Clinical and Molecular diagnosis of the skeletal dysplasias associated with mutations in the gene encoding Fibroblast Growth Factor Receptor 3 (FGFR3) in Portugal

Mutations in the gene that encodes Fibroblast Growth Factor Receptor 3 ( FGFR3 ) are associated with Achondroplasia (MIM 100800), Hypochondroplasia (MIM 146000), Muenke Syndrome (MIM 602849), Thanatophoric Dysplasia (MIM 187600, MIM 187601) and Lacrimo-Auriculo-Dento-Digital Syndrome (MIM 149730).Here we report a clinical and molecular study in a large cohort of 125 Portuguese patients with these skeletal disorders. The identification of the P250R mutation allowed the confirmation of the Muenke Syndrome in 9 out of the 52 cases referred. Two known mutations were found in the Thanatophoric Dysplasia referred cases. No mutations were identified in the LADD syndrome patient. In Achondroplasia and Hypochondroplasia, genetic heterogeneity was present amongst the 70 clinically diagnosed patients with 5 different mutations identified. As in other studies, complex phenotypic heterogeneity amongst patients carrying the same gene defect was observed. In several cases, the new amino acids encoded, as a consequence of mutations, were related to the severity of patients' phenotype. The presence of 10 misdiagnosed cases emphasizes the importance of performing mutation analysis of the hotspot regions responsible for both dysplasias (Ach and Hch). For patients with an unquestionable clinical diagnosis, lacking the most common mutations, a complete screening of FGFR3 is necessary.     

Treatment of Zoon's balanitis with imiquimod 5% cream

We report a case of a 43-year-old uncircumcised Caucasian, diabetic man with a 4-year history of Zoon's balanitis unresponsive to topical steroids, in whom control of the disease was achieved with topical imiquimod. A histopathological examination of a biopsy specimen was performed before and after treatment with imiquimod 5% cream applied 3 times a week. A moderate to marked increased local skin reaction occurred several times throughout the treatment period, necessitating multiple rest periods of several days' duration. Clinical but not histological resolution was obtained after 4 months of treatment, with no relapses at an 18-month follow-up. This positive treatment outcome indicates that imiquimod may have a role in the management of Zoon's balanitis. However, the dose and duration of therapy required to achieve complete clinical response still needs to be established. Also, the question of whether normalization of histology can be achieved with topical imiquimod has yet to be answered.     

高场磁共振成像仪安装的经验与教训

本文介绍我院在安装多台磁共振成像仪的过程中所出现的问题,以及所得的经验与教训,对提高预安装的工作质量有一定的帮助。     

Evolutionary evidence of the effect of rare variants on disease etiology

Gorlov IP, Gorlova OY, Frazier ML, Spitz MR, Amos CI. Evolutionary evidence of the effect of rare variants on disease etiology. The common disease/common variant hypothesis has been popular for describing the genetic architecture of common human diseases for several years. According to the originally stated hypothesis, one or a few common genetic variants with a large effect size control the risk of common diseases. A growing body of evidence, however, suggests that rare single‐nucleotide polymorphisms (SNPs), i.e. those with a minor allele frequency of less than 5%, are also an important component of the genetic architecture of common human diseases. In this study, we analyzed the relevance of rare SNPs to the risk of common diseases from an evolutionary perspective and found that rare SNPs are more likely than common SNPs to be functional and tend to have a stronger effect size than do common SNPs. This observation, and the fact that most of the SNPs in the human genome are rare, suggests that rare SNPs are a crucial element of the genetic architecture of common human diseases. We propose that the next generation of genomic studies should focus on analyzing rare SNPs. Further, targeting patients with a family history of the disease, an extreme phenotype, or early disease onset may facilitate the detection of risk‐associated rare SNPs.     

Colite lymphocytaire : apport du pathologiste et interaction entre clinicien et pathologiste

Lymphocytic colitis (LC), a rare entity in microscopic colitis, is an inflammatory disease of the colonic mucosa. The pathologist plays a key role in the positive diagnosis of LC by eliminating a number of differential diagnoses. However, this diagnosis depends on the interaction between the clinician and the pathologist and comparison between histological and clinical findings, which enable correct interpretation. The majority of recent work enhances our knowledge of the histopathogenic, causal and therapeutic factors. However, the debate about the distinction between LC and collagen colitis is still going on, in which the pathologist plays a key role. The diagnosis of microscopic colitis is purely based on the findings of histological examination of systematic colonic biopsies, with a correlation between the clinical manifestations of the patient with chronic diarrhoea and normal endoscopy and the morphology of biopsies of LC lesions. The purpose of our study is to clarify the role and contribution of the pathologist in positive and differential diagnosis of LC and to discuss the interaction between clinicians and pathologists.     

LANSOPRAZOLE PLUS CLARITHROMYCIN: EVALUATION OF A NEW DUAL THERAPY FOR Helicobacter pylori ERADICATION

SUMMARY The aim of this pilot study was to evaluate the efficacy and safety of lansoprazole plus clarithromycin for eradication of Helicobacter pylori. A total of 26 patients with H. pylori infection were randomised to receive clarithromycin, 500 mg t.i.d. for 14 days, plus either lansoprazole, 30 mg o.m., (group L30, n=13) or lansoprazole, 30 mg b.i.d., (group L60, n=13). H. pylori status was determined pre-treatment and four to six weeks after completion of the study medication by histology and ¹³C-urea breath test. Two patients were unable to complete the course of medication. Of the remaining 24 patients, 14 (58%) successfully eradicated H. pylori — 8/12 (67%) patients in group L30 and 6/12 (50%) in group L60. Side-effects were experienced by 17/26 (65%) of patients, most commonly a taste disturbance. The results from this pilot study suggest that dual therapy with lansoprazole plus clarithromycin is only a moderately effective regimen for eradicating H. pylori.