[Aspirin hypersensitivity: characteristics and diagnostic approach]. / Intolérance à l'aspirine : caractéristiques et éléments diagnostiques.

INTRODUCTION: In routine medical practice, the diagnosis of aspirin hypersensitivity (AH) remains difficult. No clinical feature or biomarker is available to reliably confirm this diagnosis and oral provocation tests (OPT) are rarely performed. AIM: To compare asthmatics with and without AH. METHOD: The clinical characteristics of 21 asthmatics with and 24 without AH respectively were determined. AH was defined by a positive OPT. A full blood count was done before and 24 hours after the OPT. RESULTS: The medical history was associated with a weak sensitivity (52%) and a good specificity (96%) for assessing the diagnosis of AH. There was a higher prevalence of AH in women, and a higher frequency of allergic rhinitis in AH, but no characteristic was useful to facilitate the diagnosis of AH in asthmatic patients. Our results demonstrate higher values of platelets in AH patients. Following OPT, in AH patients only, a decrease in blood eosinophils and an increase in neutrophils was observed. CONCLUSIONS: These results confirm that the diagnosis of AH is challenging, with the history having only weak sensitivity. The observation that fluctuations in eosinophils and neutrophils occur following OPT in AH patients only warrants further investigations and suggests a rapid pro-inflammatory role for aspirin.

Histology of solid lateral cervical masses biopsied in children.

INTRODUCTION: Solid cervical lateral neck masses in children may require surgical biopsy to confirm appropriate diagnostic and begin a directed therapeutic treatment. We aimed to describe the contribution of pathological results and compare them with the clinical diagnosis and the paraclinical tools. METHODS: A retrospective review of surgical biopsies for solid lateral neck masses in children over a ten year period in a pediatric tertiary center was conducted. Demographic, imaging, laboratory analysis, surgical and pathological data were collected and analyzed using descriptive statistics with SPSS 17.0. RESULTS: 44 biopsies were done between 2002 and 2012. Inflammatory masses were found in 26/44 biopsies with half of them (13/26) being nontuberculous mycobacterial (NTM) lymphadenitis. Non-inflammatory/benign masses represented 9/44 biopsies and 5/44 masses were of malignant etiology. Malignant masses imaging had a sensitivity and specificity of 33% and 75%, respectively, for ultrasound, whereas Neck CT scan had 33% and 77%, respectively. The contribution of pathological results to the clinical management was questionable in 39% (17/44) of biopsies. CONCLUSION: Inflammatory masses with NTM lymphadenitis were the most common diagnosis. Imaging was not helpful in establishing the diagnosis. Heterogeneity in the management of solid lateral neck masses between clinicians was important and indicates the need for guideline approach.

Espectrofotometria derivada: uma contribuição prática para o desenvolvimento de métodos / A contribution to the derivative spectrophotometry method

A espectrofotometria derivada (ED) tem sido utilizada como uma importante ferramenta no controle de qualidade de medicamentos para a determinação simultânea de fármacos em sistemas multicomponentes. Esta técnica oferece uma alternativa para melhorar a sensibilidade e a seletividade na análise de misturas e está acessível à maioria dos laboratórios. O procedimento é simples, rápido e não necessita extração prévia da amostra. Este trabalho tem como objetivo fornecer subsídios para o desenvolvimento de método por espectrofotometria derivada, utilizando a técnica do ponto de anulação, visando utilizá-la como um método alternativo no controle de qualidade de fármacos associados e, em especial, nos estudos de dissolução. Muitos subsídios foram retirados da literatura, outros de experiências vivenciadas no laboratório durante o desenvolvimento do método por ED aplicado na análise de dois inibidores da protease do vírus da imunodeficiência humana. Várias ordens de derivadas, diferentes valores de lambda delta e diferentes velocidades de varredura foram avaliados.

Derivative spectrophotometry has been successfully used as a quality control tool in pharmaceutical analysis for the simultaneous determination of drugs in multicomponent formulations. This technique, accessible to most laboratories, offers an alternative means of enhancing the sensitivity and specificity in mixture analysis. The procedure is simple, rapid and does not require any preliminary separations or treatment of the samples. The aim of this study is to provide pointers for the development of methods of analysis by derivative spectrophotometry (DS), using the zerocrossing technique, and to encourage professionals and researchers to use DS as an alternative method for quality control of drug combinations, especially in the study of dissolution. Much information, extracted from the literature, has been assembled here, together with the laboratory experience gained while developing a DS method to analyze a combination of two human immunodeficiency virus protease inhibitors. Various orders of derivatives, values of delta lambda and scan speeds were tested.

MR findings of the brain in children and adolescents with portal hypertension and the relationship with blood manganese levels.

BACKGROUND: Few studies have evaluated abnormalities on brain magnetic resonance imaging (MRI) in children and adolescents with chronic liver disease. AIMS: The aim of this study was to investigate the presence of T1 hyperintensity in the basal ganglia of pediatric patients with portal hypertension and its association with blood manganese levels. METHODS: A case control study of 22 patients with portal hypertension (14 Child-Pugh A cirrhosis, 8 non-cirrhotic portal hypertension) and 15 controls was conducted from 2006 to 2007. Blood manganese levels were measured using atomic absorption spectrophotometry. Brain MRI scans were performed using a 1.5 Tesla (Philips) scanner. RESULTS: Blood manganese levels were 26.01+/-12.82 microg/L for patients with portal hypertension (cirrhotic: 22.73+/-11.67 microg/L, non-cirrhotic: 32+/-13.32 microg/L) and 15.64+/-6.61 microg/L for controls (p=0.003). 14/22 patients with portal hypertension presented T1 hyperintensity in the basal ganglia [6/14 cirrhotic; 8/8 non-cirrhotic (p=0.018); zero controls (p=0.001)]. Mean blood manganese levels of patients with liver disease and normal vs. abnormal brain MRI scans were 18.45+/-8.38 microg/L and 30.47+/-13.07 microg/L, respectively (p=0.04). CONCLUSIONS: Brain MRI showed a high frequency (64%) of T1 hyperintensity in the basal ganglia of patients with portal hypertension, which correlated positively with blood manganese levels. This abnormality was found in 100% of the patients with portal hypertension and in 43% of those with mild cirrhotic disease.

Diffusion-weighted MR imaging for evaluation of pediatric recurrent cholesteatomas.

OBJECTIVE: To compare the efficiency of diffusion-weighted MR imaging (MRI) vs. high resolution CT in predicting recurrent or residual cholesteatoma in children who underwent prior middle ear surgery. DESIGN: Prospective study. SETTING: Tertiary care university hospital. PATIENTS: Seventeen patients (4 with 2 recurrences) aged 5-17 years (mean 11.4) previously surgically treated for a cholesteatoma of the middle ear, were included for follow-up with systematic CT scan and MRI, between 2005 and 2007. METHODOLOGY: CT scan was performed on a Siemens Somaton 64 (0.5/0.2 mm slices reformatted in 0.5/0.3 mm images), parallel and perpendicular to the lateral semi-circular canal for each ear (100 mmx100 mm FOV). MRI was undertaken on a Siemens Avanto 1.5 T unit, with an adapted protocol for young children. Diagnosis of recurrent cholesteatoma was based on the evidence of a hyperintense image at B1000 on diffusion-weighted images. Results of CT scan and MRI were compared with operative diagnosis. RESULTS: Nine patients had a positive MRI, among which 8 had cholesteatoma confirmed during revision surgery. In the 12 negative MRI cases, 5 were positive on revision surgery. None of these lesions was over 3mm. Two of them were diagnosed on the CT scan. CT scan alone had a positive predictive value of 75%, and a negative predictive value of 58%. CONCLUSION: Diffusion-weighted MRI is associated with a high positive predictive value for the detection of recurrent cholesteatoma. CT scan remains the first choice imaging technique. In case of doubtful CT scan, diffusion-weighted MRI could confirm a recurrence or, when negative, avoid second-look surgery.

[Evaluation of 3D imaging software to study computed tomography images of middle ear defects]. / Evaluation d'un logiciel de reconstruction 3D à l'étude TDM des malformations de l'oreille moyenne.

OBJECTIVE: Evaluate the contribution of original 3D reconstruction software based on the principle of region growing segmentation of CT images to diagnosis of ossicular malformations of the middle ear. METHOD: Prospective study on a population of ten patients presenting uni- or bilateral transmission deafness. Twenty ears were studied using multislice CT. All the data were treated using original software segmentation based on the principle of region growing segmentation. The 3D images were compared with the original CT slices to judge the software's potential contribution to the management of these patients. RESULTS: All the images obtained were deemed of sufficient diagnostic quality. The two normal ears on the CT slices were also found to be normal on the 3D images. Typical CT images of otospongiosis found in two patients were not visible on the 3D images. The 18 ossicular malformations were well analyzed on the images obtained, which also provided better visualization of the abnormalities and associated lesions (particularly the anomalies in facial nerve position), thus providing quality surgical planning as judged by the surgeon. CONCLUSION: The image reconstruction method studied, using region growing segmentation seems to be, in this limited sample, a useful complement to classical CT images in the study of constitutional abnormalities of the middle ear.

[Endoscopy versus microsurgery: results in a consecutive series of nonfunctioning pituitary adenomas]. / Résultats comparés de la chirurgie endoscopique et de la microchirurgie dans une série consécutive de macroadénomes hypophysaires non fonctionnels.

Microsurgical removal of nonfunctioning pituitary adenomas (NFPAs) is often subtotal. Removing the blind spots as viewed through the microscope, endoscopic surgery may improve the quality of removal. Our purpose was to compare the results of the two techniques in a series of NFPA patients operated on by a single surgeon. Thirty-six patients with newly diagnosed NFPAs were operated on using a purely endoscopic procedure and 29 with a microsurgical technique. All patients were explored pre- and postoperatively (at 3 and 6 months and then every 12 months) by endocrine assays, ophthalmologic exam, and 3D MRI. The endocrine and ophthalmologic results as well as the quality of resection and the complications from the two techniques were compared. The follow-up duration and the mean tumor volume (higher in the microsurgical group) were the only differences observed between the two groups. Tumor height and the invasion of the cavernous sinus were not different. All patients with preoperative visual impairment in the endoscopic group improved, whereas in the microsurgical group 90.9% improved, 4.5% were stabilized, and 4.5% worsened (p=ns). Regarding anterior pituitary functions, 42.8% of the patients improved in the endoscopic group, 45.7% remained stable, and 11.4% worsened compared to, respectively, 31, 44,8, and 24.1% in the microsurgical group (p=ns). Gross total removal was achieved in 86.1% for the endoscopic group and in only 65.5% for the microsurgical group (p=0.075). Morbidity was similar in the two groups. This retrospective series showed that endoscopic surgery compared to microsurgery increases the quality of NFPA removal with similar morbidity.

Contribution of CT-assisted navigation and microdebriders to endoscopic sinus surgery in cystic fibrosis.

OBJECTIVE: To demonstrate the interest of CT-assisted navigation and the microdebrider in rhino-sinus surgery for cystic fibrosis. METHODS: A retrospective study included 20 patients with cystic fibrosis who had undergone endoscopic sinus surgery using CT-assisted navigation and microdebrider between 1998 and 2006. RESULTS: Surgery was indicated for the following symptoms resistant to medical management: incapacitating nasal obstruction (n=18, 90%) and headache or periorbital pain (n=14, 70%). At 3 years follow-up, six patients (30%) were symptom-free, six (30%) had required re-operation, and symptoms were well controlled by medication in the other eight (40%). Mean initial bilateral surgery time was 61 min. There were no complications. CONCLUSION: The advent of microdebriders and CT-based navigation has improved endoscopic sinus surgery in cystic fibrosis. It has permitted the control of medication-resistant symptoms, especially nasal obstruction and pain. Precision is satisfactory, with reduced surgery time. No major complications have been observed. Two- or three-step surgery is possible where endoscopic anatomic landmarks have suffered alteration. The resultant control of symptoms encourages extending indications, with repeat procedures, in view of improving patients' quality of life. Further assessment on a larger series will be needed.

Balance in healthy individuals assessed with Equitest: maturation and normative data for children and young adults.

OBJECTIVE: The purpose of the present prospective study was to obtain normative data for Equitest computerized dynamic posturography (CDP) in children and young adults and to observe the balance maturation process. METHODS: Equilibrium pattern and SOT of 195 healthy children aged from 6 to 14 years were compared to those of 64 young adults aged 20 years, using Equitest. RESULTS: The mean stability scores for children progressively improve with age and are significantly lower than those of young adults. Furthermore, sensory organization scores were lower in children compared to young adults, whereas visual preference scores were similar for the whole studied groups. CONCLUSIONS: According to previous literature, it may be stressed that due to a presumed incomplete development of vestibular system and central nervous system integration, children unlike young adults have lower equilibrium scores, especially when visual information was not available or was incorrect. Our results confirm previous ones obtained in children and young adults with Equitest CDP. This study also provides Equitest data for these age groups, which complete those that have been previously reported.

Vestibular assessment with Balance Quest Normative data for children and young adults.

OBJECTIVE: The purpose of the present study was to compare equilibrium pattern in 12-year-old children with 20-year-old young adults and to obtain normative data for the BQ in both groups. METHODS: Mean stability percentages and synthesis ratios of 29 healthy children aged 12 years were compared to those of 68 young adults aged 20 years, using BQ. RESULTS: The mean stability percentages for children were significantly lower than for young adults. Vestibular ratios were lower in children compared to young adults, whereas somesthesic ratios were similar for the two groups. Visual dependence was significant higher in children. CONCLUSIONS: Children unlike young adults had lower stability percentages when visual information was not available or was incorrect. Ratio synthesis pattern was different in the two groups. Our results on BQ partially confirms previous results obtained in children assessed with Equitest CDP. This study also provides BQ normative data for these two age groups.

Tracheotomy in children: evolution in indications.

OBJECTIVES: To evaluate the evolution of indications for tracheostomy in children. METHODS: A retrospective review of 46 children undergoing tracheostomy between 1996 and 2001. RESULTS: The indications for tracheostomy were classified in two groups:(1) prolonged ventilator dependence (57%), (2) upper airway obstructions (43%). The average age of the tracheostomy was 3 years and 8 months. This was higher in the first group (5.5 years). Decannulation was accomplished in 52%. The indications for tracheostomy were evaluated and were found to decrease in frequency for upper airway obstructions. An increasing indication was for chronic disorders requiring prolonged ventilator dependence. Complications occurred in 50% of children. Overall mortality was 13-2.7% directly related to the tracheostomy. CONCLUSIONS: Evolving indication has been ventilator dependence. Upper airway obstruction as an indication has diminished in frequency, especially with the concomitant progress of endoscopic techniques.

Long-term renal and hearing toxicity of carboplatin in infants treated for localized and unresectable neuroblastoma: results of the SFOP NBL90 study.

BACKGROUND: A secondary end point of the NBL90 protocol (Rubie H et al. Pediatr Oncol 2001;36:247-250) was the concern in this infant population for possible carboplatin-(CBDCA) induced late side effects including impaired renal and hearing functions. PROCEDURE: Glomerular filtration rate (GFR), tubular function (TF), pure tone audiometry (PTA), high-frequency, and transient evoked-otoacoustic emission were prospectively assessed in 30 children alive and disease-free 6 years after the end of the treatment. RESULTS: Median age at diagnosis and at assessment was 4.7 months and 7 years, respectively. Blood pressure was < or =97.5 centile in all children. The mean estimated GFR was 114 +/- 13 ml/min/1.73 m(2) by Schwartz formula [range 87-145]. TF assessment failed to demonstrate any impairment. 29/30 children had grade 0 ototoxicity and all transient evoked otoacoustic emission were normal. CONCLUSIONS: With a 6-year follow-up the combination of VP16 and carboplatin given at conventional doses is safe on renal and hearing functions in infants with unresectable neuroblastomas treated according to SFOP NB90.

Mebendazol: identificaçào das formas polimórficas em diferentes matérias-primas e medicamentos (referência e genéricos) disponíveis no mercado nacional / Mebendazole: identification of polymorphs of the drug in several different bulk substance and dosage forms (reference brand and generic) avaiable in Brazil

A presença de polimorfos diferentes em uma formulação pode comprometer a dissolução de um fármaco a partir de sua forma farmacêutica, uma vez que os polimorfos freqüentemente apresentam diferentes solubilidades.No entanto, as monografias farmacopéicas não apresentam, normalmente, ensaios para a identificação das possíveis formas polimórficas de um mesmo fármaco.O mebendazol possui três formas polimórficas diferentes, conhecidas como formas A, B e C, que apresentam diferentes propriedades físico-químicas e biofarmacêuticas.Estas formas apresentam, inclusive, diferentes comportamentos in vivo, sendo o polimorfo C o recomendado para formas farmacêuticas sólidas de uso oral.No presente trabalho utiliza-se a espectroscopia de infravermelho e o perfil de dissolução in vitro para caracterizar matérias-primas e comprimidos (referência e genéricos) existentes no mercado brasileiro.O perfil de dissolução para três medicamentos que apresentavam as formas polimórficas A, B e C, foi obtido utilizando-se método da Farmacopéia Americana modificado, uma vez que o meio de dissolução farmacopéico não possibilita a distinção entre as formas polimórficas do mebendazol, devido à adição de lauril sulfato de sódio ao meio.Os resultados obtidos demonstram que as três formas polimórficas do mebendazol estão presentes nos medicamentos e duas delas em matérias-primas, sugerindo que um maior controle deveria ser utilizado para a seleção de matérias-primas que apresentam polimorfismo, assegurando, através de testes simples e rápidos, a qualidade de medicamentos genéricos.

[Anti-viral injectable treatment (cidofovir) in laryngeal papillomatosis]. / Apport du traitement anti-viral injectable (Cidofovir) dans le traitement de la papillomatose laryngée.

Laryngeal papillomatosis, due to type 6 and 11 papova-virus A, causes devastating lesions leading to difficult clinical situations (severe dysphonia, or laryngeal dyspnea). Recurrence requires repeated endoscopy with CO2 laser treatment to keep the airways free and prevent the lesions spreading. In patients presenting aggressive papillomatosis, such repeated intervention causes irreversible lesions which have a very negative impact on the vocal prognosis. In this context, developing a form of minimally invasive surgery would help avoid vocal sequelae as far as possible. Thus, anti-viral agents can be injected directly into the lesion per-operatively so as best to preserve the healthy mucosa and muscles, thereby managing the lesions with precision and less iatrogenic impact than with CO2 laser. Twenty six patients since 1998 have undergone Cidofovir endoscopy. Total remission was achieved in eight of them (31%), after between two and eight interventions. Twenty seven (65%) showed clinically significant partial remission. Such positive results were obtained in both adults and children. Associated lesion excision was required in cases of obstructive or persistent papilloma. Intralesion Cidofovir injection thus seems to have proved highly effective in the clinical management of laryngeal papillomatosis. Combined Cidovir injection and surgical excision remains necessary in case of large or persistent papillomas. These results have lead us to indicate this procedure as primary treatment for laryngeal papillomatosis in adults and children.

Viral RNA in middle ear mucosa and exudates in patients with chronic otitis media with effusion.

OBJECTIVE: To evaluate viral and cytokine signaling correlates of the persistent inflammation associated with chronic otitis media with effusion (OME). DESIGN: Prospective study. METHOD: Reverse transcriptase-polymerase chain reaction targeting RNA viruses frequently associated with OME (respiratory syncytial virus and parainfluenza virus type 3, the proinflammatory cytokines interleukin 8 and interleukin 1beta, and RANTES [regulated upon activation, normal T cell expressed and secreted]) was performed on mucosal biopsy samples and on samples of the liquid and cellular compartments of inflammatory exudates obtained from 26 children (49 ears) with infected middle ears. Ribonucleic acid extracted from rapidly frozen samples was reverse transcribed by Moloney murine leukemia virus reverse transcriptase and amplified for 35 cycles using previously validated primers. Amplicons were evaluated by molecular size after agarose gel electrophoresis with ethidium bromide. RESULTS: Most children had evidence of the presence of an RNA virus in at least one specimen. Respiratory syncytial virus was present in 40% and parainfluenza virus type 3 in 8% of effusions. Interleukin 8 messenger RNA was present in 21% of inflammatory exudates but never in cells from the mucosal biopsy samples. CONCLUSIONS: Our data support a viral contribution to the cause of OME and suggest that the inflammatory cytokines observed derive more from cells in the inflammatory exudate than from those in the middle ear mucosa.

Assay of fluoxetine hydrochloride by titrimetric and HPLC methods.

Two alternative methods were proposed to assay Fluoxetine Hydrochloride: a titrimetric method and another by HPLC using as mobile phase water pH 3.5: acetonitrile (65:35). These methods were applied to the determination of Fluoxetine as such or in formulations (capsules). The titrimetric method is an alternative for pharmacies and small industries. Both methods showed accuracy and precision and are an alternative to the official methods.

Management of subglottic haemangioma.

Two contrasting methods of treatment for paediatric subglottic haemangioma are presented. Dr Hoeve describes his results using intralesional steroids and short-term intubation, and Dr Froehlich discusses his outcomes with open surgical excision. Mr Bailey then reviews the currently available therapeutic options with special reference to each of the above techniques, and suggests an optimum plan of management given our current state of knowledge. The conclusion is that very small haemangiomas may not require treatment, or may be amenable to CO2 laser vaporization. Medium-sized lesions seem suitable for intra-lesional steroids and intubation, but large ones are probably best managed by primary submucous resection. Very large haemangiomas, and especially those which are circumferential or in which magnetic resonance imaging (MRI) shows extension down into the trachea and/or through the tracheal wall into the surrounding tissues, may be more safely dealt with by performing a tracheostomy and awaiting spontaneous involution.

A selective HPLC/RIA for the determination of budesonide.

A combined HPLC/RIA procedure is described for the selective determination of budesonide (BUD) in plasma. The assay involves the extraction of plasma or serum samples with ethylacetate, consequent HPLC separation of intact budesonide from cross-reacting metabolites on a C8 reversed phase column, collection of the budesonide containing fraction and determination of budesonide immunoreactivity with the budesonide antiserum. The method was accurate, sensitive (IC50 value of 0.9 ng ml-1) and reproducible (intra- and inter-day less than 15%) with a limit of quantification of 0.133 ng ml-1 (RSD < 25%). The evaluation of a limited number of clinical samples after oral administration of budesonide by both the HPLC/RIA procedure and a direct RIA using the same antiserum differed in average by a factor of 2, with the ratio of HPLC/RIA-RIA results declining as a function of time. Thus, this ratio might be a suitable indicator for probing for the ratio of budesonide and overall metabolites on a semi-quantitative level.

[Chronic rhinosinusitis in children: evolution of concepts]. / Rhinosinusite chronique de l'enfant: évolution des concepts.

The concept of chronic rhinosinusitis in children has been recently individualized. The diagnosis is based upon the clinical history. It may be part of a diffuse inflammatory disease of the respiratory tract. Allergic and environmental polluting factors are possibly involved and must be looked for. Drainage of the rhinopharynx and local steroids are usually the first line treatment. In case of failure, a CT-scan of the sinuses should be performed looking for an obstructive anomaly of the sinuses requiring functional endoscopic sinus surgery.