An improved tetra-primer PCR approach for the detection of the FGFR3 G380R mutation responsible for achondroplasia

Achondroplasia is the most common form of dwarfism and has an incidence of approximately 1/7500. In more than 98% of cases, the disease is associated with a G to A or G to C substitution at nucleotide position 1138 (p.G380R) of the fibroblast growth factor receptor 3 (FGFR3) gene. We have developed a sensitive single tube tetra-primer PCR assay to detect both the c.1138G>A and c.1138G>C mutations and can successfully distinguish DNA samples that are homozygous and heterozygous for the c.1138G>A mutation. Titration studies showed that the assay could reliably detect one copy of the mutant allele in a mix of 100 wild-type alleles. The assay has been tested in 50 healthy controls, 3 known patients with achondroplasia, and 5 amniotic fluids suspected of having achondroplasia and for whom we had previously determined the genotypes for the c.1138G>A mutation by PCR-RFLP. We have observed complete concordance between methods. Our tetra-primer PCR assay is sensitive, low-cost, and easy to use method for FGFR3 p.G380R genotyping, which could be used even in "low-tech" laboratories.     

Secondary aortoenteric fistula in Beh?et's disease.

Vascular manifestations of Beh?et's disease include venous and arterial occlusions, arterial aneurysm and pseudo-aneurysm formation. The main problem of the surgical treatment of vascular lesions in Beh?et's disease is the high incidence of complications such as recurrent aneurysms, thrombosis and fistulization to the adjacent organs. Here we present a case of Beh?et's disease with multiple complications after aortic reconstructive surgery, including perigraft infection, abscess distal to the graft, occlusion of arteries of the lower extremities, aortoenteric fistula and distal anastomotic site aneurysm rupture.     

Synthesis and preliminary evaluation of aminoalkanol derivatives of selected azatricycloundecane system for binding with beta-adrenergic and 5HT1A and 5HT2A receptors

A series of aminoalkanol derivatives of 8,11-dimethyl-3,5-dioxo-4-azatricyclo[5.2.2.0(2,6)] undec-8-en-1-yl acetate and 1,11-dimethyl-4-azatricyclo[5.2.2.0(2,6)]undecane-3,5,8-trione was prepared. The pharmacological profile of selected compounds was evaluated for affinity to beta-adrenoreceptors and serotoninergic receptors (5HT1A and 5HT2A).     

Endoscopic treatment of primary sclerosing cholangitis.

BACKGROUND/AIMS: Dominant stricture of an extrahepatic bile duct is responsible for symptoms and an exacerbation of cholestasis in 15-20% of patients with primary sclerosing cholangitis. The aim of this study was to evaluate the efficacy and safety of endoscopic treatment in this selected patient group. METHODS: Retrospectively, we evaluated 16 patients who were treated endoscopically due to elevation of serum biochemical liver tests and symptoms which were attributable to dominant bile duct strictures during the period 1990 to 2003. Symptoms and biochemical liver tests were compared before and after treatment. RESULTS: Sixteen patients underwent a total of 58 therapeutic endoscopic retrograde cholangiopancreatographies (ERCP). Sixteen endoscopic sphincterotomies, 15 balloon dilatations, 6 bougie dilatations, 3 stone/sludge extractions and 8 stentings were performed. Endoscopic therapy was technically successful in all patients (100%). Biochemical liver tests were significantly improved when compared with pretreatment values (p<0.001). Patients have been followed-up without stents except for the patients who had cholangiocarcinoma and cirrhosis at the beginning. Procedure-related early complications occurred in 8.6% of therapeutic endoscopic biliary procedures. There was no mortality due to endoscopic treatment. Two patients whose stents were changed every two to three months had cholangitis due to stenting during 13 stent periods. Four patients whose stents were changed in seven to 10 days developed suppurative cholangitis (total 6 stent periods). CONCLUSIONS: Endoscopic therapy of symptomatic dominant strictures in primary sclerosing cholangitis is safe and effective. The cholangitis seen in long-term stenting seems to be solved by short-term stenting.     

Circadian variation of QTc dispersion in children with vasovagal syncope

AIMS: To assess the validity of QTc dispersion to cardiac autonomic nervous function status. METHOD AND RESULTS: Prospective comparisons of QTc dispersion measurements in 77 neurally mediated cardiac syncope (NMCS) patients (29 boys, 48 girls, mean age 13.4+/-0.78) were evaluated. Head-up tilt test (HUT) was positive in 38 patients and negative in 39 patients. QTc dispersion was significantly higher early morning and late night in HUT-positive group compared with HUT-negative group (p<0.001). Although there was a circadian rhythm in HUT-positive group, there was no change on the QTc dispersion within a day in the HUT-negative group. QTc dispersion in the HUT-positive group was high in accordance with their high sympathetic nervous stimulation. Moreover, QTc dispersion was higher during late night and early morning than the rest of the day. CONCLUSION: These results may explain why the HUT-positive patients usually have their syncope attacks early in the morning. Additionally, we can use QTc dispersion measurement as a new noninvasive electrocardiographic test to evaluate cardiac sympathetic nervous system in NMCS.