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J R Hess

Publications and source records attributed to J R Hess.

At least 37 records · Page 2Linked to original sources

Successful storage of RBCs for 10 weeks in a new additive solution.

BACKGROUND: The effect of storing packed RBCs suspended in 300 mL of an alkaline, experimental additive solution (EAS 64) was explored. STUDY DESIGN AND METHODS: RBC units prepared from blood collected from healthy donors into CPD were WBC reduced and stored for 10 weeks under blood bank conditions after the addition of 300 mL of EAS 64 (adenine, 2 mM:; dextrose, 50 mM:; mannitol, 20 mM:; NaCl, 75 mM:; Na(2)HPO(4), 9 mM:). For comparison, non-WBC-reduced units from the same donors were stored in a different additive solution (AS-1, Baxter Healthcare) for 6 weeks. Standard methods were used for the in vitro assays. The 24-hour in vivo recoveries were measured by using (51)Cr- and (99m)Tc-labeled RBCs. RESULTS: Mean recovery in the EAS 64 units after 10 weeks was 84 +/- 8 percent, the same as in the AS-1 units stored for 6 weeks. For EAS 64 and AS-1 units, respectively, the ATP of the RBCs was 85 percent and 64 percent of the initial value, hemolysis was 0.43 percent and 0.63 percent, supernatant potassium was 24 mEq per L and 44 mEq per L, and the morphologic index was 98 and 71. CONCLUSION: RBCs suspended in 300 mL of EAS 64 can be stored satisfactorily for 10 weeks. Longer RBC storage should reduce outdating, increase availability of transfusions in remote locations, and improve the efficiency of autologous donor programs.

Adenosine Triphosphate↗

Fibrin sealant foam sprayed directly on liver injuries decreases blood loss in resuscitated rats.

OBJECTIVE: The majority of early trauma deaths are attributable to uncontrolled hemorrhage from truncal sites. A hemorrhage-control technique that reduced bleeding in the prehospital phase of treatment without requiring manual compression may improve the outcome of these patients. We conducted this preliminary study to determine whether an expanding fibrin sealant foam (FSF) would reduce bleeding from a severe liver injury even during resuscitation. METHODS: Rats (n = 31; 291 +/- 5 g; 37.4 +/- 0.3 degrees C; mean +/- SEM), underwent a 60 +/- 5% excision of the median hepatic lobe. The animals received one of three treatments: (1) FSF, (2) immunoglobulin G placebo foam (IgGF), or (3) no treatment. All animals were resuscitated with 40 degrees C lactated Ringer's solution at 3.3 mL/ min/kg to a mean arterial pressure of 100 mm Hg. Total blood loss, mean arterial pressure, and resuscitation volume were recorded for 30 minutes. A qualitative measure of foam coverage and adherence to the cut liver edge was recorded. RESULTS: The total blood loss was less (p < 0.01) in the FSF group (21.2 +/- 5.0 mL/kg) than in either IgGF (41.4 +/- 4.3 mL/kg) or the no treatment group (44.6 +/- 4.7 mL/kg), which did not differ. The resuscitation volume was not different. The amount of foam used in the treated groups, 9.1 +/- 1.0 g in the FSF group and 10.0 +/- 1.0 g in the IgGF group, did not differ. Survival for 30 minutes was not different among groups. There was no difference in the amount of cut liver covered by either foam, but the clots were more adherent (p < 0.05) in the FSF group than in the IgGF group. CONCLUSION: In rats with a severe liver injury, spraying fibrin foam directly on the cut liver surface decreased blood loss when compared with placebo foam and no treatment. This pilot study suggests a future possible treatment for noncompressible truncal hemorrhage.

Administration, Topical↗

The viability of autologous human red cells stored in additive solution 5 and exposed to 25 degrees C for 24 hours.

BACKGROUND: No data exist on the viability of red cells (RBCs) stored in modern additive solution systems and allowed to warm above 10 degrees C. STUDY DESIGN AND METHODS: In a randomized crossover study, 3 units of blood were collected at least 8 weeks apart from 11 volunteer donors and stored in additive solution 5 (AS-5). Of 3 units from each volunteer, 1 was stored for 6 weeks at 4 degrees C, 1 for 5 weeks at 4 degrees C except for 24 hours at 25 degrees C on Day 14, and 1 for 5 weeks at 4 degrees C except for 24 hours at 25 degrees C on Day 28. Units were sampled periodically during storage; at the end of storage, viability was measured by the 99mTc/51 Cr double-label method. RESULTS: RBC viability was not significantly different in the storage protocols. Less than 1 percent of stored cells hemolyzed. RBC ATP concentrations at the end of storage correlated with viability and were approximately equal in the warmed units after 30 days' storage and the conventionally stored units after 42 days. CONCLUSIONS: The data suggest that RBCs stored in AS-5 and allowed to warm to 25 degrees C for 24 hours lose about 12 days of their shelf life.

Adenosine Triphosphate↗

Effect of dry fibrin sealant dressings versus gauze packing on blood loss in grade V liver injuries in resuscitated swine.

BACKGROUND: We conducted this study to determine whether the dry fibrin sealant dressing (DFSD) would stop bleeding from a grade V liver injury and to evaluate the effects of leaving the absorbable DFSD in survival animals. METHODS: Twenty-four swine (40+/-3.0 kg) received a uniform grade V liver injury and were randomized to one of four 1-hour treatment groups: (1) gauze packing, (2) DFSD, (3) immunoglobulin G placebo dressing, and (4) no treatment. All animals were resuscitated with lactated Ringer's solution. Total blood loss (TBL), mean arterial pressure, resuscitation volume, and laboratory data were monitored for 1 hour after injury. Four swine were treated with the DFSD after grade V injury and allowed to survive for 7 or 14 days. RESULTS: The TBL was 1,104+/-264 mL (mean +/- SEM), 544+/-104 mL, 4,223+/-1,555 mL, and 6,026+/-1,020 mL for groups 1, 2, 3, and 4 respectively. TBL in DFSD animals was less than that in animals treated with gauze packing (p = 0.06). Grade V injuries were uniform among the 1-hour groups, and no evidence of intrahepatic abscess, unusual adhesions, or hepatic vein, vena caval, or pulmonary thromboses were noted in the long-term survival animals. CONCLUSION: In this model of grade V liver injury, blood loss with the DFSD was 51% of that observed with standard gauze packing (not statistically different). Initial survival data revealed no complications attributable to the fibrin dressing. DFSD may provide simple, rapid, and definitive hemorrhage control in life-threatening liver injuries without the need for reoperation.

Animals↗

Dry fibrin sealant dressings reduce blood loss, resuscitation volume, and improve survival in hypothermic coagulopathic swine with grade V liver injuries.

OBJECTIVE: The majority of early trauma deaths are caused by uncontrolled hemorrhage, and are frequently complicated by hypothermic and dilutional coagulopathies. Any hemorrhage-control technique that achieves rapid hemostasis despite a coagulopathy should improve the outcome of these patients. We conducted this study to determine whether dry fibrin sealant dressings (DFSD) would stop bleeding from grade V liver injuries in swine that were hypothermic and coagulopathic. METHODS: Nineteen swine weighing 39.7 kg (mean and 95% confidence interval, 36.3-43.1), underwent a 60% isovolemic, hypothermic exchange transfusion with 33 degrees C 6% hetastarch to produce a dilutional and hypothermic coagulopathy. The animals then received a grade V liver injury and one of three treatments: DFSD, conventional liver packing with gauze sponges, or immunoglobulin G (IgG) placebo sealant dressing (blinded control). All animals were resuscitated with lactated Ringer's solution to their preinjury mean arterial pressure. Blood loss after treatment, mean arterial pressure, resuscitation volume, hematologic variables, and core temperature were monitored for 1 hour. RESULTS: At the time of injury, core temperature = 33.3 degrees C (95% confidence interval, 33.2-33.4), hemoglobin concentration = 4.4 g/dL (4.2-4.6), platelet count = 132 x 10(5)/microL, (93-171), prothrombin time = 21.6 seconds (19.6-23.5), activated partial thromboplastin time = 25.2 seconds (range, 22.9-27.5 seconds), and fibrinogen = 83 mg/dL (range, 76-89 mg/dL) across treatments. The posttreatment blood loss in the DFSD group was 669 mL, (range, 353-1,268 mL), which was lower (p < 0.01) than the means of 3,321 mL (range, 1,891-5,831 mL) and 4,399 mL (range, 2,321-8,332 mL) observed in the packing and IgG groups, respectively. The resuscitation volume in DFSD was 2,145 mL (range 1,310-3,514 mL), which was lower (p < 0.05) than the means of 5,222 mL (range 3,381-8,067 mL) and 5,542 mL (range 3,384-9,077 mL) in the packing and IgG groups, respectively. One-hour survival in the DFSD group was 83%, whereas survival in the packing and IgG groups were 0% (p < 0.05). CONCLUSION: In swine with a grade V liver injury complicated by a dilutional and hypothermic coagulopathy, DFSD provided simple, rapid hemorrhage control, decreased fluid requirements, and improved survival.

Animals↗

Effect of 24-hour storage at 25 degrees C on the in vitro storage characteristics of CPDA-1 packed red cells.

BACKGROUND: Packed red cells (RBCs) warmed above 10 degrees C are generally discarded. Few data exist on the degree of accelerated metabolism and increased hemolysis of packed RBCs allowed to warm. STUDY DESIGN AND METHODS: Twenty-four CPDA-1 packed RBC units were combined in 3-unit pools and subdivided into 2 test units and a control unit. One test unit from each pool was warmed to 25 degrees C for 24 hours on Day 6 and the other test unit was warmed on Day 20; control units were maintained at 1 to 6 degrees C. RBC and supernatant chemistries and RBC morphology were measured weekly (Days 0, 7, 14, 21, and 28) and on the day before warming (Days 6 and 20). RESULTS: Warming CPDA-1 packed RBCs accelerated the catabolism of glucose 10-fold and produced concentrations of glucose, lactate, and ATP after 25 days of storage that were equivalent to those in unwarmed units at 35 days. Supernatant sodium and potassium concentrations were corrected partially with warming. RBC morphology transiently normalized with warming and without increased hemolysis; no bacteria growth was detected. CONCLUSION: One day of 25 degrees C storage of CPDA-1 packed RBCs accelerates essential metabolite break-down equivalent to 10 days of storage at 1 to 6 degrees C. It does not appear to matter whether the packed RBCs are warmed on Day 6 or Day 20. This information may be useful in determining the acceptability of blood allowed to warm above 10 degrees C.

Adenine↗

An improved process for the production of sterile modified haemoglobin solutions.

The process for manufacturing bulk quantities of sterile solutions of human haemoglobin (Hb) cross-linked between the alpha chains (alphaalphaHb) with bis(3,5-dibomosalicyl) fumarate (DBBF) was modified to: (1) improve product purity; (2) increase product yield; (3) eliminate non-United States Pharmacopoeia materials; (4) reduce reagent costs; and (5) reduce production time. These process modifications were the result of increased scientific understanding of the Hb cross-linking chemistry and were in the form of engineering and procedure controls that reflect current good manufacturing practices (cGMP). Purity, as reflected in the fractional yield of the desired alphaalphaHb product, has increased from 60% to 90+% of total Hb, and uncross-linked Hb was virtually eliminated. Impurities such as pyrogens, methaemoglobin, phospholipid, and free iron were reduced. The net yield of alphaalphaHb was increased from 33% to 58% of starting Hb content. Production time, the use of overtime, the consumption of expensive reagents and filters, and losses because of contamination have all been reduced. As a result, cost per gram of alphaalphaHb produced has decreased 60%. With this improved process, efficient production of very pure alphaalphaHb is possible.

Chemistry, Pharmaceutical↗

Implications of new dry fibrin sealant technology for trauma surgery.

Trauma patients have been bleeding to death for thousands of years. The methods used to control hemorrhage (tourniquets, pressure, bandages, and ligatures) have not changed for 2000 years. Technology now exists to amplify the normal clotting system with human proteins, thus providing almost instant hemorrhage control in the face of bleeding. The increasing body of clinical and animal research and safety data regarding new fibrin sealant technologies is compelling. When combined with the evolving concepts of extended trauma resuscitation, acceptance of this technology will finally add a new method of rapid, easy hemostasis to the armamentarium of the surgeon faced with an unstable hemorrhaging patient. Several important issues remain unresolved, such as optimal thrombin and fibrinogen content, amount of material required for hemostasis, long-term effects, distribution of breakdown products, and role of recombinant proteins. These issues are under active investigation. Despite these unanswered questions, the field of absorbable, off-the-shelf, rapidly active hemostatic agents that do not require refrigeration is an exciting area that should yield significant improvements in the care of injured patients.

Bandages↗

Monoclonal antibodies against the plant cytokinin, dihydrozeatin riboside.

Three monoclonal antibodies (all IgG1) were prepared against the plant cytokinin dihydrozeatin riboside (diH[9R]Z) and characterized for suitability in the isolation and quantification of dihydrozeatin-type phytohormones. These antibodies detected as little as 5-10 pg of the homologous cytokinin when used in both competitive and noncompetitive immunoassays and each had characteristic crossreactivity with structurally-related cytokinins. One antibody was used to quantify HPLC-purified diH[9R]Z recovered from wheat tissue. The same antibody also was linked to an insoluble support for use in affinity purification of a mixture of cytokinins. These antibodies will be useful for purification and quantification of dihydrozeatin and its 9-riboside and 9-glucoside in plant tissue.

Animals↗

Cardiovascular toxicity of human cross-linked hemoglobin in a rabbit endotoxemia model.

OBJECTIVE: To determine the possible adverse effects of human cross-linked hemoglobin in endotoxemia. DESIGN: Prospective, controlled, laboratory trial. SETTING: Animal research laboratory. SUBJECTS: New Zealand white rabbits. INTERVENTIONS: Conscious rabbits received intravenous infusions of either lipopolysaccharide (LPS) alone (10 micrograms/kg, Escherichia coli 0111:B4), human hemoglobin cross-linked between the alpha chains (alpha alpha Hb, 0.7 g/kg), or both LPS and alpha alpha Hb. The cardiovascular effects of alpha alpha Hb and LPS as single agents or administered together were then studied in anesthetized rabbits. MEASUREMENTS AND MAIN RESULTS: Mortality in conscious animals that received alpha alpha Hb followed by LPS 4 hrs later (n = 5), or LPS and alpha alpha Hb at the same time (n = 6) was 60% and 67%, respectively. In anesthetized animals, infusion of both LPS and alpha alpha Hb (n = 6) resulted in hypoxia, lactic acidosis, ventricular arrhythmias, and decreased myocardial contractility and left ventricular pressure. In contrast, anesthetized rabbits that received alpha alpha Hb (n = 5) or LPS (n = 5) alone did not develop hypoxia, acidosis, alteration in myocardial contractility, or arrhythmias. Furthermore, death did not occur in any of the conscious animals that received either LPS (n = 7) or alpha alpha Hb (n = 4) as single agents. CONCLUSIONS: In an animal model of nonlethal endotoxemia, infusion of alpha alpha Hb significantly increases mortality. Our data suggest that mortality may be due to the acute increased cardiopulmonary toxicity of alpha alpha Hb in animals with underlying endotoxemia.

Acidosis, Lactic↗

Subunit dissociations in natural and recombinant hemoglobins.

A precise and rapid procedure employing gel filtration on Superose-12 to measure the tetramer-dimer dissociation constants of some natural and recombinant hemoglobins in the oxy conformation is described. Natural sickle hemoglobin was chosen to verify the validity of the results by comparing the values with those reported using an independent method not based on gel filtration. Recombinant sickle hemoglobin, as well as a sickle double mutant with a substitution at the Val-6(beta) receptor site, had approximately the same dissociation constant as natural sickle hemoglobin. Of the two recombinant hemoglobins with amino acid replacements in the alpha 1 beta 2 subunit interface, one was found to be extensively dissociated and the other completely dissociated. In addition, the absence of an effect of the allosteric regulators DPG and IHP on the dissociation constant was demonstrated. Thus, a tetramer dissociation constant can now be determined readily and used together with other criteria for characterization of hemoglobins and their interaction with small regulatory molecules.

Allosteric Regulation↗

Alternative oxygen carriers.

Alternative oxygen carriers are being evaluated in human studies. Information from the clinical evaluation of these "blood substitutes" is not publicly available. Preclinical studies of solutions of modified cell-free hemoglobin and of perfluorocarbon emulsions have demonstrated significant toxicity. Hemoglobin inactivates endothelium-derived nitric oxide, participates in free-radical reactions, is a neurotoxin, activates the immune system, potentiates the effects of bacterial endotoxin, and increases the lethality of certain bacterial infections. Perfluorocarbon emulsions activate complement and cause lung dysfunction. Both materials have short intravascular half-lives. Safe doses of perfluorocarbon emulsions have very limited oxygen-carrying capacity. Protein engineering to reduce the toxicities of the modified hemoglobins is ongoing. A safe and effective erythrocyte substitute is still a distant goal.

Blood Substitutes↗

Blood substitutes.

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Blood Substitutes↗

Efficacy of a fibrin hemostatic bandage in controlling hemorrhage from experimental arterial injuries.

OBJECTIVE: To determine if a pressure dressing containing fibrinogen and thrombin could provide more effective control of arterial hemorrhage than a pressure dressing alone in an animal model of arterial injury. DESIGN: Randomized acute (nonsurvival) experiment in swine. SETTING: Federal biomedical research institute. ANIMALS: Six anesthetized Yorkshire swine. INTERVENTIONS: Uncontrolled arterial hemorrhage was induced in anesthetized swine by creating femoral artery lacerations. Hemorrhage was controlled by a gauze bandage containing fibrinogen and thrombin, applied with 1 minute of 3.5-kg pressure. The dressings were left in place for 1 hour after the pressure was removed. The contralateral limbs received identical treatment with plain gauze dressings. MAIN OUTCOME MEASURES: Total blood loss, mean arterial pressure, and mortality were measured after 1 hour. RESULTS: After 1 hour, blood loss in the fibrin bandage group was 123 +/- 48 mL, compared with 734 +/- 134 mL in the control group (P = .0022). In the group treated with the fibrin bandages, there was no significant decrease in the mean arterial pressure after arterial laceration. In contrast, there was a decrease of 30 mm Hg in the group treated with gauze dressings alone. There was no animal mortality during the study period. CONCLUSIONS: Bandages containing fibrinogen and thrombin significantly reduced the amount of blood loss and allowed mean arterial pressures to be maintained in animals with uncontrolled hemorrhage from femoral artery lacerations. A hemostatic bandage may be an important adjuvant for controlling severe extremity hemorrhage in the prehospital setting.

Animals↗

Review of modified hemoglobin research at Letterman: attempts to delineate the toxicity of cell-free tetrameric hemoglobin.

In the final two years, June 1991 to June 1993, of the Letterman Army Institute of Research, a variety of cell, tissue, organ, and animal systems were used to explore the toxicities of model hemoglobin (Hb) solutions produced in the sterile Hb production facility. Human mononuclear cells release TNF alpha and Il-8 when exposed to chromatographically purified human Hb (HbA0). Mixed cultures of fetal mouse neurons and glial cells exhibit neuronal death with exposure to HbA0 in a dose and time dependent manner while the glial cells are not injured. Isolated perfused rabbit hearts were used to explore the reversibility of coronary vasoconstriction after Hb and cyanomet-Hb administration, and deferoxamine was shown to partially protect that reversibility. In rabbits HbA0 and human Hb cross-linked with bis(3,5-dibromosalicyl) fumarate (alpha alpha Hb) caused hypertension and pulmonary arteritis. In swine, HbA0 and alpha alpha Hb caused systemic and pulmonary hypertension and a doubling of the vascular resistance that was equivalent to that seen with inhibition of nitric oxide synthesis. Elevations of creatine kinase and lactic dehydrogenase activity were observed after Hbs were infused, but not after blockade of nitric oxide synthesis. Acute renal failure seen after administration HbA0, did not appear after alpha alpha Hb. Infusion of cyanomet-alpha alpha Hb did not cause the increased vascular resistance seen after alpha alpha Hb. The infusion of 1-arginine or nitroglycerine with alpha alpha Hb did not prevent the increased vascular resistance and decreased cardiac output or allow the increased oxygen carrying capacity provided by Hb in the plasma from translating into improved oxygen delivery or improved oxygen consumption.

Animals↗

A monoclonal antibody against the plant growth regulator, abscisic acid.

Monoclonal antibodies were prepared against the plant growth regulator abscisic acid (ABA) conjugated to keyhole limpet hemocyanin through C-4. One of these antibodies was characterized for use in a competition fluorescence enzyme-linked immunosorbent assay (F-ELISA). The antibody detected femtomole quantities of ABA when used in the F-ELISA and showed minimal cross-reactivity with ABA metabolites and structural analogs. Dilution analysis suggested that the F-ELISA could be used to determine the ABA content of methanolic extracts of crude samples of wheat seeds without further purification. The F-ELISA was used to determine the effect of seed priming on ABA levels in wheat seeds. The antibody also was used in a modified noncompetitive indirect ELISA to measure ABA content of wheat caryopses. The noncompetitive ELISA was more sensitive than the F-ELISA, although the F-ELISA had a broader measuring range. When our anti-ABA antibody and a commercially available anti-ABA antibody were compared by indirect ELISA, there were no significant differences between the ABA estimates.

Abscisic Acid↗

Trauma and military applications of blood substitutes.

PURPOSE: To review potential clinical uses of erythrocyte substitutes in treating military battlefield casualties, with specific emphasis on combat injury rates and wounding patterns, resuscitation doctrine and logistic requirements. METHODS: Review of published medical literature and of unclassified documents from the U.S. Armed Forces Blood Program. RESULTS: Hemorrhage is the leading cause of death on the battlefield. Early intervention, with definitive treatment, could save up to 30% of soldiers who are killed in action or who die of wounds. Hemorrhage control and rapid volume expansion in appropriate casualties are the main priorities in pre-hospital resuscitation of battlefield casualties. The role for oxygen-carrying fluids in the initial management of military injuries is undefined; however, erythrocyte substitutes could reduce the logistic requirements for blood in field hospitals. In recent wars, outdating of stored blood resulted in 60-95% of units being discarded: 60% of 1.3 million units in Vietnam and 95% of 120,000 units in the Persian Gulf War. CONCLUSIONS: Safety, long storage life, light unit weight, and tolerance to environmental extremes are all characteristics that are necessary for erythrocyte substitutes to extend or replace the use of stored blood in treating battlefield casualties.

Blood Substitutes↗