Early abnormal fibrinolysis and mortality in patients with thermal injury: a prospective cohort study.

INTRODUCTION: Abnormal fibrinolysis early after injury has been associated with increased mortality in trauma patients, but no studies have addressed patients with burn injury. This prospective cohort study aimed to characterize fibrinolytic phenotypes in burn patients and to see if they were associated with mortality. METHODS: Patients presenting to a regional burn centre within 4 h of thermal injury were included. Blood was collected for sequential viscoelastic measurements using thromboelastography (RapidTEG™) over 12 h. The percentage decrease in clot strength 30 min after the time of maximal clot strength (LY30) was used to categorize patients into hypofibrinolytic/fibrinolytic shutdown (SD), physiological (PHYS) and hyperfibrinolytic (HF) phenotypes. Injury characteristics, demographics and outcomes were compared. RESULTS: Of 115 included patients, just over two thirds were male. Overall median age was 40 (i.q.r. 28-57) years and median total body surface area (TBSA) burn was 13 (i.q.r. 6-30) per cent. Some 42 (36.5 per cent) patients had severe burns affecting over 20 per cent TBSA. Overall mortality was 18.3 per cent. At admission 60.0 per cent were PHYS, 30.4 per cent were SD and 9.6 per cent HF. HF was associated with increased risk of mortality on admission (odds ratio 12.61 (95 per cent c.i. 1.12 to 142.57); P = 0.041) but not later during the admission when its incidence also decreased. Admission SD was not associated with mortality, but incidence increased and by 4 h and beyond, SD was associated with increased mortality, compared with PHYS (odds ratio 8.27 (95 per cent c.i. 1.16 to 58.95); P = 0.034). DISCUSSION: Early abnormal fibrinolytic function is associated with mortality in burn patients.

Effects of an acidic environment on coagulation dynamics.

Essentials Acidosis, an outcome of traumatic injury, has been linked to impaired procoagulant efficiency. In vitro model systems were used to assess coagulation dynamics at pH 7.4 and 7.0. Clot formation dynamics are slightly enhanced at pH 7.0 in blood ex vivo. Acidosis induced decreases in antithrombin efficacy offset impairments in procoagulant activity. SUMMARY: Background Disruption of hydrogen ion homeostasis is a consequence of traumatic injury often associated with clinical coagulopathy. Mechanisms by which acidification of the blood leads to aberrant coagulation require further elucidation. Objective To examine the effects of acidified conditions on coagulation dynamics using in vitro models of increasing complexity. Methods Coagulation dynamics were assessed at pH 7.4 and 7.0 as follows: (i) tissue factor (TF)-initiated coagulation proteome mixtures (±factor [F]XI, ±fibrinogen/FXIII), with reaction progress monitored as thrombin generation or fibrin formation; (ii) enzyme/inhibitor reactions; and (iii) TF-dependent or independent clot dynamics in contact pathway-inhibited blood via viscoelastometry. Results Rate constants for antithrombin inhibition of FXa and thrombin were reduced by ~ 25-30% at pH 7.0. At pH 7.0 (+FXI), TF-initiated thrombin generation showed a 20% increase in maximum thrombin levels and diminished thrombin clearance rates. Viscoelastic analyses showed a 25% increase in clot time and a 25% reduction in maximum clot firmness (MCF). A similar MCF reduction was observed at pH 7.0 when fibrinogen/FXIII were reacted with thrombin. In contrast, in contact pathway-inhibited blood (n = 6) at pH 7.0, MCF values were elevated 6% (95% confidence interval [CI]: 1%-11%) in TF-initiated blood and 15% (95% CI: 1%- 29%) in the absence of TF. Clot times at pH 7.0 decreased 32% (95% CI: 15%-49%) in TF-initiated blood and 51% (95% CI: 35%-68%) in the absence of TF. Conclusions Despite reported decreased procoagulant catalysis at pH 7.0, clot formation dynamics are slightly enhanced in blood ex vivo and suppression of thrombin generation is not observed. A decrease in antithrombin reactivity is one potential mechanism contributing to these outcomes.

Early hemostatic responses to trauma identified with hierarchical clustering analysis.

BACKGROUND: Trauma-induced coagulopathy is a complex multifactorial hemostatic response that is poorly understood. OBJECTIVES: To identify distinct hemostatic responses to trauma and identify key components of the hemostatic system that vary between responses. PATIENTS/METHODS: A cross-sectional observational study of adult trauma patients at an urban level I trauma center emergency department was performed. Hierarchical clustering analysis was used to identify distinct clusters of similar subjects according to vital signs, injury/shock severity, and comprehensive assessment of coagulation, clot formation, platelet function, and thrombin generation. RESULTS: Among 84 total trauma patients included in the model, three distinct trauma clusters were identified. Cluster 1 (N = 57) showed platelet activation, preserved peak thrombin generation, plasma coagulation dysfunction, a moderately decreased fibrinogen concentration and normal clot formation relative to healthy controls. Cluster 2 (N = 18) showed platelet activation, preserved peak thrombin generation, and a preserved fibrinogen concentration with normal clot formation. Cluster 3 (N = 9) was the most severely injured and shocked, and showed a strong inflammatory and bleeding phenotype. Platelet dysfunction, thrombin inhibition, plasma coagulation dysfunction and a decreased fibrinogen concentration were present in this cluster. Fibrinolytic activation was present in all clusters, but was particularly increased in cluster 3. Trauma clusters were most noticeably different in their relative fibrinogen concentration, peak thrombin generation, and platelet-induced clot contraction. CONCLUSIONS: Hierarchical clustering analysis identified three distinct hemostatic responses to trauma. Further insights into the underlying hemostatic mechanisms responsible for these responses are needed.

Effect of haemodilution, acidosis, and hypothermia on the activity of recombinant factor VIIa (NovoSeven).

BACKGROUND: A range of plasma volume expanders is used clinically, often in settings where haemostasis may already be impaired. The haemostatic agent, recombinant activated factor VII (rFVIIa, NovoSeven), may be used to improve haemostasis but potential interactions with different volume expanders are poorly understood. METHODS: Clot formation was measured by thromboelastography (TEG) using blood from healthy volunteers. In vitro effects of rFVIIa with haemodilution, acidosis, and hypothermia were examined. Conditions were induced by dilution with NaCl (0.9%), lactated Ringer's solution, albumin 5%, or hydroxyethyl starch (HES) solutions [MW (molecular weight) 130-670 kDa]; by adjusting pH to 6.8 with 1 M HEPES (N-2-hydroxyethylpiperazine-N'-2-ethanesulphonic acid) buffer; or by reducing temperature to 32 degrees C. We also studied the effect of low vs high MW HES (MW 200 vs 600 kDa) and rFVIIa on in vivo bleeding time (BT) in rabbits. RESULTS: Haemodilution progressively altered TEG parameters. rFVIIa improved TEG parameters in the presence of acidosis, hypothermia or 20% haemodilution (P<0.05). At 40% haemodilution, the rFVIIa effect was diminished particularly with high MW HES. In vivo, rFVIIa shortened the BT (P<0.05) with low but not high MW HES. CONCLUSIONS: Efficacy of rFVIIa was affected by the degree of haemodilution and type of volume expander, but not by acidosis or hypothermia.

Antimicrobial efficacy of external fixator pins coated with a lipid stabilized hydroxyapatite/chlorhexidine complex to prevent pin tract infection in a goat model.

BACKGROUND: Pin tract infection is a common complication of external fixation. An antiinfective external fixator pin might help to reduce the incidence of pin tract infection and improve pin fixation. METHODS: Stainless steel and titanium external fixator pins, with and without a lipid stabilized hydroxyapatite/chlorhexidine coating, were evaluated in a goat model. Two pins contaminated with an identifiable Staphylococcus aureus strain were inserted into each tibia of 12 goats. The pin sites were examined daily. On day 14, the animals were killed, and the pin tips cultured. Insertion and extraction torques were measured. RESULTS: Infection developed in 100% of uncoated pins, whereas coated pins demonstrated 4.2% infected, 12.5% colonized, and the remainder, 83.3%, had no growth (p < 0.01). Pin coating decreased the percent loss of fixation torque over uncoated pins (p = 0.04). CONCLUSION: These results demonstrate that the lipid stabilized hydroxyapatite/chlorhexidine coating was successful in decreasing infection and improving fixation of external fixator pins.

Intravenous rFVIIa administered for hemorrhage control in hypothermic coagulopathic swine with grade V liver injuries.

BACKGROUND: Intravenous administration of recombinant activated human clotting factor VII (rFVIIa) has been used successfully to prevent bleeding in hemophilia patients undergoing elective surgery, but not in previously normal trauma patients. This study was conducted to determine whether rFVIIa was a useful adjunct to gauze packing for decreasing blood loss from grade V liver injuries in hypothermic and coagulopathic swine. METHODS: All animals (n = 10, 35 +/- 2 kg) underwent a 60% isovolemic exchange transfusion with 6% hydroxyethyl starch and were cooled to 33 degrees C core temperature. The swine then received a grade V liver injury and 30 seconds later, either 180 microg/kg rFVIIa, or saline control. All animals were gauze packed 30 seconds after injury and resuscitated 5.5 minutes after injury with lactated Ringer's solution to their preinjury mean arterial pressure. Posttreatment blood loss, mean arterial pressure, resuscitation volume, and clotting studies were monitored for 1 hour. Histology of lung, kidney, and small bowel were obtained to evaluate for the presence of microvascular thrombi. RESULTS: At the time of injury, core temperature was 33.3 degrees +/- 0.4 degrees C, hemoglobin was 6 +/- 0.7 g/dL, prothrombin time was 19.1 +/- 1.0 seconds, activated partial thromboplastin time was 29.0 +/- 4.8 seconds, fibrinogen was 91 +/- 20 mg/dL, and platelets were 221 +/- 57 x 105/mL, with no differences between groups (p > 0.05). Clotting factor levels confirmed a coagulopathy at the preinjury point. The posttreatment blood loss was less (p < 0.05) in group 1 (527 +/- 323 mL), than in group 2 (976 +/- 573 mL). The resuscitation volume was not different (p > 0.05). One-hour survival in both groups was 100%. Compared with the control group, rFVIIa increased the circulating levels of VIIa and, despite hypothermia, shortened the prothrombin time 5 minutes after injection (p < 0.05). Laboratory evaluation revealed no systemic activation of the clotting cascade. Postmortem evaluation revealed no evidence of large clots in the hepatic veins or inferior vena cava, or microscopic thrombi in lung, kidney, or small intestine. CONCLUSION: rFVIIa reduced blood loss and restored abnormal coagulation function when used in conjunction with liver packing in hypothermic and coagulopathic swine. No adverse effects were identified.

Effect of fibrin bandage fibrinogen concentration on blood loss after grade V liver injury in swine.

OBJECTIVE: To determine the effect of fibrinogen concentration of dry fibrin bandages on blood loss after grade V liver injury. METHODS: Twenty-four pigs were used. Grade V liver injuries were induced and treated with dry fibrin bandages containing 0, 4, 8, or 15 mg fibrinogen/cm2. Animals were monitored for 60 minutes. Blood loss, fluid use, hematological data, and hemostasis were assessed. RESULTS: Post-treatment blood losses (mean and 95% confidence interval [CI]) were 1,560 mL (356-6,844), 372 mL (65-2,134), 225 mL (51-992), and 127 mL (22-732) in the 0-, 4-, 8-, and 15-mg groups, respectively. Only the 15-mg group had results significantly lower than the 0-mg group (p < 0.05). Blood loss was negatively related to fibrinogen concentration (p < 0.05). CONCLUSION: Fibrinogen concentration was inversely related to blood loss after grade V liver injury. The 15-mg formulation was the only one that significantly reduced blood loss.

Different hypotensive responses to intravenous bovine and human thrombin preparations in swine.

BACKGROUND: Accidental intravenous introduction of commercial bovine thrombin (BT) during use of fibrin glue may result in profound hypotension. Commercial human thrombin (HT) is now available. This study compared the effects of intravenous BT versus HT in swine. METHODS: Swine received 30 U/kg BT, 60 U/kg BT, 30 U/kg HT, or 60 U/kg HT intravenously. Mean arterial pressure (MAP) and survival were monitored for 30 minutes. Thrombin purities and in vitro activities were examined. RESULTS: MAP nadir was lower (p < 0.05) after BT, 27.7 +/- 3.3% (mean +/- SEM) of pretreatment MAP, compared with 41.1 +/- 3.7% after HT. Five of six animals died after 60 U/kg BT, whereas all others survived (p < 0.05). Histology suggested more severe disseminated intravascular coagulation after BT. HT was purer than BT. In vitro activities were similar. CONCLUSION: Both BT and HT produced hypotension. HT appeared safer, because of higher purity. Regardless of source and purity, thrombin must be used with caution.

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.

Elimination of matrix-based interferences to a fluorescent nitrite/nitrate assay by a simple filtration procedure.

Pathophysiological levels of oxygen radical metabolites have been studied as indicators of trauma caused by burn insult. The 2, 3-diaminonaphthalene assay is routinely used in the determination of nitrite/nitrate levels in biological fluids and cellular extracts as one indicator of nitric oxide activity. Several laboratories, including ours, have noted matrix-based interferences resulting in decreased assay sensitivity during nitrite/nitrate analysis. We evaluated filtration using Millipore Ultrafree-MC 10,000 NMWL filters for the ability to eliminate matrix-based interferences from human serum and tissue culture medium, thereby restoring assay sensitivity.

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.

Failure of vitamin A to increase litter size in sows receiving injections at various stages of gestation.

To determine the effectiveness of a single injection of vitamin A to increase litter size, 1,375 sows were assigned randomly to 11 treatment groups (125 sows per treatment). Treatments included injection of 1 x 10(6) IU of vitamin A dissolved in corn oil at weaning or on d 0, 2, 6, 10, 13, 19, 30, 70, or 110 after breeding. Sows in the control group were injected with corn oil on corresponding days. A total of 396 sows were removed from the study following treatment or treatment assignment. Therefore, farrowing data were collected for 979 sows. Injection of vitamin A did not influence (P > . 10) total litter size, live litter size, litter weight, pig weight, number of runts, or number of mummies. Mean live litter size was 10.1 +/- .1 for all sows that farrowed in the experiment. Parity group affected total litter size, live litter size, live litter weight, and number stillborn (P < .01) but not pig weight, number of runts, number of mummies, or gestation length (P > . 10). In this study, a single injection of vitamin A at any time from weaning to farrowing did not increase litter size in sows.

Comparison of antiadhesive treatments using an objective rat model.

Intraperitoneal adhesions are a significant problem (increased morbidity, mortality, and cost) for patients undergoing abdominal procedures. Although a variety of approaches (e.g., fibrinolytic agents, anti-inflammatory drugs, or barrier/separation methods) have been used with some success in preventing adhesions, a comparison of these different modalities has yet to be performed in a model that objectively measures intraperitoneal adhesion formation. Our objectives were to establish an objective, reproducible model of intraperitoneal adhesion formation and to establish efficacy of different treatment modalities in decreasing the strength and extent of intraperitoneal adhesions. In this two-part study, a rat model establishing an objective measure of both the strength and extent of intraperitoneal adhesions was used to compare different treatment modalities. Fibrinolytic agents [recombinant tissue plasminogen activator (rtPA), streptokinase, and urokinase], anti-inflammatory drugs (dexamethasone and tolmetin sodium), and barrier methods [sodium carboxymethylcellulose (CMC), and sodium hyaluronate] and a control group were compared in the first phase. In the second phase, the two most successful agents (rtPA, CMC) were compared both alone and in combination against a commercially available barrier agent (Seprafilm) and a control group. In the first phase of the study, rtPA was the only agent that had a statistically significant effect in decreasing the strength of adhesions. CMC was the only agent that demonstrated a decrease in the extent of adhesions, and the difference tended toward significance. In the second phase, the combination of rtPA and CMC showed a significant decrease in both the strength and extent of adhesions when compared with those of the control group. This decrease was also observed in the group treated with Seprafilm, which showed no difference from the rtPA + CMC group. We conclude that, in this reproducible adhesion model, only the combination of rtPA + CMC and Seprafilm significantly reduced both the strength and the extent of intraperitoneal adhesions.

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.

Timing of vaccination does not affect antibody response or survival after pneumococcal challenge in splenectomized rats.

BACKGROUND: Pneumococcal vaccination after splenectomy for trauma decreases the incidence of overwhelming postsplenectomy infection. The optimal timing of vaccination has not been established. This study was conducted to determine whether timing of vaccination after splenectomy affects antibody response or survival after pneumococcal challenge. METHODS: Sprague-Dawley rats were used for all experiments. Control rats (n=30) were divided into three equal groups and underwent splenectomy followed by sham vaccination 1, 7, or 42 days after splenectomy. Treated rats (n=66) were divided into three equal groups and underwent splenectomy followed by vaccination with polyvalent pneumococcal vaccine 1, 7, or 42 days after splenectomy. All rats then underwent intraperitoneal Streptococcus pneumoniae inoculation with the predetermined lethal dose for 50% of the population 10 days after vaccination. Rats were observed for a 72-hour period after inoculation, and mortality was recorded. Immunoglobulin G and immunoglobulin M antibody titers were determined before vaccination and before inoculation to determine antibody response. RESULTS: Mortality was greater in the control group than in the treatment group (21 of 30 [70%] vs. 2 of 64 [3%]; p < 0.01). There were no differences in mortality within either the control group (1 day, 6 of 10; 7 days, 7 of 10; 42 days, 8 of 10; p=0.62) or the treatment group (1 day, 0 of 21; 7 days, 0 of 21; 42 days, 2 of 22; p=0.14). Immunoglobulin G and immunoglobulin M antibody responses were greater in vaccinated than in nonvaccinated rats. There was no effect of timing of vaccination on antibody response. CONCLUSION: Pneumococcal vaccine reduces mortality from postsplenectomy infection. Timing of vaccination after splenectomy does not affect survival from a pneumococcal challenge or antibody response in rats. This study supports the practice of administering vaccine within 24 hours of splenectomy when vaccine cannot be administered before surgery.

Accuracy of orthognathic evaluation using telemedicine technology.

OBJECTIVE: Telemedicine technology has the ability to project highly specialized medical and dental expertise anywhere in the world. This is particularly important to many small, isolated communities that do not have access to medical and dental specialists. Telemedicine also has the potential to reduce unnecessary travel, time away from work, and unneeded hospital admissions. For this technology to be successful, however, clinicians need to have confidence in its capabilities. This study was conducted to determine the accuracy of an orthognathic evaluation using telemedicine. MATERIALS AND METHODS: Thirteen patients were randomly selected for review by two surgeons each using telemedicine and clinical examinations. Clinically acceptable differences were established, and the results of the two examination methods were compared. RESULTS: A main effect of the examination method was observed in 7 of the 18 continuous measurements taken. Examination of the absolute value of the within-subject difference between the two examination methods demonstrated that the mean absolute difference was statistically different from zero for 13 of 18 measurements taken. CONCLUSIONS: These data demonstrate that a relatively accurate orthognathic examination can be performed with this technology. With this in mind, clinicians may feel comfortable using this technology for other clinical applications.

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.

Lack of a nocturnal rise in serum concentrations of melatonin as gilts attain puberty.

Twenty prepubertal crossbred gilts (Yorkshire x Hampshire x Duroc) weighing 98.1 +/- 4.2 kg at 5 mo of age were placed in an environmentally controlled room having a temperature of 18 degrees C and light:dark cycle of 12 h:12 h. Light intensity measured 700 lx at eye level to the gilts. Three mature ewes were penned adjacent to the gilts to serve as positive controls for the light-dark cycles. After a 30-d acclimation period, 10 gilts from the pool determined to be prepubertal (serum progesterone < 500 pg/mL) were fitted with surgically implanted jugular catheters. Blood samples were drawn at 1100 (4 h after onset of light), 1130, 1200, 2300 (4 h after onset of darkness), 2330, and 2400 for 4 d. On d 5 of sampling, gilts were transported in an open-bed truck for 15 min, returned to their original environment, and exposed to boars for 20 min. Boar exposure was repeated every day throughout the remainder of the experimental period. Blood samples were drawn from each gilt until 7 d after estrus or for 12 d in those gilts that did not exhibit estrus. Blood samples were drawn by venipuncture from the ewes during the entire experimental period. For each sampling day, within an individual gilt or ewe, means of serum concentrations of melatonin (MEL) for night (scotophase) and day (photophase) samples were calculated. After three replications were conducted, four classes of animals were obtained: ewes (n = 9); nonpubertal gilts (n = 10); and two classes of gilts that ultimately reached puberty (prepubertal [n = 16] and postpubertal [n = 16]). Across all gilts, only 65 of 406 bleeding periods (16.0%) had a nocturnal (scotophase) rise in serum MEL. The proportion of gilts expressing a nocturnal rise in serum MEL did not differ as gilts approached puberty (P > .05). Incidence of nocturnal rises of MEL was similar (P > .05) in gilts that attained puberty and gilts that did not attain puberty. Nocturnal rises in MEL were observed in 86.2% of the bleeding periods of ewes housed in the same environment. These data indicate clearly that nocturnal rises in serum MEL are not necessary for a gilt to attain puberty.

Maternal recognition of pregnancy in swine. I. Minimal requirement for exogenous estradiol-17 beta to induce either short or long pseudopregnancy in cycling gilts.

Five experiments were conducted to determine the minimal requirement for estradiol-17 beta (E2) injections to induce either short pseudopregnancy (SPP) or long pseudopregnancy (LPP) in cycling gilts. In experiments 1 through 5, E2 was injected i.m. on combinations of days between 11 and 25 days postestrus. Exogenous E2 on Days 12 and 13 or on Days 12 through 19 was optimal for induction of SPP or LPP, respectively. The duration of E2-induced diestrus was clearly demarcated between SPP (n = 73, duration 23-35 days) and LPP (n = 23, duration > 50 days). A sixth experiment was conducted to determine the minimum dose of intrauterine E2 required to induce SPP, and these gilts received intrauterine infusions of 0, 4, 40, or 400 micrograms E2 per 24 h on Days 12 and 13 postestrus. Pseudopregnancy was induced in 0 of 12, 1 of 4, 1 of 11, and 4 of 7 gilts in the treatment groups, respectively. These data suggest that uterine exposure alone is not sufficient to induce SPP. The present results indicate that the optimal signal for inducing LPP in unmated cycling gilts, and perhaps also for maternal recognition of pregnancy in mated gilts, may occur in two phases with continuous exposure to E2 being required from Day 12 to Days 17-19.

Maternal recognition of pregnancy in swine. II. Plasma concentrations of progesterone and 13,14-dihydro-15-keto-prostaglandin F2 alpha during the estrous cycle and during short and long pseudopregnancy in gilts.

Two experiments were conducted to determine plasma progesterone (P4) and 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM) concentrations in unmated gilts induced to have either short pseudopregnancy (SPP) or long pseudopregnancy (LPP). In experiment 1, estradiol-17 beta (E2) was injected on different combinations of days between Days 11 and 16 of the estrous cycle. For gilts induced to exhibit SPP, the interestrous interval averaged 27.0 +/- 0.4 days compared to the control interval of 20.0 +/- 0.4 days. In experiment 2, E2 injections were given on Days 12 and 13 or on Days 12 through 25. Interestrous intervals in SPP and nonpseudopregnant gilts were 25.6 +/- 0.2 and 19.9 +/- 0.6 days, respectively. Four of six gilts treated with E2 on Days 12-25 were induced to have LPP lasting more than 100 days. In both experiments, plasma P4 declined to baseline approximately 3 days before posttreatment estrus, regardless of type of pseudopregnancy induced. Plasma PGFM peaked 4-6 days before posttreatment estrus in gilts displaying each type of response. In gilts exhibiting LPP, plasma PGFM concentrations tended to increase steadily during pseudopregnancy. These data suggest that the mechanisms of luteolysis during the estrous cycle of unmated gilts and during estrogen-induced SPP and LPP may be similar. The present results suggest that luteal persistence during SPP and LPP may be due to delayed peak release of prostaglandin F2 alpha by the uterus.