A Decrease in Pulmonary Vein Diameter After Radiofrequency Ablation Predicts the Development of Severe Stenosis

A decrease in ostial pulmonary vein (PV) diameter was observed in patients on the day after radiofrequency ablation of atrial fibrillation (AF). This study examined whether a relative reduction in PV diameter on day 1 (RRPVD1) after the procedure predicts the late development of severe PV stenosis (PVS). The study included 104 consecutive patients (mean age = 55 years, range 46–61, 34 women) with drug refractory AF. Pulmonary vein diameter was measured using MR angiography (MRA) on the day before and on day 1 after the ablation procedure. The MRA was repeated every 3 months after the procedure. Severe PVS was defined as a >70% diameter reduction from the initial ostial diameter. The cut-off of RRPVD1 was prespecified as 25% decrease in initial diameter. The data are presented as medians and interquartile range. A total of 357 PV were treated. The RRPVD1 was 0.0% (0.0–11.1%). Severe PVS was found in 18 PV during a follow-up of 12 months (range 6–13). The log-rank analysis confirmed a strong association between a RRPVD1 ≥25% and the development of PVS (hazard ratio: 7.1; 95% confidence interval 3.8–13.5, P < 0.0001). By multivariate Cox regression model, after adjustment of procedure variables, RRPVD1 was the strongest predictor of development of severe PVS. RRPVD1 ≥25% was a strong independent predictor of development of severe PVS.     

Analysis of the Neutralizing Antibody Response to the Measles Virus Using Synthetic Peptides of the Haemagglutinin Protein

Infection or immunization with measles virus induces a protective immune reaction including neutralizing antibodies against the haemagglutinin and fusion protein. The reactivity of the polyclonal IgG response of sera obtained from late convalescent donors was studied, using overlapping 15mer peptides covering the complete sequence of the measles virus haemagglutinin. Most sera reacted with a similar set of peptides generating a characteristic binding pattern. The reactive peptides correspond to a region mediating cell hemolysis (aa310–325), to regions which serve as targets to neutralizing antibodies and to a putative transmembrane region (aa35–58). The latter region contains also a human T-cell epitope providing evidence of a non-random association of T- and B-cell epitopes. We also immunized different strains of mice and rabbits with measles virus. In contrast to the human sera, animal sera with strong neutralizing activities did not react with any of the H-protein peptides. The mostly weak reactivities with the linear sequences contrast with the strong neutralizing activities of the human or animal antibodies, suggesting that these primarily recognize the fusion protein or conformational epitopes of the haemagglutinin protein.     

The effect of indomethacin on cerebral blood flow and oxygen consumption in the rat at normal and increased carbon dioxide tensions

The effect of the fatty acid cyclo-oxygenase inhibitor indomethacin on cerebral blood flow (CBF) and the metabolic rate for oxygen (CMRO₂) was studied in paralyzed and artificially ventilated rats. In normocapnic animals, the drug (10 mg·kg^-1i. v.) reduced CBF to 50% of control without a measurable effect on CMRO₂. During hypercapnia (Pa_CO2 70–80 mmHg) the increase in CBF was reduced by about 80% but CMRO₂ remained unchanged. Autoradiographic evaluation of local CBF in 20 brain structures indicated that the reduction in CBF was relatively uniform throughout the brain. Dose response curves showed that an effect on CBF was evident already at an indomethacin dose of 1 mg·kg^-1 and maximal effects were obtained with 3–5 mg·kg^-1. Following i. v. injection of the drug reduction in CBF was observed already after 10 s and the full response occurred after 1–2 min. It is concluded that metabolites of arachidonic acid, possibly mainly prostacyclin, are powerful modulators of normal cerebrovascular tone, and help to mediate the CBF response to increased CO₂ tensions. However, since indomethacin does not modify the circulatory response in other conditions with increased CBF these substances do not qualify as general coupling factors controlling CBF in physiological or pathological states.     

Comparison of the antianginal efficacy of isosorbide dinitrate (ISDN) 40 mg and verapamil 120 mg three times daily in the acute trial and following two-week treatment

Fourteen male patients with exertion-related angina pectorisand reproducible ST-segment depression on stress testing wereeach treated with isosorbide dinitrate (ISDN) 40 mg three timesdaily, verapamil 120 mg three times daily and placebo threetimes daily for two weeks according to a double-blind cross-overprotocol. The mean improvement of exercise-induced ST-segment depressionamounted to 73% on the first day of ISDN treatment (P < 0.001)and to 54% following acute administration of verapamil (P <0.001). On the last day of continuous treatment, the antianginalefficacy of ISDN was somewhat mitigated (reduction of ST-segmentdepression: 54%; P<0.001), while the effect of verapamilremained unchanged (55%, P<0.001). The double product (heartrate x systolic blood pressure) at the end of stress testingdecreased most pronouncedly on day 1 of ISDN treatment ( - 21%;P<0.01). On chronic testing, both drugs similarly influencedthis parameter: 10–11% (P<0.05). The mean global ejectionfraction (EF) assessed by gated blood pool scintigraphy on day13 showed a stress-induced fall from 49 to 44% (P<0.05) afterthe administration of placebo. The respective values with ISDNwere 53% at rest and 52% on exercise (n.s.), and after givingverapamil 50% and47% (n.s.). Thus, ISDN 40 mg and verapamil 120 mg displayed beneficial anti-ischaemiceffects in patients with stable exertion-related angina pectorisafter acute and chronic administration. The efficacy of ISDNdeclined somewhat in the course of the two-week treatment, whereasthat of verapamil remained unchanged. Beneficial effects ofboth drugs were also demonstrated with regard to the rate pressureproduct. Isosorbide dinitrate 40 mg and verapamil 120 mg administeredthree times daily can be recommended for the acute and chronictherapy of patients with stable angina.     

Efficacy of a nicotine nasal spray in smoking cessation: a placebo-controlled, double-blind trial

Laboratory trials have demonstrated the efficacy of nicotine replacement in smoking cessation bur absolute success races are low. For many, nicotine gum is hard to use and transdermal nicotine is slow-acting and passive. A new, faster-acting nicotine nasal spray (NNS) can provide easily self-administered relief from cigarette withdrawal. The NNS was tested for safely and efficacy in smoking cessation. Two hundred and fifty-five smokers were randomized to NNS or a piperine placebo. Drug use was limited to 8–32 doses/day for 6 months. Subjects were tested while smoking and at post-cessation daily (week 1) with follow-up at weeks 2, 3, 6 and at 3 months, 6 months and 1 year. Continuous abstinence analyses (CO ≤8 ppm.; no slips) showed that NNS significantly enhanced success rates over placebo overall (p < 0.001) and at all test intervals. Differences at key intervals between active and placebo were: 63% vs. 40% (day 5), 51% vs. 30% (week 3), 43% vs. 20% (6 weeks), 34% vs. 13% (3 months), 25% vs. 10% (6 months) and 18% vs. 8% (1 year). Side effects were common but tolerable. Cotinine measures showed that replacement of nicotine approximated 30% of smoking levels. Hazard functions revealed relapse risks peaked at day 1, day 5 and 3 weeks for strict abstinence. It is concluded NNS is safe, efficacious and a viable alternative treatment for smoking cessation.     

The initial phase of graft‐versus‐host disease is associated with a decrease of CD4+CD25+ regulatory T cells in the peripheral blood of patients after allogeneic stem cell transplantation

The mechanisms that induce and control the alloimmune inflammation of graft‐versus‐host disease (GvHD) after allogeneic stem cell transplantation (allo‐SCT) are still incompletely understood. In the murine system, GvHD can be suppressed by CD4⁺CD25⁺ regulatory T cells (TREG), which are generally involved in the suppression of inflammatory reactions. A disruption of the homeostasis between TREG and conventional T cells might therefore be associated with the inflammatory reactions of GvHD. We repetitively measured the frequency of TREG in the peripheral blood of 29 patients within the first 71–373 days after allo‐SCT and correlated the results with the clinical course. We demonstrate that the initial phase of GvHD is associated with a significant reduction of TREG in the peripheral blood, while at later stages and during intensified immunosuppressive therapy, increased numbers of TREG appear. These results might indicate a pathogenic role for reduced numbers of TREG in the induction of human GvHD.     

SITE VARIABILITY IN A MULTISITE GERIATRIC DEPRESSION TRIAL

We studied differences in outcome and characteristics among 29 clinical sites of a multisite, double-blind antidepressant trial for geriatric depression. Six hundred and seventy-one outpatients aged 60 years or older (mean±SD=67.7±5.7) met DSM-III-R criteria for unipolar major depression, had baseline 17-item Hamilton Depression Rating Scale (HAMD₁₇) scores ≥16 and were randomized to fluoxetine (20 mg daily) or placebo. Effect sizes (ESs, expressed as mean differences between effects divided by the pooled standard deviation of the differences) were calculated for each site using selected outcome measures. ES ranged from 1.84 (favoring fluoxetine) to −0.91 (favoring placebo) for incidence of remitters (endpoint HAMD₁₇ total score of ≤8). A large, positive ES favoring fluoxetine for remission rates (ES≥0.65) was found at only six sites, moderate ES (0.35–0.64) at eight and small ES (0–0.34) at seven; ES favored placebo (<0) at eight of 29 sites. Private clinics showed an overall HAMD₁₇ ES for change scores more than twice that of university sites. These results suggest that individual practitioners may have vastly different clinical experiences in large, multisite trials for geriatric depression. Interrater reliability, subject selection, recruitment, inadequate or fixed dosing, few patients per site, brief study duration, heterogeneity of geriatric depression, financial incentive and characteristics of individual sites may contribute to response variability.