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Biomedical subjects

H C Polk

Publications and source records attributed to H C Polk.

At least 73 records · Page 4Linked to original sources
PubMed1995

Second place winner of the Conrad Jobst Award in the gold medal paper competition. Increased antibiotic effectiveness in a model of surgical infection through continuous infusion.

As long as infection remains the most common cause of morbidity and mortality in severely ill patients, there exists the need for more effective anti-infective therapy. The current study was undertaken to determine whether continuous infusion (CONT) is superior to intermittent administration (INT) of an equal amount of cefazolin (CEF) in a model of surgical infection. The thigh suture model consists of the surgical placement of 1 cm of cotton suture with absorbed K. pneumoniae into the thigh muscle of mice. The experimental groups were: 1) controls (n = 20) with thigh suture inoculation and treatment with intraperitoneal (IP) sterile saline; 2) CONT infusion group that received CEF at 60 mg/kg IP 30 minutes before inoculation followed by CONT IP infusion at 180 mg/kg/day (n = 22) for 3 days; and 3) INT injection group that received CEF at 60 mg/kg IP 30 minutes before inoculation followed by INT IP injections every 8 hours at 180 mg/kg/day (n = 20) for 3 days. All CEF treated animals received identical quantities of total CEF, and all groups were followed for 10 days. The control and INT CEF groups had 20% survival, whereas the CONT CEF group had 81% survival, (P < 0.001). Continuous CEF yielded constant serum levels of 19 +/- 1 micrograms/mL, whereas INT injections resulted in peak serum level of 74 +/- 12 micrograms/mL at one minute but declined to 3.9 +/- 0.9 micrograms/mL in 2 hours. Although there was statistically significant tissue bacterial growth in the INT injection group, there was extensive tissue bacterial clearance in the CONT infusion group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Peer review is an effective screening process to evaluate medical manuscripts.

OBJECTIVE: To measure the effectiveness of peer review as a screening process to evaluate medical manuscripts. DESIGN: Retrospective. SETTING: The editorial office of the American Journal of Surgery (AJS). METHOD: A MEDLINE search was conducted of publications from 1984 to 1992 for manuscripts that were identical or similar to those rejected by AJS between January and December 1989. Manuscripts that were submitted to AJS by foreign authors were excluded because of the presumed difficulty in tracking foreign-language publications. MAIN OUTCOME MEASURES: The percentage of manuscripts rejected by AJS that were subsequently published in journals indexed by MEDLINE, the time from rejection to ultimate publication, and the journal of publication. The reasons for rejection were also documented. We assumed that the majority of rejected manuscripts would be published within 3 years after rejection. RESULTS: One hundred twenty-five manuscripts submitted by North American authors were rejected by AJS in 1989, and 62% were not subsequently published in another core medical journal during the study period. The average duration between rejection and later publication was 17 months. Of those manuscripts subsequently published, 54% appeared in general surgical journals, including 12% that were revised, reevaluated, and later accepted by AJS. Twenty-nine percent of the rejected manuscripts were published in specialty medical journals, 10% in state and local journals, and the remainder in general medical journals. Twenty-eight percent of the authors of rejected manuscripts had previously and subsequently published manuscripts on very similar subjects. CONCLUSIONS: Our data indicate that the review process serves as a sieve and influences whether manuscripts are published in core medical journals. This was demonstrated by the fact that rejected manuscripts often were not published in other indexed medical journals.

Manuscripts as Topic↗
PubMed1994

Interferon gamma administration increases monocyte HLA-DR antigen expression but not endogenous interferon production.

OBJECTIVE: To determine the effect of the adjuvant administration of interferon gamma on monocyte HLA-DR antigen expression and mitogen-stimulated interferon gamma production following injury. DESIGN: Double-blind, randomized, placebo-controlled trial. SETTING: University Hospital, Newark, NJ, a level I trauma center. PATIENTS: Persons older than 16 years with an Injury Severity Score greater than 20 and documented bacterial contamination at the time of injury (N = 98). INTERVENTIONS: Recombinant human interferon gamma (n = 46; 0.1 mg subcutaneously) or placebo (n = 52) was given for 10 days following injury. OUTCOMES: Incidence of major infection, monocyte and lymphocyte cell surface antigen expression, and interferon gamma production at multiple time points following injury. RESULTS: Peripheral monocyte HLA-DR was measured as percent of cells staining positive and as mean channel fluorescence. Both values were significantly increased in the interferon gamma group compared with the placebo group on days 3, 5, 8, and 11. The incidence of major infection was unaffected by interferon gamma administration. Infection decreased percent of HLA-DR-positive monocytes and mean channel fluorescence as compared with noninfected patients on postinjury days 8 and 11 in the placebo group but not in the interferon gamma group. Interferon gamma production improved from 3 +/- 3 U/mL on day 1 to 15 +/- 10 U/mL by day 30 but was always significantly lower than normal (25 +/- 3 [mean +/- SD] U/mL). Interferon gamma production was unaffected by either infection or interferon gamma administration. CONCLUSIONS: Interferon gamma administration after injury stimulated monocyte HLA-DR antigen expression and density but failed to improve interferon gamma production, a T-cell-mediated function. The incidence of infection was not decreased by the administration of interferon gamma for 10 days. Improvement in monocyte HLA-DR antigen expression did not correlate with a global restoration of immune function, and other interventions will be necessary to decrease infection after injury.

Adult↗
PubMed1994

Improved survival in simulated surgical infection with combined cytokine, antibiotic and immunostimulant therapy.

A study was performed to find an ideal combination and sequence of cytokines, antibiotics and immunorestorative agents to enhance survival from serious infection. The effects of combinations of granulocyte-macrophage colony-stimulating factor (GM-CSF), tumour necrosis factor (TNF) alpha, the immune adjuvant muramyl dipeptide (MDP) and two systemic antibiotics were studied in a validated murine model of surgical infection. A single cotton suture containing absorbed Klebsiella pneumoniae was placed into the thighs of mice to produce local and systemic infection. Control mice received a volume of subcutaneous saline equal to that of the therapeutic agent; only 18 per cent survived 9 days after infection. The survival time of mice treated with any single agent was similar to that of controls. The group given maximal combined therapy (65 mice) received GM-CSF, TNF-alpha, MDP, and ampicillin-sulbactam or cefoxitin for 6 days. The survival rate in this group 9 days after the introduction of infection was 84-90 per cent (P < 0.0001), suggesting that specific combinations of cytokines, immunostimulants and antibiotics may be useful in combating lethal infection.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1994

The contribution of open extremity fractures to infection in multiply injured patients.

We sought to determine whether a contaminated open fracture was a reliable component for calculating the Outcome Predictive Score in patients with multiple injuries. We studied 41 patients whose primary source of contamination was open extremity fractures. Only one of the 41 patients developed osteomyelitis. The rate of infection from an open fracture is minimal in the multiply injured patient. Inclusion of patients with open fractures in studies that assess the likelihood of infection and the value of anti-infective agents incorrectly identified patients for clinical trials and results in an overestimation of survival based on the Outcome Predictive Score. These findings suggest that open fractures should be excluded as an entry criterion in future clinical trials.

Bacterial Infections↗
PubMed1994

Pneumonia in the surgical intensive care unit. Immunologic keys to the silent epidemic.

OBJECTIVE: The authors undertook a prospective study of trauma victims in the intensive care unit (ICU) to investigate the clinical course of pneumonia and the local and systemic immune responses to the pneumonia. SUMMARY BACKGROUND DATA: The silent epidemic of pneumonia has been an "unappreciated killer" in terms of being overlooked in surgical ICUs for the past 5 years, and specifically, the most common major infection after severe trauma. Little is known about the immune response to an acute pulmonary infection. METHODS: The authors studied 50 consecutive, critically ill trauma patients, with a mean injury severity score of 28 +/- 2, who developed pneumonia while ventilated mechanically. Patients were observed clinically, and specific immunologic parameters, including major histocompatibility antigen HLA-DR, complement receptor (CR3), and Fc receptor (FcRIII), were measured in circulating and local alveolar leukocytes for up to 30 days. Eleven patients provided unique clinical data via bronchoscopy for unilateral pneumonia, with collection of bronchoalveolar lavage (BAL) fluid from both the infected and uninfected sides. RESULTS: Patients developed clinical pneumonia 5.3 +/- 0.4 days after admission to the ICU. At diagnosis, mean temperature was 101.4 F, white blood cell count was 16,000/mm3, arterial oxygen tension was 104 +/- 14, fraction of inspired oxygen was 0.47, and positive end-expiratory pressure was 5. Thirty patients (Group A) recovered relatively promptly; 20 patients had prolonged illnesses (Group B), 15 of whom ultimately survived, and five of whom died. Patients with poor outcomes had greater leukocytosis (p < 0.05) and temperature elevation (p < 0.05) after 5 days of pneumonia. Immunologically, peripheral leukocyte expression of HLA-DR, FcRIII, and CR3 was equivalent in both groups. However, the expression of all three antigens on local alveolar leukocytes was decreased to a greater extent in the poor outcome group compared to the good outcome group, evident before any clinical differentiation between the two outcome groups. CONCLUSIONS: Pneumonia prolonged duration of mechanical ventilation, ICU and hospital stay, and overall infectious morbidity. Although immune suppression has been recognized as a result of initial injury, the development of pneumonia coincided with the nadir of immune function. Poor outcome patients were clinically identifiable 5 days after pneumonia and immunologically identifiable within 2 days. Moreover, there was localized suppression of pulmonary leukocytes at the site of the infiltrate compared to the uninfected lobes. This same alteration was noted in experimental Klebsiella pneumoniae pneumonia. This evidence suggests that there is active immune participation within the respiratory system. It also suggests that there are predispositions to pulmonary infections, and it may allow immune modulation targeted to pulmonary leukocytes to hasten clinical recovery and minimize pulmonary dysfunction.

Adult↗
PubMed1994

Detection of intraabdominal abscess by serum lysozyme estimation.

BACKGROUND: The failure of new, innovative, and often expensive tests to show the presence of intraabdominal infection caused us to reexamine the value of an inexpensive and almost forgotten one. Lysozyme is a bacteriolytic enzyme located within the lysosomes of phagocytic cells including leukocytes. METHODS: We measured serum concentrations of lysozyme by a standard turbidimetric method in both a murine model of intraabdominal infection and in trauma patients with intraabdominal abscesses or other acquired infections. RESULTS: In mice with intraabdominal abscess secondary to cecal ligation and puncture (n = 35) serum lysozyme activity increased compared with sham-operated controls (n = 20; p < 0.001). In trauma patients with intraabdominal abscess after injury and surgery (n = 19), there was also an increase in serum lysozyme activity compared with controls (n = 15; p < 0.001) or with patients with lung infection (n = 21; p < 0.001). The increase of serum lysozyme activity occurred before intraabdominal sepsis was clinically apparent. CONCLUSIONS: In this study, serum lysozyme concentration has a high specificity related to the presence of an intraabdominal abscess and is an indirect measure of the sequestration of leukocytes to the site of an established or developing collection of intraabdominal pus. The estimation of serum lysozyme may be an aid to differentiate critically ill patients with a potential occult intraabdominal abscess.

Abdomen↗
PubMed1993

Murine interferon-gamma enhances resistance to infection with strains of Pseudomonas aeruginosa in mice.

This study focused on the role of recombinant murine interferon-gamma (rMuIFN-gamma) in modulating resistance to infections produced by Pseudomonas aeruginosa in mice. CBA/C mice were treated with rMuIFN-gamma, exposed to thermal injury, and challenged with P. aeruginosa organisms. Survival of infected, burned mice was determined over a period of 14 days and compared with control animals not receiving rMuIFN-gamma. Two clinical isolates of P. aeruginosa that differed originally in the ability to produce metalloproteases, were used to infect the mice. When the mice were pretreated with rMuIFN-gamma before the infection, no statistically significant differences in survival were observed with either of the two strains of bacteria compared to controls. However, when mice were pretreated and injected therapeutically with rMuIFN-gamma (continued receipt of rMuIFN-gamma after infection), there was a significant protective effect in animals infected with one of the strains of P. aeruginosa. We conclude that rMuIFN-gamma may be useful in treating infections with certain strains of P. aeruginosa in mice.

Animals↗
PubMed1993

Factors influencing the risk of infection after trauma.

Infection after injury is characterized by the degree of contamination, the duration of attendant hypotension, and the delay in definitive surgical treatment. Factors further influencing this outcome include the age of the patient and, in most U.S. urban centers, the general health of the patient. Current antibiotic treatment of such patients may soon be assisted by selective and sequential immunostimulants, which are increasingly more specific for defined defects in host defenses after injury. An ever more significant contribution to morbidity and mortality on trauma services is pneumonia, which is often caused by gram-negative aerobes. The design of clinically significant trials with respect to infection in the injury patient will be more difficult and complex.

Humans↗
PubMed1993

A biologic basis for altered host defenses in surgically infected abscesses.

OBJECTIVE: This study determines whether there are any differences in several immunologic parameters in circulating peripheral blood leukocytes, serum, and plasma compared with pus leukocytes, and supernatant of various types of abscess. SUMMARY BACKGROUND DATA: Although there have been reports of high lysozyme levels and low complement levels within pus, there has been no systemic comparison of concentrations of these substances and others within pus compared with those within peripheral blood. METHODS: Peripheral blood and abscess pus were collected from 31 patients with abscesses and percent and mean channel of monocytes expressing complement receptor and major histocompatibility antigen HLA-DR, the percent and mean channel of polymorphonuclear leukocytes (PMN) expressing complement receptor, lysozyme level, and levels of total hemolytic complement, iC3b, C5b-9, and immunoglobulins were measured within both pus and peripheral blood. RESULTS: Percent of monocytes expressing HLA-DR and percent of monocytes and PMN expressing complement receptor, total hemolytic complement, and IgM were reduced within pus compared with peripheral blood, whereas the mean channel of monocytes expressing HLA-DR and the mean channel of PMNs expressing CR3, C5b-9, and lysozyme were increased in pus. CONCLUSIONS: There are marked differences in immunologic parameters measured within pus of abscesses versus that seen in peripheral blood.

Abdomen↗
PubMed1993

The two-edged sword of large-dose steroids for spinal cord trauma.

OBJECTIVE: In 1990, large-dose steroid administration was advocated in spine-injured patients to lessen neurologic deficits. The authors undertook both prospective and retrospective studies to evaluate the response of such profound pharmacologic intervention. SUMMARY BACKGROUND DATA: Of all sources of nonfatal injury, spinal cord trauma remains the most devastating in both cost and impact on the quality of the patient's life. One study found that routine large-dose steroid administration after injury lessened the extent of neurologic injury. After uncommonly prompt and broad lay press publicity, this practice was widely accepted. Biased by knowledge of the known immunosuppressive effects of steroids, the authors suspected that pneumonia was both more frequent and severe in steroid-treated patients. METHODS: Thirty-two patients with cervical or upper thoracic spinal injuries (C3-6, 20 patients; C6-7, 6 patients; and T1-6, 6 patients) were studied at an urban level I trauma center from January 1987 to February 1993. Complete spinal cord injury was present in 22 of 32 patients; 14 patients received steroids postinjury. There was no difference in mean age, cord level, age-adjusted injury severity score, or the percent of injury severity score caused by the spinal injury. RESULTS: The length of hospital stay was longer in steroid-treated patients (S) than in nonsteroid (NS) patients, that is, 44.4 days versus 27.7 days, respectively (p = 0.065). Seventy-nine per cent of S patients had pneumonia compared with 50% of NS patients (p = 0.614). There was no statistical difference in the episodes of pneumonia per patient between the two groups (p > 0.05). Prospectively, the authors evaluated sequentially several parameters known to be important in human immune responses to bacterial challenges in nine S and five NS patients. In S patients, both the per cent and density of monocyte class II antigen expression and T-helper/suppressor cell ratios were lower than in NS patients. However, S patients did have an initially higher, earlier boost in some host defense parameters that rapidly declined, and their subsequent response was both blunted and delayed. These differences became even clearer when stratified according to cord level and incomplete versus complete cord status. Not surprisingly, infected patients, whether S or NS, had lower levels of monocyte antigen expression, CR3, and helper/suppressor ratios. CONCLUSIONS: These data do not permit a judgment to be made whether neurologic status was improved by S administration. It is known that vital immune responses were adversely affected, that pneumonia was somewhat more prevalent, and that hospitalization was prolonged and costs therefore increased by an average of $51,504 per admission. Further clinical studies will be needed to determine to what extent these observations offset the putative benefits of large-dose steroids in the treatment of spinal trauma.

Adult↗
PubMed1993

Lymphocyte subset responses to trauma and sepsis.

One hundred five trauma patients admitted to three trauma centers with injury Severity Scores of 20 or greater had lymphocyte phenotypic subsets characterized throughout their hospital course. Total lymphocytes, pan-T (CD2), helper T (CD4), suppressor T (CD8), pan B (CD20), and DR expressing lymphocytes were quantitated by monoclonal antibodies and flow cytometric analysis. Results were analyzed between three patient groups: uninfected, uneventful recovery (n = 64); major infection (n = 26); and dead (n = 15; 7 with sepsis). A significant lymphopenia, maximal at 3 days, occurred in the first postinjury week compared with controls (p < 0.05), which recovered over the study period. A hierarchical distribution was found between the three outcome groups with the lowest numbers of several lymphocyte phenotypes in those who died. T helper and suppressor cells were similarly affected, but lowest in patients destined to develop infection or die. The helper-suppressor ratio, however, was similar in all three outcome groups. Therefore, modulation early after injury aimed at restoring these subsets may reduce the risk of subsequent infection.

Adolescent↗
PubMed1993

Regional and systemic immune responses in a murine model of empyema.

The extent to which circulating leukocytes reflect functional capacity at the site of infection is unclear despite a century of debate. We conducted experiments designed to clarify those relationships as well as the relationship of pleural and peritoneal responses to infection. Empyema was established in inbred CBA/J mice by introducing Escherichia coli and Bacteroides fragilis into the thoracic cavity through a limited thoracotomy. Walled off abscesses appeared seven days after the introduction of infection. Cell surface expression of murine class II major histocompatibility antigen was measured in peripheral leukocytes, thoracic and peritoneal cavity exudate leukocytes and abscess cells for 60 days after the introduction of infection. The peripheral antibody response was determined by measuring immunoglobulin M (IgM) and immunoglobulin G (IgG) specific for the two organisms. The results demonstrated that, after introduction of infection into the thoracic cavity, mice mounted a specific systemic humoral immune response by producing IgM and IgG. There was a pronounced concomitant cellular response in thoracic and peritoneal cavity exudate cells. However, there was no evidence of a systemic cellular response in circulating lymphocytes or monocytes and polymorphonuclear leukocytes measured as a single group. We conclude from these experiments that measurements of peripheral immune parameters may adequately reveal the humoral response to infection, but it does not reflect the local immune cellular response. Furthermore, a special relationship exists between the peritoneal and the thoracic cavities, whereby an inflammatory process in the thoracic cavity leads to a marked activation of inflammatory process in the peritoneal cavity without affecting peripheral circulating cells to the same extent.

Animals↗
PubMed1993

Laparotomy wound closure with absorbable polyglycolic acid mesh.

A knitted mesh of polyglycolic acid was used successfully in 59 critically ill patients to bridge abdominal wall defects and prevent evisceration after celiotomy. Polyglycolic acid knit mesh was used in 31 patients who had extraordinary visceral edema after resuscitation and the mesh was inserted to avoid excessive tension in the wound closure, 15 patients who had abdominal wall defects after adequate débridement for necrotizing fasciitis, and 13 patients who had losses of abdominal wall tissue caused by trauma or after resection of tumor. There were 14 hospital deaths among the seriously ill patients. Thirteen patients had enterocutaneous fistulas, seven of which occurred after meshes were inserted. The mesh material was strong, pliable and easily inserted in large abdominal wall defects. The polyglycolic acid knit mesh was infiltrated by granulation tissue within three weeks, including in heavily contaminated wounds. Two to three months after insertion, the material was absorbed. Hernia defects were common four to six months after the meshes were inserted and repairs were performed electively after patients had recovered from the primary problems. We conclude that absorbable polyglycolic acid knit mesh can be a useful technique for quickly achieving a secure tension-free closure of abdominal wounds.

Humans↗
PubMed1993

Prospective randomized study of piperacillin/tazobactam therapy of surgically treated intra-abdominal infection. The Piperacillin/Tazobactam Intra-Abdominal Infection Study Group.

A randomized prospective trial was undertaken in adult patients with serious intra-abdominal infections to determine whether a new combination of antibiotic therapy could prove as efficacious as the combination that has been widely used in practice in the recent decade (clindamycin and gentamicin). Three hundred thirty-one patients were randomized in a 2:1 ratio, with the larger number of patients being treated parenterally with piperacillin and tazobactam. The results showed that both the clinical and microbiologic performance of the piperacillin/tazobactam combination was better than that of clindamycin and gentamicin. This clinical equivalence permits overall cost savings without compromising the existing quality of antimicrobial therapy for intra-abdominal infection.

Abdomen↗
PubMed1992

A randomized prospective clinical trial to determine the efficacy of interferon-gamma in severely injured patients.

Many aspects of the normal immune response are depressed after severe injury. Reduced monocyte human leukocyte antigen-DR (HLA-DR) levels have closely correlated with the development of major infection. After a pilot study with recombinant interferon-gamma (rIFN-gamma) showed restoration of depressed HLA-DR levels after major injury, a multicenter, prospective, randomized, double-blind trial was conducted. Two hundred thirteen trauma patients who were at high risk of infection received either placebo or rIFN-gamma (100 micrograms) subcutaneously each day for 10 days after admission. One hundred ninety-three patients were evaluable with respect to primary end points. Patients treated with rIFN-gamma were older (p = 0.10) and had more severe modes of injury (p = 0.02). By the third day, both monocyte HLA-DR antigen expression and outcome predictive score were significantly better in the rIFN-gamma-treated group than in the placebo group (p = 0.0001 and p = 0.0006, respectively). Nine deaths occurred in patients treated with rIFN-gamma compared with 12 deaths in the placebo group (p = 0.46). Major infections requiring surgical drainage or debridement occurred in 17 patients treated with rIFN-gamma compared with 22 treated with placebo. No difference between treatment arms was noted in overall major or minor infection rates, but there were fewer severe infections that required reoperation or computer tomographic-guided drainage in patients receiving IFN-gamma. While these results suggest that rIFN-gamma may be useful in some aspects of infection in the patient with severe trauma, a larger trial with longer treatment will be needed to prove the comprehensive value of rIFN-gamma.

Adult↗