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Biomedical subjects

H C Polk

Publications and source records attributed to H C Polk.

At least 19 recordsLinked to original sources

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

Effect of protein malnutrition and immunomodulation on immune cell populations.

Malnutrition has deleterious effects on immune functions, which predispose to an increased risk of infection. To study the effect of protein malnutrition on such immune functions and resistance to infection, we divided C57BL/6 mice into three groups: (1) control-standard diet, (2) protein-malnourished for 14 days, and (3) protein-malnourished for 14 days followed by standard diet for 3 days. The animals were further divided into subgroups: (1) an untreated group, (2) a muramyl dipeptide (MDP)-treated group, and (3) an interferon-gamma (IFN-gamma)-treated group before cecal ligation and puncture (CLP). Malnourished mice had significantly (P less than 0.05) lower body weight, serum albumin, spleen/body weight, percentage of splenic macrophages with Ia expression (%MOIa), increased splenic T suppressor cells, and greater mortality after CLP. Refeeding plus IFN-gamma or MDP significantly increased %MOIa (P less than 0.05) and also abrogated the increase in splenic lymphocytes seen in the malnourished animals. The increase in splenic suppressor T cells was not affected by refeeding or immunomodulation. Mortality after CLP was increased from 15% in the controls to 85% in the malnourished group and was significantly decreased by refeeding, MDP, and the combination of refeeding plus immunomodulators (P less than 0.05). These data show that 14-day malnutrition adversely affected the immune response to infection and increased mortality from CLP. Refeeding and immunomodulation restored macrophage Ia expression without CLP but not after the procedure, despite the significant reduction in mortality. The use of immunomodulation in protein malnourished conditions may serve as an adjuvant role to nutritional support.

Acetylmuramyl-Alanyl-Isoglutamine

Management of diabetic midfoot ulcers.

Diabetic midfoot ulcers are caused by bone and joint disruption that occur as a consequence of progressive peripheral neuropathy associated with this disease. This results in osseus deformities and areas of high pressure on the plantar surface of the midfoot, which cause the ulcers. These lesions are difficult to heal and frequently lead to amputation. In a series of 348 patients, 40 developed 54 midfoot ulcers. Limb preservation was achieved in 33 (61%). Wound closure was achieved in 32 (60%). The amputation rate was highest (83%) in the 10 of 12 patients with peripheral vascular disease. Successful therapy for limb preservation most often included an operation combining resection of underlying osseus deformities with debridement of affected soft tissues.

Diabetic Neuropathies

Regional cellular responses to intraperitoneal infection.

Leucocytes in different body compartments were examined in a murine intra-abdominal abscess model: (i) peripheral blood; (ii) peritoneal exudate; (iii) abscess wall; and (iv) abscess pus, with respect to their phagocytic ability, CR3 expression and Ia antigen expression (murine MHC antigen). The ability of serum or supernatant in each compartment to opsonize Staphylococcus aureus was also determined. Mice responded to caecal ligation and puncture (CLP) with systemic monocytosis, an increased amount of opsonins in peritoneal fluid and an increased phagocytosis in pus leucocytes. This increased phagocytic ability and CR3 expression both subsequently decreased. Monocyte/macrophage Ia expression was reduced in all measured compartments over time. In contrast, sham-operated animals, without an intra-abdominal abscess, responded to operation with an even greater increase in peritoneal exudate phagocytic ability and in monocyte/macrophage Ia expression in all compartments which was sustained beyond 1 week. Decreased peritoneal exudate cell and peripheral blood Ia was still present after 28 days in CLP animals, compared with both sham and normal animals (P less than 0.05, P less than 0.02, respectively). For all parameters, changes observed in peripheral blood did not reflect those present near the site of infection. Proper understanding of local or regional infection must take into account and ultimately alter these generally unappreciated changes in and about the actual site of infection.

Abscess

The role of the complement system in trauma and infection.

The complement system is an important immediate host defense mechanism after trauma, extensive burn injury and after invasion by microbial pathogens. Massive complement activation, however, seems to be detrimental and may contribute further to the disease process and eventually to multiple organ failure or the septic state. In clinical situations in which complement is damaging, the logical therapy should be, if at all possible, the removal of the activated complement components from the circulation. However, much of the protein is attached to the membrane and effective locally, so prevention of the enzymatic cascade may be more appropriate. There has been little progress in manipulating the complement system to effectively alter such disease processes caused by the clinical situations and there is an important need for further research in the field.

Bacterial Infections

An editor's perspective of the future for peer-reviewed traditional surgical journals.

In the opinion of the Journal's Editor, the future of peer-reviewed surgical journals is promising. Although problems remain to be solved, including the loss of advertising revenues, the reduction of available research funds, and the potential for duplication of information, the energy and commitment of editorial board members, reviewers, surgical practitioners, and readers will continue to have a positive impact and will ensure the survival of the traditional surgical journal into the next century.

Forecasting

HLA-DR antigen expression on peripheral blood monocytes correlates with surgical infection.

Monocyte human leukocyte antigen-DR (HLA-DR) expression has correlated closely with clinical outcome in severely injured patients at high risk for infection. Monocytes from 77 asymptomatic volunteers expressed HLA-DR antigen with minimal variability in respect to age, gender, race, time of day or year, or serum alcohol level. Patients who developed infection after elective laparotomy had a significantly lower mean percentage of monocytes expressing HLA-DR antigen and a lower mean fluorescent intensity than uninfected patients (p less than 0.05). Severely infected nonsurgical patients had significantly lower values than normal volunteers (p less than 0.01), and the mean fluorescent intensity of those who died from infection was significantly lower than that of those who survived (p less than 0.05). Patients on immunosuppressive regimens after renal transplantation had levels of HLA-DR expression similar to those of the volunteers. Monocyte HLA-DR expression was found to be a reliable marker of clinical infection and showed remarkable reproducibility within the normal uninfected study population.

Adult

Intra-abdominal sepsis: the role of surgery.

The role of the surgeon in intra-abdominal sepsis is multifactorial. A comprehensive understanding of the incidence and pathophysiology of diseases which cause intra-abdominal sepsis is the key to the diagnosis and treatment of such ailments. In simplest terms, the aetiology has two basic mechanisms: (a) violation of the 'bug-body barrier' and (b) obstruction to the flow of a body fluid with subsequent bacterial overgrowth. Either of these mechanisms may affect any of the organs within the abdomen, leading to sepsis. The peritoneal cavity is a dynamic structure which responds to insults in certain predictable manners which notify the alert physician that danger is present. Recognition of these signs through history and physical examination are the most important aspects of diagnosis. Confirmation of suspicions can be obtained with radiological modalities, but they are not a substitute for clinical judgement. Treatment of intra-abdominal sepsis should always begin with resuscitation and systemic antibiotics. Alleviation of the septic source is mandatory, and this may be achieved either operatively or non-operatively (i.e. percutaneous or endoscopic procedures). When the patient does not improve after the initial procedure, then a missed focus of infection must be investigated. In some cases, a planned or staged second operation may be needed to further debride necrotic tissue. Antibiotics should be of adequate spectrum and bioavailability to kill the species of bacteria most likely to cause the infection. This regimen may be altered when culture and sensitivity reports are completed. Finally, patients whose immune system function has been altered by disease or treatment must be assumed very ill until proven otherwise. These are general guidelines in the management of patients with intra-abdominal sepsis. Individual cases may necessitate slight modifications, but all require a high level of vigilance and expertise in order to combat a very lethal disease.

Abdomen

Repeat operation for failure of antireflux procedures.

The majority of patients who receive modern antireflux operations obtain substantial long-term relief of their symptoms. About 10% to 15% will have persistent or recurrent problems, some severe enough to warrant reoperation for correction. With careful symptom review, barium study, endoscopy, and manometry, the mechanism of failure becomes evident, and remedial surgical treatment may proceed. The results at reoperation are not as good as those of the primary procedure, which emphasizes the need for proper diagnosis and choice of procedure and for reliable execution of technique at the initial treatment.

Gastric Fundus

Helicopter transport of trauma victims: does a physician make a difference?

We studied the impact of physician presence on helicopter transportation of trauma victims during two periods; when physicians were part of the flight team and when they were not. Our data failed to demonstrate that physician participation in flights had an impact on patient outcome. The groups were comparable in average distance traveled, initial Trauma Scores, number of organ systems injured, and the final Injury Severity Scores. Each group showed an improved survival over that predicted by comparison with the Multiple Trauma Outcome Study cohort. No difference was found in the number of procedures performed at the scene, en route, or on arrival at the hospital. Untreated injuries were slightly higher in the physician-present group. It appears that experienced nurses and paramedics, operating with well-established protocols, can provide aggressive care that yields equal outcome results compared with those of a flight team that includes a physician.

Aircraft

Nonthermal surgical complications in burn patients.

Patients with severe burn injuries are generally admitted to specialized units and managed by physicians who specialize in burn care. Complications requiring operative intervention and not directly related to the burn wound occur frequently but are easily overlooked. To determine the nature and frequency of these complications, we conducted a retrospective study of all burn cases in our burn unit over a 5-year period. Twenty-three of the 309 patients (7%) had 45 complications not related directly to the burn wound and required surgical intervention or consultation. The population with surgical complications was generally older (52 vs 42 years), more severely burned (36% vs 25% total body surface area), and had a higher mortality (44% vs 13%). Sixteen of the 23 patients with complications had a single surgical problem, while seven patients sustained multiple complications. In six of the 10 deaths, the surgical complication was believed to be either directly related or significantly contributory to the cause of death. Because the number of burn patients requiring surgical intervention is high, burn patients must be thoroughly examined for possible complications.

Adult

Misconduct and fraud in research: social and legislative issues symposium of the Society of University Surgeons.

The symposium was concluded with a question and answer period, which served to clarify and further emphasize the aforementioned issues. Many concerns of coauthorship responsibilities, due process, and potential sanctions were discussed. Moral and ethical issues reflecting the extent of punishment, reporting of misconduct to hospitals and specialty boards, and the almost assured litigation and counter-litigation were approached with considerable apprehension and concern. Misconduct in science will clearly be monitored more closely than in the past. Increasing coauthorship responsibility, conscientious senior investigator supervision, and institutional cooperation will provide the framework to discourage dishonesty in science and encourage proper educational development of both young and established investigators in a milieu of scientific integrity.

Biomedical Research

Endotoxin filtration and immune stimulation improve survival from gram-negative sepsis.

Polymyxin B, when bound to a polystyrene fiber (PMX-F), has been used experimentally as an extracorporeal blood filter to reduce serum lipopolysaccharide levels, which are believed to be responsible for physiologic alterations in the septic state. To validate our theory that a combination of PMX-F, systemic antibiotics, and immune stimulation would improve survival, 78 rats were given intravenous doses of Escherichia coli (range, 4.6 to 6.2 X 10(8) colony-forming units/ml). They were then randomized into groups receiving either systemic gentamicin (n = 10); pretreatment with muramyl dipeptide (n = 11); or extracorporeal hemoperfusion through either a sham column (n = 8), PMX-F-packed column with systemic gentamicin (n = 8); or PMX-F-packed column with systemic gentamicin and muramyl dipeptide pretreatment (n = 8). Thirty-three control rats received no treatment. Sham hemoperfusion (13%) and control (21%) rats had the lowest survival rate, although increased improvement was noted in rats treated with gentamicin (30%) or the combination of PMX-F filtration and gentamicin (50%). The most significant improvements occurred in rats pretreated with muramyl dipeptide (53%) and in rats treated with a combination of PMX-F, gentamicin, and muramyl dipeptide (88%). These data show that lipopolysaccharide filtration and nonspecific immune stimulation are additive to antibiotic therapy and are useful as adjunctive measures in the multimodal treatment of experimental gram-negative bacterial infection.

Acetylmuramyl-Alanyl-Isoglutamine

There is an answer to the shortage of organ donors.

From a retrospective review of 32,562 deaths that occurred in 1988 in the service area of Kentucky Organ Donor Affiliates, an area with a population of 3.4 million, 173 potential solid organ donors were identified for a rate of 50.8 donors per million population base. There were only 38 actual solid organ donors from this potential pool. The physician failed to recognize the potential for donation in 29 instances and in 92, the family refused consent for donation. In the second phase of the study, we analyzed 155 consecutive medically suitable organ donor referrals for one year. A specific focus on the process and timing of the request for donation was made in this review. In 143 of these instances (92 per cent), a clear temporal separation of the explanation of death or the certainty of family acceptance of death before the request for donation yielded a donor success in 53 of 82 instances. In contrast, only 11 of 61 instances resulted in a consent when the discussion of death and donation were combined into one discussion with the family (p less than 0.05). From this study, there seemed to be adequate numbers of organs available to provide for the current pool of recipients within the state of Kentucky. Educational assistance and an ongoing individual patient review of each death improved the donor rate during the time frame of this study. It is essential to allow a temporal separation between the explanation of death and the request for organ donation to maximize actual organ donation.

Adolescent

Effects of early tangential excision and grafting on survival after burn injury.

This report quantifies the increase of burn survival, which we believe is associated with the use of early tangential excision and grafting as opposed to conventional therapy in adult patients with burns. To quantify the increase, we compared the lethal area 50 of various age groups with that of previous historical studies that used other techniques. These data suggest that early excision and grafting are associated with a marked improvement in survival in patients 41 to 60 years of age with 20 to 65 per cent total body surface area burns.

Adult

Procurement and transplantation of colonized cadaver skin.

Cadaver skin is an important adjunct to burn care. This study was designed to measure the percentage of its contamination prior to grafting and to determine the clinical safety of its use. Cadaveric homografts from 19 donors were harvested, frozen, thawed, and used as a biological dressing. Cultures were obtained at the time of harvest, after incubation in antibiotics, and at actual transplantation. The homografts were 43 per cent, 68 per cent, and 50 per cent contaminant-free, respectively. Two of 14 patients lost their homografts due to infection. However, no patient developed an infection or lost the homograft due to an organism identified during the pretransplantation processing. Therefore, contaminant-free and slightly contaminated cadaver skin can be used safely as homografts.

Adolescent

Interferon gamma and tumor necrosis factor alpha. Use in gram-negative infection after shock.

Shock increases the propensity to develop infection after injury or operation. This study evaluated the effect of cefoxitin, interferon gamma (INF-gamma), and tumor necrosis factor alpha (TNF-alpha) on the development of a polymicrobial soft-tissue infection. After sham operation or hemorrhagic shock and resuscitation, Sprague-Dawley rats were inoculated with 1 x 10(8) Escherichia coli and 1 x 10(9) Bacteroides fragilis in a 5% fecal suspension. Animals received either no treatment, cefoxitin, recombinant rat INF-gamma, recombinant human TNF-alpha, or cefoxitin/cytokine combinations. Cefoxitin reduced abscess size by 57% in animals without shock but only by 26% after shock. Although neither INF-gamma nor TNF-alpha alone had a salutary effect when given with cefoxitin in animals after shock, INF-gamma and TNF-alpha reduced abscess size by 50% and 55%, respectively. These results suggest that INF-gamma and TNF-alpha may be useful to reduce the severity of mixed gram-negative infections after shock with bacterial contamination.

Abscess