Manometria anorretal em crianças com constipação intestinal crônica funcional refratária a tratamento Anorectal manometry in children with chronic functional intestinal constipation refractory to treatment

OBJETIVO: Descrever os resultados da manometria anorretal dos pacientes com constipação intestinal crônica funcional (CICF), refratária aos tratamentos habituais, quanto ao tônus esfincteriano, presença do reflexo inibitório retoanal (RIRA), capacidade de expulsão do balão intrarretal e comportamento durante manobra evacuatória. MÉTODOS: Estudo retrospectivo por meio de análise de prontuários médicos entre janeiro de 2003 e junho de 2007, avaliando-se 31 pacientes ambulatoriais com CICF refratária a tratamentos convencionais por manometria anorretal com cateter de quatro canais (processador MPX 816 e software Proctomaster 5.0, Dynamed). RESULTADOS: Dos 31 pacientes, 24 (77%) eram do sexo masculino. A idade média foi 8,9±2,6 anos. A média de pressão máxima fisiológica do canal anal foi 82±38mmHg. Dos 31 pacientes, 15 (48%) apresentaram esfíncter anal normotônico e 16 (52%), hipertônico. O RIRA esteve presente em todos os casos. A prova de expulsão do balão intrarretal foi positiva em 12/31pacientes, sendo 4/12 com esfíncter normotônico e 8/12 com esfíncter hipertônico (p=0,22). Anismo foi detectado em 6/15 pacientes com esfíncter normotônico (40%) e em 4/16 com esfíncter hipertônico (25%) (p=0,45). CONCLUSÕES: Houve predomínio de esfíncter anal normotônico nos casos de CICF refratária. Pouco mais de 1/3 dos pacientes conseguiram a expulsão do balão durante a prova evacuatória, independentemente da tonicidade do esfíncter anal e cerca de metade dos pacientes apresentavam anismo sem relação com a tonicidade do esfíncter anal. A manometria anorretal é apropriada para o estudo da fisiologia e dinâmica evacuatória e pode ser útil para orientar o tratamento.<br>OBJECTIVE: To evaluate anorectal manometry results in children with chronic functional intestinal constipation refractory to conventional treatment regarding mean anal sphincter resting pressure, presence of recto-anal inhibitory reflex (RAIR), expulsion capability of the intra-rectal balloon and behavior during the defecation maneuver. METHODS: Retrospective study by review of medical records from January 2003 to June 2007 with 31 patients who presented chronic functional constipation refractory to standard treatment. Anorectal manometry was performed by a four-channel catheter (MPX 816 processor and Proctomaster 5.0 software, Dynamed). RESULTS: Among the 31 studied children, 24 (77%) were male. The mean age was 8.9±2.6 years. The mean maximal squeeze pressure of the anal sphincter was 82±38 mmHg. Among the patients, 15 (48%) had normotonic anal sphincter and 16 (52%) hypertonic anal sphincter. RAIR was present in all patients. Intra-rectal balloon expulsion was positive in 12/31 patients, being 4/12 with normotonic sphincter and 8/12 with hypertonic sphincter (p=0.22). Anism was detected in 6/15 patients with normotonic sphincter (40%) and in 4/16 patients with hypertonic sphincter (25%) (p=0.45). CONCLUSIONS: There was a predominance of normotonic anal sphincter in children with refractory chronic functional constipation. More than 1/3 of the patients were able to expulse the balloon during the defecation test, regardless of anal sphincter resting pressure, and about half of them presented anism not related to the anal sphincter tonus. The anorectal manometry is appropriate to study physiology and evacuatory dynamic, and can be useful to guide the treatment

Antibiotics and cure rates in childhood febrile urinary tract infections in clinical trials: a systematic review and meta-analysis

Purpose: Urinary tract infections (UTIs) are common bacterial infections among children. Objective: To systematically review the antimicrobials used for febrile urinary tract infections in pediatric clinical trials and meta-analyze the observed cure rates and reasons for treatment failure. Materials and Methods: We searched Medline, Embase and Cochrane central databases between January 1, 1990, and November 24, 2016, combining MeSH and free-text terms for: “urinary tract infections”, AND “therapeutics”, AND “clinical trials” in children (age range 0–18 years). Two independent reviewers assessed study quality and performed data extraction. The major outcome measures were clinical and microbiological cure rates according to different antibiotics. Results: We identified 2,762 published studies and included 30 clinical trials investigating 3913 cases of pediatric febrile urinary tract infections. Children with no underlying condition were the main population included in the trials (n=2,602; 66.5%). Cephalosporins were the most frequent antibiotics studied in trials (22/30, 73.3%). Only a few antibiotics active against resistant urinary tract infections have been tested in randomised clinical trials, mainly aminoglycosides. The average point cure rate of all investigational drugs was estimated to 95.3% [95% CI 93.5-96.9%]. Among 3,002 patients for whom cure and failure rates were reported, only 3.9% (3.9%; 118/3,002) were considered clinically to have treatment failure, while 135 (4.5%; 135/3,002) had microbiological failure. Conclusions: We observed high treatment cure rates, regardless of the investigational drug chosen, the route of administration, duration and dosing. This suggests that future research should prioritise observational studies and clinical trials on children with multi-drug resistant infections

Identification of Small Molecules with Type I Interferon Inducing Properties by High-Throughput Screening

The continuous emergence of virus that are resistant to current anti-viral drugs, combined with the introduction of new viral pathogens for which no therapeutics are available, creates an urgent need for the development of novel broad spectrum antivirals. Type I interferon (IFN) can, by modulating the cellular expression profile, stimulate a non-specific antiviral state. The antiviral and adjuvant properties of IFN have been extensively demonstrated; however, its clinical application has been so far limited. We have developed a human cell-based assay that monitors IFN-β production for use in a high throughput screen. Using this assay we screened 94,398 small molecules and identified 18 compounds with IFN-inducing properties. Among these, 3 small molecules (C3, E51 and L56) showed activity not only in human but also in murine and canine derived cells. We further characterized C3 and showed that this molecule is capable of stimulating an anti-viral state in human-derived lung epithelial cells. Furthermore, the IFN-induction by C3 is not diminished by the presence of influenza A virus NS1 protein or hepatitis C virus NS3/4A protease, which make this molecule an interesting candidate for the development of a new type of broad-spectrum antiviral. In addition, the IFN-inducing properties of C3 also suggest its potential use as vaccine adjuvant