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Biomedical subjects

T F Zuck

Publications and source records attributed to T F Zuck.

At least 19 recordsLinked to original sources

Demographic characteristics and prevalence of serologic markers among donors who use the confidential unit exclusion process: the Retrovirus Epidemiology Donor Study.

BACKGROUND: Most blood centers utilize a confidential unit exclusion (CUE) process, intended to reduce the risk of transfusion-associated infectious diseases by allowing high-risk donors confidentially to exclude their blood from use for transfusion. The effectiveness of this method remains controversial. STUDY DESIGN AND METHODS: Confirmatory or supplemental test results for antibodies to human immunodeficiency virus, human T-lymphotropic virus type I, and hepatitis C virus, as well as hepatitis B surface antigen and syphilis and screening test results for antibodies to hepatitis B core (antigen) and alanine aminotransferase levels were obtained for approximately 1.8 million units donated during 1991 and 1992 at five blood centers within the United States. The prevalences of these infectious disease markers in units that the donors confidentially excluded (CUE+) and units that the donors did not exclude (CUE-) were calculated and examined within demographic subgroups. RESULTS: Units that were CUE+ were 8 to 41 times more likely to be seropositive for antibodies to human immunodeficiency virus and hepatitis C virus, hepatitis B surface antigen, and syphilis and three to four times more likely to react for antibody to hepatitis B core (antigen) or to have elevated alanine aminotransferase levels than units that were CUE- (p < 0.001). The positive predictive value of CUE (the percentage of CUE+ units that were confirmed seropositive for any marker) was 3.5 percent, and the sensitivity of CUE (the percentage of confirmed-seropositive units that were CUE+) was 2.3 percent. CONCLUSION: The current CUE process has low sensitivity and apparently low positive predictive value, and in many cases, it appeared that donors misunderstood it. Yet, CUE was not a "random process," as CUE+ units were more likely to be seropositive for any infectious disease marker than CUE- units. This suggests that efforts to improve the CUE system may be warranted. As risk factors for transfusion-transmitted infection become more difficult to identify by history-based screening, however, such efforts may have limited effect.

Adolescent

Current status of injectable oxygen carriers.

In this review the current status of what commonly are termed "blood substitutes" is discussed. The term blood substitute is a misnomer because the formulations under development at this time transport respiratory gases but do not perform the metabolic, regulatory, and protective functions of blood. Either hemoglobin or a perfluorochemical form the base to transport oxygen; the advantages and disadvantages of each base are discussed. The availability of a blood substitute in the U.S. will require approval by the Food and Drug Administration (FDA) and, by law, both its efficacy and safety must be demonstrated prior to approval. Showing efficacy of any blood substitute is complicated by the oxygen reserve and the compensatory mechanisms to acute blood loss in man. The challenge is to prove that the administration of these formulations offer clinical advantages compared with replacement of volume alone. Several efficacy models, the most attractive among them being perioperative hemodilution, should provide data that would bring these formulations into clinical practice. When hemoglobin is not within the favorable environment of the red cell, whether the hemoglobin is derived from expression vectors developed through recombinant biotechnology or from lysed human red cells, it acquires a left-shifted oxygen disassociation curve. Further, because the tetramer disassociates when injected intravenously and the resulting dimers are cleared rapidly from the circulation by the kidneys, intravascular dwell time is brief. Hemoglobins have been modified chemically and linked intramolecularly, intermolecularly, and to macromolecules to correct these problems. While these manipulations have normalized the p50 and extended the dwell time significantly, some toxicity problems remain unresolved. The binding of nitric oxide to hemoglobin preparations and the presumably resultant systemic and pulmonary hypertension observed in animals may be the most difficult to overcome, although the implications of these reactions in man is poorly understood. Perfluorochemicals (PFC) provide a fundamentally different and simpler approach to oxygen transport than hemoglobin formulations. Typically, the PFCs used are liquids composed of 8 to 10 carbon atoms that dissolve oxygen and obey Henry's law. Thus, the recipient's inspired oxygen and cardiac output assume importance. Because they are insoluble in water, PFCs are administered as emulsions, that is, as small droplets about 0.1 to 0.2 microns in diameter. In this respect, they are very similar to the lipid emulsions widely used for parenteral nutrition. Egg yolk phospholipid and poloxamers are most commonly used as emulsifiers. PFCs are not metabolized and are excreted unchanged by the lungs, following temporary storage by the monocyte-macrophage system (MMS).(ABSTRACT TRUNCATED AT 400 WORDS)

Blood Substitutes

Difficulties in demonstrating efficacy of blood substitutes.

Currently, the fear of infectious disease transmission by allogenic blood transfusions has spurred interest in developing a blood substitute FDA approval requires that a sponsor demonstrate that the substitute is effective. The challenge in designing efficacy studies in man is proving that the substitute offers significant advantages over conventional therapies for acute blood loss. This task is complicated by the oxygen reserve and the response to hemodilution following treatment of acute blood loss in man. Paradoxically, the technique that relies on these protective physiologies-isovolemic perioperative hemodilution-many offer the best experimental model to establish efficacy of a blood substitute in man.

Animals

Experience with a transfusion recipient education program about hepatitis C.

Shortly after test kits for antibodies to the hepatitis C virus (HCV) were licensed in May of 1990, our medical community undertook a public education program encouraging previous transfusion recipients to see their physicians about the wisdom of being tested for anti-HCV. In response, 1034 samples were received for testing. All samples repeatably reactive (RR) with anti-HCV enzyme-linked immunoassay (EIA) were tested further with a research recombinant immunoblot assay (RIBA). Overall, 76 of the 1034 (7.4%) recipient samples were RR and 64 of these (84.2%) were reactive with RIBA. Recipients transfused prior to surrogate testing (alanine aminotransferase [ALT] and anti-hepatitis B core [anti-HBc]) in 1986 showed a 8.6 percent reactivity with RIBA and those transfused after surrogate testing showed a 4.8 percent reactivity, a 44 percent reduction. Of the 57 recipient samples reactive with RIBA and suitable for assay, 11 (19.3%) had an elevated ALT. Among 76 randomly selected blood donors with RR EIAs studied for comparison with recipients, 20 (26.3%) were reactive with RIBA, 9 of which had an abnormal surrogate test that would have disqualified them. ALT concentrations were abnormal in 6 (30%) of the donors who were reactive on RIBA. We conclude that an education program that encourages previous transfusion recipients to seek medical advice about anti-HCV testing is practical from the standpoint of the blood center. We believe more widespread implementation of similar programs should be considered.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Viral

Legal liability for transfusion injury in the acquired immunodeficiency syndrome era.

The emergence of the acquired immunodeficiency syndrome has wrought changes that have affected not only medicine and science, but many aspects of our social and political structures. In 1983 when it clearly became evident that acquired immunodeficiency syndrome could be transmitted by transfusions of blood components and products, blood banks became the focus of intense scrutiny by the public as well as by the mass media. Suddenly it was known that people could contract acquired immunodeficiency syndrome even though they had not engaged in activities known to place them at increased risk for acquiring infection with the human immunodeficiency virus type 1. In many ways the general fear evoked was, and remains, disproportionate to the risks posed by transfusions. This fear coupled with a general distrust of blood banks may also be reflected in the legal response to people infected with human immunodeficiency syndrome type 1 through transfusions. Further, whether the fault system of our tort law is an appropriate way to determine compensation for people injured by transfusion has been brought into question. For those people injured prior to our recognition of acquired immunodeficiency syndrome, the failings of the current system are most obvious.

Acquired Immunodeficiency Syndrome

Morphologic effects following massive exchange transfusions with a stroma-free hemoglobin solution. II. Kidney.

The effects on renal morphology of exchange transfusion with stroma-free hemoglobin solutions (SFHS) were compared in rats to the results obtained using an asanguineous resuscitative fluid containing albumin. Animals underwent 75 per cent blood volume replacement, and tissue collected at intervals after the exchange transfusion was examined by light and electron microscopy. Urine volumes, osmolarity, and pH also were determined, and serum creatinine and blood urea nitrogen were measured both before and after exchange transfusion. Hemoglobin was filtered through the renal glomerular basement membrane, and a portion was reabsorbed into the proximal tubular cells in the form of absorption droplets. Unabsorbed hemoglobin was excreted in the urine. Despite a distention of proximal and distal tubules 5 hours after exchange transfusion with SFHS, there was no ultrastructural evidence of renal parenchymal damage. Proximal tubular cells of albumin-exchanged animals contained fewer protein absorption droplets and no intraluminal material. The apparent higher rate of glomerular filtration of hemoglobin over albumin probably reflected the dissociation of hemoglobin into dimers, resulting in a diuresis. Urine volumes were 3 times greater in SFHS-exchanged animals than in albumin-treated rats, and the urine was relatively hypoosmolar in the former. The greater urine volumes in SFHS-treated animals also were associated with a large reduction in intravascular fluid volume. There was no alteration of serum creatinine or blood urea nitrogen after exchange transfusion with albumin and only a mild elevation in blood urea nitrogen in SFHS-treated rats. The latter most likely was a result of prerenal hypovolemia. SFHS, even when exchange-transfused in massive quantities, does not appear to affect renal function or ultrastructural morphology adversely. However, the rapid disappearance of hemoglobin from the intravascular space, the consequent loss of intravascular fluid volume, and the diuresis induced by its administration are complications which must be overcome before the product can be a useful adjunct in the treatment of hemorrhagic shock.

Animals