Monitoring for undertransfusion

BACKGROUND: Most published reviews and audits of blood and blood component transfusion have focused on the issue of overtransfusion and on the inappropriate use of red cell components. There is growing concern that efforts to curb unnecessary transfusions may result in a trend toward undertransfusion of patients. There is little published information that addresses this issue or the magnitude of this practice. STUDY DESIGN AND METHODS: Undertransfusion was evaluated by examining the transfusion records from a 3-month period for 55 patients who met the study criteria of having either a hemoglobin level < 7 g per dL or a platelet count of < 10 × 10(9) per L. If the identified patient did not receive a transfusion within 24 hours of the reported hemoglobin level or platelet count, the medical record was reviewed by a resident physician. RESULTS: A total of 213 individual hemoglobin levels and platelet counts, representing the 55 patients, met our transfusion criteria. All except 8 of the identified patients received red cells and/or platelet transfusions. Reasons for not transfusing red cells included the patient's response to nutritional support and iron supplementation, refusal of blood, and noncompliance. Reasons for not transfusing platelets included falsely low platelet count because of platelet clumping in vitro, contraindication based on clinical diagnosis (e.g., immune thrombocytopenic purpura), and the patient's death before transfusion. CONCLUSION: Red cell and platelet transfusions were appropriately ordered for all patients who met the transfusion criteria. Undertransfusion is not a problem at this institution according to the criteria established. It is recommended that other institutions expand their blood utilization audits to include investigation for evidence of undertransfusion. Further research regarding the issue of undertransfusion is warranted and could be expanded to include other components.     

Treatment of Felty's syndrome with the haemopoietic growth factor granulocyte colony-stimulating factor (G-CSF)

Felty's syndrome (FS) (rheumatoid arthritis with neutropenia and splenomegaly) has a poor prognosis, largely because of the high risk of severe infection. Granulocyte colony-stimulating factor (G-CSF) is an emerging treatment for chronic neutropenia. We prospectively monitored its use in eight patients with recurrent infections or who required joint surgery. Significant side-effects were documented in five, including nausea, malaise, generalized joint pains, and in one patient, a vasculitic skin rash. In two patients treatment had to be stopped, and in these cases G-CSF had been started at full vial dosage (300 micrograms/ml filgrastim or 263 micrograms/ml lenograstim) alternate days or daily. G-CSF treatment was continued in three patients by restarting at reduced dose, and changing the proprietary formulation. G- CSF raised the neutrophil count, reduced severe infection, and allowed surgery to be performed. A combined clinical and laboratory index suggested that long-term treatment (up to 3.5 years) did not exacerbate the arthritis. Once on established treatment, it may be possible to use smaller weekly doses of G-CSF to maintain the same clinical benefit. One of the three patients whose FS was associated with a large granular T-cell lymphocytosis showed a reduction in this subset of lymphocytes during G-CSF treatment.      

Long-term follow-up testing of red cell alloantibodies

BACKGROUND: In previous studies, 29 to 34 percent of potentially hemolytic red cell antibodies were not detected after short-term follow- up. STUDY DESIGN AND METHODS: To examine long-term detection, records were reviewed for 44 consecutive patients who were tested more than 5 years after their potentially hemolytic red cell antibodies were first identified in this hospital. RESULTS: After 5 to 10 years, 14 (39%) of 36 Rh, Kell, and Duffy system antibodies were not detected on at least one occasion. Twenty-two other such antibodies were sought again after more than 10 years; 10 (45%) were not detected. When restimulation by pregnancy was excluded, these rates were 42 and 48 percent, respectively. CONCLUSION: Clinically significant red cell antibody formation is probably more common than previously realized, because nearly half of these antibodies are undetected after long-term follow- up.     

Severe malaria in children in Papua New Guinea

The clinical features of severe falciparum malaria and risk factors for mortality were studied in 489 children admitted with malaria to Madang Hospital, Papua New Guinea. The most common severe manifestations of malaria were severe anaemia (22%) and coma (16%). Children with severe anaemia were younger than those with coma (median age 2.2 vs. 3.7 years) and had been ill for longer before admission (median 7 vs. 4 days, respectively). Although the clinical features of coma in Madang children with malaria resembled closely those reported in African children, mortality was lower (8% vs. 17-25%, respectively). Overall, 17 (3.5%) children died, most within 12 h of admission. A high level of plasma lactate (> or = 5 mmol/l) was common (20%) and was the major predictor of death in multiple regression analysis. Raised plasma creatinine and decreased plasma bicarbonate were also independent predictors of mortality. Coma was not predictive of death, although a high proportion of children with profound coma died. Investigation of the causes of acidosis in children with malaria is a high research priority. In view of the short time interval between admission and death in many children, emphasis must be placed on the prevention or early recognition and treatment of acidosis in the district health clinic as well as the central hospital.      

How much would the safety of blood transfusion be improved by including p24 antigen in the battery of tests?

BACKGROUND: Because p24 antigen may be detectable during seroconversion, before antibodies, some of the infected blood undetected by antibody screening could be identified through antigen screening. STUDY DESIGN AND METHODS: The potential benefit of antigen screening was evaluated in a simulation model incorporating present knowledge of the time sequence from antigen exposure to antibody development during seroconversion and the incidence of seroconversion among repeat donors. The model was designed so that the results were consistent with the observed rate of antibody-positive blood donations and the CIs of surveys that did not find any antibody-negative/antigen- positive donated blood. RESULTS: In the United States in 1990, the number of expected, undetected, contaminated blood components was estimated at 68; of these 8 to 17 could have been identified by antigen screening, depending on the hypothesis explored. (In 1992, 20 undetected, contaminated blood components were expected according to this model, of which 2 to 5 could have been identified by antigen screening.) In France, the comparable figures were 1 to 4 of 13 in 1990 and 1 to 2 of 7 in 1992. CONCLUSION: The projected benefit must be weighted against possible negative consequences, including 1) an increase in recently infected persons seeking p24 antigen screening at blood banks (assuming this test is not incorporated into screening in non-blood bank settings) and 2) the need for additional quality assurance procedures to avoid operational flaws associated with the increase in the donor screening test battery. In any case, the best way of increasing the safety of blood is improvement in the selection of donors, which can diminish the residual risk of transmission of any viruses.     

膈下逐瘀汤对肝癌Bel-7402细胞增殖的抑制及其机制

目的:观察中药复方膈下逐瘀汤对肝癌Bel-7402细胞增殖的抑制及其相关机制。方法:实验于2005-09/2006-07在南方医科大学细胞生物实验室完成。膈下逐瘀汤(按《医林改错》方组成:五灵脂6g,当归9g,川芎6g,桃仁9g,丹皮6g,赤芍6g,乌药6g,延胡索3g,甘草9g,香附5g,红花9g,枳壳5g。均购自南方医院中药房)经研粉、煮沸、离心、过滤配成质量浓度为25,50,100,200mg/L的药液;顺铂配制成质量浓度为0.5,1.0,1.5,2.0mg/L的药液(作为阳性对照),均作用于Bel-7402细胞,并设空白对照(未加任何药物)。采用甲基噻唑基四唑(methyl thiazoly ltetrazolium,MTT)比色法检测膈下逐瘀汤各组对Bel-7402细胞生长的影响,用酶标仪测定培养细胞在600nm处吸光度值,并计算细胞抑制率,抑制率(%)=(实验组吸光度值-对照组吸光度值/对照组吸光度值)×100%。用蛋白印迹试验检测不同质量浓度药物作用48,72h时第10号染色体同源丢失性磷酸酶-张力蛋白基因蛋白的表达水平。结果:①中药复方膈下逐瘀汤对Bel-7402细胞增殖的影响:膈下逐瘀汤对肝癌Bel-7402细胞有明显的生长抑制作用,呈良好的剂量-效应关系。膈下逐瘀汤质量浓度在200mg/L时其48h细胞生长抑制率介于0.5mg/L顺铂组与1.0mg/L顺铂组之间(分别为41.27%,34.01%,47.49%);膈下逐瘀汤质量浓度在50,25mg/L时,其细胞抑制率明显低于顺铂组,72h细胞抑制率结果基本相同。②药物作用肝癌Bel-7402细胞48h后第10号染色体同源丢失性磷酸酶-张力蛋白基因蛋白的表达:第10号染色体同源丢失性磷酸酶-张力蛋白基因蛋白的表达增多,200mg/L膈下逐瘀汤组介于0.5mg/L顺铂组和1.0mg/L顺铂组之间。结论:中药复方膈下逐瘀汤抑制Bel-7402细胞的增殖机制可能是第10号染色体同源丢失性磷酸酶-张力蛋白基因表达增多的原因。     

Candidal infection of bone. Assessment of serologic tests in diagnosis and management

In this case report, 30 sera from a 25-year-old heroin abuser with intervertebral candidosis were treated for the presence of anti-Candida albicans antibodies by agglutination, counterimmunoelectrophoresis, and indirect immunofluorescent assay. Sera were also adsorbed with heat-killed blastospores to remove antibodies against yeast-phase cells and tested by indirect immunofluorescent assay for anti-C. albicans germ tube antibodies (CAGTAs). Humoral responses to candidal 47-kD antigen were studied by immunoblotting in 23 unadsorbed sera. Anti-C. albicans antibodies were found in high titers by the three procedures but correlated poorly with the clinical evolution of the disease. CAGTAs were present from the beginning of the infection: Titers decreased in association with antifungal treatment and the patient's improvement, eventually becoming negative. Only class IgG antibodies to the 47-kD antigen were detected. These were present during the full course of the infection, failing to disappear at the end of the study. In this case, detection of CAGTAs appeared to be an important aid to diagnosis of the bony candidal infection, as they are detected early during the illness and seemed to have a prognostic significance.     

Factors affecting Yersinia enterocolitica (serotype O:8) viability in deliberately inoculated blood

Interpretation of in vitro experiments using Yersinia enterocolitica in blood components requires information on factors affecting the organism's survival. Several factors were found to influence the survival of Y. enterocolitica (serotype O:8) in blood components. A 20- minute room-temperature incubation with plasma-containing components resulted in approximately 2 log10 inactivation. Inactivation could be prevented by preincubation treatment of the plasma at 55 degrees C for 1 hour, which suggests the involvement of heat-labile plasma factors. No antibacterial activity was observed in washed red cells during the 20-minute room-temperature incubation. However, Y. enterocolitica colony-forming units declined by up to 2 log10 in washed red cells during the first days of 4 degrees C storage. Use of a white cell- reduction filter on freshly inoculated samples removed approximately 1 log10 of the organism regardless of whether bacteria were suspended in saline or washed red cells. Thus, bacterial levels may be affected by plasma, cellular components, and white cell-reduction filters. However, caution should be exercised in interpreting in vitro spiking studies designed to investigate the potential benefits of white cell reduction to eliminate the growth of Y. enterocolitica because of potential differences between naturally infected and experimentally inoculated blood.     

Memory B cells at successive stages of differentiation. Affinity maturation and the role of IgD receptors

The following evidence, mainly presented here, suggests that IgD receptors play a crucial role in determining the potential for affinity maturation in memory B cell populations. IgD receptors are present on the first memory B cells to appear after priming. These memory cells give rise to more-mature memory cells that have lost their IgD receptors. The proportions of early (IgD(+)) and mature (IgD(-)) memory cells found in individual donors vary with time, priming conditions, and the availability of T cell help, and both populations frequently coexist for long periods of time. IgD(+) and IgD(-) memory cells carry IgG receptors and give rise to IgG responses with identical isotype representation in adoptive recipients. IgD(+) memory cells, however, always give rise to predominantly low-affinity antibody responses, whereas IgD(-) memory cells consistently generate responses of substantially higher average affinity. This affinity differential is maintained between early and mature memory populations in the same donor and does not appear to be a result of selective differentiation of higher-affinity IgD(+) memory cells into the IgD(-) memory pool. Thus, the selective forces responsible for affinity maturation appear to operate mainly in mature memory cell populations that have already lost IgD receptors; or, stated conversely, little or no selection towards high-affinity memory appears to occur among memory cells that retain IgD receptors. In discussing these findings, we suggest that the IgD receptors themselves are responsible for maintaining early memory populations at a lower average affinity than IgD(-) populations in the same animal. The IgD receptors, we argue, serve to increase the antigen-binding capacity of lower-affinity memory cells so that these cells can survive, expand, and differentiate (to IgD(-)) at antigen concentrations that select against expansion of low- affinity memory cells no longer carrying IgD receptors. Thus, when antigen is limiting, IgD(-) memory populations will be selectively expanded to higher average affinities, whereas coexisting IgD(+) populations will retain their initial affinity profile. This hypothesis suggests that mechanisms that regulate expression and loss of IgD receptors are central to the adaptability of the immune system in its response to invading pathogens. Two related roles can be envisioned for the IgD receptors in this regard. First, they extend the lower boundary of the affinity range of early memory cell populations induced by a given antigenic stimulus and therefore broaden the diversity of responses obtainable from these populations. Secondly, they support the persistence of low-affinity memory populations under conditions where antigen becomes limiting and eventually disappears. These persisting populations then serve as a diversely reactive reservoir from which mature memory populations can be drawn with higher affinities either for the original antigen or, more importantly, for related antigens that the animal may subsequently encounter. Thus the existence of IgD receptors on early memory cells maintains the full range of response diversity despite ongoing selective expansion of (mature) memory populations to produce antibodies with high combining affinities for individual antigens. The flexibility inherent in such an organizational system, we believe, could be expected to account for the evolutionary development of IgD receptors and the regulatory capabilities that support operation of the system.