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Biomedical subjects

H C Polk

Publications and source records attributed to H C Polk.

At least 109 records · Page 6Linked to original sources

Shock, transfusion, and pneumonectomy. Death is due to right heart failure and increased pulmonary vascular resistance.

To determine the physiologic cardiopulmonary abnormalities leading to death when pneumonectomy is required to stop bleeding in patients in hemorrhagic shock, we compared cardiopulmonary responses to resuscitation in pigs undergoing hemorrhagic shock alone, pneumonectomy alone, and hemorrhagic shock plus pneumonectomy. Four shock-plus-pneumonectomy pigs died acutely from right heart failure. When the five remaining shock-plus-pneumonectomy pigs were compared to the two control groups, pulmonary vascular resistance (PVR) increased to significantly higher levels than would be expected from the increase in PVR noted with resuscitation from shock alone and pneumonectomy alone. Right ventricular compensation maintained cardiac index in the hemorrhage-alone group and the pneumonectomy-alone group but could not maintain cardiac index in the shock-plus-pneumonectomy group, despite maximal increases in right ventricular systolic pressure, heart rate, and right ventricular end diastolic volume. These data indicated that resuscitation from shock plus pneumonectomy cannot be effectively accomplished because increased PVR leads to right ventricular failure, which limits left ventricular preload to levels that are insufficient to maintain cardiac index.

Animals↗

Packing and planned reexploration for hepatic and retroperitoneal hemorrhage: critical refinements of a useful technique.

We evaluated 35 consecutive patients treated with temporary intraabdominal packing for control of bleeding to determine factors that could improve hemorrhage control, morbidity from infection, and mortality. Twelve patients could not be resuscitated from hemorrhagic shock and died in the operating or recovery room. Bleeding was controlled in the remaining 23 patients; however, five (22%) died of complications other than hemorrhage. Intra-abdominal abscesses occurred in seven of the 21 patients who survived longer than 5 days and were more frequent in patients who had gastrointestinal perforation (50% versus 27%) and selective hepatic artery ligation (80% versus 19%). Four patients with either retrohepatic vena cava injury, hepatic vein injury, or both, were packed without attempted repair; three underwent delayed repair and survived. Coagulopathy occurred in 55% of patients who received greater than 15 units of blood before packing but in only 17% who received less than 15 units. The abdomens of ten patients were closed with a prosthetic mesh which did not prevent hemorrhage control, and only one patient developed a wound infection compared to 42% of patients with primary suture closure. We therefore conclude: 1) packing is more effective if instituted early (when less than 15 units of blood have been transfused) and is not contraindicated before either repair of retrohepatic vena cava injury, hepatic vein injury, or both; 2) selective hepatic artery ligation should be avoided if packing alone stops bleeding; 3) abdominal closure with a synthetic mesh decreases the incidence of wound infection; and 4) patients should be returned to the operating room for repacking if 24-hour postoperative blood requirements exceed 10 units.

Abdominal Injuries↗

Containment as a mechanism of nonspecific enhancement of defenses against bacterial infection.

Observations made during the study of nonspecific enhancement of antimicrobial host defenses permitted some physiologic dissection of the anatomic basis for normal protective processes. Local growth of bacteria in the hind limb in muramyl dipeptide-treated mice was suppressed modestly, but lymphatic filtration was markedly improved, especially between the ipsilateral groin and iliac lymph nodes. Spontaneous containment, when it occurred in saline-treated controls, proceeded similarly. Certain regional lymph nodes acted to restrict the dissemination of bacteria from an anatomically isolated infection, reducing the degree of bacteremia and improving survival. Containment of local bacterial infection appears more important in a favorable host response than does dispersion and is accentuated by muramyl dipeptide.

Acetylmuramyl-Alanyl-Isoglutamine↗

A randomized prospective study of topical antimicrobial agents on skin grafts after thermal injury.

We prospectively studied 52 consecutive patients who were treated by early tangential excision and grafting following thermal injury. The usefulness of two topical antimicrobial agents--0.5% silver nitrate (Ag) and neomycin (1 gm/liter) plus bacitracin (50,000 units/liter) (NB)--was compared with the effectiveness of Ringer's lactate (RL) for prevention of autogenous skin-graft loss due to infection. Graft loss of 10 percent or more occurred in 17 patients (33 percent)--due to infection in 16. Skin-graft loss was a minor problem in patients with less than 20 percent total body surface area (TBSA) burn (Ag: 0 of 6, NB: 1 of 6, RL: 1 of 5). The use of either antimicrobial (Ag or NB) resulted in less graft loss (1 of 14) than RL (4 of 6; p less than 0.05) in the 20 to 40 percent TBSA burn group. Large burns (greater than 40 percent) had a very high incidence of at least 10 percent graft loss (67 percent) regardless of treatment. Infection in the area of graft loss was caused by antibiotic-resistant organisms or yeast in 50 percent of the Ringer's lactate group and the entire neomycin plus bacitracin group. No graft infections were caused by resistant organisms or yeast in the silver nitrate group. This study demonstrates that topical antimicrobial agents reduce infection-related skin-graft loss in patients with medium-sized (20 to 40 percent TBSA) burns and that neomycin plus bacitracin is associated with rapid emergence of drug-resistant organisms whereas silver nitrate is not.

Administration, Topical↗

An experimental assessment of the effect of blood transfusion on susceptibility to bacterial infection.

Clinical investigations in patients who have undergone transplantation and patients with cancer and infection suggest that blood transfusions have an immunosuppressive effect. To investigate the impact on responses to infection, an experimental transfusion model was developed in the rat with allogeneic or syngeneic transfusions. Animals were given either a moderate or severe bacterial challenge, both simulating a clinical surgical infection, immediately after transfusion or 1 week later; hypotension and hemodilution were especially avoided. Blood transfusion adversely affected the animals' capacity to resist immediate moderate challenge, but not a later one. The effect was maximized by allogeneic transfusion but was not demonstrable after severe bacterial challenge, whether immediate or late.

Animals↗

Comparison of antibody response with delayed hypersensitivity in severely injured patients.

Twenty-seven severely injured patients had antibody response to gram-negative organisms measured of whom 25 also had skin testing. Twenty-three patients (92%) were anergic at admission. Injury Severity Scores were greater in patients who remained anergic for three weeks compared with patients whose skin tests became positive. Patients with major infection had longer anergy duration than uninfected patients. Twenty-two (81%) of 27 anergic patients mounted antibody responses. Initial bacterial contamination determined the clinical outcome and antibody response. Six of eight patients with moderate contamination mounted IgM responses to all organisms and/or an IgG response to Escherichia coli, and they remained uninfected. Of the other two patients, one died, and the other developed chronic infection. Seven of eight patients with heavy contamination developed major sepsis despite mounting several antibody responses. Six patients without contamination mounted no antibody responses and remained uninfected.

Antibodies, Bacterial↗

Individual treatment for malignant melanoma.

Much has been learned in the recent decade about the predictable biologic behavior of cutaneous malignant melanoma. Indeed, such knowledge permits highly individualized treatment based on simple demographic data on the patient, location of the lesion, and its thickness according to the Breslow scale. The thoughtful surgeon may individualize his treatment according to the likely biologic behavior of the tumor, minimizing treatment morbidity while maintaining optimum results from primary and secondary surgical treatment.

Combined Modality Therapy↗

Association of cytomegalovirus infection with increased morbidity is independent of transfusion.

Forty-three consecutive trauma patients with an injury severity score greater than 20 were studied prospectively for evidence of cytomegalovirus (CMV) infection. Twenty-one patients had serologic conversion: 3 with primary CMV infections, 18 with reactivation of CMV infection (CMV group). Twenty-two patients had no serologic conversion (no CMV group). To differentiate the effects of CMV and transfusion, the CMV group and the no CMV group were each divided into high (more than 10 units) and low (less than 10 units) transfusion subgroups. Similar fever peaks, leukocyte counts, lymphocyte counts, and incidence of major bacterial sepsis were recorded for the four subgroups. Several factors were significantly associated with CMV infection independent of transfusion, including increased duration of major bacterial sepsis and number of septic episodes per patient; prolonged duration of anergy; increased duration of intensive care unit and hospital stay; increased duration of ventilatory assistance and rate of tracheostomy; and increased suppressor cells, decreased helper: suppressor ratios, increased functional suppressor cells, and increased natural killer cells. Although mortality was not increased with CMV infection, our data suggest that such infection after trauma may delay recovery from major bacterial infection, often resulting in a major increase in morbidity.

Antibodies, Viral↗

Experimental and clinical significance of endotoxin-dependent HLA-DR expression on monocytes.

For much of the last decade, an increasing number of surgeons have been interested in objective assessment of cellular contributors to host defense function. In order to study many of these processes, it is apparently desirable that the cells be isolated to the extent feasible for the purpose of analyzing a more or less pure population of cellular elements. The purpose of this paper is to describe the physiologic activation of mononuclear cells that occurs as a result of the isolation process. Therefore, it follows logically that such cells are therein intrinsically less responsive to further physiologic manipulation in vitro. Analyses of such data without an awareness of this intrinsic aberration will undoubtedly lead to misinterpretation of the capacity of such cells for further modulation by immunostimulants or by the intrinsic processes related to injury, anesthesia, and operation. Furthermore, it may indicate that certain agents, e.g., cytokines, are unable to stimulate cellular function when, in fact, the defense function of the cell has been initially stimulated by the isolation procedure. Fractionation of human peripheral blood over Hypaque-Ficoll and subsequent purification of monocytes by adherence to plastic lead to an increase in the relative density of HLA-DR on monocytes. This increase occurred when carried out in endotoxin lipopolysaccharide (LPS)-contaminated or LPS-depleted reagents. LPS, added experimentally to whole blood, enhanced HLA-DR expression on monocytes without further manipulation. Monocyte HLA-DR expression measured in whole blood was reduced in patients with major sepsis (n = 19) compared to normal subjects (n = 10).(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies↗

Enhancement of survival from murine polymicrobial peritonitis with increased abdominal abscess formation.

Muramyl dipeptide (MDP), a purified synthetic immune adjuvant, has been shown to increase murine intraabdominal abscess formation in a monomicrobial model using Bacteroides fragilis. This effect required live bacteria and was abolished by appropriate antibiotics. A polymicrobial model of peritonitis and abdominal abscess formation using Streptococcus fecalis, Escherichia coli, and B. fragilis was initially used to determine mortality rates at various concentrations and obtain an appropriate LD50. Animals were then pretreated with MDP or its inert buffer and underwent intraperitoneal injection of the appropriate bacterial suspension. Mortality and abdominal abscess formation were then assessed at 2 weeks after injection. There was a significant reduction in mortality (P less than 0.03) in mice treated with MDP compared to the controls. In surviving animals, there was also a significant increase in the number of animals forming abscesses (P less than 0.05) following treatment with MDP. This study has shown that nonspecific immune stimulation by MDP provided enhanced protection against a polymicrobial intraperitoneal challenge and paradoxically increased the formation of abdominal abscesses at the same time. This may be regarded as enhancement of the natural history of survival from peritonitis via bacterial containment through intraabdominal abscess formation, a manifestation of beneficial outcome in experimental peritonitis.

Abdomen↗

Comparison of trauma assessment scores and their use in prediction of infection and death.

Current trauma assessment scores do not include an assessment of immune competence and have not been designed to predict late death from or risk of infection. We have compared the use of the Outcome Predictive Score (OPS) with other standard scales to predict clinical outcome after trauma. The OPS combines the Injury Severity Score (ISS) corrected for age (%LD50), degree of bacterial contamination, and monocyte HLA-DR antigen expression on hospital admission. The OPS was compared to the ISS, %LD50, Revised Trauma Score (RTS), Combined Trauma Score-ISS (TRISS), and Anatomical Index (AI). Sixty-one seriously ill patients were studied. Patient outcome was defined as uneventful recovery (n = 18), major infection (n = 27), and death (13 of 16 deaths resulted from infection). The assessment scores were compared for their use in prediction of these outcomes, as well as their ability to distinguish patients with good outcome from those patients who developed major infection or died, and to differentiate survival from death. Only the OPS was able to significantly segregate all five outcome groups (p less than 0.05). Although the age-adjusted ISS distinguished between survival and death (p less than 0.05), only OPS consistently distinguished between good outcome and sepsis/death (p less than 0.05), and therefore best identified the patients who developed infection. AI, RTS, and TRISS had little predictive value.

Age Factors↗

The use of a new assay for detecting antibody to Staphylococcus aureus in severely injured patients.

Investigation of the antibody response to Staphylococcus aureus infection has been hindered by lack of a simple and specific assay. We report an enzyme-linked immunosorbent assay (ELISA) using a strain of S. aureus devoid of Protein A, a frequent cause of false positive results in ELISAs, and have used this assay to study antibody responses of 23 severely injured patients. This IgM ELISA had a diagnostic sensitivity for major Staphylococcal infection of 70% (seven of ten patients with major infection) and a specificity of 92% (12 of 13 patients without major infection). Of three patients with major Staphylococcal infections who mounted no IgM response, two died and the other developed severe chronic Staphylococcal infection, and hence prompt initiation of appropriate therapy was necessary. Furthermore, the ability to mount IgM response to Staphylococcal infections appears to contribute to an orchestrated host defense response against this organism.

Antibodies, Bacterial↗

Institutionally shared trauma rotations are viable solutions to deficiencies in trauma training.

Numerous national trauma leaders have expressed concern about the lack of uniformity of trauma training in this country. In 1984 we instituted a trauma rotation between the University of Louisville (U.L.), with a large trauma volume, and Loyola University (L.U.) in the planning stages of trauma center development. Third year L.U. residents rotated at U.L. in 3-month blocks with an increased level of responsibility monthly, culminating in major decision-making roles and operative treatment under the chief resident's direction. The L.U. residents functioned as full members of the team and not as passive observers. Fifteen L.U. residents and 12 U.L. residents rotated during this period. Yearly major trauma visits, helicopter flights, and trauma service admissions average 1,908, 700, and 1,520, respectively. U.L. chief residents averaged 136 major operative trauma cases and 115 nonoperative trauma cases each were managed during this time period (RRC records greater than 85th percentile for all U.L. residents). L.U. residents performed an average of 30 major operative cases, nine as teaching assistant, in 3 months. Each managed more than 75 nonoperative cases. Several elements are critical in such a multi-institutional rotation: 1) active communication among the program directors, 2) commitment to one sharing arrangement only, 3) financing and malpractice for off-site residents, 4) housing, and 5) the ability to assimilate off-site residents as true trauma team members. The resident-to-resident interplay is crucial and has succeeded because both residency staffs have had excellent early training.(ABSTRACT TRUNCATED AT 250 WORDS)

Academic Medical Centers↗

Interferon-gamma treatment increases HLA-DR expression on monocytes in severely injured patients.

Traumatic injury and sepsis reduce HLA-DR expression on monocytes. This study assessed the effect of interferon-gamma (IFN-gamma) on the expression of HLA-DR on monocytes taken from severely injured patients. The mononuclear layer of each blood sample was incubated with either 500 units IFN-gamma or control media. The mean baseline HLA-DR expression of the trauma group (n = 11) was 32%, significantly less than the mean HLA-DR expression of 91% for the control group (n = 10). In the trauma group, HLA-DR expression after culturing with IFN-gamma was 81%, significantly greater than both the mean baseline HLA-DR expression (32%). In the control group, HLA-DR expression after culturing with IFN-gamma was 94%, similar to the mean baseline HLA-DR expression of 91%. These data confirm that HLA-DR on monocytes of severely injured patients is markedly reduced and show that it can be increased significantly in vitro by IFN-gamma.

Cells, Cultured↗

Pharmacodynamics of antibiotic penetration of tissue and surgical prophylaxis.

The morbidity and mortality of infection in surgical treatment remains substantial. Many principles for the prevention and treatment of surgical infections have been established. Proper selection and preparation of patients and meticulous operative techniques are of primary importance in the prevention of surgical infections. Surgical antibiotic prophylaxis is also beneficial when an adequate tissue level is present before and throughout the duration of the procedure. The level attained in the tissues is dependent on many factors that affect the pharmacokinetics of antibiotic distribution and excretion. One factor is protein binding, which alters the fraction of free drug available for diffusion into tissues. However, the singular importance of this effect on the concentration of antibiotics in tissues is minimal. In surgical prophylaxis, the maintenance of antibiotic tissue activity at the sites of potential infection for the duration of the operation is crucial. Failure to provide persistent antibiotic tissue activity throughout the entire procedure results in an increased number of surgical infections. The pharmacokinetics of distribution and the half-life of antibiotics in the serum are directly related to the duration of activity of antibiotic in the tissue. Antibiotics with longer half-lives maintain levels in the tissues for longer periods than do antibiotics with shorter half-lives. The maintenance of the levels of a given antibiotic is similar for all tissues. The application of the pharmacokinetic properties of antibiotics to surgical prophylaxis can provide the surgeon with certainty that adequate coverage and protection with antibiotics are achieved before and throughout the operation.

Anti-Bacterial Agents↗