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Biomedical subjects

G S Moss

Publications and source records attributed to G S Moss.

At least 19 recordsLinked to original sources
PubMed1998

The first randomized trial of human polymerized hemoglobin as a blood substitute in acute trauma and emergent surgery.

BACKGROUND: Human polymerized hemoglobin (PolyHeme) is a universally compatible, disease-free, oxygen-carrying resuscitative fluid. This is the first prospective, randomized trial to compare directly the therapeutic benefit of PolyHeme with that of allogeneic red blood cells (RBCs) in the treatment of acute blood loss. STUDY DESIGN: Forty-four trauma patients (33 male, 11 female) aged 19-75 years with an average Injury Severity Score (ISS) score of 21+/-10 were randomized to receive red cells (n = 23) or up to 6 U (300 g) of PolyHeme (n = 21) as their initial blood replacement after trauma and during emergent operations. RESULTS: There were no serious or unexpected adverse events related to PolyHeme. The PolyHeme infusion of 4.4+/-2.0 units (mean +/- SD) resulted in a plasma [Hb] of 3.9+/-1.3 g/dL, which accounted for 40% of the total circulating [Hb]. There was no difference in total [Hb] between the groups before infusion (10.4+/-2.3 g/dL control vs. 9.4+/-1.9 g/dL experimental). At end-infusion the experimental RBC [Hb] fell to 5.8+/-2.8 g/dL vs. 10.6+/-1.8 g/dL (p < 0.05) in the control, although the total [Hb] was not different between the groups or from pre-infusion. The total number of allogeneic red cell transfusions for the control and experimental groups was 10.4+/-4.2 units vs. 6.8+/-3.9 units (p < 0.05) through day 1, and 11.3+/-4.1 units vs. 7.8 +/-4.2 units (p = 0.06) through day 3. CONCLUSIONS: PolyHeme is safe in acute blood loss, maintains total [Hb] in lieu of red cells despite the marked fall in RBC [Hb], and reduces the use of allogeneic blood. PolyHeme appears to be a clinically useful blood substitute.

Adult↗
PubMed1997

Clinical utility of human polymerized hemoglobin as a blood substitute after acute trauma and urgent surgery.

We have previously documented the safety of 1 unit (50 gram) of human polymerized hemoglobin (Poly SFH-P) in healthy volunteers. This report describes the first patient trial to assess the therapeutic benefit of Poly SFH-P in acute blood loss. Thirty-nine patients received 1 (n = 14), 2 (n = 2), 3 (n = 15), or 6 (n = 8) units of Poly SFH-P instead of red cells as part of their blood replacement after trauma and urgent surgery. There were no safety issues related to the infusion of Poly SFH-P. The plasma hemoglobin concentration ([Hb]) after the infusion of 6 units (300 gram) of Poly SFH-P was 4.8 +/- 0.8 g/dL (mean +/- SD). Although the red cell [Hb] fell to 2.9 +/- 1.2 g/dL, the total [Hb] was maintained at 7.5 +/- 1.2 g/dL. Poly SFH-P maintained total [Hb], despite the marked fall in red cell [Hb] due to blood loss. The utilization of O2 (extraction ratio) was 27 +/- 16% from the red cells and 37 +/- 13% from the Poly SFH-P. Twenty-three patients (59%) avoided allogeneic transfusions during the first 24 hours after blood loss. Poly SFH-P effectively loads and unloads O2 and maintains total hemoglobin in lieu of red cells after acute blood loss, thereby reducing allogeneic transfusions. Poly SFH-P seems to be a clinically useful blood substitute.

Adult↗
PubMed1995

The development of hemoglobin solutions as red cell substitutes: hemoglobin solutions.

Although the efficacy of hemoglobin-based oxygen carriers was established more than 60 years ago, all prior clinical trials have demonstrated significant toxicity characterized by renal dysfunction, gastrointestinal distress, and systemic vasoconstriction. The mechanisms of these toxicities now appear to be understood. Tetrameric forms of the hemoglobin molecule extravasate from the circulation and interact with endothelial derived relaxing factor, leading to unopposed vasoconstriction. Although numerous efforts are underway to chemically modify the native tetramer, it is likely that all tetrameric forms of the hemoglobin molecule will continue to extravasate. We have focused on developing a polymerized form of hemoglobin that is virtually free of unreacted tetramer. The development and characterization of this polymerized pyridoxylated hemoglobin solution (Poly SFH-P) is described. Clinical trials have been completed successfully in volunteers, and are now underway to assess the safety and efficacy of Poly SFH-P as a clinically useful red cell substitute in the treatment of acute blood loss in the setting of trauma and surgery.

Animals↗
PubMed1993

Hypovolemic shock.

This article defines a rational approach to the treatment of hemorrhagic shock. All patients that are hypovolemic following hemorrhage require fluid resuscitation. Some patients require red cell restoration and very few require correction of any clotting deficiencies. A physiologic approach to these problems will lead to optimal patient care in these circumstances.

Blood Transfusion↗
PubMed1992

Comparing the transfusion medicine content of the NBME's examinations in 1984-1985 and 1989-1990.

Recognition of the seriousness of transfusion-transmitted diseases has been demonstrated by U.S. medical schools through the integration of transfusion medicine (TM) content into their curricula. To evaluate the degree to which these changes in curricula have been reflected in the National Board of Medical Examiners' (NBME) examinations, a study conducted in 1991 evaluated the proportions of TM-related items on Parts I and II of the NBME examinations for 1984-1985 versus 1989-1990. Both Part I (basic sciences) and Part II (clinical sciences) demonstrated significant gains in TM items between the comparison periods (p less than .001), with Part II having the higher gain. An analysis of students' knowledge revealed that students in 1989-1990 tended to perform better on TM items than on examination items generally. The increases in TM content and student performance on TM items on the 1989-1990 examinations suggest that the national effort to expand and improve teaching of TM in U.S. medical schools has been effective.

Blood Transfusion↗
PubMed1992

Artificial blood: current status of hemoglobin solutions.

Attempts to develop a hemoglobin-based red cell substitute have spanned many decades, but no clinically useful product has been produced to date. The issues preventing clinical application primarily are ones of safety--not efficacy. Numerous animal studies have documented the efficacy of SFH. Although effective, the solution has limitations that have caused concern. Oncotic considerations limit the concentration of the infusate SFH to 6 to 8 g/dL, or half-normal. Owing to the loss of organic phosphate modulators of P50, such as 2,3-DPG, the P50 of SFH is typically between 12 and 14 mm Hg, which is also half the normal value. And finally, the intravascular half-life of SFH is too short, ranging only from 2 to 6 hr. Polymerization provides a means of correcting these limitations. The high oxygen affinity can be greatly diminished by covalent binding of pyridoxal-5'-phosphate to the N-terminal of the chains. Colloid osmotic pressure exerted by a protein solution is proportional to the number of discrete colloid particles. Through polymerization, the number of colloid particles is reduced, leading to a decrease in COP. Data show that this can be achieved in a reproducible fashion. The rate at which COP diminishes determines the yield of polymeric species, as well as their molecular weight distribution. Polymerization can be controlled to result in a yield of 75% to 85% polymers with a molecular weight distribution of 128 to 400 kd. The number average and the weight average molecular weights indicate that the large proportion of polymers represent the cross linking of two tetramers. The data that reflect the interaction of oxygen with poly-SFH-P indicate that the oxygen carrying function of hemoglobin has not been significantly altered by the chemical modifications. The binding coefficient of oxygen is unchanged. As anticipated, there is a loss of cooperativity (diminished Hill coefficient) between the hemoglobin chains, suggesting structural restrictions in the polymeric species because of cross linking. A reduced alkaline Bohr effect is the expected result, and data confirm this. Finally, some increase in oxygen affinity is to be expected with polymerization. This is indeed the case, although the P50 of poly-SFH-P is comparable to banked blood (18 to 22 mm Hg). To be clinically useful, a modified hemoglobin solution requires a reasonable shelf-life.(ABSTRACT TRUNCATED AT 400 WORDS)

Blood Gas Analysis↗
PubMed1991

Erythropoietin deficiency after coronary artery bypass procedures.

Erythropoietin is the primary regulator of erythropoiesis. Erythropoietin has been shown to increase exponentially in response to linear decreases in hematocrit in normal, unstressed animals. However, the effect of operation, with its attendant stress, on erythropoietin levels is unknown. The purpose of this study is to evaluate the effect of surgical stress on erythropoietin. Twenty otherwise healthy patients scheduled for elective surgical procedures were studied. The cholecystectomy group included 10 patients who underwent cholecystectomy for documented stone disease. Ten patients who underwent coronary artery bypass procedures constituted the coronary artery bypass grafting group. Patients were studied preoperatively as well as on the first and second postoperative days. The hematocrit and erythropoietin levels were similar in both groups preoperatively. The hematocrit in the coronary artery bypass grafting group was lower than that of the cholecystectomy group on postoperative day 1 (0.31 versus 0.36; p less than 0.003) and postoperative day 2 (0.30 versus 0.36; p less than 0.001). During the first two postoperative days the erythropoietin levels were similar between groups. The data show that postoperative erythropoietin levels are similar after coronary artery bypass grafting, despite more severe anemia, when compared with cholecystectomy. This suggests that after coronary artery bypass grafting there is a relative deficiency of erythropoietin. Administration of recombinant human erythropoietin to patients undergoing surgical procedures could correct the erythropoietin deficiency and accelerate postoperative erythropoiesis.

Adult↗
PubMed1991

Blood transfusion costs: a multicenter study.

The cost of delivering a unit of blood (whole blood or red cells) to a hospitalized patient was examined in 19 United States teaching hospitals. The average hospital acquisition cost was calculated by using the prices charged by regional blood centers for blood products. To this cost was added an estimate of costs incurred by hospitals for handling, testing, and administering blood. Across study sites, the average hospital cost per unit transfused was $155 and the average charge to the patient was $219. Acquisition cost, the price that hospitals pay for blood, was 37 percent of the total cost to the hospital; the other 63 percent of the hospital cost included costs for blood bank handling (13%), laboratory tests (43%), and blood administration (7%). Significant variations in blood transfusion cost were found within our sample. Most of the variability can be attributed to geographic location of the blood supply source, type of red cell product transfused, prices charged by blood transfusion services, and the frequency of laboratory tests. The results of this transfusion cost study may be helpful in determining the costs of health care delivery, especially when blood transfusions are indicated.

Blood Transfusion↗
PubMed1990

The efficacy of polymerized pyridoxylated hemoglobin solution as an O2 carrier.

A polymerized pyridoxylated hemoglobin solution (Poly SFH-P) has been prepared with a normal [Hb] of 14 g/dL, a normal COP of 20 to 25 torr, a P50 of 16 to 20 torr, and a plasma T1/2 of 40 to 46 hours. Animals underwent a total exchange transfusion with Poly SFH-P to assess its ability to support hemodynamics and oxygen transport in the absence of red cells. All animals survived the exchange transfusion. Mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), and oxygen consumption (VO2) remained at baseline values at zero hematocrit after the exchange. The final plasma [Hb] at Hct less than 1% was 9.7 +/- 0.4 g/dL. These results are significantly better than previous data with unmodified tetrameric hemoglobin solution (SFH). Poly SFH-P supports life in the absence of red cells. In contrast to SFH, Poly SFH-P achieves a nearly normal [Hb], a longer T1/2, and maintains baseline hemodynamics and oxygen consumption at zero hematocrit. These results document that Poly SFH-P is an effective oxygen carrier that offers greater potential than previous products as a clinically useful red cell substitute.

Animals↗
PubMed1990

Erythropoietic response to acute anemia.

Reliance on a brisk erythropoietic response to untreated blood loss is an alternative to transfusion of homologous blood. Slow erythropoiesis has been observed in ICU patients who refused blood. Many of these patients received supplemental oxygen therapy and Fluosol-DA, a temporary red cell substitute. This study reports the erythropoietic response, in the baboon, to moderate (Hct 20%) and severe (Hct 10%) anemia. In addition, the effect of oxygen therapy (FIO2 0.6 for 1 wk) and fluorocarbon emulsions (Oxypherol) on erythropoiesis was evaluated. Baboons uniformly survived acute normovolemic anemia with Hct 10%. In all cases, the response to anemia was characterized by a lag period (with no change in Hct), and a nonlinear recovery period. A lag period of 3 days was observed in both moderate and severe anemia for baboons breathing room air or FIO2 0.6. The lag period was prolonged to 1 wk in the presence of Oxypherol. The recovery period exhibited a uniform and negative correlation between the rate of Hct change and the Hct, in all cases. The theoretical maximum rate of increase of Hct was 2.6%/day. In untreated blood loss, shortening the lag period and increasing the slope of the recovery period will decrease the length of time that the patient is anemic.

Acute Disease↗
PubMed1990

Effect of hemoglobin solution on compensation to anemia in the erythrocyte-free primate.

Hemoglobin solutions are undergoing clinical trials as erythrocyte substitutes. Some of these solutions have higher O2 affinities compared with normal erythrocyte hemoglobin. Also, they appear to interact with endothelial-derived smooth muscle relaxation. The purpose of this study was to evaluate the nature and limits of compensation to acute normovolemic anemia in the erythrocyte-free primate maintained with a hemoglobin solution. The experimental group consisted of six anesthetized paralyzed adult baboons (Papio anubis) that were exchange transfused (ET) with a pyridoxylated polymerized hemoglobin solution [hemoglobin concentration [( Hb]) = 14 g/dl, O2 half-saturation pressure of hemoglobin (P50) = 19.6 Torr] until a hematocrit less than 1% was achieved. They underwent a second ET with Dextran-70 until [Hb] = 1 g/dl. A control group (n = 6) underwent an ET with Dextran-70 until [Hb] = 1 g/dl. Both groups maintained O2 consumption (VO2) until [Hb] = 3 g/dl. Both groups were stable until [Hb] less than 1 g/dl, and both groups increased their cardiac output. The relation between VO2 and O2 delivery was similar for both groups. In vivo P50 and mixed venous O2 tension were significantly lower in the experimental group. The nature and limits of compensation to diminished O2 delivery due to anemia were similar in the two groups.

Anemia↗
PubMed1989

Glutamine-supplemented total parenteral nutrition improves gut immune function.

Glutamine has been demonstrated to be an important source of fuel for the gut. The purpose of this study was to evaluate the effect of glutamine-supplemented hyperalimentation on gut immune function. Thirty-six female Fischer rats were randomized into three groups: group 1 (chow) was fed rat chow and water ad libitum, group 2 (total parenteral nutrition) received a standard hyperalimentation formula, and group 3 (total parenteral nutrition-glutamine) received a hyperalimentation solution that contained 2% glutamine. Animals were maintained on their respective diets for 2 weeks and then killed. Mesenteric lymph nodes were harvested for culture, bile was assayed for secretory IgA, and bowel was excised to assay bacterial adherence. Results indicated that glutamine-supplemented total parenteral nutrition protects against bacterial translocation from the gut seen with standard formulas. This effect may be mediated by the secretory IgA immune system.

Animals↗
PubMed1989

Treatment of acute postoperative anemia with recombinant human erythropoietin.

Risks inherent in the administration of blood products have increased efforts to avoid homologous transfusion. Although this has increased interest in autologous transfusion and intraoperative salvage, little attention has been focused on efforts to enhance endogenous erythropoiesis as a method of minimizing exposure to homologous blood. Recombinant human erythropoietin (rHuEPO) has been shown to enhance erythropoiesis. The purpose of this study is to evaluate the effect of rHuEPO, administered postoperatively, on a model of acute blood loss. Eleven adult male baboons were randomized into two groups. All animals underwent a laparotomy and an exchange transfusion, with 6% hetastarch, to a final hematocrit of 15%. Group I (N = 6) received 1,000 units/kg of recombinant human erythropoietin daily for the first 14 postoperative days. Group II (N = 5) received an equivalent volume of placebo. All animals were given supplemental vitamin B12, folate and 200% of shed iron, as iron dextran IV, after exchange transfusion. Response was observed for a period of 35 days. All animals survived the protocol. There were no adverse reactions to rHuEPO or surgical complications. The hematocrits were similar between groups at baseline and after exchange transfusion. The maximal rate of erythropoiesis was significantly faster in the rHuEPO group (2.1 vs. 1.3%/day; p less than 0.01). The time required to return to hematocrits of 30% (9.9 vs. 17.4 days, p less than 0.001) and to baseline hematocrits (11.9 vs. 32.1 days, p less than 0.01) were both significantly shorter in the rHuEPO group. The data show that rHuEPO accelerates the recovery from anemia in the postoperative setting. Acceleration of erythropoiesis represents another alternative to homologous transfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia↗
PubMed1989

Perioperative recombinant human erythropoietin.

The risks of transfusion-associated infectious disease have made increased efforts to avoid homologous transfusion imperative. Little attention has been focused on efforts to accelerate erythropoiesis as a method of reducing homologous blood use. Recombinant human erythropoietin (rHuEPO) has been shown to enhance erythropoiesis. The purpose of this study was to evaluate the effects of perioperative rHuEPO administration on postoperative erythropoiesis. Fifteen baboons were divided into three groups of five each. Group I received no rHuEPO. Group II received five daily preoperative doses of rHuEPO (1000 U/kg). Group III received five daily preoperative doses and 14 daily postoperative doses of rHuEPO (1000 U/kg). All animals underwent a laparotomy followed by an exchange transfusion to a final hematocrit of 15%. The time in days required to recover to hematocrits of 20% was significantly shorter in both groups that received preoperative doses of rHuEPO when compared with that of controls (3.3 vs 5.7 days, p less than 0.01). The recovery times to hematocrits of 25%, 30%, and baseline levels were all significantly shorter in the group that received both preoperative and postoperative doses of rHuEPO. The data show that perioperative dosage of rHuEPO significantly accelerates postoperative erythropoiesis. Perioperative administration of rHuEPO may reduce the requirements for homologous transfusion.

Animals↗
PubMed1988

Plasma expanders. An update.

This review of the literature has revealed that isotonic fluids, such as 0.9 percent sodium chloride and Ringer's lactate, are effective plasma volume expanders. Despite the continued use of a variety of colloid solutions in resuscitation, there is no good evidence to document a benefit of these solutions over the crystalloid solutions. The additional cost of colloid compared with crystalloid is another argument against colloid use. The most interesting solution currently being assessed is hypertonic saline solution. Its major benefit is that a small volume of fluid can achieve effective resuscitation. The smaller weight gain and lower incidence of peripheral edema may also prove to be significant benefits. Further evaluations are needed to verify the efficacy of this therapy. Finally, a recent National Institute of Health consensus panel identified the appropriate indications for fresh frozen plasma. They concluded that there is no indication for the use of fresh frozen plasma as a volume expander.

Animals↗
PubMed1988

Characteristics of polymerized pyridoxylated hemoglobin.

Polymerization of SFH-P currently provides the only approach that leads to a hemoglobin solution that approximates the O2 carrying capacity of whole blood and can be infused without altering the COP of plasma. It appears to have an adequate O2 loading and unloading characteristic and a greatly improved intravascular half-life. In addition, stable shelf-life at 4 degrees C of greater than five months, makes it a prime candidate for future pre-clinical and clinical investigations.

Animals↗