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Biomedical subjects

N Blumberg

Publications and source records attributed to N Blumberg.

At least 19 recordsLinked to original sources

Malignant melanoma: primary presentation in bone marrow and lymph node.

We describe an unusual presentation of malignant melanoma with simultaneous lymph node and bone marrow metastasis. In addition the disease was associated with immune-mediated thrombocytopenia. A brief remission was obtained with combination chemotherapy.

Antineoplastic Combined Chemotherapy Protocols

Antibodies to plasma proteins: an association with platelet transfusion refractoriness.

We hypothesized that antibodies to HLA-linked polymorphic plasma proteins could be involved in platelet refractoriness by an 'innocent bystander' or immune complex mechanism. Employing a kinetic enzyme-linked immunosorbent assay (ELISA) technique the ability of IgG from the plasma of refractory patients to bind to albumin, fibrinogen, complement components C2 and C4 was measured. As compared with controls a high percentage of refractory patients had increased IgG capable of binding to all four plasma proteins: C2 (83%), C4 (83%), albumin (75%), fibrinogen (34%). In the presence of exogenous plasma proteins these antibodies mediated increased deposition of IgG onto normal donor platelets. The plasma protein binding IgG consisted both of monomeric IgG and a broad range of high molecular weight complexes. IgG anti-plasma protein antibody could be eluted from platelets of refractory patients. The development of anti-plasma protein IgG was studied during the course of platelet transfusion therapy and found to increase progressively so that by the 20th transfusion greater than 90% of samples were positive. The presence of plasma protein binding activity correlated with the development of increased levels of platelet bound IgG and refractoriness. Multiple platelet transfusions lead to sensitization to polymorphic determinants on C2 and C4 as well as the formation of high molecular weight complexes. These antibodies and complexes contribute to the deposition of IgG on platelets and may contribute to refractoriness.

Albumins

Homologous blood transfusion as a risk factor for postoperative infection after coronary artery bypass graft operations.

Homologous transfusions are immunosuppressive and associated with a higher risk of postoperative infection. In this retrospective analysis, we studied 238 consecutive patients who underwent first-time coronary operations by a single surgeon in 1988 to 1989 and collected clinical and laboratory data relevant to postoperative infections including pulmonary, urinary, and wound sites. Culture-proved postoperative infections occurred in 16 of the 238 patients (6.7%), with only 3 (1.3%) being deep sternal wound infections. Seven of 16 (44%) of the infections were away from the wound sites, suggesting that nonsurgical variables contributed to at least some infections. Factors significantly associated with an increased risk of postoperative infection by univariate analysis included female sex, diabetes mellitus, and transfusion dose. Infections occurred in 3.9% of patients receiving up to 2 units of red cells and whole blood, 6.9% receiving 3 to 5 units, and 22% of those receiving 6 units or more. Multiple linear and logistic regression analysis showed that transfusion dose was the most significant predictor of infection, days of fever, days of antibiotic therapy, and length of hospital stay. Homologous transfusion is associated (in a dose-dependent fashion) with a threefold to eightfold increased risk of postoperative infection in patients undergoing coronary artery operations. This increased risk of infection may be due to transfusion-induced immunosuppression of the patient.

Aged

Severe fetal hydrops resulting from ABO incompatibility.

Severe fetal hydrops was diagnosed at 34 weeks' gestation. Funipuncture revealed a normal 46,XX karyotype and a hematocrit of 20%. Cesarean delivery was performed. Neonatal blood testing showed blood type B positive, positive direct and indirect Coombs, and an anti-B antibody titer of 1:64. The maternal blood group was O positive with a titer of 1:65,536 immunoglobulin G (IgG) anti-B antibody (after inactivation of IgM anti-B antibody). This report documents a rare case of fetal hydrops resulting from ABO incompatibility with neonatal survival.

ABO Blood-Group System

Transfusion-induced immunomodulation and its clinical consequences.

The bulk of experimental and clinical data support the theory that homologous transfusion causes significant down-regulation of immunologic functions in a number of settings. These changes in immune function may account for the beneficial associations of transfusion with increased renal allograft survival, and decreased recurrence in Crohn's disease. Conversely, these transfusion-induced effects may be responsible in part for the deleterious association of homologous transfusion with increased cancer recurrence, and increased posttransfusion bacterial and viral infection rates. Host defenses against malignancy and infection may in some instances be severely compromised by transfusions of homologous blood, but the circumstances under which this occurs need to be better defined. Likewise, the hypothesis that modification of blood components to contain fewer leukocytes or less plasma might ameliorate these effects is attractive, but little or no data exist to support or refute it. Future clinical studies will no doubt address these issues.

Blood Transfusion

The relationship of blood transfusion, tumor staging, and cancer recurrence.

Previous research demonstrated a relationship between transfusions of whole blood, or large numbers of red cell concentrates, and later recurrence of cancers of the colon, rectum, cervix, and prostate. It is possible that the transfusion of whole blood may represent a surrogate marker for advanced or more aggressive clinical disease. The relationship of clinical or histologic tumor stage, blood transfusion status, and disease outcome was studied in detail. Patients receiving no transfusions or small numbers of red cells (less than or equal to 3 units) had uniformly better recurrence and survival experiences than patients receiving similar amounts of blood that included at least 1 unit of whole blood, regardless of the patient's clinical or histologic tumor stage. In multivariate analyses, stage was an independent predictor of outcome, and transfusion status was not a surrogate marker for stage. The effects on recurrence of stage and transfusion appear to be cumulative. These results are consistent with but do not prove the hypothesis that the transfusion of large amounts of stored plasma and cellular debris impairs the host defenses against cancer, regardless of the underlying biologic and clinical aggressiveness of the cancer.

Blood Transfusion

Association of transfusion with postoperative bacterial infection.

Homologous blood transfusion has been implicated as a modulator of the host immune system in a number of clinical settings. Improved renal allograft survival is observed in patients receiving pretransplant transfusions. Decreased recurrence of active inflammatory bowel disease has been recently reported in transfused patients with Crohn's disease. Conversely, deleterious immunomodulatory effects of transfusion may explain the association between transfusion and increased susceptibility to cancer recurrence and bacterial and viral infection. Clinical studies regarding cancer recurrence and transfusion are retrospective and conflicting. There is epidemiologic evidence for more rapid progression of HIV-1 infection in heavily transfused patients. Studies on transfused surgical patients have shown transfusion to be associated with an increased frequency of postoperative bacterial infections. Some studies have come to different conclusions. These investigators have suggested that transfusion may represent a surrogate marker for other risk factors for infection. Animal models designed to control for confounding factors have supported an association between transfusion and bacterial infection severity in most, but not all, reports. Attempts to define the immunologic alterations associated with transfusion have revealed a generalized impairment of cellular immunity in both humans and animals. Although the preponderance of data supports an association between perioperative transfusion and increased susceptibility to postoperative bacterial infection, it is not certain to what extent this relationship constitutes cause and effect.

Animals

The fine specificity of Lewis blood group antibodies. Evidence for maturation of the immune response.

Eight human Lewis blood group antibodies were characterized for their fine specificity by the use of specific immunoadsorbents and a kinetic enzyme-linked immunosorbent assay technique. Examination of sera following immunoglobulin fractionation showed IgM anti-Le(a) exhibiting broad cross-reactivity with structures biochemically related to the Lewis antigens. IgG anti-Le(a) binding was restricted to Le(a) and Le(b) These findings are consistent with the concept of affinity maturation of the immune response, which has been previously demonstrated only in animal model systems.

Antibody Specificity

Transfusion and recipient immune function.

For some time it has been known that allogeneic blood transfusions have immunologic effects on animal and human recipients. These effects include increased numbers of suppressor T cells, decreased natural killer-cell function, decreased function of macrophages and monocytes, induction of anti-idiotypic antibodies that suppress allogeneic antigen recognition, and decreases in alloreactivity of mononuclear cells in mixed lymphocyte cultures. The meaning of these changes is not clearly understood, nor is the exact clinical importance of these alterations known. However, these decreases in immunologic function may explain a number of clinical consequences some investigators believe are the sequelae of homologous blood transfusions. Clinically important outcomes that are associated with transfusions are improved survival of renal allografts and increased risks of bacterial infection and cancer recurrence after perioperative transfusions. Transfusion of plasma-rich blood components (eg, whole blood) has been specifically associated with earlier cancer recurrence and better renal allograft survival in some patient groups. The new hypothesis that transfusion of stored plasma is a major factor in altering host immune defenses is supported by the observation that patients infected with human immunodeficiency acquired immunodeficiency syndrome more rapidly if they have been transfused with large amounts of plasma. Contrary to previous belief, the transfusion of homologous stored blood plasma may have as great or greater effects on immunity than transfusion of white blood cells. We believe investigation into the immunologic effects of transfusions is likely to have a significant impact on transfusion medicine research and practice over the coming years.

Acquired Immunodeficiency Syndrome

Perioperative blood transfusions and prostate cancer recurrence and survival.

This retrospective clinical study of patients with nonmetastatic prostate cancer demonstrates that patients transfused at the time of initial diagnosis or operation have a higher frequency of recurrence (54 percent) and death due to cancer (19 percent) than patients not receiving blood transfusions (recurrence rate 31 percent, p = 0.005; death rate 10 percent, p = 0.08). This difference is not explained by the transfused patients being older, having a less favorable clinical stage of disease, or less differentiated tumor histology. A multivariate analysis confirmed that the additional risk of dying from prostate cancer was 2.82-fold higher in transfused patients than in those not transfused. As in previous studies, the risk of recurrence may be greater in those receiving whole blood transfusions. Prospective studies of the association between perioperative blood transfusion and cancer recurrence are needed. For the present, prudent clinical practice should include avoidance of whole blood, fresh frozen plasma, and platelet transfusions and greater reliance on autologous blood transfusions.

Humans

Correction of severe penile curves with tunica albuginea autografts.

Nesbit's technique of excising ellipses of the tunica albuginea has been effective in correcting penile curvatures. When this procedure is used for severe angulations, penile shortening can be significant. We report the use of Nesbit ellipses autografted to the contralateral corpus for correction of severe penile curvatures in 3 men. This method resulted in a straight penis with minimal shortening.

Humans

Further evidence supporting a cause and effect relationship between blood transfusion and earlier cancer recurrence.

Studies of associations between perioperative blood transfusions and later recurrence of solid tumors have yielded conflicting results. A previous analysis of transfused patients suggested that recurrence was associated with transfusion of whole blood as opposed to red blood cell concentrates. Additional analyses were performed on patients with cancers of the colon, rectum, cervix, and prostate to determine if patients receiving whole blood, red blood cells only, or no transfusions had differing outcomes. Patients receiving 1 unit or more of whole blood had uniformly poor outcomes compared with nontransfused patients (p less than 0.001). In contrast, patients receiving only red blood cells had progressively worse recurrence and death rates with increasing numbers of transfusion, suggesting the presence of a dose-effect relationship. Employing multivariate techniques, blood transfusion of less than or equal to 3 units that included any whole blood were independently and significantly associated with earlier recurrence (p = 0.003) and death due to cancer (p = 0.02). Transfusions of less than or equal to 3 units of blood comprised solely of red blood cell concentrates were associated with no greater risk of recurrence than that seen in patients receiving no transfusion (p = 0.50). These results provide a potential explanation for the disparate results reported in studies of blood transfusion and cancer outcome. The marked difference in outcome seen between patients receiving a few units of red blood cells and comparable patients receiving even one unit of whole blood are consistent with the hypothesis that transfusion of stored blood plasma causes earlier tumor recurrence in some instances. Strategies for reducing these risks might include avoidance of whole blood transfusions when only 1-3 units are required, more conservative transfusion practice, use of autologous blood transfusions, and perhaps, use of red blood cells washed free of plasma and white cell debris. Clinical trials to test these hypotheses are urgently needed.

Colonic Neoplasms

A rapid and accurate single-drop modification of the acid-elution technique for detecting fetomaternal hemorrhage.

A single-drop modification of the acid-elution technique (Kleihauer-Betke) for quantitating fetomaternal hemorrhage is described. It obviates the need for the tedious and time-consuming manual counting of background adult cells. Rather, this is achieved by automated red-blood cell counting of the initial specimen and delivery of a standard volume (1 microliter) of a standard dilution (1:1,000) in the form of a droplet to a microscope slide. The droplet is left to dry undisturbed at room temperature and then stained. The fetal cells are manually counted while the total number of cells is calculated from the initial red-blood cell count, standard volume, and standard dilution. Determinations on 4 different concentrations of fetal/adult red cell mixtures are performed. Results indicate improved accuracy and precision relative to the standard technique in significantly less time for volumes of fetomaternal hemorrhage requiring more than the standard dose of Rho(D)-immune globulin.

Cell Adhesion