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Biomedical subjects

R J Benjamin

Publications and source records attributed to R J Benjamin.

At least 19 recordsLinked to original sources
PubMed2001

Nucleic acid testing: update and applications.

Nucleic acid testing (NAT) holds the promise of closing the window of infectiousness for hepatitis C virus (HCV) and the human immunodeficiency virus (HIV) in the general blood supply. Pioneering work by the source plasma industry with NAT for hepatitis A virus (HAV), hepatitis B virus (HBV), and parvovirus B19 suggests that, in the future, the risk of other viral infections may be reduced using similar technology. The European Commission decree that, by July 1999, all source plasma for fractionation should be NAT nonreactive for HCV at a sensitivity of 100 viral IU/mL, has driven the implementation of NAT in the United States. It is estimated that more than 95% of the US blood supply is currently tested by one of two investigational tests for HCV and HIV, and many institutions restrict the release of red blood cell (RBC) and plasma products prior to the release of NAT results. NAT implementation has been hampered by a lack of fully automated, low-cost technologies; the absence of Food and Drug Administration (FDA)-approved and validated clinical tests; and lagging turnaround times. Results from US investigational trials of the Procleix Transcription Mediated Amplification (TMA) HCV/HIV (Chiron Corp, Emeryville, CA) and the COBAS AmpliScreen (Roche Diagnostics, Indianapolis, IN) polymerase chain reaction (PCR) assays have begun to substantiate their value. While NAT assays will not replace serologic tests, they lay the groundwork for further reducing the already low risk of infection transmission through transfusion of blood components and their factor derivatives.

Blood Donors↗
PubMed2000

The chemokine receptor CXCR3 is expressed in a subset of B-cell lymphomas and is a marker of B-cell chronic lymphocytic leukemia.

Chemotaxis in leukocytes is mediated through binding of soluble chemokines to transmembrane G-protein coupled receptors. The chemokine receptor CXCR3 has been previously shown to be widely expressed on activated T cells and to mediate T-cell chemotaxis on binding to various ligands, including Mig, IP-10, and ITAC. By using immunohistochemical and flow cytometric analysis, we report that CXCR3 is also expressed on a subset of peripheral blood B cells and in distinct subtypes of B-cell lymphoma. CXCR3 immunohistochemical or flow cytometric expression was seen in 37 of 39 cases of chronic lymphocytic leukemia/small lymphocytic lymphoma (diffusely positive in 33 cases), whereas mantle cell lymphoma (30 cases), follicular lymphoma (27 cases), and small noncleaved cell lymphoma (8 cases) were negative in all but 2 cases. Strong CXCR3 expression was also seen in splenic marginal zone lymphoma (14 of 14 cases) and in the monocytoid and plasmacytic cells in extranodal marginal zone lymphoma (15 of 16 cases). This differential expression of CXCR3 in B-cell tumors contrasts with that of another B-cell-associated chemokine receptor, BLR1/CXCR5, which we show here is expressed on all types of B-cell lymphoma tested. We also report that the CXCR3 ligand, Mig, is coexpressed on tumor cells in many cases of CLL/SLL (10 of 13 cases examined) with Mig expression less frequently seen in other B-cell lymphoma subtypes. Coexpression of CXCR3 and its ligand, Mig, may be an important functional interaction in B-CLL, as well as a useful diagnostic marker for the differential diagnosis of small cell lymphomas. (Blood. 2000;95:627-632)

B-Lymphocytes↗
PubMed1999

Plateletpheresis efficiency: a comparison of the spectra LRS and AMICUS separators.

BACKGROUND: Optimizing the yields of plateletpheresis by increasing collection efficiencies may provide several benefits: to patients, by increasing the dose in single-donor platelet (SDP) units; to the collection center, by increasing the percentage of components that may be split into double units; and/or to the donor, by reducing the duration of donation. STUDY DESIGN AND METHODS: A prospective, randomized study was undertaken to compare the efficiency of platelet collection in paired donations by 21 donors on two cell separators (Spectra LRS, version [v] 5.1; and AMICUS, v2.37). The order of donation was randomly assigned; donations were performed at least 2 weeks apart. A fixed blood volume (4000 mL) was processed by utilizing standard protocols. Findings were confirmed in a retrospective, matched study that compared the two separators by using fixed collection times (90 min). RESULTS: The AMICUS and Spectra LRS separators consistently produced white cell-reduced (<1 x 10(6) white cells) components. The AMICUS harvested 32 percent more platelets on average (median, 4.9 x 10(11); range, 1.5-8.7 x 10(11)) than the Spectra LRS (median, 3.7 x 10(11); range, 2.1-7.7 x 10(11)) (p = 0.03), with mean times of 71.5 and 66.0 minutes (p = 0.03), respectively, to process 4000 mL. Mild donor reactions tended to be more common on the AMICUS separator, which used significantly more ACD (median 482 mL vs. 389 mL; p<0.0001) than on the Spectra LRS. CONCLUSIONS: The AMICUS separator harvested more platelets per unit of blood volume processed than the Spectra LRS. Possible benefits include increased dose in each single-donor unit, increased double-unit harvests, and/or shorter donation time.

Cell Separation↗
PubMed1999

ABO incompatibility as an adverse risk factor for survival after allogeneic bone marrow transplantation.

BACKGROUND: Graft ABO incompatibility has not been thought to affect patient survival after allogeneic bone marrow transplantation, although it may be associated with prolonged erythroid aplasia and immediate or delayed hemolysis. STUDY DESIGN AND METHODS: A retrospective analysis of a cohort of 292 allogeneic transplant recipients measured survival in a subgroup of ABO-incompatible bone marrow graft recipients. RESULTS: Patients with acute myelogenous leukemia or myelodysplastic syndrome receiving non-T-cell-depleted bone marrow grafts had an 85-percent greater risk of death within 100 days of transplant (relative risk, 1.85, 95% CI, 1.33-2.58; p = 0.003) than comparable patients receiving ABO-compatible grafts. Both ABO major- and minor-mismatched graft recipients were at risk. The increased mortality rate was not due to an increase in graft failure or acute graft-versus-host disease; rather, patients died of multiple-organ failure and sepsis, which is consistent with regimen-related toxicity. This effect was not seen in a larger group of 112 chronic myelogenous leukemia patients undergoing similar treatment. CONCLUSION: ABO incompatibility may be a significant prognostic risk factor after allogeneic bone marrow transplantation in susceptible subgroups of recipients. Care is necessary to design hematopoietic stem and progenitor cell-processing and -transfusion policies to minimize this risk.

ABO Blood-Group System↗
PubMed1999

Transfusion with blood from a donor with chronic myelogenous leukemia: persistence of the bcr/abl translocation in the recipient.

BACKGROUND: Transfusion of cells harvested from patients with chronic myelogenous leukemia (CML) as a therapeutic measure for patients with granulocytopenia was popular in the 1970s, when studies examining the persistence of transfused donor cells were limited by a lack of molecular techniques. Blood samples from a patient who recently received an inadvertent transfusion of CML cells were evaluated for the presence of the bcr/abl translocation characteristic of CML. CASE REPORT: The patient, a 67-year-old man with a history of congestive heart failure, myocardial infarct, hypertension, diabetes mellitus, and chronic renal failure, was transfused for bleeding from colonic angiodysplasia. A volunteer blood donor reported that he had been diagnosed with CML 10 days after his donation. Three days after the donation, blood components from the donor with CML had been administered to the patient as nonirradiated red cells and platelets. Evaluation of donor blood by a reverse-transcriptase polymerase chain reaction showed the b3a2 transcript, indicating a bcr/abl translocation. Periodic testing of the patient's peripheral blood by the same technique demonstrated the presence of the b3a2 transcript on Days 74 and 75 after transfusion. The patient died of congestive heart failure 8 months after the transfusion. CONCLUSION: In this rare case of accidental transfusion of neoplastic cells, the findings document the persistence of the donor's neoplastic clone in the recipient for 75 days.

Aged↗
PubMed1999

The pathology of transfusion-related acute lung injury.

Transfusion-related acute lung injury is an uncommon condition characterized by the rapid onset of respiratory distress soon after transfusion. Our understanding of its pathophysiology is based on animal models of complement (C5a) and antibody-induced lung injury and a limited number of autopsies. These models suggest that transfusion-related acute lung injury is induced by granulocytes that aggregate in the pulmonary microvasculature after activation by transfusion-derived antibodies or biologically active lipids. The published autopsy reports provide little support for this model, as they are invariably confounded by underlying pulmonary infection, preexisting disease, and resuscitation injury. We report the case of a previously well 58-year-old man who died of transfusion-related acute lung injury within 2 hours of the onset of pulmonary distress; autopsy showed evidence of massive pulmonary edema with granulocyte aggregation within the pulmonary microvasculature and extravasation into alveoli. Electron microscopy revealed capillary endothelial damage with activated granulocytes in contact with the alveolar basement membranes. These findings provide direct support for the proposed model of transfusion-related acute lung injury pathogenesis.

Basement Membrane↗
PubMed1999

Massive myocardial necrosis in thrombotic thrombocytopenic purpura: a case report and review of the literature.

Thrombotic thrombocytopenic purpura (TTP) is an uncommon syndrome resulting from diffuse occlusion of small arterioles and capillaries by hyaline microthrombi. It is characterized by fever, thrombocytopenic purpura, microangiopathic hemolytic anemia, and neurologic and renal dysfunction. While cardiac pathology in TTP is commonly seen at autopsy, clinical cardiac dysfunction is rare and typically results from conduction system involvement. While 3% to 8% of patients with TTP report chest pain on admission, reports of fatal ventricular pump failure are extremely rare. We now report a case of TTP resulting in death from widespread myocardial necrosis. This patient presented with elevated cardiac enzymes and electrocardiographic disturbances that mimicked viral myocarditis, as well as a profound thrombocytopenia. Such a case may represent the extreme of a distribution of cardiac involvement in TTP or the consequence of an unidentified autoimmune process capable of precipitating severe myocardial TTP.

Fatal Outcome↗
PubMed1998

Prolonged erythroid aplasia after major ABO-mismatched transplantation for chronic myelogenous leukemia.

Erythroid engraftment after non-T cell-depleted allogeneic bone marrow transplant (BMT) is reviewed in 112 patients treated for chronic myelogenous leukemia (CML). Twenty-two of 76 evaluable patients were transplanted over a major ABO-mismatch compatibility barrier. These patients showed an increased delay in erythroid engraftment and in time to red blood cell transfusion independence when compared with ABO-identical or minor mismatched recipients. No difference in granulocyte or platelet engraftment was evident. Erythroid engraftment usually occurred spontaneously without specific intervention. One patient was found to have erythroid hypoplasia at day 201 after BMT, despite therapy with intravenous immunoglobulin and high-dose erythropoietin. An anti-A titer of 16,000 was documented. This patient was successfully treated with an aggressive course of 18 plasmapheresis procedures and with donor-type plasma replacement. Delayed erythroid engraftment is common after non-T cell-depleted major ABO-mismatched BMT in CML, but rarely requires intervention other than transfusion support. Rare cases of refractory erythroid aplasia may be treated without additional immunosuppression by aggressive plasma exchange with donor-type plasma.

ABO Blood-Group System↗
PubMed1998

Biliary excretion of Tc-99m EC in renal studies.

The role of biliary excretion in Tc-99m ethylenedicysteine (EC) renal imaging was studied. Of 2,215 dynamic renal studies performed with Tc-99m EC, only nine cases of gallbladder visualizations and/or biliary excretion were identified. In no case did biliary excretion affect the interpretation of the renal study.

Adult↗
PubMed1997

Preapheresis peripheral blood CD34+ mononuclear cell counts as predictors of progenitor cell yield.

BACKGROUND: Peripheral blood progenitor cells, harvested by apheresis after mobilization, provide rapid hematologic recovery after high-dose chemotherapy. However, because harvesting these cells is expensive and time-consuming, there has been much interest in optimizing collection protocols. An investigation was made to determine whether, in this clinical setting, peripheral blood progenitor cell yields may be predicted from preapheresis progenitor cell counts, allowing the length of each procedure to be "fine tuned" to achieve specific target goals. STUDY DESIGN AND METHODS: Preapheresis peripheral blood CD34+ cell and total colony-forming cell counts were assessed before 78 peripheral blood progenitor cell collections from 13 consecutive patients were performed. Preapheresis counts were correlated with actual progenitor cell yields. Factors affecting this correlation were analyzed. RESULTS: With the use of linear regression analysis preapheresis progenitor cell counts were found to correlate significantly but weakly with actual yields per kg of body weight per liter of blood processed (CD34+ cells: r = 0.43; colony-forming cells: r = 0.56). Further analysis revealed two possible causes: 1) circulating progenitor cell concentrations fluctuate widely during harvest, which implies that preapheresis counts are not representative of actual concentrations during apheresis, and 2) the efficiency with which apheresis machines extract mononuclear cells varies greatly between procedures. CONCLUSION: Preapheresis CD34+ and colony-forming cell counts correlated poorly with subsequent yields in this clinical setting, which suggests that it is not practical to use such counts to predict with certainty the length of apheresis needed to achieve a target yield.

Adult↗
PubMed1997

Liquid nitrogen freezers: a potential source of microbial contamination of hematopoietic stem cell components.

BACKGROUND: The recent report of hepatitis B transmission between hematopoietic progenitor and putative stem cell (HPC) components stored in liquid nitrogen led to the questioning of whether evidence existed for similar contamination by bacterial or fungal elements. STUDY DESIGN AND METHODS: Microbial contamination rates were reviewed for 704 HPC components from 255 patients over an 18-month period. Five liquid nitrogen freezers were surveyed for microbial contamination. The literature was reviewed to ascertain the published experience of other laboratories with HPC component contamination first documented on thawing. RESULTS: Seven (1.2%) of 583 thawed components were found to be contaminated with a variety of environmental or waterborne organisms, despite a meticulous protocol to prevent contamination during thawing. All of these components had been sterile on cryopreservation. Literature review revealed a similar incidence of post-thaw contamination from other centers. Microbial survey of liquid nitrogen freezers revealed low-level contamination in four of five. The organisms represented were similar to those cultured from thawed HPC components. One freezer was heavily contaminated by Aspergillus species. CONCLUSION: Liquid nitrogen freezers are not sterile, and both the liquid and vapor phases are potential sources of microbial contamination of HPC components. While low-level contamination by environmental organisms may be common, the occurrence of heavy contamination by potential pathogens such as Aspergillus species suggests that monitoring of liquid nitrogen sterility may be indicated. Strategies to assess and prevent microbial transmission from liquid nitrogen to HPC components need further development.

Acinetobacter Infections↗
PubMed1995

The collection and evaluation of peripheral blood progenitor cells sufficient for repetitive cycles of high-dose chemotherapy support.

BACKGROUND: The development of an optimized peripheral blood progenitor cell (PBPC) harvest protocol to provide support for repetitive chemotherapy cycles is described. STUDY DESIGN AND METHODS: PBPCs mobilized by cyclophosphamide plus granulocyte-colony-stimulating factor (G-CSF) were studied in 163 leukapheresis harvests from 26 lymphoma patients. Harvested cells were transfused with two chemotherapy cycles and with an autologous bone marrow transplant. Progenitor cell content was examined in the context of hematopoietic engraftment. RESULTS: Mobilization allowed the harvest of large numbers of PBPCs. Peak harvests tended to occur after the recovering white cell count exceeded 10 x 10(9) per L. CD34+ lymphomononuclear cell (MNC) and colony-forming units-granulocyte-macrophage (CFU-GM) counts correlated poorly, but both measures peaked within 24 hours of each other in 21 of 26 patients, which demonstrated PBPC mobilization. Engraftment of platelets (> 50 x 10(9)/L) and granulocytes (> 500 x 10(6)/L) was achieved in a median of 20.5 and 16 days, respectively. A minimum number of progenitors necessary to ensure engraftment could be derived. CONCLUSION: Cyclophosphamide and G-CSF allowed the harvest of sufficient PBPCs to support multiple rounds of chemotherapy. Harvest should commence when the recovery white cell count exceeds 10 x 10(9) per L. PBPC harvest CD34+MNC counts are as useful as CFU-GM results in the assessment of PBPC content, and they may allow harvest protocols to be tailored to individual patients.

Adult↗
PubMed1994

Glycated protein update: implications of recent studies, including the diabetes control and complications trial.

On the basis of the results of the Diabetes Control and Complications Trial (DCCT), the American Diabetes Association (ADA) now recommends tight control of blood glucose to near-normal concentrations as the primary goal for most eligible insulin-dependent diabetic patients. In the DCCT, intensive therapeutic intervention was based on frequent self-monitoring of blood glucose and monthly measurements of glycohemoglobin. The importance of glycohemoglobin assessments serves to highlight the present inadequacies in laboratory measurements of this analyte, which hinders wide implementation of the ADA recommendations. Clinical interventions aimed at achieving the DCCT's published therapeutic goals may place patients at a significantly increased risk for life-threatening hypoglycemia, if the therapy is based on nonstandardized laboratory results. Clinical laboratories will now be under increasing pressure to provide reproducible, standardized measurements of glycohemoglobin, a goal that recent research has shown to be realistic, if widespread interlaboratory calibration is adopted. Finally, recent advances in measuring glycated serum proteins appear to warrant reevaluation of such assays during future intensive therapy trials, as potentially important tools for fine-tuning tight blood glucose control.

Blood Glucose↗
PubMed1993

Structural diversity in the HLA-A10 family of alleles: correlations with serology.

The HLA-A10 crossreacting group consists of the A25, A26, A34, A43 and A66 antigens. Here, we report allelic sequences for A43 and for 2 subtypes of both A26 and A34. Combining these results with previously determined sequences for A25, A26 and A66 enables molecular comparison of all the serologically defined A10 antigens. They form a closely related and well-defined group of alleles which may have originated with A*2601. Patterns of serological crossreactivity are correlated with sequence and a public epitope shared by A33 and members of the A10 family is localized to residues R62 and N63. The A*2501, A*4301 and A*6601 alleles appear to have derived from A*2601 by single gene conversion events with other HLA-A alleles. In the case of A*4301, the donor allele was probably an A29 allele as A*4301 has a small element of sequence in the alpha 1 helix (residues L62 and Q63) uniquely shared with A29. The chimaeric structure of A43 explains the reactivity of A43 molecules with both A10 and A29 alloantisera. The rare Oriental variant of A26 (A26v*) is encoded by an allele (A*2602) that differs from A*2601 by a unique nucleotide substitution which changes aspartate to asparagine at position 116 in the floor of the peptide binding groove. Thus A*2602 is a functionally distinct allele that originated by a point mutation. Alleles encoding A34 and A66 antigens are found to have very similar structures, explaining the difficulty in their serological definition.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗
PubMed1992

Distinctive HLA-A,B antigens of black populations formed by interallelic conversion.

Alleles encoding five HLA-A and B Ag characteristic of black populations have been isolated and their nucleotide sequences determined. In each case, the "black" allele is similar to a "related" allele found in caucasoid populations. The primary differences between these pairs of alleles are localized clusters of nucleotide substitutions that change two to five residues of the Ag recognition site. The pattern of differences indicates that the pairs of black and caucasoid alleles diverged primarily as a result of interallelic conversion events.

Africa↗