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Biomedical subjects

A L Rosen

Publications and source records attributed to A L Rosen.

At least 19 recordsLinked to original sources
PubMed1998

Controversies regarding radial neck fractures in children.

Fractures of the radial neck in children are not uncommon, yet several aspects of their management remain controversial. Until a consensus is reached regarding the determination of displacement, acceptability of initial angulation, treatment, and outcome, the complication rate of these fractures will remain high. The authors recommend measuring the displacement as the angle between a line perpendicular to the articular surface of the radial head with a line down the shaft of the proximal radius. Fractures that are angulated less than 30 degrees require immobilization alone. Fractures angulated more than 30 degrees should be treated with an attempt at closed reduction. If closed reduction fails, a percutaneous reduction should be attempted before open reduction. Internal fixation should be performed using an oblique extraarticular Kirshner wire for all unstable fractures. Grading outcome based on range of motion and the presence or absence of pain is recommended. It is hoped that once the controversies surrounding these fractures are resolved, the long term results of these troublesome injuries will improve.

Adolescent↗
PubMed1993

Effects of recombinant human erythropoietin and interleukin-3 on erythropoietic recovery from acute anemia.

The risks inherent in the use of homologous blood products have increased efforts toward identifying alternatives to transfusion. We have previously shown that the administration of recombinant human erythropoietin (rhEpo) enhances the erythropoietic response to acute blood loss. Recombinant human interleukin-3 (rh-IL-3) is a hematopoietic growth factor that has been shown to act synergistically with rhEpo in accelerating erythropoiesis in vitro. The purpose of this study in a primate model was to determine if the administration of rhIL-3 in combination with rhEpo could augment the erythropoietic response to acute blood loss more than rhEpo therapy alone. Twenty-four adult male baboons were randomized into four groups. The induction of acute normovolemic anemia to a hematocrit of 20% was accomplished via exchange-transfusion with 6% hetastarch. The groups were then treated for 7 consecutive days with the following growth factors: group I (n = 7), no growth factors; group II (n = 5), rhIL-3 alone (100 micrograms/kg/d); group III (n = 6), rhEpo alone (1000 U/kg/d); group IV (n = 6), rhEpo (1000 U/kg/d) plus rhIL-3 (100 micrograms/kg/d). All animals received folate, vitamin B12, and intravenous iron-dextran immediately following the exchange-transfusion. Response to therapy was monitored for 35 days. There were no adverse reactions following growth factor administration. The analysis of erythropoietic rates between study days 1 through 11, as determined via linear regression analysis, revealed that hematocrits increased significantly faster in the groups receiving rhEpo compared to controls. The administration of rhIL-3, however, did not increase the rate of erythropoiesis when compared to controls, nor did it augment response when added to the rhEpo regimen. The results of this study demonstrate that the administration of rhIL-3 alone had no significant effect on erythropoiesis in this setting of acute blood loss. Further, despite promising in vitro data, rhIL-3 provided no additional stimulation of erythropoiesis in animals receiving rhEpo. Nevertheless, the study confirms that the pharmacologic acceleration of erythropoiesis by rhEpo alone remains an attractive alternative to homologous transfusion.

Acute Disease↗
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↗
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

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

Liposome-encapsulated hemoglobin as an artificial red blood cell: characterization and scale-up.

Encapsulation methods using high pressure extrusion and homogenization were developed which produce hemoglobin-containing liposomes, approximately one micron or less in diameter with an oxygen-carrying capacity of more than half that of red blood cells (RBCs). These methods were developed for scaling-up liposome-encapsulated hemoglobin (LEH) production. Previously, the lack of adequate scale-up methods has been a serious barrier to full scale efficacy and toxicity testing for all the researchers engaged in such investigations. The scale-up methods and characterization of the resulting LEH preparations are presented.

Blood Substitutes↗
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

Coronary vascular actions of stroma-free hemoglobin preparations.

The left anterior descending coronary artery was cannulated in anesthetized, open-chest dogs for use as a coronary test bed to assess the coronary vascular actions of oxygenated, unmodified and pyridoxylated, partially cross-linked (polymerized), stroma-free hemoglobin solutions (SFHS). The actions of these SFHSs were assessed in this test bed, by comparison with perfusion with whole blood. Unmodified SFHS caused significant vasoconstriction, whereas pyridoxylated, partially polymerized SFHS did not do so. The existing coronary flow during perfusion with either SFHS preparation, under basal conditions, did not increase during intracoronary infusion of adenosine. Coronary flow-autoregulation was also altered during perfusion with either SFHS, because the "normal" reactive hyperemia response, observed in the control experiments, was not seen. These findings suggest that both unmodified and pyridoxylated cross-linked (70% polymers) hemoglobin preparations possess some vascular activity when tested in the canine coronary circulation.

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↗
PubMed1988

Limits of cardiac compensation in anemic baboons.

The risk of homologous blood may cause physicians to withhold red cell treatment after acute blood loss. We believe that in the euvolemic patient with acute anemia, the heart is the principal organ at risk. The cardiac compensation to extreme anemia is unknown and is the purpose of this report. Fourteen adult baboons were anesthetized, paralyzed, and ventilated with room air. Left atrial and coronary sinus catheters were inserted surgically. Experimental animals (n = 7) were hemodiluted at constant left atrial pressure with 5% human serum albumin. Control animals (n = 7) underwent similar volume exchanges with fresh, cross-matched, homologous red blood cells resuspended in human serum albumin, also at constant left atrial pressure. Six of seven experimental animals survived until hematocrit levels were 4%. Adequate cardiac compensation was observed until hematocrit levels were less than 10%. Increased flow, without increases in the O2 extraction ratio, was the mechanism of compensation used by the healthy heart with patent coronary vessels.

Adaptation, Physiological↗
PubMed1988

Recombinant human erythropoietin and autologous blood donation.

Risks of transfusion are minimized with autologous blood. However, autologous donation programs require 2 to 5 weeks to yield only 2.2 units per patient. Recombinant human erythropoietin (r-HuEPO) has been shown to increase erythropoiesis. This study evaluated the effects of r-HuEPO on an aggressive autologous donation program. Twelve adult male baboons were randomized into two groups of six. All animals were studied three times per week for 5 weeks. A unit of blood was donated when on any study day the hematocrit was greater than 30%. Animals received intravenously either 750 units/kg of r-HuEPO (n = 6) or placebo (n = 6) on each study day. Iron dextran was given intravenously to replace 150% of shed iron. The r-HuEPO group had an earlier onset of reticulocytosis (2.7 vs 5.5 days, p less than 0.01) and donated 35% more blood (13.5 vs 10.0 units, p = 0.01) than the control group. No adverse reactions to r-HuEPO were observed. The data show that an aggressive autologous donation program can yield 10 units of blood over a 5-week period. Further, r-HuEPO increases that yield by an additional 35%. This aggressive autologous donation program with r-HuEPO may significantly reduce the need for homologous transfusion and its attendant risks.

Animals↗
PubMed1987

Oxygen extraction ratio: a valid indicator of myocardial metabolism in anemia.

We have shown that primates adequately compensate for acute normovolemic anemia to hematocrits (HCT) of 10%. We have described a whole-body extraction ratio (O2 consumption/O2 delivery; ER) of 50% as a reliable physiologic indicator of transfusion need. There is concern that whole-body ER may not accurately reflect impaired myocardial metabolism. The onset of significant lactate production by the left ventricle is an indicator of anaerobic metabolism. Our purpose is to compare left ventricular lactate metabolism (arterial-coronary sinus lactate; delta [L]) to ER in acute normovolemic anemia. Fourteen adult baboons were anesthetized, paralyzed, and ventilated on room air. Left atrial, coronary sinus, aortic, and Swan-Ganz catheters were inserted. Experimental animals (N = 7) were hemodiluted, at constant left atrial pressure (LAP), with 5% human serum albumin (HSA) to a HCT below 4%. Control animals (N = 7) underwent similar volume exchanges, also at constant LAP, with homologous RBCs resuspended in HSA. Whole-body extraction ratio and left ventricular lactate production were measured at baseline and at hematocrits of 20, 10, 6, and 4% in the experimental group. Data were obtained at similar volume exchange points in the control group. Significant lactate production occurred only in the experimental animals (P less than 0.05) when extraction ratio exceeded 50%. Significant lactate production does not occur before the whole-body ER exceeds 50%. ER appears to be a valid indicator of myocardial metabolism in anemia, in this setting.

Anemia↗
PubMed1986

Fluosol-DA as a red-cell substitute in acute anemia.

We assessed the safety and efficacy of Fluosol-DA as a red-cell substitute in acute anemia. Twenty-three surgical patients with blood loss and religious objections to receiving blood transfusions were evaluated. Fifteen moderately anemic patients with a mean hemoglobin level (+/- SE) of 7.2 +/- 0.5 g per deciliter had no evidence of a physiologic need for increased arterial oxygen content and did not receive Fluosol-DA. Eight severely anemic patients with a mean hemoglobin level of 3.0 +/- 0.4 g per deciliter met the criteria of need and received the drug until the physiologic need disappeared or a maximal dose of 40 ml per kilogram of body weight was reached. We observed no adverse reactions to Fluosol-DA. The average peak increment in arterial oxygen content with the drug was only 0.7 +/- 0.1 ml per deciliter. There were no appreciable beneficial effects of Fluosol-DA, perhaps because of the small increase in arterial oxygen content, the brief half-life of the drug (24.3 +/- 4.3 hours), and the limited total dose. Six of the eight patients receiving Fluosol-DA died. One of the survivors received red-cell transfusions against his wishes, under a court order, after his total Fluosol-DA dose. Fourteen of the 15 moderately anemic patients survived. The data in this select group of patients refusing blood products suggest that, after blood loss, Fluosol-DA is unnecessary in moderate anemia and ineffective in severe anemia.

Acute Disease↗