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Biomedical subjects

A Gerson Greenburg

Publications and source records attributed to A Gerson Greenburg.

9 recordsLinked to original sources
PubMed2006

Toward 21st century blood component replacement therapeutics: artificial oxygen carriers, platelet substitutes, recombinant clotting factors, and others.

In this brief overview, recent progress and current status of blood substitute research and development is summarized. Current blood substitute development efforts are focused on red blood cell substitutes but substitutes for platelets and other blood components are also in progress. Red cell substitutes currently in various stages of development are semi-synthetic or synthetic oxygen carriers that include "stealth" or "masked" red cells, hemoglobin-based oxygen carriers and perfluorocarbon-based oxygen carriers. Artificial platelets (or platelet substitutes) are in early stages of development and include human platelet fragments or particles of synthetic/semi-synthetic materials or recombinant human serum albumin coupled with platelet surface receptor fragments. Of note, some recombinant clotting factors (Factors VII, VIII, IX) have already been successfully developed and licensed for treatment of hemophilia. In addition, some future approaches and prospects of blood component replacement therapeutics are discussed.

Blood Coagulation Factors↗
PubMed2005

Mechanisms for vasoconstriction and decreased blood flow following intravenous administration of cell-free native hemoglobin solutions.

Acellular free hemoglobin-based oxygen carriers (HBOC) are being developed as red cell substitutes. However, following intravenous administration of some HBOC, decreased systemic blood flow and decreased functional capillary density have been observed. In isolated blood vessels, hemoglobin (Hb) in solution free of erythrocyte membranes has been shown to elicit vascular contraction. Therefore, the decreased blood flow and functional capillary density may be due to inherent vasoactive property of native Hb. There are two plausible mechanisms for the Hb-mediated vasoconstriction: nitrosylation of heme-irons and S-nitrosation of reactive beta-chain cysteines (Cys93beta). In this study, we investigated whether Hb Cys93beta thiols play a role in Hb-mediated vascular contraction using functional bioassays with isolated rat thoracic aorta. To better define the roles of globin thiols and heme-iron, Hbs modified at the heme-iron and/or Cys93beta sites were prepared and their vasoactivities tested. In addition, vasoactivities of natural heme proteins with heme and/or cysteine sites unavailable for NO reaction were also examined.

Alkylation↗
PubMed2004

Hemoglobin-based oxygen carriers.

Transfusable fluids that may be used as alternatives to red blood cell transfusion offer the promise of preserving tissue perfusion and minimizing hypoxic cellular damage, and this promise may soon be fulfilled. Clinical testing of hemoglobin-based oxygen carriers has faced and met challenges involving molecular design, safety, efficacy, and regulatory requirements. Three leading candidates have emerged: two human (PolyHeme and HemoLink) and one bovine-based hemoglobin solution (Hemopure). Because a survival benefit has been difficult to demonstrate, avoidance of allogeneic transfusion has been adopted as the standard efficacy end-point for these agents. An update on clinical trial status is provided, and the potential utility of hemoglobin-based oxygen carriers in surgery combined with intraoperative autologous donation is discussed.

Animals↗
PubMed2004

Use of an oxygen therapeutic as an adjunct to intraoperative autologous donation to reduce transfusion requirements in patients undergoing coronary artery bypass graft surgery.

BACKGROUND: The benefits of intraoperative autologous donation (IAD) in reducing the need for allogeneic blood transfusion in surgery have been debated for several years. The purpose of this study was to determine if IAD alone or in conjunction with hemoglobin raffimer (HR) confers a reduction in red cell or blood component transfusion compared with results in standard clinical practice. STUDY DESIGN: The Phase III clinical trial was a multicenter, randomized, double-blind study to determine the efficacy and safety of HR versus 10% pentastarch when used to facilitate IAD in 299 patients undergoing primary coronary artery bypass grafting. The patients received HR or pentastarch as an adjunct to IAD immediately before cardiopulmonary bypass. Results were compared with transfusion requirements for 150 matched patients in the reference group. RESULTS: The frequency of allogeneic RBC transfusion in the HR, pentastarch, and reference groups was 56%, 76%, and 95%, respectively. The number of allogeneic red cell units used was 49 in the HR group, 104 in the pentastarch group, and 480 in the reference group (p < 0.001). The total number of non-RBC units administered was 150 in the HR group, 238 in the pentastarch group, and 270 in the reference group. CONCLUSIONS: In this study, patients treated with HR in conjunction with IAD received fewer transfusions overall and a lower volume of allogeneic RBCs and non-RBC allogeneic blood products than did the two comparison groups. This confers a real benefit on the overall blood supply by decreasing use and increasing availability.

Aged↗
PubMed2004

Civilian uses of hemoglobin-based oxygen carriers.

This article briefly discusses a few key issues related to transfusion, the concept of hemoglobin-based red blood cell substitutes (HBOCs), and some parameters useful in evaluating the current properties of solutions. Potential uses of HBOCs in civilian applications are identified and listed. Use of HBOCs as a hemodiluent for intraoperative autologous blood donation (IAD) is a particular application that has relevance in many surgical settings and this is discussed in some detail. Data from a Phase III clinical trial is presented to show the potential for avoiding the use of allogeneic blood and blood products in a clinical model of large volume red cell use. Extrapolation to a general use model, primarily based in the potential for surgery, will be noted. Some general parametric values of HBOCs are presented. These values are by no means considered optimal for all HBOCs and are subject to exploration, fine tuning, correction, or even rejection.

Blood Substitutes↗
PubMed2004

Artificial oxygen carriers as red blood cell substitutes: a selected review and current status.

Two distinct approaches are being explored in red blood cell substitute (RCS) development: hemoglobin-based oxygen carriers (HBOCs) and perfluorocarbon-based oxygen carriers (PFBOCs). HBOCs are based on intra- and/or intermolecularly "engineered" human or animal hemoglobins (Hbs), optimized for O2 delivery and longer intravascular circulation. Some are currently being evaluated in Phase II/III clinical studies. PFBOCs are aqueous emulsions of perfluorocarbon derivatives that dissolve relatively large amounts of O2. A PFBOC based on a 60% (wt/vol) emulsion of perfluorooctyl bromide has been evaluated in Phase II/III clinical trials. Although current PFBOC products generally require patients to breathe O2 enriched air, they render certain advantages since they are totally synthetic. This article provides a short review of the basic principles, approaches, and current status of RCS development. Results of preclinical and clinical studies including recent Phase II/III clinical studies are discussed.

Blood Substitutes↗
PubMed2002

The effect of improving communication competency on the certifying examination of the American Board of Surgery.

BACKGROUND: Since 1991 the authors have offered a course that identifies content deficits, but only provides instruction directed at improving verbal and nonverbal behaviors. We report the outcome of this 10-year effort as success on the certifying examination of the American Board of Surgery between 1991 and 2001. METHODS: Sixteen 5-day courses were scheduled over 10 years. Participants included those who had not taken the oral examination or had failed at least once and invited senior faculty (n = 26). Sites were chosen to replicate the actual examination setting. RESULTS: There were 122 participants, with follow-up data available on 88. Success in the certifying examination after completing the course is 96 percent. CONCLUSIONS: Evaluation of communication deficits and training to improve them is strongly associated with success. Clearly, this course is effective at identifying communication behaviors that are interfering with success on the certifying examination of the American Board of Surgery.

Adult↗
PubMed2002

Nitric oxide scavenging, alone or with nitric oxide synthesis inhibition, modulates vascular hyporeactivity in rats with intraperitoneal sepsis.

Elevated levels of nitric oxide (NO) may be a primary cause of the vascular hyporeactivity (vasoplesia) and refractory hypotension in sepsis. This study was initiated to determine the efficacy of NO scavenging with acellular hemoglobin (Hb) solution in modulating sepsis-mediated vasoplesia. Male Sprague Dawley rats were subjected to sepsis by cecal ligation and puncture (CLP). Twenty-four hours post-CLP, the animals were randomly assigned to one of four groups (n = 5-6 each) and given an intravenous injection of 0.5 mL bovine serum albumin (BSA; 5 g/dL), 0.5 mL human Hb (7g/dL), 50 microL Nomega-nitro L-arginine methyl ester (NAME; 1 M), or both Hb and NAME. Blood pressure (BP), cardiac output, systemic vascular resistance, and vascular reactivity (VR) to norepinephrine (NE; 40 ng/Kg) were assessed before and after an experimental treatment. In some animals, inducible NO synthase (iNOS) mRNA expression was assessed in selected tissue samples harvested at the conclusion of experiment using a reverse transcription-polymerase chain reaction (RT-PCR) method. Treatment with Hb, NAME, or NAME + Hb elicited a significant improvement in mean BP and VR compared with the control (BSA) group (P < 0.05, analysis of variance and Neuman-Keuls tests). Tissue samples from 24-h CLP rats clearly exhibited iNOS gene expression; higher iNOS gene expression in the intestine compared with aorta suggests that the intestine may be a major source of the elevated NO level in this model. In conclusion, NO scavenging with Hb, alone, or in combination with NO synthesis inhibition, appears to be effective in modulating sepsis-mediated vascular hyporeactivity and may reduce complications associated with global NO synthesis inhibition.

Animals↗