Billy E. Buck

Bone transplantation and human immunodeficiency virus. An estimate of risk of acquired immunodeficiency syndrome (AIDS).

The possibility of transplanting a bone allograft from a donor infected with human immunodeficiency virus (HIV) is remote, provided there is a combination of rigorous donor selection and exclusion, screening for the HIV antigen and antibody, and histopathologic studies of donor tissues. The chance of obtaining a bone allograft from an HIV-infected donor who failed to be excluded by the above techniques is calculated to be one in well over a million, using average estimates. On the other hand, if adequate precautions are not taken (for example, by testing only for antibodies to HIV), the risk might be as high as one in 161.

Acquired immunodeficiency syndrome in infants

Fourteen infants with clinical and laboratory features of an acquired immunodeficiency syndrome were identified in a single metropolitan area from November 1980 to July 1983. Patients were predominantly of Haitian parentage, although two cases occurred in offspring of non-Haitian intravenous drug abusers. Only one patient had received a blood transfusion before the development of clinical findings. The predominant clinical findings included failure to thrive, persistent infection of the oral mucosa by Candida albicans, chronic pulmonary infiltrates, hepatosplenomegaly, lymphadenopathy, and diarrhea. Immunologic studies showed most of the infants to have inverted ratios of T-cell subsets, greatly increased immunoglobulin levels, and circulating immune complexes. Lymphopenia was not common, as it is in adult patients. Infectious agents responsible for opportunistic infections in this series included Pneumocystis carinii, herpesviruses, particularly cytomegalovirus, and C. albicans. Bacterial infections were common, and gram-negative sepsis was the major cause of death in the seven infants who have died. At autopsy, two infants had disseminated lymphadenopathic Kaposis sarcoma. These observations suggest the likelihood of transplacental, perinatal, or postnatal transmission of an as yet unidentified infectious agent that causes this disease.

Human immunodeficiency virus cultured from bone. Implications for transplantation

This study demonstrates by a virologic culture method that human immunodeficiency virus (HIV) resides in bone. After freezing, some initially positive specimens no longer yielded virus, but those that continued to yield virus were not further altered by subsequent washing, which removed essentially all marrow, or by freeze-drying. The safeguards against potential transmission of HIV by a bone allograft are principally the screening and testing methods previously described, although there may be a further reduction of the remote residual risk by the freezing step in the usual technical sequence for tissue banking by sterile techniques.

Medication Development of Ibogaine as a Pharmacotherapy for Drug Dependencea

ABSTRACT: 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.

Incidence of clostridial contamination in donors’ musculoskeletal tissue

Reports of infection by Clostridium sordellii associated with allograft transplantation have generated considerable interest. We report our experience in recognising clostridial contamination in cadaver donors of musculoskeletal tissue. Tissues obtained from 795 consecutive donors were excised using standard surgical techniques. Samples of blood and bone marrow were also obtained. Donors with clostridia recovered from any site were matched with the preceding donor without clostridia as a procedural and environmental control. The histories of the donors were analysed to determine which variables had a relationship to contamination by running a contingency table and chi-squared test on the variables against the event of a donor being contaminated. Sixty-four donors (8.1%) had clostridia, most commonly C. sordellii. Clostridia were grown from the blood, marrow and tissue samples of 52, 37 and 30 donors, respectively. In eight cases, they were cultured from the tissue samples alone. There was no significant difference in age or gender between the contaminated donors and the control group. Open wounds were more common in control than in contaminated subjects, but only death by drowning in the contaminated group was statistically significant (p = 0.02). The time between death and the excision of tissue which was contaminated (16 hrs 10 mins) compared with control (11 hrs 10 mins) donors was also significant (p < 10(-6)). We conclude that there is clostridial contamination in a significant number of tissue donors, particularly with increasing time between death and tissue excision. Among the most commonly encountered species is C. sordellii. Multiple microbiological cultures, including blood, are necessary in order to identify clostridial contamination.

Distribution and number of transferrin receptors in Parkinson's disease and in MPTP-treated mice

Transferrin is a glycoprotein that functions primarily to deliver iron to the cell. Recent studies suggest that the transferrin receptor mediates the intracellular delivery and transport of iron bound to transferrin in the CNS. Iron-catalyzed free radical generation has been proposed as a possible cause of nigral cell death in Parkinsons disease. Our hypothesis is that abnormal iron handling by the transferrin receptor may contribute to the formation of free radical species which catalyze the lipid peroxidation of nigral cell membranes. We have assessed the number of transferrin receptors on membrane fractions prepared from the human striatum from control subjects and patients with Parkinsons disease. Equilibrium-binding studies demonstrated a reversible, saturable, and high-affinity transferrin binding site (KD = 3 nM) in human brain membranes. Regional binding assays indicate that the number of transferrin receptors in the putamen was reduced significantly in Parkinsons disease. The density of transferrin receptors was unaltered in membranes prepared from the caudate nuclei and the globus pallidus. To address the possibility that transferrin receptors are located on dopaminergic terminals, we have examined the distribution and number of transferrin receptors in the striatum of MPTP-treated mice using in vitro autoradiographic methods. In these experiments, the loss of dopaminergic terminals in the striatum was visualized by differential [3H]mazindol uptake site autoradiography. A marked reduction in the density of both transferrin receptors and [3H]mazindol binding sites was observed in the mouse striatum 7 days post-MPTP treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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.

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.

Cultivation of Human Chondrocytes on Cartilage Fluff Matrix without Loss of Phenotypic Expression

Chondrocytes grown from cartilage explants and then cultured with rehydrated previously desiccated thin strands of cartilage called “cartilage fluff matrix” or “fluff” filled the gaps between the strands of fluff making new cartilage and invaded the cartilage strands. The cells stained similar to the deep layers of normal articular cartilage though at least 60 days of culture. The chondrocytes binded the cartilage strands together and filled the gaps with new cartilage creating a solid construct.