Origins and breakpoint analyses of copy number variations: up close and personal.

Array-based methods have enabled the detection of many genomic gains and losses. These are stated as copy number variants (CNVs) and comprise up to 13% of the human genome. Based on their breakpoints and modes of formation CNVs are termed recurrent or nonrecurrent. Recurrent CNVs are flanked by low copy repeats and are of a fixed size. They arise as a result of misalignment during meiosis by a mechanism named nonallelic homologous recombination. Several of such recurrent CNVs have been linked to human diseases. Nonrecurrent CNVs, which are not flanked by low copy repeats, are of variable size and may arise via mechanisms like nonhomologous end joining and replication-based mechanisms described by the fork stalling and template switching and microhomology-mediated break-induced replication models. It is becoming clear that most disease-causing CNVs are nonrecurrent and generally arise via replication-based mechanisms. Furthermore, it is now appreciated that genomic features other than low copy repeats play a role in the formation of nonrecurrent CNVs. This review will discuss the different mechanisms of CNV formation and how high resolution analyses of CNV breakpoints have added to our knowledge of their precise structure.

[Resorbable rods and screws for fixation of ankle fractures. A randomized clinical prospective study]. / Resorbierbare Stäbe und Schrauben zur Fixierung von Knöchelfrakturen. Eine randomisierte klinische Prospektivstudie.

A prospective randomized clinical trial was performed to evaluate the use of self-reinforced absorbable composites (Biofix) in the fixation of ankle fractures. The aim of this study was to demonstrate that fixation with Biofix rods and screws is as good as the standard A.O. fixation. The benefits of Biofix rods and screws are: a reduction in costs since no secondary operation is needed, prevention of stress-shielding and thereby diminishing the risk of bone porosity. Patients aged between 16 and 75 years old with closed, non-comminuted fractures of the lateral and/or medial malleolus and dislocation of the fracture fragments greater than 2 mm were included in the study. 22 patients were treated with Biofix rods and screws and the control group of 19 patients with a standard technique. After 3, 6 and 12 months, rontgenograms were taken. At the same time functional results were evaluated following the criteria of Olerud and Molander. Two patients were withdrawn from the trial for non-medical reasons. 22 patients (12 from the Biofix group, 10 from the AO group) operated two or more years ago were contacted to see if any complications had occurred since they were last seen. In 4 cases a Biofix screw broke down just beneath the head during insertion. This did not result in an insufficient fixation of the fracture. There were no early post-operative complications. The functional and rontgenological results in both groups were equal. In three cases a sterile sinus developed at the site of screw insertion. Biofix rods and screws, made of polylactic acid, are a good alternative for the fixation of fractures of the ankle. The use of resorbable fracture fixation material has the advantage that a second operation to remove osteosynthesis material is not necessary. The long term results are good. There is, however, a possibility of development of tissue reaction to the resorbable material.

Orthodromic pacemaker circus movement tachycardia.

We report on the case of a 33-year-old woman with sick sinus syndrome who had an orthodromic pacemaker circus movement tachycardia (PCMT), with antegrade atrioventricular (AV) conduction and a retrograde pathway by means of a DDD (AV universal) pacemaker. This PCMT was provoked and sustained by premature ventricular contraction-synchronous atrial stimulation (PVC-SAS), which is a new feature for the prevention of antidromic PCMTs. The conditions for occurrence of this tachycardia were: PVC-SAS; atrial undersensing; first degree AV block. Recommendations for prevention of this pacemaker-mediated tachycardia are given.

Effects of intravenous captopril on inducible sustained ventricular tachycardia one week after experimental infarction in the anaesthetized pig.

The effect of captopril on inducible sustained ventricular tachycardia (VT) one week after myocardial infarction was studied in 6 Yorkshire swine. In 24 pigs, controlled myocardial infarction (MI) was produced by reversible occlusion of the left anterior descending artery during 60 minutes using an inflatable balloon catheter. Four animals died during this procedure and another 4 during the first week. After 7 days, programmed electrical stimulation (PES) was performed in the surviving animals. Seven animals showed inducible VT, which could not be terminated in one. Subsequently, intravenous captopril (0.6-1.2 mg/kg) was administered as a rapid bolus injection. PES was repeated after 5 minutes and VT was no longer inducible in all 6 pigs (P less than 0.05). Right ventricular refractoriness decreased from 253 to 228 ms (n.s.). Blood pressure and heart rate were not significantly changed. We conclude that captopril can protect the heart against PES-induced VT late after MI. It is suggested that inhibition of angiotensin II and subsequent inhibition of noradrenaline may be responsible for this effect.