Novel Cyclic Biphalin Analogue with Improved Antinociceptive Properties

d-Ala residues in position 2,2′ of biphalin with two residues of d-penicillamine or l-penicillamine and by forming a disulfide bond between the thiol groups. The so-obtained compound 9 containing d-penicillamines showed excellent μ/δ mixed receptor affinities (K_i^δ = 5.2 nM; K_i^μ = 1.9 nM), together with an efficacious capacity to trigger the second messenger and a very good in vivo antinociceptive activity, whereas product 10 was scarcely active. An explanation of the two different pharmacological behaviors of products 9 and 10 was found by studying their conformational properties.     

Persistence of the right venous sinus valve simulating a right atrial myxoma in a case of total anomalous pulmonary venous return. Echocardiographic, anatomo-clinical and surgical aspects

A case of persistence of the right venous sinus valve that on echocardiographic examination simulated right atrial myxoma is reported in a patient with total abnormal pulmonary venous return in the coronary sinus. Echocardiography showed a mobile, pedunculated mass present in systole in the right atrium that shifted to diastole in the right ventricle, highly suggestive of right atrial myxoma. The right ventricle also showed a volume overload and a space without echoes behind the left atrium. A membrane was encountered in the right atrium at surgery. This was removed and the venous return corrected.     

Magnetic resonance imaging is an accurate and reliable method to evaluate non-cystic fibrosis paediatric lung disease

Background and objective: Chest MRI is increasingly used to assess pulmonary diseases, but its utility compared with high‐resolution computed tomography (HRCT) has never been evaluated in children using specific performance outcomes. The aim of this study was to assess the accuracy and reliability of MRI compared with HRCT in children with non‐cystic fibrosis (CF) chronic lung disease. Methods: Fifty subjects aged 5.9–20 years, with primary ciliary dyskinesia (n = 17), primary immunodeficiency (n = 17) or recurrent pneumonia (n = 16), underwent chest HRCT and MRI. The prevalence of lung abnormalities on HRCT was evaluated, and sensitivity, specificity, accuracy and positive and negative likelihood ratios for MRI versus HRCT were calculated. MRI and HRCT scans were also assessed using a modified Helbich score. Results: Bronchiectasis, mucous plugging, peribronchial wall thickening, consolidation, bullae, abscesses and emphysema were detected by HRCT in 72, 68, 66, 60, 10, 8 and 8% of subjects, respectively. Sensitivity, specificity, accuracy and positive and negative likelihood ratios for MRI were good or excellent for most of the changes that were assessed. Median total Helbich scores for HRCT and MRI were 10 (range 0–20) and 10 (range 0–18), respectively. There was good‐to‐excellent agreement between the two techniques for all scores (r ≥ 0.8). A Bland–Altman plot confirmed this agreement between total scores (bias value: 0.2 ± 1.18; 95% limits of agreement of mean difference: ?2.12–2.52). Conclusions: Chest MRI was equivalent to HRCT to determine the extent of lung disease in children with non‐CF lung disease. The findings support the use of chest MRI as an alternative to HRCT in diagnostic pathways for paediatric chronic lung disorders.     

Routine clinical application of the FRAXA Pfu PCR assay: limits and utility

Fragile X genotype is characterized by the excessive amplification of an unstable region of DNA: a trinucleotide repeat CGG of variable copy number present in the FRAXA locus. Methods based on polymerase chain reaction (PCR) amplification of the CGG repeat region could facilitate the development of a rapid screening assay. Unfortunately, amplification across CGG repeats can be inefficient and unreliable due to their 100% G+C base composition. The utility of the exonuclease-deficient Pfu polymerase for amplification and detection of the CGG repeats at the FRAXA locus has been reported. In the present study we analysed the utility of a Pfu PCR assay as a rapid initial screening method to rule out a diagnosis of fragile X syndrome in males with mental retardation. Affected males did not show any amplification products or a smear of amplification products between 350 and 550 bp. Only 10% of affected male samples did not show any amplification products, while the vast majority showed the amplification smear. The amplification smears represent a serious drawback of the method, since they cannot be distinguished from the amplification products of normal samples after separation in 1 % agarose gel. Several modifications of the PCR conditions were attempted to eliminate this problem, but none was appropriate for clinical applications. However, the problem was easily solved by using a higher resolution electro-phoretic system that allows a clear distinction of normal bands from pathological smears. We tested the specificity of the Pfu PCR assay, followed by an improved MetaPhor gel electrophoretic separation of PCR products, on 50 samples from normal males and 24 samples from affected males. The results showed that this method is a rapid, sensitive and specific assay for the exclusion of fragile X syndrome diagnosis in mentally retarded males.