Pulmonary vein isolation in patients with paroxysmal atrial fibrillation : Long-term clinical outcomes with first- and second-generation cryoballoons.

BACKGROUND: The aim of this study was to evaluate the long-term success rates of pulmonary vein isolation (PVI) using only first-generation cryoballoon (CB-1) and second-generation CB (CB-2) in patients with paroxysmal atrial fibrillation (PAF). PATIENTS AND METHODS: A total of 114 drug-refractory patients with PAF (mean age: 62 ± 10 years; 62.3 % males) were enrolled. All index ablation procedures were performed using a 28-mm CB. All patients were scheduled for outpatient clinic visits, followed by 24-h or 7­day Holter electrocardiogram (EGC) evaluation. RESULTS: All PVs in the CB-1 group and 367 of 368 (99.7 %) PVs in the CB-2 group were completely isolated during the index procedure. The most commonly observed complication was phrenic nerve palsy in four (4.3 %) patients with CB-2. The mean follow-up period for CB-1 and CB-2 was 33.4 ± 14.9 and 27.2 ± 10.6 months, respectively. Freedom from AF was 42.9 % for CB-1 and 74.2 % for CB-2 at the end of the follow-up period. The European Heart Rhythm Association score improved in patients without AF recurrence after the procedure (2.8 ± 0.4 vs. 1.2 ± 0.5, p < 0.001), whereas no significant improvement was observed in the symptomatic status of patients with recurrence (2.8 ± 0.4 vs. 2.2 ± 0.9, p = 0.149). CONCLUSION: Second-generation CB provided significantly better clinical outcomes than its predecessor and was associated with low peri- and postprocedural complications.

Hyperpolarised 3He MRI versus HRCT in COPD and normal volunteers: PHIL trial.

The aim of the present study was to apply hyperpolarised (HP) (3)He magnetic resonance imaging (MRI) to identify patients with chronic obstructive pulmonary disease (COPD) and alpha(1)-antitrypsin deficiency (alpha(1)-ATD) from healthy volunteers and compare HP (3)He MRI findings with high-resolution computed tomography (HRCT) in a multicentre study. Quantitative measurements of HP (3)He MRI (apparent diffusion coefficient (ADC)) and HRCT (mean lung density (MLD)) were correlated with pulmonary function tests. A prospective three centre study enrolled 122 subjects with COPD (either acquired or genetic) and age-matched never-smokers. All diagnostic studies were completed in 94 subjects (52 with COPD; 13 with alpha(1)-ATD; 29 healthy subjects; 63 males; and 31 females; median age 62 yrs). The consensus assessment of radiologists, blinded for other test results, estimated nonventilated lung volume (HP (3)He MRI) and percentage diseased lung (HRCT). Quantitative evaluation of all data for each centre consisted of ADC (HP (3)He MRI) and MLD measurements (HRCT), and correlation with forced expiratory volume in 1 s (FEV(1))/forced vital capacity (FVC) indicating airway obstruction, and the diffusing capacity of the lung for carbon monoxide (D(L,CO)) indicating alveolar destruction. Using lung function tests as a reference, regional analysis of HP (3)He MRI and HRCT correctly categorised normal volunteers in 100% and 97%, COPD in 42% and 69% and alpha(1)-ATD in 69% and 85% of cases, respectively. Direct comparison of HP (3)He MRI and CT revealed 23% of subjects with moderate/severe structural abnormalities had only mild ventilation defects. In comparison with lung function tests, ADC was more effective in separating COPD patients from healthy subjects than MLD (p<0.001 versus 0.038). ADC measurements showed better correlation with D(L,CO) than MLD (r = 0.59 versus 0.29). Hyperpolarised (3)He MRI correctly categorised patients with COPD and normal volunteers. It offers additional functional information, without the use of ionising radiation whereas HRCT gives better morphological information. We showed the feasibility of a multicentre study using different magnetic resonance systems.

Cellular and humoral immune responses induced by intradermal or intramuscular vaccination with the major hepatitis B surface antigen.

The vaccination route may influence the success of immunization against pathogens. The conventional intramuscular (i.m.) application of a vaccine containing the hepatitis B virus (HBV) surface antigen (HBsAg) led to protective anti-HBs antibody levels in the majority of vaccine recipients. In this study, we vaccinated healthy volunteers and a group of i.m. vaccine nonresponders via the intradermal (i.d.) route and analyzed the HBV-specific B-cell response as well as class-II- and class-I-restricted T-cell responses by (3)H-thymidine uptake, enzyme-linked immunosorbent assay (ELISA) and enzyme-linked immunospot assay (ELISPOT). The results were then compared with i.m. vaccinated controls. I.d. vaccinations were well tolerated and induced neutralizing anti-HBs antibodies in all naive vaccine recipients and, importantly, all but one former i.m. nonresponder developed protective anti-HBs serum antibody levels after 2 or 3 i.d. immunizations. On the cellular level, i.d. vaccine recipients showed significantly higher anti-HBs producing B-cell frequencies and more vigorous class-II-restricted T-helper (Th) cell responses than i.m. controls. However, although the HBsAg-specific T cells were characterized by their cytokine release as Th1-like cells in both groups, human leukocyte antigen (HLA)-A2+ individuals who received the soluble HBsAg via the i.d. route developed higher peptide-specific cytotoxic CD8+ T cell precursor (CTLp) frequencies. In conclusion, i.d. HBsAg vaccination is more effective even in former i.m. vaccine nonresponders with respect to antibody induction and specific B- and T-cell responses. The induction of virus-specific CTLp may provide the rationale to study the i.d. HBsAg vaccine in the treatment of chronic hepatitis B.

Granulocyte colony-stimulating factor (G-CSF) serum levels in surgical intensive care patients.

The granulocyte colony-stimulating factor (G-CSF) regulates neutrophil differentiation and function. Serum levels of G-CSF increase during acute infectious processes. The levels of G-CSF were measured in 59 surgical intensive care unit (ICU) patients. In general, G-CSF was only elevated during the first 2 days after admission to the ICU. Higher G-CSF levels were more frequently observed in patients without infectious complications and in patients who survived. Later on, G-CSF levels were below 100 pg/ml in almost all patients studied. The highest G-CSF level (20,000 pg/ml) was observed in one patient with septic shock 36 h after leukopenia. The patient recovered from septic shock and multiple organ failure and was discharged. It is proposed that surgical ICU patients with low or undetectable G-CSF serum levels may benefit from exogenous G-CSF substitution protocols.

Cloning and recombinant expression of a barred sand bass (Paralabrax nebulifer) cDNA. The encoded protein displays structural homology and immunological crossreactivity to human complement/cofactor related plasma proteins.

A new cofactor related cDNA in the bony fish Paralablax nebulifer, (barred sand bass) was isolated from a sand bass liver cDNA library. The clone (c71) is 1040 bp in size and the predicted translation product of 204 amino acids contains a hydrophobic signal peptide, which is followed by a region of three short consensus repeats (SCRs). The three SCRs display high homology to SCRs of the 110 kDa chain of the sand bass plasma cofactor protein, and to a lesser degree to human complement factor H related protein 3 (FHR-3) and to human factor H. Recombinant expression of the c71 cDNA in the baculovirus system shows a product of an apparent molecular mass of 27 kDa, which is secreted and glycosylated. It also contains a His-tag for purification purposes. Removal of the His-tag yields a 24 kDa protein, and deglycosylation further reduces the molecular mass to 21 kDa. This size is in agreement with the calculated molecular mass based on amino acid composition. The sand bass SBCFR-1 protein is immunologically related to the human complement proteins, factor H and factor H-related protein 3. The recombinantly expressed protein reacted with antisera against the human FHR-3 protein and SCRs 19-20 of human factor H. The presence of SCR-containing proteins in sand bass plasma and their structural and immunological homology to human FHR-3 and factor H suggests for a common function between these evolutionary related proteins.

Cloning and characterization of a cDNA representing a putative complement-regulatory plasma protein from barred sand bass (Parablax neblifer).

It has been demonstrated previously that plasma from a number of vertebrate species including the phylogenetically old barred sand bass possesses molecules that cleave the alpha'-chain of the activated third (C3b) and fourth (C4b) components of the human complement system. A specific protease and a cofactor protein were identified to be responsible for this cleavage. The cofactor activity in sand bass correlated with a 110 kDa polypeptide chain of a 360 kDa plasma protein. The evolutionary conservation was probed at the cDNA level and subsequently a cDNA clone of barred sand bass was isolated that represents a protein with structural similarity to mammalian complement-regulatory proteins. The cDNA (SB1) was identified by immunoscreening of a sand bass liver expression library using affinity-purified IgG antibodies raised against the isolated 110 kDa material. The cDNA is 3397 bp in size and the open reading frame represents a protein of 1053 amino acid residues with a hydrophobic signal peptide indicative of a secreted protein. The calculated mass of the mature protein (SBP1) is 115.2 kDa which is in good agreement with the molecular mass of 110 kDa determined for the sand bass serum protein. Similarly to mammalian complement-regulatory proteins, the protein deduced from the sand bass cDNA is organized into short consensus repeats (SCR). It consists of 17 SCRs, of which SCRs 2, 12 and 16 exhibit significant homology to SCRs 2, 15 and 19 of human factor H, and SCRs 11, 12 and 13 have homology to SCRs 1, 2 and 3 of human C4b-binding protein. For the first time a complete cDNA representing a putative complement-regulatory protein which is structurally related to mammalian complement proteins has been isolated from a bony fish.