Oxigenoterapia domiciliar prolongada em crianças e adolescentes: uma análise do uso clínico e de custos de um programa assistencial

OBJETIVOS: Descrever as características clínicas e laboratoriais dos pacientes em oxigenoterapia domiciliar prolongada acompanhados pelo programa de atendimento domiciliar do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, durante um período de 8 anos, e comparar os grupos com e sem hipertensão pulmonar secundária. Estimar o custo do programa utilizando concentradores versus cilindros de oxigênio arcados pela instituição. MÉTODOS: Estudo descritivo retrospectivo e de coorte dos pacientes em oxigenoterapia domiciliar prolongada, em seguimento no período de 2002 a 2009, na Unidade de Pneumologia do Instituto da Criança do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. RESULTADOS: Foram estudados 165 pacientes, 53% do sexo masculino, com as medianas: idade de início da oxigenoterapia - 3,6 anos; tempo de oxigenoterapia - 7 anos; e tempo de sobrevida após início da oxigenoterapia - 3,4 anos. Os principais diagnósticos foram: fibrose cística (22%), displasia broncopulmonar (19%) e bronquiolite obliterante (15%). Dos 33 pacientes que realizaram espirometria, 70% apresentavam distúrbio ventilatório obstrutivo grave. O exame ecocardiográfico foi executado em 134 pacientes; 51% deles tinham hipertensão pulmonar secundária. Houve associação estatisticamente significante entre: presença de hipertensão pulmonar e necessidade de maiores fluxos de oxigênio (qui-quadrado, p = 0,011); e presença de hipertensão pulmonar e maior tempo de oxigenoterapia (Logrank, p = 0,0001). Não houve diferença estatisticamente significante entre tempo de sobrevida após início da oxigenoterapia e presença de hipertensão pulmonar. Os custos médios mensais do programa foram: US$ 7.392,93 para os concentradores e US$ 16.630,92 para cilindros. CONCLUSÕES: A oxigenoterapia domiciliar prolongada foi empregada em distintas doenças crônicas, predominantemente em lactentes e pré-escolares. Houve alta frequência de hipertensão pulmonar associada a maiores períodos de uso e fluxos de oxigênio, sem associação à sobrevida. A substituição dos cilindros por concentradores poderá reduzir custos significativamente.

Early morphological and histochemical alterations in rats subjected to ileocystoplasty

PURPOSE: To study morphologic and histochemical alterations arising at the ileocystoplasty site. METHODS: Sixteen Wistar female rats were subjected to ileocystoplasty and sacrificed after eight weeks. Material collected was divided into four groups for histological and histochemical studies: Group I (control) - isolated ileum segment removed during ileocystoplasty; Group II - ileoileal anastomosis; Group III - ileovesical anastomosis and Group IV - ileal segment from the neobladder. Histological and histochemical study assessed dysplasia, metaplasia, acute and chronic inflammation, fibrosis, atrophy, hypertrophy, total mucins, sialomucins and sulfomucins. The non-parametric Wilcoxon and Mann-Whitney tests were employed in statistical analysis. RESULTS: None of the groups presented dysplasia. Acute inflammation and atrophy occurred in Groups II, III and IV, not reaching statistical significance. Metaplasia was significant only in Group III (p=0.012). Chronic inflammation, fibrosis and hypertrophy were significant in Groups II, III and IV. There was a significant increase in total mucin content in Group IV (p=0.014) and a reduction in Group III (p=0.016). Increases in sialomucins were observed in samples for Groups III (p=0.003) and IV (p=0.002) along with reduced sulfomucins in samples from Groups III (p=0.013) and IV (p=0.008). CONCLUSION: Ileocystoplasty in female rats caused squamous metaplasia, chronic inflammatory infiltration, fibrosis, hypertrophy, increase in sialomucin content, reduction in sulfomucins, and alterations in total mucin content with statistical significance, as well acute inflammatory infiltration and muscular atrophy with less intensity.

Avaliação radiográfica da cobertura acetabular à cabeça femoral, após osteotomia tripla e aplicação de cunha sacroilíaca, em pelve de cadáveres de cães

Na tentativa de evitar algumas das dificuldades associadas à osteotomia pélvica tripla (OPT), foi desenvolvido experimentalmente o método de aplicação de cunha na junção sacroilíaca para aumentar a ventroversão acetabular. O objetivo deste estudo foi aplicar as técnicas de cunha sacroilíaca e OPT em cadáveres e avaliar radiograficamente a eficácia da ventroversão acetabular. Para tal, foram utilizados 10 cadáveres de cães, adultos, com 15-25 kg. Em cada hemipelve direita foi realizada OPT com placas de 20° e 40°. Na hemipelve esquerda foram aplicadas cunhas nas articulações sacroilíacas de 20° e 40°. Avaliações radiográficas em projeções ventrodorsais foram realizadas para mensuração da cobertura acetabular à cabeça femoral nas duas técnicas. De acordo com os dados obtidos pode-se observar que não houve diferença entre a técnica de OPT e o uso de cunha sacroilíaca utilizando implantes de 20° e 40°, mas ocorreu diferença significativa (p<0,05) entre os cães antes e após a aplicação dos implantes de 20° e 40°, e também entre os que receberam implantes de 20° e os de 40°. A aplicação de cunha sacroilíaca produziu resultados semelhantes à OPT, e também se mostrou como de mais fácil aplicação.

Influência do local de nascimento e do transporte sobre a morbimortalidade de recém-nascidos prematuros

OBJETIVO: Verificar a influência do local de nascimento e do transporte sobre a morbimortalidade de recém-nascidos prematuros na Região Sul do Brasil. MÉTODOS: Estudo de coorte com recém-nascidos prematuros transferidos para a unidade de tratamento intensivo de referência (grupo transporte = 61), tendo sido acompanhados até a alta. Os dados sobre o atendimento no hospital de origem e transporte foram obtidos no momento da internação. Esse grupo foi comparado com neonatos da maternidade de referência, pareados por idade gestacional (grupo controle = 123), tendo como desfecho primário o óbito e desfechos secundários as alterações da glicemia, temperatura e saturação de oxigênio no momento da internação e a incidência de enterocolite necrosante, displasia broncopulmonar e sepses. Na associação entre as variáveis e o desfecho, foi utilizado o risco relativo. Foi adotado um nível de significância de α = 5% e β = 90%. RESULTADOS: A distância média percorrida foi de 91 km. A idade gestacional média foi de 34 semanas. Entre os recém-nascidos transferidos, 23% (n = 14) não tiveram atendimento pediátrico na sala de parto. No transporte, 33% dos recém-nascidos foram acompanhados por pediatra, e os equipamentos utilizados foram: incubadora (57%), bomba de infusão (13%), oxímetro (49%) e aparelho para aferição da glicemia (21%). O grupo transporte apresentou maior incidência de hiperglicemia, risco relativo (RR) = 3,2 (2,3-4,4), hipoglicemia, RR = 2,4 (1,4-4,0), hipertermia, RR = 2,5 (1,6-3,9), e hipoxemia, RR = 2,2 (1,6-3,0). Foram observados 18% de óbitos no grupo dos transferidos e 8,9% no grupo controle, RR = 2,0 (1,0-2,6). CONCLUSÕES: A pesquisa expõe deficiências no atendimento e transporte dos recém-nascidos, sendo necessária uma melhor organização do atendimento perinatal e do transporte na região nordeste do Rio Grande do Sul.

Morphology and morphometry of the foramen magnum in Toy Poodle and Yorkshire terrier dogs

The occipital dysplasia has been characterized by a dorsal enlargement of the foramen magnum which can vary in size and shape. Clinical signs may be present or not in animals with occipital dysplasia. The purpose of this study was to radiographically analyze the morphology and morphometry of the foramen magnum of thirty healthy dogs. This study chose to use fifteen Yorkshire terrier dogs and fifteen Toy Poodle dogs in order to characterize the radiographic aspects of the foramen magnum and contribute to the diagnosis and critical analysis of the occipital dysplasia importance. According to the foramen magnum morphology and tracings, it was possible to classify the radiographic aspects into different shapes varing from oval and quadrangular. Out of 26 (86.7%) animals had a dorsal enlargement and 4 (13.3%) showed normal foramen magnum. Animals without any clinical signs that are radiographically classified as dysplastic dogs may simply represent an anatomic variation of the foramen magnum.

Ventilação oscilatória de alta freqüência em pediatria e neonatologia

Este trabalho teve por objetivo rever a literatura e descrever a utilização da ventilação oscilatória de alta freqüência em crianças e recém-nascidos. Revisão bibliográfica e seleção de publicações mais relevantes sobre ventilação de alta freqüência utilizando as bases de dados MedLine e SciElo publicadas nos últimos 15 anos. As seguintes palavras-chave foram utilizadas: ventilação oscilatória de alta freqüência, ventilação mecânica, síndrome do desconforto respiratório agudo, crianças e recém-nascidos. Descreveu-se o emprego da ventilação oscilatória de alta freqüência em crianças com síndrome do desconforto respiratório agudo, síndrome de escape de ar e doença pulmonar obstrutiva. Avaliou em recém-nascidos, síndrome do desconforto respiratório, displasia broncopulmonar, hemorragia peri-intraventricular, leucoencefalomalácia e extravasamento de ar. Também, abordou a transição da ventilação mecânica convencional para a ventilação de alta freqüência e o manuseio específico da ventilação de alta freqüência quanto à oxigenação, eliminação de gás carbônico, realização de exame radiológico, realização de sucção traqueal e utilização de sedação e bloqueio neuromuscular. Foram abordados o desmame deste modo ventilatório e as complicações. Em crianças maiores a ventilação oscilatória de alta freqüência é uma opção terapêutica, principalmente na síndrome do desconforto respiratório agudo, devendo ser empregada precocemente. Também pode ser útil em casos de síndrome de escape de ar e doença pulmonar obstrutiva. Em recém-nascidos, não há evidências que demonstram superioridade da ventilação oscilatória de alta freqüência em relação à ventilação convencional, sendo a síndrome de escape de ar a única situação clínica em que há evidência de melhores resultados com este modo ventilatório.

Mucin pattern reflects the origin of the adenocarcinoma in Barrett's esophagus: a retrospective clinical and laboratorial study

Background: Mucin immunoexpression in adenocarcinoma arising in Barrett's esophagus (BE) may indicate the carcinogenesis pathway. The aim of this study was to evaluate resected specimens of adenocarcinoma in BE for the pattern of mucins and to correlate to the histologic classification. Methods: Specimens were retrospectively collected from thirteen patients who underwent esophageal resection due to adenocarcinoma in BE. Sections were scored for the grade of intestinal metaplasia. The tissues were examined by immunohistochemistry for MUC2 and MUC5AC antibodies. Results: Eleven patients were men. The mean age was 61 years old (varied from 40 to 75 years old). The tumor size had a mean of 4.7 +/- 2.3 cm, and the extension of BE had a mean of 7.7 +/- 1.5 cm. Specialized epithelium with intestinal metaplasia was present in all adjacent mucosas. Immunohistochemistry for MUC2 showed immunoreactivity in goblet cells, while MUC5AC was extensively expressed in the columnar gastric cells, localizing to the surface epithelium and extending to a variable degree into the glandular structures in BE. Tumors were classified according to the mucins in gastric type in 7/13 (MUC5AC positive) and intestinal type in 4/13 (MUC2 positive). Two tumors did not express MUC2 or MUC5AC proteins. The pattern of mucin predominantly expressed in the adjacent epithelium was associated to the mucin expression profile in the tumors, p = 0.047. Conclusion: Barrett's esophagus adenocarcinoma shows either gastric or intestinal type pattern of mucin expression. The two types of tumors developed in Barrett's esophagus may reflect the original cell type involved in the malignant transformation.

Comparison of multispectral wide-field optical imaging modalities to maximize image contrast for objective discrimination of oral neoplasia

Multispectral widefield optical imaging has the potential to improve early detection of oral cancer. The appropriate selection of illumination and collection conditions is required to maximize diagnostic ability. The goals of this study were to (i) evaluate image contrast between oral cancer/precancer and non-neoplastic mucosa for a variety of imaging modalities and illumination/collection conditions, and (ii) use classification algorithms to evaluate and compare the diagnostic utility of these modalities to discriminate cancers and precancers from normal tissue. Narrowband reflectance, autofluorescence, and polarized reflectance images were obtained from 61 patients and 11 normal volunteers. Image contrast was compared to identify modalities and conditions yielding greatest contrast. Image features were extracted and used to train and evaluate classification algorithms to discriminate tissue as non-neoplastic, dysplastic, or cancer; results were compared to histologic diagnosis. Autofluorescence imaging at 405-nm excitation provided the greatest image contrast, and the ratio of red-to-green fluorescence intensity computed from these images provided the best classification of dysplasia/cancer versus non-neoplastic tissue. A sensitivity of 100% and a specificity of 85% were achieved in the validation set. Multispectral widefield images can accurately distinguish neoplastic and non-neoplastic tissue; however, the ability to separate precancerous lesions from cancers with this technique was limited. (C) 2010 Society of Photo-Optical Instrumentation Engineers. [DOI: 10.1117/1.3516593]

Identification of protein-coding and non-coding RNA expression profiles in CD34(+) and in stromal cells in refractory anemia with ringed sideroblasts

Background: Myelodysplastic syndromes (MDS) are a group of clonal hematological disorders characterized by ineffective hematopoiesis with morphological evidence of marrow cell dysplasia resulting in peripheral blood cytopenia. Microarray technology has permitted a refined high-throughput mapping of the transcriptional activity in the human genome. Non-coding RNAs (ncRNAs) transcribed from intronic regions of genes are involved in a number of processes related to post-transcriptional control of gene expression, and in the regulation of exon-skipping and intron retention. Characterization of ncRNAs in progenitor cells and stromal cells of MDS patients could be strategic for understanding gene expression regulation in this disease. Methods: In this study, gene expression profiles of CD34(+) cells of 4 patients with MDS of refractory anemia with ringed sideroblasts (RARS) subgroup and stromal cells of 3 patients with MDS-RARS were compared with healthy individuals using 44 k combined intron-exon oligoarrays, which included probes for exons of protein-coding genes, and for non-coding RNAs transcribed from intronic regions in either the sense or antisense strands. Real-time RT-PCR was performed to confirm the expression levels of selected transcripts. Results: In CD34(+) cells of MDS-RARS patients, 216 genes were significantly differentially expressed (q-value <= 0.01) in comparison to healthy individuals, of which 65 (30%) were non-coding transcripts. In stromal cells of MDS-RARS, 12 genes were significantly differentially expressed (q-value <= 0.05) in comparison to healthy individuals, of which 3 (25%) were non-coding transcripts. Conclusions: These results demonstrated, for the first time, the differential ncRNA expression profile between MDS-RARS and healthy individuals, in CD34(+) cells and stromal cells, suggesting that ncRNAs may play an important role during the development of myelodysplastic syndromes.

Hepatocellular carcinoma

Hepatitis C infection is associated with the development of hepatocellular carcinoma, and progress has been made in a number of areas. Transgenic mice lines expressing the hepatitis C core protein develop hepatic steatosis, adenomas, and hepatocellular carcinomas, with no significant hepatitis or fibrosis. This implies that hepatitis C can lead directly to malignant transformation, A new lesion, irregular regeneration, has been described in chronic hepatitis C infection and is associated with a 15-fold increase in the relative risk of developing hepatocellular carcinoma. A minority of patients with hepatitis C-related hepatocellular carcinoma have intense lymphocytic infiltration of the cancer, a feature associated with a better prognosis, Several studies have confirmed the association between large cell dysplasia and hepatocellular carcinoma, However, large cell dysplasia may not be a premalignant lesion and instead may be a marker for premalignant alterations elsewhere in the liver. Oral contraceptives previously have been linked to an increased risk of hepatocellular carcinoma. A large multicenter European case-control study has shown minimal increased risk of hepatocellular carcinoma with use of steroidal contraception. Tamoxifen had shown promise in the management of advanced hepatocellular carcinoma. However, a randomized placebo-controlled study of 477 patients with hepatocellular carcinoma found no benefit from tamoxifen, In a preliminary study, however, octreotide has shown improved survival and quality of life in patients with advanced hepatocellular carcinoma, Finally, interferon treatment continues to be linked to a reduced risk of hepatocellular carcinoma in patients with hepatitis C, These studies generally are not randomized, and a randomized prospective study is required to address this issue. (C) 1999 Lippincott Williams & Wilkins, Inc.

Study of acetylcholinesterase activity in rectal suction biopsy for diagnosis of intestinal dysganglionoses: 17-year experience of a single center

Although the utility of the acetylcholinesterase (AChE) histochemistry on rectal suction biopsy in diagnosing Hirschsprung`s disease (HD) has been documented, few reports address a great number of biopsies and patients. Our aim is to present a 17-year experience on the method of rectal suction biopsy and AChE histochemical staining for diagnosis of intestinal dysganglionoses. Between August 1989 and July 2006, 297 children suspected of having HD were submitted to rectal suction biopsies that were evaluated by the same two surgeons. There were 18 complications (6.0%), namely one self-limited rectal bleeding and 17 (5.7%) inadequate procedures that were repeated. A total of 157 patients (52.8%) showed no increased AChE activity and the remaining patients (140-47.2.0%) presented patterns of increased AChE activity confirming the diagnosis of HD or neuronal intestinal dysplasia. Among the 140 cases suspected as having HD, in 131 children the diagnosis of HD was confirmed and they were operated on. The histological studies showed that 111 children presented the classic form of HD or a long spastic segment. Sixteen children presented total colonic aganglionosis and four children proved to have intestinal neuronal dysplasia, according to histological and radiological criteria. Nine (6.6%) newborns were identified as false-positives and no false-negative results were verified. The rectal suction biopsy combined with AChE staining is advantageous for the differentiation between normal bowel and intestinal dysganglionoses. The rectal suction method is simple and can easily be performed by experienced surgeons. The histological evaluation is very objective and can be performed by a non-pathologist.

Elevated expression of MeCP2 in cardiac and skeletal tissues is detrimental for normal development

MeCP2 plays a critical role in interpreting epigenetic signatures that command chromatin conformation and regulation of gene transcription. In spite of MeCP2`s ubiquitous expression, its functions have always been considered in the context of brain physiology. In this study, we demonstrate that alterations of the normal pattern of expression of MeCP2 in cardiac and skeletal tissues are detrimental for normal development. Overexpression of MeCP2 in the mouse heart leads to embryonic lethality with cardiac septum hypertrophy and dysregulated expression of MeCP2 in skeletal tissue produces severe malformations. We further show that MeCP2`s expression in the heart is developmentally regulated; further suggesting that it plays a key role in regulating transcriptional programs in non-neural tissues.

Effects of tidal volume and positive end-expiratory pressure during resuscitation of very premature lambs

Background: Guidelines recommend neonatal resuscitation without controlling tidal volume or positive end-expiratory pressure (PEEP). However, these may improve gas exchange, lung volume and outcome. Aim: To investigate resuscitation of very premature lambs with a Laerdal bag without PEEP versus volume guarantee ventilation with PEEP. Methods: Anaesthetized lambs (n = 20) delivered at 125 d gestation were randomized to three groups receiving 15 min resuscitation: (1) Laerdal bag and no PEEP; (2) ventilation with a tidal volume of 5 ml/kg and 8 cm H2O PEEP; (3) ventilation with 10 ml/kg and 8 cm H2O PEEP. They were then all ventilated for 2 h with tidal volumes of 5 or 10 ml/kg, and 8 cm H2O PEEP. Ventilation parameters and blood gases were recorded. Results: Different tidal volumes affected PaCO2 within minutes, with 10 ml/kg causing severe hypocarbia. PEEP had little effect on PaCO2. Oxygenation improved significantly with PEEP of 8 cm H2O, irrespective of tidal volume. Conclusion: Very premature lambs can be resuscitated effectively using volume-guarantee ventilation and PEEP. Tidal volumes affected PaCO2 within minutes but had little effect on oxygenation. PEEP halved the oxygen requirement compared with no PEEP. Resuscitating premature babies with controlled tidal volumes and PEEP might improve their outcome.

Two novel mutations in the EIF2AK3 gene in children with Wolcott-Rallison syndrome

Wolcott-Rallison syndrome (WRS, OMIM 226980) is a rare autosomal recessive disorder characterized by permanent neonatal diabetes mellitus, epiphyseal dysplasia, and other multisystemic clinical manifestations. We described two novel mutations in the EIF2AK3 gene in two consanguineous families with WRS from Brazil and Morocco. We have observed in case 1 a homozygous C > T replacement at base pair c.1192 at exon 7, generating a stop codon at position 398 (Gln398Stop). Both of his parents were found to be heterozygous for the mutation. We detected in both parents of case 2, a deceased Moroccan girl, a duplication of base pair c.851A at exon 5 (c.851dupA) leading to a frameshift and a stop codon at position 285 (p.Pro285AlafsX3). Both cases 1 and 2 had neonatal diabetes mellitus, multiple epiphyseal dysplasia, and growth delay, and presented episodes of acute hepatic dysfunction. Case 1 presented central hypothyroidism, developmental delay, and mild mental retardation. Case 2 presented a fatal episode of acute renal failure. The clinical phenotype associated with the syndrome can be variable, but a combination of infancy-onset diabetes mellitus, multiple epiphyseal dysplasia, and hepatic and/or renal dysfunction is the mainstay of diagnosis.

The usefulness of acetic acid wash and chemiluminescent illumination (Vizilite) in the visualization of oral mucosal white lesions

A diligent and careful examination of the mouth and oral structures has been historically deficient in revealing premalignant and malignant oral lesions. Conventional screening practice for oral neoplastic lesions involves visual scrutiny of the oral tissues with the naked eye under projected incandescent or halogen illumination. Visualization is the principal strategy used to find patients with lesions at risk for malignant transformation; hence, any procedure which highlights neoplastic lesions should aid the clinician. This pilot study examined the usefulness of acetic acid wash and chemiluminescent light (Vizilite) in enhancing visualization of oral mucosal white lesions, and its ability to highlight malignant and potentially malignant lesions. Fifty five patients referred for assessment of a white lesion, were prospectively screened with Vizilite, and an incisional biopsy performed for a definitive diagnosis. The age, sex, and smoking status of all patients were recorded, and all lesions were photographed. The visibility, location, size, border, and presence of satellite lesions, were also recorded. The Vizilite tool enhanced intraoral visualization of 26 white lesions, but it could not distinguish between epithelial hyperplasia, dysplasia, or carcinoma. Indeed, all lesions appeared ‘‘aceto-white’’, regardless of the definitive diagnosis. On one occasion, Vizilite aided in the identification of a satellite lesion that was not observed by routine visual inspection. Vizilite appears to be a useful visualization tool, but it does not aid in the identification of malignant and potentially malignant lesions of the oral mucosa.