Screening of PAX6 gene in Italian congenital aniridia patients revealed four novel mutations

Purpose: To uncover underlying mutations in a cohort of Italian patients with aniridia, a rare congenital panocular condition with an incidence ranging from 1:64,000 to 1:100,000. The disease may be found isolated or in association with other syndromes characterized by partial or complete absence of the iris and iris hypoplasia.

Methods: We analyzed the PAX6 gene in 11 patients with aniridia fulfilling the following inclusion criteria: partial or complete absence of the iris and age < 18 years at the time of diagnosis. DNA sequence analysis was integrated with Multiple Ligation Probe Assay (MLPA) analysis.

Results: We identified seven PAX6 mutations, including four novel ones. The majority of mutations lie in the DNA-binding domain and all produce a truncated protein. All tested patients did not have WT1 gene deletions thus excluding the WAGR syndrome. We present the clinical findings in the four cases harboring novel mutations. We were unable to identify mutations in four cases with complete aniridia thus indicating that other gene/s could be involved in the disease.

Conclusions: It is important to establish the molecular diagnosis early to avoid repeated and long-term screening for Wilms tumor. Our work further emphasizes that a wide range of ocular phenotypes are associated with loss of function PAX6 mutations. In addition to the possibility of stochastic variations, other genetic variations could play a role as modifier genes, thus giving rise to the observed different ocular phenotypes.     

Platelet hyperaggregability in obesity: is there a role for nitric oxide impairment and oxidative stress?

Epidemiological evidence has shown that platelet activation markers are consistently elevated in obesity, contributing to its prothrombotic state. In order to improve the understanding of the regulation of platelet function in obesity, the aim of this study was to investigate the l ‐arginine‐nitric oxide (NO) pathway in obese adults without other cardiovascular risk factor. Seventeen obese (body mass index [BMI] 35.9±1.0 kg/m²) and eighteen age‐matched normal weight subjects (BMI 22.0±0.6 kg/m²) were included in this study. l ‐arginine influx was measured with incubation of l ‐[³H]‐arginine. NO synthase (NOS) and arginase activities were determined by the citrulline assay and the conversion of l ‐[¹⁴C]‐arginine to [¹⁴C]‐urea, respectively. Cyclic guanosine monophosphate (cGMP) content was evaluated by enzyme‐linked immunosorbent assay. In addition, the study analyzed: platelet aggregation; intraplatelet antioxidant enzymes, via superoxide dismutase (SOD) and catalase activities; and systemic levels of l ‐arginine, fibrinogen, and C‐reactive protein (CRP). Obese patients presented a significant decrease of platelet l ‐arginine influx, NOS activity, and cGMP levels, along with platelet hyperaggregability. On the presence of NO donor, platelet aggregation was similar between the groups. The fibrinogen and CRP systemic levels were significantly higher and SOD activity was reduced in obesity. No significant differences were observed in plasma levels of l ‐arginine and intraplatelet arginase and catalase activities between groups. The diminished NO bioavailability associated with inflammatory status and impaired enzymatic antioxidant defence may contribute to future cardiovascular complications in obesity.     

Sodium mercaptoundecahydro-closo-dodecaborate (BSH), a boron carrier that merits more attention

Boron neutron capture therapy relies on the preferential delivery of a ¹⁰B-compound to tumor cells. The BSH-biodistribution was investigated in nu/nu mice and human patients. The boron concentration was measured with prompt gamma ray spectroscopy. BSH accumulates to a very low extent not only in brain, but also in fat tissue, bone and muscle, which makes BSH an interesting drug not only for brain lesions but also for tumors located at the extremities. The differential uptake in different organs indicates a complex mechanism.     

Outcome after Open Repair of Ruptured Abdominal Aortic Aneurysm in Patients >80?Years Old: A Systematic Review and Meta-analysis

Background  

The role of open repair in the management of ruptured abdominal aortic aneurysm (RAAA) in patients >80 years old is questioned by the perceived high operative risk of these patients. This issue has been investigated in the present meta-analysis of observational studies.     

Studies on the effects of heparin products on pregnancy-associated plasma protein A

BackgroundIntravenous low molecular weight (LMWH) and unfractionated heparin (UFH) increase the circulating concentrations of pregnancy-associated plasma protein A (PAPP-A), a novel cardiac risk marker, in haemodialysis and coronary angiography patients.MethodsTo further investigate the mechanisms of heparin effects, free PAPP-A was analysed in serial serum samples collected during haemodialysis (intravenous LMWH), carotid endarterectomy or abdominal aortic aneurysm surgery (intravenous UFH), treatment at intensive care unit (subcutaneous LMWH), and coronary angiography (intravenous bivalirudin). PAPP-A was extracted from plaque tissue samples of endarterectomy and aneurysm patients. The interaction between heparin products and free PAPP-A was studied with gel filtration.ResultsAfter intravenous UFH and LMWH free PAPP-A increased significantly but bivalirudin had no effect. After LMWH bolus in haemodialysis patients 85% of free PAPP-A was cleared with a half-life of 13.1 min and the rest with a half-life of 96.6 min. Subcutaneous LMWH led to lower and slower free PAPP-A elevation. PAPP-A extracted from plaque tissues was in free form and extraction was strongly enhanced by LMWH. Heparin products increased the molecular size of free PAPP-A.ConclusionsThe heparin-induced PAPP-A elevation is seen in various patients and should be taken into account when PAPP-A is studied as a biomarker.     

The caudal septum angle of deflection: an objective analysis for caudal septum deviation

ObjectivesThe purposes of the study were to describe an objective technique for the evaluation of caudal septum deviation (CSD) and to evaluate the effectiveness of an open septorhinoplasty technique for treatment of CSD.

Study design

A retrospective review of septorhinoplasty cases involving CSD was performed. For all patients, preoperative basal view photographs were analyzed. All patients underwent an external septorhinoplasty approach for treatment of their CSD. After a minimum of 4 months, postoperative basal view photographs were analyzed.

Results

Seventeen patients had significant CSD and airway obstruction. The mean change in their caudal septum angle of deflection was 22° (P < .05). All patients had subjective improvement in their nasal airway obstruction. There were no complications.

Conclusion

We describe a method to objectively analyze CSDs in septorhinoplasty candidates. An external approach using nasal base reconstruction techniques results in an improvement of CSD and subsequent nasal airway patency.