Novel blended SNRPE-related spliceosomopathy phenotype characterized by microcephaly and congenital atrichia.

Variants in genes encoding core components of the spliceosomes are associated with craniofacial syndromes, collectively called craniofacial spliceosomopathies. SNRPE encodes a core component of pre-mRNA processing U-rich small nuclear ribonuclear proteins (UsnRNPs). Heterozygous variants in SNRPE have been reported in six families with isolated hypotrichosis simplex in addition to one case of isolated non syndromic congenital microcephaly. Here, we report a patient with a novel blended phenotype of microcephaly and congenital atrichia with multiple congenital anomalies due to a de novo intronic SNRPE deletion, c.82-28_82-16del, which results in exon skipping. As discussed within, this phenotype, which we propose be named SNRPE-related syndromic microcephaly and hypotrichosis, overlaps other craniofacial splicesosomopathies.

Cyclins in aspergilli: Phylogenetic and functional analyses of group I cyclins.

We have identified the cyclin domain-containing proteins encoded by the genomes of 17 species of Aspergillus as well as 15 members of other genera of filamentous ascomycetes. Phylogenetic analyses reveal that the cyclins fall into three groups, as in other eukaryotic phyla, and, more significantly, that they are remarkably conserved in these fungi. All 32 species examined, for example, have three group I cyclins, cyclins that are particularly important because they regulate the cell cycle, and these are highly conserved. Within the group I cyclins there are three distinct clades, and each fungus has a single member of each clade. These findings are in marked contrast to the yeasts Saccharomyces cerevisiae, Schizosaccharomyces pombe, and Candida albicans, which have more numerous group I cyclins. These results indicate that findings on cyclin function made with a model Aspergillus species, such as A. nidulans, are likely to apply to other Aspergilli and be informative for a broad range of filamentous ascomycetes. In this regard, we note that the functions of only one Aspergillus group I cyclin have been analysed (NimECyclin B of A. nidulans). We have consequently carried out an analysis of the members of the other two clades using A. nidulans as our model. We have found that one of these cyclins, PucA, is essential, but deletion of PucA in a strain carrying a deletion of CdhA, an activator of the anaphase promoting complex/cyclosome (APC/C), is not lethal. These data, coupled with data from heterokaryon rescue experiments, indicate that PucA is an essential G1/S cyclin that is required for the inactivation of the APC/C-CdhA, which, in turn, allows the initiation of the S phase of the cell cycle. Our data also reveal that PucA has additional, non-essential, roles in the cell cycle in interphase. The A. nidulans member of the third clade (AN2137) has not previously been named or analyzed. We designate this gene clbA. ClbA localizes to kinetochores from mid G2 until just prior to chromosomal condensation. Deletion of clbA does not affect viability. However, by using a regulatable promoter system new to Aspergillus, we have found that expression of a version of ClbA in which the destruction box sequences have been removed is lethal and causes a mitotic arrest and a high frequency of non-disjunction. Thus, although ClbA is not essential, its timely destruction is essential for viability, chromosomal disjunction, and successful completion of mitosis.

Sodium nitroprusside in the treatment of Prinzmetal's variant angina.

A patient had attacks of Prinzmetal's angina, resistant to sublingual nitrates in high doses and to a calcium antagonist. All the crises wee resolved by sodium nitroprusside therapy. This report suggests that nitroprusside merits further evaluation in the treatment of Prinzmetal's angina, particularly in cases resistant to usual therapy in which the evolution towards myocardial infarction is very likely.

Echocardiographic findings in a case of acquired pulmonic stenosis from extrinsic compression by a mediastinal cyst.

A peculiar echocardiographic pattern was recorded in a case of cystic teratoma of the left anterior and upper mediastinum, causing a mild stenosis at the pulmonary valve level. The usefulness of echocardiography in the evaluation of anterior mediastinal masses as they distort normal cardiac anatomy is discussed.

Acute effects of chewable nifedipine on hemodynamic responses to upright exercise in patients with prior myocardial infarction and effort angina.

To evaluate the hemodynamic effects of nifedipine on anginal patients during exercise in the upright position, a placebo (P) and 20 mg of nifedipine were administered in a double-blind random sequence to ten patients presenting with exertional angina and a healed myocardial infarction. All patients had previously undergone coronary angiography. The effects of nifedipine in the upright position at rest, at the anginal threshold, and at the maximal level of exercise were studied. Nifedipine decreased systemic vascular resistances in upright position and increased the cardiac index. It reduced the severity of angina and allowed a higher physical work capacity without anginal symptoms. The most important beneficial effect of nifedipine appears to be the reduction in afterload, but an improvement of left ventricular function cannot be ruled out.

Dilating cardiomyopathy as the expression of Xp21 Becker type muscular dystrophy.

A 35-year-old man with severe progressive dilating cardiomyopathy and no clinical signs of muscle disease underwent muscular investigations because of markedly increased serum creatine kinase. Muscle biopsy demonstrated Becker type muscular dystrophy with dystrophin of low molecular weight. Genetic analysis showed a deletion spanning from exon 45 to exon 46 in the Xp21 region. Xp21 Becker type muscular dystrophy must be considered in the differential diagnosis of dilating cardiomyopathy.

Atrial septal defect in patients over the age of 50.

Clinical, haemodynamic and follow-up data are presented for a group of 49 patients with atrial septal defect who first presented between the ages of 50 and 79. The incidence of supraventricular arrhythmias, pulmonary vascular disease and "heart failure" all increased with increasing age. Those who had the defect closed tended to be the more symptomatic and surgery resulted in symptomatic improvement in almost all. The combined early and late surgical mortality was 6.6%. Surgery appears to be of benefit in symptomatic patients below the age of 70. Above this age our small experience would suggest caution in recommending closure of the defect.

Italian BiodivYsio open registry (BiodivYsio PC-coated stent): study of clinical outcomes of the implant of a PC-coated coronary stent.

UNLABELLED: Rapid technological developments have made new materials available for percutaneous coronary intervention procedures. The coronary stent in particular has undergone progressive structural improvements leading to the recent availability of a third generation of stents, namely, coated stents. The rapid evolution of the stent has often made its evaluation problematical, since trials are frequently confined to small groups of patients in single centers. The purpose of this registry was to verify the safety and efficacy of the BiodivYsio stent (a stent coated with phosphorylcholine polymer) in a broad population of patients who reflect the daily reality of coronary intervention in a cardiac catheterization laboratory. METHODS AND RESULTS: The registry was designed to collect the principal angiographic and clinical data of a consecutive series of Oreal worldO patients. Patients were treated with a BiodivYsio stent (Biocompatibles, Galway, United Kingdom) in 12 centers (11 Italian and 1 Swiss) between January 1998 and January 1999. Procedural, in-hospital, 30-day and six-month follow-up data were collected. The monitoring, data entry and statistical analyses were carried out by an independent center. During the study, 218 patients were enrolled; 165 (76%) male and 53 (24%) female, with an average age of 61.6 +/- 9.4 years (range, 36Eth 84 years). A total of 258 stents were implanted in 233 lesions (1.1 stents per lesion), of which 233 (90%) were the BiodivYsio PC coated stent, the remaining 25 implants were of other stent types. The percutaneous transluminal coronary angioplasty and stenting procedure were carried out in 109 (50%) patients with unstable angina, 65 (30%) with stable angina, 29 (13%) with acute myocardial infarction, and 15 (7%) patients with silent ischemia. Procedural success was achieved in 217/218 (99.5%) patients. Optimal results were achieved in 212 (97.7%) patients. In 34 (15.6%) cases, patients were treated with periprocedural abciximab. During the hospitalization period, one (0.4%) death occurred on day 7 due to subacute occlusion of the stent, and 3 (1.4%) myocardial infarctions were reported. At 30-day follow-up, 211 (97.2%) patients were asymptomatic, as were 189 (87%) patients at clinical follow-up at 6 months. CONCLUSIONS: This study evaluated the safety and efficacy of a third-generation stent. The results demonstrate a high procedural success rate and a low incidence of major adverse cardiac events at short- and medium-term follow-up. It appears that the BiodivYsio stent should be considered safe in clinical and/or anatomical situations with a high risk of complications, confirming the hypothesis that PC may have non-thrombogenic properties. To corroborate these results, an appropriately designed study would be required to measure the stentOs efficacy in the most suitable clinical context, i.e., clinical situations that are at the highest risk of ischemic relapse.

Pulmonary embolism due to compression of the inferior vena cava by a hepatic hemangioma.

We describe a 35-year-old man who had a pulmonary embolism with thrombosis of the inferior vena cava, apparently resulting from compression by a hepatic hemangioma. The diagnosis of pulmonary embolism was confirmed by pulmonary angiography; however, the hemangioma was detected only incidentally, as a hyperechoic mass, during an echocardiogram for intracardiac thrombosis. Abdominal sonography, computed tomography, celiac angiography, technetium 99m-labeled red blood cell scintigraphy, and ultrasound-guided liver biopsy all assisted in the diagnosis of hepatic hemangioma and its compression of the inferior vena cava. Because of the multisegmental and perihilar involvement of the tumor, surgery was not performed. For dissolution of the clots, the patient was given thrombolytic therapy followed by heparin administration. He was then placed on long-term warfarin therapy and is well after 5 years; the size of the hemangioma is unchanged. Cases of pulmonary embolism due to diseases of the upper abdominal organs are rare and probably underestimated. This case stresses the need for a systematic investigation of the abdomen when a pulmonary embolism is present without evidence of deep vein thrombosis.

Early thrombosis of a tricuspid valve prosthesis: two-dimensional echocardiographic demonstration.

We report on the case of a 35-year-old woman who had undergone tricuspid valve replacement with a Lillehei-Kaster prosthesis 7 weeks prior to admission to our institution. Real-time two-dimensional echocardiography indicated a large mass on the inferolateral surface of the right atrium, as well as a dense band of echoes on the atrial and ventricular surfaces of the prosthesis. The diagnosis, confirmed by angiography, was early, acute thrombosis of the tilting disc prosthesis. After an unsuccessful infusion of urokinase, the patient was taken to emergency surgery; at operation, a large thrombus was discovered on the inferolateral wall, and the valve replaced. The patient recovered uneventfully, with no recurrence of thrombosis. Our experience confirms that two-dimensional echocardiography is the preferred technique for identifying intracardiac thrombi, and that surgery with replacement of the prosthesis is the treatment of choice in cases such as this where the size and age of the clot contraindicate fibrinolytic treatment.