RESUMO
The Meier-Gorlin syndrome (MGS) or ear, patella, short stature syndrome (MIM #224690) is a rare disorder with bilateral microtia, aplasia or hypoplasia of the patellae and severe intra-uterine and post-natal growth retardation. We report the case of a 10-year-old male with MGS diagnosis, his parents were related, he also showed conductive hearing loss and maloclussion and long upper central incisors, more importantly he had asymmetry of the left cerebral hemisphere and ventricular system, his intelligence was normal. As far as we know, these abnormalities have not been previously described in patients with MGS and the present report corresponds to the first Mexican case described so far.
Assuntos
Anormalidades Múltiplas/patologia , Ventrículos Cerebrais/anormalidades , Orelha/anormalidades , Transtornos do Crescimento/patologia , Micrognatismo/patologia , Patela/anormalidades , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/fisiopatologia , Criança , Microtia Congênita , Consanguinidade , Orelha/patologia , Orelha/fisiopatologia , Transtornos do Crescimento/genética , Transtornos do Crescimento/fisiopatologia , Humanos , Masculino , México , Micrognatismo/genética , Micrognatismo/fisiopatologia , Patela/patologia , Patela/fisiopatologiaRESUMO
Accurate diagnosis of malignant pleura mesothelioma (MPM) is challenging. Differential diagnosis of MPM versus lung adenocarcinoma (AD) is particularly difficult, yet clinically important since the two neoplasias call for different treatment approaches. Circulating miRNA-profiling to identify miRNAs that can be used to distinguish MPM from AD has not been reported. We conducted a wide screening study of miRNA profiles in serum pools of MPM patients (N = 11), AD patients (N = 36), and healthy subjects (N = 45) to identify non-invasive biomarkers for differential diagnosis of MPM and AD, using deep sequencing. Sequencing detected up to 300 known miRNAs and up to 25 novel miRNAs species in the serum samples. Among known miRNAs, 7 were upregulated in MPM and 12 were upregulated in AD compared to healthy controls. Of these, eight were distinctive for AD and three were unique for MPM. Direct comparison of the miRNA profiles for MPM and AD revealed differences in miRNA levels that could be useful for differential diagnosis. No differentially expressed novel miRNAs were found. Further bioinformatics analysis indicated that three upregulated miRNAs in MPM are associated with the p38 pathway. There are unique alterations in serum miRNAs in MPM and AD compared to healthy controls, as well as differences between MPM and AD profiles. Differing miRNA levels between MPM and AD may be useful for differential diagnosis. A potential association to p38 pathway of three upregulated miRNAs in MPM was revealed.
RESUMO
OBJECTIVE: To evaluate the effect of all-trans retinoic acid (ATRA) as treatment for chemotherapy-induced peripheral neuropathy in an experimental animal model and in a randomized, double-blinded, controlled trial in patients with non-small-cell lung cancer (NSCLC). METHODS: Forty male Wistar rats were randomized in 5 groups: group A, control; groups B and C, treated with cisplatin; and groups D and E, treated with paclitaxel. ATRA (20 mg/kg PO) was administered for 15 days in groups C and E. We evaluated neuropathy and nerve regeneration-related morphologic changes in sciatic nerve, the concentration of nerve growth factor (NGF), and retinoic acid receptor (RAR)-α and RAR-ß expression. In addition, 95 patients with NSCLC under chemotherapy treatment were randomized to either ATRA (20 mg/m(2)/d) or placebo. Serum NGF, neurophysiologic tests, and clinical neurotoxicity were assessed. RESULTS: The experimental animals developed neuropathy and axonal degeneration, associated with decreased NGF levels in peripheral nerves. Treatment with ATRA reversed sensorial changes and nerve morphology; this was associated with increased NGF levels and RAR-ß expression. Patients treated with chemotherapy had clinical neuropathy and axonal loss assessed by neurophysiology, which was related to decreased NGF levels. ATRA reduced axonal degeneration demonstrated by nerve conduction velocity and clinical manifestations of neuropathy grades ≥2. CONCLUSIONS: ATRA reduced chemotherapy-induced experimental neuropathy, increased NGF levels, and induced RAR-ß expression in nerve. In patients, reduction of NGF in serum was associated with the severity of neuropathy; ATRA treatment reduced the electrophysiologic alterations. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that ATRA improves nerve conduction in patients with chemotherapy-induced peripheral neuropathy.