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.

Creutzfeldt-Jakob disease in a recipient of a dura mater graft processed in the US: cause or coincidence?

Iatrogenic Creutzfeldt-Jakob disease (CJD) has never been reported among recipients of dura mater grafts processed in the US. We recently investigated a report of such a case in a 72-year-old man with a typical clinical presentation of CJD. We found no evidence of CJD in either the 34-year-old donor or in other, proximal patients undergoing craniotomies. Although the graft may have caused the illness, sporadic CJD is a more likely explanation, with the graft being coincidental.

Medication development of ibogaine as a pharmacotherapy for drug dependence.

The potential for deriving new psychotherapeutic medications from natural sources has led to renewal 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 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.

The potential for HIV transmission through allogeneic bone. A review of risks and safety.

Over the past two decades, oral and maxillofacial surgeons have gained a greater appreciation for the biology of allogeneic bone healing, resulting in a dramatic increase in its indications and use. Unfortunately, this time period has also ushered in near epidemic proportions of HIV-infected persons, some of whom might be considered as potential donors of allogeneic bone. As this article will discuss, surgeons and tissue bank teams alike must be aware of the clinical and serologic criteria associated with an acceptable donor. Only in this way can contamination-free specimens be obtained and surgically implanted.

Human bone and tissue allografts. Preparation and safety.

Currently, modern tissue banks routinely supply requested bone and soft-tissue allografts. These allografts are safe if tissue-bank personnel adhere to the existing methodology for excluding any donors with potential for disease transmission. The authors' discard rate after excision of tissues has been approximately 18%, reflecting their concern for allograft safety. The preparation of significant numbers of allografts is labor intensive and very expensive, as is multiphasic screening of donors. However, long-term success with a large number of bone or soft-tissue recipient patients has led physicians and patients to have confidence in the safety of allografts prepared as described.

Detection of hepatitis C virus infection among cadaver organ donors: evidence for low transmission of disease.

OBJECTIVE: To determine the prevalence of antibodies to hepatitis C virus (anti-HCV) and HCV RNA among cadaver organ donors and to correlate these results with donor liver histologic abnormalities and evidence for transmission of disease through organ transplantation. DESIGN: Retrospective testing of stored serum samples from cadaver organ donors for anti-HCV and HCV RNA. SETTING: Transplantation service of the University of Miami/Jackson Memorial Medical Center and other cooperative medical centers furnishing follow-up data. SUBJECTS: Of 1096 cadaver organ donors harvested between 1 January 1979 and 28 February 1991, 484 had stored serum samples available for analysis. Recipients of organs from recombinant immunoblot assay (RIBA)-positive donors for whom adequate follow-up was available were also included in the analysis. MEASUREMENTS: Samples were tested for anti-HCV by enzyme-linked immunosorbent assay (ELISA). Confirmatory testing was done using a second-generation RIBA. Hepatitis C viral RNA was detected in serum using the polymerase chain reaction. Liver biopsies were obtained from the organ donor and interpreted blindly by a pathologist unaware of the clinical data. Liver chemistry profiles and serum sample analysis for HCV RNA were done for transplant recipients. RESULTS: From the 484 cadaver organ donors, 89 samples (18%; 95% Cl, 15% to 21%) were reactive by ELISA. Of these, 33 (6.8%; Cl, 4.6% to 9%) were RIBA seropositive. Hepatitis C viral RNA sequences were detected in 50% of the RIBA-positive serum samples tested. Liver tissue was available from 24 of the 33 RIBA-positive donors and showed chronic active hepatitis in 16, chronic persistent hepatitis in 2, and no abnormality in 6. Among the 46 recipients of a kidney from a RIBA-positive donor, 13 (28%; Cl, 15% to 41%) developed post-transplant liver disease, of which only 4 cases were highly suggestive of viral transmission from the donor. Little morbidity and no mortality could be attributed to liver disease in this cohort of recipients. CONCLUSIONS: These data suggest that HCV transmission by organ transplantation is low and that the consequences of infection are small. If the medical condition of the potential recipient is so serious that other options no longer exist, the use of an organ from an anti-HCV-seropositive donor should be considered.

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 Parkinson's 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 Parkinson's 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 Parkinson's 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)

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.

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.

S100-protein-containing dendritic cells in fetal and newborn epidermis and thymus.

Skin and thymus were obtained from abortuses of varying ages and from neonatal autopsies to determine if S100-protein-containing dendritic cells were present. Using an unlabeled antibody peroxidase-antiperoxidase method, we could not detect these dendritic cells in epidermis prior to live birth, but did detect them at all fetal ages in thymus. Within 24 hours of live, full-term delivery, dendritic cells containing S100 protein were identified in epidermis.

Autopsy findings and syndromic diagnoses: Bayesian calculations for pediatric pathologists.

Application of a standard statistical method known as a Bayesian calculation to the findings in pediatric anatomic pathology may help the pediatric pathologist to recognize and express the likelihood of syndromic diagnoses. This assessment can be useful in counseling and deciding which (if any) confirmatory tests are warranted. An example shows the method and its utility.

Carcinoembryonic antigen in fetal eccrine glands: an immunohistochemical study.

Developing fetal eccrine glands were examined for the presence of carcinoembryonic antigen (CEA) using an unlabeled antibody peroxidase-antiperoxidase technique and rabbit antibody to human CEA. The earliest sign of commitment to the formation of an eccrine gland was the presence of CEA within a single keratinocyte in fetal epidermis. As the eccrine unit evolved, we found CEA in both acrosyringeal cells and the ductal cells. Although the function of CEA in eccrine gland remains undefined, this substance may play an integral role in the earliest development of the gland as well as in its normal function in the adult.

Single coronary artery originating from the right pulmonary artery.

An infant with a single coronary artery originating from the right pulmonary artery branch is the subject of this report. He survived to the age of one month possibly because of the association of two ventricular septal defects. While the pulmonary vascular resistance remained high, perfusion of the heart muscle was accomplished due to the pulmonary hypertension. The electrocardiogram did not show typical signs of infarction, but poor left ventricular contractility was observed by echocardiogram. The diagnosis was made postmortem. This specific coronary malformation has not been previously described and needs to be included in the classification of congenital coronary arteries anomalies.

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 Kaposi's sarcoma. These observations suggest the likelihood of transplacental, perinatal, or postnatal transmission of an as yet unidentified infectious agent that causes this disease.

Danger of urography in hyperuricemic children with Burkitt's lymphoma.

During three years, four patients with diffuse abdominal involvement by North American Burkitt's lymphoma presented at Children's Hospital of Philadelphia. In three of these untreated patients, an intravenous urogram showed prolonged nephrograms or tubular stasis secondary to urate nephropathy. Careful attention must be given to uric acid levels and, in some instances, nuclear and ultrasonic scanning may replace the traditional urogram or computerized tomography with contrast in the evaluation of the pediatric patient with an abdominal mass, particularly if serum uric acid levels are elevated.

Necrotizing enterocolitis in the unfed infant.

From 1974 to 1981, 139 infants with neonatal necrotizing enterocolitis (NEC) were treated at our institution. Fourteen of these infants had not been fed prior to development of NEC. The unfed infants who developed intestinal necrosis had lower birth weights, were less mature, and had lower Apgar scores. The incidence of respiratory distress syndrome (RDS) and perinatal asphyxia were significantly higher in the entire unfed group. Unfed infants generally had longstanding indwelling umbilical artery catheters. Pneumatosis intestinalis was not often seen in unfed infants, even in those who developed intestinal necrosis and perforation. Anatomic location of the disease as determined at surgery was sometimes atypical. The pathologic lesion present in the intestine of the unfed infant suggested a primarily, if not purely, ischemic etiology.