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Biomedical subjects

Thomas J Reid

Publications and source records attributed to Thomas J Reid.

13 recordsLinked to original sources

A salmon thrombin-fibrin bandage controls arterial bleeding in a swine aortotomy model.

BACKGROUND: Recently, a wide variety of bandages have been formulated to attempt to improve the effectiveness of emergency intervention in situations of uncontrolled bleeding. The best of these dressings contain a mixture of human thrombin and fibrinogen. The presence of human components in these bandages, although effective, increases the cost of the dressing and raises questions of availability of raw materials and transmission of pathogens. The purpose of this study was to investigate the efficacy of dressings composed of salmon thrombin and fibrinogen in a swine aortotomy model. METHODS: A 4.4-mm aortotomy was produced in the abdominal aorta of 19 anesthetized, splenectomized swine. The United States Army standard field gauze was applied to 8 animals, and the salmon thrombin-fibrin dressing (SFD) was applied to 11 animals. Survival, blood loss, and other parameters were measured over a 60-minute period. RESULTS: All 11 animals that received the SFD survived the aortotomy injury, and bleeding stopped within 7.5 +/- 1.5 min. Seven of 8 animals in the control group were killed when bleeding continued and blood pressures decreased to the cutoff values as outlined in the animal protocol. Bleeding was significantly less in the SFD group compared with the gauze group (241 +/- 65.3 vs. 932.7 +/- 142.4 mL). CONCLUSION: Fibrin dressing using salmon-derived thrombin and fibrinogen is effective in controlling severe, uncontrolled bleeding. This dressing may offer an alternative to dressings composed of human coagulation proteins.

Animals↗

New insulation technology provides next-generation containers for "iceless" and lightweight transport of RBCs at 1 to 10 degrees C in extreme temperatures for over 78 hours.

BACKGROUND: There is a universal need, in both civilian and military settings, for a lightweight container capable of maintaining RBCs at 1 to 10 degrees C in remote areas, during extended transit times, and under austere environments. The use of ice in insulated containers or small commercial coolers for these purposes often results in loss of RBCs due to failure to maintain temperatures within the requisite range. A lightweight and thermally efficient container capable of carrying 4 to 6 units of RBCs at 1 to 10 degrees C for over 72 hours under extreme conditions would help resolve current problems in RBC transportation. STUDY DESIGN AND METHODS: Six different prototype containers incorporating phase-change materials (PCMs) in their designs were evaluated for their ability to maintain RBCs between 1 and 10 degrees C while exposed to external temperatures of -24 degrees C and 40 degrees C. In separate experiments, a container was opened and a RBC unit removed. RESULTS: One container weighing 10 pounds with four units of RBCs was capable of maintaining the temperature of the units between 1 and 10 degrees C for over 78 hours, 96 hours, and 120 hours at 40 degrees C, -24 degrees C, and 23 degrees C, respectively. Opening the container decreased these times by 2 to 3 hours. CONCLUSIONS: An energy-efficient and lightweight container that maintains RBCs at 1 to 10 degrees C under austere environments for over 78 hours is now available. This container, known as the Golden Hour container (GHC), will facilitate transport of RBCs. The GHC will have additional applications (transport and/or storage of vaccines, other biologics, organs, reagents, etc).

Blood Preservation↗

Modulation of Janus kinase 2 by cisplatin in cancer cells.

Constitutive activation of Janus kinases (JAKs) is frequently detected in various human cancers. The activation of JAKs results in the phosphorylation and activation of signal transducers and activators of transcription (STATs). The constitutive activation of JAK/STAT pathway may play an important role in growth and survival of human cancer cells. In this study, we examined whether a chemotherapeutic agent cisplatin could inhibit the JAK/STAT pathway. In ovarian cancer and sarcoma cells that express constitutively active JAK2, cisplatin significantly inhibited tyrosine phosphorylation and kinase activity of JAK2 in a dose- and time-dependent manner. Meanwhile, cisplatin also inhibited Stat3 tyrosine phosphorylation and down-regulated BcL-XL anti-apoptotic protein in the cancer cells tested. In leukemia cells expressing high level of TEL-JAK2 fusion protein, cisplatin dramatically inhibited tyrosine phosphorylation of TEL-JAK2 as well. Furthermore, our results have shown that down-regulation of JAK2 by cisplatin might be through modulation of a tyrosine phosphatase SHP-1 but not SOCS family members. Taken together, our observations demonstrated that cisplatin down-regulated the JAK/STAT pathway through de-phosphorylation of JAK/STAT in cancer cells.

Antineoplastic Agents↗

Advanced hemostatic dressing development program: animal model selection criteria and results of a study of nine hemostatic dressings in a model of severe large venous hemorrhage and hepatic injury in Swine.

BACKGROUND: An advanced hemostatic dressing is needed to augment current methods for the control of life-threatening hemorrhage. A systematic approach to the study of dressings is described. We studied the effects of nine hemostatic dressings on blood loss using a model of severe venous hemorrhage and hepatic injury in swine. METHODS: Swine were treated using one of nine hemostatic dressings. Dressings used the following primary active ingredients: microfibrillar collagen, oxidized cellulose, thrombin, fibrinogen, propyl gallate, aluminum sulfate, and fully acetylated poly-N-acetyl glucosamine. Standardized liver injuries were induced, dressings were applied, and resuscitation was initiated. Blood loss, hemostasis, and 60-minute survival were quantified. RESULTS: The American Red Cross hemostatic dressing (fibrinogen and thrombin) reduced (p < 0.01) posttreatment blood loss (366 mL; 95% confidence interval, 175-762 mL) and increased (p < 0.05) the percentage of animals in which hemostasis was attained (73%), compared with gauze controls (2,973 mL; 95% confidence interval, 1,414-6,102 mL and 0%, respectively). No other dressing was effective. The number of vessels lacerated was positively related to pretreatment blood loss and negatively related to hemostasis. CONCLUSION: The hemorrhage model allowed differentiation among topical hemostatic agents for severe hemorrhage. The American Red Cross hemostatic dressing was effective and warrants further development.

Animals↗

Platelet substitutes in the management of thrombocytopenia.

A variety of agents can improve hemostasis and reduce blood loss caused or exacerbated by congenital or acquired defects in platelet number of function. This review discusses several available approaches for the practicing clinician to reduce bleeding (diffuse or localized) in this clinical setting.

Antifibrinolytic Agents↗

Epsilon-amino caproic acid additive decreases fibrin bandage performance in a swine arterial bleeding model.

epsilon -Amino caproic acid (EACA), a lysine analog that inhibits the activity of plasmin, was added to Nycomed (TC-S) fibrin bandages, and the bandages were tested for hemostatic efficacy in a swine femoral artery bleeding model. The blood loss using the bandage with EACA (TC-S+EACA; 728.8+/-132 g, n=5) was much greater as compared to the TC-S bandage alone (TC-S; 237.8+/-47.9 g, n=6, p=.02). The time to "cessation of bleeding" (T(b)) was also increased for animals treated with TC-S+EACA bandages compared to the TC-S controls (33.6+/-10.8 min vs. 9.2+/-2.2 min; p=.05). Although plasma fibrinogen concentration decreased in animals treated with the TC-S+EACA bandage, activated partial thromboplastin times (aPTT) and thrombin times (TT) were decreased. Animals treated with the TC-S control bandage exhibited no changes in fibrinogen, aPTT or TT. Prothrombin times (PT) were unchanged in either group. In conclusion, addition of EACA to the Nycomed product decreased fibrin bandage efficiency.

Aminocaproic Acid↗

Addition of a propyl gallate-based procoagulant to a fibrin bandage improves hemostatic performance in a swine arterial bleeding model.

Fibrin bandages manufactured by Nycomed Austria (TC-S) were modified by the addition of Hemostyptin (HS), a proprietary platelet-activating reagent containing propyl gallate. HS was added as an additional layer to TC-S fibrin bandages and the bandages were tested for hemostatic efficacy in a swine femoral artery bleeding model. Injuries were treated with a TC-S+HS bandage preparation using HS lyophilized onto a bandage surface that was then attached to the fibrin dressing. This preparation qualitatively and quantitatively exhibited more robust blood clotting at the surgical site than the control bandages. TC-S+HS bandages were more effective than control bandages with a difference in blood loss of 251.8+/-66.5 g for TC-S bandage alone, n=12 vs. 121+/-40.7 g, n=13 for the TC-S+HS bandage, P=0.05. Bleeding times were shortened for animals treated with the HS fortified bandages and residual platelets counts in these animals were higher.

Animals↗

Hypertonic resuscitation and blood coagulation: in vitro comparison of several hypertonic solutions for their action on platelets and plasma coagulation.

Resuscitation with hypertonic saline (HS) appears to aggravate bleeding in a model of uncontrolled hemorrhage [J. Trauma 28 (1988) 751; J. Trauma 29 (1989) 79; Arch. Surg. 127 (1992) 93]. This property may be related to the anticoagulant effects of HS on plasma clotting factors and platelets [J. Trauma 31 (1991) 8]. The hypothesis in this study is that a hypertonic solution can be developed that would not disturb the blood coagulation mechanism and could be used as an alternative to hypertonic saline.HS and four different 2400 mosM solutions containing monosaccharides and/or glycine were screened for their in vitro effects on plasma clotting times and platelets. Significant prolongations falling outside the normal range were detected in prothrombin time (PT) and thrombin rime (TT) when only 5% of the volume of normal plasma is HS. Platelet function as measured by extent of shape change (ESC) induced by ADP and aggregation induced by thrombin were also critically impaired by HS at a 5% dilution. All alternative solutions-hypertonic glucose, sorbitol, glycine, glucose/glycine, glucose/mannitol/glycine, sorbitol/glycine-caused a significantly reduced impairment in platelet function and the plasma coagulation system. Hypertonic glycine showed a unique ability to fully preserve the function and integrity of the plasma coagulation system. Considering the pre-deposition of the trauma patient to coagulopathy, administration of HS which clearly is a potent anticoagulant and anti-platelet risks further aggravating the coagulopathy. In contrast, hypertonic glycine preserves the blood coagulation mechanism and exhibits the potential for numerous therapeutic applications. Therefore, prompt evaluation of hypertonic glycine as a resuscitative fluid is highly desirable.

Blood Coagulation↗

Characterization of the main phase transition in 1,2-dipalmitoyl-phosphatidylcholine luvs by 1H NMR.

The main phase transition (Tm) of 100 nm large unilamellar vesicles (LUVs) of 1,2-dipalmitoylphosphatidylcholine (DPPC) was investigated using 1H NMR (proton magnetic resonance) in deuterium oxide, and both DSC (differential scanning calorimetry) and IR (infrared) spectroscopy in water and deuterium oxide. The ability of 1H NMR to determine Tm was demonstrated and the values obtained were in general agreement with those observed with DSC and IR. However, the temperature range of the transition observed by NMR was significantly broader than that observed with either DSC or IR. The effect of deuterium oxide on Tm was studied by comparing results obtained in water and deuterium oxide with DSC and IR. The results showed no significant difference in Tm or temperature range of transition determined in these solvents.

1,2-Dipalmitoylphosphatidylcholine↗

Transfusion-sparing hemostatic agents.

A variety of agents are available to improve hemostasis and reduce blood loss in multiple clinical settings. These agents are most commonly used to reduce bleeding when an underlying hemostatic defect is present. Some new agents offer the potential to decrease blood loss even in the absence of an obvious underlying hemostatic defect. The authors discuss the use of a variety of products to reduce bleeding and minimize transfusion of blood products in the setting of clotting factor deficiency or inhibition, platelet deficiency and/or dysfunction, increased fibrinolysis, therapeutic anticoagulation, and coagulopathies caused by dilution and consumption in the setting of trauma and surgery. The authors primarily focus on the available pharmaceuticals.

Antifibrinolytic Agents↗