L Bruce Pearce - Academia.edu (original) (raw)
Papers by L Bruce Pearce
Mathematical and Statistical Skills in the Biopharmaceutical Industry, 2019
Mathematical and Statistical Skills in the Biopharmaceutical Industry, 2019
After glancing at the book title, we initially thought the focus would be on mathematical formula... more After glancing at the book title, we initially thought the focus would be on mathematical formulas and statistical methodologies that are often used in clinical trials. To our pleasant surprise, th...
Mathematical and Statistical Skills in the Biopharmaceutical Industry, 2019
Mathematical and Statistical Skills in the Biopharmaceutical Industry, 2019
Mathematical and Statistical Skills in the Biopharmaceutical Industry, 2019
American Journal of Physiology-Renal Physiology, 1981
The renal tubular transport of the organic cations tetraethylammonium (TEA), N1-methylnicotinamid... more The renal tubular transport of the organic cations tetraethylammonium (TEA), N1-methylnicotinamide (NMN), and choline was studied in anesthetized rabbits by the urinary clearance technique. The clearance ratio of [14C]TEA/inulin was 5.72 +/- 0.44 and the clearance ratio of [14C]TEA/p-aminohippuric acid (PAH) was 0.98 +/- 0.02. The clearance ratio of the 14C label/inulin when [14C]NMN was being infused was only 1.31. The clearance ratio of choline/inulin was less than 1 at choline infusion loads from 0 to about 6 mumol . kg-1 . min-1, which produced a plasma choline level of 100 microM. At higher infusion rates the urinary clearance ratio of choline/inulin rose to a maximum of 2 at plasma choline levels of 300–500 microM. Renal metabolism of choline and NMN were revealed by the use of the isolated perfused rabbit kidney. [14C]Choline was extensively metabolized by the kidney into betaine. The renal metabolite of [14C]NMN comigrated with nicotinamide in electrophoresis. The relatively...
Toxicology and Applied Pharmacology, 1994
Advances in Experimental Medicine and Biology, 2003
Biopure's hemoglobin-based oxygen carrier, HBOC-2... more Biopure's hemoglobin-based oxygen carrier, HBOC-201 (Hemopure), enhances oxygen transport by promoting both the convective and diffusive components of transport in the microcirculation. Convective transport is modified by HBOC-201 in three ways; (i) volume expansion promotes organ and tissue perfusion, (ii) the low viscosity of HBOC-201 improves flow to tissues, and (iii) oxygen delivery by HBOC Hb in the plasma is relatively insensitive to mechanisms regulating RBC distribution in the microcirculation. Diffusive oxygen transport is increased by the higher P50 compared with native RBC Hb which increases the off-loading of oxygen to tissues. Oxygen transport is also increased by reducing the diffusional barrier to oxygen transport associated with the plasma, in which oxygen is sparingly soluble. Biopure's HBOC solutions have been shown in vitro and in vivo to take up and off-load oxygen more efficiently than RBC Hb, and when added to blood can increase the efficiency of RBC oxygen transport.
Clinical Pharmacology & Therapeutics, 2003
Clinical Pharmacology & Therapeutics (2003) 73, P67–P67; doi:
The Journal of pharmacology and experimental therapeutics, 1986
An aqueous extract of brain has recently been shown to contain a factor (substance B) that antago... more An aqueous extract of brain has recently been shown to contain a factor (substance B) that antagonizes presynaptic inhibition of evoked [3H]acetylcholine release from guinea pig ileal synaptosomes. This factor antagonized the inhibition of electrically evoked contractions of the intact guinea pig longitudinal muscle-myenteric plexus preparation by a variety of pharmacological agents including clonidine, 2-chloroadenosine, morphine and phencyclidine. pA2App values for substance B antagonism of these four agonists were very similar. Schild plot analysis suggests a functional competition between substance B and each of these receptor agonists. In the absence of any agonist, substance B had a minimal effect on the force of contraction. This reversal of inhibition by substance B was not altered by the ganglionic blocking agent hexamethonium. Substance B was not able to reverse the inhibition of contractions elicited by atropine. In addition to its localization in brain, the factor was al...
Journal de physiologie, 1986
A factor (Substance B) has been isolated from brain which reverses the presynaptically-modulated ... more A factor (Substance B) has been isolated from brain which reverses the presynaptically-modulated inhibition of evoked ACh release from both guinea-pig myenteric plexus-longitudinal muscle synaptosomes and the intact strip. Inhibitory modulating agents whose activity is reversed by Substance B include oxotremorine, 2-chloroadenosine, clonidine, and morphine. In addition to brain, Substance B is also present in heart and ileum but not in liver or kidney. As determined by Biogel P2 chromatography, this factor appears to have a molecular weight of around 700. It is not destroyed by preincubation with periodate, amylase, adenosine deaminase, pronase, trypsin, phospholipase C or carboxypeptidase Y.
Maniatis/Alternatives to Blood Transfusion in Transfusion Medicine, 2010
In 1988 the National Institutes of Health held a consensus conference addressing perioperative hu... more In 1988 the National Institutes of Health held a consensus conference addressing perioperative human red blood cell product transfusion practice [1]. The objective of the conference was the elucidation of the risks and potential benefits of blood product ...
Shock, 2000
In the setting of rapidly exsanguinating hemorrhage, resuscitation with intravenous (i.v.) crysta... more In the setting of rapidly exsanguinating hemorrhage, resuscitation with intravenous (i.v.) crystalloid solution may not sustain survival before availability of allogenic blood transfusion and surgery. This study tested the hypothesis that bovine hemoglobin-based oxygen carrier, HBOC-201, would improve resuscitation and extend early survival from exsanguinating hemorrhage. This study simulated the prehospital scenario of rapidly exsanguinating hemorrhage with prolonged prehospital time and lack of blood availability. Severe hemorrhagic shock was induced in swine by using multiple liver lacerations. At 9 min after the onset of bleeding, swine were randomized to receive approximately 10 mL/kg/min of i.v. lactated Ringer's solution (n = 10) or HBOC-201 (n = 7) to achieve a mean aortic pressure (MAP) of 60 mmHg. Thereafter, infusion rate was adjusted to maintain MAP at 60 mmHg for up to 2 h. All animals were initially successfully resuscitated. The results showed 2-h survival was 1 of 10 with lactated Ringer's and 7 of 7 with HBOC-201 (P = 0.0004). Nine lactated Ringer's swine had cardiovascular collapse at 36 +/- 10 min. Lactate at 30 min was 18 +/- 3 mmol/L with lactated Ringer's and 12 +/- 2 mmol/L with HBOC-201 (P < 0.05). Hematocrit was <1% in 9 of 10 lactated Ringer's and 6 of 7 HBOC-201 animals. These data indicate that HBOC-201 improved early survival and stabilized hemodynamic and metabolic parameters vs. lactated Ringer's in this swine model of liver injury with uncontrolled, lethal hemorrhage that simulates the prehospital care environment where allogenic blood is unavailable.
Mathematical and Statistical Skills in the Biopharmaceutical Industry, 2019
Mathematical and Statistical Skills in the Biopharmaceutical Industry, 2019
After glancing at the book title, we initially thought the focus would be on mathematical formula... more After glancing at the book title, we initially thought the focus would be on mathematical formulas and statistical methodologies that are often used in clinical trials. To our pleasant surprise, th...
Mathematical and Statistical Skills in the Biopharmaceutical Industry, 2019
Mathematical and Statistical Skills in the Biopharmaceutical Industry, 2019
Mathematical and Statistical Skills in the Biopharmaceutical Industry, 2019
American Journal of Physiology-Renal Physiology, 1981
The renal tubular transport of the organic cations tetraethylammonium (TEA), N1-methylnicotinamid... more The renal tubular transport of the organic cations tetraethylammonium (TEA), N1-methylnicotinamide (NMN), and choline was studied in anesthetized rabbits by the urinary clearance technique. The clearance ratio of [14C]TEA/inulin was 5.72 +/- 0.44 and the clearance ratio of [14C]TEA/p-aminohippuric acid (PAH) was 0.98 +/- 0.02. The clearance ratio of the 14C label/inulin when [14C]NMN was being infused was only 1.31. The clearance ratio of choline/inulin was less than 1 at choline infusion loads from 0 to about 6 mumol . kg-1 . min-1, which produced a plasma choline level of 100 microM. At higher infusion rates the urinary clearance ratio of choline/inulin rose to a maximum of 2 at plasma choline levels of 300–500 microM. Renal metabolism of choline and NMN were revealed by the use of the isolated perfused rabbit kidney. [14C]Choline was extensively metabolized by the kidney into betaine. The renal metabolite of [14C]NMN comigrated with nicotinamide in electrophoresis. The relatively...
Toxicology and Applied Pharmacology, 1994
Advances in Experimental Medicine and Biology, 2003
Biopure's hemoglobin-based oxygen carrier, HBOC-2... more Biopure's hemoglobin-based oxygen carrier, HBOC-201 (Hemopure), enhances oxygen transport by promoting both the convective and diffusive components of transport in the microcirculation. Convective transport is modified by HBOC-201 in three ways; (i) volume expansion promotes organ and tissue perfusion, (ii) the low viscosity of HBOC-201 improves flow to tissues, and (iii) oxygen delivery by HBOC Hb in the plasma is relatively insensitive to mechanisms regulating RBC distribution in the microcirculation. Diffusive oxygen transport is increased by the higher P50 compared with native RBC Hb which increases the off-loading of oxygen to tissues. Oxygen transport is also increased by reducing the diffusional barrier to oxygen transport associated with the plasma, in which oxygen is sparingly soluble. Biopure's HBOC solutions have been shown in vitro and in vivo to take up and off-load oxygen more efficiently than RBC Hb, and when added to blood can increase the efficiency of RBC oxygen transport.
Clinical Pharmacology & Therapeutics, 2003
Clinical Pharmacology & Therapeutics (2003) 73, P67–P67; doi:
The Journal of pharmacology and experimental therapeutics, 1986
An aqueous extract of brain has recently been shown to contain a factor (substance B) that antago... more An aqueous extract of brain has recently been shown to contain a factor (substance B) that antagonizes presynaptic inhibition of evoked [3H]acetylcholine release from guinea pig ileal synaptosomes. This factor antagonized the inhibition of electrically evoked contractions of the intact guinea pig longitudinal muscle-myenteric plexus preparation by a variety of pharmacological agents including clonidine, 2-chloroadenosine, morphine and phencyclidine. pA2App values for substance B antagonism of these four agonists were very similar. Schild plot analysis suggests a functional competition between substance B and each of these receptor agonists. In the absence of any agonist, substance B had a minimal effect on the force of contraction. This reversal of inhibition by substance B was not altered by the ganglionic blocking agent hexamethonium. Substance B was not able to reverse the inhibition of contractions elicited by atropine. In addition to its localization in brain, the factor was al...
Journal de physiologie, 1986
A factor (Substance B) has been isolated from brain which reverses the presynaptically-modulated ... more A factor (Substance B) has been isolated from brain which reverses the presynaptically-modulated inhibition of evoked ACh release from both guinea-pig myenteric plexus-longitudinal muscle synaptosomes and the intact strip. Inhibitory modulating agents whose activity is reversed by Substance B include oxotremorine, 2-chloroadenosine, clonidine, and morphine. In addition to brain, Substance B is also present in heart and ileum but not in liver or kidney. As determined by Biogel P2 chromatography, this factor appears to have a molecular weight of around 700. It is not destroyed by preincubation with periodate, amylase, adenosine deaminase, pronase, trypsin, phospholipase C or carboxypeptidase Y.
Maniatis/Alternatives to Blood Transfusion in Transfusion Medicine, 2010
In 1988 the National Institutes of Health held a consensus conference addressing perioperative hu... more In 1988 the National Institutes of Health held a consensus conference addressing perioperative human red blood cell product transfusion practice [1]. The objective of the conference was the elucidation of the risks and potential benefits of blood product ...
Shock, 2000
In the setting of rapidly exsanguinating hemorrhage, resuscitation with intravenous (i.v.) crysta... more In the setting of rapidly exsanguinating hemorrhage, resuscitation with intravenous (i.v.) crystalloid solution may not sustain survival before availability of allogenic blood transfusion and surgery. This study tested the hypothesis that bovine hemoglobin-based oxygen carrier, HBOC-201, would improve resuscitation and extend early survival from exsanguinating hemorrhage. This study simulated the prehospital scenario of rapidly exsanguinating hemorrhage with prolonged prehospital time and lack of blood availability. Severe hemorrhagic shock was induced in swine by using multiple liver lacerations. At 9 min after the onset of bleeding, swine were randomized to receive approximately 10 mL/kg/min of i.v. lactated Ringer's solution (n = 10) or HBOC-201 (n = 7) to achieve a mean aortic pressure (MAP) of 60 mmHg. Thereafter, infusion rate was adjusted to maintain MAP at 60 mmHg for up to 2 h. All animals were initially successfully resuscitated. The results showed 2-h survival was 1 of 10 with lactated Ringer's and 7 of 7 with HBOC-201 (P = 0.0004). Nine lactated Ringer's swine had cardiovascular collapse at 36 +/- 10 min. Lactate at 30 min was 18 +/- 3 mmol/L with lactated Ringer's and 12 +/- 2 mmol/L with HBOC-201 (P < 0.05). Hematocrit was <1% in 9 of 10 lactated Ringer's and 6 of 7 HBOC-201 animals. These data indicate that HBOC-201 improved early survival and stabilized hemodynamic and metabolic parameters vs. lactated Ringer's in this swine model of liver injury with uncontrolled, lethal hemorrhage that simulates the prehospital care environment where allogenic blood is unavailable.