Solvent/detergent plasma for prevention of bleeding in recessively inherited coagulation disorders: dosing, pharmacokinetics and clinical efficacy.

BACKGROUND AND OBJECTIVES: This open-label multicenter trial of solvent/detergent (SD) plasma involving 17 patients with recessively inherited coagulation disorders (one afibrinogenemia, four FV, six combined FV and FVIII, one FX and five FXI deficiencies) evaluated the pharmacokinetics of the deficient factors and hemostatic efficacy. DESIGN AND METHODS: In vivo recovery (IVR) of the deficient coagulation factor was determined in a non-bleeding state in all patients and the mean values for FV, FVIII, FX, FXI and fibrinogen were 1.3, 1.2, 1.5, 1.3 and 1.5 dL/Kg, respectively. The mean plasma half-life of FV, FVIII and FX was 18, 43 and 33 hours, respectively. All patients underwent replacement therapy for elective procedures at risk of bleeding (surgery in 14 cases and vaginal delivery in two patients), except one treated for a central nervous system surgical emergency. RESULTS: Treatment courses with SD plasma were judged fully effective in 13/16 cases (81%). In the remaining three cases, mild bleeding occurred after major surgery in a FV deficient patient with a factor level of 43% and in a FXI deficient patient when factor levels were between 20% and 41%; and after minor surgery in a patient with FV and FVIII deficiency when factor levels were 41% and 18%, respectively. Bleeding was controlled by continuing or increasing treatment with SD plasma. INTERPRETATION AND CONCLUSIONS: These results suggest that, even though the current absolute risk of blood-borne infections associated with fresh-frozen plasma is relatively small, SD plasma should be preferred in patients with recessively inherited coagulation disorders who need replacement therapy when virus-inactivated single-factor concentrates are not available.

Removal of organic debris from bovine dentin shavings.

A common problem with root canal failures is chronic inflammation at the apex caused by overfilling of root canal materials. Dentin filings have been suggested as an apical plug to create a biocompatible barrier between the filling material and the periapical tissue. Unfortunately residual organic material, such as pulp remnants or bacteria, still may be part of the filings. Dentin filings removed from the tooth, cleaned, and then used to form a barrier might serve as an effective barrier. The purpose of this study was to evaluate methods of cleaning dentin of organic debris. NaOCl, sodium dodecyl sulfate, and 1% Triton X-100 were used to treat dentin shavings and were evaluated by a micro bicinchoninic acid protein analysis assay. Two series of experiments were performed. One compared the effect of temperature while using phosphate-buffered saline as a control and the second compared exposure times. The percentage of protein extracted from dentin samples increased with temperature. Sodium hypochlorite at room temperature extracted 24.6%, NaOCl at 37 degrees C extracted 26.9%, and NaOCl at 70 degrees C extracted 33.9%. Only NaOCl at 37 degrees C and 70 degrees C showed statistically significant differences from phosphate-buffered saline at room temperature with p-values of 0.028 and 0.019, respectively. The exposure time series showed a difference between a phosphate-buffered saline solution and 6.25% NaOCl. NaOCl removed approximately 90% of protein compared with 60% for the phosphate-buffered saline. A 10-min exposure to 70 degrees C 6.25% NaOCl may be an efficient means of removing organic material from dentin shavings.

A novel surfactant nanoemulsion with broad-spectrum sporicidal activity against Bacillus species.

Two nontoxic, antimicrobial nanoemulsions, BCTP and BCTP 401, have been developed. These emulsions are composed of detergents and oils in 80% water. BCTP diluted up to 1:1000 inactivated>90% of Bacillus anthracis spores in 4 h and was also sporicidal against three other Bacillus species. This sporicidal activity is due to disruption of the spore coat after initiation of germination without complete outgrowth. BCTP 401 diluted 1:1000 had greater activity than BCTP against Bacillus spores and had an onset of action of <30 min. Mixing BCTP or BCTP 401 with Bacillus cereus prior to subcutaneous injection in mice reduced the resulting skin lesion by 99%. Wound irrigation with BCTP 1 h after spore inoculation yielded a 98% reduction in skin lesion size, and mortality was reduced 3-fold. These nanoemulsion formulas are stable, easily dispersed, nonirritant, and nontoxic compared with other available sporicidal agents.

Transurethral enzyme injection--future management of benign prostatic hyperplasia.

Although benign prostatic hyperplasia, a common condition among elderly men, has been effectively treated with transurethral resection of the prostate, this surgical procedure is associated with many well-recognized risks and complications. Because of this potential morbidity and mortality, various alternative treatment strategies for benign prostatic hyperplasia have been proposed. The use of enzyme solubilization and ablation of prostatic tissue to alleviate urinary outlet obstruction has proved effective in dogs and warrants investigation in human trials. Transurethral enzyme injection of the prostate has the potential for being a treatment modality with minimal invasiveness, limited requirements for anesthesia, and minimal associated toxicity for the management of benign prostatic hyperplasia.

Immune response inhibition by irrigating subchondral bone with cytotoxic agents.

Attempts have been made (in the recent past) to inhibit the immune response to fresh osteoarticular (shell) allografts because the occurrence and the magnitude of this response is considerably greater and more harmful than that seen after frozen bone and soft tissue allografts. To decrease in immunogenicity of these fresh grafts, the subchondral bone of rat distal femur allografts was irrigated with Betadine scrub solution (n = 10) or Triton-X (n = 11) before transplantation (Study 1). The Triton-X significantly reduced the immunogenicity of the grafts, but the Betadine scrub solution had no effect. A similar experiment with Triton-X was done in sheep where trochlear knee autografts (n = 3) were compared with unirrigated allografts (n = 3) and allografts receiving irrigation with Triton-X (n = 3) (Study 2). All 3 Triton-X irrigated allografts had no immune response, and showed much improved grafts compared with the control allografts (where an immune response developed in 2 of 3). Neither of the 2 allograft groups were as good as the autografts. These techniques may prove useful for inhibiting the recipient immune responses to fresh osteoarticular allografts in humans requiring partial joint reconstruction.