the Mid-Atlantic region. Of the clozapine cases without a history of diabetes/hyperglycemia, 27.7% developed diabetes after initiation of clozapine. There were no new cases of diabetes/hyperglycemia in the depot group after initiation of depot neuroleptic. All patients receiving neuroleptic treatment should be monitored for changes in weight, lipid, and glucose levels so that appropriate preventive and therapeutic measures can be promptly initiated.

Autism associated with conditions characterized by developmental errors in early embryogenesis: a mini review.

Autism is a complex developmental disorder without an established single etiology but with significant contributions from genetic studies, functional research, and neuropsychiatric and neuroradiologic investigations. The purpose of this paper is to review the findings in five studies involving individuals manifesting the characteristic findings of autism spectrum disorder associated with malformations and dysfunctions known to result from early embryogenic defects. These investigations include two associated with teratogens (thalidomide embryopathy, Mobius sequence with misoprostol) and three (most Mobius sequence cases, CHARGE association, Goldenhar syndrome) with no known etiology. These studies suggest that early embryonic development errors often involving cranial nerve palsies, internal and external ear malformations, ophthalmologic anomalies, and a variety of systemic malformations may be associated with autism spectrum disorders statistically more frequently than expected in a normal population. Although the exact time of developmental insult for each condition cannot be identified, the evidence is that it may occur as early as week 4 to 6+ of embryogenesis.

Formação de Oftalmopediatras no Brasil / Pediatrics ophthalmology training in Brazil

RESUMO: Este estudo teve como objetivo analisar a formação de oftalmopediatras nos Cursos de Especialização em Oftalmologia, credenciados pelo Conselho Brasileiro de Oftalmologia, verificando-se a presença de departamentos especializados para o atendimento da população peiátrica tais como: estrabismo, visão sub-normal e catarata congênita. Foi realizada uma survey nos serviços que oferecem Curso de Especialização em Oftalmologia credenciado pelo Conselho Brasileiro de Oftalmologia (CBO). Os questionários foram enviados via eletrônica, pelo correio, por fax e feito contato telefônico. Os dados foram expressos por suas freqüências. Foram respondidos 33 questionários. Em quatro serviços existe curso formal de oftalmologia pediátrica; nos quais, nos últimos seis anos, foram formados 40 profissionais nesta área. Dos entrevistados, cinco não Possuíam Departamento de Oftalmopediatria, sendo o atendimento às crianças realizado pelo oftalmologista generalista. Isto reflete uma deficiência importante, tendo em vista ser de consenso, que o atendimento oftalmológico das crianças deve ser realizado por profissionais com treinamento específico

Sequencia de Mobius: resultados preliminares da correção cirúrgica do estrabismo / Mobius sequence: preliminary findings of strabismus surgical outcome

Objetivos: Analisar os resultados cirúrgicos preliminares encontrados em uma série consecutiva de pacientes com a Sequencia de Mobius, submetidos à correção cirúrgica do estrabismo. Pacientes e Métodos: Dez portadores de Sequencia de Mobius atenderam aos critérios de inclusão. Média idade de 6 +/- 2,8 anos. Todos apresentaram esotropia no exame pré-operatório variando de 15 a 85 dioptrias prismáticas, média de 67,1. Todos os pacientes demonstraram hipofunção dos músculos retos laterais, alguns apresentaram hipertropia associada e outros anisotropia em A ou em V. Os pacientes foram submetidos de forma consecutiva a cirurgia para a correção do estrabismo, de acordo com um protocolo previamente elaborado. O procedimento cirúrgico constitui em retrocesso dos músculos retos mediais de ambos os olhos nos pacientes com estrabismo convergente, e aqueles que apresentavam desvio vertical foram também submetidos à cirurgia dos retos verticais e da musculatura oblíqua. Os pacientes foram reavaliados no primeiro, décimo, quadragésimo quinto e nonagésimo dia do pós-operatório com relação à medida do desvio, estética e socialização. Resultados: Os pacientes apresentaram resultado visual satisfatório final em sete casos. Todos os pacientes apresentaram correção da anisotropia e melhora da limitação da abdução. Conclusões: O resultado cirúrgico dos pacientes estudados mostrou-se bastante satisfatório, elevando a auto-estima e a de seus genitores, facilitando a inclusão social dos mesmos.

Achados oftalmológicos em 28 crianças portadoras da seqüência de Mõebius / Mõebius sequence: clinical ophthalmological findings in 28 cases

OBJETIVO: Analisar os principais achados oftalmológicos encontrados em uma série de casos de seqüência de Mõebius. MÉTODOS: Foram estudados 28 pacientes com o diagnóstico de seqüência de Mõebius, atendidos em três centros oftalmológicos de referência do Estado de Pernambuco, Brasil. RESULTADOS: Foi observado: presença de epicanto em 25 pacientes (89,3 por cento), blefaroptose em 14 (50,0 por cento), ceratopatia de exposição em cinco (17,8 por cento) e alteração do reflexo de Bell em três (11,1 por cento). A acuidade visual monocular variou de 0,03 a 1. Deficiência da acuidade visual esteve presente em 13 pacientes (46,4 por cento). A ametropia mais encontrada foi o astigmatismo, diagnosticado em 33 olhos (58,9 por cento) do total de 56 examinados. Na posição primária do olhar, 16 pacientes (57,2 por cento) apresentaram esotropia, 2 (7,1 por cento) apresentaram exotropia e 7 (25,0 por cento) ortotropia. O exame de fundo de olho foi normal em 26 pacientes (92,8 por cento). CONCLUSAO: Foi observado que os pacientes portadores da seqüência de Mõebius apresentavam alterações oftalmológicas importantes no que diz respeito à presença de deficiência da acuidade visual, desvio ocular, ceratopatia de exposição e ametropias. Sugere-se que esses pacientes sejam avaliados precocemente por um oftalmologista, visando o diagnóstico e tratamento adequado.

Autism with ophthalmologic malformations: the plot thickens.

PURPOSE: To review the association of autism spectrum disorder (ASD) in individuals manifesting thalidomide embryopathy and Möbius sequence and compare them with three new studies in which ASD was also associated with ocular and systemic malformations: (1) a Swedish study of individuals with CHARGE association (Coloboma, Heart, choanal Atresia, developmental or growth Retardation, Genital anomaly, and Ear involvement); (2) a Swedish study of Goldenhar syndrome; and (3) Brazilian Möbius syndrome (sequence) study. METHODS: In the Swedish CHARGE study, 31 patients met the inclusion criteria (3+ or 4 of the common characteristics of the CHARGE syndrome). The same team of investigators also evaluated 20 Swedish patients with Goldenhar syndrome. In the Brazilian Möbius study, 28 children with a diagnosis of Möbius sequence were studied; some children had a history of exposure during their mother's pregnancy to the abortifacient drug misoprostol in an unsuccessful abortion attempt. RESULTS: In the CHARGE study, five patients had the more severe autism disorder and five had autistic-like condition. In the Goldenhar study, two had autism disorder and one had autistic-like condition. In the Brazilian Möbius study, the systemic findings of the misoprostol-exposed and misoprostol-unexposed patients were almost undistinguishable, and ASD was present in both groups (autism disorder in five and autistic-like condition in three). CONCLUSION: Autism spectrum disorder has been reported in two conditions with known early pregnancy exposure to the teratogenic agents thalidomide and misoprostol. In the Brazilian Möbius study, autism also occurred in both the misoprostol-exposed and misoprostol-unexposed groups. Autism also was present in patients with both CHARGE association and Goldenhar syndrome.

Secuencia de Mobius: hallazgos genético-clínicos

Introducción: La teoría más aceptada en cuanto a la etiopatogenia de la Secuencia de Mõbius, es la que resulta de una disrupción vascular en la edad temprana de la embriogenesis debido a factores genéticos o ambientales. Este estudio tiene como objetivo principal, describir los hallazgos Clínico-genéticos en pacientes con Secuencia de Mobius cuyas madres usaron o no, misoprostol durante el embarazo. MÉTODOS: fueron examinados 28 pacientes con el diagnóstico previo de secuencia de Mõbius, atendidos em tres servicios de referencia, através de un estudio clínico de corte transversal. Se realizó una completa evaluación por un equipo multidisciplinario, siguiendo un protocolo previamente elaborado. Los critérios de inclusión para dicho estudio fueron: la presencia de parálisis congênita, uni o bilateral del Vl y Vll nervios craneanos. Se evaluaron los pacientes en cuanto a los hallazgos genético-clínicos. RESULTADOS: un total de 28 casos atendieron a los criterios de inclusión para el estudio, con edades comprendidas entre 1 a 141 meses, media de 43 meses, desvación estandard de 41 meses. El periodo de daño al embrión fue en media en la quinta semana post fertilización. Fui evidenciado el epicanto en 25 casos (89.3 por cento). La limitación a la abducción fue vista en todos los pacientes (100.0 por cento), boca de cúpido en 18 casos (66.7 por cento),pies equinovarus en 12 casos (44.4 por cento). La secuencia Poland-Mõbius y la anomalia de Poland-Mõbius, fueran vistas en un caso (3,6 por cento) respectivamente. Tres casos (10.7 por cento) tuveron antecedentes familiares positivos de patologías de miembros en el grupo de pacientes no expuestos al misoprostal. CONCLUSIÓN: En este estudios los principales hallazgos clínico-genéticos observados fueron anomalías craneo-faciales y de miembros, habiendo también compromiso de los nervios craneanos. En la muestra estudiada hubo elevada asociación entre el uso del misoprostol y la secuencia de Mõbius. Otros autores sugieren que esta droga actuaría como probable teratógeno, aumentando la incidencia de anomalías congénitas.

Transcription profiling of estrogen target genes in young and old mouse uterus.

The goal of this study was to identify age-related changes in the expression of estrogen target genes in mouse uterus. We developed a novel 'estrogen response element (ERE) Chip' microarray bearing 297 genes including both known estrogen target genes and genes identified by searching the mouse genome database to have EREs, AP-1 sites, and Sp1 sites, all targets of estrogen receptor (ER) regulation. 400-500 bp PCR products of these 297 genes were printed onto nylon membranes creating the 'ERE Chip' microarray. This microarray is unique because it is the first estrogen-responsive gene-specific microarray to identify changes in uterine gene expression in young versus old mice. Using this ERE microarray we identified 10 uterine genes whose expression was up-regulated in old mice, e.g. beta-actin, calcium binding protein 45a, Sp1, and COUP-TFII. In contrast, the expression of only 4 uterine genes, i.e., complement C3, lactoferrin, Muc-1, and 17-beta-hydroxysteroid dehydrogenase 8 (H2-Ke6) was down-regulated in old mice. These changes may reflect an increase in stromal and a decrease in glandular epithelial gene expression, and may be associated with age-related changes in these tissue compartments within the uterus, possibly leading to the decline in reproductive function in C57Bl/6 mice.