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Biomedical subjects

M E Brecher

Publications and source records attributed to M E Brecher.

At least 37 records · Page 2Linked to original sources
PubMed2001

Likelihood of D heterozygosity in Mestizo Mexicans and Mexican Americans.

Information on the gene frequencies of the Rh system in the Mexican or Mexican American population is currently not available in the medical literature, thus hindering management of pregnancies at risk for development of hemolytic disease of the newborn. Data from four recent large studies in the broader scientific literature of Mestizo Mexicans and Mexican Americans is reviewed. Gene frequencies are calculated from the pooled data. A table of gene frequencies in the Caucasian and African American population is provided for comparison.

Journal Article↗
PubMed2000

Comparison of granulocyte colony-stimulating factor (G-CSF)--mobilized peripheral blood progenitor cells and G-CSF--stimulated bone marrow as a source of stem cells in HLA-matched sibling transplantation.

HLA-identical bone marrow or stem cell transplantation from a sibling is the preferred treatment for patients with chronic myelogenous leukemia, bone marrow failure syndromes, relapsed acute leukemia, and specific inborn errors of metabolism. Several groups have shown that granulocyte colony-stimulating factor (G-CSF)--mobilized peripheral blood progenitor cells (PBPCs) obtained from HLA-matched siblings are effective in reconstitution of marrow function after marrow ablative conditioning therapy. To evaluate whether G-CSF treatment before bone marrow harvest leads to enhanced recovery of PBPC counts and recovery from limited graft-versus-host disease (GVHD), we assessed the outcome of a sequential cohort of patients treated identically and then given either G-CSF--mobilized PBPCs or G-CSF--stimulated bone marrow from HLA-identical siblings. We show that the time to neutrophil engraftment is identical in the 2 cohorts, whereas platelet engraftment is earlier with the use of PBPCs. The incidence of acute GVHD was decreased, and that of chronic GVHD significantly decreased, in the group receiving bone marrow. Overall survival was not different between the 2 groups. Thus, G-CSF--stimulated bone marrow offers a source of stem cells that allows for early neutrophil engraftment with a decreased risk of GVHD.

Adolescent↗
PubMed2000

Antibiotic-labeled probes and microvolume fluorimetry for the rapid detection of bacterial contamination in platelet components: a preliminary report.

BACKGROUND: Approximately 1 platelet in 2000 components is bacterially contaminated. Most commonly, contaminating organisms are gram positive skin saprophytes (such as Staphylococcus sp. or Bacillus sp.). A novel approach to the rapid diagnosis of gram positive contamination by the use of a fluorescence-labeled antibiotic probe with affinity for the gram positive cell was investigated. STUDY DESIGN AND METHODS: Two isolates of Staphylococcus epidermidis were inoculated into bags of Day 0 platelets. Quantitative cultures along with a semi-automated screening assay on a microvolume fluorimeter employing a fluorescence-conjugated vancomycin probe was performed for each day of storage. In addition, serial dilutions of the bacteria were added to sterile platelets to achieve a range spanning 10(1) to 10(8) CFUs per mL. RESULTS: All samples with a bacterial contamination of > or =10(5) CFU per mL were detected. Sterile samples were nonreactive. The entire procedure requires three pipetting steps and took less than 1 hour to perform. CONCLUSION: These preliminary results with the use of fluorescence-labeled antibiotics as probes combined with microvolume fluorimetry for the rapid detection of bacterial contamination of platelet components suggest that this is a promising approach. Further studies with additional organisms and alternative conjugates, bacteria, and antibiotics are underway.

Anti-Bacterial Agents↗
PubMed2000

Growth of bacteria in inoculated platelets: implications for bacteria detection and the extension of platelet storage.

BACKGROUND: Recent reports from Europe have advocated the use of bacterial culturing of platelets on Day 2 or 3 of storage to extend the shelf life of platelets to 7 days, thereby reducing the outdating of platelets and preserving a limited medical resource. To assess the optimal timing, the necessary sensitivity, and the possible efficacy of bacterial detection, the bacterial growth characteristics were reviewed in 165 platelet units, each inoculated on the day of collection with one of the following organisms: Bacillus cereus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Serratia marcescens, Staphylococcus aureus, and Staphylococcus epidermidis from four previously published studies. STUDY DESIGN AND METHODS: Quantitative culture data from inoculated platelet concentrates from five sites and four studies were combined into one database and analyzed for bacterial concentration thresholds (> or =10(1), > or =10(2), > or =10(3), > or =10(4), > or =10(5) CFU/mL) by day of storage. RESULTS: All examples of B. cereus, P. aeruginosa, K. pneumoniae, S. marcescens, and S. aureus had concentrations > or =10(2) CFU per mL by Day 3 after inoculation. By Day 4, all units with these organisms contained > or =10(5) CFU per mL. Units contaminated with S. epidermidis showed slower and more varied growth. By Day 3 after inoculation, 81.3 percent had 10(2) CFU per mL. By Day 4 after inoculation, 46 (95.8%) of 48 units had concentrations > or =10(2) CFU per mL. CONCLUSION: These experiments suggest that an assay capable of detecting 10(2) CFU per mL on Day 3 of storage would detect the vast majority of bacterially contaminated platelet units, prevent many cases of platelet-associated bacterial sepsis, and provide a scientific basis for the extension of the current platelet storage time. It would be expected that a rare, slow-growing organism could escape such a detection scheme.

Bacteria↗
PubMed1999

Apheresis and the thrombotic thrombocytopenic purpura syndrome: current advances in diagnosis, pathophysiology, and management.

Endeavors to optimize the management of thrombotic thrombocytopenic purpura (TTP) syndrome and improve mortality and relapse rates are hindered by its poorly understood pathophysiology. Variability in the application of therapeutic plasma exchange (TPE), including replacement fluid strategies, desirable endpoints in the platelet count, serum lactate dehydrogenase concentration, and the use of a TPE taper, limit comparisons among published studies. The diversity of adjunctive therapies such as antiplatelet agents, steroids, and splenectomy further clouds comparisons. Recent progress in the diagnosis, pathophysiology, and management of TTP syndrome are summarized. The possible role of occult infection and newly emerging associations such as ticlopidine therapy are discussed. Advances in possible pathogenic mechanisms, the rationale for different replacement fluids including the recently licensed solvent-detergent treated plasma, and progress in the apheresis management of TTP syndrome are presented.

Blood Component Removal↗
PubMed1999

Where does preoperative erythropoietin therapy count? A mathematical perspective.

BACKGROUND: The administration of erythropoietin (EPO) can be used to increase a patient's hematocrit (Hct) in the preoperative period and thus possibly preclude the need for allogeneic red cells. However, the exact effect on the postoperative Hct of a given rise in Hct in the preoperative period (and on the avoidance of allogeneic blood) has not been thoroughly evaluated. STUDY DESIGN AND METHODS: Equations were developed on the basis of previously described relationships that allowed the assessment of the impact of a given preoperative Hct increase on the postoperative Hct under a variety of clinical situations. RESULTS: Equations were derived that related the change in preoperative Hct after the administration of EPO to the final Hct after a given blood loss. In a typical example (blood volume = 5000 mL, pre-EPO Hct of 40%, post-EPO Hct of 45% after blood losses of 1000, 2000, 3000, 4000, 5000, and 6000 mL), an additional 205, 168, 137, 112, 92, and 75 mL of red cells, respectively, would be present postoperatively over the volume in the same patient who did not receive EPO. For a smaller patient, such as a child (blood volume, 2500 mL), an additional 17 mL (5000-mL blood loss) to 83 mL (1000-mL blood loss) of red cells would be present postoperatively. Hemodilution and EPO act synergistically to yield additional postoperative red cell volume. CONCLUSION: The use of preoperative EPO with a preoperative increase in Hct results in an increased postoperative Hct after a surgical blood loss. Such a postoperative increase is a function of the volume of blood lost and the patient's blood volume but is independent of the patient's initial Hct. The final postoperative red cell volume increase associated with a preoperative increase in Hct of 1 to 5 percent is limited, however (generally equivalent to a fraction of 1 unit of allogeneic blood). Much of the increase in the patient's Hct vanishes at higher blood losses, and this therapy is most effective with blood loss of <4000 mL. EPO therapy alone may be most effectively used in patients with mild anemia who are undergoing routine surgical procedures that commonly require blood transfusion.

Blood Loss, Surgical↗
PubMed1999

The value of oxygen-carrying solutions in the operative setting, as determined by mathematical modeling.

BACKGROUND: The use of oxygen carriers (red cell [RBC] substitutes) in acute trauma and in surgery, with or without the use of acute normovolemic hemodilution (ANH), is being investigated. Mathematical modeling was used to assess the impact of RBC substitutes, with or without ANH, in the elective surgical setting. STUDY DESIGN AND METHODS: Mathematical equations and computer models were developed on the basis of previously described mathematical principles, for better understanding of the potential efficacy of RBC substitutes for blood needs with or without ANH. Savings were calculated for a patient with a blood volume of 5000 mL and an initial hematocrit (Hct) of 45 or 30 percent. RESULTS: Substantial increases in the tolerable blood losses (or reduced allogeneic RBC needs) were most evident when the use of an RBC substitute to achieve severe ANH to a Hct that the patient might not otherwise have been able to tolerate was combined with the use of RBC substitutes as replacement for the surgical blood subsequently lost. However, the benefit was greatly dependent on the patient's initial Hct. For example, for a patient with a blood volume of 5000 mL and an initial Hct of 45 percent, a blood loss of approximately 2500 mL resulted in a final Hct of 28 percent without the use of an RBC substitute or ANH. In contrast, with the combined use of staged ANH with an RBC substitute and the RBC substitute for lost surgical blood, a blood loss of up to 14.5 L could be tolerated. However, in an anemic patient (blood volume 5000 mL, initial Hct 30%), a Hct of 28 percent cannot be sustained without the use of allogeneic RBCs for any of the described strategies, even when blood losses were as low as 1 L. CONCLUSION: The use of RBC substitutes has the potential to result in a substantial reduction in allogeneic RBC exposure. This benefit is essentially limited to the nonanemic patient when the use of an RBC substitute is combined with severe ANH and there is concomitant large perioperative blood loss. Anemic patients can be expected to have only limited benefit, because of an inability to sequester an adequate volume of autologous RBCs via ANH.

Blood Substitutes↗
PubMed1999

MUC1 expression in hematopoietic tissues.

The MUC1 gene encodes the core protein of episialin, which is recognized by several antibodies. Reverse transcription-polymerase chain reaction (RT-PCR) detection of MUC1 transcripts has been proposed for the detection of micrometastases from breast cancers. MUC1 expression in hematopoietic tissues has been reported but not confirmed. Our preliminary RT-PCR studies confirmed MUC1 expression by MDA-231 breast cancer cells. Western blots of MDA-231 proteins stained with anti-MUC1 core gave one 68-kd (core protein) band, with an additional high molecular weight (HMW) band in blots stained with anti-epithelial membrane antigen (EMA). MUC1 expression was detectable by RT-PCR in 4 samples each of peripheral blood, bone marrow, and lymph node. MUC1 expression was detectable by Western blot analysis using anti-MUC1 core and anti-EMA in 2 peripheral blood samples and all bone marrow samples. Western blots from all lymph node samples stained positively with anti-EMA for the HMW product, but the 68-kd product was less prominent. Separated peripheral blood lymphocytes and granulocytes showed similar levels of MUC1 expression. RT-PCR studies demonstrated MUC1 expression in various hematopoietic cell lines. Western blots showed the 68-kd and HMW products in a granulopoietic line, with only the 68-kd product in 3 lymphoblastoid lines. MUC1 is expressed ubiquitously in hematopoietic tissues and is unsuitable for use as a marker for epithelial micrometastases.

Biomarkers, Tumor↗
PubMed1999

A prospective randomized comparison of three blood conservation strategies for radical prostatectomy.

BACKGROUND: Preoperative autologous blood donation is a standard of care for elective surgical procedures requiring transfusion. The authors evaluated the efficacy of alternative blood-conservation strategies including preoperative recombinant human erythropoietin (rHuEPO) therapy and acute normovolemic hemodilution (ANH) in radical retropubic prostatectomy patients. METHODS: Seventy-nine patients were prospectively randomized to preoperative autologous donation (3 U autologous blood); rHuEPO plus ANH (preoperative subcutaneous administration of 600 U/kg rHuEPO at 21 and 14 days before surgery and 300 U/kg on day of surgery followed by ANH in the operating room); or ANH (blinded, placebo injections per the rHuEPO regimen listed previously). Transfusion outcomes, perioperative hematocrit levels, postoperative outcomes, and blood-conservation costs were compared among the three groups. RESULTS: Baseline hematocrit levels were similar in all groups (43%+/-2%). On the day of surgery hematocrit decreased to 34% +/-4% in the preoperative autologous donation group (P < 0.001), increased to 47%+/-2% in the rHuEPO plus ANH group (P < 0.001), and remained unchanged at 43%+/-2% in the ANH group. Allogeneic blood exposure was similar in all groups. The rHuEPO plus ANH group had significantly higher hematocrit levels compared with the other groups throughout the hospitalization (P < 0.001). Average transfusion costs were significantly lower for ANH ($194+/-$192) compared with preoperative autologous donation ($690+/-$128; P < 0.001) or rHuEPO plus ANH ($1,393+/-$204, P < 0.001). CONCLUSIONS: All three blood-conservation strategies resulted in similar allogeneic blood exposure rates, but ANH was the least costly technique. Preoperative rHuEPO plus ANH prevented postoperative anemia but resulted in the highest transfusion costs.

Aged↗
PubMed1998

Successful treatment of transient acquired factor X deficiency by plasmapheresis with concomitant intravenous immunoglobulin and steroid therapy.

Two patients with no history of previous bleeding diatheses presented with active bleeding from multiple body sites, declining hemoglobin levels, and markedly prolonged prothrombin times (PT) and activated partial thromboplastin times (aPTT) with incomplete correction on PT mix assays. Both patients demonstrated a severe deficiency of factor X (F.X) (<1%; reference range 60-150%). F.X levels and bleeding were refractory to multiple transfusions of fresh frozen plasma (FFP) in both patients. In contrast, daily therapeutic plasma exchange (PLEX) with concomitant administration of intravenous immunoglobulin (IV IgG) and steroids produced a rapid increase in F.X levels with cessation of bleeding, followed by stabilization and normalization of F.X levels and progressive correction of coagulation times. Neither patient has demonstrated a recurrence of the bleeding tendency following discontinuation of steroid therapy. These patients had transient acquired F.X deficiency, a rare coagulopathy, which can result in a lethal bleeding diathesis. An IgG inhibitor that selectively inhibited F.X activation in Russell's viper venom or tissue factor/F.VIIa assays was demonstrated in one patient's pretreatment plasma. Previous treatment of hemorrhage in transient acquired F.X deficiency has been prothrombin complex and/or activated clotting concentrates, which can be associated with transient hypercoagulable states. This is the first reported use of PLEX in transient acquired F.X deficiency. PLEX is safe, efficacious, and rapidly restores hemostasis in this rare acquired bleeding disorder.

Adult↗
PubMed1998

Cellular source of serum lactate dehydrogenase elevation in patients with thrombotic thrombocytopenic purpura.

Elevated serum lactate dehydrogenase (LDH) is a characteristic finding in patients with thrombotic thrombocytopenic purpura (TTP). It is widely accepted that total serum LDH principally rises due to the release of red blood cell LDH as a consequence of intravascular hemolysis. To identify the cellular source of serum LDH in TTP, we prospectively analyzed total serum LDH and LDH isoenzyme profiles in 10 consecutive patients with classic, acute idiopathic TTP within 5 days of clinical presentation. Total LDH was quantitated on a Hitachi 911 Analyzer (Indianapolis, IN), using the lactate to pyruvate reaction. LDH isoenzymes were measured by serum protein electrophoresis, using the Beckman LDH Isoenzyme Kit (Anaheim, CA). Isoenzymes attributable to erythrocytes (LDH1, LDH2) were not disproportionately elevated in 9 of 10 patients. LDH3 was below or within normal limits for all 10 patients, and one patient showed a slightly increased LDH4. Serum LDH5, the isoenzyme derived primarily from liver and skeletal muscle, was elevated 1-2 times normal in all patients. Evidence supporting hemolysis as the major contribution to the elevated total serum LDH frequently encountered in acute TTP was not identified in this study. The isoenzyme fractions LDH and LDH2 elevated by erythrocyte injury were not disproportionately elevated in this series. LDH 5, the isoenzyme found in skeletal muscle and liver, was consistently 1- to 2-fold greater than normal in all patients. We propose that the elevation of serum LDH seen in patients with TTP is due to release of LDH from a variety of tissues damaged as a result of systemic ischemia.

Erythrocytes↗
PubMed1998

Apheresis platelets: emerging issues related to donor platelet count, apheresis platelet yield, and platelet transfusion dose.

Emerging issues in stimulating apheresis platelet donors with platelet growth factors, the relative costs of apheresis and random donor platelet concentrates, optimal platelet transfusion dose, and leucoreduction of platelet products have caused renewed debate regarding apheresis products vs. random, pooled concentrates. The future role of apheresis products in platelet transfusion therapy will in large part be determined by costs, which are increasingly recognized to be influenced by donor platelet count, apheresis yield, and platelet transfusion dose.

Blood Donors↗
PubMed1998

United States Thrombotic Thrombocytopenic Purpura Apheresis Study Group (US TTP ASG): multicenter survey and retrospective analysis of current efficacy of therapeutic plasma exchange.

Thrombotic thrombocytopenic purpura (TTP) remains enigmatic from the perspective of its etiology, pathophysiology, and treatment. Once recognized, the accepted standard of care for TTP is daily therapeutic plasma exchange (TPE). However, the diversity in TPE treatment protocols has made comparisons of clinical research between institutions difficult. This study strived to assess the current practice of TPE in order to provide direction for prospective controlled clinical trials. Twenty large apheresis centers within the United States comprising the US TTP ASG responded to a survey to establish the current status of TPE in TTP. A retrospective analysis from data provided by 14 of 20 centers included 115 initial presentations of primary TTP with an overall mortality rate of 10% and relapse rate of 37%. The majority of deaths (58%) occurred within 48 hours of presentation. Variation in therapeutic targets (platelet count [plt] and serum LDH) and the number of plasma volumes exchanged per procedure did not affect the relapse rate. Initial plt and LDH were not predictive of mortality. Response, relapse, and mortality rates with the combination of 5% albumin for the initial 50% of TPE followed by plasma for the final 50% of TPE as replacement were comparable or possibly better than plasma-only replacement strategies. Forty percent of centers routinely used a TPE taper; however, there was no statistical difference in relapse rates comparing the taper and non-taper sub-groups. By controlling for adjunctive modalities such as steroids and anti-platelet agents, it is hoped that future prospective clinical trials may optimize the role of TPE in TTP, minimize patient exposure to blood products and procedures, shorten the clinical course of TTP, and reduce mortality.

Blood Component Removal↗