Hemofilia A em cão: relato de caso

Hemophilia A is an X-linked inherited disorder characterized by a Factor VIII (FVIII) deficiency, being therefore transmitted by female dogs to their offspring. Since it is a secondary hemostatic defect, the main clinical signs are hematomas and deep hemorrhage in body cavities, muscles and joints. A four-month-old male Boxer was presented to the Veterinary Hospital at the School of Veterinary Medicine and Animal Science in Botucatu with excessive bleeding due to an incision made three days prior by another veterinarian to drain a local hematoma. Laboratory results showed platelet count within the reference range, as well as prolonged whole blood clotting and activated partial thromboplastin times. FVIII activity was 0,96%, which characterizes the most severe degree of hemophilia A.

Feasibility of Intralaminar, Lateral Mass, or Pedicle Axis Vertebra Screws in Children Under 10 Years of Age: A Tomographic Study

BACKGROUND: There are several techniques for screw insertion in upper cervical spine surgery, and the use of the 3.5-mm screw is usually the standard. However, there is no consensus regarding the feasibility of using these screws in the pediatric population. OBJECTIVE: To determine the measurement of the lamina angle, lamina and pedicle length and thickness, and lateral mass length of the topographic axial view of the axis vertebra of 2- to 10-year-old children to guide the use of surgical screws. METHODS: Seventy-five computed tomography scans from 24- to 120-month-old patients were studied. Measurements were taken in an axial view of C2 and correlated with 2 age groups and both sexes. Statistical analysis was performed with the Student t test. RESULTS: In the 24- to 48-month age group, only 5.5% of the lamina and 8.3% of the pedicles had thicknesses < 3.5 mm. In the 49- to 120-month age group, there were no lamina thickness values < 3.5 mm, and 1.2% of pedicle thicknesses were < 3.5 mm. Both age groups had no lamina and pedicle lengths < 12 mm and no lateral mass lengths > 12 mm. CONCLUSION: In the majority of cases, the use of 3.5-mm lamina and pedicle screws in children is feasible. A base value of 45 degrees for the spinolaminar angle can be adopted as a reference for insertion of screws in the C2 lamina. This information can be particularly useful for decision making during preoperative planning for C1-C2 or craniocervical arthrodesis in children.

Age of First Dental Visit and Predictors for Oral Healthcare Utilisation in Preschool Children

Purpose: To assess the age the of the first dental visit and the association of self-perceived oral health, socioeconomic and clinical indicators with healthcare utilisation in Brazilian preschool children. Materials and Methods: An epidemiological survey with 455 5- to 59-month-old children was conducted on National Children's Vaccination Day in Santa Maria, RS, Brazil. Data about age and reasons for the first dental visit, healthcare utilisation, socioeconomic status and self-perceived oral health were collected by means of a parental semi-structured questionnaire. Calibrated examiners evaluated the prevalence of dental caries (WHO) and dental trauma. The assessment of the association used Poisson regression models (prevalence ratio; 95% confidence interval [Cl]). Results: A total of 24.2% (95% Cl: 20.3% to 28.4%) of the study sample had already had a first dental visit. Older children, those with dental caries and dental trauma and whose mothers had a higher level of education were more likely to have gone to the dentist. Children of low socioeconomic status were more likely to have visited public than private healthcare services. The reasons for the first dental visit were associated with clinical indicators of the sample. The distribution of utilisation of the types of oral healthcare services (public or private) varied across the socioeconomic groups. Non-white children with dental caries and dental trauma tended to visit a dentist only for treatment reasons. Conclusion: Socioeconomic and clinical indicators are associated with the use of dental services, indicating the need for strategies to promote public health and reorientation of services that facilitate dental access for preschool children.

Role of nitric oxide and endocannabinoids in synaptic plasticity in the perirhinal cortex and in visual recognition memory

Introduction and aims of the research Nitric oxide (NO) and endocannabinoids (eCBs) are major retrograde messengers, involved in synaptic plasticity (long-term potentiation, LTP, and long-term depression, LTD) in many brain areas (including hippocampus and neocortex), as well as in learning and memory processes. NO is synthesized by NO synthase (NOS) in response to increased cytosolic Ca2+ and mainly exerts its functions through soluble guanylate cyclase (sGC) and cGMP production. The main target of cGMP is the cGMP-dependent protein kinase (PKG). Activity-dependent release of eCBs in the CNS leads to the activation of the Gαi/o-coupled cannabinoid receptor 1 (CB1) at both glutamatergic and inhibitory synapses. The perirhinal cortex (Prh) is a multimodal associative cortex of the temporal lobe, critically involved in visual recognition memory. LTD is proposed to be the cellular correlate underlying this form of memory. Cholinergic neurotransmission has been shown to play a critical role in both visual recognition memory and LTD in Prh. Moreover, visual recognition memory is one of the main cognitive functions impaired in the early stages of Alzheimer’s disease. The main aim of my research was to investigate the role of NO and ECBs in synaptic plasticity in rat Prh and in visual recognition memory. Part of this research was dedicated to the study of synaptic transmission and plasticity in a murine model (Tg2576) of Alzheimer’s disease. Methods Field potential recordings. Extracellular field potential recordings were carried out in horizontal Prh slices from Sprague-Dawley or Dark Agouti juvenile (p21-35) rats. LTD was induced with a single train of 3000 pulses delivered at 5 Hz (10 min), or via bath application of carbachol (Cch; 50 μM) for 10 min. LTP was induced by theta-burst stimulation (TBS). In addition, input/output curves and 5Hz-LTD were carried out in Prh slices from 3 month-old Tg2576 mice and littermate controls. Behavioural experiments. The spontaneous novel object exploration task was performed in intra-Prh bilaterally cannulated adult Dark Agouti rats. Drugs or vehicle (saline) were directly infused into the Prh 15 min before training to verify the role of nNOS and CB1 in visual recognition memory acquisition. Object recognition memory was tested at 20 min and 24h after the end of the training phase. Results Electrophysiological experiments in Prh slices from juvenile rats showed that 5Hz-LTD is due to the activation of the NOS/sGC/PKG pathway, whereas Cch-LTD relies on NOS/sGC but not PKG activation. By contrast, NO does not appear to be involved in LTP in this preparation. Furthermore, I found that eCBs are involved in LTP induction, but not in basal synaptic transmission, 5Hz-LTD and Cch-LTD. Behavioural experiments demonstrated that the blockade of nNOS impairs rat visual recognition memory tested at 24 hours, but not at 20 min; however, the blockade of CB1 did not affect visual recognition memory acquisition tested at both time points specified. In three month-old Tg2576 mice, deficits in basal synaptic transmission and 5Hz-LTD were observed compared to littermate controls. Conclusions The results obtained in Prh slices from juvenile rats indicate that NO and CB1 play a role in the induction of LTD and LTP, respectively. These results are confirmed by the observation that nNOS, but not CB1, is involved in visual recognition memory acquisition. The preliminary results obtained in the murine model of Alzheimer’s disease indicate that deficits in synaptic transmission and plasticity occur very early in Prh; further investigations are required to characterize the molecular mechanisms underlying these deficits.

Sorveglianza dell’infezione da virus dell’epatite E (HEV) in Italia: from farm to table

L'epatite E è una malattia umana con caratteristiche di epatite acuta, causata da un ssRNA virus (HEV). Nel 1997, HEV è stato identificato per la prima volta nei suini (SwHEV). In seguito, diverse evidenze, tra cui la vicinanza genetica tra ceppi umani e suini, suggerirono la trasmissione zoonotica del virus. Nella presente tesi, l’identificazione di SwHEV è stata condotta mediante ricerca di porzioni di genoma virale attraverso RT-PCR. Dal 2011 al 2013, sono stati analizzati 343 campioni fecali (da 19 allevamenti) e 70 bili (da 2 macelli) prelevati da altrettanti suini, in diverse Regioni italiane. E’ stato inoltre condotto uno studio retrospettivo su 78 feci (da 3 allevamenti) raccolte nel 2000. Il virus è stato identificato nel 24,5% e 19,2% delle feci raccolte rispettivamente nel 2011-2013 e nel 2000. Nessuna bile è risultata positiva. Mediante sequenziamento del genoma intero di uno dei virus identificati, è stata condotta l’analisi filogenetica per valutarne il grado di correlazione con alti ceppi suini e umani. La presenza di HEV è stata valutata lungo la filiera di produzione suina, dal macello al punto vendita. Trentaquattro campioni di feci, fegato e muscolo sono stati raccolti in un macello da altrettanti suini sani (età:6-7 mesi). Quattordici feci e 2 fegati, sono risultati positivi per HEV. Sono state prelevate 129 salsicce sia allo stabilimento di trasformazione sia alla vendita, ma nessuna è risultata positiva. La presenza di HEV è stata valutata anche nelle salsicce di fegato, fresche e secche, acquistate presso una macelleria. Il genoma virale è stato rilevato nel 22,2% delle salsicce fresche e nel 4,3 % di quelle secche ma la vitalità del virus non è stata dimostrata. In conclusione, lo studio condotto ha confermato l’ampia circolazione di HEV nei suini e la possibile contaminazione dei prodotti carnei derivati, confermando la necessità di una continua sorveglianza.

Giant Cardiac Fibroma: An Unusual Cause of Failure to Thrive

Cardiac fibromas are extremely rare in the general pediatric population and may present with a wide spectrum of clinical signs, including life-threatening arrhythmias and sudden death. We report a 14-month-old boy who presented with failure to thrive as the only symptom. Echocardiography showed a large cardiac fibroma in the right ventricle. Cardiac magnetic resonance imaging confirmed the diagnosis. After complete surgical tumor resection, the boy showed normal catch-up growth. This case underlines the diversity of clinical features of cardiac tumors, which implies that they should be considered early in the differential diagnosis of infants with failure to thrive.

Ventilatory response to nitrogen multiple-breath washout in infants

BACKGROUND Nitrogen multiple-breath washout (N2 MBW) using 100% oxygen (O2 ) has regained interest to assess efficiency of tracer gas clearance in, for example, children with Cystic Fibrosis (CF). However, the influence of hyperoxia on the infants' respiratory control is unclear. We assessed safety and impact on breathing pattern from hyperoxia, and if exposure to 40% O2 first induces tolerance to subsequent 100% O2 for N2 MBW. METHODS We prospectively enrolled 39 infants aged 3-57 weeks: 15 infants with CF (8 sedated for testing) and 24 healthy controls. Infants were consecutively allocated to the protocols comprising of 100% O2 or 40/100% O2 administered for 30 breaths. Lung function was measured using an ultrasonic flowmeter setup. Primary outcome was tidal volume (VT ). RESULTS None of the infants experienced apnea, desaturation, or bradycardia. Both protocols initially induced hypoventilation. VT temporarily declined in 33/39 infants across 10-25 breaths. Hypoventilation occurred independent of age, disease, and sedation. In the new 40/100% O2 protocol, VT returned to baseline during 40% O2 and remained stable during 100% O2 exposure. End-tidal carbon dioxide monitored online did not change. CONCLUSION The classical N2 MBW protocol with 100% O2 may change breathing patterns of the infants. The new protocol with 40% O2 induces hyperoxia-tolerance and does not lead to changes in breathing patterns during later N2 washout using 100% O2 . Both protocols are safe, the new protocol seems an attractive option for N2 MBW in infants. Pediatr Pulmonol. © 2013 Wiley Periodicals, Inc.

Hepatic fungal infection in a young beagle with unrecognised hereditary cobalamin deficiency (Imerslund-Gräsbeck syndrome)

A 12-month-old beagle presented for anorexia, pyrexia and vomiting. The dog had been treated intermittently with antibiotics and corticosteroids for inappetence and lethargy since five months of age. Previous laboratory abnormalities included macrocytosis and neutropenia. At presentation, the dog was lethargic, febrile and thin. Laboratory examination findings included anaemia, a left shift, thrombocytopenia, hypoglycaemia and hyperbilirubinaemia. Multiple, small, hypoechoic, round hepatic lesions were observed on abdominal ultrasound. Cytological examination of hepatic fine needle aspirates revealed a fungal infection and associated pyogranulomatous inflammation. The dog's general condition deteriorated despite supportive measures and treatment with fluconazole, and owners opted for euthanasia before hypocobalaminaemia was identified. Subsequent genomic analysis revealed a CUBN:c.786delC mutation in a homozygous state, confirming hereditary cobalamin malabsorption (Imerslund-Gräsbeck syndrome). Similar to human infants, dogs with Imerslund-Gräsbeck syndrome may rarely be presented for infectious diseases, distracting focus from the underlying primary disorder.

Effects of breastfeeding and naturally acquired immunity on infection with {\it Giardia lamblia}: A study in a cohort of Mexican infants

Giardia lamblia is one of the most common causes of gastrointestinal tract infection among young children worldwide. Yet host protection against this parasite and the effect of infection with Giardia on infant growth are poorly understood. It was hypothesized that among young children, protection against infection with Giardia is afforded by breastfeeding and previous infection with the parasite and further, that infection with Giardia decreases growth velocity. From 4/88 to 4/90, 197 infants in a poor area of Mexico City were followed from 0 to 18 months of age, with stool specimens, symptoms and feeding status data collected weekly. A total of 6,031 stool specimens were tested for Giardia antigen by enzyme-linked immunosorbent assay. There were 1.0 Giardia infections per child-year; 25% were symptomatic and 54% lasted more than 1 month; 94 infants had 1, and 33 had 2 or more infections. Breastfeeding status was coded and analyzed for each child-week of follow up. 91% of study infants were breastfed from birth, 57% at 6 months and 38% at 12 months of age. Rate ratios for non-breastfeeding adjusted for confounding factors were calculated from stratified analyses and the Cox proportional hazards model. Not breastfeeding was a significant risk factor for first infection with Giardia vs. any breastfeeding (adjusted RR = 1.8; 1.1, 2.8) at all ages; a dose response was demonstrated by degree of breastfeeding. The adjusted rate ratio for non-breastfeeding vs. partial breastfeeding was 1.6 (1.03, 2.6) and for non-breastfeeding vs. complete breastfeeding was 4.7 (1.4, 15.9). Among Giardia infected infants, breastfeeding did not protect against diarrheal symptoms or shorten the duration of carriage. First and repeat infections with Giardia did not differ in duration or the percent symptomatic. The analysis of growth and Giardia infection was inconclusive but suggested that a history of Giardia infection might be associated with decreased weight velocity, while an immediate chronic infection might be associated with increased weight velocity. In summary, these data indicate that breastfeeding protects infants against infection with Giardia; provide no evidence of protection against repeat infections resulting from a prior infection and suggest but do not establish that a history of Giardia infection might be associated with decreased growth in young children. ^

A study of the association between timing of solid food introduction in infants and overweight and obesity in pre-school aged children in NHANES 2003-2008

Background. Previous studies suggest an association between timing of introduction of solid food and increased risk of obesity in pre-school aged children, but no study included a representative sample of US children. We sought to examine whether there was any association between the timing of solid food introduction and overweight/obesity in pre-school aged children. Design/methods. Cross-sectional study of a nationally representative sample (N=2050) of US children aged 2 to 5 years with information on infant feeding practices and measured weight and height from the National Health and Nutrition Examination Survey 2003–2008. The main outcome measure was BMI for age and sex ≥ 85th percentile. The main exposure was timing of solid food introduction at < 4, 4–5, or ≥ 6 months of age. Binomial logistic regression was used in the analysis controlling for child's sex, birth weight and breastfeeding status as well as maternal age at birth, smoking status and socio-demographic variables. Results. Two thousand and fifty children were included in the sample; 51% male and 49% female; 57.1% Non-Hispanic White, 21.9% Hispanic, 14.0% Non-Hispanic Black, and 7% other race/ethnicity. Twenty-two percent of the children were overweight or obese. Sixty-nine percent were breastfed or fed breast milk at birth and 36% continued breastfeeding for ≥ six months. Solid foods were introduced before 4 months of age for 11.2% of the children; 30.3% received solid foods between 4 to 5 months; with 58.6% receiving solid foods at 6 months or later. Timing of solid food introduction was not associated with weight status (OR= 1.36, 95% CI [0.83–2.24]). Formula-fed infants and infants breastfed for < 4 months had increased odds of overweight and obesity (OR=1.54, 95% CI [1.05–2.27] and OR= 1.60, 95% CI [1.05–2.44], respectively) when compared to infants breastfed for ≥ 6 months. Conclusion. Timing of solid food introduction was not associated with weight status in a national sample of US children ages 2 to 5 years. More focus should be placed on promoting breastfeeding and healthy infant feeding practices as strategies to prevent obesity in children. ^

Investigation of I -compounds (newly discovered indigenous DNA modifications) by different approaches

I-compounds are newly discovered covalent DNA modifications detected by the $\sp{32}$P-postlabeling assay. They are age-dependent, tissue-specific and sex-different. The origin(s), chemistry and function(s) of I-compounds are unknown. The total level of I-compounds in 8-10 month old rat liver is 1 adduct in 10$\sp7$ nucleotides, which is not neglectable. It is proposed that I-compounds may play a role in spontaneous tumorigenesis and aging.^ In the present project, I-compounds were investigated by several different approaches. (1) Dietary modulation of I-compounds. (2) Comparison of I-compounds with persistent carcinogen DNA adducts and 5-methylcytosine. (3) Strain differences of I-compounds in relation to organ site spontaneous tumorigenesis. (4) Effects of nongenotoxic hepatocarcinogenes on I-compounds.^ It was demonstrated that the formation of I-compounds is diet-related. Rats fed natural ingredient diet exhibited more complex I-spot patterns and much higher levels than rats fed purified diet. Variation of major nutrients (carbohydrate, protein and fat) in the diet, produced quantitative differences in I-compounds of rat liver and kidney DNAs. Physiological level of vitamin E in the diet reduced intensity of one I-spot compared with vitamin E deficient diet. However, extremely high level of vitamin E in the diet gave extra spot and enhanced the intensities of some I-spots.^ In regenerating rat liver, I-compounds levels were reduced, as carcinogen DNA adducts, but not 5-methylcytosine, i.e. a normal DNA modification.^ Animals with higher incidences of spontaneous tumor or degenerative diseases tended to have a lower level of I-compounds.^ Choline devoid diet induced a drastic reduction of I-compound level in rat liver compared with choline supplemented diet. I-compound levels were reduced after multi-doses of carbon tetrachloride (CCl$\sb4$) exposure in rats and single dose exposure in mice. An inverse relationship was observed between I-compound level and DNA replication rate. CCl$\sb4$-related DNA adduct was detected in mice liver and intensities of some I-spots were enhanced 24 h after a single dose exposure.^ The mechanisms and explanations of these observations will be discussed. I-compounds are potentially useful indicators in carcinogenesis studies. ^

Escala de inteligencia para adultos de Wechsler. Wais - III. Indice de comprensión verbal : Normas para los subtests : Vocabulario, analogías e información, para la Ciudad de La Plata edades : 16 a 24 años

En este trabajo se presentan los resultados de la investigación destinada a la estandarización de los subtests que conforman el Indice de Comprensión Verbal de la Escala Wechsler para la medida de la inteligencia del adulto, Wais-III, población general de 16 a 24 años, en la ciudad de La Plata. Este Indice, constituye un valioso instrumento de evaluación de la Comprensión Verbal, se refiere a la conceptualización, conocimientos y expresión verbal. El sujeto debe contestar a preguntas que miden conocimientos prácticos, significados de palabras, razonamiento y habilidad para expresar ideas con palabras. Está constituido por los subtests de Vocabulario, Analogías e Información. En esta oportunidad se analiza el desempeño en dichos subtests de 887 estudiantes de ambos sexos, que cursan estudios secundarios y terciarios universitarios y no universitarios. Se utilizó una modalidad colectiva de administración. A partir de las respuestas obtenidas, los análisis realizados nos permiten efectuar algunas observaciones: a) no se observan para las distintas edades, diferencias significativas por género; b) a medida que aumenta la edad se incrementan los valores promedio obtenidos en los subtests de Vocabulario y Analogías situación que no se observa en el subtest de Información

Escala de inteligencia para adultos de Wechsler. Wais - III. Indice de comprensión verbal : Normas para los subtests : Vocabulario, analogías e información, para la Ciudad de La Plata edades : 16 a 24 años

En este trabajo se presentan los resultados de la investigación destinada a la estandarización de los subtests que conforman el Indice de Comprensión Verbal de la Escala Wechsler para la medida de la inteligencia del adulto, Wais-III, población general de 16 a 24 años, en la ciudad de La Plata. Este Indice, constituye un valioso instrumento de evaluación de la Comprensión Verbal, se refiere a la conceptualización, conocimientos y expresión verbal. El sujeto debe contestar a preguntas que miden conocimientos prácticos, significados de palabras, razonamiento y habilidad para expresar ideas con palabras. Está constituido por los subtests de Vocabulario, Analogías e Información. En esta oportunidad se analiza el desempeño en dichos subtests de 887 estudiantes de ambos sexos, que cursan estudios secundarios y terciarios universitarios y no universitarios. Se utilizó una modalidad colectiva de administración. A partir de las respuestas obtenidas, los análisis realizados nos permiten efectuar algunas observaciones: a) no se observan para las distintas edades, diferencias significativas por género; b) a medida que aumenta la edad se incrementan los valores promedio obtenidos en los subtests de Vocabulario y Analogías situación que no se observa en el subtest de Información

Escala de inteligencia para adultos de Wechsler. Wais - III. Indice de comprensión verbal : Normas para los subtests : Vocabulario, analogías e información, para la Ciudad de La Plata edades : 16 a 24 años

En este trabajo se presentan los resultados de la investigación destinada a la estandarización de los subtests que conforman el Indice de Comprensión Verbal de la Escala Wechsler para la medida de la inteligencia del adulto, Wais-III, población general de 16 a 24 años, en la ciudad de La Plata. Este Indice, constituye un valioso instrumento de evaluación de la Comprensión Verbal, se refiere a la conceptualización, conocimientos y expresión verbal. El sujeto debe contestar a preguntas que miden conocimientos prácticos, significados de palabras, razonamiento y habilidad para expresar ideas con palabras. Está constituido por los subtests de Vocabulario, Analogías e Información. En esta oportunidad se analiza el desempeño en dichos subtests de 887 estudiantes de ambos sexos, que cursan estudios secundarios y terciarios universitarios y no universitarios. Se utilizó una modalidad colectiva de administración. A partir de las respuestas obtenidas, los análisis realizados nos permiten efectuar algunas observaciones: a) no se observan para las distintas edades, diferencias significativas por género; b) a medida que aumenta la edad se incrementan los valores promedio obtenidos en los subtests de Vocabulario y Analogías situación que no se observa en el subtest de Información

Methionine adenosyltransferase 1A knockout mice are predisposed to liver injury and exhibit increased expression of genes involved in proliferation

Liver-specific and nonliver-specific methionine adenosyltransferases (MATs) are products of two genes, MAT1A and MAT2A, respectively, that catalyze the formation of S-adenosylmethionine (AdoMet), the principal biological methyl donor. Mature liver expresses MAT1A, whereas MAT2A is expressed in extrahepatic tissues and is induced during liver growth and dedifferentiation. To examine the influence of MAT1A on hepatic growth, we studied the effects of a targeted disruption of the murine MAT1A gene. MAT1A mRNA and protein levels were absent in homozygous knockout mice. At 3 months, plasma methionine level increased 776% in knockouts. Hepatic AdoMet and glutathione levels were reduced by 74 and 40%, respectively, whereas S-adenosylhomocysteine, methylthioadenosine, and global DNA methylation were unchanged. The body weight of 3-month-old knockout mice was unchanged from wild-type littermates, but the liver weight was increased 40%. The Affymetrix genechip system and Northern and Western blot analyses were used to analyze differential expression of genes. The expression of many acute phase-response and inflammatory markers, including orosomucoid, amyloid, metallothionein, Fas antigen, and growth-related genes, including early growth response 1 and proliferating cell nuclear antigen, is increased in the knockout animal. At 3 months, knockout mice are more susceptible to choline-deficient diet-induced fatty liver. At 8 months, knockout mice developed spontaneous macrovesicular steatosis and predominantly periportal mononuclear cell infiltration. Thus, absence of MAT1A resulted in a liver that is more susceptible to injury, expresses markers of an acute phase response, and displays increased proliferation.