Atresia das choanas bilateral no recém nascido : revisão a propósito de 2 casos clínicos

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Mapping of autosomal recessive chronic distal spinal muscular atrophy to chromosome 11q13

Distal spinal muscular atrophy is a heterogeneous group of neuromuscular disorders caused by progressive anterior born cell degeneration and characterized by progressive motor weakness and muscular atrophy, predominantly in the distal parts of the limbs. Here we report on chronic autosomal recessive distal spinal muscular atrophy in a large, inbred family with onset at various ages. Because this condition had some of the same clinical features as spinal muscular atrophy with respiratory distress, we tested the disease gene for linkage to chromosome 11q and mapped the disease locus to chromosome 11q13 in the genetic interval that included the spinal muscular atrophy with respiratory distress gene (D11S1889-D11S1321, Z(max) = 4.59 at theta = 0 at locus D11S4136). The sequencing of IGHMBP2, the human homologue of the mouse neuromuscular degeneration gene (nmd) that accounts for spinal muscular atrophy with respiratory distress, failed to detect any mutation in our chronic distal spinal muscular atrophy patients, suggesting that spinal muscular atrophy with respiratory distress and chronic distal spinal muscular atrophy are caused by distinct genes located in the so-me chromosomal region. In addition, the high intrafamilial variability in age at onset raises the question of whether nonallelic modifying genes could be involved in chronic distal spinal muscular atrophy.

Congenital cystic adenomatoid malformation of the lung: indications and timing of surgery

We review a single surgeon and surgical centre's experience with congenital cystic adenomatoid malformation of the lung (CCAML) in relation to clinical spectrum, operative experience, and postoperative course. A retrospective hospital record review was done on surgically treated cases of CCAML over a 10-year period, focusing on number with antenatal diagnosis, spectrum of postnatal presentation, type of surgery performed, and outcome. Forty-seven patients from birth to 14 years of age underwent surgery for CCAML. Antenatal diagnosis (ante) was made in 30 cases. Of these, 10 became symptomatic before surgery. Six of the 17 postnatally-diagnosed (pnd) cases were an asymptomatic incidental finding. Overall, 16 were symptomatic in the 1st year of life, and five were symptomatic beyond 1 year of age. Symptoms varied from respiratory distress (seven ante, six pnd) to chronic cough (three, and recurrent chest infection (three ante, two pnd). All preoperative diagnoses were confirmed with chest CT. Most patients (25) were operated on before 3 months of age. Eleven were operated on in the first 2 weeks of life as emergency surgery for respiratory distress. The most common lobe involved was the right upper lobe (16), and lobectomy was performed in 42 cases, segmentectomy in four, and pneumonectomy in one. Seventeen cases were extubated immediately postoperatively; 29 required postoperative ventilation overnight, and nine needed more prolonged ventilation. Early postoperative complications included pneumothorax (two), pleural effusion (one), and chylous effusion (one). Late complications included recurrence in three cases (all segmentectomy), who then subsequently underwent lobectomy. There was one death from respiratory failure. Because there is an increasing trend in the detection of asymptomatic antenatally-diagnosed CCAML, consideration of early surgical excision to prevent complications is suggested by our series. CT scanning is mandatory for postnatal evaluation because chest x-ray could be normal. Safe elective excision after 3 months is supported by our low morbidity and less need for postoperative ventilation. Lobectomy is the procedure of choice to prevent recurrence.

Clinical signs and duration of cyanide toxicosis delivered by the M-44 ejector in wild dogs

Sodium cyanide poison is potentially a more humane method to control wild dogs than sodium fluoroacetate (1080) poison. This study quantified the clinical signs and duration of cyanide toxicosis delivered by the M-44 ejector. The device delivered a nominal 0.88 g of sodium cyanide, which caused the animal to loose the menace reflex in a mean of 43 s, and the animal was assumed to have undergone cerebral hypoxia after the last visible breath. The mean time to cerebral hypoxia was 156 s for a vertical pull and 434 s for a side pull. The difference was possibly because some cyanide may be lost in a side Pull. There were three distinct phases of cyanide toxicosis: the initial phase was characterised by head shaking, panting and salivation; the immobilisation phase by incontinence, ataxia and loss of the righting reflex; and the cerebral hypoxia phase by a tetanic seizure. Clinical signs that were exhibited in more than one phase of cyanide toxicosis included retching, agonal breathing, vocalisation, vomiting, altered levels of ocular reflex, leg paddling, tonic muscular spasms, respiratory distress and muscle fasciculations of the muzzle.

Métabolisme des glucocorticoïdes dans le poumon murin en développement : la voie surrénalienne

Lorsqu’une femme est à risque d’accoucher prématurément, des glucocorticoïdes lui seront administrés afin d’accélérer la maturation pulmonaire du bébé. Après la naissance, différents protocoles peuvent être mis en place pour aider l’enfant à respirer dont l’administration du surfactant et la ventilation. Les glucocorticoïdes ont un effet positif sur la maturation pulmonaire. Par contre, ils nuisent au processus de la septation après la naissance. Les glucocorticoïdes retrouvés dans le poumon en développement peuvent provenir de deux sources, soit de la voie classique de la synthèse des glucocorticoïdes par les surrénales, soit des gènes exprimés dans le poumon. Les sites d’expression des gènes codant pour les enzymes de la synthèse des glucocorticoïdes dans le poumon sont inconnus ainsi que le gène de la 20α-hydroxystéroïde déshydrogénase (20α-HSD). Cette dernière inactive le substrat et le produit de la 21-hydroxylase. Des poumons de fœtus de souris au jour de gestation 15,5, 17,5 et 19,5 ainsi que de souriceaux âgés de 0, 5 et 15 jours ont été utilisés pour des hybridations in situ. Cette étude a montré qu’avant la naissance, l’ARNm de la 21-hydroxylase est situé au niveau des cellules épithéliales distales alors que l’ARNm de la 20α-HSD se retrouve plutôt au niveau des capillaires. Les gènes de la 21-hydroxylase et de la 20α-HSD sont exprimés dans les cellules épithéliales proximales ainsi que dans les cellules endothéliales de veines dans la période entourant la naissance. À la fin du stade sacculaire et pendant le stade alvéolaire, le gène de la 21-hydroxylase est exprimé seulement dans les septa et les parois minces tout comme le gène de la 20α-HSD sauf dans le stade alvéolaire où il n’y avait pas de signal significatif. Ainsi, ces résultats suggèrent que la 20α-HSD pourrait participer au contrôle du niveau d’activité de la 21-hydroxylase en modulant la disponibilité de son substrat.

Aspiração de corpo estranho na criança: um perigo escondido

Introdução: A aspiração de corpo estranho (ACE) é uma emergência pediátrica e uma causa importante de morte acidental na criança. A maioria dos casos ocorre com objetos orgânicos e inorgânicos de pequenas dimensões, sobretudo em idade pré-escolar. A ACE cursa com amplo espectro de manifestações e o seu diagnóstico representa muitas vezes um desafio. Caso clínico: Descrevemos o caso clínico de uma criança de dois anos que recorreu ao Serviço de Urgência por tosse, disfonia e disfagia. Ao exame objetivo apresentava acessos de tosse estridulosa, tiragem supra-esternal ligeira e auscultação pulmonar com sibilos inspiratórios/expiratórios e roncos dispersos bilateralmente. A telerradiografia do tórax evidenciava um reforço hilar bilateral, mais notável à direita. A avaliação por Otorrinolaringologia, incluindo a nasolaringofibroscopia, não de- mostrou alterações. A broncoscopia revelou a presença de corpo estranho vegetal condicionando obstrução superior a 50% do lúmen do brônquio principal direito. Conclusão: Pretendemos com este caso salientar a necessidade de manter alto índice de suspeição perante a possibilidade de ACE, pois o atraso no seu reconhecimento condiciona o seu tratamento e o eventual aparecimento de sequelas irreversíveis.

Is facility based neonatal care in low resource setting keeping pace? A glance at Uganda’s National Referral Hospital.

Objectives: To identify reasons for neonatal admission and death with the aim of determining areas needing improvement. Method: A retrospective chart review was conducted on records for neonates admitted to Mulago National Referral Hospital Special Care Baby Unit (SCBU) from 1st November 2013 to 31st January 2014. Final diagnosis was generated after analyzing sequence of clinical course by 2 paediatricians. Results: A total of 1192 neonates were admitted. Majority 83.3% were in-born. Main reasons for admissions were prematurity (37.7%) and low APGAR (27.9%).Overall mortality was 22.1% (Out-born 33.6%; in born 19.8%). Half (52%) of these deaths occurred in the first 24 hours of admission. Major contributors to mortality were prematurity with hypothermia and respiratory distress (33.7%) followed by birth asphyxia with HIE grade III (24.6%) and presumed sepsis (8.7%). Majority of stable at risk neonates 318/330 (i.e. low APGAR or prematurity without comorbidity) survived. Factors independently associated with death included gestational age <30 weeks (p 0.002), birth weight <1500g (p 0.007) and a 5 minute APGAR score of < 7 (p 0.001). Neither place of birth nor delayed and after hour admissions were independently associated with mortality. Conclusion and recommendations: Mortality rate in SCBU is high. Prematurity and its complications were major contributors to mortality. The management of hypothermia and respiratory distress needs scaling up. A step down unit for monitoring stable at risk neonates is needed in order to decongest SCBU.

Sequestro pulmonar : trabalho de revisão

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Risk of Wheezing Attacks in Infants With Transient Tachypnea Newborns

Background: The most common reason of respiratory distress in the newborn is transient tachypnea of the newborn (TTN). There are some reports saying that TTN is associated with increased frequencies of wheezing attacks. Objectives: The aims of this study were to determine the risk factors associated with TTN and to determine the association between TTN and the development of wheezing syndromes in early life. Materials and Methods: In a historical cohort study, we recorded the characteristics of 70 infants born at the Shohadaye Kargar Hospital in Yazd between March 2005 and March 2009 and who were hospitalized because of TTN in the neonatal intensive-care unit. We called their parents at least four years after the infants were discharged from the hospital and asked about any wheezing attacks. Seventy other infants with no health problems during the newborn period were included in the study as the control group. Results: The rate of wheezing attacks in newborns with TTN was more than patients with no TTN diagnosis (P = 0.014). TTN was found to be an independent risk factor for later wheezing attacks (relative risk [RR] = 2.8). Conclusions: The most obvious finding of this study was that TTN was an independent risk factor for wheezing attacks. So long-term medical care is suggested for these patients who may be at risk, because TTN may not be as transient as has been previously thought.

Reduced transcription of TCOF1 in adult cells of Treacher Collins syndrome patients

Background: Treacher Collins syndrome (TCS) is an autosomal dominant craniofacial disorder caused by frameshift deletions or duplications in the TCOF1 gene. These mutations cause premature termination codons, which are predicted to lead to mRNA degradation by nonsense mediated mRNA decay (NMD). Haploinsufficiency of the gene product (treacle) during embryonic development is the proposed molecular mechanism underlying TCS. However, it is still unknown if TCOF1 expression levels are decreased in postembryonic human cells. Methods: We have estimated TCOF1 transcript levels through real time PCR in mRNA obtained from leucocytes and mesenchymal cells of TCS patients (n = 23) and controls (n = 18). Mutational screening and analysis of NMD were performed by direct sequencing of gDNA and cDNA, respectively. Results: All the 23 patients had typical clinical features of the syndrome and pathogenic mutations were detected in 19 of them. We demonstrated that the expression level of TCOF1 is 18-31% lower in patients than in controls (p < 0.05), even if we exclude the patients in whom we did not detect the pathogenic mutation. We also observed that the mutant allele is usually less abundant than the wild type one in mesenchymal cells. Conclusions: This is the first study to report decreased expression levels of TCOF1 in TCS adult human cells, but it is still unknown if this finding is associated to any phenotype in adulthood. In addition, as we demonstrated that alleles harboring the pathogenic mutations have lower expression, we herein corroborate the current hypothesis of NMD of the mutant transcript as the explanation for diminished levels of TCOF1 expression. Further, considering that TCOF1 deficiency in adult cells could be associated to pathologic clinical findings, it will be important to verify if TCS patients have an impairment in adult stem cell properties, as this can reduce the efficiency of plastic surgery results during rehabilitation of these patients.

Serum Vitamins in Adult Patients With Short Bowel Syndrome Receiving Intermittent Parenteral Nutrition

Background: Short bowel syndrome (SBS) occurs after massive intestinal resection, and parenteral nutrition (PN) therapy may be necessary even after a period of adaptation. The purpose of this study was to determine the vitamin status in adults with SBS receiving intermittent PN. Methods: The study was conducted on hospitalized adults with SBS who were receiving intermittent PN therapy (n = 8). Nine healthy volunteers, paired by age and sex, served as controls. Food ingestion, anthropometry, plasma folic acid, and vitamins B(12), C, A, D, E, and K were evaluated. Results: The levels of vitamins A, D, and B(12) in both groups were similar. SBS patients presented higher values of folic acid (21.3 +/- 4.4 vs 14.4 +/- 5.2, P = .01) and lower values of vitamin C (0.9 +/- 0.4 vs 1.2 +/- 0.3 mg/dL, P = .03), alpha-tocopherol (16.3 +/- 3.4 vs 24.1 +/-+/- 2.7 mu mol/L, P < .001), and phylloquinone (0.6 +/- 0.2 vs 1.0 +/- 0.5 nmol/L, P < .03). Eight-seven percent of patients had vitamin D deficiency, and all patients presented with serum vitamin E levels below reference values. Conclusions: Despite all efforts to offer all the nutrients mentioned above, SBS patients had lower serum levels of vitamins C, E, and K, similar to those observed in patients on home PN. These findings suggest that the administered vitamins were not sufficient for the intermittent PN scheme and that individual adjustments are needed depending on the patient`s vitamin status. (JPEN J Parenter Enteral Nutr. 2011;35:493-498)

Role of China in the quest to define and control severe acute respiratory syndrome

China holds the key to solving many questions crucial to global control of severe acute respiratory syndrome (SARS). The disease appears to have originated in Guangdong Province, and the causative agent, SARS coronavirus, is likely to have originated from an animal host, perhaps sold in public markets. Epidemiologic findings, integral to defining an animal-human linkage, may be confirmed by laboratory studies; once animal host(s) are confirmed, interventions may be needed to prevent further animal-to-human transmission. Community seroprevalence studies may help determine the basis for the decline in disease incidence in Guangdong Province after February 2002. China will also be able to contribute key data about how the causative agent is transmitted and how it is evolving, as well as identifying pivotal factors influencing disease outcome.