Immunogenicity and safety in adults of a new chromatographically purified Vero-cell rabies vaccine (CPRV): a randomized, double-blind trial with purified Vero-cell rabies vaccine (PVRV).

Recent improvements in chromatographic purification procedures have made it possible to develop a new chromatographically purified rabies vaccine (CPRV) by further purifying the current rabies vaccine prepared from Vero-cell culture (Verorab; Pasteur Mérieux Connaught). The immunogenicity and safety of primary immunization, followed by a booster at one year, with CPRV was compared to that of the purified Vero cell vaccine (PVRV) in a randomized, double-blind study carried out at four veterinary schools in France. A total of 330 healthy, male and female, first-year veterinary students, aged at least 18 years and who required pre-exposure rabies prophylaxis, were enrolled in this study. Included subjects were randomly assigned either CPRV (n = 163) or PVRV (n = 167) to be given as a primary immunization series of three intramuscular injections (D0, D7, D28), followed by a booster after 1 year (D365). Blood samples for serological analysis were taken at D0 (before first injection), D28, D42, D180, D365 (before booster) and D379. All subjects developed a strong immune response to the primary series, and at D42, all subjects had seroconverted for rabies neutralizing antibody (serum titre > or = 0.5 IU/ml). The rabies virus-neutralizing antibody GMT value at D42 in the CPRV group (23.0 IU/ml) was non-inferior to that in the PVRV group (29.6 IU/ml), according to a one-sided non-inferiority test. While antibody titres tended to decrease over the period of follow-up, at D365 (before booster), 97.5% subjects in the CPRV group and 98.8% of subjects in the PVRV group remained seroconverted. After booster, although the rabies antibody GMT value in the CPRV group was lower than that in the PVRV group, all subjects in both groups were seroconverted, and the difference is probably not clinically important. The incidence of local and systemic reactions tended to decrease with each dose during the primary immunization series, followed by a slight increase after booster (significant time-effect in an exploratory logistic regression analysis). Although mild or moderate local reactions tended to be more frequent after injection with CPRV compared to PVRV, systemic reactions were reported less often (significant group-effects in exploratory logistic regression analyses). One serious adverse event possibly related to vaccine occurred during this study (severe asthenia after the third dose of PVRV). This comparative study in healthy young adults demonstrates that the new chromatographically purified rabies vaccine is as immunogenic as PVRV, and seems to be associated with fewer systemic reactions.

[Functional results following complicated injuries of the extremities--how can they be improved?]. / Funktionsergebnisse nach komplizierten Extremitäten-Traumen--Wie lassen sie sich verbessern?

This study evaluates the critical points in the management of 48 patients with injured arteries of the lower limb between 1980 and 1986. 77% of the traumas were resultant from blunt vehicular traffic mishaps. 13 patients were treated within 6 h, 8 patients later than 6 h, 21 patients later than 24 h post injury. Delays in diagnosis occurred due to lack of or no indication for vascular trauma. Careful physical examination and aggressive use of angiography is essential in improving limb salvage rates, while doppler investigation may lead to improper diagnosis. Overall limb salvage was 69%, however, no reconstruction was possible in 6 cases (13%). 38 of the 42 arterial reconstructions required interposition of venous bypass grafts, four end to end anastomoses. Eleven patients had associated venous injuries, which in nine cases were repaired. Venous ligation in three cases was attributed with increased complication. In three cases ischemia time was shortened by the use of temporary javid shunts for rapid restoration of arterial flow. 50% of the patients were found to require fasciotomy, either pre- or postvascular repair. Early fasciotomy, however was found to be most beneficial. Fractures were treated in 15 cases with the external fixator, in 21 cases with internal fixation. Delayed revascularization after 24 h combined with aggressive debriding of muscle necrosis and the employment of vascularized muscular and skin flaps resulted in a decline in amputation rates and improved functional results.