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Biomedical subjects

E E Jacobs

Publications and source records attributed to E E Jacobs.

At least 19 recordsLinked to original sources

Acute effects of massive transfusion of a bovine hemoglobin blood substitute in a canine model of hemorrhagic shock.

The capability of stroma-free hemoglobin solutions to act as a plasma expander with oxygen and carbon dioxide transport properties has encouraged the idea of their possible use in settings of massive blood loss. Using a canine hemorrhagic shock model (systolic arterial pressure < or = 50 torr for 60 min), we evaluated the efficacy of an ultra-pure stroma-free bovine hemoglobin solution (PBHg) as a resuscitation fluid in hypovolemic and acidotic animals, using homologous blood (PRBC) and 10% human serum albumin (HSA) as control solutions. Following volume replacement, dogs were studied for 2 h under anesthesia and for 4 h subsequently while awake. Resuscitation with PBHg (30 +/- 3 ml/kg) was able to restore stable hemodynamics and correct acidosis to an extent comparable to that in animals treated with PRBC. Additionally, oxygen transport was maintained at a higher level than that in dogs treated with HSA. Administration of PBHg in this shock model revealed no significant cardiopulmonary toxicity or adverse effects. These short-term results suggest that PBHg may be useful for effective resuscitation after major blood loss.

Animals

Ultra-pure polymerized bovine hemoglobin blood substitute: effects on the coronary circulation.

The effects of stroma-free hemoglobin (SFHgb) on the coronary circulation remain unclear. An intact canine model utilizing intracoronary adenosine to abolish the confounding effect of autoregulation was used to study maximal myocardial oxygen delivery during progressive hemodilution with polymerized bovine SFHgb. The circumflex coronary artery was instrumented with a flow probe, hydraulic constrictor, and proximal and distal catheters for adenosine infusion and distal pressure measurement, respectively. This preparation was used to generate diastolic coronary pressure-flow relations during maximal vasodilation. Maximal coronary conductance and maximal myocardial oxygen delivery were determined in two groups of 7 dogs each following hemodilution, first with 6% hetastarch (Control), followed by further hemodilution with ultra-pure, polymerized, bovine SFHgb. After hemodilution with SFHgb, maximal coronary flow increased slightly without evidence of coronary vasoconstriction. Since hemodilution with this material increases oxygen carrying capacity, maximal oxygen delivery is greater than Control, despite the very low canine hematocrit. These findings suggest: 1) SFHgb can provide adequate oxygen delivery to the myocardium despite extreme degrees of hemodilution, and 2) in this intact model, there is no evidence of adverse coronary vasomotion.

Animals

Hemodynamic effects and oxygen transport properties of a new blood substitute in a model of massive blood replacement.

Recent concerns regarding the safety of the national blood supply have rekindled interest in the development of blood substitutes. Clinical studies have dampened the initial enthusiasm for fluorocarbon solutions as blood substitutes. The potential of hemoglobin solutions as blood substitutes has continued to stimulate investigations. However, the development of an ideal hemoglobin-derived blood substitute has eluded investigators for the past century. A persistent problem has been the inability to develop hemoglobin solutions that provide adequate oxygen and carbon dioxide exchange, while avoiding toxicity that precludes clinical safety and long-term survival. Traditionally, investigators have focused on human hemoglobin solutions. The use of outdated banked blood or pedigree human donor blood as a hemoglobin source poses continued disease transmission risks and a prohibitively limited supply. We evaluated the hemodynamic and gas transport effects of a new purified, polymerized bovine hemoglobin preparation. Bovine hemoglobin oxygen affinity is regulated by chloride ion. The concentration of chloride ions in human plasma results in excellent oxygen transport properties in a stroma-free environment. In addition, unlike human blood, bovine blood is a more disease-free hemoglobin source that is available in large supply. We exchange-transfused eight conscious sheep with this new polymerized bovine hemoglobin solution. All animals tolerated greater than or equal to 95% exchange transfusion to reach a final ovine hematocrit of 2.4 +/- 0.5% with stable hemodynamics and no clinical evidence of distress. The exchange transfusion with bovine hemoglobin polymer resulted in a final plasma hemoglobin concentration of 6.1 +/- 1.6 gm/dl, which supported oxygen consumption at baseline levels. All animals that were exchange transfused with this preparation survived long term with rapid resynthesis of ovine erythrocytes.

Animals

Ultrapure, stroma-free, polymerized bovine hemoglobin solution: evaluation of renal toxicity.

Because of recent concern about the safety of our national blood supply, there is increased interest in finding safe and effective blood substitutes. One option is the use of stroma-free hemoglobin (SFH) solutions. Recently, a SFH solution based on ultrapure, polymerized bovine hemoglobin (UPPBHg) has been shown to be effective in oxygen transport. We examined the potential renal toxicity of this material. Sprague-Dawley rats were infused with UPPBHg at doses of 25, 50, 75, and 100 ml/kg. Additional groups of rats were infused with UPPBHg at these doses with the addition of bicarbonate at a dose adequate to alkalinize the urine. Further groups of rats received UPPBHg intentionally contaminated with raw bovine blood lysate. Renal function was examined by subsequent determination of serum creatinine. UPPBHg infusion up to 50 ml/kg caused no significant change in serum creatinine; at higher doses, there was a reversible rise in creatinine at 24 hr following infusion. Addition of bicarbonate diminished the amount of reversible toxicity seen, even at doses of 100 ml/kg. In contrast, with hemolysate-contaminated UPPBHg, there were sharp increases in creatinine 24 hr after infusion of all doses tested, even at 25 ml/kg; these did not decrease significantly by 48 hr following infusion. At the higher doses tested, death occurred. These observations were not affected by simultaneous bicarbonate infusion. This study shows that UPPBHg may be administered in very large doses with only mild, reversible renal toxicity. The observation that urine alkalinization ameliorates this toxicity suggests that this may occur by hemoglobin precipitation or by a toxic effect in the renal tubules.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Osteomyelitis of the frontal bone.

Osteomyelitis of the frontal bone and its complications remain a diagnostic and therapeutic challenge to the head and neck surgeon. This paper will deal with the etiology, pathogenesis, diagnosis, and treatment of osteomyelitis of the frontal bone, and its complications and sequelae. Special emphasis is placed on techniques for repair of forehead defects.

Acute Disease

Improved case finding for pediatric hearing loss: cost analysis of school screening programs.

The majority of school hearing conservation programs employ pure tone identification audiometry as a basis of referral for further evaluation. An analysis of the cost impact of school screening programs is presented and a method of relating costs to screening program accuracy is described. This type of analysis may be used as a model for estimating cost impact and cost-benefit for pure tone audiometry and other techniques of screening for hearing loss.

Child

Hydroxylysinuria.

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Adolescent

Enzyme substrate reactions in high magnetic fields.

The reaction rates of two enzyme substrate systems, ribonuclease-RNA and succinate-cytochrome c reductase, were followed as a function of magnetic field from zero to 48,000 gauss. The reaction rates remained constant to within 10 per cent.

Chemical Phenomena