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Biomedical subjects

N Blumberg

Publications and source records attributed to N Blumberg.

At least 73 records · Page 4Linked to original sources

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↗

Perioperative blood transfusion and solid tumour recurrence.

Evidence regarding the association of blood transfusions with recurrence of solid tumours is largely conflicting. This is perhaps unsurprising given the retrospective nature of the studies performed to date, the complexity of the disease and its treatment, and variations in local transfusion practices. Nonetheless, new data demonstrating that transfusions of whole blood, as opposed to red cell concentrates, are associated with earlier cancer recurrence are most readily explained by a cause and effect relationship. There is a growing literature documenting previously unforeseen immunologic consequences of homologous blood transfusion. These possible clinical consequences include earlier cancer recurrence and increased susceptibility to infection with bacteria and viruses. The questions raised in this review can be answered conclusively only by controlled prospective studies. For the present the prudent clinician will select red blood cells rather than whole blood for transfusion, employ autologous transfusions whenever feasible, and recognize that blood transfusion is a therapy with considerable benefits, but also considerable risks.

Humans↗

Comparison of monoclonal antisera with conventional antisera for Lewis blood group antigen determination.

Monoclonal blood grouping sera provide a means of overcoming difficulties inherent in the use of conventional polyclonal reagents. Two murine monoclonal anti-Lewis reagents were tested and found to be comparable to conventional reagents for use in red cell phenotyping. These reagents may detect Le(a) antigen on Le(a-b+) red cells with greater sensitivity than previously available polyclonal anti-Lewis reagents.

Antibodies, Monoclonal↗

Perioperative blood transfusion and solid tumor recurrence--a review.

Evidence regarding the association of blood transfusions with recurrence of solid tumors is largely conflicting. This is perhaps not surprising given the retrospective nature of the studies, the complexity of the disease and its treatment, and variations in local transfusion practices. Nonetheless, data demonstrating that transfusions of whole blood are associated with earlier cancer recurrence are most readily explained by a cause and effect relationship. There is a growing literature documenting previously unforeseen immunologic consequences of homologous blood transfusion. These possible clinical consequences may include earlier cancer recurrence, and increased susceptibility to infection with bacteria and viruses. The questions raised in this review will likely be answered by further studies. For the present, the prudent clinician will select red blood cells rather than whole blood for transfusion, and recognize that blood transfusion is a therapy with considerable benefits, but also considerable risks.

Acquired Immunodeficiency Syndrome↗

An evaluation of crossmatching, HLA, and ABO matching for platelet transfusions to refractory patients.

Refractoriness occurs in many patients receiving multiple platelet transfusions. We used a sensitive ELISA assay to assess the utility of crossmatching HLA-A,B matched single donor platelets in 51 consecutive, typical refractory patients. Of the 222 transfusions evaluated at 1 to 4 hours posttransfusion, only 17 of 54 (31%) with positive crossmatches had corrected platelet count increments of greater than or equal to 7,500/microL. In contrast, 95 of 168 (57%) of those with negative crossmatches had such increments (P less than .001). Regardless of the results of the crossmatch, HLA-A,B, and ABO matching had independent influences on transfusion outcome. The median corrected 1- to 4-hour increment for crossmatch negative transfusions was 13,300/microL for A/BU grade matches, 9,700 for BX, and 7,800 for C. Increments were 10,000/microL for ABO-identical transfusions and 5,900 for transfusions of platelets ABO incompatible with the recipient's plasma antibodies. When the donor platelets were ABO compatible, but the donor plasma contained ABO antibodies to the recipient's platelets, the increment was intermediate (8,200/microL). The most important factor in predicting platelet survival was the crossmatch, followed by HLA-A,B and ABO, each having independent predictive value. These data demonstrate that the predictive value of a negative crossmatch may be considerably less than that reported in previous studies with stable, less ill patients. In typical refractory patients, there appear to be mechanisms of platelet destruction that are related to HLA-A,B and ABO but are not detected with current crossmatch methods. We hypothesize that soluble plasma HLA-A,B and ABO antigens contribute to the destruction of donor and sometimes recipient platelets by an immune complex or other "innocent bystander" mechanism. With our crossmatching technique, HLA-A,B and ABO match grades remain relevant to platelet transfusion therapy in some refractory patients.

ABO Blood-Group System↗

Association between transfusion of whole blood and recurrence of cancer.

Transfusion affects the immune response to renal transplantation and may be associated with recurrence of various human neoplasms. Data from patients with colonic, rectal, cervical, and prostate tumours showed an association between transfusion of any amount of whole blood or larger amounts of red blood cells at the time of surgery and later recurrence of cancer. Recipients of one unit of whole blood had a significantly higher incidence of recurrence (45%) than recipients of a single unit of red cells (12%) (p = 0.03). Recipients of two units of whole blood also had a higher rate of recurrence (52%) than those receiving two units of red cells (23%) (p = 0.03). Recipients of any amount of whole blood had similar recurrence rates (38-52%). Recipients of four or more units of red blood cells had a higher rate of recurrence (55%) than those receiving three or fewer units of red blood cells (20%) (p = 0.005). Mortality due to cancer in patients receiving three or fewer units of red blood cells (2%) was similar to that in patients who did not have transfusions (7%) and significantly lower than that observed in patients receiving three or fewer units of whole blood (20%) (p = 0.003). A proportional hazards risk analysis showed that transfusion of any whole blood or more than three units of red blood cells was significantly associated with earlier recurrence and death due to cancer. These data support an association between transfusion and recurrence of cancer. They also suggest that some factor present in greater amounts in whole blood, such as plasma, may contribute to the increased risk of recurrence in patients who have undergone transfusion. Until the questions raised by retrospective studies of cancer recurrence and transfusion can be answered by prospective interventional trials with washed red blood cells, red blood cells should be transfused to patients with cancer in preference to whole blood when clinically feasible.

Blood Transfusion↗

Detection of anti-Lea in Le(a-b+) individuals by kinetic ELISA.

Utilizing a kinetic enzyme-linked antiglobulin binding assay, eight examples of anti-Lea were detected in individuals whose Lewis phenotype is Le(a-b+). These antibodies were not detectable by routine hemagglutination techniques, but were indistinguishable from anti-Lea made by Le(a-b-) individuals in terms of their immunologic fine specificity. However, unlike most anti-Lea antibodies from Le(a-b-) individuals, none of the anti-Lea antibodies had an IgG component. Anti-Lea antibodies in Le(a-b+) individuals may represent immune responses on the continuum between autoimmunity and alloimmunity.

Antibody Specificity↗

Disparities in estimates of IgG bound to normal platelets.

Estimates of the number of IgG molecules bound to normal platelets have ranged from several hundred to several tens of thousands. The lower estimates were generated from direct binding assays and stoichiometric assumptions. The higher values derive from competitive binding assays, in which platelet-associated IgG (PAIgG) is calculated from a standard curve using soluble IgG standards. Using a kinetic-ELISA (enzyme-linked immunosorbent assay) antiglobulin assay, we measured normal platelet IgG to be 21,200 +/- 9,400 molecules per platelet when a competitive assay and soluble IgG standards were used. Direct measurement of bound antiglobulin by kinetic-ELISA and stoichiometric assumptions yielded a measurement of 259 +/- 117 IgG molecules per platelet. Soluble IgG and PAIgG are not comparable in their ability to bind anti-IgG. Disparities in estimates of normal PAIgG are probably due to methodological differences. The estimate most likely to be correct is several hundred IgG or less per normal platelet.

Binding, Competitive↗

Relation between recurrence of cancer of the colon and blood transfusion.

Data suggest that blood transfusion can cause immunosuppression. The incidence of recurrence of tumours was examined retrospectively in patients who had undergone potentially curative operations for cancer of the colon during 1970-81. Tumours recurred in six of 68 patients (9%) who had not been given transfusions and in 56 of 129 patients (43%) who had (p much less than 0.0001). Transfusion was also found to be significantly associated with the time to recurrence after adjustment for other baseline prognostic factors (p less than 0.05). Perioperative transfusion may be a significant risk factor in the prognosis of cancer of the colon. Whether this association is causal is unknown.

Adult↗

Detection of IgG anti-Lewis (a) antibodies in cord sera by kinetic Elisa.

Lewis blood group antibodies rarely, if ever, cause hemolytic disease of the newborn. This observation has been attributed to the absence both of Lewis antigens on fetal cells and of maternal IgG Lewis antibody. In the present study, sera from 13 mother-infant pairs were tested for the presence of anti-Lewis (a) by hemagglutination and by a sensitive and specific kinetic enzyme-linked immunosorbent assay. By routine hemagglutination methods, anti-Lea was present in all maternal samples but absent in all cord samples. By kinetic enzyme-linked immunosorbent assay, IgG anti-Lea was present in 13 of 13 maternal samples and in 12 of 13 cord samples. These results indicate that IgG anti-Lea antibodies are common and do cross the placenta. This suggests that they do not cause hemolytic disease of the newborn because of the low levels of Lewis antigens on fetal red cells.

Enzyme-Linked Immunosorbent Assay↗

Correlation of humoral immunity to Lewis blood group antigens with renal transplant rejection.

Recent studies suggest that the Lewis blood group antigens are important for human renal transplantation. A possible mechanism by which Lewis blood group incompatibility could influence allograft rejection was investigated by measuring Lewis antibodies in sera from renal transplant recipients and appropriate controls using conventional hemagglutination and a sensitive and specific kinetic enzyme-linked immunosorbent assay (k-ELISA). The two methods yielded identical results with 14 positive control sera known to contain Lewis antibodies and with 43 sera from negative controls. Antibody was not detected in 16 Lewis-positive transplant patients. However, antibody was detected by k-ELISA in 4/11 Lewis-negative transplant candidates and in 8/8 Lewis-negative recipients of Lewis-incompatible grafts. All 8 grafts were rejected. The one Lewis-negative recipient of a Lewis-negative graft did not develop Lewis antibody nor reject his graft. Of the 12 renal patients in whom antibody was detected by k-ELISA, in only 4 was antibody also demonstrable by hemagglutination. These results indicate that hemagglutination may not be sensitive enough for antibody detection and that Lewis antibodies may play a role in renal allograft rejection.

Blood Group Incompatibility↗

Should chronic transfusions be matched for antigens other than ABO and Rho(D)?

It has been recommended that red blood cell transfusions to patients with hemoglobinopathy or aplastic anemia be matched for antigens other than ABO and Rho(D). We studied 1,010 patients with disorders that often lead to repetitive transfusion. The frequency of transfused patients with clinically important antibodies was not significantly different among the disease groups except for those with lymphocytic leukemia. The frequency of multiple red cell antibodies was about 3% overall. Most antibodies (71%) developed early in the transfusion course, before the 15th transfusion. From the standpoints of frequency of alloimmunization, multiplicity of antibodies, and time course of antibody development, patients with hemoglobinopathy and aplastic anemia were not significantly different from other transfused patients. Matching for antigens other than ABO or Rho(D) might increase costs in our hospital by 40,000-370,000 dollars per year for these patients. Because morbidity or mortality due to these antibodies is rare, antigen matching for other than ABO and Rho(D) is not cost-effective.

ABO Blood-Group System↗

Removal of HLA-A,B antigens from platelets.

Recent evidence suggests that HLA-A,B antigens present on human platelets, are acquired from plasma. Using hypertonic acid chloroquine (200 mg/ml, pH 5.0, 1 hr, 4 degrees C), we demonstrate elution of most or all HLA-A2 and HLA-B7,40 immunoreactive material from platelets. Corresponding antigens on human lymphocytes were not affected by this treatment. These findings are consistent with the hypothesis that HLA-A,B antigens are adsorbed onto platelet surfaces.

Antibodies, Monoclonal↗