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Biomedical subjects

R D Davenport

Publications and source records attributed to R D Davenport.

At least 19 recordsLinked to original sources

Apheresis treatment of recurrent focal segmental glomerulosclerosis after kidney transplantation: re-analysis of published case-reports and case-series.

A systematic re-analysis of published cases was performed to better define the role of plasmapheresis in the treatment recurrent focal segmental glomerulosclerosis after renal transplantation. Forty-four cases were identified, of which 32 responded to apheresis. The median number of treatments to response was 9. There was no difference between responders and nonresponders in the total number of treatments performed. The presence of sclerosis on biopsy predicted treatment failure. Relapse after first successful treatment was reported in 10 cases. The median number of treatments received was less and the time from diagnosis to first treatment was greater for patients who relapsed than for patients in whom relapse was not reported, but the differences were not statistically significant. On the basis of this analysis, we recommend early treatment after diagnosis with a regimen of three daily plasmapheresis treatments followed by 6 treatments on an every other day basis.

Biopsy↗

Revisiting the issue: can the reading for serologic reactivity following 37 degrees C incubation be omitted?

BACKGROUND: Omitting the 37 degrees C reading from screening tests for unexpected antibodies results in failure to detect some Rh, K, and Jk agglutinins of potential significance (wanted positives). However, this measure avoids unwanted positive tests due to cold agglutinins. STUDY DESIGN AND METHODS: Using data from prior publications, actual risk calculations (ARCs) were made to predict the risk of eliminating the 37 degrees C reading, pretransfusion direct antiglobulin test (DAT), and routine indirect antiglobulin crossmatch (IAT-XM). ARCs used the equation: wanted positives missed x 0.34 (or 0.80) x 5 x percent antigen-positive, where 0.34 = percent of patients transfused (ARCs for 37 degrees C reading and DAT); 0.80 = percent of crossmatched patients transfused (ARCs for IAT-XM); 5 = average number of units transfused. Following elimination of the 37 degrees C reading, the impact of this change on patient care was monitored. Antibody detection and identification data and transfusion reaction reports for 6 months after the change were reviewed. Recently transfused patients with new antibodies were evaluated for immune hemolysis by review of clinical and laboratory data. The findings were compared with those from the same dates of the preceding year. RESULTS: The risk of transfusing incompatible blood by eliminating the DAT, IAT-XM, and 37 degrees C reading is approximately 1:13,000, 1:2,000, and 1:2,400 units transfused, respectively. The cumulative risk from eliminating all three tests is approximately. 1 :1,000 units. With respect to the 37 degrees C reading, there were no differences between the pre-change and post-change study periods in the incidence of reported transfusion reactions or cases of immune hemolysis associated with newly formed antibodies. However, unwanted positive tests decreased from 162 to 61 following elimination of the 37 degrees C reading. This represents a decrease of 20 percent in the number of samples requiring antibody identification annually. CONCLUSIONS: Eliminating the 37 degrees C reading from pretransfusion antibody screening tests imposes less risk than omitting the routine IAT-XM, and it avoids the time and costs of evaluating unwanted positive tests, thus reducing expenditures and delays in patient care.

Actuarial Analysis↗

Monocyte chemoattractant protein production in red cell incompatibility.

BACKGROUND: Mononuclear phagocytes play a central role in hemolytic transfusion reactions by erythrophagocytosis and production of inflammatory mediators. Factors that affect the number or function of monocyters would be expected to alter the clinical course of hemolytic transfusion reactions, and thus the production of monocyte chemoattractant protein-1 (MCP-1), a recently described chemotactic and activating cytokine specific for monocytes, was investigated in two distinct settings of red cell (RBC) incompatibility. STUDY DESIGN AND METHODS: Fresh heparinized whole blood was incubated with ABO-compatible or -incompatible RBCs. Isolated peripheral blood mononuclear cells were incubated with anti-D-coated or uncoated RBCs. MCP-1 was measured in the plasma or culture medium by enzyme-linked immunosorbent assay. MCP-1 gene expression was detected by Northern blot analysis of buffy coat or mononuclear cell total RNA. RESULTS: Significant levels of MCP-1 protein in plasma or medium were detected 24 hours after the addition of incompatible RBCs, but not in the first 6 hours. Nonimmune hemolysis of added RBCs did not stimulate MCP-1 production. The inactivation of complement by heat treatment of plasma prior to the addition of RBCs to whole blood did not prevent MCP-1 production. Nor did neutralizing antibodies to tumor necrosis factor prevent MCP-1 production in ABO incompatibility. MCP-1 production was associated with increased steady-state levels of white cell MCP-1 mRNA, which occurred more rapidly in ABO than Rh incompatibility. CONCLUSION: The monocyte-specific chemotactic cytokine MCP-1 is produced by peripheral blood leukocytes in response to RBC incompatibility. MCP-1 may act in a positive feedback loop to recruit and activate monocytes during hemolytic transfusion reactions, thus contributing to the maintenance of these reactions.

ABO Blood-Group System↗

In vitro production of interleukin-1 receptor antagonist in IgG-mediated red cell incompatibility.

BACKGROUND: Recently, proinflammatory cytokines including interleukin 1 (IL-1) have been implicated in the pathophysiology of immune-mediated hemolysis. Little is known, however, about the mechanisms by which inflammatory events in these reactions may be downregulated. IL-1 receptor antagonist (IL-1ra) inhibits the actions of IL-1 by competition for cellular receptors, and thus it may regulate the biologic actions of IL-1 during immune-mediated hemolysis. The production of IL-1ra by peripheral blood mononuclear cells (PBMNCs) in response to IgG-coated red cells in vitro was investigated. STUDY DESIGN AND METHODS: Fresh PBMNCs were obtained by density gradient separation of heparinized whole blood. PBMNCs were cultured in the presence of anti-D-coated, Rh-positive red cells or uncoated Rh-negative red cells under nonadherent conditions. IL-1ra concentrations in the culture media were measured by enzyme-linked immunosorbent assay. IL-1ra and IL-1 beta gene expression was assessed by Northern blot analysis of PBMNC mRNA. RESULTS: IL-1ra production was evident 4 hours after stimulation with IgG-coated red cells and increased progressively over 24 hours. Gene expression of IL-1ra was first detected at 2 hours, lagging behind that of IL-1 beta. IL-1ra gene expression was not inhibited by neutralizing polyclonal antibodies to IL-1. Immunocytochemical staining to determine the cellular source localized IL-1ra production to monocytes engaged in erythrophagocytosis. IL-1ra production was inhibited by dexamethasone (10(-7) M). CONCLUSION: These results suggest that IL-1ra production may partly account for the variable pathophysiologic events seen in IgG-mediated autoimmune hemolysis and hemolytic transfusion reactions. Steroid treatment may also downregulate anti-inflammatory cytokine production in immune hemolysis.

Anemia, Hemolytic, Autoimmune↗

Cytokine production in IgG-mediated red cell incompatibility.

The transfusion of incompatible red cells may result in fever and systemic symptoms. The mechanisms by which these symptoms are produced in the setting of antibodies that do not usually fix complement, as in the Rh system, are obscure. It has been hypothesized, on the basis of their known biologic activities, that a specific set of cytokines may be involved in such transfusion reactions. Therefore, the production of the inflammatory cytokines interleukin-1 beta (IL-1 beta), tumor necrosis factor (TNF), interleukin-6 (IL-6), and interleukin-8 (IL-8) by human monocytes in response to red cells sensitized with anti-D was investigated, as a model of IgG-dependent hemolytic transfusion reactions. IL-1 beta, IL-6, and IL-8 were detectable in the culture supernatants at 4 to 6 hours and increased up to 24 hours, whereas TNF peaked at 6 hours. Immunocytochemical stains of cell preparations demonstrated IL-1 beta, IL-8, and TNF in monocytes engaged in erythrophagocytosis. IL-8 production and phagocytosis could be inhibited by monomeric IgG, but Fab fragments of a monoclonal antibody specific for the low-affinity IgG receptor Fc gamma RII could not be, which suggests the involvement of the high-affinity receptor Fc gamma RI. Neutralizing antisera to IL-1 beta and TNF did not abrogate the production of IL-8, which suggests that sensitized red cells serve as a primary signal for this cytokine. These findings indicate that the production of inflammatory cytokines by phagocytes may be responsible for the symptomatology of IgG-mediated hemolytic transfusion reactions.

ABO Blood-Group System↗

Molecular genetic analysis of the ABO blood group system: 1. Weak subgroups: A3 and B3 alleles.

We have determined the nucleotide sequences of the coding region in the last two coding exons of ABO genes (which occupy 91% of the soluble form of A1 transferase) from 7 individuals with weak subgroup phenotypes. Four of the individuals had an A3 phenotype and 3 individuals had a B3 phenotype. We determined the nucleotide sequences based on PCR followed by subcloning and DNA sequencing of the amplified fragments. Two cases of the A3 allele and 1 case of the B3 allele were found to contain a single-base substitution which resulted in an amino acid substitution. However, no other cases of A3 and B3 alleles were found to contain differences in this region. This finding demonstrates for the first time heterogeneity among these weak subgroups at the nucleotide level.

ABO Blood-Group System↗

Detection of circulating donor white blood cells in patients receiving multiple transfusions.

Significant morbidities are associated with the routine administration of blood products. Although the exact etiology of these complications may be unknown, many are thought to arise from the incidental cotransfusion of "donor" lymphocytes. We have developed an assay to detect small numbers of male white blood cells (WBCs) circulating in female patients who have received multiple blood transfusions using the polymerase chain reaction (PCR). Twenty female patients undergoing major surgical procedures were studied and received an average of 9.3 U of packed red blood cells (4.8 U from male donors) and 11.7 U of platelets (6.1 U from male donors). DNA was extracted from whole blood or peripheral blood buffy coats posttransfusion and PCR performed using oligonucleotides designed to amplify a segment within the repetitive Y-chromosome DYZ1 locus. Posttransfusion, 15 of 20 women showed evidence of circulating male WBCs for an average of 2.0 days (range, 1 to 6). We conclude that (1) DYZ1 PCR analysis is a useful approach for the detection of small numbers of circulating transfused male WBCs in female patients; and (2) circulating donor WBCs persist for a mean of 2.0 days in the majority of women receiving multiple transfusions. Future application of this technique may detect persisting or proliferating WBCs and lead to an improved understanding of common transfusion-related morbidities.

Base Sequence↗

Transfusion management of patients with IgA deficiency and anti-IgA during liver transplantation.

Severe anaphylactic or allergic reactions may occur during blood transfusion to patients who are IgA-deficient and have anti-IgA in their blood, particularly those with class-specific antibodies. These patients are a particular challenge to the hospital transfusion service when large volumes of blood components are required for transfusion support, as in liver transplantation. We have successfully provided blood components for 3 such patients undergoing liver transplantation. Red cells were washed manually or by automated technique. Platelets were washed manually. All plasma was from IgA-deficient donors. One patient's entire plasma requirements were supplied by autologous plasmapheresis. Serial determinations of IgA levels and anti-IgA titers in 1 patient demonstrated an abrupt fall in anti-IgA with the appearance of barely detectable amounts of IgA during the surgery. IgA-containing plasma cells were demonstrated in the biopsies of liver homografts of 2 patients following transplantation. IgA deficiency with anti-IgA can be successfully managed during liver transplantation with advance planning.

Adolescent↗

Non-Hodgkin's lymphoma of the brain after Hodgkin's disease. An immunohistochemical study.

Non-Hodgkin's lymphoma (NHL) of the central nervous system (CNS) is a rarely reported complication of Hodgkin's disease (HD). Two patients with NHL of the brain after HD were studied by histologic and immunohistochemical methods. Both patients were in the second decade, had been treated with radiation and chemotherapy, had experienced a relapse of HD before development of NHL, had no evidence of HD at the time of diagnosis of NHL, and died within 1 year of diagnosis. Both brain neoplasms were large cell immunoblastic lymphomas of B-cell lineage. Patients with HD appear to be at increased risk for NHL of the CNS, which may have a poor prognosis.

Adolescent↗

Red cell ABO incompatibility and production of tumour necrosis factor-alpha.

Tumour necrosis factor-alpha (TNF) is a major mediator of diverse pathophysiological events similar to those of haemolytic transfusion reactions (HTR), such as fever, intravascular coagulation and organ failure. However, the possible role of TNF in HTR has not been investigated. We have constructed an in vitro whole blood model of HTR to examine whether TNF may be produced in red cell ABO incompatibility. TNF was observed in plasma, in a dose dependent manner, when ABO incompatible red cells were added, but not with compatible (group O) cells. Plasma TNF levels were maximal at 2 h, and declined to control levels by 24 h. Haemolysis of incompatible red cells was accompanied by TNF production. Immune haemolysis induced TNF gene expression by buffy coat leucocytes, as determined by Northern blot analysis. Heat inactivation of plasma abolished TNF production, whereas prior treatment with interferon-gamma augmented the response. These results demonstrate that a major cytokine is produced in response to red cell incompatibility, and suggest that TNF may play a role in the pathogenesis of haemolytic transfusion reactions.

ABO Blood-Group System↗

Patterns of antigenic expression of human glioma cells.

Gliomas are known to express over a hundred antigens, and no doubt make many more unknown antigens. Major categories of glioma cell antigens include glial antigens, ECM antigens, muscle antigens, melanoma antigens, "tumor-specific" antigens, and cellular proliferation antigens. A strikingly low number of cultured gliomas express glial antigens. They commonly express not only ectodermal, but also mesenchymal ECM antigens. Tumor-specific antigens have been an elusive goal of neuro-oncologists, but there are bright new prospects in need of further study. These include direct screening of hybridoma supernatants on glioma tissue and targeting glycolipids, glycoproteins, and oncogene products. Cellular proliferation antigens will become increasingly important in predicting prognosis of gliomas. Proliferation antigens of cultured gliomas are under intense scrutiny at present. The extent and evolution of antigenic heterogeneity of neoplastic cells in gliomas raise basic biologic questions with profound clinical ramifications. Individual glioma cell lines may generate more than 30 subtypes of cells with minor to major differences in antigen expression. These include expression of antigens representing multiple different cell lineages. Mesenchymal drift is the tendency of gliomas to progressively lose glial and gain mesenchymal features. Models of in vivo mesenchymal drift occur in glioma cell culture where mechanisms are more easily investigated than in situ. Neither exogenous protein absorption nor fibroblast overgrowth explain the phenomenon. Cells with the mesenchymal marker, fibronectin, overgrow GFAP-positive cells during explanation of gliomas. Many of these fibronectin-positive cells express cytologic and growth characteristics of neoplasia. The source of these cells is unknown. A leading candidate for the source of these neoplastic fibronectin-positive cells is the proliferation of vascular and mesenchymal cell elements of glioma tissue commonly called "endothelial proliferations". However, these elements in tissue do not display the same abnormalities of neoplasia as the fibronectin-positive cells in culture. Understanding this "tissue/explant paradox" may solve the conundrum of mesenchymal drift. In the absence of a counterpart in tissue of these neoplastic fibronectin-positive cells so abundant in glioma cell cultures, mechanisms of mesenchymal drift other than overgrowth of neoplastic mesenchyme must be considered. The occurrence of "dual cells" which express antigenic markers of entirely different cellular lineages suggests the possibility that neoplastic glia generate mesenchymal drift by altered gene expression. Various studies which suggest the capacity of cultured gliomas to alter phenotypic expression of their genes are critically examined and their relevance to mesenchymal drift discussed.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

The tall cell variant of papillary carcinoma of the thyroid gland. Comparison with the common form of papillary carcinoma by DNA and morphometric analysis.

The tall cell variant of papillary carcinoma of the thyroid manifests a more aggressive behavior than the usual form of papillary carcinoma of the thyroid. Morphometric analysis of nuclear features and DNA analysis may yield information predictive of aggressive behavior. Accordingly, the DNA content and morphometric features of the neoplastic cells of the tall cell variant were measured and compared with measurements obtained from neoplastic cells of the usual form of papillary carcinoma. Six of the 11 tall cell neoplasms were aneuploid, as were four of the eight usual papillary neoplasms. Although benign cells were separated from malignant cells in each case, differences between tall and usual papillary carcinoma cells were not observed regarding DNA content, chromatin texture, or nuclear size and shape. Differences in the clinical behavior of these neoplasms will likely need to be explained on the basis of other characteristics.

Carcinoma, Papillary↗

Interleukin-8 production in red blood cell incompatibility.

Hemolytic transfusion reactions (HTR) are characterized by fever, shock, organ system failure, intravascular coagulation, and possibly death. The same findings may be associated with sepsis. Neutrophils have been implicated in the pathogenesis of HTR, although a mechanism for neutrophil activation has not been shown. In addition, the possible role that cytokines may play in HTR has not been investigated. We show that interleukin-8 (IL-8), a cytokine with chemotactic and neutrophil-activation properties, is produced in whole blood following addition of ABO-incompatible red blood cells, in a dose- and time-dependent manner related to the degree of hemolysis, and is inhibited by inactivation of complement. IL-8 production is accompanied by increased gene expression in the buffy coat. This observation has implications for the understanding of the pathogenesis of and for the treatment of HTR.

ABO Blood-Group System↗

Cytologic diagnosis of fibrolamellar carcinoma of the liver by fine-needle aspiration.

Two cases in which the diagnosis of fibrolamellar carcinoma of the liver was made by fine-needle aspiration are presented. The cytologic findings were characteristic and permitted these tumors to be differentiated from the usual hepatocellular carcinoma. Since fibrolamellar carcinoma has unique clinical and pathologic features, and is much more likely to be resectable, making this diagnosis is important.

Adult↗

Rapid on-site evaluation of transbronchial aspirates.

A technique for immediate interpretation of transbronchial aspirates at bronchoscopy is described. Comparing 73 aspirates using the technique with 134 routinely processed aspirates, the technique produced a significant increase in the percentage of specimens containing malignant cells, from 31 to 56 percent, and, importantly, a large decrease in the percentage of specimens that were inadequate for diagnosis, from 56 to 18 percent. The technique was equally applicable to central and peripheral lung aspirates and to all types of primary and metastatic pulmonary neoplasms. The use of rapid on-site evaluation significantly improves the diagnostic yield of transbronchial aspirates.

Amyloidosis↗