First insights into cryoballoon-based pulmonary vein isolation taking the individual time-to-isolation into account.

AIMS: Cryoballoon (CB)-based pulmonary vein isolation (PVI) is an established treatment for symptomatic atrial fibrillation (AF). In the present study, we sought to assess the efficacy and safety of CB-based PVI taking the individual time-to-isolation (TTI) into account. METHODS AND RESULTS: Sixty consecutive patients with drug-refractory paroxysmal atrial fibrillation [n = 49 (82%)] or short-standing persistent atrial fibrillation [n = 11 (18%)] underwent ablation with a 28-mm second-generation CB. The TTI was assessed by spiral mapping-catheter recordings and subsequently followed by an additional freeze-time of 120 s. No bonus freeze-cycle was applied. If the TTI could not be assessed, a fixed freeze-cycle duration of 240 s was applied and successful PVI confirmed thereafter. Clinical follow-up (FU) included 12-lead ECGs and 24 h Holter-ECGs at 3, 6, and 12 months. A blanking period of 3 months was defined. A total of 239 pulmonary veins (PVs) were identified and successfully isolated. The mean TTI assessed in 170/239 (71%) PVs was 52 ± 32 s. The mean number of CB applications was 1.2 ± 0.5; mean freeze-cycle duration was 192 ± 41 s. Mean procedure and fluoroscopy times were 80 ± 24 min and 16 ± 7 min, respectively. Transient phrenic nerve palsy occurred in one patient (2%). During a mean FU of 405 ± 67 days, 43 patients (72%) remained in stable sinus rhythm. CONCLUSIONS: Integrating an individual TTI protocol to CB-based PVI results in shorter freeze-cycle applications in a substantial portion of targeted PVs and an arrhythmia-free survival comparable to conventional ablation protocols. The complication rate is low.

Continuous and discrete on-site detection of radon-222 in ground- and surface waters by means of an extraction module.

A robust and straightforward method for on-site determination of radon-222 activity concentrations in water is presented. The methodical approach is based on the principle of liquid-gas-membrane extraction. An extraction module, which consists of hollow polypropylene fibres, allows radon stripping from the water of interest into a connected closed air-loop. The resulting radon-in-air activity concentration, which can easily be reconverted into the original radon-in-water activity concentration is measured by means of a standard mobile radon-in-air monitor. The experimental set-up allows radon detection in discrete water samples as well as continuous water pump streams. The technique, covering a wide activity concentration range, is in particular advantageous for measurements of radon-in-water in the field or on research cruises.

Glycosylation of therapeutic proteins in different production systems.

UNLABELLED: Glycosylation plays an important role in a number of therapeutic proteins, including monoclonal antibodies. The enzymatic activity of a therapeutic protein is mainly determined by the protein structure, whereas the pharmacokinetics, pharmacodistribution, solubility, stability, enhancement of effector function and receptor binding are all influenced by the carbohydrate moiety. Hyperglycosylated proteins show increased serum half-life, are less sensitive to proteolysis and more heat-stable compared with the non-glycosylated forms. Molecular engineering of the TNK-tissue plasminogen activator molecule results in a more complex type of glycosylation and increases the half-life of the protein, which allows a single bolus injection at a lower dose for the treatment of acute myocardial infarction. Antibody-dependent cell cytotoxicity (ADCC) is determined partially by the specific N-glycosylation of the Fc domain of the monoclonal antibody. Specific glycoforms of monoclonal antibodies, which interact solely with the FcgammaRIIIa receptor of natural killer cells, result in superior ADCC compared with heterogeneous glycoforms that interact with different Fc receptors. This demonstrates that glycoengineering for directed glycosylation of therapeutic proteins can improve the therapeutic effect. While the amino acid sequence of the therapeutic protein is determined by the nucleotide sequence of the inserted gene, glycosylation depends on the glycosylating enzymes in the endoplasmatic reticulum and the Golgi apparatus of the eukaryotic host cell. In addition, the glycosylation of the therapeutic protein is affected by the culture medium used, the efficiency of protein expression and the physiological status of the host cell. CONCLUSION: For a given protein, changes in the type of host cell, composition of the culture media and fermentation conditions during process development will most likely result in changes in the site occupation and heterogeneity of glycosylation. This, of course, can influence the therapeutic profile. Therefore, the early selection of the host cell and selection of upstream parameters are key in the process development of a product.