The certifying examination of the american board of surgery: the effect of improving communication and professional competency: twenty-year results.

Purpose: In 1985, a small research group identified variables affecting applicant success on the oral Certifying Examination (CE) of the American Board of Surgery (ABS). This led to the design of an oral examination course first taught in 1991. The success of and need for this program led to its continuation.

Relative roles of heme-irons and globin-thiols in the genesis of acellular hemoglobin mediated vasoconstriction.

In addition to heme-irons, reactive (beta-globin thiols (betaCys93s) of hemoglobin (Hb) also have been shown to interact with endogenous nitric oxide (NO) thereby contributing to vascular tone regulation. What relative roles do these NO binding sites contribute to the overall Hb-mediated vasoactivity? Several test Hbs with either or both the NO binding sites preliganded or blocked were prepared and tested in a rat thoracic aortic ring model. Hbs tested were: NEM-Hb (ferrous Hb with masked thiols), HbNO (ferrous Hb preliganded with NO), Hb(+)CN (ferric Hb liganded with CN(-)), NEM-HbNO and NEM-Hb(+)CN (Hbs with both heme-iron and cysteine sites preliganded or blocked).

When blood is not an option: factors affecting survival after the use of a hemoglobin-based oxygen carrier in 54 patients with life-threatening anemia.

Background: In consenting Jehovah's Witness patients and others for whom blood is contraindicated or not available, hemoglobin-based oxygen carrier (HBOC)-201 may enable survival in acutely anemic patients while underlying conditions are treated.

Methods: Survival factors were identified in a multicenter, unblinded series of severely anemic "compassionate use" patients receiving available standard treatment plus consultant-supported HBOC-201 administration by novice users. Predictors of outcome were sought and compared between survivors and nonsurvivors.

The ideal blood substitute.

There is an ongoing need for a red cell substitute, an oxygen-carrying solution to use primarily as a bridge until red cells are available. The replacement of oxygen-carrying capacity has driven the field of research, primarily with the development of hemoglobin-based oxygen carriers, but they are less than ideal. The formulation of a complete substitute for blood, if it can be realized, must take into account all the cellular and molecular components of the immune and coagulation systems.

HBOC-201: the multi-purpose oxygen therapeutic.

Clinical and preclinical studies have revealed a diverse array of indications in which the effectiveness of HBOC-201 has been demonstrated or appears likely. Included among these are indications involving cardiac and peripheral ischaemia in which this oxygen therapeutic may prove to be an important tool in the armamentarium of the cardiologist and surgeon. Preclinical studies and clinical trials are under way to further delineate and optimise the role of HBOC-201 as an oxygen therapeutic in cardiovascular medicine.

Clinical contextualization and the assessment of adverse events in HBOC trials.

Establishing an acceptable safety and efficacy profile for hemoglobin based oxygen carriers, HBOCs, is essential. Understanding the data that describes an HBOC "safety profile" requires consideration beyond counting "events" typically associated with intent to treat analysis. The imputation of causation from numerical counts alone, without clinical context, is an incomplete description of a complex situation.

HBOC-201 as an alternative to blood transfusion: efficacy and safety evaluation in a multicenter phase III trial in elective orthopedic surgery.

Background: The ability of hemoglobin based oxygen carrier-201 (HBOC-201) to safely reduce and/or eliminate perioperative transfusion was studied in orthopedic surgery patients.

Methods: A randomized, single-blind, packed red blood cell (PRBC)-controlled, parallel-group multicenter study was conducted. Six hundred eighty-eight patients were randomized to treatment with HBOC-201 (H, n = 350) or PRBC (R, n = 338) at the first transfusion decision.

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.

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.

Hemoglobin mediated contraction of the isolated rat thoracic aorta: why is precontraction necessary?

A primary mechanism for the hemoglobin (Hb) mediated vascular contraction is believed to be Hb scavenging of endothelial nitric oxide (NO). In the isolated rat thoracic aorta, however, the Hb mediated contraction occurs only after an agonist-induced precontraction. Why? To investigate the question, a rat thoracic aortic ring model was used.

Temporal effect of hemoglobin resuscitation on sepsis survival.

Hemoglobin (Hb)-based oxygen carriers are promising resuscitation fluids for hemorrhagic shock. However, infusion of large amounts of Hb-based material could interfere with reticuloendothelial function potentiating postresuscitation sepsis mortality. We investigated the temporal relationship between hemorrhage-resuscitation and sepsis survival.

Active myogenic tone: a requisite for hemoglobin mediated vascular contraction?

Acellular free hemoglobin (Hb), when intravenously administered to animals and humans, elicits vascular contraction. A primary mechanism for the Hb mediated vasoconstriction is Hb scavenging of nitric oxide (NO), a potent relaxation factor, constitutively secreted by the vascular endothelium. However, in the isolated rat thoracic aorta in basal state, Hb does not elicit contraction.

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.

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.

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).

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 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.

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).