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Biomedical subjects

H C Polk

Publications and source records attributed to H C Polk.

At least 37 records · Page 2Linked to original sources
PubMed1999

Heparin and enoxaparin enhance endotoxin-induced tumor necrosis factor-alpha production in human monocytes.

OBJECTIVE: To determine whether heparin or the low-molecular-weight heparin enoxaparin alter lipopolysaccharide (LPS)-induced monocyte activation. SUMMARY BACKGROUND DATA: Heparin is widely used in clinical practice to inhibit the coagulation cascade. However, heparin also is a naturally occurring glucosaminoglycan and a pleiotropic immunomodulator that binds to a variety of proteins. LPS is a component of gram-negative bacteria and is thought to be responsible for many of the deleterious effects seen in sepsis. The binding of LPS to CD14 induces a signaling cascade that results in the release of many inflammatory mediators, including tumor necrosis factor-alpha (TNF-alpha). METHODS: Monocytes from healthy volunteers were isolated and cultured in the presence of saline, LPS (10 ng/ml), heparin (0.1 to 1000 microg/ml), or enoxaparin (0.1 to 1000 microg/ml). In blocking experiments, cells were pretreated for 60 minutes with the monoclonal anti-CD14 antibody MY4 (10 microg/ml) or with isotype-matched control IgG2 (10 microg/ml). TNF-alpha values were measured with enzyme-linked immunosorbent assay. Significance was assessed with analysis of variance. RESULTS: Heparin (10 to 1000 microg/ml) and enoxaparin (1000 microg/ml) significantly enhanced LPS-induced TNF-alpha release. Heparin (1000 microg/ml) or enoxaparin (1000 microg/ml) did not produce TNF-alpha in the absence of LPS. Blockade of CD14 abrogated both LPS-induced TNF-alpha release and the effect of heparin or enoxaparin to enhance LPS-induced TNF-alpha release. CONCLUSIONS: The effect of heparin to enhance LPS-induced TNF-alpha release is a biologic phenomenon that reveals a novel and potentially important host defense mechanism during endotoxemia and sepsis. Binding of LPS to CD14 is necessary to induce this phenomenon, suggesting that both heparin and enoxaparin induce signaling mechanisms that are downstream from the initial binding of LPS on CD14.

Anticoagulants↗
PubMed1999

Quantification of phagocytosis in human neutrophils by flow cytometry.

Phagocytosis represents a central element of the host response to microbial invasion. We describe a flow cytometric method for measuring the kinetics of phagocytosis of two bacteria by human polymorphonuclear leukocytes (PMNs). Over a 60-min period, isolated human PMNs were exposed to Staphylococcus aureus (rapidly phagocytosed) and Klebsiella pneumoniae (slowly phagocytosed). This method distinguished adherent from ingested bacteria by quenching fluorescein isothiocyanate-labeled extracellular bacteria with ethidium bromide. This further allowed the exclusion of dead, highly permeable, and subsequently bright-red fluorescent PMNs. Our experiments with two different bacteria, various PMN-to-bacteria ratios (1:1, 1:10, 1:100), and different individuals proved that 1) flow cytometric analysis is accurate and useful for characterizing phagocytosis, 2) adherent bacteria can be distinguished from ingested bacteria after quenching with ethidium bromide, and that 3) phagocytosis kinetics of two bacteria with different onsets of phagocytosis can be determined by flow cytometry and the assessment of a score that quantifies phagocytosis.

Bacterial Adhesion↗
PubMed1999

The continuing challenge of Fournier's gangrene in the 1990s.

Fournier's disease is a potentially fatal acute, gangrenous infection of the scrotum, penis, or perineum associated with a synergistic bacterial infection of the subcutaneous fat and superficial fascia. Thrombosis of small subcutaneous arterioles with resultant ischemia contributes to the rapid extension of the infection. During a 12-year period, the clinical and operative records of 14 patients with Fournier's gangrene were analyzed. All patients were treated with broad spectrum antibiotics and serial surgical debridements. Nine patients had polymicrobial isolates from the initial wound culture; two patients had Group A Streptococcus species as the sole isolate. The etiology of the infection was identified in 12 patients. Five patients died for an overall mortality of 38 per cent. The mean age of survivors was 51 years compared with 75 years for nonsurvivors (P<0.05). The last six patients in this series survived. The mean hospital stay was 29 days. Four patients (31%) had a prior history of diabetes; however, 11 patients (85%) had elevated serum glucose levels (>120 mg/dL) on admission. All patients were hypoalbuminemic on admission. Survivors had an average serum creatinine on admission of 1.28 mg/dL compared with 3.1 mg/dL for nonsurvivors. Although supportive care is required in these patients, the mainstay for treatment of Fournier's gangrene entails an aggressive approach with frequent and extensive soft tissue debridements to control the invasive nature of the infection with delayed wound coverage once the infection has been controlled. Elderly patients with evidence of renal dysfunction on admission have a poor prognosis despite aggressive therapy.

Adult↗
PubMed1998

Non-operative management of blunt hepatic trauma.

BACKGROUND: Non-operative management is currently considered the treatment of choice in over 50 per cent of adult patients with blunt liver injury. This report reviews the criteria for non-operative management and its potential downside. METHODS: English language publications were reviewed. RESULTS: Most reports from major trauma centres in the USA support the non-operative treatment of patients with blunt liver injury if well established criteria are met. Using such criteria, non-operative treatment is successful in 50-80 per cent of cases. Adjunctive radiological techniques may be helpful in managing some complications of non-operative treatment. CONCLUSION: Non-operative management is safe in haemodynamically stable patients with blunt liver injury. Computed tomography (CT) of the abdomen is extremely useful to document the extent of the damage and the presence of associated injuries, but it is not possible, based on CT alone, to predict failure; careful physiological monitoring in selected patients is indicated to avoid catastrophic complications.

Adult↗
PubMed1998

Modulation of lipopolysaccharide-induced monocyte activation by heparin-binding protein and fucoidan.

Activated polymorphonuclear leukocytes release heparin-binding protein (HBP; also known as CAP37 or azurocidin) from azurophilic granules. HBP is a strong chemoattractant for monocytes that also prolongs monocyte survival and potentiates endotoxin (lipopolysaccharide [LPS])-induced production of tumor necrosis factor alpha (TNF-alpha). We investigated the binding of fluorescein isothiocyanate-conjugated HBP to human monocytes in the presence of EDTA and the polysaccharide fucoidan. EDTA, which chelates divalent cations, has been widely used to study the role of divalent cations in receptor-ligand interactions or enzyme activity. Fucoidan has been used to inhibit the binding of various ligands to scavenger receptors or selectins. Scavenger receptors are multiligand receptors that mediate endocytosis of proteases, protease-inhibitor complexes, lipoproteins, and LPS-lipid A. Fucoidan also interferes with leukocyte rolling by binding to L-selectins (expressed on leukocytes) and P-selectins (expressed on platelets and endothelium). We demonstrate that the binding of the neutrophil-derived protein HBP to monocytes is inhibited in the presence of EDTA and fucoidan. In addition, fucoidan and EDTA abrogate the enhancing effect of HBP on LPS-induced TNF-alpha production. These data provide supporting evidence that HBP binds to a receptor expressed on monocytes. This receptor is dependent on divalent cations and is possibly related to the scavenger receptor. Furthermore, we demonstrate that fucoidan, by itself, stimulates TNF-alpha release from isolated monocytes in a CD14-independent fashion. This is an important finding for the interpretation of results from studies that use fucoidan to "block" either scavenger receptors or L- or P-selectins.

Antimicrobial Cationic Peptides↗
PubMed1997

Bacterial cell wall products increase monocyte HLA-DR and ICAM-1 without affecting lymphocyte CD18 expression.

Bacterial cell wall products such as lipopolysaccharide (LPS) and muramyl dipeptide (MDP) have the capacity to enhance immune responses to antigens. The expression of surface class II major histocompatibility antigens and the costimulatory receptors CD18 and CD54/ICAM-1 (intercellular adhesion molecule) was used to evaluate the comparative influence of these immunostimulators. On monocytes, both LPS and MDP increased the expression of human leukocyte antigen (HLA)-DR (maximal at 6 hr), CD18 (maximal at 1-3 hr), and ICAM-1 (maximal at 18-24 hr for LPS and 12 hr for MDP) without increasing the production of superoxide. MDP-induced ICAM-1 expression on monocytes returned to baseline values after 12 hr. On lymphocytes, only LPS increased ICAM-1 (after 18 hr) without affecting CD18, and a differential analysis demonstrated a generalized ICAM-1 upregulation in lymphocyte subsets after 18 hr: the most pronounced effect was measured in natural killer cells, followed by CD8(+) T cells, B cells, and CD4(+) T cells. MDP did not alter ICAM-1 or CD18 expression on lymphocytes. These similar but smaller effects of MDP may, in part, explain the lesser toxicity of MDP when compared to LPS.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1997

Treatment of pneumonia in mechanically ventilated trauma patients. Results of a prospective trial.

OBJECTIVES: To determine the efficacy and magnitude of associated adverse effects of 2 different antibiotic regimens for the treatment of pneumonia in intubated surgical patients and to assay and compare blood samples and bronchoalveolar lavage fluid with respect to some host-defense parameters, especially in patients with unilateral pneumonia. DESIGN: Randomized, prospective, unblinded clinical comparison of 2 treatment arms with respect to intent to treat and clinical and microbiologically evaluable patients. SETTING: Six university surgical services in teaching hospitals with modern and well-staffed intensive care units. INTERVENTIONS: The consistency and objectively of the diagnosis of pneumonia was improved by the use of a grid of diagnostic parameters. Aggressive mechanical approaches to pneumonia in intubated surgical patients were supplemented by therapeutic use of aztreonam and vancomycin hydrochloride or combined imipenem and cilastatin sodium. RESULTS: Patients randomized to the aztreonam-vancomycin group were somewhat more ill, fared slightly better, and had fewer serious drug-related side effects than did those treated with imipenem-cilastatin (all P > .05). Immunologic parameters assessed by evaluation of bronchoalveolar lavage fluid showed differences between infected pulmonary lobes and noninfected ones; some changes were also noted in patients who recovered compared with those whose pneumonia persisted or recurred. CONCLUSIONS: Clinical studies of pneumonia in surgical patients need to be stratified to assure comparability, to identify patients in whom treatment is likely to fail, and to display differences between more and less effective therapies. Studies of blood and bronchoalveolar lavage samples showed that certain local and systemic immunologic parameters correlate with clinical status and outcome.

Aztreonam↗
PubMed1997

Twelfth rib resection. Preferred therapy for subphrenic abscess in selected surgical patients.

OBJECTIVE: To assess the role of 12th rib resection in the treatment of postoperative, subphrenic abscesses. DESIGN: Consecutive case series. SETTING: University hospital, level I trauma center. PATIENTS: Operative logs for a 13-year period were reviewed for all patients undergoing 12th rib resection for drainage of a postoperative subphrenic abscess. Each individual medical record was reviewed for demographic data, primary diagnosis, computed tomographic scan findings, and clinical status (temperature, white blood cell count, and Acute, Physiologic, Age, and Chronic Health Evaluation II score) at the time of rib resection. MAIN OUTCOME MEASURES: Operative results, microbiological data, complications, and outcomes. RESULTS: Twenty-six patients underwent 27 rib resections for a secondary left subphrenic (23) or a right subhepatic (4) abscess. All patients had undergone at least 1 prior laparotomy (average, 1.5; range, 1-4). Sixteen patients had traumatic injuries, and 7 had complicated pancreatitis. Twelve patients had undergone prior failed attempts at percutaneous drainage before rib resection. Fourteen patients underwent operative drainage without attempted percutaneous drainage, mainly for peripancreatic (7) or multiloculated (3) abscesses. There were 3 postoperative complications (3/27 [11%]): a gastrocutaneous fistula, a gastrocolic-cutaneous fistula requiring laparotomy and temporary colostomy, and fasciitis in the resection site. Four (15%) of the 26 patients died: 3 died of progressive multiple system organ failure, and 1 died of an unrelated injury. The remaining 20 (77%) of the patients were discharged from the hospital with healing wounds and no further episodes of intra-abdominal infection. CONCLUSIONS: Twelfth rib resection is an effective alternative therapy for secondary subphrenic abscesses. The nature of the incision allows for open, dependent drainage; avoids subsequent laparotomy; and effectively controls intra-abdominal infections. Twelfth rib resection remains a useful tool in the treatment of subphrenic abscess and may be the preferred approach when other attempts at abscess drainage have failed.

Adult↗
PubMed1997

Prostaglandin E2 modulates monocyte MHC-II (Ia) suppression in biomaterial infection.

Staphylococcus epidermidis biomaterial infection is associated with local cellular immune suppression measured by a depressed monocyte (M phi) Ia expression. The purpose of this study was to define the effect of proinflammatory mediators on Ia expression and bacterial clearance in experimental biomaterial infection. A 1-cm-long Dacron tube graft, sterile or colonized with Staphylococcus epidermidis (1 x 10(7) cfu/ml2), was implanted in Swiss-Webster mice. Perigraft fluid was collected at 7, 10, 14, and 28 days and assayed by enzyme-linked immunoassays for tumor necrosis factor alpha (TNF alpha), interleukin (IL)-I alpha, IL-4, IL-10, and prostaglandin E2 (PGE2). Grafts were sonicated and plated for quantitative growth. In vivo effector inhibitions was accomplished with anti-TNF alpha, anti-IL-1 alpha antibodies (7 micrograms/24 hr), or indomethacin (50 micrograms/24 hr) via an Alzet 7-day microinfusion pump. M phi Ia expression was determined by flow cytometry. A significant elevation of TNF alpha, IL-1 alpha, and PGE2 was found during the first 10 days in the infected compared with sterile (P < or = 0.05) grafts and correlated with maximal Ia suppression. Neither IL-4 nor IL-10 was significantly different in the sterile or infected perigraft fluid. Indomethacin completely prevented M phi Ia suppression, while anti-IL-1 alpha only partially (94%) prevented M phi Ia suppression with a corresponding decrease in PGE2 production in infected grafts. Anti-TNF alpha increased PGE2 production by 189% and was associated with depressed M phi Ia expression. Indomethacin treatment improved mean graft-adherent bacterial clearance by 54% at 7 days and 75% at 28 days compared with control (not significant). Interleukin-1 alpha but not TNF alpha increases PGE2 production which modulates M phi Ia suppression. To improve treatment of biomaterial infections, local immunomodulation of PGE2 and IL-1 alpha is promising.

Animals↗
PubMed1997

The relationship between criteria used to select residents and performance during residency.

PURPOSE: Can data available at time of interview and evaluation predict level of performance during residency? METHODS: General surgery residents were studied. Applicant information available prior to admission was used to predict performance during residency as measured by faculty judgment of residents' knowledge, technical skill, maturity and judgment, and overall ability. RESULTS: No relationship was found between admission data and final evaluation (using Spearman's coefficient r(s) = 0.27; p = 0.13). We could not distinguish between the top 10 and the bottom 10 ranked residents on admission variables. Nine of the top 10 and 3 of the bottom 10 residents remained in general surgery. Performance on the American Board of Surgery In-Training Examination accounted for 37% of the variance in faculty grading (F(5,28;.05) = 3.26; P = 0.02). CONCLUSIONS: Residents' interpersonal and technical skills and qualities of character may have a significant role in faculty perception of success during surgical residency. These qualities are not well reflected in candidates' credentials at admission.

Career Choice↗
PubMed1997

Venous thromboembolism in the high-risk trauma patient: do risks justify aggressive screening and prophylaxis?

OBJECTIVE: Deep venous thrombosis (DVT) and pulmonary embolism (PE) are considered to be a major source of morbidity and mortality among trauma patients. Several reports have identified high-risk patients with recommendations for management ranging from frequent duplex scanning to placement of prophylactic inferior vena cava (IVC) filters. We reviewed our experience with a large trauma population to determine whether such approaches are justified. METHODS: We analyzed 2,868 consecutive trauma admissions over 22 months and identified 280 patients (10%) in high-risk groups who survived > or = 48 hours: (1) severe closed head injury with mechanical ventilation > or = 72 hours, (2) closed head injury with lower extremity fractures, (3) spinal column/cord injury, (4) combined pelvic and lower extremity fractures, and (5) major infrarenal venous injuries. The remaining nonthermal injury patients constituted the low-risk group. RESULTS: There were 280 high-risk patients, 213 of whom (76%) received prophylaxis with compression therapy. There were 12 cases of DVT (5%) with four nonfatal PE (1.4%). Six patients (2%) had therapeutic IVC filters inserted and only one patient had prophylactic placement. There were 38 deaths in this group, attributable primarily to severe closed head injury or spine injuries, and none were caused by PE. In the 2,249 low-risk patients, there were three cases of DVT (0.1%, p < 0.05 vs. high risk) and no PE (p < 0.05 vs. high risk). CONCLUSIONS: Although these patients were at increased risk for thromboembolic events, the overall incidence of DVT was still extremely low with no apparent PE deaths. In our patient population, aggressive screening and prophylactic IVC filters would not have benefited 95% of "high-risk" patients without DVT and would not have prevented any deaths. We could not identify any population, except perhaps venous injuries, where such expensive and potentially harmful maneuvers seemed justified. Our experience with DVT and PE does not support either aggressive screening or prophylactic IVC filters as the standards of care.

Adolescent↗
PubMed1997

Impact of level III verification on trauma admissions and transfer: comparisons of two rural hospitals.

PURPOSE: To study the impact of Level III verification and other changes in rural hospitals on trauma delivery and to examine factors affecting transfer to a Level I trauma center. SETTING: Two rural Kentucky hospitals and a Level I trauma center. METHOD OF REVIEW: Concurrent review of all trauma patients in 1988 and re-review of the same parameters in 1995. FINDINGS: In 1988, both hospitals had similar management practices in trauma care. A significant number of patients were transferred for (a) patient choice, (b) serious and/or multiple trauma, (c) specialty care in non-life threatening situations, and (d) to exclude a potentially serious problem seen on radiologic evaluation (usually questionable cervical spine or widened mediastinum). Both hospitals had major changes in trauma delivery. One hospital received Level III verification, and the other had changes that lessened the general surgeon's involvement with initial evaluation and treatment. A re-review in 1995 disclosed major changes at both institutions. Transfers to exclude radiologic abnormalities had virtually disappeared. The Level III status had increased the surgical involvement in that hospital; there was actually an increase in patients transferred to the Level I hospital and an increase in patient acuity. More operations were performed locally, and the care was more efficiently delivered. The other hospital had a large increase in transfers and decreased admissions locally as general surgical involvement decreased. CONCLUSIONS: The factors related to patient transfer for trauma care are complex and require careful elucidation to improve care. The development of a Level III trauma service appeared to increase the number of seriously injured patients treated in the rural hospital and the efficiency of the care delivered.

Concurrent Review↗