Canine keratoconjunctivitis sicca therapeutics: literature review / Terapêutica da ceratoconjuntivite seca canina: revisão bibliográfica

Keratoconjunctivitis sicca (KCS) is a disease commonly seen in dogs that is characterized by the reduction or absence of lacrimal secretions. It can be classified as qualitative or quantitative, and both categories are able to elicit conjunctival and corneal inflammation, ocular pain, progressive corneal disease, and vision impairment. This disease's treatment is based on reestablishing and maintaining ocular surface homeostasis. Patients may benefit from different therapeutic protocols, such as the use of lacrimomimetics, that increase lacrimal stability, helping to retain ocular humidity; lacrimostimulants, that promote lacrimal secretion; fatty acids, which play a role on meibum synthesis and block pro-inflammatory cytokine genic expression; blood products, based on promotion of epithelial growth factors; and stem cells, due to their self-renewing capabilities. Stable cases may benefit from the use of steroidal or non-steroidal anti-inflammatory agents on the control of clinical signs. Refractory cases may eventually benefit from surgical therapies, which include techniques for parotid duct transposition, gland transplants, and lacrimal puncta occlusion.

A ceratoconjuntivite seca (CCS) é uma doença comumente observada em cães caracterizada pela ausência ou redução das secreções lacrimais. Pode ser classificada como qualitativa ou quantitativa, sendo que ambas as categorias são capazes de desencadear inflamação da conjuntiva e da córnea, dor ocular, doença corneana progressiva e redução da visão. O tratamento desta doença é contínuo e se baseia no restabelecimento e manutenção da homeostase do sistema da superfície ocular. Os pacientes podem se beneficiar de diferentes protocolos terapêuticos, tais como o uso de lacrimomiméticos, que aumentam a estabilidade lacrimal ajudando na retenção da umidade ocular; lacrimoestimulantes para a promoção de secreção de lágrimas; ácidos graxos, que desempenham papel na síntese de meibum e bloqueiam a expressão gênica de citocinas pró-inflamatórias; produtos derivados do sangue, baseando-se nos fatores de crescimento de promoção epitelial; e células tronco, devido à sua capacidade de auto renovação. Em casos estáveis, o uso de anti-inflamatórios esteroidais ou não esteroidais pode ser benéfico no controle de sinais clínicos. Casos refratários ao tratamento podem eventualmente se beneficiar de terapias cirúrgicas, que incluem as técnicas de transposição de ducto parotídeo, transplantes glandulares e oclusão da puncta lacrimal.

The eye of the giant anteater (Myrmecophaga tridactyla): Ophthalmic examination findings and diagnostic tests.

OBJECTIVE: To describe ophthalmic examination and diagnostic values for Schirmer tear test (STT), intraocular pressure (IOP), corneal horizontal diameter (CHD), palpebral fissure length (PFL), fundoscopy, and palpebral conjunctiva microbiota from healthy giant anteaters. ANIMALS STUDIED: Twelve giant anteaters (Myrmecophaga tridactyla), 11 adults and one juvenile, five males and seven females. PROCEDURES: The animals were submitted to general anesthesia and ophthalmic evaluation with portable slit-lamp biomicroscope, Finoff transilluminator, and fundoscopy, as well as STT, bacterial culture from palpebral conjunctiva, rebound tonometry IOP, and measurement of PFL and CHD. Data compiled were analyzed with ANOVA and Tukey tests. RESULTS: The results (mean ± standard deviation) were as follows: STT 8.04 ± 6.21 mm/min; IOP 10.92 ± 2.45 mmHg; PFL 0.75 ± 0.11 cm; CHD 0.96 ± 0.10 cm. Out of the 24 eyes swab samples for bacterial culture, 17 were positive, with three genera of Gram-positive bacteria identified Staphylococcus spp., Bacillus sp., and Corynebacterium sp. Gram-negative bacteria were not isolated from any of the samples. CONCLUSIONS: As conservation work in this vulnerable species continues, this report on basic ophthalmic examination and diagnostic parameters will be helpful improve their treatment and care. More ophthalmic studies are encouraged in animals within the Pilosa order.

Laparoscopy as a Facilitator in the Early Diagnosis of a Mullerian Aplasia During Ordinary Surgery.

Laparoscopy was introduced more than 100 years ago. However, in some fields its use still meets resistance. Technology such as laparoscopy may help to identify rare and complex disorders, even in very ordinary procedures, such as inguinal hernia repair. This report highlighted the importance of early diagnosis of a complex condition using commonly available technology. To the best of our knowledge, there has not been a similar reported case in such a young patient during laparoscopic inguinal hernia repair.

Spontaneous Pubertal Onset in a Male Patient With Mixed Gonadal Dysgenesis With Mosaicism 45,X/ 46, X, mar (Y)/ 47,X,mar(Y),+mar(Y) - Pediatric Case Report.

This report describes an adolescent with Mixed Gonadal Dysgenesis and unexpected mosaicism [karyotype 46,X,mar(Y)/ 47,X, mar(Y),+mar(Y)].). Diagnosis with 1 month of age due to atypical genitalia. He presented a right streak gonad, which was removed due to the risk for germ cell tumor, and a left testis with epididymis barely connected and without vas deferens. Left testis maintenance was sufficient for him to undergo spontaneous puberty. The patient was non-responsive to growth hormone. Webbed neck was the only dysmorphic feature. To the best of our knowledge, there were no similar cases reported with spontaneous pubertal progress reported in the literature.

Laparoscopic gonad-sparing procedure in Ovotesticular disorder of sex development - Case video technique.

INTRODUCTION: Ovotesticular disorder of sex development (OTD) is a rare condition. There's a lack of literature addressing gonad-sparing surgery for OTD. OBJECTIVE: Report the laparoscopic partial gonadectomy technique - gonad-sparing surgery - in an 11-year-old child, 46, XX karyotype with OTD with atypical genitalia. MATERIAL AND METHODS: After a complete diagnostic evaluation the patient underwent feminizing genitoplasty followed by laparoscopic partial gonadectomy (gonad-sparing surgery). The patient was positioned on supine position and Trendelenburg. One 5 mm port was placed on the umbilicus and two 3 mm ports in both flanks. A gonadal wedge biopsy was performed to achieve histopathological confirmation before resection. The testicular component of the ovotestis is clearly identified based on macroscopic aspects, and resected with laparoscopic scissors and limited use of electrocautery. DISCUSSION: This case was classified as bipolar or terminal ovotestis. At the 5-month follow-up, the patient attained menarche. No adverse outcomes have been recorded. Postoperative third year follow-up hormone evaluation revealed a= female pattern characteristic and ultrasound demonstraed uterine volume increase, as well as bilateral ovarian tissue development with follicles. CONCLUSIONS: Gonad-sparing procedure is feasible and desirable whenever possible, especially in 46, XX patients with female sex of rearing, since it preserves the fertility potential. The risk of malignancy must be monitored.

Ocular examination findings and measurements of tear production and tonometry of ring-tailed coatis (nasua nasua).

OBJECTIVE: To describe ocular anatomical features and to determine tear production and tonometry in normal anesthetized ring-tailed coati (Nasua nasua). ANIMALS: Eight male and seven female ring-tailed coatis (30 eyes) were evaluated, with ages ranging from 7 months to 10 years old. PROCEDURES: The animals were anesthetized with isoflurane and had STT 1, rebound and applanation tonometry, and palpebral fissure length (PFL) measured in both eyes. Rebound tonometry was measured with both TonoVet® and TonoVet Plus®. All eyes were evaluated with slit-lamp biomicroscopy. Following pharmacological mydriasis, direct fundoscopy was performed. ANOVA and Tukey tests were used for the data analysis. RESULTS: There were upper and lower eyelids, as well as a third eyelid. Eyelashes were present on the upper eyelid, while meibomian glands openings were visible on both. The bulbar conjunctiva was pigmented. The pupil was obliquely horizontally ovoid and teardrop shaped when miotic. The color of the iris and tapetum lucidum varied with age. The optic disk was round, and the retina was holangiotic. The mean ± standard deviation values obtained were as follows: STT: 2.50 ± 2.39 mm/min; rebound tonometry: 9.50 ± 2.43 mmHg (TonoVet®, calibration P), 14.60 ± 2.82 mmHg (TonoVet®, calibration D), 18.93 ± 3.99 mmHg (TonoVet Plus®, calibration dog); applanation tonometry: 18.66 ± 4.16 mmHg; PFL: 10.98 ± 1.67 mm. CONCLUSIONS AND CLINICAL RELEVANCE: Anatomical and clinical ophthalmic data presented in this study are unprecedented for this species. The results can be used as clinical reference parameters, allowing for better care of these species. The lack of data for the Procyonidae family must be regarded as an incentive for more studies.

Prevalência de eventos cardiovasculares tardios após radioterapia para câncer de mama em pacientes acima de 65 anos / Prevalence of late cardiovascular events after breast cancer radiotherapy in patients over 65 years

INTRODUÇÃO: Câncer de mama é a forma mais frequente de câncer feminino. Com a melhora gradativa dos métodos de diagnóstico e de tratamento, espera-se aumento da sobrevida e do crescimento das doenças cardiovasculares nessa população. O tratamento dessa neoplasia pode levar à cardiotoxicidade. OBJETIVOS: Avaliar a evolução cardiovascular em pacientes submetidas à radioterapia para tratamento de tumores primários da mama, acompanhadas no A.C.Camargo Cancer Center. MÉTODOS: Estudo de coorte retrospectivo, a partir de dados de prontuários, com análise em amostra de conveniência e não sequencial. Incluídas pacientes com neoplasia de mama, com idade maior ou igual a 65 anos e de qualquer tipo histológico e estadiamento no momento do diagnóstico, tratadas de 2002 a 2013, que permaneceram vivas após 1 ano do diagnóstico, e que tiveram, no mínimo, 1 ano de acompanhamento na instituição. RESULTADOS: Do total de 201 pacientes, a idade média no momento do diagnóstico foi de 72,2 + 4,8 anos e o tempo médio de seguimento de 68 + 32 meses. Fatores de risco para desenvolvimento de doença cardiovascular (DCV) estavam presentes em 165 pacientes (82,1%) ao diagnóstico do câncer e 31 pacientes (15,4%) já apresentavam histórico de DCV. A Fração de Ejeção do Ventrículo Esquerdo (FEVE) média após tratamento foi de 66 + 8 (p<0,001). Trinta e cinco pacientes (17,4%) apresentaram pelo menos um Evento Cardiovascular (ECV). O tempo médio entre diagnóstico do câncer e ocorrência de ECV foi de 34,6 + 35,6 meses. A mortalidade total foi de 9% (n=18), sendo de causa cardiovascular em 3 pacientes (1,5%). A sobrevida estimada pelo método de Kaplan-Meier foi significantemente afetada pela ocorrência de ECV (p=0,012). Na análise por regressão logística simples, hipertensão arterial sistêmica (HAS) provocou significante aumento da chance de ECV (OR=3,4; 95% IC 1,3-9,4; p=0,014), bem como a presença de doença cardíaca prévia (OR=4,03; 95% IC 1,7-9,4; p=0,001). Em regressão logística múltipla, HAS apresentou OR=2,7 (95% IC 0,9-7,6; p=0,057) para ocorrência de ECV, enquanto que presença de doença cardíaca prévia resultou em uma OR=3,1 (95% IC 1,3-7,6; p=0,009). Uso de drogas cardioprotetoras ao diagnóstico do câncer não apresentou relação com a incidência de ECV. A frequência de ECV foi maior nos pacientes submetidos ao tratamento com antracíclicos (n=64), porém sem diferença estatística em relação a quem não o fez (42,9% vs 30,2 %; p=0,2). A frequência de queda da FEVE maior do que 10% nos ecocardiogramas pré- e pós-tratamento foi mais alta nos pacientes que utilizaram antraciclina (9,3% vs 4,7%; p=0,004). A frequência de ECV foi significantemente maior entre aqueles com quedas maiores do que 10% na FEVE (16,6% vs 9%, p=0,033). Lateralidade, dose total de radiação e uso de terapia hormonal não afetaram a frequência de ECV. CONCLUSÕES: A frequência encontrada de novos eventos cardiovasculares em pacientes portadoras de doença cardiovascular antes do início do tratamento oncológico reforça a importância da presença de um time de especialistas em cardio-oncologia em centros oncológicos, com elaboração de rotinas para atuação em todos os níveis de cuidado com os pacientes com câncer

INTRODUCTION: Breast cancer is the most common form of female cancer. With the gradual improvement of diagnostic and treatment methods, it is expected to increase the survival and growth of cardiovascular diseases in this population. The treatment of this cancer can lead to cardiotoxicity. OBJECTIVES: To assess cardiovascular evolution of patients that underwent radiotherapy for the treatment of primary breast cancer and are followed up at the A.C.Camargo Cancer Center. METHODS: Retrospective cohort study, based on the review of from medical records from a convenience and non-sequential non-breast cancer patient sample. We included patients with breast cancer, aged 65 years or older, and with any histological breast carcinoma subtype and staging at the time of diagnosis, treated from 2002 to 2013, who remained alive after 1 year of diagnosis, and who had, at least, 1 year of follow-up at the institution. RESULTS: Among 201 patients, the average age at the time of diagnosis was 72.2 + 4.8 years and the average follow-up time was 68 + 32 months. Risk factors for the development of cardiovascular disease (CVD) were present in 165 patients (82.1%) at the time of cancer diagnosis and 31 patients (15.4%) already had a history of CVD. The mean left ventricular ejection fraction (LVEF) after treatment was 66 + 8 (p<0.001). Thirty-five patients (17.4%) had at least one Cardiovascular Event (ECV). The average time between cancer diagnosis and the occurrence of ECV was 34.6 + 35.6 months. Total mortality was 9% (n=18), being of cardiovascular cause in 3 patients (1.5%). The estimated overall survival was significantly affected by the occurrence of ECV (p=0.012). In the analysis by simple logistic regression, hypertension caused a significant increase in the chance of ECV (OR=3.4; 95% CI 1.3-9.4; p=0.014) and the presence of previous heart disease increased chance of ECV (OR=4.03; 95% CI 1.7-9.4; p=0.001). After multivariate logistic regression, hypertension resulted in an OR=2.7 (95% CI 0.9-7.6; p=0.057), while the presence of previous heart disease resulted in an OR=3.1 (95% CI 1.3-7.6; p=0.009). Use of cardioprotective drugs at the diagnosis of cancer was not associated with the incidence of ECV. The frequency of ECV was higher in patients undergoing treatment with anthracycline (n=64), but this difference was not statistically different (42.9% vs 30.2%; p=0.2). The frequency of LVEF fall greater than 10% in pre and post-treatment echocardiograms was higher in patients who used anthracycline (9.3% vs 4.7%; p=0.004). The frequency of ECV was significantly higher among those with falls greater than 10% in LVEF (16.6% vs 9%, p= 0.033). Laterality, total radiation dose and use of hormone therapy did not affect the frequency of ECV. CONCLUSIONS: The frequency found of new cardiovascular events in patients with cardiovascular disease before the start of cancer treatment reinforces the importance of the presence of a team of specialists in cardio-oncology in oncology centers, with the elaboration of routines to work at all levels of care for cancer patients

Ophthalmic contributions to assessing eyes of two neotropical canids: Cerdocyon thous and Chrysocyon brachyurus.

OBJECTIVE: To describe selected ophthalmic tests and anatomical features of eyes of crab-eating foxes (Cerdocyon thous) and maned wolves (Chrysocyon brachyurus). ANIMALS STUDIED: Six crab-eating foxes (12 eyes), eight maned wolves (16 eyes). PROCEDURES: Intramuscular and/or inhalatory anesthesia, ophthalmic evaluation with portable slit-lamp biomicroscope, Schirmer tear test (STT), intraocular pressure measurement with rebound and applanation (crab-eating fox only) tonometers, measurement of palpebral fissure length (PFL), gonioscopy, and fundoscopy. Data were analyzed with ANOVA and Tukey's tests. RESULTS: Both species presented upper and lower eyelids, both with eyelashes and Meibomian glands openings. A third eyelid was also present. In partial miosis, pigmented projections were observed along the edge of the pupil. The draining angle was open, with thin pectinate ligaments. The retina was holangiotic. For crab-eating foxes, mean ± standard deviation values were as follows: STT: 4.33 ± 2.96 mm/min; PFL: 17.45 ± 1.55 mm; rebound tonometry: 10.70 ± 3.43 mm Hg (TonoVet® calibration D),5.66 ± 3.44 mm Hg (TonoVet® calibration P), 17.00 ± 4.64 mm Hg (TonoVet® Plus calibration dog); and applanation tonometry: 11.70 ± 5.70 mm Hg(TonoPen® XL). For maned wolves, the mean ± standard deviation values were as follows: STT: 9.31 ± 7.40 mm/min; PFL: 22.79 ± 1.63 mm; rebound tonometry: 11.00 ± 2.77 mm Hg (TonoVet® calibration D), 6.78 ± 2.58 mm Hg (TonoVet® calibration P), and 18.29 ± 3.47 mm Hg(TonoVet® Plus calibration dog). CONCLUSIONS: This study contributes with knowledge that can help the clinical assessment regarding eyes of crab-eating foxes and maned wolves. The data herein presented for rebound tonometry are new for both species.

Impact of peri-intraventricular haemorrhage and periventricular leukomalacia in the neurodevelopment of preterms: A systematic review and meta-analysis.

CONTEXT: Whether all degrees of periventricular leukomalacia (PVL) and peri-intraventricular haemorrhage (PIVH) have a negative impact on neurodevelopment. OBJECTIVE: To determine the impact of PVL and PIVH in the incidence of cerebral palsy, sensorineural impairment and development scores in preterm neonates. Registered in PROSPERO (CRD42017073113). DATA SOURCES: PubMed, Embase, SciELO, LILACS, and Cochrane databases. STUDY SELECTION: Prospective cohort studies evaluating neurodevelopment in children born preterm which performed brain imaging in the neonatal period. DATA EXTRACTION: Two independent researchers extracted data using a predesigned data extraction sheet. STATISTICAL METHODS: A random-effects model was used, with Mantel-Haenszel approach and a Sidik-Jonkman method for the estimation of variances, combined with Hartung-Knapp-Sidik-Jonkman correction. Heterogeneity was assessed through the I2 statistic and sensitivity analysis were performed when possible. No funnel plots were generated but publication bias was discussed as a possible limitation. RESULTS: Our analysis concluded premature children with any degree of PIVH are at increased risk for cerebral palsy (CP) when compared to children with no PIVH (3.4, 95% CI 1.60-7.22; 9 studies), a finding that persisted on subgroup analysis for studies with mean birth weight of less than 1000 grams. Similarly, PVL was associated with CP, both in its cystic (19.12, 95% CI 4.57-79.90; 2 studies) and non-cystic form (9.27, 95% CI 5.93-14.50; 2 studies). We also found children with cystic PVL may be at risk for visual and hearing impairment compared to normal children, but evidence is weak. LIMITATIONS: Major limitations were the lack of data for PVL in general, especially for the outcome of neurodevelopment, the high heterogeneity among methods used to assess neurodevelopment and the small number of studies, which led to meta-analysis with high heterogeneity and wide confidence intervals. CONCLUSIONS: There was no evidence supporting the hypothesis that PIVH causes impairment in neuropsychomotor development in our meta-analysis, but review of newer studies show an increased risk for lower intelligence scores in children with severe lesions, both PIVH and PVL. There is evidence to support the hypothesis that children with any degree of PIVH, especially those born below 1000 grams and those with severe haemorrhage, are at increased risk of developing CP, as well as children with PVL, both cystic and non-cystic.

A 46,XX testicular disorder of sex development caused by a Wilms' tumour Factor-1 (WT1) pathogenic variant.

Molecular diagnosis is rarely established in 46,XX testicular (T) disorder of sex development (DSD) individuals with atypical genitalia. The Wilms' tumour factor-1 (WT1) gene is involved in early gonadal development in both sexes. Classically, WT1 deleterious variants are associated with 46,XY disorders of sex development (DSD) because of gonadal dysgenesis. We report a novel frameshift WT1 variant identified in an SRY-negative 46,XX testicular DSD girl born with atypical genitalia. Target massively parallel sequencing involving DSD-related genes identified a novel heterozygous WT1 c.1453_1456del; p.Arg485Glyfs*14 variant located in the fourth zinc finger of the protein which is absent in the population databases. Segregation analysis and microsatellite analysis confirmed the de novo status of the variant that is predicted to be deleterious by in silico tools and to increase WT1 target activation in crystallographic model. This novel and predicted activating frameshift WT1 variant leading to the 46,XX testicular DSD phenotype includes the fourth zinc-finger DNA-binding domain defects in the genetic aetiology of 46,XX DSD.

The Unlicensed and Off-label Prescription of Medications in General Paediatric Ward: An Observational Study.

BACKGROUND: Unlicensed (UL) and Off-label (OL) prescription of medications is common in paediatrics and does not constitute negligent practice since there is often no approved alternative according to FDA bulary. AIM: The study aimed to determine the current frequency of UL and OL prescriptions in children from one month to 12 years of age in a Paediatric Inpatient Unit (PIU). METHODS: This is an observational, prospective study, reviewing the prescriptions of all patients admitted to the PIU in a university hospital in a single week in August 2014 and a single week in January 2015. RESULTS: We included 157 patients of median age 18 months and median length of stay 24 days. There were 1,328 prescription items (average of 8.4 items/patient) and only two patients without UL/OL use. During the winter season (August), 27% of prescriptions were classified as UL and 44.6% as OL, and during summer (January), 29.6% as UL and 45.1% as OL. We identified 188 medications, of which the most prescribed were paracetamol (11%) and dipyrone (9.5%). The most frequent OL classification was regarding drug formulation (15.8%). In the winter week, the most frequent reasons for admission were respiratory (44%), followed by other clinical causes (CC) (17.3%), while in the summer week, they were CC (26.3%), followed by surgical and gastrohepatic (23.7%). CONCLUSION: The OL prescription of medicines for children in Brazil is in accordance with the international literature. The higher prevalence of OL due to formulation found in this study is related to the use of formulations other than those used by the FDA.

Preterm Neonates with Respiratory Distress Syndrome: Ventilator-Induced Lung Injury and Oxidative Stress.

Ventilator-induced lung injury is well recognized, and appropriate arterial saturation target is unknown, so gentle modes of ventilation and minimizing oxidative stress have been well studied. Our objective was to analyze any association between the oxygen levels at blood sampling and plasma levels of the interleukins IL-6, IL-1ß, IL-10, and IL-8 and TNF-α in preterm newborns under mechanical ventilation (MV) in their first two days. Methods. Prospective cohort including neonates with severe respiratory distress. Blood samples were collected right before and 2 hours after invasive MV. For analysis purposes, newborns were separated according to oxygen requirement: low oxygen (≤30%) and high oxygen (>30%) groups. Interleukins were measured using a commercially available kit. Results. 20 neonates (gestational age 32.2 ± 3 weeks) were evaluated. Median O2 saturation levels pre-MV were not different in both oxygen groups. In the high oxygen group, IL-6, IL-8, and TNF-α plasma levels increased significantly after two hours under MV. Conclusions. Despite the small sample studied, data showed that there is a relationship between VILI, proinflammatory cytokines, and oxygen-induced lung injury, but a study considering oxidative marker measurements is needed. It seems that less oxygen may keep safer saturation targets playing a less harmful role.

Controversies on Timing of Sex Assignment and Surgery in Individuals With Disorders of Sex Development: A Perspective.

Appropriate management of disorders of sex development (DSD) has been a matter of discussion since the first guidelines were published in the 1950s. In the last decade, with the advent of the 2006 consensus, the classical methods, especially regarding timing of surgery and sex of rearing, are being questioned. In our culture, parents of DSD newborns usually want their children to undergo genital surgery as soon as possible after sexual assignment, as surgery helps them to confirm the assigned sex. Developmental psychology theories back this hypothesis. They state that anatomic differences between sexes initiate the very important process of identification with the parent of the same sex. Sex-related endocrinological issues also demand early care. For example, using dihydrotestosterone cream to increase penile length or growth hormone treatment to improve final height require intervention at young ages to obtain better results. Although the timing of surgery remains controversial, recent evidence suggests that male reconstruction should be performed between 6 and 18 months of age. Feminizing surgery is still somewhat controversial. Most guidelines agree that severe virilization requires surgical intervention, while no consensus exists regarding mild cases. Our perspective is that precocious binary sex assignment and early surgery is a better management method. There is no strong evidence for delays and the consequences can be catastrophic in adulthood.

Avian ophthalmic peculiarities / Particularidades oftálmicas em aves

Morphology and physiology of bird eyes are similar to mammals; although, there are peculiarities that should be considered for a correct interpretation of an ophthalmic examination. While the ophthalmology of domestic species is already well established, there are gaps to be filled regarding birds, particularly due to the large number of existing species. This literature review consists of a brief contribution regarding peculiarities of anatomy, physiology, and ophthalmic semiotechnique of the avian eye.(AU)

A morfologia e a fisiologia dos olhos das aves são similares àquelas de mamíferos, mas existem particularidades que devem ser consideradas para a correta interpretação do exame oftálmico. Enquanto a oftalmologia de espécies domésticas já é bem estabelecida, ainda há diversas lacunas no que tange às aves, particularmente devido ao grande número de espécies existentes. Este trabalho objetiva realizar uma revisão bibliográfica abrangendo anatomia, fisiologia e semiologia oftálmica de aves.(AU)

Avian ophthalmic peculiarities / Particularidades oftálmicas em aves

ABSTRACT: Morphology and physiology of bird eyes are similar to mammals; although, there are peculiarities that should be considered for a correct interpretation of an ophthalmic examination. While the ophthalmology of domestic species is already well established, there are gaps to be filled regarding birds, particularly due to the large number of existing species. This literature review consists of a brief contribution regarding peculiarities of anatomy, physiology, and ophthalmic semiotechnique of the avian eye.

RESUMO: A morfologia e a fisiologia dos olhos das aves são similares àquelas de mamíferos, mas existem particularidades que devem ser consideradas para a correta interpretação do exame oftálmico. Enquanto a oftalmologia de espécies domésticas já é bem estabelecida, ainda há diversas lacunas no que tange às aves, particularmente devido ao grande número de espécies existentes. Este trabalho objetiva realizar uma revisão bibliográfica abrangendo anatomia, fisiologia e semiologia oftálmica de aves.

Dose não usual de varfarina para alcançar rni terapêutica em uma criança de quatro meses: fatores de risco não genéticos ainda são um desafio / Unusual warfarin dose to achieve therapeutic inr in a 4-month old child: non-genetics risk factors are still a challenge

RESUMO Objetivo: Descreve se uma criança do sexo feminino, com quatro meses de idade, que necessitou de varfarina 0.7 mg/kg/dia (5 mg). Discutem se os fatores de risco clinicamente relevantes para prescrição de altas doses do anticoagulante em crianças. Descrição do caso: Em novembro de 2015, uma criança de 5 kg (36 semanas, pré termo) foi admitida no pronto atendimento por status epilepticus e febre. Diazepam, fenitoína e ceftriaxona foram prescritos inicialmente. A pesquisa no líquor revelou presença de sete leucócitos, 150 mg/dL de proteínas, 1 mg/dL de glucose e cocos Gram positivos. Em tomografia de crânio, foram observados sinais hipodensos em cerebelo, lobo temporal e núcleos de base à esquerda, sugerindo vasculite infecciosa por meningite pneumocócica. Após o quadro agudo da encefalite, a criança desenvolveu uma trombose e necessitou de anticoagulação com enoxaparina e, posteriormente, com varfarina. Dez dias de tratamento com o segundo fármaco foram necessários para atingir relação normalizada internacional (RNI) terapêutica, tendo sido realizados cinco ajustes de dose desde a primeira prescrição de varfarina. Comentários: Os fatores de risco determinantes para necessidade de doses maiores de varfarina foram idade e uso de nutrição enteral. Fenobarbital e prednisona também podem ter contribuído para o uso de uma das maiores doses de varfarina já relatadas na literatura. A despeito da importância dos testes de polimorfismo genético, os pediatras devem estar atentos para identificar os fatores que contribuem para a prescrição de maiores doses de varfarina, de forma a minimizar os riscos de trombose, reduzindo os custos com internação e exames laboratoriais.

ABSTRACT Objective: To report a case of a 4-month old girl that required 0.7 mg/kg/day (5 mg) of warfarin and discuss relevant risk factors for requiring higher doses. Case Description: In November 2015, a 5 kg female infant (36-week preterm) was admitted to the hospital due to status epilepticus and fever. Diazepam, phenytoin and ceftriaxone were prescribed. Cerebrospinal fluid contained 7 leukocytes, 150 mg/dL proteins, 1 mg/dL glucose and gram positive cocci were observed. Cranial tomography suggested hypodense signs in the cerebellum, right temporal lobe and left basal nuclei, which was consistent with pneumococcal meningitis-induced infectious vasculitis. She required low molecular weight heparin and warfarin for post-encephalitis thrombosis. About 10 days were required to achieve therapeutic INR, and warfarin was adjusted five times since the initial prescription. Comments: The risk factors for higher warfarin doses were age and enteral tube feeding. Phenobarbital and prednisone might also have contributed with one of the highest warfarin dose ever reported. Despite current importance given to genetics testing, clinicians should attempt to identify common contributing factors for prolonged non-therapeutic INR, to minimize the risk of coagulation, and to reduce costs of hospital stay and laboratory exams.

UNUSUAL WARFARIN DOSE TO ACHIEVE THERAPEUTIC INR IN A 4-MONTH OLD CHILD: NON-GENETICS RISK FACTORS ARE STILL A CHALLENGE. / DOSE NÃO USUAL DE VARFARINA PARA ALCANÇAR RNI TERAPÊUTICA EM UMA CRIANÇA DE QUATRO MESES: FATORES DE RISCO NÃO GENÉTICOS AINDA SÃO UM DESAFIO.

OBJECTIVE: To report a case of a 4-month old girl that required 0.7 mg/kg/day (5 mg) of warfarin and discuss relevant risk factors for requiring higher doses. CASE DESCRIPTION: In November 2015, a 5 kg female infant (36-week preterm) was admitted to the hospital due to status epilepticus and fever. Diazepam, phenytoin and ceftriaxone were prescribed. Cerebrospinal fluid contained 7 leukocytes, 150 mg/dL proteins, 1 mg/dL glucose and gram positive cocci were observed. Cranial tomography suggested hypodense signs in the cerebellum, right temporal lobe and left basal nuclei, which was consistent with pneumococcal meningitis-induced infectious vasculitis. She required low molecular weight heparin and warfarin for post-encephalitis thrombosis. About 10 days were required to achieve therapeutic INR, and warfarin was adjusted five times since the initial prescription. COMMENTS: The risk factors for higher warfarin doses were age and enteral tube feeding. Phenobarbital and prednisone might also have contributed with one of the highest warfarin dose ever reported. Despite current importance given to genetics testing, clinicians should attempt to identify common contributing factors for prolonged non-therapeutic INR, to minimize the risk of coagulation, and to reduce costs of hospital stay and laboratory exams.

OBJETIVO: Descreve se uma criança do sexo feminino, com quatro meses de idade, que necessitou de varfarina 0.7 mg/kg/dia (5 mg). Discutem se os fatores de risco clinicamente relevantes para prescrição de altas doses do anticoagulante em crianças. DESCRIÇÃO DO CASO: Em novembro de 2015, uma criança de 5 kg (36 semanas, pré termo) foi admitida no pronto atendimento por status epilepticus e febre. Diazepam, fenitoína e ceftriaxona foram prescritos inicialmente. A pesquisa no líquor revelou presença de sete leucócitos, 150 mg/dL de proteínas, 1 mg/dL de glucose e cocos Gram positivos. Em tomografia de crânio, foram observados sinais hipodensos em cerebelo, lobo temporal e núcleos de base à esquerda, sugerindo vasculite infecciosa por meningite pneumocócica. Após o quadro agudo da encefalite, a criança desenvolveu uma trombose e necessitou de anticoagulação com enoxaparina e, posteriormente, com varfarina. Dez dias de tratamento com o segundo fármaco foram necessários para atingir relação normalizada internacional (RNI) terapêutica, tendo sido realizados cinco ajustes de dose desde a primeira prescrição de varfarina. COMENTÁRIOS: Os fatores de risco determinantes para necessidade de doses maiores de varfarina foram idade e uso de nutrição enteral. Fenobarbital e prednisona também podem ter contribuído para o uso de uma das maiores doses de varfarina já relatadas na literatura. A despeito da importância dos testes de polimorfismo genético, os pediatras devem estar atentos para identificar os fatores que contribuem para a prescrição de maiores doses de varfarina, de forma a minimizar os riscos de trombose, reduzindo os custos com internação e exames laboratoriais.

Inositol 1, 4, 5-trisphosphate-dependent nuclear calcium signals regulate angiogenesis and cell motility in triple negative breast cancer.

Increases in nuclear calcium concentration generate specific biological outcomes that differ from those resulting from increased cytoplasmic calcium. Nuclear calcium effects on tumor cell proliferation are widely appreciated; nevertheless, its involvement in other steps of tumor progression is not well understood. Therefore, we evaluated whether nuclear calcium is essential in other additional stages of tumor progression, including key steps associated with the formation of the primary tumor or with the metastatic cascade. We found that nuclear calcium buffering impaired 4T1 triple negative breast cancer growth not just by decreasing tumor cell proliferation, but also by enhancing tumor necrosis. Moreover, nuclear calcium regulates tumor angiogenesis through a mechanism that involves the upregulation of the anti-angiogenic C-X-C motif chemokine 10 (CXCL10-IP10). In addition, nuclear calcium buffering regulates breast tumor cell motility, culminating in less cell invasion, likely due to enhanced vinculin expression, a focal adhesion structural protein. Together, our results show that nuclear calcium is essential for triple breast cancer angiogenesis and cell migration and can be considered as a promising strategic target for triple negative breast cancer therapy.

Reference values for selected ophthalmic tests of the blue-and-yellow macaw (Ara ararauna) / Valores de referência para selecionados testes oftálmicos para a arara canindé (Ara araruna)

The aim of this study was to establish reference values for selected ophthalmic diagnostic tests in healthy blue-and-yellow macaws. We investigated a total of 35 adult macaws (70 eyes) of undetermined sex and with an average weight of 1 kg, who were living in captivity in the Federal District, Brazil. Tear production using the Schirmer tear test (STT), normal conjunctival flora, intraocular pressure (IOP) using a rebound tonometer and horizontal palpebral fissure length (HPFL) were evaluated. In this study, 84.1% of samples were positive for microbial growth. Bacteria, fungi and yeasts were isolated, and Staphylococcus spp. (21.9%) and Bacillus spp. (26.8%) were the most frequently isolated microorganisms. The mean value for STT was 7.6±4.6mm/min in the right eye (OD) and 6.6±4.4mm/min in the left eye (OS) (median = 7,11±0,76mm/min). Mean IOP was 11.4±2.5mm Hg OD and 11.6±1.8mm Hg OS (median = 11.49±0.22mm Hg), prior to anesthesia, and 7.6±2.4mm Hg OD and 7.8±1.8mm Hg OS (median 7.71±0.08mmHg) after anesthesia. The IOP was significantly lower when the animals were under anesthesia as compared to when they were conscious (p≤0.05). Horizontal palpebral fissure length was 11.7±0.1mm OD and 11.8±0.1mm OS (median = 11.72±0.07mm). The STT showed a positive correlation with palpebral fissure measurement for this species. These selected ophthalmic reference values will be particularly useful in diagnosing pathological changes in the eyes of blue-and-yellow macaws.(AU)

Objetivou-se determinar os valores normais para testes oftálmicos diagnósticos selecionados para a Arara Canindé. Trinta e cinco Ara ararauna (70 olhos), de sexo indeterminado, adultas, com peso médio de 1kg e provenientes de cativeiro no Distrito Federal, foram avaliadas. Aferiram-se a produção lacrimal pelo Teste lacrimal de Schirmer (TLS), a avaliação microbiológica da conjuntiva ocular, a pressão intra-ocular (PIO) utilizando a tonometria de rebote e o comprimento horizontal da rima palpebral Neste estudo 84.1% das amostras analisadas foram positivas para crescimento microbiológico. Bactérias, fungos e hifas foram isolados e Staphylococcus spp. (21.9%) e Bacillus spp. (26.8%) foram isolados mais frequentemente. Os valores médios do teste de Lacrimal de Schirmer (TLS) foram de 7.6±4.6 e 6.6±4.4mm/min para olhos direito (OD) e esquerdo (OE), respectivamente (média = 7,11±0,76mm/min). A pressão intraocular média foi de 11.4±2.5 (OD) e 11.6±1.8mmHg (OE) anteriormente à anestesia (média 11,49±0,22 mmHg) e 7.6 ± 2.4 mmHg (OD) e 7.8 ± 1.8 mm Hg (OE) (média 7,71±0,08mm Hg) após a anestesia, verificando-se que a PIO foi significativamente menor quando os animais se encontravam sob anestesia comparativamente ao momento em que não estavam anestesiados. O comprimento horizontal da rima horizontal palpebral foi de 11.7±0.1mm OD e de 11.8±0.1mm OE (média 11,72±0,07mm). Verificou-se correlação positiva do TLS com o comprimento da fissura palpebral para a espécie estudada. Estes valores de referencia serão úteis no diagnóstico de alterações oculares da Arara Canindé.(AU)

Reference values for selected ophthalmic tests of the blue-and-yellow macaw (Ara ararauna) / Valores de referência para selecionados testes oftálmicos para a arara canindé (Ara araruna)

The aim of this study was to establish reference values for selected ophthalmic diagnostic tests in healthy blue-and-yellow macaws. We investigated a total of 35 adult macaws (70 eyes) of undetermined sex and with an average weight of 1 kg, who were living in captivity in the Federal District, Brazil. Tear production using the Schirmer tear test (STT), normal conjunctival flora, intraocular pressure (IOP) using a rebound tonometer and horizontal palpebral fissure length (HPFL) were evaluated. In this study, 84.1% of samples were positive for microbial growth. Bacteria, fungi and yeasts were isolated, and Staphylococcus spp. (21.9%) and Bacillus spp. (26.8%) were the most frequently isolated microorganisms. The mean value for STT was 7.6±4.6mm/min in the right eye (OD) and 6.6±4.4mm/min in the left eye (OS) (median = 7,11±0,76mm/min). Mean IOP was 11.4±2.5mm Hg OD and 11.6±1.8mm Hg OS (median = 11.49±0.22mm Hg), prior to anesthesia, and 7.6±2.4mm Hg OD and 7.8±1.8mm Hg OS (median 7.71±0.08mmHg) after anesthesia. The IOP was significantly lower when the animals were under anesthesia as compared to when they were conscious (p≤0.05). Horizontal palpebral fissure length was 11.7±0.1mm OD and 11.8±0.1mm OS (median = 11.72±0.07mm). The STT showed a positive correlation with palpebral fissure measurement for this species. These selected ophthalmic reference values will be particularly useful in diagnosing pathological changes in the eyes of blue-and-yellow macaws.(AU)

Objetivou-se determinar os valores normais para testes oftálmicos diagnósticos selecionados para a Arara Canindé. Trinta e cinco Ara ararauna (70 olhos), de sexo indeterminado, adultas, com peso médio de 1kg e provenientes de cativeiro no Distrito Federal, foram avaliadas. Aferiram-se a produção lacrimal pelo Teste lacrimal de Schirmer (TLS), a avaliação microbiológica da conjuntiva ocular, a pressão intra-ocular (PIO) utilizando a tonometria de rebote e o comprimento horizontal da rima palpebral Neste estudo 84.1% das amostras analisadas foram positivas para crescimento microbiológico. Bactérias, fungos e hifas foram isolados e Staphylococcus spp. (21.9%) e Bacillus spp. (26.8%) foram isolados mais frequentemente. Os valores médios do teste de Lacrimal de Schirmer (TLS) foram de 7.6±4.6 e 6.6±4.4mm/min para olhos direito (OD) e esquerdo (OE), respectivamente (média = 7,11±0,76mm/min). A pressão intraocular média foi de 11.4±2.5 (OD) e 11.6±1.8mmHg (OE) anteriormente à anestesia (média 11,49±0,22 mmHg) e 7.6 ± 2.4 mmHg (OD) e 7.8 ± 1.8 mm Hg (OE) (média 7,71±0,08mm Hg) após a anestesia, verificando-se que a PIO foi significativamente menor quando os animais se encontravam sob anestesia comparativamente ao momento em que não estavam anestesiados. O comprimento horizontal da rima horizontal palpebral foi de 11.7±0.1mm OD e de 11.8±0.1mm OE (média 11,72±0,07mm). Verificou-se correlação positiva do TLS com o comprimento da fissura palpebral para a espécie estudada. Estes valores de referencia serão úteis no diagnóstico de alterações oculares da Arara Canindé.(AU)