A near-fatal reaction during granulocyte transfusion of a neonate

Although reactions to granulocyte transfusions in neonates are rarely reported, we observed a near-fatal pulmonary reaction, presumably due to white cell antibodies, in a neonate with Rh hemolytic disease. The hemolytic disease was being treated with exchange transfusions, and at 2 days after the infant's birth, bacterial sepsis was suspected and granulocyte transfusions were begun. The first granulocyte transfusion (Day 3) was uneventful. Five minutes after the beginning of the second granulocyte transfusion (Day 4), severe respiratory distress, hypotension, bradycardia, cyanosis, and acidosis suddenly occurred. The infant's serum obtained after the reaction contained granulocytotoxic and B-lymphocytotoxic antibodies that reacted with leukocytes from the second granulocyte donor. Antibodies could not be detected either in the initial infant serum or in maternal serum. However, an antileukocyte antibody was present in the serum of a parous woman donor. We used plasma from this woman to prepare reconstituted whole blood for the exchange transfusion that we performed immediately preceding the second granulocyte transfusion. Despite the sequence of events, an irrefutable cause-and-effect mechanism could not be established because the properties of the donor and neonatal antibodies were similar, but not identical. However, this catastrophic event emphasizes both the potential for adverse effects of granulocyte transfusions in neonates and the need for caution when transfusing blood from parous women.     

Isolation and partial characterization of lymphocyte surface immunoglobulins

Immunoglobulins were isolated from the surfaces of lymphocytes from a variety of lymphocyte populations including murine and human thymus lymphocytes and murine spleen and thoracic duct lymphocytes. Cell surface proteins were labeled with iodide-¹²⁵I by lactoperoxidase-catalyzed iodination, and recovered in solution either by solubilization in dissociating solvents or active metabolic release. Immunoglobulins were identified and isolated by immunological coprecipitation. The polypeptide chain structure of immunoglobulins isolated from lymphocyte surfaces was analyzed by polyacrylamide gel electrophoresis of reduced, alkylated samples in acid urea. Human and murine thymus lymphocytes possessed only IgM immunoglobulin on their surfaces. This protein contained light chains and µ-type heavy chains and was characterized by a molecular weight of approximately 200,000. Murine splenic lymphocytes from CBA x C57 animals and congenitally athymic (nu/nu) mice possessed both IgM and IgG on their surfaces. The ratio of µ-chain to γ-chain was about 3/1. The presence of IgM on thymus lymphocytes probably does not reflect trace contamination by B lymphocytes because comparable quantities of IgM were isolated from both cell populations. Metabolic turnover data suggest that this immunoglobulin is synthesized by the cell population studied. These results provide direct evidence for the presence of immunoglobulins composed of light and heavy polypeptide chains on the surfaces of lymphocytes of all classes.     

Using the Exception from Informed Consent Regulations in Research

This article reflects the proceedings of a breakout session, “Using the Regulations in Research” at the 2005 Academic Emergency Medicine Consensus Conference, “Ethical Conduct of Resuscitation Research.” There have been two organized studies, and a number of anecdotal reports, describing the decline in cardiac arrest resuscitation research in the United States since the implementation of the Final Rule. Paradis and colleagues found that the volume of human cardiac arrest research published in the United States was significantly less in a four‐year period after the Final Rule was adopted as compared to the earlier period. Nichol and colleagues reported that both the absolute number of US‐based randomized cardiac arrest trials and the proportion of US‐based trials (vs. foreign trials, based on the mailing address of the first author) decreased by about 15% annually. Despite the concern about a negative impact, there are at least five published trials, one in progress and one in planning that have been or are being conducted under the regulations. Those completed include the Diaspirin Cross‐Linked Hemoglobin, Public Access Defibrillation, Multicenter Vest CPR, Brain‐CPR, and Pre‐Hospital Treatment of Status Epilepticus trials. Reports of how investigators met the regulations and their experience in doing so are reviewed. A summary table of the federal regulations is provided. Participants discussed what additional information and research about using the regulations would be helpful for the promotion of quality resuscitation and emergency care research in the United States. Areas suggested for further investigation include: impact on the quality as well as quantity of such research; current level of understanding of the regulations by investigators, regulatory/IRB personnel and potential subjects (the general public); costs incurred: additional time required for preparation, approval and conducting community consultation and public disclosure; impact on research on non–life‐threatening conditions; value and cost of a registry; use of a standard reporting template for issues regarding meeting the requirements in individual clinical trials; whether more specific guidance would be helpful or restrictive; what constitutes effective community consultation and public disclosure; and whether titration of community consultation and public disclosure based on the risk of the proposed intervention to subjects is feasible and acceptable.     

Plasma and oral fluid pharmacokinetics and pharmacodynamics after oral codeine administration

BACKGROUND: The ease, noninvasiveness, and safety of oral fluid collection have increased the use of this alternative matrix for drugs-of-abuse testing; however, few controlled drug administration data are available to aid in the interpretation of oral fluid results. METHODS: Single oral codeine doses (60 and 120 mg/70 kg) were administered to 19 volunteers. Oral fluid and plasma were analyzed for free codeine, norcodeine, morphine, and normorphine by solid-phase extraction combined with gas chromatography-mass spectrometry (SPE/GC-MS). Physiologic and subjective effects were examined. RESULTS: Mean (SE) peak codeine concentrations were 214.2 +/- 27.6 and 474.3 +/- 77.0 micro g/L in plasma and 638.4 +/- 64.4 and 1599.3 +/- 241.0 micro g/L in oral fluid. The oral fluid-to-plasma ratio for codeine was relatively constant ( approximately 4) from 1 to 12 h. The mean half-life (t(1/2)) of codeine was 2.2 +/- 0.10 h in plasma and 2.2 +/- 0.16 h in oral fluid. Significant dose-related miosis and increases in sedation, psychotomimetic effect, and "high" occurred after the high dose. Mean codeine oral fluid detection time was 21 h with a 2.5 microg/L cutoff, longer than that of plasma (12-16 h). Detection times with the proposed Substance Abuse and Mental Health Services Administration cutoff (40 microg/L) were only 7 h. Norcodeine, but not morphine or normorphine, was quantified in both plasma and oral fluid. CONCLUSIONS: The disposition of codeine over time was similar in plasma and oral fluid, but because of high variability, oral fluid codeine concentrations did not reliably predict concurrent plasma concentrations. Oral fluid testing is a useful alternative matrix for monitoring codeine exposure with a detection window of 7-21 h for single doses, depending on cutoff concentrations. These controlled drug administration data should aid in the interpretation of oral fluid codeine results.     

Anesthesia for children in Sub-Saharan Africa – a description of settings, common presenting conditions, techniques and outcomes

Anesthesia in developing countries deserves special attention. The most common technique is general anesthesia (with spontaneous or manually assisted ventilation). Nonmedical anesthetists with limited training and supervision and lacking the most common drugs and anesthetic equipment administer anesthesia, usually for emergency surgery. There are important safety issues, especially for pediatric anesthesia. Regarding pediatric surgery, the major workload is due to abdominal emergencies, mainly neonatal bowel obstruction or peritonitis due to typhoid perforation. The morbidity and mortality rate for these conditions is high.