Circular mapping and ablation of the pulmonary vein for treatment of atrial fibrillation: impact of different catheter technologies

OBJECTIVES: We conducted this study to compare the efficacy and safety of different catheter ablation technologies and of distal versus ostial pulmonary veins (PV) isolation using the circular mapping technique. BACKGROUND: Electrical isolation of the PVs in patients with atrial fibrillation (AF) remains a technical challenge. METHODS: Two hundred eleven patients (163 men; mean age 53 +/- 11 years) with symptomatic AF were included in this study. In the first 21 patients (group 1), distal isolation (> or = 5 mm from the ostium) was achieved targeting veins triggering AF. In the remaining 190 patients (group 2), ostial isolation of all PVs was performed using 4-mm tip (47 patients), 8-mm tip (21 patients), or cooled-tip (122 patients) ablation catheters. RESULTS: Distal isolation was able to eliminate premature atrial contractions (PACs) and AF in six of 21 patients (29%) and 10 of 34 PVs. After a mean follow-up time of 6 +/- 4 months, no patients treated with the 8-mm tip catheter experienced recurrence of AF, whereas 21% (10 of 47 patients) and 15% (18 of 122 patients) of the patients ablated with the 4-mm tip and the cooled-tip ablation catheters experienced recurrence of AF after a mean follow-up of 10 +/- 3 and 4 +/- 2 months, respectively. Significant complications including stroke, tamponade, and severe stenosis occurred in 3.5% (8/211) of patients. CONCLUSIONS: Catheter technologies designed to achieve better lesion size appeared to have a positive impact on procedure time, fluoroscopy time, number of lesions, and overall efficacy. Although distal isolation can be achieved with fewer lesions, ostial isolation is required in the majority of patients to eliminate arrhythmogenic PACs and AF.     

The management of stage I--II Hodgkin's disease with irradiation alone or combined modality therapy: the Stanford experience

At Stanford University, between 1968 and 1978, 230 patients with pathologic stage I--II Hodgkin's disease were treated on prospective clinical trials with either irradiation alone or irradiation followed by 6 cycles of adjuvant combination chemotherapy. The actuarial survival at 10 yr was 84% for patients in either treatment group. Freedom from relapse at 10 yr was 77% among patients treated with irradiation alone and 84% after treatment with combined modality therapy [p(Gehan) = 0.09]. Freedom from second relapse at 10 yr was 89% and 94%, respectively [p(Gehan) = 0.56]. Several prognostic factors were evaluated in order to identify patients at high risk for relapse or with poor ultimate survival after initial treatment with irradiation alone. Systemic symptoms, histologic subtype, age, and limited extranodal involvement (E-lesions) did not affect the prognosis of patients and failed to identify patients whose survival could be improved by the routine use of combined modality therapy. Patients with large mediastinal masses (mediastinal mass ratio greater than or equal to 1/3) had a significantly poorer freedom from relapse when treated with irradiation alone than when treated initially with combined modality therapy [45% versus 81% at 10 yr, p(Gehan) = 0.03). The 10-yr survival of these patients, however, was not significantly different (84% versus 74%). The implications of these observations on the management of patient with early stage Hodgkin's disease are discussed.     

Improvement in disease-free survival of melanoma patients in conjunction with serologic response in a phase Ia/Ib Southeastern Cancer Study Group trial of vaccinia melanoma oncolysate

Thirty-nine patients with malignant melanoma who were disease-free after surgery but at high risk for recurrence were treated with vaccinia melanoma oncolysate (VMO) for 12 months. Clinical results, after a mean follow-up of 17 months showed that 25 of 39 patients had no evidence of disease. Comparison of disease-free survival of patients in this study with that of 39 matched controls from other adjuvant trials shows statistically significant advantage of VMO therapy. Evaluation of serological responses of patients undergoing VMO treatment by an enzyme-linked immunosorbant assay (ELISA) showed a positive correlation between IgG antibody binding to cultured melanoma cells and disease-free survival.     

The effect of interferon-β on blood—brain barrier disruptions demonstrated by constrast-enhanced magnetic resonance imaging in relapsing—remitting multiple sclerosis

Magnetic resonance imaging (MRI) has been a valuable tool to understand the pathophysiology and natural history of multiple sclerosis (MS), and increasing attention is focusing on the use of MRI findings as outcome measures in treatment trials in MS. The recently completed trial of interferon-β-1b (IFN-β1b) demonstrated a decrease in accumulation of diseased tissue on T2-weighted images and a reduction in new lsions on T2-weighted images. To examine the effect of IFN-β1b on blood-brain barrier (BBB) breakdown, and to provide additional insights into the usefulness of MRI in the evolution of effectiveness of experimental treatments in MS, we used the contrast-enhanced lesion frequency of 7-month baseline MRIs compared with the enhanced lesion frequency for 6-month treatment period MRIs in 14 relapsing-remitting (RR) MS patients. Longer baselines were also available for analysis in a subset of 8 patients, as these patients had been followed by monthly MRI in a natural history study for up to 4 years prior to the current study. A significant reduction in the total or new enhancing lesion frequency was detected in the patients analyzed as a whole, and 13 of 14 of the patients demonstrated a reduction in enhancing lesion frequency on treatment over the 6 months studied. These findings suggest that IFN-β has a mechanism of action that at least temporarily inhibits the opening of the BBB in RRMS patients. This trial also illustrates the usefulness of a baseline versus treatment trial design to evaluate the effect of drug therapy in MS.     

Inhibition of heparin activity in plasma by soluble fibrin: evidence for ternary thrombin-fibrin-heparin complex formation

The ability of heparin to dramatically enhance the inactivation of thrombin (IIa) by antithrombin III (ATIII) in buffer is negated through formation of a IIa-fibrin-heparin ternary complex (Hogg and Jackson, Proc Natl Acad Sci USA 86:3619, 1989; Hogg and Jackson, J Biol Chem 265:241, 1990). IIa, in this ternary complex, is protected from inactivation by ATIII. Our aim was to determine whether fibrin also compromises heparin efficacy in plasma. We found that soluble fibrin ablated the heparin-mediated prolongation of the thrombin time with half-maximal effect at 60 nmol/L fibrin. The heparin-mediated prolongation of the activated partial thromboplastin time (APTT) was also reduced by fibrin with half-maximal effects at 140 nmol/L fibrin using 0.12 U/mL heparin and 500 nmol/L fibrin using 0.25 U/mL heparin. The mechanism of inhibition of heparin activity by fibrin in plasma was determined by measuring IIa-ATIII complexes by enzyme-linked immunosorbent assay (ELISA). Fibrin was found to inhibit the heparin- catalyzed inactivation of IIa by ATIII with half-maximal effect at 97 +/- 19 nmol/L fibrin. Fibrin had no effect on the heparin-catalyzed inactivation of factor Xa by ATIII in plasma, using either standard heparin, a heparinoid preparation (Orgaran; Organon, Lane Cove, Sydney, Australia), or low-molecular weight heparin. These findings imply that fibrin is a potent modulator of heparin activity in vivo by inhibiting heparin-catalyzed IIa-ATIII complex formation through formation of ternary IIa-fibrin-heparin complexes.     

JEWISH RELIGIOUS PRACTICES RELATED TO CHILDBEARING*

Practices related to childbearing and the postpartum period are influenced by religious beliefs and traditional customs. Among the Jewish people, these practices vary in accordance with the identification of the Jew with either an Orthodox, Conservative, or Reform group. The nurse-midwife must be familiar with the practices of her clients. The Jewish religion has a profound influence on the total life of the individual Jew. Specific laws govern the dietary habits, the important days of the calendar, marriage, and childbearing. Most of these religious laws are derived from statements in the Bible and the commentaries of the rabbis of old. Circumcision, one of the fundamental religious rites and ceremonies of Judaism, must be observed in a ritual manner on the eighth day after birth. At this time a Hebrew name is bestowed on the male child. A female child is named in the synagogue soon after birth. Members of the Jewish faith adhere to many different customs. It behooves the nurse-midwife to be familiar with some of the major concepts of the Jewish religion in order to better care for her Jewish clients and their families.     

Inhibition of macrophage-induced tumor cell cytostasis and cytolysis by tumor-promoting phorbol diesters

The effects of 3 tumor-promoting phorbol diesters and the corresponding inactive polyol phorbol on cytostatic and cytolytic activities of activated murine peritoneal macrophages toward target tumor cells derived from skin cells of the same species were examined. In both cases the diesters, without showing concurrent toxicity, considerably suppressed in dose-related fashion, the activity of the macrophages at concentrations active in promotion in vivo, being active even in nanogram quantities. The order of activity among different diesters for cytostasis or cytolysis was the same as that observed toward tumor promotion in mouse skin. The non-promoter phorbol was inactive in all instances. These findings concur with proposals for an important role for abrogation of normal antitumor defense mechanisms in promotion of mouse skin carcinogenesis by active phorbol diesters.