Dose-Specific Effects of Alcohol on the Lifespan of Mice and the Possible Relevance to Man

To determine the effects on lifespan of daily consumption of alcohol throughout adulthood, three groups of 100 male mice each (strain C57BL/J0J)-housed one to a cage-were given 3.5%, 7.5% and J2% v/v alcohol in distilled water as the only source of drinking fluid. On the basis of relative metabolic capacity, the resulting consumption levels could be considered comparable to a range in man from a moderate to an alcoholic intake. Two control groups of 100 mice each-one group singly housed and the other housed five to a cage-received distilled water ad libitum. There was no difference between the survival curves of the low alcohol and water-drinking singly housed controls. The medium alcohol mice had the longest mean lifespan of the five groups and the high alcohol mice had the shortest. There were no clear alcohol-related group differences in post mortem histology, although the early deaths in the high alcohol group showed evidence of a high rate of liver abnormality. The applicability of the findings to man is discussed.     

Thromboembolic Risk of Patients Referred for Radiofrequency Catheter Ablation of Typical Atrial Flutter Without Prior Appropriate Anticoagulation Therapy

GRÖNEFELD, G.C., et al.: Thromboembolic Risk of Patients Referred for Radiofrequency Catheter Ablation of Typical Atrial Flutter Without Appropriate Prior Anticoagulation Therapy. Background: Radiofrequency catheter ablation of isthmus dependent atrial flutter is considered the therapy of choice. There is, however, controversy with regard to the thrombogenicity of atrial flutter in comparison with atrial fibrillation. Methods: Consecutive patients scheduled for catheter ablation of documented typical atrial flutter receiving insufficient (INR < 2.0) or no anticoagulation during the three weeks preceding the procedure underwent multiplane transesophageal echocardiography (TEE). Patients with exclusive documentation of atrial flutter were classified as group I, whereas patients with additional documentation of atrial fibrillation were classified as group II. Results: The study included 201 patients, 62 of whom were not on therapeutic anticoagulation (mean age   64 ± 9   years, 87% men). In 10 of these 62 patients (16%), TEE detected a left atrial (LA) appendage thrombus in 4, or dense spontaneous echo contrast (SEC) in 6 patients. Comparison of patients with versus without SEC or thrombus, revealed a higher incidence of valvular heart disease (60% vs 26%,   P = 0.05   ), but no differences with respect to age, gender, LA diameter, left ventricular end-diastolic diameter, or left ventricular ejection fraction. The incidence of positive TEE findings in group I was 1 in of 36 versus 9 of 26 in group II (3% vs 35%, P < 0.001), and the relative risk for thromboembolism in group II versus group I was 12.5 (95% CI: 3-55, P < 0.001). Conclusion: There is a significant risk for thromboembolism in patients referred for ablation of typical atrial flutter who have not been appropriately anticoagulated. (PACE 2003; 26[Pt. II]:323–327)     

Successful hip arthroplasty in an adult male with severe factor XI deficiency using Hemoleven®, a factor XI concentrate

Summary. Severe factor XI (sFXI) deficiency is a rare bleeding disorder (RBD). FXI replacement is most often required for surgical hemostasis. Plasma, the sole US treatment option, is often complicated by life‐threatening allergic reactions. In such circumstances, the FDA offers a mechanism for institution‐industry collaboration to facilitate limited use of replacement products licensed abroad. A 58 years old man with sFXI deficiency, required hip replacement. In the past, he received prophylactic plasma for thyroidectomy and experienced a severe allergic reaction. A single use institutional IND FDA application was initiated in collaboration with LFB (Les Ulis, France) to access Hemoleven^®, a plasma‐derived FXI concentrate. The application required an investigator‐initiated IRB‐approved protocol for treatment and safety/efficacy monitoring that included: preoperative thrombophilia, FXI inhibitor and pharmacokinetic (PK) evaluations; peri‐ postoperative administration of ≤ 4 doses of 10‐15 U/kg Hemoleven^®; DIC monitoring; postoperative thromboprophylaxis; observation for product efficacy and potential complications. PK study demonstrated the expected 1.8% FXI recovery per U/kg with half‐life of 62 hours. Mild D‐Dimer elevation was noted 6‐9 hours post‐infusion. The initial dose (15U/kg) was administered 15 hours before surgery; subsequently, 3 doses (10U/kg) were infused every 72 hours. Hemostasis was excellent. No complications were observed. Collaboration allowed for successful patient access to Hemoleven^® with excellent PK, safety, and efficacy. This case underscores the need for additional efforts to ensure safe and effective licensed replacement therapies for RBD patients.     

Of Pacemakers and Statistics: The Actuarial Method Extended

Pacemakers cease functioning because of either natural battery exhaustion (nbe) or component failure (cf). A study of four series of pacemakers shows that a simple extension of the actuarial method, so as to incorporate Normal statistics, makes possible a quantitative differentiation between the two modes of failure. This involves the separation of the overall failure probability density function PDF(t) into constituent parts pdf_nbe(t) and pdf_cf(t). The approach should allow a meaningful comparison of (he characteristics of different pacemaker types.