Induction of neural tissue markers by micronized human spinal cord implants.

The osteoinductive capacity of biological noncellular material has been widely recognized. Studies using bone morphogenetic proteins and acellular bone matrix demonstrate that host mesenchymal cells can be readily transformed into osteoprogenitor cells. The current study sought to determine whether another biological noncellular material, human spinal cord matrix, could induce transformation of host cells into a neural lineage. We demonstrate the formation of neural tissue and the expression of neural-specific lineage markers in host cells colonizing implanted spinal cord fragments and adjacent tissue along with the lack of expression of nonneural lineage markers. These studies demonstrate that the inductive capacity of biological noncellular material is not limited to the osteogenic lineage and suggest that acellular spinal cord matrix could be used to generate host-derived cells for use in neural repair and regeneration.

A comparison of two microbial detection methods used in aseptic processing of musculoskeletal allograft tissues.

Tissues from 78 musculoskeletal donors were concurrently tested for microorganisms using both a swab and liquid culture method. An aggregate total of 20 organisms were detected by both methods. The swab detected 4/20 organisms while the liquid culture detected 18/20 organisms. The swab method yielded sensitivity and negative predictive values of 20 and 92.3%, respectively. Comparatively, the liquid culture displayed a sensitivity of 90% and a negative predictive value of 99%. These results clearly demonstrate that the liquid culture method is superior to swab cultures in microbial detection. Additional studies are necessary to determine the optimal culture conditions for different types of tissues when utilizing the liquid culture method.

Optic canal decompression: a cadaveric study of the effects of surgery.

PURPOSE: To simulate a transphenoidal medial optic canal decompression and determine the anatomic effect on the optic nerve. METHODS: A medial optic canal decompression was performed on 5 cadaveric optic canals within 12 hours of death. Two canals were decompressed under direct visualization and 3 were decompressed by a transphenoidal endoscopic approach. The optic canal was subsequently removed en bloc, beginning at the annulus of Zinn and extending to the optic chiasm. Each specimen was processed and examined grossly. Serial coronal step sections of the entire length of the intracanalicular optic nerve were assessed histologically. RESULTS: Microscopic examination of the intracanalicular portion of optic nerve revealed incision in an extraocular muscle at the annulus, incomplete bone removal, fraying of the dural sheath, incomplete dural/arachnoid release, and incision in the pia and optic nerve. CONCLUSIONS: Transphenoidal medial wall decompression of the optic nerve canal with dural sheath opening may induce physical damage to the nerve. Any hypothetical value in dural-arachnoid sheath opening must be weighed against the potential for harm to the optic nerve caused by the surgical intervention.

Blood and marrow cultures as indicators of bone contamination in cadaver donors.

Of 770 cadaver bone donors evaluated, 185 had positive blood or ilium marrow aspirate cultures. These donors were matched with an immediately preceding or subsequent donor with negative blood and marrow cultures. Donors with cultures positive for skin contaminants only were not included in the study. Samples of the blood and bone marrow, surface swab cultures, and cultures of tissue samples of the excised skeletal tissues were obtained at the time of tissue procurement. There were 88 (48%) donors with similar microbial species recovered from the blood and ilium marrow. These donors had a higher rate of positive bone cultures (30%) than donors with positive blood (15%) or marrow cultures only (11%) or donors with negative blood and marrow culture results (7.3%). Recovery of similar isolates from the blood and marrow had a positive predictive value of 72% for the isolation of the same types of organisms from the excised tissues compared with 38% for donors with positive blood cultures only. Although not absolute predictors of tissue contamination, combined blood and bone marrow cultures were more reliable indicators of tissue contamination than blood cultures alone.

Medication Development of Ibogaine as a Pharmacotherapy for Drug Dependencea.

The potential for deriving new psychotherapeutic medications from natural sources has led to renewed interest in rain forest plants as a source of lead compounds for the development of antiaddiction medications. Ibogaine is an indole alkaloid found in the roots of Tabernanthe iboga (Apocynaceae family), a rain forest shrub that is native to equatorial Africa. Ibogaine is used by indigenous peoples in low doses to combat fatigue, hunger and in higher doses as a sacrament in religious rituals. Members of American and European addict self-help groups have claimed that ibogaine promotes long-term drug abstinence from addictive substances, including psychostimulants and cocaine. Anecdotal reports attest that a single dose of ibogaine eliminates withdrawal symptoms and reduces drug cravings for extended periods of time. The purported antiaddictive properties of ibogaine require rigorous validation in humans. We have initiated a rising tolerance study using single administration to assess the safety of ibogaine for the treatment of cocaine dependency. The primary objectives of the study are to determine safety, pharmacokinetics and dose effects, and to identify relevant parameters of efficacy in cocaine-dependent patients. Pharmacokinetic and pharmacodynamic characteristics of ibogaine in humans are assessed by analyzing the concentration-time data of ibogaine and its desmethyl metabolite (noribogaine) from the Phase I trial, and by conducting in vitro experiments to elucidate the specific disposition processes involved in the metabolism of both parent drug and metabolite. The development of clinical safety studies of ibogaine in humans will help to determine whether there is a rationale for conducting efficacy trials in the future.