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Biomedical subjects

T R Howdieshell

Publications and source records attributed to T R Howdieshell.

At least 19 recordsLinked to original sources
PubMed2001

Antibody neutralization of vascular endothelial growth factor inhibits wound granulation tissue formation.

OBJECTIVE: The goal of this work was to test the functional role of vascular endothelial growth factor (VEGF) in promoting the vigorous granulation tissue formation, wound fluid accumulation, and angiogenic responses characteristic of this wound model. BACKGROUND: Formation of vessel-rich granulation tissue is central to wound repair and is thought to be regulated by locally liberated angiogenic factors. Despite the clinical importance of granulation tissue formation in the early stage of wound healing, surprisingly little is known about the molecular identity of signals leading to granulation tissue invasion of a wound space. Methods. A ventral hernia, surgically created in the abdominal wall of 15 swine, was repaired using silicone sheeting and skin closure. An osmotic minipump, inserted in a remote subcutaneous pocket, delivered saline (n = 5), an irrelevant control antibody (n = 5), or neutralizing anti-VEGF antibody (n = 5) into the wound environment. Serial ultrasonography on Days 2, 4, 7, 9, 11, and 14 was used to determine the dimensions of the subcutaneous granulation tissue and wound fluid compartment. VEGF and transforming growth factor beta1 (TGF-beta1) levels in serial wound fluid samples were quantitated by ELISA. On Day 14, animals were sacrificed and the abdominal wall was harvested for histologic, biochemical, and molecular analyses. RESULTS: In animals receiving saline or an irrelevant antibody, a nearly linear 4-fold increase in granulation tissue thickness and 7-fold increase in wound fluid volume were measured over the 14-day study interval. In contrast, in animals receiving anti-VEGF neutralizing antibody, Day 14 granulation tissue thickness and wound fluid volume measurements were essentially unchanged from Day 2 values. Moreover, in the anti-VEGF animals, ultrasonography was unable to resolve the "angiogenic zone" typical of both controls, and correspondingly, wound vessel count and vascular surface area estimates derived from image analysis of histological sections were 3-fold lower in the anti-VEGF animals compared with the saline and antibody controls. Finally, VEGF levels in wound fluid detectable by ELISA analysis were strikingly (10-fold) reduced in anti-VEGF animals on Postsurgery Days 7-14. In contrast, TGF-beta1 levels were unaffected by the anti-VEGF treatment. CONCLUSION: Functional VEGF is a key mediator in wound angiogenesis, fluid accumulation, and granulation tissue formation.

Abdominal Muscles↗
PubMed2001

Nitric oxide synthase isoform expression in a porcine model of granulation tissue formation.

BACKGROUND: This study was designed to determine whether the nitric oxide (NO) pathway is involved in wound granulation tissue formation. METHODS: A section of the pig abdominal wall (excluding the skin) was excised, creating an incisional hernia. The resulting defect was repaired with silicone sheeting in a manner that mimics a temporary abdominal wall closure. During the 14-day experimental period, porcine omentum adhered to the peritoneal edges of the defect and a highly vascularized granulation tissue formed on both sides of the sheeting. Granulation tissue thickness and wound fluid volume were monitored by ultrasonography and epigastric artery flow velocity was monitored by color Doppler flow analysis at days 2, 4, 7, 9, 11, and 14. Fluid was serially harvested from the wound compartment at days 2, 4, 7, 9, 11, and 14 for nitrite/ nitrate (NOx) analysis. Finally, granulation tissue was harvested at day 14 for immunohistochemical and molecular analyses. RESULTS: There was a significant increase in granulation tissue thickness and wound fluid volume during the 14-day study period. Blood flow to the wound increased significantly by day 4 and returned toward baseline by day 14. Wound fluid NOx levels significantly increased from days 7 to 11 and then decreased to near baseline values by day 14. Wound fluid arginine levels significantly decreased when compared with peritoneal fluid and plasma levels at day 14, while wound fluid ornithine levels significantly increased. Immunohistochemical analysis of granulation tissue at day 14 revealed nitric oxide synthase (NOS) 2 was present in the majority of the cells in the granulation tissue. NOS 3 was expressed in endothelial cells only, and NOS 1 expression was not observed in the granulation tissue. CONCLUSIONS: This study suggests that NO, NOS 2, and arginine may play critical roles in granulation tissue formation and wound healing. Arginase and NOS 2 may compete for available arginine as a substrate, thereby limiting later NO production in favor of sustained ornithine synthesis.

Abdominal Injuries↗
PubMed2000

Clinical anatomy of the popliteal blood vessels.

The surgical management of venous injuries in the popliteal fossa is a contested issue. The basic options are ligation or repair. Most anatomy textbooks briefly describe a single popliteal vein, and the literature contains few references on venous patterns in this region. Although the primary objective of this study was to analyze venous variability in 52 dissected cadaveric popliteal fossae and 63 venograms, data were also collected on the popliteal artery. Nine groups (A-I) were designated regarding the manner of formation of the popliteal vein. These groupings were based primarily on differences in the union of the anterior tibial, posterior tibial, and fibular (peroneal) veins to form medial and lateral (popliteal) veins, and whether these two veins fused to form a singular popliteal vein proximal or distal to the transverse plane at the level of the distal edge of the femoral condyles (FC). In the majority of the dissections and venograms, multiple veins crossed the FC, and the medial vein was larger in diameter than the lateral vein. Two patterns of popliteal artery termination were observed based on differences in the site of origin of the fibular artery. The results were compared with anatomy and vascular surgery textbook descriptions and sparse literature reports on vascular variations in the popliteal fossa. It is hoped that these data will benefit surgeons performing procedures in this region.

Cadaver↗
PubMed2000

Peer teaching and computer-assisted learning: An effective combination for surgical skill training?

BACKGROUND: The surgical literature suggests that collaborative learning using peers may be a valid way to teach surgical skills and there is a growing interest in the use of computer-assisted learning for this purpose. Combining this evolving technology with this type of teaching would theoretically offer a number of advantages including a reduction in the amount of faculty time devoted to this task. In this study, we evaluate the efficacy of a type of collaborative learning in a computer-assisted learning environment. MATERIALS AND METHODS: We designed a prospective, randomized study comparing novice learners who were allowed to work in pairs with those who worked independently in a specially equipped computer-assisted learning classroom. Both pretest and posttest assessments were performed by videotaping this skill. Three experts then evaluated the videotapes, in a blinded fashion. Three different outcomes were assessed. RESULTS: Seventy-seven subjects were enrolled in and completed the study. Comparison of the outcome measures demonstrated no between group difference in the average performance scores or posttest times. The proportion of subjects who correctly tied a square knot was significantly lower in the computer-assisted peer teaching group when compared with the computer-assisted learning alone group (P = 0.04). CONCLUSIONS: Collaborative learning in a computer-assisted learning environment is not an effective combination for teaching surgical skills to novices.

Computer-Assisted Instruction↗
PubMed2000

The impact of external feedback on computer-assisted learning for surgical technical skill training.

BACKGROUND: Computer-assisted learning (CAL) offers a number of potential advantages for surgical technical skills teaching. The purpose of this study was to evaluate the impact of individualized external feedback on surgical skill acquisition when a CAL package is used for instruction. METHODS: Freshman and sophomore students participated in a 1-hour CAL session designed to teach them how to tie a two-handed square knot. One group received individualized external feedback during the session and the other group did not. Subjects were videotaped performing the skill before and after the session. The tapes were independently analyzed, in blinded fashion, by three surgeons. Three measures were obtained: the total time for the task, whether or not the knot was square, and the general quality of the performance using a rating scale. RESULTS: Data from 105 subjects were available for final analysis. For both groups there were significant increases in the proportion of knots that were square when the posttest performance was compared with the pretest performance but there was no difference between groups on this measure. Comparison of the performance scores demonstrated that both groups had a significant improvement after the session but the performance scores were significantly better in the group that had received feedback. CONCLUSIONS: Novices in both groups using CAL showed improvement in two of the outcomes measured, suggesting that subjects in both groups attained some degree of competence with this skill. The higher posttest performance score for the group receiving feedback demonstrates that external feedback results in a higher level of mastery when CAL is used to teach surgical technical skills.

Analysis of Variance↗
PubMed1998

Computer-assisted learning versus a lecture and feedback seminar for teaching a basic surgical technical skill.

BACKGROUND: Rapid improvements in computer technology allow us to consider the use of computer-assisted learning (CAL) for teaching technical skills in surgical training. The objective of this study was to compare in a prospective, randomized fashion, CAL with a lecture and feedback seminar (LFS) for the purpose of teaching a basic surgical skill. METHODS: Freshman medical students were randomly assigned to spend 1 hour in either a CAL or LFS session. Both sessions were designed to teach them to tie a two-handed square knot. Students in both groups were given knot tying boards and those in the CAL group were asked to interact with the CAL program. Students in the LFS group were given a slide presentation and were given individualized feedback as they practiced this skill. At the end of the session the students were videotaped tying two complete knots. The tapes were independently analyzed, in a blinded fashion, by three surgeons. The total time for the task was recorded, the knots were evaluated for squareness, and each subject was scored for the quality of performance. RESULTS: Data from 82 subjects were available for the final analysis. Comparison of the two groups demonstrated no significant difference between the proportion of subjects who were able to tie a square knot. There was no difference between the average time required to perform the task. The CAL group had significantly lower quality of performance (t = 5.37, P <0.0001). CONCLUSIONS: CAL and LFS were equally effective in conveying the cognitive information associated with this skill. However, the significantly lower performance score demonstrates that the students in the CAL group did not attain a proficiency in this skill equal to the students in the LFS group. Comments by the students suggest that the lack of feedback in this model of CAL was the significant difference between these two educational methods.

Computer-Assisted Instruction↗
PubMed1998

Normoxic wound fluid contains high levels of vascular endothelial growth factor.

OBJECTIVE: To examine the temporal integration of vascular endothelial growth factor (VEGF), which has been shown to be present in wound fluid, with the putatively related processes of wound fluid oxygen content, wound angiogenesis, and granulation tissue formation. SUMMARY BACKGROUND DATA: During cutaneous wound repair, new tissue formation starts with reepithelialization and is followed by granulation tissue formation, including neutrophil and macrophage accumulation, fibroblast ingrowth, matrix deposition, and angiogenesis. Because angiogenesis and increased vascular permeability are characteristic features of wound healing, VEGF may play an important role in tissue repair. METHODS: A ventral hernia, surgically created in the abdominal wall of female swine, was repaired using silicone sheeting and skin closure. Over time, a fluid-filled wound compartment formed, bounded by subcutaneous tissue and omentum. Ultrasonography was performed serially to examine the anatomy and dimensions of the subcutaneous tissue and wound compartment. Serial wound fluid samples, obtained by percutaneous aspiration, were analyzed for PO2, PCO2, pH, and growth factor concentrations. RESULTS: Three independent assays demonstrate that VEGF protein is present at substantially elevated levels in a wound fluid associated with the formation of abdominal granulation tissue. However, the wound fluid is not hypoxic at any time. Serial sampling reveals that transforming growth factor beta-1 protein appears in the wound fluid before VEGF. CONCLUSIONS: The results suggest that VEGF is a prominent regulator of wound angiogenesis and vessel permeability. A factor other than hypoxia, perhaps the earlier appearance of another growth factor, transforming growth factor beta-1, may positively regulate VEGF appearance in the wound fluid.

Abdominal Muscles↗
PubMed1998

Immunoglobulin E and eosinophil counts are increased after sepsis in trauma patients.

OBJECTIVES: To determine the time course of plasma immunoglobulin E (IgE) concentration increases after traumatic injury, if increased IgE concentrations were related to clinical events or complications, and if increased peripheral eosinophil counts could be related to trauma, sepsis, or organ-specific complications. DESIGN: Data relating to severity of injury, clinical complications, plasma concentrations of IgE, and peripheral eosinophil counts were prospectively collected. SETTING: Trauma service, tertiary-care medical center. PATIENTS: One hundred adult trauma patients admitted to the intensive care unit. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Plasma IgE concentrations increased in most patients. However, the greatest increases were observed in patients with sepsis (p = .03), renal dysfunction (p = .04), or pneumonia (p = .02). IgE increases were not related to severity or mechanism of injury, allergy history, or age. The day of highest observed IgE concentration was related to the day of onset of sepsis (p = .012, r = .39), and occurred a mean of 3.8 days after sepsis. Most patients had increased peripheral eosinophil counts and eosinophil percentages of white blood cells during their intensive care unit stays. Eosinophil counts were greater in patients with sepsis (p < .0001), severe sepsis (p < .0001), or pneumonia (p < .002). CONCLUSIONS: Increased IgE concentrations and eosinophil counts were found after sepsis and do not appear to be related to the initial injury. Since IgE and eosinophil production are enhanced by interleukin-4 and interleukin-5, respectively, these findings suggest that T-helper lymphocyte type 2 cytokines are activated in response to sepsis after traumatic injury.

Adolescent↗
PubMed1998

Abdominal compartment syndrome.

BACKGROUND: The abdominal compartment syndrome (ACS) is a newly appreciated and potentially fatal consequence of increased intra-abdominal pressure. It can be due to either trauma or surgery, as well as numerous medical conditions. Prolonged, unrelieved elevation of intra-abdominal pressure can produce pulmonary compromise, renal impairment, cardiac failure, shock, and death. A high index of suspicion is imperative. Measurement of the intravesical pressure provides a urometric window for detecting and monitoring this condition. CONCLUSIONS: Reopening the abdominal incision (decompressive celiotomy) has proven a life-saving intervention. Use of delayed wound closure (staged celiotomy) may prevent development of this condition in high-risk surgical patients. It is urgent that all physicians, and surgeons in particular, be alerted to this potentially lethal complication.

Abdomen↗
PubMed1997

Heparin versus citrate regional anticoagulation during autotransfusion in a porcine intra-abdominal hemorrhage model.

Our objective was to determine the effects of anticoagulants and blood loss on hemodynamic, hematologic, and coagulation parameters following autotransfusion in an animal model of intraabdominal hemorrhage. We performed a prospective, randomized observational animal study at an animal research laboratory at a university medical center. Eight Landrace, domestic pigs, weighing 17-23 kg, each underwent jugular venous and iliac arterial catheterization and laparotomy with retroperitoneal dissection for aortic exposure to simulate an operative environment. Following baseline laboratory and hemodynamic determinations, intra-abdominal hemorrhage was accomplished via aortotomy in three sequential 10 mL/kg blood volumes. After allowing pooling in the exposed retroperitoneum to ensure tissue contact, the shed blood was suctioned, processed, and washed in an autotransfusion device utilizing either heparin (n = 4) or acid-citrate-dextrose (n = 4) as a system anticoagulant. Prior to autologous transfusion, each pig received a 20 mL/kg intravenous bolus of 0.9 per cent saline to treat shock. The processed blood was then infused, and laboratory and hemodynamic measurements were repeated following each cycle of hemorrhage and autotransfusion. Sequential fixed volume hemorrhage resulted in significant reductions in mean arterial pressure. Despite crystalloid infusion and transfusion of processed shed blood, postresuscitation mean arterial pressure did not return to baseline values, with no difference noted between anticoagulant groups. Infusion of increasing volumes of autologous blood resulted in significant reductions in hematocrit, platelet count, fibrinogen, antithrombin III, ionized calcium, and total protein. The decrease in concentration of each variable was independent of the choice of anticoagulant with the exception of antithrombin III, with higher levels noted in animals receiving blood anticoagulated with acid-citrate-dextrose. Prothrombin time and partial thromboplastin time were unaffected by volume of autologous transfusion or choice of anticoagulant. We conclude that changes in hemodynamic, hematologic, and coagulation parameters associated with hemorrhage and autotransfusion appear related more to the volume of blood loss and the cumulative pheresis of plasma than to the choice of anticoagulant.

Animals↗
PubMed1996

The dimensions and vascular anatomy of the cricothyroid membrane: relevance to emergent surgical airway access.

Following traumatic injury, rapid surgical access to the airway may be required, with surgical cricothyroidostomy the procedure of choice. Immediate complications of cricothyroidostomy include unsuccessful or incorrect site of tube placement and hemorrhage. Subglottic stenosis is the most common late complication. This project was undertaken to better define the dimensions and vasculature of the cricothyroid region. In 15 cadaveric specimens, cervical dissection revealed the average width of the cricothyroid membrane visible between cricothyroid muscles to be 8.2 mm, and the average height 10.4 mm. Latex injection of the carotid artery demonstrated a transverse cricothyroid artery arising from the superior thyroid artery in 93% of cases. The cricothyroid artery crossed the upper one-half of the cricothyroid membrane in all but one specimen. Branches of the cricothyroid artery penetrated the membrane and ascended along the undersurface of the thyroid cartilage. Unilateral superior thyroid artery injection demonstrated anastomoses between right and left cricothyroid arteries. In 54% of specimens, the superior thyroid artery coursed anterior to the sternothyroid muscle and then the lateral edge of the cricothyroid membrane. The membrane was also crossed by venous tributaries to the superior and inferior thyroid veins. To lessen the possibility of complications following cricothyroidostomy, a knowledge of the dimensions, relations, and vasculature of the cricothyroid membrane is of inestimable value.

Aged↗
PubMed1996

Effects of intraluminal and extracorporeal inferior vena caval bypass on canine hemodynamics.

OBJECTIVE: To compare inferior vena cava-right atrial extracorporeal bypass with intraluminal atriocaval shunting during hepatic vascular isolation. DESIGN: Prospective, randomized, controlled animal study. SETTING: University research laboratory. SUBJECTS: Adult mongrel dogs (n = 5) weighing 20 to 27 kg. INTERVENTIONS: Anesthetized dogs underwent laparotomy and sternotomy for vascular isolation. For atriocaval shunting, 20- and 24-Fr intraluminal shunts were inserted into the inferior vena cava via right atriotomy. For extracorporeal bypass, each animal underwent inferior vena cava, portal vein, and right atrial cannulation for venovenous bypass, utilizing a centrifugal pump. Hemodynamic data were recorded at baseline and at intervals after caval occlusion, Pringle maneuver, and caval occlusion with Pringle maneuver. MEASUREMENTS AND MAIN RESULTS: Isolated Pringle maneuver and caval occlusion with Pringle maneuver produced significant reductions in mean arterial pressure (MAP) and cardiac output, irrespective of pulmonary artery occlusion pressure. Extracorporeal bypass, including both caval and portal venous return, produced significant increases in MAP and cardiac output during caval occlusion with Pringle maneuver, while atriocaval shunting and extracorporeal bypass without portal venous return did not improve MAP or cardiac output. CONCLUSION: Venovenous extracorporeal bypass with portal return, acting as a right ventricular assist device, is superior to intraluminal atriocaval shunting in maintaining hemodynamic stability during hepatic vascular isolation.

Animals↗
PubMed1996

Abdominal wall reconstruction after temporary abdominal wall closure in trauma patients.

We retrospectively analyzed 36 patients requiring temporary abdominal wall closure on admission to a level I trauma center from 1988 to 1992. There were 10 deaths (28%) in the study population. Of the 26 survivors, 8 patients (31%) had primary fascial closure at initial hospitalization, whereas 18 patients (69%) required split-thickness skin grafting to visceral granulation tissue. Of these 18 patients, 13 have had ventral herniorrhaphy at subsequent admission. Eight of these patients had primary fascial closure, 4 required primary fascial approximation with prosthetic onlay reinforcement, and 1 required multiple operations including prosthetic reconstruction and eventual complex tissue transfer. Complications occurred in 3 patients (14%) and included two wound seromas, which were drained nonoperatively, and a wound infection necessitating removal of prosthetic material and subsequent reconstruction with complex tissue transfer. Follow-up reveals no recurrent hernia at 24 months. Abdominal wall reconstruction after temporary closure can be done safely and promptly, with good functional and esthetic results.

Abdominal Injuries↗
PubMed1995

Association of interleukin-4 plasma levels with traumatic injury and clinical course.

OBJECTIVES: To determine if interleukin-4 (IL-4) could be detected in plasma of trauma patients and if IL-4 activity is associated with patterns of clinical events, complications, or outcomes. METHODS: A prospective case series conducted in a tertiary care referral center with a level I trauma center. One hundred patients admitted to the trauma intensive care unit for at least 3 days were included. Plasma concentrations of IL-4 and IgE were determined from admission to intensive care unit discharge. Data on clinical outcome were collected, including death, sepsis, severe sepsis, adult respiratory distress syndrome, pneumonia, and renal dysfunction. RESULTS: Interleukin-4 was detected in the plasma of 87 patients. Patients with an Injury Severity Score of greater than 25 had higher admission IL-4 levels (P = .03) and greater maximal IL-4 levels (P < .001). Admission hypotension (P = .04) and age 30 years or younger (P < .001) were also associated with higher admission IL-4 levels. Increases in IL-4 levels were significantly greater for patients in whom sepsis, severe sepsis, or pneumonia developed (P < .05). A low admission IL-4 level was associated with a greater incidence of nosocomial pneumonia (P < .001). Additional indirect evidence of IL-4 activation included increased plasma IgE levels. CONCLUSIONS: Anti-inflammatory cytokine mechanisms are activated after injury and are associated with the development of infectious complications (sepsis, severe sepsis, and pneumonia). Exogenous administration of interleukin-4 should be evaluated as an experimental therapeutic approach after trauma and associated sepsis.

Adult↗
PubMed1995

Biloma and biliary fistula following hepatorraphy for liver trauma: incidence, natural history, and management.

From 1986-1992, more than 6250 patients were admitted to a Level I Trauma Center, with 175 patients requiring hepatorraphy. Eleven patients (6%) developed either a biloma (1), biliary fistula (2), or both (8 patients). Patients' ages ranged from 15-40 years with a mean Injury Severity Score of 23. Seven patients (64%) suffered penetrating injury and four (36%) were victims of blunt trauma. The right lobe was injured in 10 patients (91%), with one patient (9%) sustaining left lobe injury. All liver injuries were either grade 3 (seven patients, 64%) or grade 4 (four patients, 36%). No patient sustained extrahepatic biliary tract injury. Bilomas and fistulas were diagnosed 14-30 days post injury (mean 24 days) by CT and HIDA scans. All were managed by CT-guided percutaneous drainage. One patient also required percutaneous transhepatic cholangiography with biliary stent placement due to bile ascites. Fistulas persisted from 5-120 days (mean 44 days). No patient required further operative intervention and all fistulas closed spontaneously without complication.

Adolescent↗
PubMed1994

Lipopolysaccharide-reactive immunoglobulin E is associated with lower mortality and organ failure in traumatically injured patients.

Antilipopolysaccharide (anti-LPS) immunoglobulin G (IgG) and IgM have been associated with protection from LPS effects in vivo. We investigated the presence of IgE and anti-LPS in 32 patients that had experienced severe traumatic injury and in 35 healthy volunteers; we also investigated whether IgE anti-LPS was associated with important clinical events. Plasma samples were collected daily from patients in the intensive care unit and on one occasion from volunteers; the samples were assayed for IgE anti-LPS. IgE anti-LPS was assayed by enzyme-linked immunosorbent assay with monoclonal anti-human IgE as the capture antibody. Detection was accomplished with biotin-labeled LPS (Escherichia coli J5 mutant) followed by streptavidin-peroxidase with 2,2'-azino(3-ethylbenzthiazoline)sulfonic acid as the substrate. The assay was demonstrated to be specific for IgE and LPS-biotin by nonreactivity of control sera with high-titer anti-LPS IgG and IgM and by inhibition with unlabeled LPS. IgE anti-LPS was detected in 1 of 35 healthy controls (2.9%) and 25 of 32 traumatically injured patients (78%) (P < 0.001). The presence of IgE anti-LPS was associated with a lower incidence of death (P = 0.026) and of renal failure (P = 0.0012). There was no apparent temporal relationship between detection of IgE anti-LPS and clinical events. IgG anti-LPS was detected more frequently in patients that were positive for IgE anti-LPS (P = 0.06) but was not associated with clinical events. The inability to detect IgE anti-LPS may be related to adverse clinical events through depletion of specific IgE due to LPS exposure after trauma or through saturation of the assay by IgE with other specificities. We have reported increased total IgE concentrations in these patients. (J.T. DiPiro, R.G. Hamilton, T. R. Howdieshell, N. F. Adkinson, and A. R. Mansberger, Ann. Surg. 215:460-466, 1992).

Acute Kidney Injury↗