Correction to: Comparison of the 1-year clinical outcome of a novel cryoballoon to an established cryoballoon technology

Journal of Interventional Cardiac Electrophysiology -     

T-cell-depleted peripheral blood stem cell transplantation for alpha-mannosidosis

Alpha-mannosidosis (alpha-mannosidosis) is a lysosomal storage disease characterized by accumulation of oligosaccharides in various tissues leading to symptoms such as coarse facial features, dysostosis multiplex, hearing disabilities, mental developmental delay and skeletal involvement (dysostosis multiplex). Without treatment, the severe infantile onset form of this autosomal recessive disease leads to progressive neurodegeneration and sometimes to early death. Stem cell transplantation has been shown to be an effective treatment. In the five patients published so far, correction of skeletal abnormalities and improvement of neuropsychological capabilities have been observed. We report the first patient who received a T-cell-depleted peripheral blood stem cell transplantation (PBSCT) for alpha-mannosidosis. The diagnosis of alpha-mannosidosis was made at the age of 14 months. At the age of 24 months, he underwent PBSCT with T-cell depletion by CD34-positive selection from his HLA phenotypically identical mother. Conditioning was carried out with busulfan (20 mg/kg), cyclophosphamide (200 mg/kg), OKT3 and methylprednisolone. The patient is alive and well 27 months after PBSCT and has made significant developmental progress. The pattern of urinary oligosaccharides has returned to almost normal. CD34-positive-selected PBSCT is a feasible option to reduce risk for GVHD for these patients.     

Isolated myocardial noncompaction in childhood-case report and review of the literature

The diagnostic work-up for the first syncopal episode of a 14-year-old female adolescent revealed the morphology of an isolated myocardial non-compaction on echography. Angiography and biopsy of the left ventricle confirmed the diagnosis. Despite a reduced shortening fraction (FS 21%) and frequent premature atrial beats, there were no further cardiac or extracardiac symptoms. After establishment of therapy with beta-blockade, digitalis, angiotensin converting enzyme inhibition and acetylsalic acid, the follow-up over 24 months was good; the implantation of an automatic implantable cardioverter-defibrillator is planned.     

Association of hypertensive status and its drug treatment with lipid and haemostatic factors in middle-aged men: the PRIME study

Aims: To assess the association of hypertensive status and antihypertensive drug treatment with lipid and haemostatic levels in middle-aged men.Methods and results: Hypertensive status, antihypertensive drug treatment, total and high-density lipoprotein (HDL) cholesterol, triglyceride, apoproteins A-I and B, lipoparticles LpA-I, LpE:B and Lp(a), fibrinogen, plasminogen activator inhibitor-1 (PAI-1) activity and factor VII were assessed in a sample of men 50-59 years living in France (n = 7050) and Northern Ireland (n = 2374). After adjustment for age, body mass index, smoking status, educational level, country, alcohol drinking and hypolipidaemic drug treatment, untreated hypertensive subjects had higher levels of total cholesterol, triglyceride, apoproteins A-I and B and PAI-I activity than normotensive subjects. On univariate analysis, diuretics decreased total and HDL-cholesterol and apoproteins A-I and B; those differences remained after multivariate adjustment. Treatment with beta-blockers decreased total and HDL-cholesterol, apoprotein A-I and LpA-I, and this effect remained after multivariate adjustment. Calcium channel blockers decreased total cholesterol and apoproteins A-I and B; those differences remained significant after multivariate adjustment. ACE inhibitors decreased total cholesterol, triglycerides, apoprotein B and LpE:B; and this effect remained after multivariate adjustment. Analysis of the subjects on monotherapy showed beta-blockers to decrease total cholesterol and HDL parameters and angiotensin-converting enzyme (ACE) inhibitors to decrease low-density lipoprotein (LDL)-related parameters, while no effect was found for the other antihypertensive drugs.Conclusions: Hypertensive status is associated with an unfavourable lipid and haemostatic profile in middle-aged men. Antihypertensive treatment with beta-blockers decreases HDL parameters, whereas treatment with ACE inhibitors appears to decrease total cholesterol and LDL-related parameters.     

The gonadotropin-releasing hormone pituitary receptor interacts with a guanosine triphosphate-binding protein: differential effects of guanyl nucleotides on agonist and antagonist binding

Binding of the GnRH agonist [DAla6,NMe-Leu7,Pro9Net]GnRH to bovine anterior pituitary membranes is inhibited by guanyl nucleotides. The effect of guanyl nucleotides is temperature dependent, in that significant binding inhibition is observed when the receptor-hormone interaction is measured at 37 C, and no inhibition is seen at 4 C. Micromolar concentrations of the nonhydrolyzable GTP analog 5'-guanylylimidodiphosphate [Gpp(NH)p] displace the bound agonist in a dose-dependent manner, with half-maximal displacement occurring in a concentration range of 0.1-0.5 microM, and maximum displacement occurring at a concentration of 50 microM Gpp(NH)p. At a concentration of 50 microM, the other nucleotides GTP and GDP inhibit binding to a lesser extent, while GMP, cGMP, 5'-adenylylimidodiphosphate [App(NH)p], ATP, and cAMP have no effect on the binding. At 37 C, Gpp(NH)p reduces the affinity of the agonist by a factor of 6 and increases its dissociation rate. In the presence of Gpp(NH)p at 37 C, there is also a 2-fold increase in the total number of binding sites. Under the same conditions as those used for the agonist, there is no displacement of the bound antagonist [Ac-D2Nal1,4ClDPhe2,D3Pal3,DLys6,Lys8,D Ala10]-GnRH by doses up to 50 microM Gpp(NH)p. The modulation of the binding of the agonist, but not that of the antagonist, by guanyl nucleotides is characteristic of receptors that are coupled to GTP-binding proteins. Thus, the GnRH receptor appears to be coupled to a GTP-binding protein that may play a role in the mechanism of action of GnRH at the pituitary.